Corneal epithelial bullae after short-term wear of small diameter ...

Contact Lens and Anterior Eye 40 (2017) 116–126

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Case report

Corneal epithelial bullae after short-term wear of small diameter scleral lenses Alex D. Nixon, OD, MS, FAAO* , Joseph T. Barr, OD, MS, FAAO, Dean A. VanNasdale, OD, PhD, FAAO The Ohio State University, 338 W 10th Avenue, Columbus, OH 43210, United States

A R T I C L E I N F O

Article history: Received 16 June 2016 Received in revised form 7 October 2016 Accepted 21 November 2016 Keywords: (3–6) Scleral lens Optical coherence tomography Bullae Contact lens Cornea Complication

A B S T R A C T

Complications of scleral lens wear are not well documented or understood. While multiple studies focus on oxygen transmission during scleral lens wear and associated corneal swelling, little is known about the effects of varying scleral lens fitting relationships, especially when there is corneal interaction. Scleral lenses, by convention, are designed to completely clear the corneal surface and rest on the conjunctival and scleral tissue. However, some designs maximize oxygen transmission by reducing the lens diameter, thickness, and recommended corneal clearance.While the modifications increase oxygen transmission in any scleral lens design, they also distribute the lens mass closer to the limbus and make visualization of corneal clearance, especially narrow in the limbal region, more difficult. The sequelae from mechanical interaction between scleral lenses and the ocular surface, in particular the cornea, remain uncertain. This case series will describe corneal epithelial bullae, molding, and epithelial erosions as unintended scleral lens complications. These corneal changes corresponded to areas of contact lens-corneal bearing confirmed utilizing a combined scanning laser ophthalmoscopy (SLO) and anterior segment OCT. This case series will discuss epithelial bullae detection, their etiology, and suggestions for application of this information into scleral lens fitting protocols. © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Recently, the availability and popularity of scleral contact lenses have increased dramatically [2,3]. While the precise definition of the lens varies, the Scleral Lens Education Society (SLES) has described scleral lenses as contact lenses that rest entirely on the sclera and conjunctiva, avoiding corneal interaction [1]. The rationale for using scleral lenses is to improve lens comfort and stability, compared to corneal rigid lenses, by moving the contact lens support away from the densely innervated cornea. Based on the SLES definition, a scleral lens should entirely vault the cornea and the limbus, a critical site for regeneration of the corneal epithelium and location of the corneal epithelial stem cells [4]. Historically, scleral lenses have been used in eyes with corneal ectasia or other surface abnormalities [5,6], but the advent of more highly oxygen transmissible materials and advances in contact lens manufacturing have expanded their use to eyes with normal corneal shape and vision [7]. The expected benefit of rigid lens use, compared to soft contact lenses, is that rigid contact lenses may provide better visual quality, especially in eyes with regular and

irregular corneal astigmatism [8,9]. Despite the recent increase in popularity of scleral lens designs, the safety of the scleral lens modality has not been fully established. For example, while scleral lenses themselves are made from a highly oxygen permeable material, the thickness of the scleral lens and the tear reservoir beneath the lens are considerable barriers to corneal oxygen availability, limiting their ability to meet previously described oxygen transmission guidelines for contact lens wear [10,11]. Some scleral lens designs maximize oxygen transmission by reducing the lens diameter, thickness, and recommended corneal clearance. While these modifications increase oxygen transmission in any scleral lens design, they also distribute the lens mass closer to the limbus and make visualization of corneal clearance, especially narrow in the limbal region, more difficult. The sequelae from mechanical interaction between these large diameter lenses and the ocular surface, in particular the cornea, remain uncertain [2]. There is justified concern that interaction between the contact lens and corneal surface could damage the epithelial stem cells present in the limbus, potentially altering epithelial regeneration and compromising the corneal surface.

* Corresponding author. E-mail addresses: [email protected], [email protected] (A.D. Nixon). http://dx.doi.org/10.1016/j.clae.2016.11.007 1367-0484/© 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

A.D. Nixon et al. / Contact Lens & Anterior Eye 40 (2017) 116–126

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1. Patients

Fig. 1. En face scanning laser ophthalmoscopy image (top) with corresponding cross sectional image (bottom) acquired simultaneously. The location of the cross section is delineated by the dashed line in the en face image. The location of the lens edge and the limbus can be seen clearly and are shown to be corresponding in the two imaging modalities (A and B, respectively). The OCT cross section shows the location of initial corneal clearance in this temporal quadrant, which can be mapped to the en face image (C).

