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SOUTH AFRICAN GUIDE TO TOPICAL OPHTHALMIC DRUGS

CPD PROGRAMME

Dirk J. Booysen

2016 EDITION

XAILIN –

DRY EYE RELIEF BOTH DAY AND NIGHT

CMC Carmellose HPMC Hypromellose HA Hyaluronic Acid Carbomer Ointment Soft White Paraffin VISCOSITY ACCORDING TO PATIENT PREFERENCE AND SEVERITY OF SYMPTOMS

THE NEW NAME IN QUALITY DRY EYE LUBRICANTS

References: 1. Xailin Hydrate Instructions for use. Nicox Pharma. 2. Xailin Fresh Instructions for Use, Nicox Pharma. 3. Xailin Gel Instructions for use. Nicox Pharma. 4. Xailin Night Instructions for Use, Nicox Pharma. 5. Xailin HA Instructions for use. Nicox Pharma. Genop Healthcare (Pty) Ltd. PO Box 3911, Halfway House, 1685, South Africa. Reg. No.: 1984/011575/07. www.genop.co.za. 02/2016/NS/42.

Are we there yet? In the third edition of the “guide” drugs no longer available on the SA market have been removed and a few new drugs have been included. In the section on glaucoma the treatment protocol has been revised according to the latest information available from the European Glaucoma Society publication - Terminology and Guidelines for Glaucoma. I have also included two slides which indicated the importance of maintaining and adjusting target pressure in primary open angle glaucoma to save sight. In the previous edition a table on the ocular side effects of systemic drugs was included. This table has been updated and additionally a new table showing the systemic side effects of commonly used topical ophthalmic drugs have been included. In terms of prescription rights for Optometrists some positive progress has been made in the past two years. The PBODO (Professional board of Optometry and Dispensing Opticians) of the HPCSA (Health Professional Council of South Africa) applied to the MCC (Medicines Control Council) for Optometrist to acquire, possess and use specific schedule 1, 2, 3, and 4 substances for diagnosis and therapeutic purposes. A specific list of medicines including topical antibacterial, antiviral and antifungal, antihistamines, mast cell stabilizers, vasoconstrictors, mydriatics and cycloplegics, local anaesthetics, anti-glaucoma, steroidal anti-inflammatory and oral analgesics have been approved with the provision that prescribing rights for paediatric use are not authorised. Where applicable these drugs have been highlighted in this issue of the guide. So are we there yet, and can optometrists write prescriptions for drugs on this list? The answer is yes for the diagnostic drugs but no for the therapeutic drugs. The next step in the process is to enrol in an approved course to train practitioners to effectively use therapeutic drugs, only after this course has been completed and the appropriate legislation have been changed will “qualified” optometrists be allowed to legally prescribe drugs on this list. I sincerely hope this guide has some value in your practice, keep the comments coming. Dirk J. Booysen

“Dirk Booysen’s “South African Guide to Topical Ophthalmic Drugs” is a comprehensive clinical and academic overview of this category of drugs. All practicing optometrists would find the contents to be enormously helpful in gaining an excellent understanding of the ophthalmic medicines. Each drug class, and individual drug, is carefully described, and its clinical relevance is clearly explained. This text is a masterful work that should be read, studied, and applied by all optometrists in South Africa. We think this publication can set the foundation to launch a major advance in eye care for all South African citizens. We applaud Dirk’s dedication in developing this timely and important clinical masterpiece for the benefit of South African optometry. We urge its complete reading. Ron Melton and Randall Thomas North Carolina, USA

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South African Guide to Topical Ophthalmic Drugs by Dirk Booysen

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EYESITE.co.za DISCLAIMER The South African Guide to Topical Ophthalmic Drugs is owned by the author Dirk Booysen. © Copyright 2016. Unless otherwise noted, the contents of the South African Guide to Topical Ophthalmic Drugs , including all text, graphics, video and other visual material and the selection, arrangement and layout thereof are copyright of EyeSite and all rights are reserved. Reproduction, downloading or copying of any material from this site, in any form whatsoever, will constitute a copyright infringement and will result in civil and criminal law penalties Whilst every effort has been made to ensure the accuracy of its contents, neither EYESITE.co.za, nor Dirk Booysen can be held responsible for any omissions or errors; or for any misfortune, injury or damages which may arise there from.

ALCON AIR OPTIX * PLUS WITH HYDRAGLYDE DISCOVER THE WORLD OF LONG LASTING MOISTURE For further information contact ALCON at 011 840 2300

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90 C 0 40 M/ Lab 60 Lab Telephone: (011) 326 0245 / Lab Mobile: 081 763 2256 Fax: 086 619 2503 Email: [email protected] / Web: www.contactlenssa.co.za South African Guide to Topical Ophthalmic by Dirk Booysen 100 Y Drugs 100

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Contents 1. Diagnostic drugs �� 10

d. Polypeptides �� 44

A. Vital dyes �� 10

e. Aminoglycosides �� 44

a. Flourescein �� 10

f. Chloramphenicol �� 45

b. Fluorexon �� 12

g. Tetracyclines �� 46

c. Rose Bengal �� 12

h. Macrolides �� 47

d. Lissamine green �� 13

i. Fluoroquinolones �� 47

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Ester type �� 16 Y 100 Y 100

a. Amethocaine �� 16

b. Oxybuprocaine �� 17 G 81 G 130

c. Proxymethacaine �� 20

Amide type �� 20

a. Lignocaine �� 20

C. Mydriatics and cycloplegics �� 20

a. Atropine sulphate �� 24

b. Homatropine �� 26

c. Cyclopentolate HCI �� 27

d. Tropicamide �� 30

e. Phenylephrine �� 32

f. Combination drugs �� 34

D. Miotics �� 36

a. Physiostigmine �� 36

b. Pilocarpine nitrate �� 37

2. Antibiotics �� 38 Introduction �� 38

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Topical Antibiotics �� 42

a. Fusidic acid �� 42

b. Sodium sulphacetamide �� 42

c. Propamidine isethionate & dibromopropamidine isethionate �� 43

3. Anti-inflammatory �� 52 A. Non-steroidal anti-inflammatory drugs 52

a. Ketorolac tromethamine �� 53

b. Sodium diclofenac �� 54

c. Nepafenac ophthalmic�� 55

B. Topical corticosteroids �� 56

Steroids with maximum clinical action 64

a. Prednisolone �� 64

b. Dexamethasone �� 65

c. Loteprednol �� 65

Moderate clinical action �� 66

a. Fluorometholone �� 66

C. Immunomodulatory drugs �� 66

a. Cyclosporine A �� 66

4. Corticosteroid / Antibiotic combinations

�� 67

a. Maxitrol® �� 68

b. Tobradex® �� 68

c. Spersadex Comp® �� 69

d. FML Neo® �� 69

e. Betnesol N® �� 69

f. Sofradex® �� 70


INNOVATION IN DRY EYE THERAPY

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Caring for the 3 layers between your eyes and the world1 Lipid deficiencies Aqueous tear-deficiencies Mucin deficiencies

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References: 1. Liposic Product Monograph. Data on file, Bausch&Lomb Inc.

Scheduling status: S0 Proprietary name and dosage form: Liposic Eye Gel. Composition: Each 1 g contains: 2 mg carbomer, triglycerides – medium chain, sorbitol, sodium hydroxide and purified water, Cetrimide 0,01 % m/m (preservative). Pharmacological classification: A 15.4 Ophthalmic preparations - Other. Indications: Substitution of tear fluid for management of dry eye conditions such as symptomatic treatment of keratoconjunctivitis sicca. Registration number: 37/15.4/0224. © 2003 Bausch & Lomb Incorporated. ®/™ denote trademarks of Bausch & Lomb Incorporated. Applicant: SofLens (Pty) Ltd. Reg. No.: 1968/11787/07. Marketed by: Bausch & Lomb (SA) (Pty) Ltd. Reg. No.: 1996/003931/07. 15E Riley Road, Bedfordview, Gauteng, South Africa, 2008. Tel: +27 11 087 0000 www.bausch.co.za BL94/15

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Contents 5. Anti-allergy drugs and decongestants �� 71 a. Phenylephrine �� 74

b. Naphazoline, oxymetazoline, tetrahydrozoline �� 75

2. Travoprost �� 95

3. Bimatoprost �� 96

c. Topical carbonic anhydrase inhibitors 96

A. Decongestants or vasoconstrictors �� 74

1. Acetazolamide �� 98

2. Dorzolamide & brinzolamide �� 98

3. Cosopt® �� 99

ISO LESO GREEN B. Antihistamines and mast cell stabilizersISO LESO YELLOW 4. Azarga®�� 99 �� 76 C 90 C 0 d. Adrenergic agonists or sympathomimetic M 40 M 60 �� 100 a. Mast cell stabilizers �� 76

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�� 78

3. Lodoxamide �� 78

b. Antihistamines �� 78

1. Antazoline �� 80

e. Cholinergic agonists �� 103

7. Topical anti-viral drugs

�� 106

2. Levocabastine �� 80 3. Azelastine �� 80 4. Emedastine �� 80 5. Ketotifen �� 81 6. Olopatadine �� 81 7. Epinastine �� 81

c. Trifluorothymidine �� 106

d. Acyclovir �� 107

8. Tear supplements�� 108 9. Ocular adverse effects of systemic drugs�� 115

6. Primary open angle Glaucoma �� 82 GLOSSARY �� 130 A. Medical Management of Primary open angle Glaucoma �� 82 a. Introduction �� 82

CPD PROGRAM �� 136

b. Quality of life issues �� 85 c. Historical perspective �� 85 B. Topical anti-glaucoma drugs �� 90 a. β-blockers �� 90 b. Prostaglandin F2α (PGFα) analogues �� 93

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1. Latanoprost �� 94


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1. Diagnostic drugs

with the highest visibility in the eye care practitioner’s office today are fluorescein, rose Bengal, lissamine green B, and high molecular weight fluorescein.

Diagnostic drugs are commonly used inophthalmic practice and include the vital dyes, anaesthetics, myotics, mydriatics and cycloplegics. Although complications a. Flourescein are relatively rare when using these drugs This is a yellow acid dye of the xanthene responsibly, great care should be taken series and was first used on the eye in by the clinician to prevent serious side 1882 when researchers discovered that effects such as angle closure glaucoma it could reveal corneal epithelial defects. when using a mydriatic or cycloplegic. The ISO LESO GREEN ISO LESOWhen YELLOWexposed to light, fluorescein absorbs astute clinician will also be current on the certain wavelengths and emits fluorescent C 90 C 0 necessary treatment protocols for treating M 40 M 60 light of a longer specific wavelength. For Y or 100 complications. Y 100 such serious side effects K 45 K 0 dilute concentrations of fluorescein, light R 4 R 245 of wavelengths 530nm produces the G 130 A. Vital dyes G 81 maximum intensity of fluorescence. B

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Diagnostic dyes represent one of the most efficient, objective, non-invasive, directly visible means of identifying and tracking ocular surface changes at the cellular level. The use of diagnostic dyes was first reported in the late 1800s following Bayer’s synthesis of fluorescein in 1871. The dyes

The examination sequence 1. Histories (ocular, medical, family) 2. Visual acuity (pinhole included) 3. External examination 4. Pupillary examination 5. Ocular motility (cover test) 6. Refraction (cycloplegic if indicated) 7. Biomicroscopy (vital dyes) 8. Goldmann tonometry (pachymetry) 9. Fundus examination (mydriatic if needed) 10. Speciality tests if indicated (threshold fields, photography, OCT, GDX, topography)

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Since fluorescein is a weak acid and, depending on the solution, it can exist in various ionic states. Below pH 2, the cationic form predominates and a weak blue-green fluorescence occurs. Between pH 2–4, the cations dissociate to neutral molecules. At pH 7, negative ions prevail and are associated with a brilliant yellow-green fluorescence. Factors that alter the fluorescence are: - Concentration, maximum at 0.001% - pH of the solution, maximum fluorescence at physiological pH of 7 - Presence of other substances - Intensity and wavelength of the absorbed light Fluorescein in solution is highly susceptible to bacterial contamination, especially by Pseudomonas aeruginosa. Pseudomonas g row e a s i l y i n t h e p re s e n c e o f fluorescein. For tunately, the use of fluoresceinimpregnated sterile filter paper strips has been devised to eliminate the risk. In clinical practice, fluorescein is used to detect lesions of the ocular surface.


Due to the high degree of ionization at physiological pH, fluorescein does not penetrate the intact corneal epithelium well, nor does it form a firm bond with any vital tissue. From the ocular surface perspective, the wa te r-s ol u b l e dye molecules diffuse into the intracellular spaces between living cells. The intensity of the stain is increased in areas of cellular degeneration or death where the damage to cells, cell membranes, and cell-to-cell junctions allows for the intracellular spaces to be more highly penetrated by the dye.

fluorescein diffusion between adjacent

It is this property that makes the dye most useful for observing permeability in corneal epithelial and endothelial cells. In conjunctival epithelial cells, observation is made difficult by the dye’s presence in both the cells and the intracellular spaces.

lens insertion and resolves after 6 to

cells. This research highlights the limitations of using fluorescein as an ambiguous tool for assessing the ocular surface health and call into question the dogmatic viewpoints of corneal staining strictly representing corneal damage or injury. SICS or solution induced corneal staining is characterized by asymptomatic, transient corneal staining associated with the use of multipurpose solutions (MPS). This phenomenon is typically seen 30 minutes to 4 hours after soft 8 hours depending on the particular combination of MPS and contact lens material. The intense appearance of SICS may indicate a solution induced corneal toxicity reaction; however, the lack of symptoms and the fact that the reaction lasts on average only a few hours is markedly different from a true toxicity reaction which is symptomatic and can take days to resolve. Concomitant signs such as limbal or bulbar hyperemia and corneal infiltrates are also absent. The three historical mechanisms mentioned

Dendritic ulcer

However, new evidence challenges the previously held view that corneal staining is caused by surface ingress around cells, surface pooling, and uptake by dead or damaged cells. Recent research has demonstrated that fluorescein molecules c an e nter a nd leave he al t hy and intact epithelial cells that concurrently demonstrate mitotic activity, indicating that the cellular metabolic activity remains normal despite cells being fluorescein “stained”. Furthermore, daughter cells that contain fluorescein demonstrate healthy functioning. Lastly, there is evidence of


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earlier do not explain SICS. Research has shown that MPS containing PHMB (polyhexamethylene biguanide) interact with fluorescein and the ocular surface leading to benign transient corneal hyperfluorescence (SICS) observed in MPS users. SICS can be dramatically reduced by applying a drop of rewetting solution

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containing carboxymethelcellulose.

Topical administration of fluorescein for the evaluation of corneal abrasions, ulcers, dry

C 0 and tear break Mup time 60(TBUT). South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

eye, the nasolacrimal system, epithelial defects, contact lens fitting, Seidel’s sign,

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The cobalt blue filter of the slit lamp is used and the defects are outlined in vivid green fluorescence. Using a golden yellow barrier filter (Wratten #12) over the observation system of the slit lamp will greatly enhance the visibility of the stained areas, especially on the conjunctiva. Good clinical practice when using the

fluorescein, has a molecular weight of 710 and is less readily absorbed by the soft lens material, making it more useful in fitting and evaluating soft and hybrid contact lenses. It is paler and yellow-brown in colour and staining characteristics are similar to those of fluorescein sodium, except that it will stain devitalized tissue. Fluorexon is vulnerable to bacterial contamination, dye dictates that the TBUT is evaluated supporting bacterial growth for longer immediately after instillation of micro than a comparable fluorescein sodium quantities of the dye; however, the ISO LESO GREEN ISO LESO YELLOW solution. It will stain the soft lens if it remains presence of the dye in the tear film can C 90 C 0 in contact with the lens for more than a M 40 It is therefore M 60 obscure surface defects. Y 100 Y 100 few minutes; however repeated rinsing recommended that the ocular surfaceK is 0 K 45 with saline will remove the dye from the evaluated once the dye has diffused from R 4 R 245 lens. Fluorexon is not recommended for use G 81 surface afterGa 130 the tear film to the ocular B 41 B 32 in highly hydrated soft lenses with a water few minutes (usually 3-4 minutes). content of 60% or higher. Significant dye can be absorbed in these lenses leading Minims Fluoroscein Sodium to lens discoloration. M i n i m s F l u o ro s c e i n S o d i u m 2 % (Bausch+Lomb), schedule 1.

c. Rose Bengal

Minims Fluoroscein Sodium

b. Fluorexon Fluorescein sodium can penetrate into soft contact lenses, discolouring the lenses and causing cosmetic problems. The boundary between the lens and the tears is obscured, precluding the use of fluorescein in soft contact lens fitting. Fluorexon, a molecule similar to

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Rose Bengal is a derivative of fluorescein. Both dyes are hydroxyxanthines. When viewed with white light, tissues stained with rose Bengal display a vivid pink or magenta colour. It is formulated as a 1% solution in the form of a sterile impregnated filter paper strip. Rose Bengal is a photoreactive compound. In the presence of 550nm light and oxygen, a singlet oxygen molecule is generated. This can inactivate enzymes and damage single stranded DNA and cell membranes. Rose Bengal is cytotoxic, and can kill microorganisms including herpes simplex-1 virus (HSV-1) and protozoa. It stains not only dead or dying cells as previously thought, but actually stains normal healthy living cells as well. The dye localizes primarily in cellular nuclei and, to a lesser degree, in other organelles.


additive. It is available as a 1% individually packaged filter paper strip.

Rose Bengal staining

How then do we explain its selective staining in dry eye or Sjögren’s syndrome? It turns out that rose Bengal is blocked from staining the ocular surface where molecules such as mucins, albumin or even artificial tear compounds such as carboxymethylcellulose are present. Rose Bengal penetrates the ocular surface in areas where there are breaks in the tear film integrity or a dysfunction i n t h e produc tion o f t he tear f ilm components. Rose Bengal can therefore not be termed a “vital stain”. Lastly, it is widely known that patient discomfort, particularly stinging on instillation which can become severe, is often a deterrent from using rose Bengal. It will stain skin, clothing and contact lenses. Due to its antiviral and antibacterial properties, the use of rose Bengal may cause a further dilemma if a culture is needed for diagnosis. Rose Bengal is difficult to obtain in SA.

d. Lissamine green Lissamine green B has been known by a variety of names: Wool Green S, Food Green, Acid Green S, Fast Light Green, Pontacyl Green S, Cyanol Green B, Calcoid Green S extra, and Pyronin G. Unlike the hydroxyxanthines previously discussed, lissamine green is classified as a phenyl methane dye. It is widely used as a nonophthalmic drug and cosmetic food


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Lissamine green staining

Lissamine green preferentially stains membrane damaged or devitalized cells localized in the cell nucleus. It does not stain healthy, proliferating ocular surface cells and has a minimal effect on cell viability. It has no carcinogenic or cellular toxicity properties. There is no stinging or discomfort with topical administration. In red eyes, due to the contrast, the visibility of the dye is enhanced, quite unlike the pink colour of rose Bengal which may be somewhat masked. The vital dyes (fluorescein or fluorexon) and lissamine green complement each other with the fluorescein staining between the devitalized cells indicating areas of greater permeability and the lissamine green staining the devitalized cells which then appear particularly clearly on the conjunctiva. The use of these vital dyes greatly enhances the diagnostic ability of the eye care profession.

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B. Topical Anaesthetics Karl Koller is widely credited with the discovery of local anaesthesia. In 1884 he instilled a drop of cocaine solution into the eye of a frog and observed that the frog’s


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The duration of action is proportional to the time the anaesthetic is in contact with the neural tissue and any substance that can prolong this will prolong the period of anaesthesia.

Topical ophthalmic anaesthetics available in South Africa Amethocaine HCl 1.0%, Tetracaine HCl 0.5% - 0.50–1.0% (B&L Minims, Smith & Nephew) - 0.5% Covostet® (Covan) Oxybuprocaine HCl, Benoxinate HCl 0.4% - 0.4% (B&L Minims) ISO LESO GREEN

- 0.4% Novesin® Wander (Restan) C 90 Proxymetacaine HCl 0.5% M 40

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In clinical practice, vasoconstrictors help to localize the anaesthetic at the desired site and also slow the absorption into the systemic circulation which then reduces the potential for systemic toxicity. in current clinical use have ISO LESOAnaesthetics YELLOW relatively low systemic and ocular toxicity. C 0 M 60 Compared with cocaine, they do not alter Y 100 pupil size or accommodation, making K 0 them ideal for use in ocular procedures R 245 G 130 s u ch as to n o me t r y, sut ure re mova l , B 32 gonioscopy, and foreign body removal.

cornea could be touched. He then tested the drug on his own eye and observed that his cornea was devoid of sensation. He also noticed that his palpebral aperture widened, his accommodation was affected, and his pupil dilated. Within a year of Koller’s discovery, cocaine was widely used in ophthalmic practice until its success was dampened by reports of both acute and chronic adverse effects due to local and systemic toxicity. This resulted in intense efforts to develop an anaesthetic with a more favourable therapeutic index. Local anaesthetics prevent both the generation and conduction of nerve impulses. The main site of action appears to be the cell membrane where they block the transient increase in membrane permeability to sodium ions. Following application, the anaesthetic crosses the cell membrane in the uncharged (lipid soluble) form, and at the site of action the charged form binds to the receptor. 14

When used in recommended dosages, s eve re lo ca l re a ct io n s to to p ica l anaesthetics are exceedingly rare with Clinical pearls - R epeated instillation of topical anaesthetics retard wound healing. - T opical anaesthetics increase the cornea’s permeability to other drugs. - T emporary occlusion of the canaliculi by digital pressure minimises the risk of systemic absorption.

