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Persistent Corneal Edema in Aphakic Eyes from Daily-Wear and Extended-Wear Contact Lenses
PERSISTENT CORNEAL E D E M A IN APHAKIC EYES FROM DAILY-WEAR A N D EXTENDED-WEAR CONTACT L E N S E S V E R I N D E R S. N I R A N K A R I , M.D., Baltimore,
A N D J O H N C. B A E R ,
M.D.
Maryland
Corneal edema developed in seven aphakic eyes of six patients (three men and three women ranging in age from 60 to 88 years) who used daily- or extended-wear hydrophilic and silicone contact lenses. This edema, which developed suddenly, persisted despite discontinuation of contact lens wear and treatment with topical corticosteroids. The onset of the edema occurred in two patterns. In three eyes, edema occurred soon (30 minutes to 30 days) after the contact lens was first worn and persisted during follow-up periods averaging 15 months. In the other four eyes, the edema developed late, after 20 to 66 months. In three of these eyes, edema resolved after follow-up periods averaging seven months. In the fourth eye, it was still present after 18 months. Of the affected eyes in which peripheral endothelial cell densities could be measured, all but one had fewer than 800 cells/mm2. Central cell densities in the five uninvolved fellow eyes averaged 1,964 cells/mm2. Marked polymegathism and cornea guttata were present in all affected and fellow eyes. We believe this condition is a complication of aphakic contact lens wear, distinct from contact-lens-intolerance syndrome and aphakic bullous keratopathy.
Among the corneal complications asso ciated with contact lenses in aphakic eyes are epithelial defects, neovascularization, infectious and sterile ulcers, corneal infil trates, and changes in refractive error. 1 ' 8 Corneal edema has also been report ed.1'5,9,10 Small increases in corneal thick ness may be asymptomatic, 3 but more severe swelling is characterized by de creased vision, pain, photophobia, conjunctival and ciliary injection, and ante rior chamber cells and flare.1,3,4 Corneal edema induced by contact lenses in aphaAccepted for publication July 2, 1984. From the Cornea Service, Department of Ophthal mology, University of Maryland School of Medicine, Baltimore, Maryland. Reprint requests to Verinder S. Nirankari, M . D . , Cornea Service, Department of Ophthalmology, Uni versity of Maryland School of Medicine, 22 S. Greene St., Baltimore, MD 21201.
kic eyes has been considered to be rapid ly reversible after discontinuation of con tact lens wear. 3 ' 5 ' 9 We retrospectively studied seven apha kic eyes (six patients) that were corrected with daily- or extended-wear contact lenses and later developed acute corneal edema. All the patients were referred here when the edema persisted despite discontinuation of the contact lens wear and conventional medical management. S U B J E C T S AND M E T H O D S
The six patients (three men and three women) had an average age of 71 years (range, 60 to 88 years) at the time of cataract extraction. Two right eyes and five left eyes had undergone five intracapsular extractions, one planned extracapsular extraction, and one unplanned extracapsular extraction. Visual acuity on
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referral ranged from 20/80 to counting fingers, with five of the seven eyes having visual acuities of 20/200 or worse. Four eyes had undergone uncomplicat ed cataract extractions. In the other three eyes, the surgical complications included retinal detachment, vitreous strands in the wound, unplanned extracapsular ex traction with vitreous loss, and vitreous herniation into the anterior chamber, touching the posterior corneal surface, after neodymium-YAG laser posterior capsulotomy. At the time corneal edema developed, two patients (three affected eyes) were wearing daily-wear soft contact lenses (Softens) and two were wearing extendedwear contact lenses (Sauflon). The other two patients had previously worn extended-wear contact lenses but had switched to silicone daily-wear lenses (Silsoft) because of contact lens intoler ance despite good fits. The onset of edema occurred in two patterns, early and late. Three of the affected patients (three eyes) developed edema early, within 30 days of being fitted for contact lenses. One of these patients was fitted postoperatively with a high-water-content extended-wear lens (Sauflon) and developed corneal edema within 48 hours. Each of the two other patients who had been fitted previously with extended-wear lenses that .were dis continued because of lens intolerance was later fitted with a silicone daily-wear lens (Silsoft). Corneal edema recurred within 30 minutes in one patient and was noted at a four-week follow-up visit in the other. In the other four eyes, symptoms of corneal decompensation developed long after the original fitting of the contact lenses. The onset of symptoms was sud den, as in the first three eyes, but the lenses had been fitted an average of 50 months previously (range, 20 to 66 months).