This case series describes unanticipated scleral lens induced changes to the corneal surface in fourteen consecutive patients fit with the same small diameter scleral lens design intended for normal eyes. The changes observed included molding, epithelial erosions, and epithelial bullae present in regions of contact lens and corneal interaction. Of these fourteen patients, all had definite corneal touch present in the limbal region, which could not be alleviated by available lens parameter changes within this scleral lens design. Of the 14 patients with corneal touch, 13 developed positive corneal staining and six developed epithelial bullae within the region of corneal bearing. Interestingly, while all patients demonstrated peripheral corneal bearing, not all developed the same lens-induced changes, indicating that additional factors may influence the location, type, and extent of corneal compromise that ultimately develops. This case series illustrates the development of corneal epithelial bullae, discusses their possible mechanism of development and differentiates the bullae from other forms of corneal pathology.

Fifteen patients were consecutively fit into a commercially available scleral contact lens design by one clinician (AN) with specialized contact lens training at The Ohio State University College of Optometry. All patients included in this series were habitual contact lens wearers found to be clinically normal by comprehensive examination. One patient did not complete the fitting process due to poor subjective comfort and vision with the scleral lens design. Patients included four males and ten females, ranging in age from 22 to 37 years. The average age of the patients was 27.29 5.47 years. The mean spherical equivalent refractive error was 4.97 2.44 diopters (D) with refractive astigmatism of 0.48 0.39D. Corneal topography was completed on all patients, revealing normal corneal curvature in all patients with the flat keratometry ranging from 40.62 to 46.00. The average flat keratometry value was 43.48 1.28D. Baseline ocular health findings, including a complete cornea evaluation, were unremarkable. 2. Scleral lens fit assessment Each patient was fit in the same lens design using diagnostic lenses which were 14.60 mm in diameter with a 300 mm center thickness. The scleral lens brand, or design, was standardized because the purpose of the scleral lens wear for these patients was a research oriented comprehensive vision quality assessment. Based on manufacturer recommendations, the initial lens selected was 0.30 mm steeper that the flattest corneal meridian. Assessment of the contact lens fit included slit lamp examination with topical ophthalmic fluorescein dye. Simultaneous scanning laser ophthalmoscopy (SLO) and cross sectional anterior segment optical coherence tomography (OCT) images were also acquired using the Heidelberg Spectralis Anterior Segment Module (Heidelberg Engineering, Carlsbad, CA). Imaging constraints in this specific instrument resulted in an insufficient imaging depth to capture the entire cross section of the cornea and contact lens in a single image. For this reason, multiple images were acquired during each session, centered on either the corneal apex or the limbus (Figs. 1–2). OCT imaging was completed at each new scleral lens dispense and a separate visit following at least six hours of lens wear (Fig. 3).

Fig. 2. Combined en face and cross sectional images centrally (Top), nasally (Middle), and temporally (Bottom). The achievable depth by the Spectralis Anterior Segment Module is restricted. The central image demonstrates that one image is insufficient to assess the entire lens and cornea when the lens vault is this high, necessitating changes in gaze to acquire images of the lens interaction at the limbus.

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Fig. 3. Cross-sectional OCT images of the right eye of patient #6 centrally (1), temporally (2), and nasally (3) at dispense (subscript A) and after at least six hours of settling (subscript B). These images show corneal touch present near the limbus nasally and temporally even before settling, which was representative of all patients, with the most anterior point of touch at dispense indicated by the red line. While settling is generally measured centrally, the images (2) and (3) show increased contact lens to cornea interaction in the peripheral corneal after settling.

Fig. 4. The following anterior segment photos of patient #2 demonstrate the broad view of the scleral lens on eye (A) and the clearance present after settling centrally (C), mid-peripherally (B), and in the peripheral cornea (D) after greater than six hours of lens wear. Image D demonstrates no clearance is visible near the temporal limbus.


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Fig. 5. The above images demonstrate OCT (A, B) and anterior segment photos with fluorescein (C, D) present temporally (B, C) and nasally (A, D) in the right eye of patient #2.