Maximum dose of topical anaesthetics - C ocaine – 20mg or 5 drops to each eye of the 4% solution. - T etracaine – 5mg or 7 drops to each eye of the 0.5% solution. - P roparacaine – 10mg or about 14 drops to each eye of the 0.5% solution.


systemic reactions even more uncommon.

and tear film instability associated with

In general, patients who are particularly

decreased reflex tearing, infrequent

susceptible to the development of adverse

blinking, and increased tear evaporation.

reactions include those with:

It is usually mild and of no clinical

- known drug allergies

significance, but occasionally it can be

- asthma

extensive enough to reduce acuity to 6/24

- cardiovascular disease

or 6/60. In its most severe form it may be

- liver disease

characterized by a diffuse necrotizing

- hyperthyroidism

epithelial keratitis with filament formation,

- the elderly, debilitated and infants.

epithelial and stromal edema, folds in

Local toxicity includes relatively minor allergic or toxic involvement of the cornea, conjunctiva, or lids. The usual clinical presentation is that of a mild blepharoconjunctivitis characterized by conjunctival hyperaemia and chemosis, swelling of the lids, lacrimation, and itching.

Decemet’s membrane, and conjunctival hyperaemia (1 in 1000 patients). Treatment consists of lubrication in milder cases with more severe cases requiring treatment similar to that of corneal abrasions with pressure patches, topical antibiotics, and cycloplegics.

The signs and symptoms usually appear

Topical ocular anaesthetics are rapidly

5 to 10 minutes after the instillation of the

absorbed into the systemic circulation and

anaesthetic. Treatment consists of topical

their blood levels rise almost as rapidly it

decongestants and cold compresses. A

does after an intravenous injection. The

record of the reaction should be kept in

mechanisms listed below are implicated in

the patient’s chart to avoid using the same

this rapid absorption.

anaesthetic during future visits. In general, most of the serious ocular or systemic side effects from local anaesthesia have been associated with the use of cocaine, anaesthesia for infiltration, regional nerve block, or have developed as a result of prolonged use by means of self medication. Long-term impairment or loss of corneal sensory innervation (trigeminal nerve) is responsible for neurotrophic keratopathies including corneal epithelial

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defects, ulcers, melting, and perforation.

1. Too large a dose of the anaesthetic. 2. High absorption of the drug in patients with marked conjunctival hyperaemia. 3. Slow drug detoxification in patients with liver disease. 4. Slow elimination of the drug in patients with kidney disease. Toxic effects may involve the central nervous system (CNS), cardiovascular system, or respiratory system. Central nervous system (CNS) toxicity appears initially as stimulation

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and may manifest itself clinically as

However, in some older individuals (50+)

nervousness, tremors, or convulsions. Central

a localized or diffuse desquamation of

nervous system depression (CNS), observed

the corneal epithelium becomes evident,

clinically as a loss of consciousness and

C 90 Crespiration, 0 usually follows. depression of instillation of the anaesthetic. The epithelial T h e earliest signs of cardiovascular M 40 M hypertension, 60 tachycardia, reaction probably results from exposure involvement are South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 frequently 5 to 30 minutes after the

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and, occasionally, cardiac arrhythmias. Late cardiovascular signs are hypotension, absent pulse, and a weak or absent heartbeat. The cardiovascular effects can develop simultaneously with CNS depression, or they may develop alone. If allowed to continue, cardiac depression and the resultant peripheral vasolidation a re fo l l owe d by re s p i ra to r y fa i l u re . Fortunately, the liver metabolizes large doses of local anaesthetics rapidly and ISO LESO GREEN ISO LESO YELLOW CNS depression or stimulation is short lived. C 90should therefore C 0 Management objectives M 40 M 60 focus on temporaryY respiratory and 100 Y 100 K 45 K 0 cardiovascular support. R G

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Contraindications for topical anaesthetics 1. H ypersensitivity to the drug or preservative. 2. L iver disease: anaesthetics containing an amide linkage are primarily metabolized by the liver. 3. C oncomitant medications such as anticholinesterase drugs (Mestinon®, Antilirium®) can be problematic with anaesthetics containing an ester linkage. 4. D ry eye testing due to reduced reflex secretions, disrupted epithelial microvilli, and decreased mucus adherence lowering TBUT. 5. P erforating ocular injury; anaesthetics may cause endothelial toxicity and irreversible corneal edema. 6. C ultures, due to antibacterial properties of the preservative and toxicity of the anaesthetic to micro-organisms. 7. S elf administration by patients - severe corneal lesions and permanent reduction of visual acuity can result.

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Neurotrophic keratopathy

Ester type a. A methocaine or tetracaine HCl 1.0% or 0.5% (Covostet® by Covan), schedule 4 Bausch & Lomb Minims schedule 4 The onset of action of this anaesthetic is 9 to 20 seconds and the duration of anaesthesia is 10 to 20 minutes. Moderate stinging or burning accompanies instillation and lasts for 20 to 30 seconds.Amethocaine (tetracaine) produces a greater corneal comprise than proparacaine. It does not cause pupil dilation and is ideally suited for minor corneal and conjunctival procedures, foreign body removal, tonometry, and gonioscopy in cases of suspected narrow angle glaucoma.


Amethocaine (tetracaine) is metabolized to aminobenzoic acid which inhibits the action of sulphonamides.

Minims Tetracaine

substantial bactericidal properties, making the combination ideal for use in clinical practice. It causes less corneal compromise than amethocaine (tetracaine) and can be safely used in patients with allergies to amethocaine (tetracaine). We have used Novesin® in our clinic for many years without any complications.

Indications for pupil dilation 1. Visual acuity not correctable to 20/20 2. Flashes and floaters

Minims Tetracaine

3. Visual field loss

Minims Tetracaine (Amethocaine) 1.0% (Bausch+Lomb), schedule 4

b. Oxybuprocaine or benoxinate HCl 0.4% (Novesin Wander® by Novartis), schedule 4 Bausch & Lomb Minims schedule 4

4. Cataract or other media opacities 5. Diabetes 6. Myopia > 6.00D 7. Ocular contusion injury 8. Family history of retinal disease 9. Transient vision loss 10. APD (Marcus Gunn pupil) 11. Elevated IOP 12. Unexplained headaches 13. History of metastatic tumours 14. Unexplained ocular pain or redness 15. History of drugs with known toxicity to lens, retina or optic nerve 16. Miotic pupils

Novesin Wander®

ISO LESO GREEN

17. Nystagmus or unsteady fixation

C M Y

19. Any symptoms suggesting posterior segment involvement

The onset of action is 6 to 20 seconds and the duration of anaesthesia is around 15 minutes. Little conjunctival irritation and hyperaemia occurs and benoxinate has no effect on the pupil. Benoxinate in solution with fluorescein has shown

90 40 100

ISO LESO YELLOW

18. History of lattice degeneration, retinal holes or retinal detachment

C 0 20. Macular degeneration M 60 South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

17

18

ISO LESO GREEN

ISO LESO YELLOW

C

90

C

0

M Y K

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M Y K

60 100 0

R G

4 81

R G

245 130

B

41

B

32



90 40 100

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19

Minims Oxyuprocaine

Minims Proxymetacaine (Bausch+Lomb), schedule 4

0.5%

Amide type a. Lignocaine or lidocaine HCl 2 – 4% in combination with fluorescein (Minims), schedule 4

Minims Oxyuprocaine

Minims Oxybuprocaine (Bausch+Lomb), schedule 4

0.4%

This anaesthetic is amide linked and can be used in patients with known sensitivity ISO LESO GREEN ISO LESO YELLOW to the ester linked anaesthetics. It exhibits C 90 or C 0 enhanced vasodilator action, resulting c. Proxymethacaine M 40 M 60 proparacaine YHCl 100 0.5% Y 100 in a shorter duration of action and rapid K 45 K 0 systemic absorption. (Ophthetic® or Minims), schedule 4 R 4 schedule 4 R 245 Bausch & Lomb Minims G

81

G

130

B

41

B

32

The onset of action is 6 to 20 seconds and the duration of anaesthesia is around 15 minutes. Proparacaine has a greater potency than amethocaine, but it does not penetrate into the cornea and conjunctiva as just as well as amethocaine does. It produces little discomfort or irritation upon instillation and is well tolerated by patients. Once opened, the solution must be refrigerated and discarded if discoloration is seen. Deep anaesthesia can be obtained by using one drop every 5 minutes till 5 to 7 drops have been administered. Proparacaine is not recommended for paediatric use or in the presence of severe inflammation.

Minims Proxymetacaine

Minims Proxymetacaine 20

Minims Lidocaine & Fluorescein

Minims Lidocaine & Fluorescein

M i n i m s L i d o c a i n e & F l u o re s c e i n , (Bausch+Lomb), schedule 4 Tetracaine (amethocaine) and oxybuprocaine (benoxinate) are thought to be safe in porphyria, whereas lidocaine should be avoided.

C. Mydriatics and cycloplegics The proper use of mydriatics enables the practitioner to identify and more accurately diagnose various anomalies of the eye that may otherwise go undetected. When considering the various clinical and legal factors that governs patient care, a comprehensive examination should include a dilated examination,


especially when the patient’s history,signs or symptoms seem to indicate that dilation is necessary. Failure to dilate could result in legal issues of negligence. If you prefer not to dilate, make sure the patient sees a practitioner that is capable and prepared to perform the examination – “when in doubt, send it out”. In rare clinical situations dilation of the pup il m ay be c ont rai ndi c ate d. However, if the patient’s history, signs or symptoms seem to indicate that dilation is necessary the practitioner should proceed with caution or refer the patient to a colleague with more experience to ensure proper patient care.

Contraindications for pupil dilation 1. Extremely narrow or closed anterior chamber angles or plateau iris. 2. Possible drug interactions. 3. Iris fixed IOL. 4. Subluxated IOL or crystalline lens. 5. History of angle closure glaucoma.

Van Herrick, Schaffer and Schwartz method Narrow vertical slit beam placed at temporal limbus just inside the corneoscleral junction. Depth of anterior chamber is compared to corneal thickness. - Grade 4: open angle, depth equal to corneal thickness or greater, angle incapable of closure. - Grade 3: depth ½ of corneal thickness, angle incapable of closure. - Grade 2: depth ¼ of corneal thickness, narrow angle - perform gonioscopy. - Grade 1: depth < ¼ of corneal thickness, dangerously narrow angle – perform a gonioscopy.

Van Herrick test, narrow angle

Dilation procedures should be done at the conclusion of the routine examination, which would include the following critical pre-dilation procedures: - visual acuity - anterior chamber angle evaluation - drug sensitivity history - tonometry.


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and Schwartz method and if it is grade 1 or 2, gonioscopy is indicated. With gonioscopy you need to see 100% of the trabecular meshwork in all four quadrants, i.e. a 2+ angle before dilating.

ISO LESO YELLOW

C 0 Goldmann 3 mirror M lens60 South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

The anterior chamber angle is easily estimated by using the Van Herrick,Schaffer

21

Gonioscopy provides the most definitive

When viewed gonioscopically, the

assessment of the anterior chamber

normal anterior chamber angle most

angle. The procedure allows direct

often appears narrower superiorly, widest

or indirect visualization of the anterior

inferiorly, and has a depth between the

chamber angle structures, indicating

two at the temporal and nasal aspects.

with greater accuracy the risk of angle

The major anatomical landmarks of the

closure associated with pupil dilation. The

angle are therefore used to evaluate and

most commonly employed techniques

document the entire 360 degrees of the

involve the use of the Goldmann 3 mirror

angle. A useful acronym to remember the

and Sussman or Posner gonio prisms,

structures is:

each prism allowing an indirect view of

“I can’t see this stuff”

ISO LESO GREEN

ISO LESO YELLOW

C

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0

M Y K

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M Y K

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4

R G

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B

32

the angle by reflection through a mirror.

General guidelinesG for 81 pupil B 41 dilation 1. Topical anaesthesia before instilling the mydriatic enhances corneal permeability of the mydriatic and reduces stinging.

1. Atropine sulphate 1% Atropine® (Covan) Minims (Bausch & Lomb, Smith & Nephew) Isopto-atropine ® 1% (Alcon)

2. The goal of dilation is a maximally dilated pupil. Minimally dilated pupils pose the risk of pupillary block glaucoma that is not present with maximal dilated pupils. However, maximal dilation is rarely achieved in clinical optomertic practice.

2. Homatropine hydrobromide 1-5% for cycloplegia and 0.25-0.5% as mydriatic Isopto-homatropine®2% (Alcon) Homatropine hydrobromide® (Smith& Nephew)

3. Manual nasolacrimal occlusion can minimise the nasolacrimal drainage of the drug and subsequent systemic absorption. 4. Combination of adrenergic and cholinergic agents (tropicamide and phenylephrine) can be used to achieve optimal dilation. 5. Multiple instillations of mydriatics are rarely required to achieve wide pupil dilation. However, in patients whose pupils are anticipated to dilate slowly (diabetics, darkly pigmented irides), 2 drops in rapid succession may potentiate the mydriatic response.

22

Mydriatics and cycloplegics available in South Africa

3. Cyclopentolate HCl 1.0% Cyclogel® 1% (Alcon) Minims cyclopentolate HCl 1% (Bausch & Lomb) 4. Tropicamide HCl 1% Mydriacyl® (Alcon) Mydriaticum® (Restan) Minims (Bausch & Lomb, Smith & Nephew) 5. Phenylephrine HCl® 10% (Covan) Minims (Bausch & Lomb, Smith & Nephew) 6. Cyclopentolate HCl in combination with Phenylephrine Cyclomydril® (Alcon)



90 40 100

ISO LESO YELLOW


23

Grade (Schaffer). Structures visible

Angular subtense (degrees)

No angle anatomy visible

0

0°

Only Schwalbe’s line visible

1

10° or less

Trabecular meshwork visible

2

10 to 20°

Narrow angle

Scleral spur visible

3

20 to 30°

Angle incapable of closure

Cilliary body band visible

4

30 to 45°

Angle incapable of closure

Visible angle anatomy

ISO LESO GREEN

ISO LESO YELLOW

B

B

Implications Closed angle Dangerously narrow angle

Ciliary body band, scleral spur, trabecular The University of Iowa has a great website C 90 C 0 meshwork, and Schwalbe’s line on gonioscopy featuring numerous videos M 40 M 60 Y 100 Y 100 of normal and abnormal angles. This is a K 45 K 0 must for any clinician and worth a visit R 4 R 245 (www.gonioscopy.org). G 81 G 130 41

32

a. Atropine sulphate, schedule 3 Angle structures

The results can be recorded for each of the four quadrants and the angle classified from the anterior to posterior structures (see insert). Also, remember to record the presence of pigment, iris processes, angle recession, and any other significant details for each quadrant. Dilate only if two or more structures are seen in all quadrants. Systemic reactions to atropine in

Isopto Atropine®

Atropine is the most potent mydriatic and cycloplegic currently available.

children - Diffuse cutaneous flush

Atropine contraindications

- Thirst

1. Hypersensitivity to belladonna alkaloids.

- Fever - Urinary retention

- Excitement and hallucinations

3. Children with Down’s syndrome, hyperactive papillary response (mydriatic and cycloplegic effects are overly prolonged).

- Convulsions

4. Pregnancy and lactation.

- Tachycardia - Somnolence

24

2. Open or closed angle glaucoma.


Depending on the concentration used, mydriasis can last up to 10 days and cycloplegia 7 to 12 days. Atropine binds to pigment, resulting in a prolonged effect in more heavily pigmented eyes attributed to the subsequent release of accumulated drug over time onto the muscarinic receptors of the iris and ciliary body. Since the elderly and children are more susceptible to anticholinergic toxicity, atropine should be used with caution in these patients. Atropine is indicated for cycloplegic refraction, particularly in younger actively accommodating children with suspected accommodative esotropia. It should never be used for cycloplegic refraction in adults, because other short-acting agents are as effective and the prolonged effect renders patients visually handicapped. Other clinical uses include: - Treatment of uveitis by relieving pain associated with the inflammatory process by relaxing the ciliary muscle, preventing posterior synechiae by dilating the pupil as well as reducing flare and cells in the anterior chamber. - Treatment of progressive myopia. - Treatment of amblyopia (drug penalisation). Atropine inhibits the actions of the neurotransmitter acetylcholine (ACh) on effector sites innervated by autonomic nerves and on smooth muscle cells that lack cholinergic autonomic innervation. The neurotransmitter at the effector cell junction, that is the pupil sphincter muscle and ciliary muscle, is ACh. These drugs block muscarinic receptor sites and are collectively known as anti-muscarinics, cholinergic antagonists, cholinergic


90 40 100

blocking agents, competitive antagonists to ACh or anticholinergics. In addition to mydriasis and cycloplegia, atropine also has other effects on the eye. Most notably the lacrimal gland also receives parasympathetic innervation, so tears are reduced and the lysozyme concentration is increased when antimuscarinic drugs are used. Other peripheral pharmacological actions of atropine are listed next: - Effects on cardiac smooth muscle, increased heart and pulse rate. - O ther smooth muscle effects: vasodilation and slowing of intestinal peristalsis. - Effects on exocrine glands: decreased bronchial, salivary gland and intestinal gland secretions; dry mouth is usually the first sign of toxicity. - Facial flushing and decreased sweating can also occur. - Increased intraocular pressure. Paralysis of the ciliary muscle allows increased blood supply to the iris, ciliary body, and the anterior choroid. Relaxation of the meridional fibres of the ciliary muscle causes partial collapse of the epichoroidal venous network, resulting in a reduced outflow of blood through the vorticose veins (uveoscleral outflow). Dilation of the intraocular capillaries increases permeability. The net result is a temporary increase in intraocular pressure. Central or systemic effects include: - S mall doses cause vagal excitation slowing the heart rate before the characteristic tachycardia or atropineinduced parasympathetic block. - Larger (toxic) doses cause more prominent excitation followed by restlessness, irritability, disorientation, hallucinations or delirium;

ISO LESO YELLOW


25

then depression, drowsiness and later coma.

concentration of atropine had very little effects

Medullary paralysis may cause death.

on accommodation and the pupil, no effect on the retina and near vision, but still reduced

a. A tropine sulphate recommended dosage

myopia progression by 50% (049 ± 0.63D & 0.41 ± 0.32mm). Although a 0.01% solution is

One drop of 1% solution results in mydriasis

not commercially available, Donald Tan and

within 15 to 20 minutes which reaches a

his group in Singapore now recommends the

maximum at 30 to 40 minutes, and recovers

use of 0.01% atropine (in combination with

in 3 to 4 days. Even with one application,

other non pharmacological treatments) in

partial cycloplegia is reached in 1 to 3

an effort to reduce the progression of myopia.

hours and full ciliary muscle recovery may

Although it is not clear what mechanism

ISO LESO GREEN

is responsible for the effects of atropine on

ISO LESO YELLOW

take 3 to 7 days. One drop of 1% solution

90 C 0 for 3 consecutive daysC results in mydriasis M

40

M

60

ocular growth, cycloplegia does not play a

Y 100 Y 100 role. Recent evidence indicates a possible and cycloplegia within 30 minutes, reaching K 45 K 0 a maximum on the 3rd day. Recovery of effect on the scleral fibroblasts. We may R 245 therefore soon see the introduction of a weak the pupil occurs withinR104 to 14 days, and G 81 G 130 B 32 solution of atropine specifically designed to accommodation at 7B to41 10 days. Most

patients can read from day 4 to 5.

treat progressive myopia.

