Jul 28, 1977 - Decreased microcyst formation occurred in all three patients with Mees- mann's dystrophy ... Case 3: June 25, 1984, left eve. D)aily soft contact ...
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SOFT CONTACT LENS WEAR DECREASES EPITHELIAL MICROCYSTS IN MEESMANN'S CORNEAL DYSTROPHY* BY William M. Bourne, MD INTRODUCTION
MEESMANN'S
EPITHELIAL CORNEAL DYSTROPHY IS A RARE AUTOSOMAL DOMINANT
disease, in which small round vesicles or microcysts (10 to 50 Jim in diameter)' are present in the corneal epithelium of both eyes throughout life. First described by Pameijer2 in 1935, the disease was more fully characterized by Meesmann3 in 1938. Often there are no ocular symptoms, but some affected individuals experience mild visual loss, glare, photophobia, and ocular irritation. Burns4 conducted a thorough review and study of the disease, published in 1968. Histopathologically, the microcysts contain the degenerated products of epithelial cells.5 The epithelial basement membrane is thickened, and the basal epithelial cells usually contain increased amounts of glycogen6; both findings probably reflect increased cellular metabolism and turnover.4'5 The characteristic ultrastructural feature4 is an intracytoplasmic "peculiar substance,"5 an amorphous material with both granular and filamentary components. Some cells with increased amounts of peculiar substance apparently develop cytoplasmic vacuoles and degenerate, forming the microcysts that gradually migrate to the epithelial surface with continued epithelial cell turnover.4'6 Treatment for Meesmann's dystrophy is usually unnecessary because of the paucity of symptoms. The cysts recur after scraping of the epithelium or lamellar keratoplasty.6 They apparently do not recur after superficial keratectomy in which Bowman's membrane is removed.4 I have found no reports of soft contact lens therapy for Meesmann's dystrophy. In 1977, I examined a man with symptomatic Meesmann's dystrophy whose symptoms (and microcysts) were almost eliminated by daily soft contact lens wear. In the ensuing years, I have observed two other *From the Department of Ophthalmology, Mayo Clinic. Supported in part by NIH grant EY 02037, Research to Prevent Blindness, Inc, New York, New York, and the Mayo Foundation, Rochester, Minnesota. TR. AM. OPHTH. Soc. vol. LXXXIV, 1986
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individuals with Meesmann's dystrophy who have worn soft contact lenses; in both, the corneal epithelial microcysts and symptoms were greatly reduced after daily wear of the lenses for several weeks. CASE REPORTS CASE 1
In July of 1977, a 38-year-old white man was referred to the Mayo Clinic for consultation regarding "corneal epithelial microvacuoles." He complained of mild ocular irritation, mild decreased vision, and monocular diplopia in both eyes. Corneal epithelial microcysts had been noted by his referring ophthalmologist, who had also noted that the symptoms and the microcysts disappeared after daily wear of either Sofcon or Baush and Lomb soft contact lenses for approximately 3 weeks. He had also worn hard contact lenses, but they did not appear to affect the microcysts. When I examined him, he had worn no contact lenses for over 1 month at my request. His best vision with refraction was 20/30-1 in each eye with bilateral monocular diplopia. Each eye had diffuse-epithelial microcysts in the central three-fourths of the cornea (Fig 1), many of which stained with fluores-
FIGURE 1
Case 1: July 28, 1977, right eye. No contact lenses for more than 1 month. Note prominent corneal epithelial microcysts by retroillumination.
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cein. The remainder of the ocular examination was normal. I examined the patient's sister and found a similar corneal appearance. Corneal epithelial microcysts had also been seen by ophthalmologists in the sister's son and in two of the patient's sons. I suggested that the patient use his contact lenses again. He returned after 1 month of daily soft contact lens wear; no microcysts were present in his left eye and only a few small microcysts were present in his right eye (Fig 2), all of which were in the peripheral cornea. His visual acuity had improved to 20/25 and the monocular diplopia was gone. He returned 1 year later, continuing to wear the lenses daily. He remained asymptomatic, although there were a few fine microcysts centrally located in each cornea. He elected to have a corneal biopsy to confirm the diagnosis. Contact lens wear was discontinued, and he was examined after 3 weeks without contact lenses. There were diffuse prominent microcysts throughout the central corneal epithelium of each eye, extending almost to the limbus in the palpebral apertures (Fig 3). A 2-mm superficial corneal biopsy was performed superiorly in the left cornea, removing epithelium and Bowman's membrane. Sections of the specimen exhibited findings characteristic of Meesmann's dystrophy: intracytoplasmic "pe-
FIGURE 2
Case 1: August 25, 1977, right eye. Daily soft contact lens wear for 1 month. Few microcysts remain.