The clearance was evaluated at the tallest central corneal point and in each quadrant of the peripheral cornea (Fig. 4). Central clearance was optimized by steepening or flattening the base curve to achieve nearly 300 mm of central clearance before settling. If peripheral corneal clearance was inadequate, the lens diameter was increased, as permitted within the lens design, and the base curve steepened to relieve bearing. The contact lens edge alignment was evaluated in each quadrant and steepened or flattened accordingly to optimize contact lens fit. Based on the results of the diagnostic fitting, scleral lenses were customized for each patient and ordered in the hexafocon B material with a center thickness of 300 mm. Lens thickness was increased in some patients to rule out the contribution of lens flexure to subjective visual complaints. The fitting relationship was monitored with slit lamp biomicroscopy and anterior segment spectral domain optical

coherence tomography (OCT) at each new scleral lens dispense and following at least 6 h of wear to assess lens settling. Despite multiple attempts to optimize scleral lens fit, widespread limbal bearing persisted in this lens design, both before and after lens settling. Although corneal bearing was clearly present, signs of compromise were dependent on wearing time the date of examination, making the frequency and severity of the corneal compromise difficult to estimate. In order to more clearly understand the fitting relationship present and the extent of any corneal compromise, subjects were instructed to wear the lenses for six hours on a single day, after which the fitting relationship and ocular health were re-evaluated. Following at least six hours of scleral lens wear, all 14 patients showed peripheral corneal bearing by OCT imaging. Of the 14 patients. 13 demonstrated positive corneal staining and six

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Fig. 6. Images of the cornea from patient #6 utilizing fluorescein dye viewed with cobalt blue light and a wratten filter. This patient’s OCT images are shown before and after scleral lens settling in Fig. 3. These images demonstrate the circular ridge-like pattern with epithelial bullae present near the anterior most region of corneal compression. The bullae and ridge are seen inferiorly (A), superiorly (B), temporally (C), and nasally (D) in the patient’s right eye.

patients demonstrated circumferential negative staining (Fig. 6 ) corresponding to mechanical interaction with the contact lens. The positive staining indicated punctate epithelial erosions or

compromised epithelial cells, while the negative staining corresponded to corneal bullae located near the basal layer of the epithelium. While best visualized with fluorescein and cobalt blue light, the bullae could also be seen in direct or indirect illumination with white light (Figs. 7 and 9). Following this unanticipated result, scleral lens wear was discontinued and patients returned to their habitual vision correction, either contact lenses or glasses. All patients recovered fully, although the exact timespan needed for resolution of the bullae remains unknown. Epithelial bullae remained for at least one week of monitoring in a single subject. Specific follow-up was not planned for all subjects due to the transient nature of the corneal changes observed and the planned discontinuation of scleral lens wear in all subjects. In retrospect, a more systematic follow-up schedule would have provided useful information regarding the healing process and length of time needed for complete resolution. The following are OCT and slitlamp images depicting the scleral lens fitting relationship and corneal compromise in five separate patients who developed epithelial bullae and in a single patient who, although corneal bearing was present, did not develop epithelial bullae (Fig. 5–13 ). 3. Discussion

Fig. 7. Marginal retroillumination of epithelial bullae with the contact lens on eye in patient #6 demonstrating unreversed illumination, characteristic of epithelial bullae and epithelial vacuoles. In this image, the bullae are illuminated by light reflecting from the surface of the iris traveling from right to left, consistent with the illumination of the bullae. The appreciation of these features is difficult due to their low contrast, and is made more difficult when the contact lens remains on eye and fluorescein has not been instilled.

This case series outlined the potential difficulty fitting patients in relatively small diameter scleral lenses, which may have insufficient diameter to vault the entire cornea. Despite multiple attempts to modify the lens size and shape to achieve total corneal clearance, unintended corneal interaction persisted resulting in corneal molding, epithelial erosions, and epithelial bullae. The location of these changes was found to correspond to areas of contact lens and corneal interaction by slit-lamp biomicroscopy and confirmed using anterior segment optical coherence tomography. The OCT images were crucial because the system simultaneously acquires complimentary SLO and cross-sectional OCT images, which can be used in combination to localize regions


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Fig. 8. This figure demonstrates the OCT images following settling for patient #4 in the right eye. The OCT images demonstrate obvious corneal touch in the peripheral cornea, which corresponds to epithelial bullae formation. Also of note is the hazy appearance of the fluid layer between contact lens and cornea, characteristic of the fogging that can occur with scleral lens wear.