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Before symptoms developed, contact lenses had been tolerated with good visu al acuity and no evidence of edema. No patient had evidence of tight-fitting con tact lenses or any clinical signs of stromal or epithelial edema. Pachymetry readings were not performed. In all cases, the patients had been examined regularly by the referring ophthalmologist. Initial management of the edema had consisted of discontinuation of the contact lens and conventional medical management (in cluding topical corticosteroid eyedrops). In the three eyes in which edema de veloped early, it failed to resolve during follow-up periods averaging 15 months. Best corrected visual acuities at the last measurement were 20/80, 20/200, and 20/400. In three of the four eyes in which edema developed late, it took an average of seven months to resolve. These pa tients were monitored for an average of nine months after referral (range, eight to 12 months). Visual acuity in these three eyes ranged from 20/20 to 20/40 at the -most recent examinations. In the fourth eye with late edema, the edema did not resolve during an 18month follow-up period. This patient had a history of glaucoma, and had had in creased intraocular pressure at the time the edema developed but this was later controlled by medical therapy. None of the patients had undergone endothelial cell counts before using con tact lenses but each did undergo corneal wide-field specular microscopy here. Be cause of the edema, central endothelial cell counts were not initially possible in any of the affected eyes but peripheral endothelial cell counts were obtained in five of the seven affected eyes. In all but one of these, the cell density was less than 800 cells/mm 2 (range, 347 to 2,000 cells/mm 2 ). Marked polymegathism and cornea guttata were present in all eyes. Of the affected eyes measured, the
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three highest cell densities were in eyes with late onset of symptoms (range, 595 to 2,000 cells/mm 2 ); the two lowest cell densities were in eyes with early symp toms (range, 347 to 446 cells/mm 2 ). One patient (No. 6) underwent paracentral cell density measurement after the bilateral corneal edema had re solved. At that time the measurements were R.E.: 600 cells/mm 2 and L.E.: 1,000 cells/mm 2 . In the five unaffected fellow eyes, one of which was aphakic, the central cell densities averaged 1,964 cells/mm 2 with a range of 1,537 to 2,200 cells/mm 2 . Marked polymegathism and cornea guttata were also present in these eyes
(Table). We have selected two representative case histories for more detailed discus sion. CASE REPORTS Case 1—This 76-year-old man had undergone bi lateral uncomplicated intracapsular cataract extrac tion. Two months later, extended-wear aphakic soft contact lenses (Sauflon) were fitted, producing a visual acuity of 20/25 in both eyes. Within 48 hours, corneal edema developed bilaterally. The contact lenses were discontinued, and treatment was begun with topical fluorometholone and 5% sodium chlo ride every three hours. During the next two days, the right cornea cleared but edema persisted in the left. The patient was then referred here. Examination at that time showed a visual acuitv of R.E.: 20/20 and L.E.: 20/400. The right corneal stroma appeared to be thickened and there were fine, pigmented cornea guttata centrally. The left corneal epithelium was grossly edematous with be dewing and bullae formation, and the stroma was milky. Cornea guttata were again noted centrally. Intraocular pressure by pneumotonometry was R. E. : 18 mm Hg and L.E.: 15 mm Hg. The administration of topical fluorometholone was increased to every hour in the left eye for the next three weeks. There was no change in the edema and administration was gradually decreased to four times daily. At a followup examination seven weeks later, there was little change in the edema and the fluorometholone was discontinued and topical treatment with 5% sodium chloride was started again. During the next ten months, central bedewing and edema persisted in the left eye and stromal scarring developed in the center of the edematous area. The right cornea remained clear, and its thickness was grossly normal. Endothelial cell density measured by