Atropine use in the prevention b. Homatropine hydrobromide; Isopto-homatropine® 2% of myopia progression (Alcon), schedule 3 The ATOM (atropine in the treatment of myopia)1 & 2 studies have highlighted the effectiveness of atropine in preventing the progression of myopia. In the ATOM 1 study a 1% solution of atropine was used in one eye and a placebo in the other eye. This study showed a marked reduction in the progression of myopia in the eyes subjected to the 1% atropine at night over a two-year period. Subsequent follow up revealed that although a small rebound effect was seen after cessation of the treatment, the growth of the treated eyes were significantly less (placebo group -1.2 ± 0.69D & 0.38 ± 0.38mm and the atropine group -0.28 ± 0.92D & -0.02 ± 0.35mm) than the untreated eyes. Although significant adverse effects were limited to photophobia, lack of accommodation, and

26

Isopto Homatropine®

The maximum cycloplegia produced by atropine is rarely necessary for patients older than 6 years. Less powerful drugs may then be used when cycloplegic refraction is appropriate, as accommodation is less active than in very young patients.

allergic reactions, the ATOM 2 study tested the

Homatropine is a semi-synthetic alkaloid

efficacy of three lower doses of atropine. The

prepared from atropine. Homatropine has

0.01% (1 000 time weaker than the 1% solution)

a similar antimuscarinic action to atropine,


paralysing the sphincter pupillae and ciliary muscles. The maximum therapeutic dose

Cyclopentolate is an antimuscarinic competitive antagonist to ACh, producing

is 2mg, but it is seldom used as an oral medication. Homatropine is 1/10th as potent as atropine and is available in 1%, 2% and 5% concentrations for cycloplegia, and 0.25% to 0.50% concentrations for mydriasis. Mydriasis occurs within 15 minutes and is maximal within 30 to 40 minutes. Complete recovery of the pupil may take between 24 and 48 hours. Cycloplegia occurs within 15 minutes and is maximal between 45 to 90 minutes, with recovery within 24 hours. Side effects and contraindications are indistinguishable from those of atropine, except that it has a lower tendency to increase the intraocular pressure. Homatropine is used for cycloplegia in the older than 15 years age group. Due to its prolonged mydriatic and cycloplegic effect and relatively weak cycloplegic action, especially in darkly pigmented irides, homatropine is not a drug of choice for fundus examination or cycloplegic refraction. Its primary clinical usefulness is in the treatment of anterior uveitis where its effects are similar to that of atropine.

paralysis of the sphincter pupillae and ciliary muscles when instilled into the eye. It has superior cycloplegia to homatropine with faster onset and shorter duration. Cyclopentolate is available in a 0.5% to 1.0% solution. Cycloplegia commences almost simultaneously with mydriasis between 10 to 15 minutes after instillation, reaching a maximum between 30 to 60 minutes. Recovery of the pupil occurs after 4 to 12 hours without a miotic and reading is possible after 3 to 4 hours. The miotic of choice is 0.25% to 0.50% physostigmine sulphate, which achieves miosis within 30 to 40 minutes.

c. C yclopentolate HCl (Cyclogel® 1%, Alcon), schedule 3 Bausch & Lomb Minims schedule 3

ISO LESO GREEN C 90 Cyclogyl M 40 Y 100 ®

Cyclopentolate is the cycloplegic of choice for routine cycloplegic refractions in nearly all age groups, and especially in infants and young children. It is also useful in the treatment of anterior uveitis to prevent posterior synechiae and to rest painful sphincter and ciliary muscles as well as to relieve pain in corneal abrasions or trauma. Due to increased susceptibility to the side effects of cyclopentolate in infants, young children, and children with spastic paralysis or brain damage, use of concentrations higher than 0.5% is not recommended. Ocular adverse effects: - Transient stinging on instillation due to acid pH (pH 5). - H yperemia (rarely), discomfort, facial rash accompanied by stringy white mucus discharge and blurred vision can occur. - Increased intra-ocular pressure is not c om m on , b ut ma y o ccur w it h in 60 minutes reaching maximum in 2 hours with recovery within 4 hours. - caution is advised when using cyclopentolate

ISO LESO YELLOW


27

Ophthalmologists’

No.1

OMEGA-3

prescribed eye health supplement6 ISO LESO GREEN

ISO LESO YELLOW

C

90

C

0

M Y K

40 100 45

M Y K

60 100 0

R G

4 81

R G

245 130

B

41

B

32

Anti-inflammatory properties and promotes a healthy ocular surface1,2

WITH

Omega-3’s

Lubricant eye drops

ARTIFICIAL TEAR DROP

Temporary relief of burning and irritation

References: 1. Graham, RH. There’s nothing fishy about omega-3 fatty acids for dry eye syndrome. Medscape Ophthalmology. Available at http://www.medscape.com/viewarticle/707984_2. [Accessed January 13, 2014]. 2. Omega-3 Fatty Acids. Available at: http://umm.edu/health/medical/altmed/supplement/omega3-fatty-acids. [Accessed May 26, 2014]. 3. Liposic Product Monograph. Data on file, Bausch&Lomb Inc. 4. Mastromarino A, et al. The effect of medium chain triglycerides – containing tear substitute on the dynamics of lipid layer interference patterns (DLIP) in dry eye patients. Invest Ophthalmol Vis Sci. 2005;46:E-Abstract 2043. 5. Wang I.J., et al. A comparison of the effect of carbomer-, cellulose-, and mineral oil-based artificial tear formulations. Eur J Ophthalmol. 2007; 17(2):151-159 6. Impact Rx. Script data – May 2015. Scheduling status: S0 Proprietary name and dosage form: Bausch & Lomb Moisture Drops eye drops. Composition: Each ml contains: Potassium chloride 3,5 mg and sodium chloride 4,0 mg, benzalkonium chloride 0,01 % m/v (preservative). Pharmacological classification: A34 other. Indications: For the temporary relief of burning and irritation caused by dryness of the eye. Registration number: 28/34/0013. Ocuvite Complete soft gel capsules. Composition: Each soft gel capsule contains fish oil rich in DHA 507,7 mg: of which DHA 180 mg and total omega-3 300mg, Lutein 5 mg, zeaxanthin 1 mg, vitamin C 90 mg, vitamin E 15 mg, zinc 7,5 mg.

28


MANAGE DRY EYE by recommending complete relief and extra protection

TEAR SUBSTITUTE

Ongoing relief by replenishing and locking in moisture in all 3 layers of the tear film3-5

NEW Eye gel


90 40 100

ISO LESO YELLOW


Scheduling status: S0 Proprietary name and dosage form: Liposic Eye Gel. Composition: Each 1 g contains: 2 mg carbomer, triglycerides – medium chain, sorbitol, sodium hydroxide and purified water, Cetrimide 0,01 % m/m (preservative). Pharmacological classification: A 15.4 Ophthalmic preparations - Other. Indications: Substitution of tear fluid for management of dry eye conditions such as symptomatic treatment of keratoconjunctivitis sicca. Registration number: 37/15.4/0224. © 2003 Bausch & Lomb Incorporated. ®/™ denote trademarks of Bausch & Lomb Incorporated. Applicant: iNova Pharmaceuticals (Pty) Ltd. Reg. No.: 1952/001640/07. 15E Riley Road, Bedfordview, Gauteng, South Africa, 2008. Tel: +27 11 087 0000 www.inovapharma.co.za. Marketed by: Bausch & Lomb (SA) (Pty) Ltd. Reg. No.: 1996/003931/0ww7. 15E Riley Road, Bedfordview, Gauteng, South Africa, 2008. Tel: +27 11 087 0000 www.bausch.co.za BL98/15

29

-

-

-

-

in patients with glaucoma.Systemic Minims Tropicamide adverse effects: Toxicity is dose related and evolves in a similar way as that of atropine. U nlike atropine, cyclopentolate causes more central nervous system effects. Central nervous system effects are particularly common in children. C NS effects are characterized by Minims Tropicamide cerebellar dysfunction, and visual as well as tactile hallucinations. These Minims Tropicamide 1% (Bausch+Lomb), ISO LESO GREEN ISO LESO YELLOW can include drowsiness, ataxia, schedule 3 90 C 0 incoherent speech,C restlessness, and M 40 M 60 emotional disturbances. Y 100 Y 100 K 45 K 0 All reactions usually subside within 2 R 4 hours in adults and 4 to 6 hours Rin 245 G 81 G 130 children without permanent sequelae. B 41 B 32 P eripheral and systemic side effects that are common with atropine, such as flushing, dryness of the skin or mucous membranes, increased temperature, pulse, blood pressure and respiration, do not occur. Mydriacyl ®

Minims Cyclopentolate

Minims Cyclopentolate

Minims Cyclopentolate (Bausch+Lomb), schedule 3

HCI

d. T ropicamide HCl (Mydriacyl®1%, Alcon), schedule 3 Bausch & Lomb Minims schedule 3 30

1%

Tropicamide is an antimuscarinic competitive antagonist to ACh. It has a fast onset and short duration of action making it the mydriatic of choice for routine ophthalmoscopy. It is available as a 0.5% solution for mydriasis and 1.0% solution for cycloplegia. Mydriasis occurs within 15 minutes with recovery of the pupil within 8 to 9 hours. Using the 1% solution, two drops spaced 5 minutes apart will achieve cycloplegia within 30 minutes with recovery within 6 hours. Reading is possible within 2 to 4 hours. Unlike atropine, homatropine and c yc l ope n t o l a t e , p up il d il a t io n w it h tropicamide appears to be less dependent on iris pigmentation.


The miotic of choice is 0.25 to 0.50% physostigmine sulphate; it is, however, not available in South Africa. Side effects: - Transient stinging on instillation. - Can raise intraocular pressure in patients with glaucoma, which is clinically insignificant in most patients since it subsides in several hours without damaging the optic nerve. However, pressure increase can be significant (5 to 10mmHg) in open angle

glaucoma, especially in eyes receiving miotic therapy. It is therefore prudent to re-check IOP following dilation with tropicamide. Systemic effects are rare and since tropicamide is devoid of vasopressor effects, it is the safest drug to use in patients with systemic hypertension, angina, or other cardiovascular disease. Atropine, homatropine, cyclopentolate and tropicamide are considered safe in porphyria.

How to break an acute angle closure attack! 1. R educe the IOP with oral medication. Administer an oral carbonic anhydrase inhibitor, 2 x 250mg acetazolamide (Diamox®) tablets. - U se caution in dehydrated patients, those with congestive heart failure, or patients taking potassium depleting drugs. - P otential side effects include nausea, vomiting, severe headache, and disorientation or confusion. 2. N ext, administer an oral hyperosmotic agent (glycerin) in a dose of 1 to 1.5g per kg, chilled or on ice (juice) over a 5 minute period to avoid vomiting and nausea. In recent years this has become controversial and is often omitted in the treatment regimen. - U se oral isosorbide in diabetics as it causes less nausea and does not induce hypoglycaemia. The dose is 1.0 to 1.3g per kg. - H yperosmotic agents act as systemic dehydrating agents and are essential for reducing IOP. Expect significant results within 60 to 90 minutes lasting up to 6 hours. 3. Add topical agents. - S tart with a topical beta-blocker, 0.5% timolol (Timoptol®). Two drops within 60 minutes reduces the IOP to a level which will permit pilocarpine to activate the iris sphincter terminating the attack. - B eta-blockers act predominantly by decreasing the production of aqueous, and are contraindicated in patients with asthma, COPD, bradycardia, heart block, cardiac failure as well as in children and infants. 4. Apraclonidine (Iopidine®) 0.5 to 1% can be used if beta-blockers are contraindicated. It furthermore decreases aqueous production with little or no effect on outflow. It is contraindicated in patients using MAO inhibitors, and in patients with severe cardiovascular disease or hypertension.

ISO LESO GREEN

ISO LESO YELLOW

5. Add 2% pilocarpine; stronger solutions can cause shallowing of the angle. - P ilocarpine is ineffective in producing miosis when the IOP is over 50mmHg due to ischaemia of the iris sphincter.

C 90 C 0 - Wait till IOP reduces with orals and other topicals before administering 1 drop of 2% pilocarpine (15 minutes apart to eliminate toxicity). M 40the angle, IOP and pupil.When the attack is over, arrange M for60 6. E valuate laser iridotomy. South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100

31

e. P henylephrine HCl® (Covan), schedule 3

Other medical uses of phenylephrine

Bausch & Lomb Minims schedule 3

1. Aid in breaking posterior synechiae. 2. Used in treatment of confirmed open angle glaucoma, with echothiophate, prevents formation of iris cysts, reduces aqueous production and lowers IOP.

ISO LESO GREEN

Phenylephrine®

C

90

M Y K

40 100 45

3. Used as a diagnostic test for Horner’s syndrome (1% solution ISO LESO YELLOW can markedly dilate the pupil with postganglionic sympathetic C 0 denervation). M 60 Y K

100 0

4 R 245 Phenylephrine is a Rsympathomimetic G 81 G 130 amine structurally similar B 41 to epinephrine. B 32 Following topical application it contracts the iris dilator muscle and smooth muscle of the conjunctival arterioles causing pupillary dilation and blanching of the conjunctiva respectively. Müeller’s muscle of the upper lid is stimulated, which widens the palpebral fissure. The IOP may decrease in normal eyes, as well as in eyes with open angle glaucoma. It appears that phenylephrinealters the blood aqueous barrier, affecting the aqueous production and flow. It does not seem to affect macular blood flow in humans. The effect of phenylephrine (and to a lesser extent parasympathetic drugs) is poor in pigmented irides, diabetes and in patients over 60 years of age due to arteriosclerosis in the radial vessels which resists the pull of the weak dilator pupillae.

One drop of a 10% solution achieves mydriasis in 30 to 40 minutes and the pupil recovers after 6 to 7 hours. The miotic of choice is pilocarpine nitrate 2% solution. 32

Ocular adverse effects: - Transient pain, lacrimation and keratitis. - Allergic dermatoconjunctivitis, scalded appearance around the eye. - Pigmented aqueous floaters released from the pigment epithelium of the iris 30 to 40 minutes following instillation of the 2.5 to 10% solution. - I n pat i e n t s o l d e r t h a n 5 0 y e a rs, rebound miosis can occur the day after administration. - R ebound conjunctival congestion is common with chronic use of low concentrations for ocular vasoconstriction. - C onjunctival hypoxia due to the reduction of blood flow caused by vasoconstriction effects. Systemic adverse effects: - Systemic hypertension, age and physical status determine patient response to topical phenylephrine. Patients with insulin dependent diabetes, cardiac disease, severe arteriosclerotic changes or thyrotoxicosis may demonstrate a dramatic increase in systolic and diastolic blood pressure in response to topical phenylephrine. Similarly,



90 40 100

ISO LESO YELLOW


33

individuals with orthostatic hypotension respond to low concentrations of phenylephrine with marked blood pressure elevations. -S evere occipital headaches, subarachnoid haemorrhage, ventricular arrhythmias, tachycardia, reflex bradycardia, ruptured aneurysms, and blanching of the skin can occur.

Minims Phenylephrine ISO LESO GREEN

1. U se with caution in patients with cardiac disease, hypotension, hypertension, aneurysms, insulindependent diabetes mellitus, and advanced arteriosclerosis. 2. Contraindicated in neonates!

C

90

C

0

M Y K

40 100 45

M Y K

60 100 0

R G

4 81

R G

245 130

B

41

B

32

Minims Phenylephrine (Bausch+Lomb), schedule 1

HCI

Phenylephrine is considered safe in porphyria.

f. C ombination drugs: Cyclomydril TM 0.2% cyclopentolate, 1% phenylephrine (Alcon), schedule 3

34

phenylephrine

3. D o not use in patients taking MAO inhibitors, TCAs, reserpine, ISO LESO YELLOW guanethidine, or methyldopa.

Minims Phenylephrine

Cyclomydril®

Contraindications for topical

10%

4. C oncomitant use with atropine is contraindicated as tachycardia and hypertension can occur. 5. O nly the 2.5% solution is indicated for infants, young children, and the elderly.

Cyclomydril® (cyclopentolate hydrochloride and phenylephrine hydrochloride ophthalmic solution) is a mydriatic prepared as a sterile topical ophthalmic solution. It contains cyclopentolate hydrochloride 0.2% and phenylephrine hydrochloride 1%. Cyclopentolate hydrochloride is an anticholinergic drug and phenylephrine hydrochloride is an adrenergic drug. This combination induces mydriasis which is greater than that of either drug alone at its respective concentration. The concentrations of cyclopentolate hydrochloride and phenylephrine hydrochloride have been selected to induce mydriasis with little accompanying cycloplegia. Heavily pigmented irides may require more doses than lightly pigmented irides. The following ocular and non-ocular adve r s e e x p e rie n ce s h a v e b e e n associated with the use of Cyclomydril ®: increased intraocular pressure, burning/


Predisposing factors that increase the risk of severe systemic reactions with cycloplegics & mydriatics (Hopkins & Lyle, 1977) - Prior use of topical anaesthetic. - C onjunctival disruption and / or bleeding. - H igh blood pressure, heart disease or thyrotoxicosis. - Multiple applications. - Concomitant medication. Cyclomydril® (cyclopentolate hydrochloride and phenylephrine hydrochloride ophthalmic solution) is a mydriatic prepared as a sterile topical ophthalmic solution. It contains cyclopentolate hydrochloride 0.2% and phenylephrine hydrochloride 1%. Cyclopentolate hydrochloride is an anticholinergic drug and phenylephrine hydrochloride is an adrenergic drug. This combination induces mydriasis which is greater than that of either drug alone at its respective concentration. The concentrations of cyclopentolate hydrochloride and phenylephrine hydrochloride have been selected to induce mydriasis with little accompanying cycloplegia. Heavily pigmented irides may require more doses than lightly pigmented irides. The following ocular and non-ocular adv ers e exp er ience s have b e e n associated with the use of Cyclomydril ®: increased intraocular pressure, burning/ irritation upon instillation, photophobia, blurred vision, and superficial punctate keratitis.


90 40 100

in children. These disturbances include ataxia, incoherent speech, restlessness, hallucinations, hyperactivity, seizures, disorientation as to time and place, and failure to recognize people. This drug produces reactions similar to those of other adrenergic and anticholinergic dr u gs ; how e v e r, t h e ce n t ra l n e rv o us system manifestations as noted above are most common. Other manifestations of adrenergic and anticholinergic topical ophthalmic drugs include tachycardia, hyperpyrexia, hypertension, vasodilation, urinary retention, diminished gastrointestinal motility, and decreased secretions by the salivary and sweat glands and also secretion decrease in the pharynx, bronchi and nasal passages. Severe manifestations of toxicity include coma, medullary paralysis, and even death.

Miotics available in South Africa 1. Pilocarpine General systemic effects of miotics - Headache - Brow ache - Marked salivation - Profuse perspiration - Nausea - Vomiting - Bronchospasm

ISO LESO YELLOW

- Pulmonary edema

- Systemic hypotension - Bradycardia

- General muscular weakness

C 0 - Respiratory paralysis M 60 South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

The use of cyclopentolate hydrochloride has been associated with psychotic reactions and behavioural disturbances

- Diarrhoea, abdominal pain

35

Cyclomydril® is considered safe in porphyria.

fibres. The duration of action is limited to more or less 12 hours. In contrast, the organophosphates, which also act in this manner, act for prolonged periods (from days to weeks) and are known as irreversible anticholinesterase drugs.

D. Miotics

Miotics are used to constrict the pupil. They are instilled into the eye after mydriatic examination when necessary or on Miosis occurs within 5 to 10 minutes, request by younger individuals. They are reaching a maximum at 30 minutes, also used in the treatment of glaucoma. and can last for up to 12 hours with the Miotics are either parasympathomimetic 0.5% solution. The 0.5%, and in particular or direct-acting cholinergic drugs the 0.25%, are the most commonly ISO LESOagonist GREEN ISO LESO YELLOW (having similar effects to ACh) such as used solutions. Physostigmine produces C 90 C 0 M 40 M 60 prolonged stimulation of the ciliary and pilocarpine or indirect-acting, reversible Y 100 Y 100 anticholinesterase drugs (increasing the sphincter pupillae muscles resulting in K 45 K 0 available ACh) such as physostigmine. spasm of accommodation and miosis R G

4 81

R G

245 130

B

41

B

32

a. P hysostigmine (not available in SA) The maximum therapeutic dose is 1.2mg. Physostigmine drops are available in 0.25 to 1% solutions. The solution is sensitive to light and air and exposure causes oxidation making it pink. Physostigmine is a reversible anticholinesterase drug. The enzyme terminating the action of the neurotransmitter acetylcholine is inhibited with the result that ACh is allowed to accumulate at the sites of cholinergic transmission, leading to continuous stimulation of the cholinergic

respectively. Conjunctival hyperaemia also occurs due to the peripheral vasodilatory effects of this miotic. The drug passes through the palpebral conjunctiva, stimulating the palpebral orbicularis oculi muscle which leads to lid myokymia, even when using the 0.25% solution. Physostigmine also lowers the intraocular pressure by the following mechanism:

Ocular side effects of miotics - A ccommodative spasm (under 40-year age group) - Miosis - Follicular conjunctivitis

Which miotic is used with which mydriaticum? - P hysostigmine is recommended with tropicamide (Mydriacyl®) and not with phenylephrine due to excessive pain from stimulated sphincter pupillae pulling against the stimulated dilator pupillae. - P ilocarpine is the myotic of choice with phenylephrine.

36

- P upillary block with secondary glaucoma - Band keratopathy - Allergic blepharoconjunctivitis - Retinal detachment - Conjunctival hyperaemia - Lid myokymia - Anterior subcapsular cataract - Iris cyst formation


- Contraction of the ciliary muscle

as dry mouth, constipation and impaired

results in constriction of the intraocular

vision, pilocarpine is used today almost

arteries and dilation of the vorticose

exclusively as a miotic. Recently however,

veins, restricting the inflow of blood and

pilocarpine (Salgen®) has been used to

facilitating its outflow.

improve ocular dryness. Pilocarpine is

- Miosis opens the anterior chamber

a direct acting parasympathomimetic

angle, aiding in aqueous drainage

agent. Topically it is available in 0.5 to 5%

through the trabecular meshwork.

solutions with the 1% solution being the

- Mild dilation of the intraocular

most commonly used. Miosis occurs within

capillaries assists in the removal of

5 minutes and reaches a maximum effect

waste products from the eye.

in 10 minutes, lasting up to 6 hours. Strength

Ciliary muscle spasm, lid twitching, and discomfort are mild with the 0.25% solution and passes within 2 to 3 hours if no near

for strength it is only about half as powerful as physostigmine; therefore, the spasm of accommodation is not nearly as marked or

work is attempted. Instructions to limit

as painful as with physostigmine.

near work activities for 4 to 6 hours should

Pilocarpine affects the cardiovascular

be given to the patient to prevent this discomfort and spasm, especially when the 0.5% concentration is used. Systemically, physostigmine can slow the heart and pulse rate, increase peristalsis, salivary, bronchial and gastric secretions as well as dilate the peripheral blood vessels.

system, exocrine glands, and smooth muscle. The effects on the cardiovascular system are complex, but pilocarpine slows the heart and pulse rates, increases salivary, gastric, pancreatic, and respiratory mucus and also the lacrimal secretions. Marked sweating and flushing of the skin, constriction of the bronchioles,

b. Pilocarpine nitrate, schedule 3

and increased peristalsis can occur. Although

the

mechanism

by

which

pilocarpine reduces IOP is not clear, the most widely accepted explanation involves the direct stimulation of the longitudinal muscle of the ciliary body which, in turn, causes the scleral spur to widen the trabecular spaces and increase aqueous outflow. This response

ISO LESO GREEN Isopto Carpine®

declines with age due to the decline in

ciliary

muscle LESO mobility. YELLOW Because ISO

pilocarpine is absorbed by melanin, patients with brown irides usually require higher concentrations. Pilocarpine is used

C 90 C open 0 angle glaucoma to treat primary Previously used to counteract the common and in the treatment of angle closure M of 40 60 effects ganglion blocking agents such glaucoma. M South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 The maximum therapeutic dose is 12mg.

37

It is contraindicated in patients with cataracts, those who are under 40 years of age, have neovascular and/or uveitic glaucoma, retinal detachments, and asthma. Use with caution in porphyria.

ISO LESO GREEN

2. S elect an appropriate antibiotic to which the organism is sensitive.

4. E stablish adequate drug levels at the site of infection:

- frequent dosage strategy, never taper to below q.i.d.

- p rescribe treatment for an appropriate length of time.