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FIGURE 3
Case 1: August 29, 1978, left eye. No contact lens wear for 3 weeks. Prominent microcysts have returned.
culiar substance," increased glycogen, thickened basement membrane, and intraepithelial microcysts (Figs 4 and 5). When last contacted in 1985, this patient continued to wear Bausch and Lomb soft contact lenses daily without complications. He stated that when he had discontinued contact lens wear in the past, he developed monocular diplopia, mild irritation, and blur approximately 3 weeks later. After reinstituting soft contact lens wear for at least 3 weeks, the symptoms disappeared. CASE 2
In July of 1978, a 20-year-old white woman came to the Mayo Clinic for consultation regarding her mild photophobia, ocular irritation, and blurred vision of 2 years' duration. Her best corrected visual acuity was 20/50 in each eye. She had diffuse epithelial microcysts throughout both corneas, many of which stained with
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FIGURE 4
Light micrograph of cornieal biopsy (epithelitim, Bowsmani's meml)rane anid aniterior stroma) from left eye of case 1 stained with periodic acid-Schiff ( x 400). Note intraepithelial cysts, some in continuity with surface, and basement membrane thickening (arrow).
FIGURE
5
Transmission electron micrograph of winig cells of corneal epitheliuim from left eve of case 1. Note fibrillograntilar pectiliar substance (arrotw) wvithin cytoplasmn. N = ntcleuis ( x 18,000).
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fluorescein. The remainder of her ocular examination was normal. Both her mother and her 10-year-old sister had similar corneal findings. A superficial biopsy from her mother's left cornea showed findings typical of Meesmann's dystrophy, similar to those shown in Figs 4 and 5. The patient was fit with Bausch and Lomb soft contact lenses. After 1 month, her visual acuity with the contact lenses was 20/30 in each eye, and she reported less photophobia and irritation. There was a smaller number of microcysts in each cornea than previously, although they were still present diffusely. Two months later, her appearance was unchanged. She did not return to the Mayo Clinic. When contacted in 1985, she said she wore the same lenses successfully for 3 years until November, 1981, when she lost a lens. Attempts by her local ophthalmologist at refitting her with newer soft contact lenses, some suitable for extended wear, were unsuccessful and her symptoms returned. She did not seek care elsewhere, and has since lost her driver's license because ofdecreased vision. CASE 3
A 26-year-old white woman came to the Mayo Clinic in March of 1984 for a contact lens fitting for myopia (approximately 3 diopters in each eye). She had been seen at the Mayo Clinic in 1968 at the age of 10, at which time the diagnosis of Meesmann's dystrophy was made. Her father and two of three siblings had the condition. She was asymptomatic. On examination, her corrected visual acuity was 20/20 in each eye. The only ocular abnormality was prominent, diffuse epithelial microcysts in both corneas (Fig 6). She was fit with Hydron soft contact lenses; after 6 weeks of lens wear (15 hours per day), the microcysts were almost gone (Fig 7). In July of 1984, the patient lost a contact lens and discontinued lens wear in both eyes. When examined 13 days later, microcysts were again present, diffusely in both eyes. Four weeks later, the microcyst were more prominent (Fig 8). She was refit with Sofcon high-water-content lenses; after 1 week of wearing the lenses 3 hours per day, the microcysts were still prominent, but had decreased in number. After 2 more weeks of wearing the lenses 6 hours per day, the microcysts were greatly decreased (Fig 9). She was seen intermittently for the next 15 months and remained asymptomatic, wearing the lenses 15 hours per day. Only a few microcysts remained in her corneas. DISCUSSION
Decreased microcyst formation occurred in all three patients with Meesmann's dystrophy that I have seen who also wore soft contact lenses. The pathophysiologic mechanism for this effect is unknown; I can think of two possible mechanisms. First, the soft contact lenses, by covering the cornea with only minor movement, may act as a splint, preventing the normal recurrent movement of the lids over the cornea, which in, some way may affect epithelial growth and metabolism. I am not aware of evidence for this effect. A second and much more likely mechanism is the
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FIGURE 6
Case 3: March 2, 1984, left eye. No contact lens wear. Note prominent corneal epithelial microcysts by retroilltiinination.