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specular microscopy was R.E.: 1,537 cells/mm 2 cen trally and L.E.: 446 cells/mm 2 peripherally. Best corrected visual acuitv when last measured was R.E.: 20/25 and L.E.: 20/80-2. Case 2—This 60-year-old woman had undergone bilateral uncomplicated intracapsular cataract extrac tions. Postoperatively, daily-wear soft contact lenses (Soflens) were fitted for aphakic correction. She tolerated contact lenses well, with a visual acuity of 20/20 in both eyes and no clinical evidence of corneal edema. Sixty-six months later, the patient noted a sudden decrease in visual acuity bilaterally but more pronounced in the left eye and went to her ophthal mologist. The contact lenses were discontinued, and the patient began using a topical dexamethasoneantibiotic combination and 5% sodium chloride four times daily. A week later, this was changed to 1% prednisolone acetate and 5% sodium chloride four times daily. The edema did not resolve during the next month and the patient was referred here. At that time, her visual acuity with spectacle correction was R.E.: 20/80 and L.E.: 20/200. A slit-lamp examina tion showed central edema with stromal thickening. Epithelial bedewing was present bilaterally but worse in the left eye. Central cornea gutatta were present in both eyes. Intraocular pressure was R. E.: 17 mm Hg and L.E.: 18 mm Hg. By specular mi croscopy, the peripheral endothelial cell density was R.E.: 2,000 cells/mm 2 and L.E.: 595 cells/min 2 with polymegathism and cornea guttata bilaterally The edema completely resolved after seven months in the right eye and after eight months in the left eye. Visual acuity was 20/20 in both eyes. Paracentral specular microscopy showed cell densities of R.E.: 600 cells/mm 2 and L.E.: 1,000 cells/mm 2 . DISCUSSION
In our six patients (seven eyes), the edema persisted for periods ranging from five to 18 months, in marked contrast to the readily reversible edema previously observed in healthy9'11,12 and aphakic eyes.3"5·9 The course of the edema followed two patterns. Those eyes that developed edema early had lower endothelial cell densities and the edema did not resolve during an average follow-up period of 15 months. Endothelial densities were high er in the eyes with late edema and the edema eventually resolved after an aver age follow-up period of seven months in all but one eye. In three patients, there was a clear temporal relationship between contact lens fitting and the onset of corneal
(yrs) eye surgery complications
1,785
2,000
1,537
2,000
2,200
Xot possible
*Had previously worn extended-wear lenses but switched because of intolerance. Peripheral cell densities; central specular microscopy was not possible in any of the affected eyes.
Fellow eye
347
Persistent
—
R.E.: 2,000; L.E.: 595
793
Cell density (cells/mm2) Affected eye 446
Persistent
Persistent
Resolved in 5 mos
Status of edema
Xot possible
20/400
20/80-2
H.M.
20/40
Persistent
R.E.: 20/80; L.E.: 20/200 R.E.: 20/20; L.E.: 20/20 Resolved (R.E.; 7 mos; L. E.: 8 mos) 20/400
20/200
20/400
20/400
CF.
20/200
8
14
15
15
18
12
Final
66 mos
30 min
30 days
Softens Daily-wear
48 hrs
Silsoft* Daily-wear
F, 60 Both Intracapsular Xone
48 mos
Silsoft* Daily-wear
M, 74 Left Extracapsular Unplanned extracapsular and vitreous loss
F, 88 Right Extracapsular Vitreous against cornea after YAG laser capsulotomy
Patient 6
20 mos
M, 76 Left Intracapsular Xone
Patient 5
Patient 4
Sauflon Extended-wear
F, 63 Left Intracapsular Xone
M, 66 Left Intracapsular Retinal detachment; vitreous strands to wound requiring YAG laser
Patient 3
Softens Daily-wear
Patient 2
Patient 1
Sauflon Extended-wear
Contact lens Brand Type Time worn before edema Length of follow-up (mos) Visual acuity Initial
Sex, age Affected Cataract Surgical
Clinical Data
TABLE SUMMARY O F CLINICAL DATA
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PERSISTENT CORNEAL EDEMA