ISO LESO YELLOW

We are constantly exposed to a variety of C 90 C 0 microorganisms, including bacteria, M 40 M 60 Y 100 Y 100 viruses, and fungi. InK most cases these 45 K 0 microorganisms do not produce infection R 4 R 245 because the skin and mucous membrane G 81 G 130 B 41 B 32 surfaces provide effective barriers against invasion. Some organisms can invade directly through these barriers, or can be introduced into the body through lesions from trauma or surgery. The immune system usually deals with them quite effectively. Conversely, some organisms possess special properties that allow them to overcome the immune system, or the patient’s immune system does not always function optimally thus allowing microorganisms that would not normally pose a problem to cause an infectious disease. Anti-infective preparations is a broad term which describes substances or agents, alone or in combination, which prevent or hinder infection, the latter being invasion of the body by pathogenic organisms and their subsequent multiplication in the body. Chemotherapy is the specific drug treatment for infections caused by the invasion and multiplication in the body of bacteria, fungi, viruses, protozoa, spirochaetes, rickettsia, and

38

1. E stablish an accurate clinical and laboratory diagnosis.

3. S elect the least toxic antibiotic drug.

2. Antibiotics Introduction

Guidelines for effective antibiotic therapy

5. A ugment drug therapy with physical procedures. worms. Chemotherapy also includes the treatment of cancer with anti-neoplastic agents. In this chapter I will deal with the most common topical chemotherapeutic antibacterial agents used in eye care as well as the bacteria commonly associated with eye infection. Before embarking on a treatment strategy it is wise to consider that the only clinical indication for the use of a topical antibiotic is treatment or prevention of bacterial infection, one of the least common entities encountered in clinical practice. Such infections are more common in children than adults. Prophylactic antibiotics are indicated where there is a significant risk of opportunistic infection with eye injuries. Red eyes are either infectious or inflammatory, and inflammation is by far the most common presentation. If the cornea is not compromised, and there is no mucopurulence, then a steroid or combination drug would be a more appropriate choice for the patient.


The new lens of choice. The 2-SpecTM Tangent DF 16.2mm Semi-Scleral Lens from The Contact Lens Laboratory of South AfricaTM offers the latest technology for semi-scleral lens fitting.

This locally produced, 8 lens diagnostic set is used to fit the following corneal conditions:

ISO

Keratoconus Keratoglobus Post Corneal Grafts and Refractive Surgery Medium, High or Irregular Astigmatism LESO GREEN ISO LESO Pellucid Marginal Degeneration Dry Eye

THE

YELLOW

C 90 C 0 CONTACT LENS M 40 M L60 AB OF SA INTERNATIONAL Lab Tel: (011) 326 0245 / Lab Mobile: 081 763 2256 / Lab Fax: 086 619 2503 Registered Contact Lens Manufacturers Email: [email protected] / Web: www.contactlenssa.co.za South African Guide to Topical Ophthalmic by Dirk Booysen 39 Y 100 Y Drugs 100

TM

defence mechanism that helps prevent pathogens from multiplying efficiently. Gram-positive Normal flora can become pathogens - Staphylococcus aureus in immune-compromised or debilitated patients. Viruses and parasites, while often - Staphylococcus epidermidis, most common organism present in asymptomatic individuals, are - Streptococcus pneumoniae, found not considered part of the normal flora. on transient basis Several studies have documented that - Corynebacterium diphtheriae, the normal flora resembles that of the more common in over 20-year age upper respiratory tract and eyelid skin. The group primary microbial organisms retrieved are - PropionibacteriumISO acnes, LESO GREEN ISO LESO YELLOW listed in the table. anaerobe from the skin also C 90 C 0 commonly found M 40 M 60 Almost any microbial organism can cause Normal flora of conjunctiva

Gram-negative

Y K

100 45

Y K

R G

4 81

R G

245 130

B

41

B

32

- Haemophilus influenzae - Escherichia coli

- Pseudomonas aeruginosa

The concept of resistance should still be considered, although, as eye care practitioners, the collective amount of antibiotics prescribed by the entire profession is negligible when compared with the utilization of oral antibiotics by primary care physicians. A study by Goldstein et al over a 5-year period showed that the resistance of especially Staphylococcus aureus to ciprofloxacin and ofloxacin had increased from 5% to 35%, but gram-negative bacteria continued to show good susceptibility. A greater degree of resistance was found in the gram-positive bacteria, especially S. aureus, than in the gram-negative bacteria. The most resistant bacteria were the streptococcal and coagulasenegative staphylococcal species. The normal conjunctiva, as with other mucous membranes, sustains a permanent fl ora o f ind ig eno u s b ac t e r i a. T he s e organisms constitute a protective host

40

100 0

infection. In immune-competent persons the primary causes of conjunctivitis are bacteria and viruses in children younger than 12 years of age, and viruses in adults and children older than 12 years. The primary bacterial pathogens are: - S taphylococcus aureus and staphylococcus epidermidis (grampositive). S.aureus is most commonly found in adults, with Moraxella catarrhalis also frequently isolated. - H aemophilus influenzae. - S treptococcus pneumoniae predominates in children (gram-negative). Adenovirus and herpes simplex are the most common viral causes. It is essential that in contact lens practice Pseudomonas aeruginosa infection should always be considered with a red eye. Although these organisms are everywhere, they rarely cause infection. As discussed previously, the immunological status of the individual is important, however, the ocular defence mechanisms also play a vital role. They are: - L ower ocular surface temperatures bacteria have very specific requirements. - Mechanical action of blinking sweeps the corneal surface three times per minute.


- Irrigation by the lacrimal system of microbes into the nasolacrimal system and nasopharynx. - Lysozyme, lactoferrin, specific immunoglobulins as well as protein complement in tears. - Intact epithelial surface of the cornea, active and passive defence mechanisms. Corneal defence mechanisms include the following: - Passive or structural defence mechanisms are due to the tight epithelial cell junctions and cell orientation or polarity. The epithelial cells are only susceptible from underneath and the tight junctions maintain polarity, preventing para-cellular bacterial penetration. - Active or biochemical defences involve β-defensin 2 which is produced by the cell nucleus and secreted by the cell when bacteria are detected. β-defensin 2 has a direct bactericidal activity. - Glycocalyx is negatively charged and repels bacteria; mucin binds bacteria and inhibits bacterial binding to

epithelial cells. - Exfoliation and normal cell sloughing removes infected cells. - The basal lamina separates the epithelium from the stroma and acts as a final barrier to infection by bacteria. It acts as a filter because its pores are smaller than the bacteria. In summary, three critical defence layers exist: the tear layer, epithelial layer, and the basal lamina. Redundancy suggests that all three layers may need to be compromised to get a corneal infection.

Exfoliation of epithelial cells and basal lamina preventing bacterial penetration

Common causes of infectious eye disease Bacterial, gram positive

Bacterial, gram negative

Viral

Chlamydial

Fungal

Staphylococcus aureus

Heamophilus infuenzae

Adenoviruses

Chlamydia trochomatis

Candida albicans

Staphylococcus epidermidis

Neisseria gonorrhoeae

Herpes simplex

Streptococcus pneumonia

Escherichia coli

Herpes zoster

Pseudomonas Molluscum ISO LESO GREEN aeruginosa contagiosum

Streptococcus pyogenes

Corynobacterium diphteria

Proteus mirabilis

C M Y

Moraxella lacunata

90 40 100

Amoebic Acanthamoeba castellanii

Aspergillus species

ISO LESO YELLOW

Enterovirus 70

C 0 Moraxella catarrhalis M 60 South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100 Epstein-Barr

41

Topical antibiotics

Antibiotic modes of action according to Weinstein

According to Weinstein, the modes of action of chemotherapeutic agents can be classified as follows:

• A gents inhibiting the synthesis of bacterial cell walls, for example, penicillins, cephalosporins, vancomycin and bacitracin.

Penicillins and cephalosporins are not used topically due to widespread resistance and allergy problems.

• A gents affecting the permeability of the cell membrane, for exmple, polymixin, amphotericin and nystatin.

a. Fusidic acid, schedule 4

Fucithalmic®

ISO LESO YELLOW

C

90

C

0

M Y K

40 100 45

M Y K

60 100 0

R G

4 81

R G

245 130

B

41

B

32

Fusidic acid works by interfering with b ac teria l p ro tein s ynt he s i s . It i s onl y effective o n g r a m-pos i t i ve b ac t e r i a such as the Staphylococcus and Corynebacterium species. It has no useful activity against streptococci, enterococci or most gramnegative bacteria. It inhibits bacterial replication and does not kill the bacteria; it is therefore bacteriostatic. Fusidic acid, derived from the fungus Fusidium coccineum, is a true antibiotic. It has a narrow spectrum of activity mainly against gram positive bacteria, including betalactamase producing Staphylococcus aureus. It is available as sodium fusidate – Fucithalmic® antibiotic drops and ointment in South Africa. Fusidic acid is most useful against methicillin resistant Staphylococcus aureus (MRSA). Fusidic acid can interact with statins and estrogen (not with topical use). Fusidic acid should not be used on its own to treat Staphylococcus aureus infections due to the development of resistance. 42

• A gents primarily inhibiting protein synthesis by their effects on ribosomes, for example, chloramphenicol, tetracyclines, aminoglycosides, fusidic acid and the macrolides.

ISO LESO GREEN

• A gents affecting nucleic acid metabolism, for example, fluoroquinolones. • A ntimetabolites, for example, sulphonamides, aminosalicylic acid and the sulphones. Fusidic acid should not be used with fluoroquinolones, with which they are antagonistic. Fusidic acid is safe in porphyria.

b. S odium sulphacetamide, schedule 1

Sulphacetamide®

The sulphonamide drugs are bacteriostatic, inhibiting growth and multiplication, rather than destroying the susceptible bacteria.


The natural defences of the body then deal with the bacteria already present. They act by inhibiting bacterial synthesis of folic

Opti-cet® (Propan) & Sulphacetamide ointment (Lennon)

Sulphacetamide 10%

acid, which is required for the synthesis of nucleic acid and protein. Bacterial cells are impermeable to folic acid, they synthesise it from para-aminobenzoic acid (PABA). Sulphonamides are structurally

c. P ropamidine isethionate and ibromopropamidine isethionate, schedule 2

similar to PABA, and they competitively inhibit the first step in the synthesis of folic acid. The presence of pus (which also contains PABA) inhibits the effectiveness of the drugs. Many patients are allergic to sulpha drugs. Concomitant use with topical anaesthetics (esters of PABA) also inhibits the action of the sulphonamides. Sulphonamide sodium is effective against most gram-positive, and a variety of gram-

Brolene®

negative, organisms including some strains

Propamidine isethionate is a synthetic ant i m i c r o b ia l co mp o un d (Bro l e n e ® eye drops, 0.1% solution). It has ant i b ac t e ria l , a n t if un g a l a n d a n t iamoebic properties. It is active against Staphylococcus aureus, Streptococcus pyogenes, other streptococci and clostridia, but not against Pseudomonas aeruginosa, Proteus vulgaris or Escherichia coli. Its antibacterial function is not inhibited by tissue fluids, serum or pus. It is well tolerated and is indicated for eye infections and the prevention of infections due to minor eye injuries.

of Pseudomonas aeruginosa. Although once

a

mainstay

of

treatment,

these drugs have now largely been replaced by other antibiotics and are now mostly used as prophylactics for minor ocular infections associated with conjunctival Ironically,

or

corneal

sodium

abrasions.

su l phac e t am i de

is n ow m a king a comeback because sulpha derivative is thought to be effective against demodex, an intradermal mite implicated in causing and exacerbating many case cases of blepharitis. Trimethoprim is bactericidal and blocks bacterial synthesis of folic acid. It is active

ISO LESO GREEN

against a broad spectrum of gram-positive and -negative organisms, but is not effective against anaerobes, Treponema pallidum, Mycobacterium tuberculosis,

Dibromopropamidine isethionate (Brolene® eye ointment, 0.15% concentration) has similar properties to Brolene eye drops with the notable exception that it also inhibits certain gram-negative bacilli, including Escherichia coli, Proteus vulgaris and some strains of Pseudomonas aeruginosa. Its action is not inhibited by pus or blood, and it is effective even

ISO LESO YELLOW

C 90 C 0 Sulphacetamide and trimethoprim are M in40 M 60 unsafe porphyria. South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 Mycoplasma, or Pseudomonas aeruginosa.

43

when instilled immediately following the

and neomycin. Polymyxin B/Bacitracin is well tolerated and has few side effects and is therefore a good choice in the treatment of bacterial blepharitis and bacterial conjunctivitis.

use of amethocaine (tetracaine). Allergic reactions may develop in some patients. Brolene ® eye drops 0.1% or ointment 0.15% is recommended for the treatment of Acanthamoeba keratitis

Maxitrol® (Alcon) suspension & ointment

in combination with Neosporin ® drops (neomycin-Polymyxin-B, gradiamycin) and administered hourly. Other topical agents, such as miconazole 1%, clotrimazole 1%,

Neomycin 0.5%, polymyxin B 6000 units/ml, dexamethasone 0.1%

e. Aminoglycosides, schedule 4

® polyhexamethyl biguanide (BaquacilISO ) LESO YELLOW ISO LESO GREEN

0.02%, and chlorhexidine 0.02% can also C 90 C 0

M 40with Brolene ® Min 60 be used in combination Y

100 45

Y K

R G

4 81

R G

245 130

B

41

B

32

the treatment regimen.³ K

d. Polypeptides

100 0

Bacitracin affects cell wall synthesis and works well against most gram-positive bacteria such as Staphylococcus and Streptococcus. Polypeptides are produced by the bacillus SPP. Most gram-negative bacteria are resistant. It does not penetrate the cornea well and is bactericidal/ bacteriostatic with a spectrum of activity similar to that of penicillin, but without the sensitisation which may occur with penicillin. It is available in combination with polymyxin B, which is more effective against gram-negative organisms. Polymyxins are petides with both hydrophilic and lipophilic groups

within

their

structure

which

functions as cationic detergents. Polymyxin B affects the cell membrane (produced by various Bacillus spp) disrupting the osmotic integrity of the cell. It increases the bacterial cell’s permeability and causes leakage of intracellular molecules. Polymyxin B is bactericidal and does not penetrate the intact cornea well. It is very effective against gram-negative bacteria, and is available in combinations with bacitracin 44

Tobrex®

Aminoglycosides are derived from strains of Streptomyces and Micromonospora. Aminoglycosides affect bacterial protein synthesis by more than one mechanism. They are bactericidal and include gentamycin, tobramycin, framycetin, and neomycin. The first two are the only members of this class with broad spectrum antibiotic properties that allow them to function as stand-alone drugs. In primary care, the aminoglycosides are not normally used systemically because they can cause irreversible ototoxicity and reversible renal toxicity; their antibiotic properties have thus not been compromised by widespread primary care use. Aminoglycosides are toxic and the clinical signs of toxicity include superficial punctuate keratitis of the inferonasal cornea, injection of the inferior cul-de-sac, and a weepy erythema


plus oedema of the eyelid tissues. These reactions are usually not serious and occur after the drugs have been used for more than a week or two. Neomycin’s weakness is its potential for toxicity. About 8% of patients experience a delayed type IV hypersensitivity reaction to neomycin. If the patient has not been exposed to the drug before, the reaction can occur 5 to 10 days after the therapy has been initiated. If they have been sensitised to the drug before though, reaction usually occurs within 12 to 72 hours. Aminoglycosides are used for serious gram-negative infections, especially Pseudomonas aeruginosa. Systemically administered aminoglycosides interact with l oo p d iu retics and c an c au s e ototoxicity as well as renal toxicity. They are active against most gram-negative aerobic bacilli, but lack activity against an aero bes a nd m ost gr am -pos i t i ve bacteria except for most staphylococci. Neomycin is no t effe c t i ve agai ns t Pseudomonas aeruginosa; tobramycin is most effective against Pseudomonas aeruginosa; and gentamycin is most effective against Serratia marcescens. Framycetin is most effective against Staphylococcus aureus, Escherichia coli, Proteus vulgaris and P. mirabilis, Salmonella, Shigella and Corynebacterium xerosis. Most strains of Pseudomonas aeruginosa are also sensitive, but streptococci, enterococci, and pneumococci are more resistant to this aminoglycoside. Aminoglycosides are also effective against Acanhtamoeba.


90 40 100

Tobradex® (Alcon) drops and ointment, S4

Tobramycin 0.3%, dexamethasone 0.1%

FML Neo® (Allergan) suspension, S4

Fluoromethalone 1mg, neomycin sulphate 5mg/ml

Maxitrol® (Alcon) drops and ointment, S4

Dexamethasone 0.1%, neomycin sulphate 0.35%, Polymyxin B 0.6%

Sofradex® (Aventis), S4

Framycetin sulphate 5mg, gramicidin 0.05mg, dexamethasone 0.5mg

Aminoglycosides are safe to use in porphyria.

f. Chloramphenicol, schedule 4 Bausch & Lomb Minims schedule 3

Chloramex®

O r i gi nal l y p ro d uce d b y a mo ul d Streptomyces venezuelae, chloramphenicol is now synthesized. It is bacteriostatic (bactericidal against hemophillis influenza) inhibiting bacterial protein synthesis, and is effective against a wide spectrum of gram-positive and gramnegative bacteria as well as Chlamydia, Rickettsiae and spirochaetes, but not Pseudomonas aeruginosa. It is a highly lipophilic drug with excellent corneal penetration, resulting in high aqueous levels after topical application. It is available in bothe a solution (0.5%) and an ointment (1%). The relative toxicity of chloramphenicol is the cause of some controversy among medical authorities. This is due to bone marrow toxicity. Two types of bone marrow depression may occur; a reversible doserelated

ISO LESO YELLOW


Amin og lyco s id es a re avai l ab l e i n combination with other drugs, for example:

45

Minims Chloramphenicol

interference with iron metabolism and an irreversible idiosyncratic form of aplastic anemia. F.T. Frauenfelder’s landmark article in 1982 linking aplastic anemia deaths

to

topical

ophthalmic

chloramphenicol effectively stopped the use of chloramphenicol in the USA.4 He revisited the topic in January 2007, and newer information revealed that Minims Chloramphenicol

highperformance liquid chromatography

does not detect chloramphenicol in the MYELLOW inims Chloramphenicol 0.5%, ISO LESO GREEN ISO LESO blood. The quoted incidence of fatal (Bausch+Lomb), schedule 4 C 90 C 0 40 aplastic anemia variesM between 1/500 Mto 60 Y

100

Y

100

1/100 000 (Penn 1980), K 45 and 1/25 000. K 0

Regarding the link Rbetween aplastic 4 R 245 G 81 G 130 anemia and chloramphenicol, the expert B

41

B

opinion is “probable”, and the general guideline is: do not use chloramphenicol if there is a personal or family history of blood cell or bone marrow disorder, or in patients with cirrhosis. Chloramphenicol should not be used systemically in the neona te a s the d r u g c annot b e metabolised and leads to the grey baby syndrome characterised by abdominal distention, pallid cyanosis, and circulatory

32

Chloromycetin® (Parke Davis), S4 Chloramex® (Lagamed), S4 Chlorcol® (Propan), S4

1% chloramphenicol ointment

Chloroptic® (Allergan), S4 Spersanicol® (Restan), S4 Minims (Smith & Nephew), S4

0.5% chloramphenicol drops

Spersadex Comp® (Adcock Ingram), S4

Dexamethasone 0.1% & chloramphenicol 0.5%

Chloramphenicol should be avoided in porphyria. (May precipitate an acute attack).

collapse. Optic neuritis has also been reported from systemic use.

g. Tetracyclines, schedule 4

In summary, chloramphenicol is efficacious,

Tetracyclines are broad spectrum antibacterial drugs active against grampositive and gram-negative aerobic and anaerobic bacteria, as well as spirochetes, Mycoplasma, Rickettsiae, Chlamydia, and some protozoa. Pseudomonas aeruginosa and Proteus vulgaris are rarely responsive to tetracyclines and one third or more of the staphylococcal strains are resistant. Tetracyclines inhibit protein synthesis and are bacteriostatic.

affordable, has a broad spectrum and very rarely causes blood dyscrasias. The drug is heavily prescribed in the UK, SA, Australia, Ireland, and the Far East, but is not used in the USA. Aplastic aneamia rarely occurs in topical use of chloramphenicol. It is available in South Africa in drop or ointment form, on its own or in combination with other antimicrobials and/or antiinflammatories.

46


Penetration of the ocular tissues after topical

Treponema, Rickettsia, and Chlamydia. They

or systemic administration is poor. In addition

have variable activity against Haemophilus

to its antibiotic action, tetracycline has other

influenzae.

properties that can change the course of disease progression. When patients with acne vulgaris, acne rosacea, and primary meibomianitis (all non-infectious inflammatory diseases) receive systemic tetracyclines, two changes occur: the

Staphylococcal infections of the eyelid are commonly treated with erythromycin ointment. Its resistance profile is poor, limiting its use to a prophylactic lubricant with antibiotic properties.

amelioration of the symptoms and reduction

Azithromycin has a prolonged intracellular

of the free fatty acids in the surface sebum.

half life, and is therefore dosed less

Since normal bacteria produce the free

frequently than the other ophthalmic

fatty acids, tetracycline is possibly effective

drugs, typically one drop every 8 to 12

in these disorders due to its interactions

hours for the first two days, and then one

with normal bacteria, not pathogens. It is

drop daily for five more days. Its greatest

therefore used systemically in the treatment

value is treating paediatric eye infections.

of blepharitis, non-infectious corneal ulcers

No longer available in South Africa.

or corneal melting, the latter due to its anticollagenase activity. Tetracyclines

cross

the

placenta

to

Erythromycin is unsafe in porphyria.

accumulate in fetal bones and teeth, and

i. Fluoroquinolones, schedule 4

are excreted in milk. They should therefore not

The fluoroquinolones inhibit DNA

be used after the 1st trimester of pregnancy,

synthesis and exhibit a concentration-

in mothers who are breastfeeding, or in

dependent bactericidal activity by

children under the age of 8 years. Topical

inhibiting the activity of DNA gyrase

formulations containing tetracyclines are no

and topoisomerase, enzymes essential

longer available in South Africa.

for bacterial DNA replication. They

In porphyria it is unsafe and should be used with extreme caution.

h. Macrolides The macrolides include erythromycin, clarithromycin and azithromycin. They inhibit protein synthesis and were previously

ISO LESO GREEN

can be divided into two groups based on antimicrobial spectrum and pharmacology. The older group includes ciprofloxacin, norfloxacin, ofloxacin, and t he n e w e r g ro up g a t if l o x a cin , gemifloxacin, levofloxacin, moxifloxacin, and travofloxacin.