epithelial hypoxia induced by soft contact lens wear.7 The presumed metabolic defect in Meesmann's dystrophy that causes production of increased amounts of "peculiar substance," basement membrane material, and glycogen may depend upon aerobic metabolism and thus be decreased or inhibited by hypoxia and the consequent shift to anaerobic pathways. Two observations are consistent with hypoxia as the cause for the decreased microcysts: First, patient 1 (case 1) experienced decreased microcysts with soft, but not hard, contact lens wear. Hard polymethylmethacrylate contact lenses, by virtue of their movement on the eye and consequent tear film exchange, may cause less epithelial hypoxia than the less-mobile soft contact lenses, despite higher oxygen transmissibility of the soft lenses.8 Second, in all three patients the attenuation in the number of microcysts was greatest in the central corneas as compared with the periphery, where the hypoxia would probably be less because of diffusion from the limbus and peripheral tear exchange associated with mild lens movement.
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FIGURE 7
Case 3: June 25, 1984, left eve. D)aily soft contact lens wear for 6 weeks. Few microcysts remaini.
Burns, as reported in his thesis on Meesmann's dystrophy,4 fitted hard contact lenses on rabbits in order to demonstrate changes in the intracellular enzymes of corneal epithelial cells. He did not fit any of his patients with Meesmann's dystrophy with contact lenses. The first and second patients (cases 1 and 2) had annoying symptoms from Meesmann's dystrophy that were ameliorated by soft contact lens wear. The symptoms were decreased even without the contact lenses in place, but returned in 3 to 4 weeks, if contact lens wear was discontinued. Soft contact lenses may thus be an effective treatment for Meesmann's dystrophy. The long-term consequences of this therapy are unknown; no adverse consequences were noted in these three patients after 1, 3, and 8 years of daily soft contact lens wear. ACKNOWLEDGMENT
I thank R. Jean Campbell, MD, for her helpful assistance with the histopathologic sections.
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FIGURE 8
Case 3: Auigust 21, 1984, left eve. No contact lens wear for 6 weeks. Prominent microcvsts have returniedl.
1. 2.
3.
4.
REFERENCES Broni AJ, Tripathli RC: Cvstic disorders of the cornieal epithelitim. I. Clinical aspects. Br J Ophthalimol 1973; 57:361-375. Pameijer JK: Ueber einie fremndartige familiare oberflach liche Hornhautverdnderung. Klin Aoionatsbl Augenheilkd 1935; 95:516-517. Meesmanin A: Ueber eine bisher nicht beschriebenie, dominant vererhte Dvstrophia Epithelialis corneae. Br Deuitsch Ophthalmol Gesellsch 1938; 52:154-156. Burns RP: Meesmann s cornieal dystrophy. Trans Am Ophthalitol Soc 1968;
66:530-635. 5. Kuwabara T, Ciccarelli EC: NMeesmanin's cornieal dystrophy: A pathological studx. Arch
Ophthalmtrol 1964; 71:676-682. WVarinig GP III, Rodriguies NINI, Laibson PR: Cornieal dvstrophies. I. D)ystrophies of the epithelium, Bowman's layer anid stroma. Surt Ophthalmol 1978; 23:71-122. 7. Poise KA, NMandell RB: Etiology of corneal striae accompanying hydrogel lenis wear. Invest Ophthalmol Vis Sci 1976; 15:553-556. 8. Poise KA: Tear flow under hvdrogel conitact lenises. Invest Ophthalmtol Vis Sci 1979;
6.
18:409-413.
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FIGURE 9
Case 3: SeI)tenlber 13, 1984, left eve. Daily soft conltact len.s wvear for 3 weeks. Number of microcysts hias (lecrease(l greatly.