edema. The patients had had clear corne as with no clinical evidence of stromal or epithelial edema at the time of fitting. Shortly after beginning to wear the con tact lenses, all three had a sudden onset of edema associated with decreased vi sion. Other associated symptoms includ ed pain, photophobia, and conjunctival and ciliary injection, all of which are found in the lens-intolerance syn drome. 1 · 3,4 In these patients, however, the corneal edema never resolved despite earlier reports of rapid resolution of contact-lens-induced edema in aphakic patients after the patients stopped wear ing the contact lenses.3"5'9 The other four eyes suddenly devel oped corneal edema long after beginning contact lens wear. These patients had had good visual acuities and no clinical evi dence of epithelial or stromal edema. The signs and symptoms were similar to those in the first three patients: the patients reported a sudden onset of pain and de creased visual acuity; examinations showed corneal edema and a pattern compatible with lens-intolerance syn drome. However, as in the first three patients, the edema persisted for eight to 18 months. These four eyes also differed from eyes with aphakic bullous keratopathy in that the edema and accompanying symptoms occurred suddenly, and in three of the four eyes the edema completely resolved. These three eyes have remained free of edema without medication. In contrast, aphakic bullous keratopathy generally oc curs as a chronic, progressive corneal edema with increased stromal thicken ing, a fine epithelial edema, bullae forma tion, and a gradual decrease in visual acuity. The edema is irreversible. 13 The two patterns of onset may repre sent part of a spectrum of contact-lensinduced edema, depending on preexist ing function of the corneal endothelium. If the healthy cornea is stressed by con
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tact lens wear, it can become edematous, but the normal deturgescent state is rap idly restored by discontinuation of the contact lens and medical therapy, if need ed. A cornea that has suffered endothelial cell loss may be susceptible to more se vere or more refractory edema. When endothelial cell function is severely com promised, contact lens wear may lead to corneal decompensation with develop ment of persistent or permanent edema. The concept of a spectrum of corneal edema is supported by the work of Binder and Woodward 3 who measured endotheli al cell counts in 70 eyes before fitting myopic or aphakic contact lenses. They used low-, medium-, and high-watercontent extended-wear lenses. Of the 12 aphakic eyes that had developed corneal edema with low- and medium-watercontent contact lenses, eight developed edema even after being switched to the high-water-content lenses. Of the pa tients who developed the lens-intoler ance syndrome, all but one had fewer than 1,200 cells/mm 2 . All but one also had increased baseline corneal thickness before the contact lens was fitted. How ever, none of these patients had corneal edema that persisted after discontinua tion of the contact lens. These patients appear to form a group between our patients who developed persistent edema and asymptomatic contact lens wearers. The work of Poise, Holden, and Swee ney 9 also suggested that the rate of reso lution of corneal edema may depend on endothelial function. They fitted 12 pa tients with unilateral aphakia with highplus extended-wear contact lenses, and noted bilateral corneal swelling after six hours during which the eyes were kept closed. The patients were then permitted to open their eyes. Corneal thickness was measured hourly. The aphakic eyes, which had approximately 10% endotheli al cell loss, showed slower resolution of the corneal swelling.
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Hypoxia seems to be the major factor causing contact-lens-induced edema.12'14'15 The corneal epithelium's primary source of oxygen is through the tear film16 and, therefore, its access to atmospheric oxy gen is blocked by the contact lens. With a contact lens in place, most of the oxygen reaches the epithelium by diffusion through the contact lens because there is little exchange of tear film under the eyes. 17 Oxygen flux through a soft contact lens is a function of permeability of the lens and its thickness. 14 Closed eyelids also reduce the available supply of oxy gen. 9 ' 14 In patients with normal ocular findings who experienced contact-lensassociated 9 · 11 or experimentally induced 12 corneal edema, there was regression of the edema when the hypoxic state was corrected. The corneal endothelial cells can ob tain an adequate supply of oxygen from the aqueous alone 16 ; how, then, does en dothelial dysfunction increase the likeli hood of corneal edema in eyes with epi thelial hypoxia? As oxygen tension in the outer cornea decreases, the epithelium depends increasingly on anaerobic me tabolism and lactic acid production in creases; osmotic forces tend to draw more water into the cornea. 18 The hypoxic epithelium's effectiveness as a waterimpermeable barrier is reduced. 1 9 The tear film adjacent to the epithelium may become more hypotonie than normal be cause the contact lens tends to reduce evaporation. 20 This also increases osmotic flow of water into the cornea. This se quence of events has been proposed as a mechanism for corneal edema associated with soft contact lenses.15·18"20 Because the endothelium seems to be the site at which water is actively pumped out of the cornea, 21 it is reasonable to assume that superimposed endothelial dysfunction could seriously compromise the cornea's ability to maintain proper hydration. We believe that this hypothesis may explain