ISO LESO YELLOW

considered bacteriostatic, but it is now

T he fl u or o quin o l o n e s a re sy n t h e t ic

believed that they have bactericidal properties

bactericidal anti-infectives with good

that depend on the organism and the drug

activity against both gram-negative

concentration. The spectrum of activity of

and gram-positive pathogens that most

C 90 C bacterial 0 conjunctivitis frequently cause (streptococci and staphylococci), gram- and keratitis. Topically we have only the M 40 M in60 negative bacilli, Neisseria, Mycoplasma, following available South Africa: South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 the macrolides includes gram-positive cocci

47

Ciprofloxacin drops 0.3% and ciprofloxacin ointment 0.3% - Ciloxan® (Alcon), Generic Foxin (Genop) - Generic 0.3% ciprofloxacin.

Besifloxacin 0.6% - Besivance® (Bausch & Lomb) (Not yet available in SA)

Besivance® Ciloxan®

ISO LESO0.3% GREEN ISO LESO YELLOW Foxin® (Generic ciprofloxacin) The older fluoroquinolones have poor

C 90 C 0 activity against streptococci and ® Ofloxacin 0.3% - ExocinM® (Allergan), Octin 40 M 60 Y 100 Y 100 anaerobes but the newer drugs have 0.3% (Cipla) K 45 K 0 reliable activity against streptococci R 4 R 245 (including Streptococcus pneumoniae) G 81 G 130 B 41 B 32 and some anaerobes. They are active against both gram-positive and gr am -ne g a t iv e b a ct e ria , in cl ud in g Neisseria, H a e m o p h i l u s i n f l u e n z a e , M o r a x e l l a catarrhalis, Mycoplasma, Chlamydia, Legionella, Enterobacteriaceae, Exocin® Octin® and particularly ciprofloxacin against Moxifloxacin 0.5% - Vigamox® (Alcon) Pseudomonas aeruginosa. Compared to the other antibacterial drugs discussed, the fluoroquinolones have the greatest potency and broadest spectrum of activity. The tear concentrations are significantly higher than the MICs (minimum inhibitory concentrations) for 90% of bacterial strains of most potential pathogens four hours after a single application of the Vigamox® 0.3% solution. Ofloxacin achieves the highest aqueous humour concentration. ® Gatifloxacin 0.3% - Zymar (Allergan) Levofloxacin 1.5% (not available in South Africa) and moxifloxacin 0.5% (Vigamox®) are self-preserved.

Zymar® 48

Besifloxacin (Besivance, Bausch & Lomb) ophthalmic suspension 0.6% is a n e w generation fluoroquinolone indicated for the treatment of bacterial conjunctivitis caused by susceptible isolates of the


following bacteria: CDC coryneform group G, Corynebacterium pseudodiphtheriticum, Corynebacterium striatum, Haemophilus influenzae,

Moraxella

lacunata,

Staphylococcus aureus, Staphylococcus epiderm id is , Staphylococcus hominis, Staphylococcus lugdunensis, Streptococcus

be administered as clinically indicated. Other adverse reactions with systemic use of fluoroquinolones include tendinitis and tendon rupture especially in patients older than 60 years taking steroids as well as worsening of myasthenia gravis symptoms

mitis group, S t r e p t o c o c c u s o r a l i s ,

Despite claims of low frequency of

Streptococcus

and

resistance to the quinolones, some

Streptococcus salivarius. Besifloxacin is not

s t aphyl oco cca l st ra in s a s w e l l a s

yet available in South Africa.

Pseudomonas are developing a relatively

pneumoniae,

As a group the fluoroquinolones are well tolerated with a low incidence of adverse reactions. As the possibility of adverse

high rate of resistance to the older drugs. The fluoroquinolones are less effective against MRSA than the aminoglycosides.

effects on the corneal permeability and

The key to using the fluoroquinolones (and

the danger of disruption of the corneal

indeed any other topical antibiotic) is

epithelium with prolonged or repeated

frequency of administration. Dosing every

usage of benzalkonium chloride preserved ophthalmological preparations cannot be excluded, regular ophthalmological examination is required. Caution should be exercised in the use of benzalkonium chloride-preserved topical medication over an extended period in patients with extensive ocular surface diseases.

few minutes initially for severe infections, or hourly for moderate infections, achieves sufficiently high MICs to achieve bacterial control in virtually all cases. Once control has been achieved, decreasing the frequency of dosing over a few days generally assures a complete clinical cure. Safety and effectiveness in infants

In patients receiving systemic quinolones,

below the age of one year have not been

including gatifloxacin, serious and

established. No overall differences in safety

occasionally

or effectiveness have been observed

fatal

hypersensitivity

(anaphylactic) reactions, some following the first dose, have been reported. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial oedema),

ISO LESO GREEN itching. If an allergic reaction

airway obstruction, dyspnoea, urticaria, and to

gatifloxacin

occurs,

the

drug

should be discontinued. Serious acute

between elderly and younger patients. Foxin® is the first generic ciprofloxacin eye drop for the treatment of corneal ulceration

and

conjunctivitis

caused

by susceptible strains of gram negative bacteria. It is also used as an ear drop to

ISO LESO YELLOW

treat otitis media in children (older than 1 year) and adults.

N ev er t ape r a n a n t i b i o t i c b e l o w

.i.d because such potentially C 90 emergency treatment. qsubtherapeutic C levels 0 could foster the Oxygen and airway management should development of resistance. M 40 M 60 South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 hypersensitivity rea ctio ns m ay r e q u i r e immedia te

49

The fluoroquinolones are probably safe

“If you are going to treat bacterial

in porphyria.

conjunctivitis,

you

had

better

treat

it quickly before it gets better on its

In summary

own” - Dr Louis Catania: Lecturer 1994

Topical antibiotics are grossly overutilized.

Pennsylvania College of Optometry,

Indication for prescription is evidence or

Philadelphia, USA.

confirmed diagnosis of a bacterial infection,

What

or a condition in which there is judged to

should

you

consider

be significant risk of opportunistic infection.

prescribing an antibiotic?

The former should be easily confirmed by

- Staphylococcus aureus is the most common cause of bacterial conjunctivitis

slit lamp examination, the latter depends ISO LESO GREEN

ISO LESO YELLOW

C

C

and blepharitis in the Western world.

on the experience of the clinician. 90

0

M 40 M 60 An absolute indication for antibiotic use Y 100 Y 100

is microbial keratitis. K

R

45

K

4

R

0 245

- Accurate diagnosis and selection of the appropriate drug is essential. - If there is inflammation associated

In children, bacterial G infections are not 81 G 130

with the infection, consider an

uncommon, but they are uncommon

antibioticsteroid combination.

B

when

41

B

32

in adults. In fact, most cases of

- Patients who present very early in the

keratoconjunctivitis in adults are the result of

course of the infection are often very

inflammation (from viral infection), and either a steroid or steroid-antibiotic combination is almost always a more appropriate selection than an antibiotic on its own.

difficult to diagnose and treat, because the nature of the condition is not readily apparent. An option is to start with an artificial tear for a day or two. During this

It is worth remembering the words of one of my professors and one of the fathers of modern optometry:

time the condition will either improve or become more definitively diagnosable. - Maintaining MIC is important, especially

Flouroquinolones Besivance, S4

Besifloxacin 0.6%

Bausch & Lomb

Not yet available in SA

Ciloxan® & Foxin®, S4

Ciprofoxacin 0.3%

Alcon/Genop

Sol/ung

Exocin® & Octin®, S4

Ofloxacin 0.3%

Allergan/Cipla

Solution

Vigamox®, S4

Moxifloxaxin 0.5%

Alcon

Solution

Zymar®, S4

Gatifloxacin 0.3%

Allergan

Solution

Aminoglycosides Tobrex® & generic, S4

50

Tobramycin 0.3%

Alcon


Sol/ung

Others

"Chloramex®, S4 Chloromycetin®, S4"

"Chloramphenicol 5.0mg/ml or 1% Chloramphenicol 2mg, neomycin sulphate 5mg, naphazoline hydrochloride nitrate 0.25mg Chloramphenicol 0.5%"

Allergan Covan ParkeDavis

"Sol/ung Sol Sol 0.5%/Ung 1%"

Fucithalmic®, S4

Fusidic acid

Al Pharm

ung

Brolene® , S2

Propamidine isethionate 0.1% solution Dibromopropamidine isethionate 0.15% ointment

Allergan

Sol/ung

Spersamide®, S1

Sodium sulphacetamide 10g, hydroxymethylcellulose

Novartis

solution

++

++

Neosporin

+

+

+

+

+

+

+

++

Brolene sol

+

+

+

+

Brolene ung

+

+

+

+

Tobrex

+

+

Fucithalmic

+++ + MRSA

Ciloxan & Foxin

++

++

+

+

++

++

Exocin/Octin

++

++

+

+

++

++

ISO LESO GREEN

C 90 +++ Vigamox Zymar M 40 +++ Y 100

+

++

++

++

+

++

++

Amoebic Acanthamoeba

++

Chlamidia

++

Moraxella catarrhalis

++

Moraxella lacunata

++

Proteus mirabilis

Nesseria gonorrhoea

++

Pseudomanas aeruginosa

Heamophilus influenzae

Chloramphenicol, ++ genrecis

Drug

Staph

Corynobac. diphteriae

Escheichiae coli

Gram -

Strep. Pyogenes

Strep. Pneumonia

Staph.Aureus

Gram +

Chlamydial

Antimicrobial spectrum of activity of various antibiotics

++

+ +

?

+

+++

++

++

+++

++

++

++

+ +

+

+ ?

?

++

++

++

++

++

++

++

++

ISO LESO YELLOW

C +++0+++ +++ +++ +++ +++ +++ +++ +++ +++ +++ ++ +++ +++ +++ +++ +++ +++ +++ ++ +++ +++ +++ M +++60 South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

51

in moderate to severe infections. Treat

catalytic enzyme phospholipase A2 early

q1h or q2h for the first two to three

in the cascade. Once arachidonic acid

days, and then taper to q.i.d for five

is formed, two different enzymes convert

or six more days until the condition is

it ultimately to either prostaglandins or

resolved.

leukotrienes. Cyclooxygenase converts

Never taper below q.i.d.

arachidonic acid into prostaglandins, and lipoxygenase converts arachidonic

- Prolonged use of antibiotics can

acid into leukotrienes. NSAIDs inhibit the

allow overgrowth of non-susceptible

enzymatic activity of cyclooxygenase,

organisms, including fungi. The vast

but have no effect on lipoxygenase,

majority of primary eye care conditions,

allowing the production of leukotrienes ISO LESO GREEN YELLOW when appropriately treated, responds ISO LESOto go unchecked. This became quite in less than a week. ItC is90therefore C 0 evident in the early days of PRK when M

40

beyond 7 to 10 days.K

45

uncommon for therapy to continue Y 100 R 4 - If there is no improvement in two to G

81

three days, suspect non-compliance, B 41

M Y K

60 100 0

NSAIDs were used postoperatively. Patients

R G

245 130

cell corneal infiltrates, until it was realised

B

32

experienced problems with white blood that leukotrienes were chemotactic

microbial resistance, sub-therapeutic

for leukocytes. NSAIDs only inhibit the

dosing frequency, inappropriate

synthesis of prostaglandins and a steroid

choice of drug, or most likely incorrect

was needed to prevent the formation

diagnosis.

of infiltrates due to its action higher up in

3. A nti-inflammatory drugs

the arachidonic cascade. Now steroids and NSAIDs are used concurrently in postoperative care. Topical

that CME develops, in part, because of

inflammation. They simply inhibit an enzyme along the synthetic pathway to

tromethamine

0.5%

0.1%

NSAIDs have no direct anti-inflammatory providing some limited activity against

ketorolac

diclophenac

A. N on steroidal anti-inflammatory drugs (NSAIDs) properties. NSAIDs ameliorate pain while

52

NSAIDs

or

are

used with prednisolone acetate 1% to treat cystoid macular edema (CME) after cataract surgery. It is believed a prostaglandin-induced breach of the blood-retinal barrier resulting in secondary retinal oedema. Topical NSAIDs inhibit the production of prostaglandins by

the production of prostaglandins, which

inhibiting the cyclooxygenase enzyme.

are powerful mediators of inflammation.

Corticosteroids inhibit phospholipase A-2,

This pathway is known as the arachidonic

which also reduces arachidonic acid

acid cascade. Cellular micro-trauma

metabolites, particularly the leukotrienes,

causes the release of membrane

which attract inflammatory cells and are

phospholipids. Corticosteroids inhibit

also potent mediators of inflammation.

the convers ion of the phos phol i pi ds

Therefore, NSAIDs and corticosteroids

to arachidonic acid by inhibiting the

act synergistically at different sites in the


Others

Others

"Aminoglycosides Tobramycin 0.3%"

1 to 2 drops every 4 hours, up to 10 days. Severe infection: 2 drops every hour

"Polymyxin B combinations"

1 to 2 drops every 3 to 4 hours for 7 to 10 days

"Macrolides Azitromycin 1.0%"

1 drop 2 times a day for 2 days, then 1 drop daily for 5 days

"Fluoroquinolones Besifloxacin 0.6%"

1 drop 3 times a day for 7 days

Ciprofloxacin 0.3%

1 to 2 drops every 2 hours for 2 days, then 1 t 2 drops every 4 hours for 5 days

Gatifloxacin 0.3%

1 to 2 drops every 2 hours up to 8 times a day for 2 days, then 1 drop up to 4 times a day for 5 days

Gatifloxacin 0.5%


Levofloxacin 0.5%


Moxifloxacin 0.5%

1 drop 3 times a day for 7 days

Oflaxacin 0.3%

1 to 2 drops every 2 to 4 hours for 2 days, then 1 to 2 drops 4 times a day for 5 days

inflammatory cascade to reduce the production of inflammatory mediators.

a. Ketorolac tromethamine; Acular® (Allergan), schedule 3

Nepafenac (Alcon) is a new NSAID that uniformly inhibits prostaglandins in the iris/cilliary body as well as retina PGE2 synthesis and demonstrates excellent properties in inhibiting the breakdown of the blood-aqueous and blood-retinal barriers. It significantly inhibits vitreous humour prostaglandin formation that can lead to CME.

ISO LESO GREEN

Acular LS®

ISO LESO YELLOW

Acular LS ® (ketorolac 0.5%, (now also available in 0.4%) is approved for the treatment of itching associated with seasonal allergies. It is also used for the treatment of postoperative pain and

C 90 C 0 M domain 40OCT of CME M 60 Fourier South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100

53

inflammation, but could be used for any clinical condition where a topical NSAID is indicated. It does not significantly impair wound healing. Its use in the treatment of CME in combination with prednisolone acetate 1% has already been discussed.

Ocular effects of prostaglandins - Pupil constriction - Vasodilation - Increased vascular permeability - Disruption of ocular blood barriers - Alteration of intraocular pressure

ISO LESO GREEN C

90

M Y K

40 100 45

Primary care uses for topical NSAIDs R

4

B

41

1. Corneal abrasions G 81 2. Post FB removal

3. Post anterior stromal puncture procedure 4. Post PK, PRK, LASIK 5. Treating cystoid macular edema 6. Allergic conjunctivitis, GPC, seasonal allergy

The most common adverse effect is transient burning, stinging and conjunctival hyperaemia in 20 to 40% of patients. To alleviate these effects, ketorolac is as tromethamine salt, which ISO LESOformulated YELLOW improves aqueous solubility and reduces C 0 M 60 ocular irritation. Other adverse effects Y 100 include punctuate keratitis, corneal K 0 infiltrates, ocular pain, and headaches in R 245 G 130 1 to 10% of patients. B

32

NSAIDs increase bleeding time by interfering with platelet aggregation. Crosssensitivity with aspirin and other NSAIDs can occur with topical administration, requiring careful monitoring of patients who are taking these drugs.

7. Some cases of photophobia 8. Post cataract surgical care 9. Treating or preventing inflamed pterygia and pingueculae

b. Sodium diclofenac; Voltaren® (Novartis), schedule 3

10. RGP adaptation

Topical NSAIDs available in South Africa 1. Acular® (Allergan) 5ml – Ketorolac tromethamine 0.5%, 0.4% solution, S3 2. Voltaren® (Novartis) 5ml – Diclophenac sodium 0.1%, also available in unpreserved single dose units 0.3ml , S3 3. Nevanac (Alcon) - nepafenac ophthalmic suspension 0.1%, S3 (2nd half of 2012)

54

Voltaren® and Voltaren® SDU

Diclophenac 0.1% is approved for control of inflammation after cataract surgery. It significantly reduces prostaglandin levels and, at higher doses, may even inhibit


leukotriene production. It also decreases corneal sensation in healthy eyes and reduces pain in patients following PRK or other ocular surgery. Diclofenac decreases early epithelial wound healing, but does not affect stromal healing. In a study comparing diclofenac with ketorolac, the decrease in corneal sensitivity in normal human corneas was more pronounced and longer lasting with diclofenac than with ketorolac. The most common adverse effect is transient burning, stinging and conjunctival hyperaemia. In addition to reducing pain, NSAIDs have been shown to affect corneal epithelial healing. Topical diclofenac retards epithelial healing to a significantly greater extent than dexamethasone. Topical diclofenac has been associated with persistent epithelial defects in patients after undergoing penetrating keratoplasty. Corneal melting has also been reported with the use of topical diclofenac. Patients receiving topical diclofenac after ocular surgery, especially cataract surgery, should be monitored closely. The frequency of administration and duration of treatment should be minimized, and as-needed use should be discouraged. A history of ocular surface disease associated with an increased risk of corneal melting is a relative contraindication for topical NSAID use, but patients without any such history may also develop severe complications.

ISO LESO GREEN

NSAIDs are safe in porphyria.

c.CN epafenac 90 ophthalmic suspension, Nevanac M(Alcon), 40 S3

Y

100

Nevanac®

Unlike conventional NSAIDs, the active forms of which decrease as they penetrate the eye, Nevanac is specifically designed to maximise intraocular efficacy. Nepafenac 0.1% suspension first touches the cornea as nepafenac, which safely delivers an analgesic effect to the corneal surface. As it penetrates the intraocular tissues, itraocular hydrolysis converts the nepafenac molecule into a highly effective cyclooxygenase inhibitor (COX) called ‘amfenac’. This gives nepafenac target specific activity that maximises its efficacy at the targeted ocular tissue sites where pain and inflammation reside. Its enzymatic activity is similar to that of an arachidonic acid pathway. Nepafenac uniformly inhibits prostaglandins in the iris/cilliary body as well as retina PGE2 synthesis and demonstrates excellent properties in inhibiting the breakdown of the blood-aqueous and blood-retinal barriers. It significantly inhibits vitreous humour prostaglandin formation that can lead to CME. Nevanac was found to be safe and well tolerated with clinical trials revealing neither evidence of epithelial, stromal, or intraocular toxcicity. Stinging

ISO LESO YELLOW


55

and burning was also minimal. The most frequent ocular adverse effects include corneal and conjunctival edema, dry eye, ocular discomfort, pain, photophobia, tearing, and lid margin crusting in 1 to 5% of patients. Nevanac will soon be available in South Africa.

sodium retention in the kidney (salt and water metabolism).

More than 50 years after the introduction of synthetic corticosteroids into ocular therapy by Gordon and McLean, steroids remain frequently used agents for the control of both posterior and severe anterior segment inflammation. They Ocular NSAIDs Dosing can be effective in protecting the ocular Drug Dose structures from many of the undesirable effects ISO LESO GREEN ISO LESO YELLOW of ocular inflammation, particularly Keratolac 1 drop three times scarring and neovascularisation. They are tromethamine 0.4 C 90 C 0 per day and 0.5% M 40 M 60 generally more effective in acute (blocking Y 100 Y 100 the exudative phase of inflammation) K 45 K 0 Diclophenac sodium 1 drop three times rather than chronic inflammatory states, R 4day R 245 0.1% per G 81 G 130 and degenerative diseases are usually B 41 B 32 completely refractory to steroid therapy. 1 drop three times Nepafenac 0.1%

per day

B. T opical Corticosteroids Corticosteroids is a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiological systems, such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behaviour. •G lucocorticoids such as cortisol, control carbohydrate, fat and protein metabolism are anti-inflammatory by pre venting p ho s phol i pi d r e l e as e , decreasing eosinophil action and a number of other mechanisms. •M ineralocorticoids such as aldosterone, control electrolyte and water levels mainly by promoting

56

The anti-inflammatory effects of steroids appear nonspecific, occurring whether the aetiology is allergic, traumatic, or infectious. They do not act directly to correct a specific disorder, but appear to modify a pre-existing or ongoing response to a foreign or endogenous substance. Steroids appear to have an effect on nearly every aspect of the immune system. They inhibit both migration of neutrophils into the extracellular space and their adherence to the vascular endothelium at the site of tissue injury. In therapeutic doses, steroids also inhibit macrophage access to the site of inflammation and interfere with lymphocyte activity in the immune response. Steroids also affect other substances that modulate inflammation. Both histamine and arachidonic acid release are inhibited (see arachidonic cascade), restraining the production of prostaglandins and leukotrienes.


5*

UNIQUE WATER GRADIENT

33%

>80%

THIS IS WHY lasting lubricity means lasting comfort.