DISCUTSSION DR JUAN J. AREN1SEN. First of all, I would like to thank Doctor- Bouirnie for having Imlailed m11e his ImllUscril)t over a imloIntlh ago, for review. I think his paper descril)es a very interestinig ol)servation that could he of great help in improving the vistual acuiity of patients with NMeesmslauinn s dystrophy. I was unal)le to find alny7tlhing in the literatture describing the disappearance of cysts in Meesmann s epithelial dvstrophy, with the use of daily wear or extendedl wear soft contact lenises. The opposite pheniolmenioni, the appearaniee of epitlhelial imicrocvsts, has been described with the use of conitact lenses. Hunphreys anld associates observed the formationi of microcvsts after several weeks of continutied wear of a Sauiflon PW lens; these cysts were seeni in the lower aspect of the cornea and the auithors felt that thev closely resembled those seeni in -Meesmann's dvstrophv,. Bergmiianison anid co-workers noticed similar chaniges b, Usinlg gas permeable lenses, in bush babvy monkeys. These cysts, whichi the authlors felt were due to traumua fromi the conitact lens, conitainied meimbraniouis by-prodlucts, as observed in Meesmann's dystrophy on1 histopathological examinationl.
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I agree with the author that epithelial hypoxia would be the most possible cause for the disappearance of these eysts. The normally increased levels of glycogen, in the basal cell layer of the epithelium in Meesmann's dystrophy, would decrease due to anoxia induced by the use of a soft contact lens. Depletion of glycogen has been reported with the use of contact lenses. And, as described by the author, a soft lens could induce relatively higher changes in oxygenation (with more reduction of oxygen and glycogen) in the central aspect of the cornea, than in the periphery, where the limbal vessels would maintain a more appropriate level. A soft contact lens would also decrease the mitotic activity of the corneal epithelium. Normally, the basal epithelial cells grow toward the surface and also centripetally. This, in Meesmann's dystrophy, would explain the higher concentration of microcysts toward the center of the cornea. In the present paper, changes in the appearance and disappearance of microcysts, closely correlate to the velocity at which the epithelium is replaced: it takes approximately 1 week for a basal cell to migrate to the surface and be desquamated. This is especially clear in case 3, where microcysts reappeared within 13 days following removal of the lens and started to decrease in number, 1 week after the lens was refit. In summary, the author has presented us with a new therapy for Meesmann's microcystic dystrophy. Hypoxia and reduced epithelial growth seem to be important components of these changes, induced by the contact lens. I look forward to trying this therapy, since most others, when needed, have been only temporarily effective. DR R. LINSY FARRIS. As Doctor Arentsen has just noted, there are reports of contact lens wear causing microcysts in contrast to this report of Doctor Bourne about getting rid of microcysts with contact lens wear. We are at somewhat of a loss to explain this varied effect of contact lens wear. I would like to mention the fact that the corneal edema associated with daily wear conitact lenses is dissipated for the most part overnight in the closed eye as a result of oxygen perfusion from the capillaries in the palpebral conjunctiva. Two additional mechanisms which may explain microcyst dissipation or formation are elevated tear film tonicity and decreased desquamation of the surface epithelial cells. My thesis just published demonstrated elevated tear osmolarity in daily wear soft contact lens wearers. Doctor Lemp and co-workers have just published specular microscopic studies of the corneal epithelium in contact lens wearers demonstrating that desquamation of surface cells was significantly decreased in contact lens wearers. Doctor Bourne's report is most interesting and an important finding which demonstrates the varied effects of contact lens wear on the corneal surface. DR KENNETH KENYON. It is interesting to see that in this conditioni, soft contact lenses are the double-edged sword that they have proved to be elsewhere, for as Doctor Arentsen indicates, not only can we create microcysts but we can treat microcysts with contact lenses. Similarly, we can both treat and create superior limbic keratoconjunctivitis with soft contact lenses. My subsequent comment, however, is by nature of pathogenic speculation and, perhaps, again it is my