Fig. 9. Slit lamp examination findings in patient #4 following 6 h of lens wear using direct illumination with cobalt blue and white light, respectively. The appearance with fluorescein and cobalt blue light (Left) revealed ovals of negative staining representing epithelial bullae scattered within fluorescein pooling near the anteriormost edge of lens compression. White light examination (right) shows the well-defined, coalesced epithelial bullae in the same corneal region. There is a more well-defined border of the bullae in the white light image due to the fluorescein pooling surrounding the bullae. The bullae appear less well-defined when fluorescein is not used for this type of image.

of contact lens and corneal interaction. OCT is a powerful technique, capable of reducing subjective interpretation when the clearance over the cornea is critically important, yet difficult to observe. Although this interaction can be difficult to assess using the standard clinical technique of visual inspection with fluorescein dye, recognition and action to amend the fitting relationship are critical to protect the corneal health long-term. The presence of corneal changes observed in this case series was a concerning unanticipated result, particularly as scleral lenses become more popular and more commonly fit in eyes with normal

and irregular corneal shapes. Perhaps most surprising is that the corneal changes observed developed after only six hours of wear on a single day. While corneal staining is common in contact lens wear, occurring in up to 19.5% percent of soft [12] and 80 percent of rigid contact lens wearers [13,14], the location and severity of the epithelial compromise found in this series were troubling given their proximity to the corneal epithelial stem cells in the basal layer of the epithelium near the limbus [4]. Although patient symptoms were not systematically assessed, the examiner observed the patients reporting only mild to moderate dryness

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Fig. 10. Cross-sectional OCT images after settling nasally (A) and temporally (D) paired with fluorescein (B & E) and white light (C & F) biomicroscopy photos in the corresponding corneal region of patient #9. The OCT images demonstrate corneal bearing which corresponds to arc shaped areas of positive staining as well as coalesced epithelial bullae and their associated negative staining.


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Fig. 11. This figure shows cross-sectional OCT images of subject #3 after lens settling centrally (A), temporally (B), and nasally (C). Corneal bearing over the limbus is apparent in the temporal and nasal OCT images.

or hyperemia, symptoms consistent in frequency and magnitude with general contact lens wear. We believe the changes found in this series were epithelial bullae, matching previous descriptions by Zantos [15], which can be differentiated from epithelial vacuoles and microcysts based on their oval shape, size larger than 40 mm, a tendency to coalesce into clustered formations, and appearance using marginal retroillumination [15,16]. The bullae in this series were most easily detected as locations of negative staining with fluorescein dye. The relatively small size and lack of contrast when viewed without fluorescein made them challenging to detect, and even more difficult when

Fig. 12. This is a fluorescein and cobalt blue slit lamp photograph from patient #3. In this image, there is clear differentiation possible of the positive fluorescein staining characteristic of punctate epithelial erosions (orange arrow) compared to the negatively staining epithelial bullae (white arrow).

viewed with the contact lens on the eye. The bullae can be differentiated from epithelial microcysts by the non-reversed directionality of the light through the bullae when viewed with marginal retroillumination (Fig. 7, 10) The non-reversed directionality seen in epithelial bullae and vacuoles indicates that their contents are of a lower index of refraction than the surrounding cornea, indicating fluid or gaseous contents [15]. Another differentiating factor is that microcysts are typically induced by low oxygen transmission in contact lens wear and may take two to three months to develop [16], contrary to the six hours needed for the corneal changes in this series. Corneal epithelial bullae and vacuoles are both examples of corneal epithelial edema, with few differentiating factors other than size and shape. Vacuoles are commonly described to be 5–30 mm in diameter and sphere shaped [17], while bullae have been reported to appear oval shaped, clustered, larger than 40 mm in size, and with relatively indistinct margins [15]. Documentation of bullae associated with contact lens wear is infrequent in the published literature and the underlying cause is not fully understood, but their presence had been suggested to be related to hypoxia. Documented cases have been reported after prolonged hypoxic stimuli, for example in aphakic subjects wearing hydrogel soft lenses for extended wear. In this series however, the location and distribution of epithelial bullae correspond to areas of mechanical compression indicative of contact lens induced epithelial edema, and less likely to be hypoxia induced. We considered a number of potential causes for the corneal changes observed in this case series, including hypoxia, mechanical force, desiccation in regions of contact lens interaction with the ocular surface, and osmolarity changes due to stagnant tear reservoir between the anterior ocular surface and the posterior contact lens. Based on the agreement between locations of epithelial bullae and contact lens/corneal bearing visible on OCT, we believe these changes are most likely the result of mechanical force weakening the tight junctions present between epithelial cells [17]. Once weakened, the tight junctions allow fluid