>80%

WATER CONTENT (%)

DAILIES TOTAL 1 ® Water Gradient Contact Lenses maintain 100% of their lubricity after a day of wear. And because lubricity is highly predictive of contact lens comfort, lasting lubricity means lasting comfort.1

>80%†

33%

>80%†

Contact Lens Cross-Section5

PERCENT OF LUBRICITY FACTOR

The First Water Gradient Contact Lens1

†

100%

50%

9.2 OUT OF 10

END-OF-DAY

COMFORT 0%

Enlarged Water Gradient5*

Prior to Application

Time of Removal 1


LASTING LUBRICITY1

100% LUBRICITY MAINTAINED

Features different surface and core water contents, optimizing both surface and core properties2

Ultrasoft, hydrophilic surface gel approaches 100% water at the outermost surface3 for exceptional lubricity

Lens maintains 100% of its initial lubricity even after a day of wear1

Let your customers experience the DAILIES TOTAL 1 100%

50%

0.0%

ISO LESO GREEN

PERFORMANCE DRIVEN BY SCIENCE

TM

®

contact lens difference today.

100%

Time of Insertion

Time of Removal

(average 14 hours)

ISO LESO YELLOW

* Adapted from cross section illustration of Dailies Total 1 water gradient contact lens 1. Draper M et al. A water gradient contact lens. Optician. 5 April 2013:24-26 2. Thekveli S, et al. Structure-property relationship of delefilcon A lenses. Cont Lens Anterior Eye. 2012;35(suppl 1):e14 3. Angelini T, Nixon R, Dunn A, et al. Viscoelasticity and mesh-size at the surface of hydrogels characterized with microrheology. Invest Opthalmol Vis Sci 2013;54: E-abstract 500. 4. Optician Awards 2014. www.opticianawards.com. 20 May 2014. 5. Pruitt J, Bauman E. The Development of Dailies Total1 Water Gradient Contact Lenses. Contact Lens Spectrum. 6/1/2013 See product instructions for complete wear, care, and safety information. Alcon Laboratories (SA) (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, Midrand, Johannesburg, 2090. Telephone: 011-840 2300. V-DT1-005-V3 May 2014 Expiry Date: May 2016

C M Y

90 40 100

4

100%


57

The Arachidonic Acid Pathway

Mast cell stabilisers inhibit degranulation

Activated Mast cell

Anti-histamines inhibit histamine

Granule release, preformed mediators

Histamine

Inhibited by non Steroidal anti-inflammatory drugs

ISO LESO GREEN

ISO LESO YELLOW

C

90

C

M Y K

40 100 45

R G B

0

M Y Cytokines, K

60 100 0

4 81

R G

245 130

41

B

32

chemotactic factors

Membrane Phospholipids Inhibited by Corticosteroids Phospholipase A2

Arachidonic acid Cyclooxygenase Lipoxygenase Endoperoxides Hydroperoxides Prostacyclin (PGI2) Thromboxane A2 Prostaglandins (PGE2, PGF2, PGD2)

Steroids also decrease capillary and fibroblast proliferation and collagen deposition, thereby influencing tissue regeneration and repair. The ability of steroids to suppress inflammation (clinical efficacy) is based 58

Leukotrienes and related compounds

on two factors: Potency (mg to mg basis) and bio-availability (ability to penetrate into target tissues). The bio-availability of topical steroids depends on their ability to penetrate the tri-layered structure of the cornea, which


has both hydrophobic and hydrophilic layers.

The

ideal

steroid

should

be

biphasic in its polarity, which would allow solubility in both the hydrophobic lipid layers (epithelium and endothelium) and the hydrophilic aqueous media of the stroma. The inherent water or lipid solubility of each steroid can be altered by modification of

Dexamethasone disodium phosphate and alcohol 0.1% Decadron phosphate® (Merck) & Maxidex® (Alcon)

4

Rimexolone 1% - Vexol® (Alcon) (Not available in SA)

4.5

"Prednisolone acetate and sodium phosphate 1% Pred Forte® (Allergan) & Inflamase forte® (Ciba vision) (Not available in SA)"

5

the steroid base into various derivatives.

In addition to the ability to influence the

Acetate or alcohol derivatives render

steroid’s penetration of the ocular surface,

the steroid molecule more lipophilic or

the base derivative also seems to influence

fat soluble, thus better able to penetrate

its anti-inflammatory efficacy. Acetate

the intact cornea. These preparations

and alcohol derivatives are more effective

are normally available as suspensions or

than phosphate derivatives in suppressing

ointments.

ocular inflammation both in the presence

Salts, such as sodium phosphate and

or absence of intact corneal epithelium.

hydrochloride, are more hydrophilic or

Principles of corticosteroid therapy

water soluble with poorer penetration

• The specific type and location of the

into the intact cornea. These preparations are normally available as solutions. Interestingly, the alcohol derivative has intermediate lipophilicity between the acetates and the salts. Drug Hydrocortisone (1%, not used much)

1

Prednisolone acetate 0.12% Pred Mild® (Allergan)

2

"Medrysone alcohol 1% HMS® (Allergan)"

2

Loteprednol etabonate 0.2% Alrex® (Bausch & Lomb)

2.5

ISO LESO GREEN

Loteprednol etabonate 0.5% Lotemax® (Bausch & Lomb)

4.5

Fluoromethalone alcohol 0.1% FML® (Allergan)

3

90 40 100

systemic, periocular or multiple routes of administration are appropriate. • Treatment should be instituted as soon as possible when indicated, and the dose should be high enough to suppress

Relative Potency

C M Y

inflammation determine whether topical,

the inflammatory response. • The appropriate dose for a specific condition is largely determined by clinical experience and must be reevaluated at frequent intervals during the course of the treatment. • High-dose or longer-term therapy should not be discontinued abruptly. The dose should be gradually tapered over time.

ISO LESO YELLOW

• Short-term, low-dose ocular therapy

generally does not produce significant side effects. • Ideally, the minimum effective dose

C 0 necessary to secure the desired clinical 4 60 response. M South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100 should be used for the shortest time

Fluoromethalone acetate 0.1% Flucon® (Alcon)

59

Why taper steroids?

occur with all routes of administration:

The administration of systemic steroids over

systemic, topical, cutaneous, nasal aerosols, and inhalation steroids. Dosage

a long period of time results in the adrenal

and duration of therapy appears to be

cortex slowing its production of physiologic

correlated with the incidence of cataract

corticosteroids. This can result in atrophy of

development. In adults, steroid-related

the adrenal cortex or even suppression of

PSC cataracts do not usually occur

pituitary function. To abruptly stop synthetic

within the first year of therapy regardless

steroids could potentially leave the body with

of dose. In children, cataract changes

abnormally low levels of endogenous steroids.

can manifest at lower doses and within

Tapering the dosage gives the adrenal cortex

shorter periods. The risks associated time to start producing ISO the normal levels ISO of LESO YELLOW LESO GREEN with short term topical use are minimal. steroids again. Although this phenomenon C

90

C

0

Y K

100 45

Y K

100 0

R G

4 81

R G

245 130

B

41

B

32

is more pronounced with systemic steroids, M 40 M 60 one study demonstrated that 0.1% dexamethasone sodium phosphate, one drop q.i.d for six weeks, resulted in decreased levels of endogenous steroids.

A more important reason for tapering ophthalmic steroids is the rebound effect of local inflammation. Steroids reduce the leukocytic elements in the blood and, consequently, white blood cells proliferate when

therapy

stops.

The

immature

cells can produce large quantities of antibodies to residual antigen in the ocular tissues. A massive polymorphonuclear leukocytic reaction follows the resultant antigenantibody reaction. If not interrupted immediately, this can lead to serious, necrotising inflammation. A good rule of thumb is to taper the dosage frequency by about 50% once control of the inflammation is established. For example, q2h for two days, then q.i.d for four days, then b.i.d for four days or, more commonly, q.i.d for one week then b.i.d for two days. Ocular side effects of corticosteroid therapy • P osterior sub-capsular cataracts (PSC) 60

Posterior subcapsular cataracts possibly

occur due to interactions between the steroid and the lens crystallins which lead to protein aggregation and the formation of reactive protein complexes. • Since steroids reduce the immunologic defence mechanisms, these drugs lower resistance to many types of infection. In general, steroids should be avoided in cases of routine bacterial infections of the lids and conjunctiva because no scarring is anticipated and steroids provide little benefit in the healing process. Steroids prolong the clinical course of dendritic keratitis and enhance ocular susceptibility to fungal infections. Minor injuries, especially those caused by vegetative matter, can lead to fungal infections i f t r e a t e d w it h st e ro id a n t ib io t ic combinations. Steroids should never be the sole therapeutic agent in conditions caused by actively replicating microorganisms. The need to maintain a balance between the steroid and chemotherapeutic agent cannot be overemphasised. • T he steroid’s effects on collagen synthesis and fibroblast activity leads to retarded corneal wound healing,


epithelial regeneration, and corneal as well as scleral thinning. • A lthough relatively rare, steroid-induced glaucoma has a number of features in common with primary open angle glaucoma (POAG). These include a stronger tendency to develop steroid response in the families of patients with POAG, the glaucoma gene, MYOC (GLCIA, TIGR) and its glucocorticoid induction in the trabecular meshwork (TM). Alterations in TM cell function, morpho log y, extr ac e l l u l ar m at r i x production and the cytoskeleton also occur in both these conditions. Clinically, steroid-induced glaucoma is characterized by elevated intraocular pressure associated with glucocorticoid administration. The eyes are quiet, asymptomatic, and the angle appears normal with gonioscopy. Failure to recognise the condition can result in the characteristic glaucomatous optic nerve damage and visual field loss. In the early 1960s Armaly and Becker independently studied the effect of potent glucocorticoids (dexamethasone & betamethasone 0.1%) on IOP. Patients used the formulations three to four times a day for 4 to 6 weeks; three levels of responses were produced in the general population.

This seems to indicate that the degree of steroid response is genetically de t e r m in e d . P a t ie n t s w it h P O A G produced a moderate to high response in nearly all subjects, and descendents of POAG subjects demonstrated a higher rate of steroid response than the general population. Finally, normal individuals classified as moderate or high steroid responders are more likely to develop POAG. Some topical ophthalmic steroid indications • Iritis, iridocyclitis, uveitis • Episcleritis • Chemical trauma, alkali burns • Corneal infiltrates • Angular blepharitis • Peripheral corneal erosions • Actinic keratoconjunctivitis • Phlyctenulosis • Contact blepharodermatitis • Glaucomatocyclitic crisis • Vernal keratoconjunctivitis • T hygeson’s superficial punctuate keratitis • Stromal keratitis • Epidemic keratoconjunctivitis • Uveitic glaucoma • Ocular trauma • S taphylococcus exotoxin blepharoinflammation • Postoperative care

Contraindications for topical ISO LESO GREEN ophthalmic steroids • H erpes simplex infectious epithelial keratitis.

• Eczemoid blepharitis

ISO LESO YELLOW

• Corneal microcystic edema • Allergic conjunctivitis • Acne rosacea keratitis

• Keratoconjunctivitis C• Significant 90 corneal epithelial C 0 sicca... and a host of other inflammatory conditions. Mcompromise. 40 M 60 South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 • Acute bacterial infections.

61

Patients with primary open angle glaucoma and their relatives show a remarkably high prevalence of pressure elevations with topical steroids. Bartlett et al. showed that 70% of first-degree offspring of individuals with primary open angle glaucoma have a response of 5mmHg when treated with a topical steroids.

inhalation (intra-nasal) administration.

- T he remainder was nonresponsive, pressures less than 20mmHg and increases less than 6mmHg.

Effects of glucocorticoids including glycosaminoglycins [GAGS]), on the trabecular meshwork (TM)

In general dexamethasone phosphate 0.1%

and betamethasone phospahte 0.1% appear more likely to induce significant IOP elevations than do prednisolone acetate 0.12%, fluoromethalone alcohol 0.1%, or loteprednol etabonate 0.2% and 0.5%. These effects are most likely due to the considerably Information regarding the patient or family shorter pharmacokinetic halflife and greater history of glaucoma therefore becomes susceptibility to metabolism of the last important when considering the use ISO of LESOthree ISO LESO GREEN YELLOW drugs compared to dexamethasone steroids. Baseline IOP measurements are phosphate 0.1%. C 90 C 0 M 40 M 60 imperative. Among other factors diabetes, Y 100 Y 100 Studies show that significant ocular high myopia (> 5.00D), K 45advanced age K 0 hypertension is unlikely to occur before (and children), and Krukenberg’s spindles R 4 R 245 three or five weeks of prolonged steroid G 81 are suggestive of steroid responders. G 130 B 41 B 32 use even in “known steroid responders”, In addition to the status of the patient, yet most cases of ocular inflammation d e v e l o p m e n t o f s t e r o i d i n d u c e d are resolved well within this time frame. glaucoma also depends on the potency, Treatment consists of discontinuing the duration, and dose of the steroid, its corticosteroid, monitoring the IOP, and route of administration and its ability standard medical or surgical glaucoma to enter the eye. In general, those treatment if indicated. agents with the highest affinity for the glucocorticoid receptor are the most likely Corticosteroids produce several alterations to induce ocular hypertension. Routes in the trabecular meshwork that also occur of administration most likely to induce in POAG. These include activation of the TM ocular hypertension are topical followed cells, increased deposition of extracellular by intraocular, periocular, systemic, and matrix material including glycosaminoglycins [GAGS]), alterations of the trabecular cytoskeleton, and increased expression of the Armaly and Becker: steroid response in the general population glaucoma gene, myocilin. These changes produce increased resistance to aqueous - 4 to 6% were high responders, pressures above 31mmHg or humour outflow (due to mucopolysaccaride increase of 15mmHg above deposition in the trabecular meshwork), baseline. elevated IOP and eventually glaucomatous - 33% were moderate responders, optic nerve damage. In the following table pressures between 20 and the effects on the trabecular meshwok are 31mmHg or increases of 6 to summarised. 15mmHg above baseline.

62


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* Adapted from cross section illustration of Dailies Total 1 water gradient contact lens **Percentage of wearers agreeing with the statement “With these lenses I sometimes forget I have them on.” 1. Thekveli S, Qiu Y, Kapoor Y, Kumi A, Liang W, Pruitt J. Structure-property relationship of delefilcon A lenses. Cont Lens Anterior Eye. 2012;35(suppl 1):e14. 2. Angelini T, Nixon R, Dunn A, et al. Viscoelasticity and mesh-size at the surface of hydrogels characterized with microrheology. Invest Opthalmol Vis Sci 2013;54: E-abstract 500. 3. In a clinical study with 80 subjects. Alcon data on file, 2011. 4. Pérez-Gómez I, Giles T. European Survey of contact lens wearers and eye care professionals on satisfaction with a new water gradient daily disposable contact lens. Clinical Optometry. 2014 6:17-23. 5. Optician Awards 2014. www.opticianawards.com. 20 May 2014. 6. Pruitt J, Bauman E. The Development of Dailies Total1 Water Gradient Contact Lenses. Contact Lens Spectrum. 6/1/2013 7. Draper M, Pérez-Gómez I and Pruitt J. A water gradient contact lens. Optician. 5 April 2013:24-26 See product instructions for complete wear, care and safety information. Alcon Laboratories (SA) (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, Midrand, Johannesburg, 2090. Telephone: 011-840 2300.

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63

TM cell function

TM cell morphology

Steroids with maximum clinical action a. Prednisolone, schedule 4

Activation of TM cells, increased endoplasmic reticulum, golgi responsiveness and secretory vesicles ISO LESO GREEN ISO LESO YELLOW Increased TM cell &C nucleus size 90 C 0 Pred Mild® Increased capacity of M 40 M 60 Y 100 Y 100 Minims biosynthesis K

64

Corticosteroids are safe in porphyria.

Inhibition of proliferation and migration Inhibition of phagocytosis IOP elevation and decreased hydraulic conductivity

45

K

TM extracellular matrix (ECM)

R 4 Increased depositionR G ECM 81 G of material in TM B 41 Increased expressionB of fibronectin, laminin, collagen and elastin Altered expression of GAGs Thickening of trabecular beams

TM cytoskeleton

Formation of crosslinked actin networks Increased expression of actinbinding proteins Generation of microtubule tangles Increased resistance to cytoskeletal disruption

TM cell junctional complexes

Altered gap-junction morphology Altered expression of select integrins Altered expression of tight junction protein

TM cell gene expression

Increased expression of glaucoma gene MYOC (TIGR) Increased expression of select ECM molecules Decreased expression of matrix metalloproteinase

0

Pred Forte®

Prednisolone

245 130 32

Minims Prednisolone

Minims Prednisolone Sod. Phos 0.5% Prednisolone has the greatest antiinflammatory efficacy of all topical ophthalmic steroids including glycosaminoglycins [GAGS]). Pred Forte® 1% is the most effective of the topical ophthalmic steroids for the treatment of uveitic and corneal inflammation. It is also well suited for treatment of severe forms of ocular inflammation such as scleritis, iritis and chemical/thermal burns of the cornea due to its ability in suspension form (prednisolone acetate) to penetrate the intact cornea and anterior chamber. The solution form (prednisolone sodium phosphate) does not penetrate the cornea and anterior chamber well, but is an excellent choice for treating ocular surface inflammation. Pred Mild® (prednisolone acetate 0.125%) is also available and indicated for milder inflammatory disorders of the lids, conjunctiva, cornea and sclera, including chemical and


thermal burns. Prednisolone phosphate is not available in SA.

Lotemax 0.5% is now available in SA.

b. Loteprednol, schedule 4 All of the traditional steroids are ketonebased formulations. Loteprednol etabonate was designed as an analogue of prednisolone according to the “soft drug” concept proposed by Bodor. Synthesis of a “soft drug” is achieved by starting with a known, inactive metabolite of an active drug. The inactive metabolite is then structurally modified to an active form that in vivo undergoes a one-step transformation back to the inactive metabolite. Lotoprednol etabonate contains a metabolically-labile ester and lacks a ketone group. The human body has abundant esterases, but no ketones. Ketone-based steroids linger in the tissues. Although their therapeutic value is increased, it concurrently places patients at risk for undesirable side effects such as increased IOP. Ester-based steroids produce excellent anti-inflammatory effects, followed by enzymatic degradation, minimising the potential for the development of side effects. Bartlett et al, compared the effects of loteprednol 0.5% on IOP in known steroid responders to prednisolone acetate 1%. Loteprednol produced less effect on IOP than prednisolone acetate.

Lotemax®

c. Dexamethasone, schedule 4

Spersadex®

Maxidex®

Available as an alcohol or sodium phosphate derivative in a 1% suspension, Maxidex ® (Alcon) and in a solution (Spersadex® Novartis). Dexamethasone alcohol has superior anti-inflammatory activity to dexamethasone sodium phosphate, both in the presence or absence of the corneal epithelium. This is probably due to the fact that the alcohol derivative binds 50 times more readily to the

Maximum strength steroids Spersadex® 5ml, S4

Dexamethasone disodium phosphate 0.1%

Solution

Novartis

Pred Forte® 5ml, S4

Prednisolone acetate 1%

Suspension

Allergan

5ml, S4 "Dexamethasone acetate 0.1%" Suspension Alcon ISO LESO GREEN ISO LESO YELLOW

Maxidex

®

Lotemax® 5ml, S4

Lotoprednol etabonate 0.5%

Suspension

Bausch & Lomb

Prednisolone acetate 0.125%

Suspension

Allergan

Moderate strength steroids Pred mild® 5ml, S4

C 90 Flucon 5ml, S4 FML S4 M 5ml,40 Y 100 ®

®

C 0 Alcon Flourometholone acetate 0.1%" Suspension Flourometholone alcohol 0.1%" M Suspension 60 Allergan South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

65

receptor than the phosphate derivative. The phosphate derivative is more bio-available than the alcohol derivative. Dexamethasone is resistant to metabolism following penetration into the aqueous humour and has a greater propensity to raise intraocular

long-term (beyond three to four weeks) therapy. Its usefulness lies in its reduced tendency to cause ocular hypertension. The acetate formulation, Flucon® (Alcon) and confers upon fluorometholone greater clinical efficacy while still enjoying the IOP sparing effect. Its clinical efficacy is about midway between FML® 0.1% and Pred Forte® 1%.

pressure than prednisolone. Dexamethasone is indicated for steroid responsive inflammatory conditions of the

Loteprednol etabonate is due for release in South Africa in a 0.2% suspension, Alrex® and anterior segment of the globe. ISO LESO GREEN ISO LESO(Bausch YELLOW & Lomb). It is indicated for the treatment of allergic conjunctivitis and other C 90 C 0 Moderate strength topical M 40 M 60 mild ocular surface inflammatory conditions. Y 100 Y 100 palpebral and bulbar conjunctiva, cornea

corticosteroids K

45

K

R 4 schedule R a. Fluorometholone, 4

0

G

81

G

245 130

B

41

B

32

C. I mmunomodulatory drugs a. C yclosporine A, Restasis 0.05% (Allergan), not scheduled, special permission required to dispense

FML®

Flucon®

Unlike prednisolone and dexamethasone which are structurally related to cortisol, fluorometholone is a fluorinated structural analogue of progesterone. It has proven to be effective against external ocular inflammation with relatively low potential for elevating intraocular pressure. Fluorometholone alcohol 0.1% (FML ® , Allergan) penetrates into the aqueous humour after topical administration, and its ability to do so depends on the state of the corneal epithelium and degree of inflammation. It is rapidly metabolised in the aqueous humour. Fluorometholone acetate metabolises more slowly. Fluorometholone alcohol suspension 0.1% is a good choice for treating mild to moderate acute and chronic ocular surface inflammatory conditions requiring 66

Restasis®

Cyclosporine is an immunosuppressive antibiotic. It specifically inhibits proliferation of T-lymphocytes as well as the response of inducer T-cells to IL-1. At the cellular level, cyclosporine binds to a specialised protein called cyclophilin, and the complex thus formed inactivates calcineurin inside the target cell. Due to this phenomenon, helper T-cells fail to respond to antigenic stimulus. Suppressor T-cells are usually unaffected. Cytokine production is inhibited.