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tendency to be a "lumper" rather than a "splitter," but it seems to me that the action in Meesmann's microcystic dystrophy is not so much in the cysts per se but, perhaps, in the accumulation of abnormal intracellular and extracellular substances (be they so-called "peculiar substance" or be they keratins is as yet unclear). Thus, I would assume that Meesmann's dystrophy has similar characteristics as Cogan's microcystic dystrophy, whereby we presume that an abnormality of primary basement membrane and adhesion properties sets the stage for aberrant epithelial cell maturation and migration, and this results in the microcyst formation with intercellular debris in the Cogan's variant. I think it would be interesting to look not toward a special hypoxic or rather metabolic basis for the beneficial effects of contact lenses, as Doctor Bourne observed, but rather a similar mechanically supportive effect as we observed treating other types of recurrent erosions. Perhaps this dystrophy simply happens to be the most microerosion variant on the map-dot-fingerprint theme. DR DAVID G. COGAN. I would also like to take issue with the sufficiency of hypoxia as an explanation for the decrease in what the authors call microcysts of the epithelium. Hypoxia seems to bear the brunt of all facile explanations. It reminds me of Doctor Verhoeffs comments on a paper at the AOS some years ago when an essayist reported limited observations on a horse. Doctor Verhoeff remarked that the conclusions were almost too much for a single horse to bear. Actually ischemia causes an increase in glycogen accumulation, not a decrease. As an alternative explanation for the observed effect of the contact glass I would suggest that it deprives the epithelium of a glucose supply for the synthesis of glycogen. We know that the corneal epithelium, especially the central portions, derives most of its glucose from the tears. It seems reasonable to assume that the diminished availability of the substrate from the tears would decrease the amount of glycogen
synthesized. I would also suggest caution in calling all the translucent vacuoles microcysts. It is true that some microcysts may be present in Meesmann's dystrophy; they occur nonspecifically in many epithelial abnormalities. But I believe much of the appearance (shown beautifully in the author's clinical photographs) is due to cells massively distended with glycogen. Microcysts in other epitheliopathies are opaque, not translucent. DR WILLIANI BOURNE. I would like to thank the members for the excellent points that they brought up and Doctor Arentsen for the very interesting discussion. He pointed out that microcysts are a common finding in soft contact lens wearers. Indeed they are. I believe that the microcysts seen in soft contact lens wear are different from those in Meesmann's dystrophy, however, in that they are smaller and disappear when contact lenses are discontinued. Doctor Farris mentioned that corneal epithelial hypoxia would not be present during the night, when the soft contact lenses were removed, and this is certainly true. There is, however, less oxygen available during the night than is normally present in the daytime. My hypothesis would be that the epithelial hypoxia induced by soft contact lens wear
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duiring the daytimiie is sufficient to redtuce the microcystic changes. Doctor Farris offered two alternative explaniationis for the decreased incrocvsts in soft contact lens wear: increased hypertonicity of the tear film and incrased desquamation of the surface cells. I think that both of these hypotheses certainly deserve consideration. Somne of the alterniative hypotheses can be tested on cases of Meesmann's dystrophy. Tear film tonicity, for example, could le increased by the administration of hypertonic drops for several weeks. I feel that the known decrease in central corneal oxygeni during soft contact lens wear possibly makes more sense to me as a cause for the decreased imicrocysts, but I certainly have no proof. Doctor Kenvon thought that we should look for a metabolic effect on the cells that would be common to all cornieal microcysts rather than just a possible effect on these cells in Meesmann's dystrophy, trying to tie together all the corneas that have microcvsts. I am not sure what metabolic effect he has in mind. All I can say is that with soft contact lens wear the microcysts decreased. It must be decreased production of the peculiar substanice which accounts for this effect, and oxygen is higher on the list of possible causes than other things that I can think of. It certainly could be any other thing associated with contact lens wear. IDoctor Cogan and Doctor Kenyon both indicated, I think, that the decreased microcvsts might reflect a decrease in epithelial glycogen, which could be due to hypoxia. I might point out that, as I mentioned in the paper, glycogen in this dystrophy is probably a secondary effect of increased cellular turnover and metabolism rather than a primary abnormality. Also, in the histologic sections that I showed stained with periodic acid-Schiff, the microcysts did not contain glycogen. Thank you all again for the lively discussion and the illuminiating comments.