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Fig. 13. Figures A–C demonstrate cross-sectional OCT images centrally (A), temporally (B), and nasally (C) in patient #7 who was not found to have corneal epithelial bullae despite obvious contact lens compression. Figures D and E show the same patient’s right eye temporally (D) and nasally (E) with cobalt blue light, demonstrating a ridge of contact lens compression without epithelial bullae. These photos demonstrate that although corneal bearing is related to epithelial bullae formation, the bearing does not translate to the same type or amount of corneal compromise in each situation.

transmission between epithelial cells that would otherwise be restricted, resulting in fluid accumulation near the basal epithelial layer [17]. The mechanical force inducing these changes originates from the mass of the lens in combination with the repeated force applied by each blink. Unlike more traditional corneal gas permeable lenses which translate with each blink, movement of corneo-scleral and scleral lenses is restricted and the force applied

by the blink is transferred to the ocular tissue supporting the lens, in this case series the peripheral cornea. This hypothesis is supported by the circular compression ring left on the cornea following lens removal and the bullae development almost exclusively at the most anterior location of corneal compression (Fig. 6, 10). This compression could mimic or be in conjunction with conjunctival compression often detected in scleral lens wear.


Hypoxia has led to a number of contact lens related problems in the past and was considered as a potential contributing etiology of the bullae in this case. Although scleral contact lenses are produced with highly oxygen permeable materials, they can be greater than four times thicker than soft contact lenses and retain a tear reservoir nearly matching the scleral lens thickness, which acts in series with the contact lens to restrict oxygen transmission to the cornea [10]. Many scleral lenses presently used, even when manufactured with highly oxygen permeable materials, fail to meet previously described oxygen transmission guidelines [10,11]. While hypoxia may be a contributing factor, it is unlikely the primary cause based on the distribution of the epithelial bullae and the fact that hypoxia more commonly manifests as stromal, not epithelial edema [18]. In addition, the thickness of the lens and tear reservoir in series is greatest near the center of the cornea, which should be the location of the greatest hypoxic environment, but does not correspond to the location of the bullae. While unlikely the primary contributor, desiccation in locations where the cornea is in prolonged contact with the posterior lens surface cannot be ruled out. If desiccation did play a role, however, it would be expected that the corneal signs would be seen throughout the areas of prolonged contact lens and corneal interaction, but they were concentrated near the anterior-most region of bearing. The distribution of the corneal compromise also makes osmolarity an unlikely primary cause, as compromise was only seen in locations of physical interaction between the lens and the ocular surface. Assuming there were changes in osmolarity within the reservoir, it would be expected that related compromise would occur more in corneal regions exposed to the tear reservoir, not subject to interaction with the contact lens. While we believe mechanical trauma to be the most likely cause, other causes cannot be ruled out as contributing factors. The commonality of these corneal changes and their persistence under prolonged contact lens wear is unclear, but to our knowledge, these changes have not been reported previously. The corneal alterations documented in this case series were only present in six of 14 patients over a short wearing period, so there is the potential that the cornea could become habituated to this type of lens. If these changes resolve spontaneously, it is possible they may never be detected during a clinical exam, especially if the lens is not removed and fluorescein dye is not used to monitor ocular health. Because it appears that the fitting relationship of the contact lens to the cornea likely plays a role, careful evaluation of the fitting relationship and the cornea following lens removal is warranted in patients wearing this lens modality. Adjustments to the lens parameters to alleviate bearing must also be carefully considered with the understanding that, depending on the available lens diameters, alterations to the base curve and diameter of a lens may fail to provide complete corneal clearance and instead distribute the lens weight nearer to the limbus. There is speculation that all corneal bearing in scleral contact lenses is bad. Presently, the primary goal of many practitioners is to vault the entire corneal surface, eliminating many concerns about weight distribution. In practice, complete corneal clearance may be difficult to achieve in some smaller diameter scleral lens designs and based on this case series, we believe that some distributions of bearing may be worse than others. For example, if the lens weight is distributed across a larger corneal region with shallower central clearance, there may be less pressure on the cornea and the likelihood of mechanical damage may be reduced. This study demonstrates the utility of combined en face and cross sectional imaging when contact lens and ocular surface interactions are critically important, yet extremely subtle and difficult to assess clinically. OCT assessment of scleral contact lenses has been described previously [19] and enables us to precisely localize physical interaction between the contact lens