Restasis® mechanism of action

Topical cyclosporine A has been advocated

is b.i.d for 6 months, then once a day

for the treatment of corneal graft

indefinitely. Initially a steroid (FML®) is used

rejection, Behcet’s disease, endogenous

q.i.d with Restasis until the pre-existing

uveitis, sympathetic ophthalmia, vernal

T-cells are eliminated.

keratoconjunctivitis, and keratoconjunctivitis sicca.

Adverse ocular effects are burning and stinging. Cyclosporine A is contraindicated

Although not a typical anti-inflammatory

in

drug, cyclosporine A has been used to

herpes simplex keratitis.

effectively address the inflammatory

normal neural signal is restored to the

4. Corticosteroid / Antibiotic ISO LESO YELLOW combinations

lacrimal gland, reducing inflammation in

This class of ophthalmic drug is

the gland and increasing tear production.

very useful and frequently used i n

cascade in the dry eye syndrome. Due to the reduction of the inflammatory

ISO LESO GREEN

components on the ocular surface, the

active

ocular

infections

including

C 90 C 0It rivals pure topical ophthalmic practice. take around 110 days to die. The dosage c o r t i c o s t e r o i d s i n t h e t r e a t m e n t o f 400.05% for dry eye treatment ocular inflammation M 60 ofM Restasis and the antibiotics South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 Pre-existing T-cells are not eliminated and ®

67

in thetreatment of bacterial infection. In order to prescribe a combination drug with clinical precision, the clinician has to have a good understanding of the properties of both antibiotics and corticosteroids. From the previous chapters it is evident that the need for topical antibiotics alone is relatively low, and almost every red eye has a significant inflammatory component.

a. Maxitrol® (Alcon), schedule 4

Maxitrol®

Maxitrol® contains neomycin 0.5%, How does the astute clinician choose ISO LESOpYELLOW olymyxin B 6000 units/ml, and ISO LESO GREEN between a pure steroid and a dexamethasone 0.1%. Its vulnerability is C 90 C 0 M 60 the neomycin reaction which occasionally combination drug? M 40 Y 100 Y 100 occurs in certain patients. It, however, K 45 K 0 The pivotal issue is the integrity of the remains a real workhorse in primary eye R 4If t he c or neRal 245 c ornea l ep itheliu m. G 81 G 130 care and is frequently prescribed on its own epithelium is intact, there is little or no B 41 B 32 or in combination with other antibiotics reason to prescribe prophylaxis for and non-steroidal anti-inflammatories oppor tu nis tic ba ct e r i al pat hoge ns . for postoperative care of the cataract As previo u s ly d is cus s e d, t he i nt ac t patient. corneal epithelium is itself an effective defence. If significant corneal epithelial compromise is present, a combination drug may be more effective therapy. In cases of bacterial conjunctivitis with significant inflammation and intact corneal epithelium, a combination drug should be considered. The decision is based on the severity of the infection and the degree of conjunctival injection. Pure bacterial infection is uncommon whereas non-infectious conjunctivitis is common. Some exceptions to the general rule above are herpes simplex keratitis and corneal abrasions. In such cases steroid therapy is contraindicated. Keratoconjunctivitis sicca, epidemic keratoconjunctivitis (EKC), Thygeson’s superficial keratopathy (SPK), and phlyctenular keratoconjunctivitis (PKC) are indications for combination drugs. 68

b. Tobradex® (Alcon), schedule 4

Tobradex®

Tobradex® contains tobramycin 0.3% and dexamethasone 0.1%. Dexamethasone provides excellent anti-inflammatory efficacy while the tobramycin provides excellent coverage against most of the common ocular pathogens, including gr am -ne g a t iv e P se ud o mo n a s. Th e propensity of dexamethasone to raise IOP is rarely a concern since the combination drugs are not often used for more than a week or two. It is the drug of choice for


moderate to severe conditions where a combination drug is indicated.

in combination with other drugs for postoperative care.

c. Spersadex Comp® (Adcock Ingram, Novartis), schedule 4

d. F ML Neo® (Allergan), schedule 4

Spersadex Comp®

FML neo®

Spersadex Comp ® is a combination of dexamethasone 0.1% and chloramphenicol 0.5%. Chloramphenicol is bacteriostatic, inhibiting bacterial protein synthesis against a wide spectrum of gram-positive and gram-negative bacteria as well as Chlamydia, Rickettsiae and spirochaetes, but not Pseudomonas aeruginosa. It is a highly lipophilic drug with excellent corneal penetration resulting in high aqueous levels with topical application. The relative toxicity of chloramphenicol is the cause of some controversy among medical authorities. This is due to bone marrow toxicity. (See previous discussion).

FML neo® is a combination of neomycin 0.5% and fluoromethalone 0.1%. Neomycin kills most gram-negative (except Pseudomonas) and gram-positive bacteria. As always, the risk of neomycin hypersensitivity exists with this combination. Fluoromethalone alcohol suspension 0.1% is a good choice for treating mild to moderate acute and chronic ocular surface inflammatory conditions requiring long-term (beyond three to four weeks) therapy. Its usefulness lies in its reduced tendency to cause ocular hypertension.

Dexamethasone is a potent antiinflammatory with excellent efficacy. The propensity of dexamethasone to raise IOP is rarely a concern since the combination drugs are not often used for more than a week or two. It is the drug of choice for moderate to severe conditions where a combination drug is indicated. This combination is well tolerated by patients with excellent efficacy and is one of the mainstays of primary eye care. It is frequently prescribed on its own or

e. B etnesol N® (Aspen), schedule 4


90 40 100

ISO LESO YELLOW

C 0 M 60 Betnesol N South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100 ®

69

Betnesol N® is a combination of betamethasone 0.1% and neomycin 0.5%. Betamethasone is a synthetic corticosteroid with minimal mineralocorticoid activity along with a potent anti-inflammatory action. The half life is much longer than that of prednisolone. Neomycin sensitivity is the Achilles heel of this but is not used much in primary eye care anymore.

f. Sofradex (Aventis), schedule 4 ®

Contraindications of steroid/ antibiotic combinations include: • A cute herpes simplex, vaccinia, varicella and other viral diseases of the cornea and conjunctiva. • T uberculosis and mycobacterial infections of the eye. • F ungal diseases of ocular structures. • A cute purulent infections (may be masked or enhanced by the presence of the steroid).

ISO LESO GREEN

ISO LESO YELLOW

C

90

C

0

M Y K

40 100 45

M Y K

60 100 0

R G

4 81

R G

245 130

B

41

B

32

• H ypersensitivity to any of the components of the medicines. • M echanical lacerations and abrasions of the eye.

Sofradex®

Combination corticosteroids/antibiotics in South Africa

70

FML Neo®, S4

“Fluoromethalone 1.0mg/ml Neomycin sulphate 5.0mg/ml”

Allergan

Suspension

Maxitrol®, S4

Dexamethasone 0.1% Neomycin 0.35% Polymyxin B

Alcon

Susp./ung

“Zylet® (Not in SA yet)”

Lotoprednol etabonate 0.5% Tobramycin 0.3%

Bausch & Lomb

Suspension

Spersadex comp® S4

“Dexamethasone disodium phosphate 1mg Chloramphenicol 5mg”

Novartis

Solution

Tobradex®, S4

Tobramycin 0.3% Dexamethasone 0.1%

Alcon

Susp./ung

Betnesol-N®, S4

Neomycin 0.5%. Betamethasone 0.1%

A&H

Solution/ung

Sofradex®, S4

Framycetin 5mg/ml, Gramicidin 0.05mg/ ml, Dexamethasone 0.5mg/ml

Aventis

Solution/ung


Sofradex ® contains a combination of

cell degranulation and chemical mediator

framycetin 5mg/ml, gramicidin 0.05mg/ml,

release. The mediators released from the

and

0.5m g/ m l .

mast cells include histamine, prostaglandin

Framycetin is an isomer of neomycin

D2, eosinophil chemotactic factor,

(aminoglycoside) and is used extensively

eosinophil granule major protein, platelet

as a topical antibiotic in general medical

activating factor, as well as several other

practice. Neomycin is a mixture of

mediators. The release of these mediators

three substances, neomycin A, B and

causes the signs and symptoms associated

C. Framycetin is otherwise known as

with ocular allergy which include itching,

d exa metha s one

neomycin B with preparations containing less than 3% neomycin C and 1% of neomycin A. It has a broad spectrum activity against gram-positive and gramnegative bacteria. Like polymyxin B, gramicidin changes the permeability of the cell membrane, killing the cell. In contrast to polymyxin B, gramicidin is effective against gram-positive bacteria. Dexamethasone provides excellent antiinflammatory activity. This combination is

tearing, mucus discharge, conjunctival vasodilatation, increased vascular permeability, papillary hypertrophy, and ocular surface alterations. Traditionally five forms of ocular allergy are recognised: - allergic rhinoconjunctivitis - atopic keratoconjunctivitis - vernal keratoconjunctivitis - giant papillary conjunctivitis - contact allergic conjunctivitis.

frequently used by general practitioners in

The pathophysiologies of these conditions

primary care.

ar e not cl e a rl y un d e rst o o d b ut t h e following four principal hypersensitivity

5. Anti-allergy drugs and decongestants

reactions have been identified.

Allergic and other hypersensitivity disorders

IgE antibodies that attach to mast cells

are caused by exaggerated immune reactions unrelated to injury or infections. The immunopathology of ocular allergy involves multiple mechanisms that are

Type 1 immediate hypersensitivity reactions Prior exposure to an allergen produces (basophils) making them susceptible to degranulation when the allergen is reintroduced. This is therefore an IgE mediated reaction where allergens bind

influenced, at least in part, by chemical

to two adjacent IgE molecules bound to

mediators released from mast cells. Each

the surface of a tissue-based mast cell

human eye (and associated adnexal

or blood-based basophil, triggering the

tissues) have approximately 50 million mast

release of mediators and other substances.

cells, containing several hundred vesicles

Hayfever allergic conjunctivitis, vernal

filled with mediators implicated in ocular

keratoconjuctivitis, asthma, and reactions

ISO LESO GREEN

ISO LESO YELLOW

C 90 0 or other chemicals to bee stings,C penicillin, has an estimated 500 000 receptors for are examples of allergies with Type 1 Mantibodies 40 which play a role in mast components.M 60 IgE South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100 allergies. The surface of each mast cell

71

Type 2 hypersensitivity reactions

conjunctivitis, and preservative-induced blepharokeratoconjunctivitis.

These reactions are also known as

What is the role of histamine?

cytotoxic, cell-stimulating or cytolytic complement-dependent cytotoxicity.

Type 1 hypersensitivity reactions underlie all

Antibodies bind to antigens on the surface

atopic and many allergic disorders. Atopy

of cells and in tissues, which activates

is an exaggerated IgE mediated immune

cytotoxic T-cells or macrophages, leading

response and allergy is any exaggerated

to cell and tissue damage. Examples of

immune response to a foreign antigen

type 2 reactions include hyperacute graft

regardless of mechanism. Therefore, all

rejection, penicillin induced haemolytic

atopic disorders are considered allergic, anaemia, and possibly cicatricial ISO ocular LESO GREEN ISO LESO YELLOW but many allergic disorders are not atopic. pemphigoid. C 90 C 0 Atopic disorders most commonly affect M 40 M 60 Y reactions 100 Y 100 the nose, eyes, skin and lungs. Type 3 hypersensitivity K

45

K

0

These reactions are known as toxic complex When an allergen binds to IgE, histamine is R 4 R 245 G 81 G 130 released from the intracellular granules of or immune complex reactions and occur B

41

B

when the circulating antibodyantigen

mast cells, which are widely distributed, but

complexes precipitate out of the tissues.

most concentrated in the skin, lungs and

This results in an acute inflammatory

gastrointestinal (GI) mucosa. Histamine

reaction. Tissues particularly at risk include

reinforces immune cell activation and is

joints, kidneys, and lungs. Type 3 reactions

the primary mediator of clinical atopy.

are infrequently encountered in ocular tissues. Examples include rheumatoid arthritis and systemic lupus erythematosus. Type 4 hypersensitivity reactions

72

32

Histamine causes local vasodilation (producing erythema), increased capillary permeability and edema ( pr odu cin g a w h e a l ), surro un d in g

These reactions are known as cell

arteriolar vasodilation mediated by

mediated or delayed reactions. They differ

neuronal reflex mechanisms (producing

from the other reactions in that sensitized

flare), and stimulation of sensory nerves

T-lymphocytes, rather than antibodies,

(producing itching). This is known as the

interact with the antigens. T-lymphocytes

triple response of Lewis. Histamine also

release lymphokines (cytokines) which

causes smooth muscle contraction in the

activate eosinophils, monocytes and

airways (bronchoconstriction) and in the

macrophages, neutrophils and/or killer

GI tract (increased GI motility) as well as

cells which lead to tissue injury. Within 24

increased salivary and bronchial gland

to 48 hours of exposure to the antigen,

secretions. When released systemically,

the patient develops erythema and

it is a potent arteriolar dilator and can

perivascular inflammation. Examples

cause extensive peripheral pooling

of type 4 reactions include most drug

of blood and hypotension. (Cerebral

allergies, allograft rejection, contact

vasodilation

dermatitis, atopic keratoconjunctivitis,

a factor in vascular headache). It

vernal keratoconjunctivitis, giant papillary

also increases capillary permeability,

may,


for

example,

be

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CONSISTENT COMFORT FROM DAY 1 TO DAY 304

SmartShieldTM surface Lipids

Silicone hydrogel lens material

ISO LESO GREEN

NEW

ISO LESO YELLOW

PERFORMANCE DRIVEN BY SCIENCE™

C M Y

90 40 100


** Compared to AIR OPTIX® AQUA contact lenses. † Compared to Senofilcon A lenses, Balafilcon A lenses, Comfilcon A lenses, and AIR OPTIX® AQUA contact lenses.

References: 1. Nash W, Gabriel M, Mowrey-Mckee M. A comparison of various silicone hydrogel lenses; lipid and protein deposition as a result of daily wear. Optom Vis Sci. 2010;87:E-abstract 105110. 2. In vitro wetting analysis: out-of-pack and wetting substantivity. Alcon data on file, 2014. 3.. In vitro study over 16 hours to measure wetting substantivity; Alcon data on file, 2015. 4.. Eiden SB, Davis R, Bergenske P. Prospective study of lotrafilcon B lenses comparing 2 versus 4 weeks of wear for objective and subjective measures of health, comfort, and vision. Eye & Contact Lens. 2013;39(4):290-294. See instructions for use for complete wear, care and safety information. Alcon Laboratories (SA) (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, Midrand, Johannesburg, 2090. Telephone: 011-840 2300. V-AIR-023-V2 April 2016 Expiry date: April 2017

73

resulting in plasma and plasma protein loss, which may worsen circulatory shock.

hyperaemia. Recently the scheduling status of all OTC decongestants and vasoconstrictors has been changed to S2 which means that they can now only be purchased from a registered pharmacy.

Non-mast cell histamine is synthesized according to cellular demands and plays a role in regulation of capillary permeability, In patients with hyperthyroidism and serves as a CNS neurotransmitter, and significant corneal damage, pupil dilation regulates gastric acid secretion. It is can occur. Reactive hyperemia occurs probably not involved in the clinical when the smooth muscle of the blood manifestations associated with mast cell vessels fail to respond to the neuronally histamine release. non-adrenaline and the vessels ISO LESO GREEN ISO LESOreleased YELLOW dilate even more. Patients often mistake C 90 C 0 Treatment of ocular allergy M 40 M 60 this as a worsening of the problem and use Y 100 Y 100 In general, treatmentK of ocular allergy the vasoconstrictor even more. Reactive 45 K 0 is based on the symptoms, severity and hyperemia or rebound hyperemia is more R 4 R 245 81 G 130 common with phenylephrine than with the characteristics of theG allergic reaction. B 41 B 32 A step care approach is advocated, other vasoconstrictors. wher eby trea tm en t aggr e s s i ve ne s s is tailored to the level of the disease. a. Phenylephrine HCl 0.12% Among the treatment options, topical (Prefrin®), schedule 2 decongestants, oral and topical antihistamines, mast cell stabilizers, NSAIDs, corticosteroids, and immunosuppressive agents have proved useful for alleviating the signs and symptoms associated with ocular allergic reactions.

A. D econgestants or vasoconstrictors Four s ynthetic a d r e ne r gi c agoni s t s , namely phenylephrine, naphazoline, oxymetazoline and tetrahydrozoline are available as ocular decongestants. Topical application to the eye results in vasoconstriction of the conjunctival blood vessels at concentrations low enough to prevent pupil dilation due to the sympathomimetic action. These agents provide only palliative therapy; they have no effect on the cause of the conjunctival

74

Prefrin®

Phenylephrine is the oldest of the available agents. At the 0.12% concentration it causes vasoconstriction due to direct stimulation of the alpha receptors on the conjunctival vasculature. The resulting clinical effect is usually a decrease in hyperaemia and edema. At the 0.12%


concentration it can occasionally dilate

Naphazoline, oxymetazoline, and

the pupil, which is most likely when

tetrahydrozoline are classified as imidazole

the co r nea l ep itheli u m i s dam age d

derivatives and are structurally different

or diseased. Chronic use can lead to

from other adrenergic agonists. These

a rebound conjunctival congestion,

agents exhibit greater alpha- than

resulting in conjunctivitis medicamentosa.

betaadrenergic receptor activity and,

I t has m inim a l ef f e c t on t he IO P .

following topical instillation, induce marked

Phenylephrine is chemically compatible

vasoconstriction. The imidazole derivatives

with a variety of compounds and can be

are less likely to induce rebound congestion

combined in ophthalmic formulations with antihistamines, corticosteroids, and antibiotics.

b. N aphazoline (Oculosan®), oxymetazoline (Oxylin®), and tetrahydrozoline (Spersallerg®), schedule 2

and pupillary dilation than phenylephrine. They can also be combined with antihistamines (Spersallerg ®, AntistinPrivin®), corticosteroids (Efemoline®) and antibiotics. In a study by Butler and associates, tetrahydrozoline 0.05% significantly lowered IOP compared to phenylephrine 0.12% and naphazoline 0.012%. Naphazoline 0.12% produced a somewhat higher IOP than the control group. Since the vasoconstrictors are adrenergic agonists, they can affect all target tissues innervated by the adrenergic division of the autonomic nervous system. Caution should be used in patients with diseased or traumatized corneas, cardiovascular disease, hyperthyroidism or diabetes. They are also contraindicated in patients with

Oxylin®

potentially occludable angles. Pupillary dilation and rebound congestion can occur with extended use. Drug-facilitated sexual assault with topical vasoconstrictors and decongestants

ISO LESO GREEN

ISO LESO YELLOW

Although topical vasoconstrictors and

decongestants are widely used in overthecounter (OTC) and prescription eye and nasal preparations, they have recently

C 90 C with 0 drug-facilitated been associated sexual assault (DFSA). The drugs remain M 40 M 60 Spersallerg® & Oculosan® pharmacologically active even when South African Guide to Topical Ophthalmic by Dirk Booysen Y 100 Y Drugs 100

75

orally consumed (more so if consumed the attack. The dose necessary to induce with alcohol) and are readily available to coma in a child has been reported as 2-5ml perpetrators. The commercial products of a 0.05% solution. The dose to produce are colourless and sold in small containers coma in an adult is unclear. The onset of (15 and 30ml). The pharmacology and action after ingestion of tetrahydrozoline mechanism of toxicity differ depending is rapid: from 15 to 30 minutes and the on whether the drug is used topically or duration of action is reported as 12 to 24 consumed orally. Tetrahydrozoline is and hours after ingestion. alpha-2 receptor agonist. Stimulation of B. Antihistamines and the alpha-2 receptor decreases cellular mast cell stabilizers cyclic-AMP production with subsequent ISO LESO GREEN ISO LESO YELLOW decreased neuronal activity. Stimulation of a. Mast cell stabilizers C 90 C 0 post-synaptic alpha-2 receptors produces M 40 M 60 Mast cell stabilizers stop the influx of calcium local vasoconstriction Ywith 100 reduced blood Y 100 ions across the cell membrane. They do not K 45 K 0 flow and subsequent decreased tissue interfere with the binding or interaction of R 4 for therapeutic R 245 swelling which is the basis G 81 G 130 the antigen to cell surface IgE molecules. use as a decongestant. Owing to Bits 32 B 41 They inhibit degranulation and reduce the lipophilic properties, there is limited systemic release of histamine, the primary mediator absorption after ocular or nasal use with of early phase symptoms of itching and no significant cardiovascular effects. conjunctival hyperaemia. They are also However, after ingestion, tetrahydrozoline effective in limiting the release of other readily crosses the bloodbrain barrier cells involved in the inflammatory process, and produces presynaptic alpha-2 such as the macrophages and eosinophils, stimulation. Clinical effects from which are responsible for the late phase of central alpha-2 receptor agonism from an allergic response. Mast cell stabilizers tetrahydrozoline are similar to other act prophylactically and their level needs imidazoline derivatives such as clonidine, to accumulate over a number of days or tizanadine, oxymetazoline, apraclonidine, weeks before they become effective. In the brimonidine, xylometazoline, and treatment of seasonal allergic conjunctivitis, naphazoline. Reported effects include mast cell stabilizers should be used several drowsiness, coma, respiratory depression, weeks before exposure to an allergen to bradycardia, hypotension, hypotonia, be effective and the treatment should be muscle flaccidity, and hypothermia. continued until well after the symptoms Concomitant use of tetrahydrozoline with have abated. Mast cell stabilizers are less another CNS depressant (such as alcohol) effective than antihistamines in alleviating may have potential additive effects, even symptoms of itching. decreasing the dose of tetrahydrozoline necessary for CNS depression. Used in 1. Sodium cromoglycate 2% this way tetrahydrozoline is a potent CNS solution (Chromohexal, depressant producing a flaccid, obtuned, Vividrin®, Stop Allerg, or comatose victim, potentially unable to Cromabak®), schedule 2 and resist or recall events that occurred during ®

Alomide (unscheduled)

76


Phenylephrine and oxymetazoline are probably safe in porphyria. Antihistamines/Vasoconstrictors

“Spersallerg®, S2 Oculosan®, S2 Antistin-Privin®, S2”

“Antazoline HCl 0.5%, Tetryzoline 0.4% Zinc sulphate 0.2mg, Naphazoline nitrate 0.05mg Antazoline sulphate 5mg/ml, Naphazoline nitrate 0.25mg/ml”

Novartis

Emadine®, S2

Emadastine difumarate 0.05%

Alcon

“Oxylin®, S2 Prefrin®, S2”

“Oxymetazoline HCl 0.25mg Phenylephrine HCl 1.2mg”

Allergan

Livostin®, S2

Levocabastine 0.5%

Novartis

Cromabak®, S2

Sodium Cromoglycate 20mg/ml (2%)

Allergan

Stop-Allerg®, S2

Sodium Cromoglycate 20mg/ml (2%)

Allergan

Vividrin®, S2

Sodium cromoglycate 20mg/ml (2%)

Bausch & Lomb

Alomide®, S2

Lodaxamide trometamine 0.1%

Alcon

Mast cell stabilizer

Combination; Antihistamine/Mast cell stabilizer/lgE inhibitors

Zaditen®, S2

Ketotifen 0.025%

Novartis

Patanol®, S2

Olopatadine 0.1%

Alcon

HCl 0.05% ISO LESOEpinastine GREEN

Relestat®, S2

C M Y

90 40 100

ISO LESOAllergan YELLOW


77

Cromobak®

Stop Allerg

Sodium cromoglycateISO produces LESO GREEN its effect ISO LESOAlomide YELLOW ® by stabilizing the membranes of the mast C 90 C 0 Lodoxamide is a mast cell-eosinophil M 40 M 60 cells, preventing the release of histamine. Y 100 Y 100 inhibitor indicated for the treatment of giant Basophils are not affected. In asthmaK it 0 K 45 papillary conjunctivitis, vernal conjunctivitis, may inhibit the B-cell Rproduction of IgE, 4 R 245 G 81 G 130 reduce the activation of macrophages, and other forms of allergic conjunctivitis. It B 41 B 32 and reduce the release of cytokines from has no anti-inflammatory, vasoconstrictor T-cells. It is used topically in the prophylactic or antihistamine properties. It is 2 500 treatment of vernal conjunctivitis and times superior to sodium cromoglycate in other allergic reactions. It has no intrinsic potency (nedocromil sodium). It can be vasoconstrictor or anti-inflammatory used in children older than 2 years. properties, and if histamine has been released its effects are limited. It can be b. Antihistamines used in children older than 4 years.

2. N edocromil sodium 2% solution, schedule 2 Nedocromil sodium is a mast cell stabilizer that appears to be superior to sodium cromoglycate, especially in its action against the mucosal type of mast cells in vitro. It is also effective against macrophages and eosinophils, inhibiting the release of chemotactic and inflammatory mediating substances. The onset time is short and dosage is b.i.d or q.i.d depending on the severity of the condition. It can be used in children older than 3 years.

(H1receptor-antagonists)

The alternative method of antagonising the action of histamine is by using a pharmacological antagonist, namely antihistamine. Histamine is synthesised and stored in nearly all tissues, with especially high concentrations in the lungs, skin, stomach, duodenum and nasal mucosa. In ocular tissue, histamine occurs in the highest concentrations in the lids, conjunctiva, sub-conjunctiva, episclera, limbus and uvea. The lens, aqueous, retina and other internal ocular structures have essentially no histamine. Histamine receptors have been divided

3. L odoxamide 0.1%solution (Alomide®) 78

into three types. H1 (classic) receptors are present in


smooth muscles and mucous membranes.

vascular effects. Blood vessels contain H1

Histamine acts on them and causes

and H2 receptors which, when stimulated,

contraction of smooth muscle in the gut,

dilate (H2) the small pre-capillary blood

bronchi (bronchoconstriction) and cells of

vessels and constrict (H1) the relatively

the small venules, exposing the basement

larger venules. In the eye, histamine

membrane and allowing plasma to pass

release produces the characteristic

into the extracellular space, causing

signs and symptoms of ocular allergy:

edema.

itching, redness, tearing, chemosis,

H2 receptors are present in gastric glands,

of

blood vessels, the heart, uterus and other tissues. On stimulation they cause various effects, including increased gastric secretion, vasodilation (effect on smooth muscle of blood vessels), stimulation of the heart, and relaxation of the uterus. H3 receptors are present in the CNS but detailed functions of these receptors are not yet well understood.

lid and conjunctival edema, dilation conjunctival

blood

vessels,

and

papillary reaction. Histamine has no effect on the retinal blood vessels. The following table summarises the distribution of H1 and H2 receptors and the effect of antihistamines on each. (Topical drugs are indicated in red). Antihistamines reversibly bind to the histamine receptors, thus preventing histamine from binding. This prevents the

When massive mast cell degranulation

physiologic or pharmacologic actions of

occ urs , his ta m ine cau s e s s i gni fi c ant

histamine and relieves signs and symptoms

Histamine receptor

Tissue

Histamine antagonist

H1

Bronchial smooth muscle Heart CNS Mucous membranes Eye (blood vessels) Blood vessels

Diphenhydramine Promethazine Pyrilamine maleate Cyclizine Terfenadine Loratadine Chlorpheniramine Antazoline Levocabastine Azelastine Emedastine Ketotifen Olopatadine Epinastine

“Gastric parietal cells ISO LESO GREEN Heart

H2

C M Y

90 40 100

Blood vessels Mast cells Eye (blood vessels) Bronchial smooth muscle CNS White blood cells”

Cimetidine ISO LESO YELLOW Ranitidine Nizatidine Famotidine


79

associated with histamine release. H1 specific antihistamines block histamine induced capillary dilation, increased capillary permeability, and the associated itching and pain. If dilation and edema have already occurred, the administration of these drugs will prevent further histamine action, but it usually does not reverse the clinical manifestations already present. Livostin 1. A ntazoline 0.5%ISOsolution LESO GREEN ISO LESO YELLOW ® (Antistin-Privin®C, Spersallerg ), Levocabastine is a potent pure H1 90 C 0 M 40 M 60 antihistamine, effective within 15 minutes schedule 2 ®

Y K

100 45

Y K

100 0

R G

4 81

R G

245 130

B

41

B

32

of topical administration, with high bioavailability (20 to 40%). Dosage is q.i.d. It can be used in children older than 3 years.

3. A zelastine 0.05% solution (Optivar®), schedule 2

Antistin-Privin®,

Spersallerg®

Antazoline is an H1 antihistamine. It is mostly used in combination with sympathomimetic vasoconstrictors because this combination is more effective than each component on its own. Two forms of antagonism, pharmacological (H1 antihistamine) and physiological (vasoconstrictor), result in

Azelastine is an H1 antihistamine with some mast cell stabilizing action, preventing the release of chemical mediators such as leukotrienes, histamine, and serotonin. It has a quick onset of action and its duration of action allows t.i.d dosage. It can be used in children older than 4 years.

4. Emedastine 0.05% solution (Emadine®), schedule 2

this additive effect. This is very effective at reducing itching, pain, photophobia and redness associated with ocular allergy. Antazoline slightly decreases IOP.

2. L evocabastine 0.5% suspension (Livostin®), schedule 2 80

Emadine®


Emedastine is an H1 antihistamine virtually identical to levocabastine and effective in the treatment of lid myokymia. Dosage is normally q.i.d for allergy and q.i.d for one week, then b.i.d for another week for lid myokymia (controversial). It can be used in children older than 3 years.

5. Ketotifen 0.025% solution (Zaditen®), schedule 2

O l opat ad in e is a v e ry sp e cif ic H 1 antihistamine without any antimuscarinic activity. It has a mast cell stabilizing action in addition to the H1 blockade. The onset of action is rapid and the duration of action is up to 8 hours, making b.i.d dosage possible. It can be used in children older than 3 years.

7. Epinastine 0.05% solution (Relestat®), schedule 2

Zaditen®

Ketotifen is similar to azelastine in that it has mast cell stabilising properties as well as selective, non-competitive inhibition of H1 receptors and eosinophils. Dosage is b.i.d or t.i.d. It can be used in children older than 3 years.

6. Olopatadine 0.1% solution (Patanol®), schedule 2

Relestat®

Epi nas t i ne is a h ig h l y e f f e ct iv e H 1 antihistamine with little antimuscarinic effect, but good mast cell stabilizing and antiserotonin effect. Dosage is b.i.d and it can be used in children older than 3 years. Antihistamine and mast cell stabilizer side effects Milder side effects of the oral H1 antihistamines are sedation and atropinelike effects. Oral terfenadine and astemizole can cause polymorphic,

ISO LESO GREEN C 90 Patanol® M 40 Y 100

ventricular tachycardia and should ne ve r b e use d w it h e ry t h ro my cin , clarithromycin, ketoconazole or itraconazole. No such effects have been reported with topical administration. Although these agents are generally well tolerated, burning, stinging and discomfort on instillation are not

ISO LESO YELLOW


81

un c omm on. Long t e r m u s e of t he antazoline-naphazoline combination

Referral guidelines based on IOP measurement

has also been implicated in corneal verticillata. Combination formulations

- R epeated measures are >28– 30mmHg even if ONH and fields are normal.

with tetrahydrozoline can cause pupil dil ation in lig ht iride s . T he s e dr u gs

- C onsider the risk of CRVO if IOP is >35mmHg, semi-urgent referral.

are contraindicated in narrow angle gl aucoma . O r a l a n t i hi s t am i ne s w i t h

- Inter eye differences of 8mmHg is usually abnormal.

strong anticholinergic properties are also contraindicated in patients with peptic ulcers, prostatic hypertrophy, ISO LESO GREEN

ISO LESO YELLOW

and bladder or pyloroduodenal

C 90 C 0 obstruction. They should not be used M Y K

40 100 45

M Y K

in the first trimester of pregnancy due to foetal malformation, and they will

60 100 0

R 4 R 245 aggravate dry eye. Mast cell stabilizers G 81 G 130

have good visual function and modest reduction in quality of life, but more advanced disease leads to considerable reduction in quality of life.

a r e r e l a t i v e l y f r e e B o41 f s i d e e f f e c tBs , 32 Individualized glaucoma treatment aims but transient stinging or burning on at providing glaucoma management instillation may occur. Mast cell stabilizers and antihistamines are safe in porphyria.

6. Primary Open Angle Glaucoma A. M edical Management of Primary Open Angle Glaucoma

tailored to the individual needs of the patient. Patients with severe functional loss or younger patients with manifest disease should have more aggressive treatment and closer follow-up than patients with little or no risk (such as patients with OHT and otherwise normal findings), or elderly patients with mild field loss and low IOP levels. Currently the only effective treatment of POAG efficient in preserving visual function is lowering of the IOP. Other areas are under investigation, including

a. Introduction The goal of glaucoma treatment is to maintain the patient’s visual function and related quality of life at a sustainable

82

managing ocular blood flow and providing neuroprotection. So far, these treatment strategies remain under investigation.

cost. The cost of treatment in terms

Prevailing IOP is a balance between

of inconvenience and side effects as

in reducing IOP, there are three basic

well as financial implications for the

medical treatment strategies:

individual and society requires careful

- Reduction of inflow by agents which

evaluation. Quality of life is closely linked

decrease aqueous secretion such

to visual function. Overall, patients with

as β-blockers, carbonic anhydrase

early to moderate glaucoma damage

inhibitors, and α-agonists.


Disc size and “normal” C/D ratios 1. S mall disc = 1.0-1.5mm², C/D 0.55 considered upper limit of normal.

Diagnosis of glaucoma, past & present

2. M edium disc = 1.4-1.7mm², C/D 0.65 considered upper limit of normal.

1. Visual field changes

3. L arger disc = 1.8-2.0mm², C/D 0.75 considered upper limit of normal.

3. Intraocular pressure

- Reduction of IOP by agents which increase outflow via conventional (trabecular) means such as pilocarpine. - Increase in outflow by non-conventional (uveoscleral) drainage routes such as achieved by prostaglandin analogues. Target pressure is a useful concept in the practical management of glaucoma patients. It can be described as the highest IOP level that is expected to prevent further glaucomatous damage or that can slow disease progression to a minimum. As can be expected, this level varies between patients and eyes and is strictly individual. The least amount of medication and thus the least amount of side effects to achieve the desired therapeutic response should be a consistent goal. One of the limitations of the target pressure approach is that we only know in hindsight whether the target pressure selected initially was adequate or not, in other words, the patient will get worse before we know the target pressure

2. Examining visual function in glaucoma 4. Examination of the ONH - direct observation - photography - HRT 5. Examination of the nerve fibre layer - OCT, GDX - direct observation 6. Gonioscopy

was inadequate. There is no single IOP level that is safe for every patient. However, a 20-40% reduction of the clinical IOP at which damage occurred is usually the initial target. Target IOP depends on: - IOP level before treatment: the lower the untreated IOP, the lower the target IOP should be. -S tage of glaucoma: the more pre-existing damage, the lower the target IOP should be. - Rate of progression during follow-up. - Age and life expectancy: younger age requires lower target IOP. - Presence of other risk factors, e.g. exfoliation syndrome.

BaltimoreGREEN eye study ISO LESO

ISO LESO YELLOW

Blue Mountain eye study

IOP (mmHg)

Prevalence of POAG (%)

IOP (mmHg)

Prevalence of POAG (%)

16-21

1.5

12-13

0.9

C 22-29 > 30 M Y

90 40 100

C 05.7 8.3 22-23 25 > 28 39 M 60 South African Guide to Topical Ophthalmic by Dirk Booysen Y Drugs 100

83

Visual field pearls A visual field can be called abnormal if ONE of the following is abnormal in the PRESENCE OF A RELIABLE TEST: 1. Glaucoma hemifield or asymmetric test is borderline or abnormal. 2. Pattern standard deviation (PSD): P +14 or < -16), ophthalmic lenses with out of range cylinder (Cyl > 6.5) and ophthalmic lenses with a special parameter (Prism > 5.5, facet, polymerisation, filter).

ISO LESO GREEN

ISO LESO YELLOW

This range of special lenses also caters for very specific vision needs and are perfectly suited for pilots, technicians and librarians. Email [email protected] for more information.

C M Y

90 40 100


129

Glossary: ACh – Acetylcholine ONH – Optic nerve head APD – Afferent pupillary defect OTC – Over the counter ACG – Angle closure glaucoma PABA – Para-aminobenzoic acid ATP – Adenosine triphosphate PGF2α – Prostaglandin F2α analogues CAIs – Carbonic anhydrase inhibitors PKC – Phlyctennular keratoconjunctivitis CBB – Cilliary body band PK – Penetrating keratoplasty C/D – Cup to disc ratio POAG – Primary open angle glaucoma CME – Cystoid macular edema PRK – Photorefractive keratectomy CNS – Central nervous system PSD – Patern standard deviation COPD – Chronic obstructive pulmonary disease PSC – Posterior subcapsular cataract CRVO – Central retinal vein occlusion RK – Radial keratotomy ISO LESO GREEN ISO LESO YELLOW CSCR – Central serous choriodal retinopathy RNA – Ribonucleic acid, mRNA refers to CSPD – Corrected pattern standard deviation C 0 mitochondrial RNA C 90 M 40 M 60 RNFL – Retinal nerve fibre layer DNA – Deoxyribonucleic acid Y 100 Y 100 ECM – Extracelluar material K 45 SF – Short term fluctuation K 0 EKC – Epidemic keratoconjunctivits SITA – Swedish interactive thresholding algorithm R 4 R 245 SPK – Superficial punctate keratitis FB – Foreign body G 81 G 130 FDT – Frequency doubling technology SWAP – Short wavelength automated perimetry B 41 B 32 GAGs – Glycoaminoglycans TBUT – Tear break up time GAT – Goldmann applanation tonometry TCA – Tricyclic antidepressants GDx VCC® – Scanning laser polarimeter (Carl TM – Trabecular meshwork Zeiss Meditec) VA – Visual acuity GI – Gastrointestinal tract VEGF – Vascular endothelial growth factor GPC – Giant papillary conjunctivitis Latin abbreviations and terms commonly used in HCl – Hydrochloric acid ophthalmic prescriptions: HRT – Heidelberg retinal tomography HSV – Herpes simplex virus b.d; b.i.d – twice daily HTG – High tension glaucoma t.i.d; t.d.s – three times a day IgE – Immunoglobulin, class E q.i.d – four times a day IOL – Intraocular lens q.2.h; q.6.h; ... – two or six hours respectively IOP – intraocular pressure c – with ISA – Intrinsic sympathomimetic activity ex-aqua – with water ISNT – Inferior, superior, nasal & temporal; related mane – in the morning to ONH examination nocte – at night LASIK – Laser in situ keratomileusis or laser assisted m et n – morning and night intrastromal keratoplasty N.P – label with correct name LGN – Lateral geniculate body N.N.P – do not label with correct name LTG – Low tension glaucoma per os – by mouth LV – Loss variance stat – at once MAO – Monoamine oxidase IV – intravenous injection or infusion MD – Mean deviation IM – intramuscular injection MIC – Minimum inhibitory concentration SC – subcutaneous MYOC – Myocilin glaucoma gene, also known as ung – ointment TIGR (trabecular meshwork induced glucocorticoid gutta/e – drop/s response) and GLCIA. MYOC is the currently p.r.n; s.o.s – when required. Used only if preferred name. accompanied by the required dosage and the NK cells – Natural killer cells period between dosages, as well as the reason for use NSAIDs – Non-steroidal anti-inflammatory drugs Example of prescription for artificial tears: NTG – Normal tension glaucoma Viscotraan 1-2 gutta, p.r.n and /or lacrilube ung, OCT – Optical coherence tomography OHT – Ocular hypertension nocte 130


Optimum by Lobob® contact lens care solutions, when used as directed offer allergy-free ease of patient compliance in the domain of cleaning, disinfecting, storage, wetting, rewetting and in-theeye lubrication for all hard and rigid gas permeable (RGP) contact lens materials.

DE LTA

Optimum by Lobob® contact lens solutions are preserved with purified Benzyl alcohol, or are preservative-free, ensuring clean and comfortable lenses throughout the wearing cycle. Optimum by Lobob® contact lens solutions does not contain thimerosal, BAK, chlorhexidine, or polyaminopropylbiguanide, to which many lens wearers are sensitive.

ISO LESO GREEN

Delta DSW Delta plus DSW disinfects, lubricates soaks and wets. Contains poloxamer specially formulated to coat the lens making it more comfortable by reducing lens-lid interactions.Compatible with all RGP material types and has excellent lens disinfection performance.

C M Y

90 40 100

OB

Delta Daily Cleaner Optimally blended preservative free cleaner containing anionic and amphoteric surfactants. Effective cleaning and removal of proteins and lipids from the lens surface.Specially designed non-abrasive formula eliminating any risk of lens damage.

B LO

The Delta RGP System consists of specially formulated Delta daily cleaner and Delta Disinfecting, Soaking and Wetting multipurpose solution (DSW), compatible with all gas permeable materials.

ISO LESO YELLOW


131

ISO C M Y K

ISO C M Y K

CPD PROGRAM MAY 2016 Visit www.eyesite.co.za/CPD to complete the May 2016 EYESITE.co.za CPD The Program includes MCQ’s from both the EYESITE.co.za Magazine May ISO LESO GREEN ISO LESO YELLOW 2016 issue and the South African Guide to Topical Ophthalmic Drugs C 90 C 0 M 40can also be M 60 2016 Edition which downloaded on the EYESITE.co.za website. • • • •

Y

100

Y

100

K available 45 0 There are 5 CEUs for thisK CPD Program The deadline date to complete this CPD Program is September 30, 2016 R 4 R 245 81 Program is R150. G 130 The cost for the GCPD B 41 B 32 Once your Answers have been marked, your Certificate will be sent via email.

For further information, please contact [email protected] or 082 320 6431

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NEW

Introducing an advancement in corticosteroid therapy for ocular inflammation1-3 High anti-inflammatory efficacy

Improved safety profile1-3

References: 1. Pavesio CE, et al. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol 2008;92:455–459. 2. Dell SJ, Lowry GM, Northcutt JA, Howes J, et al. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol 1998; 102:251-5. 3. Comstock TL, et al. Advances in Corticosteroid Therapy for Ocular Inflammation:Loteprednol Etabonate. Int J Inflam 2012; 789623:1-11. 4. Novack GD, Howes J, Crockett RS, Sherwood MB. Change in Intraocular Pressure During Long-Term Use of Loteprednol Etabonate. J Glaucoma 1998;7(4):266-269. 5. Rajpal RK, Digby D, D’Aversa G, Mah F, et al. Intraocular Pressure Elevations with Loteprednol Etabonate: A Retrospective Chart Review. J Ocul Pharmacol Ther 2011;27(3):305-308. Scheduling status: S4 Proprietary name and dosage form: Lotemax Ophthalmic Suspension, Eye Drops. Composition: Each 1 ml contains: Loteprednol Etabonate 5,00 mg (0,5 % m/v) and Benzalkonium Chloride (preservative) 0,01 % m/v. Pharmacological classification: A 15.2 Ophthalmic preparations with corticosteroids.Indications: For the treatment of allergic conjunctivitis and acute anterior chamber uveitis. Registration number: 37/15.2/0588. © 2003 Bausch & Lomb Incorporated. ®/™ denote trademarks of Bausch & Lomb Incorporated. Applicant: iNova Pharmaceuticals (Pty) Ltd. Reg. No. 1952/001640/07. 15E Riley Road, Bedfordview, Gauteng, South Africa, 2008 . Tel: +27 11 087 0000 www.inovapharma.co.za Marketed by: Bausch & Lomb (SA) (Pty) Ltd. Reg. No.: 1996/003931/07. 15E Riley Road, Bedfordview, Gauteng, South Africa, 2008. Tel: +27 11 087 0000 www.bausch.co.za BL137/15