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and cornea. The complementary SLO and OCT imaging techniques also helped demonstrate the causative link between contact lens corneal compression and the presence of corneal epithelial bullae. While the use of OCT imaging is expanding in diseases such as glaucoma or macular degeneration, it is underutilized in contact lens care but can play a significant role to guide scleral lenses safely into expanded usage. Currently, there is limited clinical evidence guiding best practice with respect to the lens diameter used and weight distribution of scleral lenses on the ocular surface, in particular the cornea. As these lens modalities become more popular and increasingly incorporated into clinical practice, more work is needed to better understand the complications that may arise and their respective etiologies. While patients with irregular corneas and ocular surface disease benefit greatly from scleral lenses, normal eyes may have less to gain and more uncertain risk of complications compared to other contact lens designs, either rigid or soft. We emphasize that lenses marketed as scleral lenses or mini-scleral lenses, especially those with relatively small diameters, should be carefully assessed for full corneal clearance and all established scleral lens wearing eyes should have a cornea evaluation with fluorescein sodium dye completed following lens removal. While scleral lenses offer promising improvements in comfort and stability compared to corneal rigid lenses, research driving the best practice for fitting relationships and investigating their influence on the ocular surface environment are critical to safely expand this exciting lens modality. Funding This work was supported by Blanchard Contact Lens, Inc (Manchester, NH),Alcon (Fort Worth, TX), DMV Corporation (Zanesville, OH), and The Ohio State University College of Optometry. References [1] Scleral Lens Education Society, Scleral Lens Nomenclature, 2013. https://www. sclerallens.org/sites/default/files/files/ SLS_Nomenclature_LtrHead06_26_2013.pdf. (Accessed 21 March 2014) [2] M.M. Schornack, Scleral lenses: a literature review, Eye Contact Lens 41 (2015) 3–11, doi:http://dx.doi.org/10.1097/ICL.0000000000000083. [3] E.S. Bennett, GP annual report, Contact Lens Spectr. 27 (2012) (2012) 26–39. http://www.clspectrum.com/articleviewer.aspx?articleID=107512. [4] L. Remington, Clinical anatomy of the visual system, 2005. [5] D.T.H. Tan, K.W. Pullum, R.J. Buckley, Medical applications of scleral contact lenses: 1. a retrospective analysis of 343 cases, Cornea 14 (1995). http:// journals.lww.com/corneajrnl/Fulltext/1995/03000/ Medical_Applications_of_Scleral_Contact_Lenses__1_.1.aspx. [6] J. Kok, R. Visser, Treatment of ocular surface disorders and dry eyes with high gas-permeable scleral lenses, Cornea (1992) http://journals.lww.com/ corneajrnl/Abstract/1992/11000/ Treatment_of_Ocular_Surface_Disorders_and_Dry_Eyes.6.aspx. (Accessed 27 July 2016).. [7] E.S. Bennett, GP annual report, Contact Lens Spectr. 28 (2013) (2013) 20–29. (Accessed 9 March 2014) http://www.clspectrum.com/articleviewer.aspx? articleID=108953. [8] T.J. Johnson, C.M. Schnider, Clinical performance and patient preferences for hydrogel versus RGP lenses: a crossover study, Int. Contact Lens Clin. 18 (1991) 130–135 http://www.sciencedirect.com/science/article/pii/ 089289679190026V (Accessed 2 January 2014). [9] D. Fonn, C.A. Gauthier, N. Pritchard, Patient preferences and comparative ocular responses to rigid and soft contact lenses, Optom. Vis. Sci. 72 (1995) 857–863 http://www.ncbi.nlm.nih.gov/pubmed/8749332 (Accessed 2 January 2014). [10] L. Michaud, E. van der Worp, D. Brazeau, R. Warde, C.J. Giasson, Predicting estimates of oxygen transmissibility for scleral lenses, Cont. Lens Anterior Eye 35 (2012) 266–271, doi:http://dx.doi.org/10.1016/j.clae.2012.07.004. [11] J.M. Jaynes, T.B. Edrington, B.A. Weissman, Predicting scleral GP lens entrapped tear layer oxygen tensions, Cont. Lens Anterior Eye 38 (2015) 44–47, doi:http:// dx.doi.org/10.1016/j.clae.2014.09.008. [12] R.L. Brautaset, M. Nilsson, N. Leach, W.L. Miller, A. Gire, S. Quintero, J.P.G. Bergmanson, Corneal and conjunctival epithelial staining in hydrogel contact lens wearers, Eye Contact Lens 34 (2008) 312–316, doi:http://dx.doi.org/ 10.1097/ICL.0b013e3181891439.

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