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the sequence of events that occurred in the three patients who had early edema. A similar sequence of events could be proposed for the eyes with late edema. Although endothelial function in these eyes was apparently sufficient to maintain a clear cornea when contact lens wear was first begun, normal senile attrition could exhaust the remaining endothelial re serve, resulting in corneal edema. Addi tionally, several reports suggest that the wearing of a contact lens can cause endo thelial damage. In a group of asympto matic patients with hard contact lenses, Caldwell 22 correlated length of contact lens wear with decreases in endothelial cell density. The study group had signifi cantly lower endothelial cell densities than did a group of age- and sex-matched controls. Hirst, Tseng, and Khodadoust 23 reported an increase in endothelial cell size, with a coefficient of skewness and kurtosis demonstrating a dramatic altera tion in cell area distribution. Endothelial blebs have been observed clinically in eyes with both hard 24 and soft15·25 contact lenses. Vannas and associates 26 histologically demonstrated endothelial blebs after short-term soft contact lens use in freshly enucleated eyes and in cadaver eyes that were still being perfused. It has been proposed that alterations in corneal metabolism induced by the con tact lens cause these endothelial chang es.15·22,24 Mechanical forces may also play a role. Miller and Weiss 27 demonstrated histologically that suction from a contact lens can cause both reversible and irre versible endothelial damage in freshly enucleated cow eyes. We believe, there fore, that metabolic or mechanical altera tions of the corneal endothelium, or both, may contribute to corneal edema induced by contact lenses. REFERENCES
1. Binder, P. S.: Complications associated with extended wear of soft contact lenses. Ophthalmology 86:1093, 1979.
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2. Nesbum, A. B. : Prolonged-wear contact lenses in aphakia. Ophthalmology 85:73, 1978. 3. Binder, P. S., and Woodward, C : Extendedwear Hydrocurve and Sauflon lenses. Am. J. Oph thalmol. 90:309, 1980. 4. Stark, W. J., Kracher, G. P., Cowan, C. L., Taylor, H. R., Hirst, L. W., Oyakawa, R. T., and Maumenee, A. E.: Extended-wear contact lenses and intraocular lenses for aphakic correction. Am. J. Ophthalmol. 88:535, 1979. 5. Gasset, A. R., Lobo, L., and Houde, W.: Permanent wear of soft contact lenses in aphakic eyes. Am. J. Ophthalmol. 83:115, 1977. 6. Farris, R. L.: Complications associated with aphakic contact lenses. Ophthalmology 86:1120, 1979. 7. Kersley, H. J., Kerr, C , and Pierse, D.: Hydrophilic lenses for "continuous" wear in aphakia. Definitive fitting and the problems that occur. Br. J. Ophthalmol. 61:38, 1977. 8. Cooper, R. L., and Constable, I. J.: Infective keratitis in soft contact lens wearers. Br. J. Ophthal mol. 61:250, 1977. 9. Poise, K. A., Holden, B. A., and Sweeney, D.: Corneal edema accompanying aphakic extended lens wear. Arch. Ophthalmol. 101:1038, 1983. 10. Holden, B. A., Mertz, G. W., and Guillon, M.: Corneal swelling response of the aphakic eye. Invest. Ophthalmol. Vis. Sei. 19:1394, 1980. 11. Binder, P. S., and Worthen, D. M.: Clinical evaluation of continuous-wear hydrophilic lenses. Am. J. Ophthalmol. 83:549, 1977. 12. Poise, K. A., and Mandell, R. B.: Etiology of corneal striae accompanying hydrogel lens wear. Invest. Ophthalmol. 15:553, 1976. 13. Gunderson, T. : Surgical treatment of bullous keratopathy. Arch. Ophthalmol. 64:124, 1960. 14. Poise, K. A., and Decker, M.: Oxygen tension under a contact lens. Invest. Ophthalmol. Vis. Sei. 18:188, 1979.
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15. Holden, B. A., Poise, K. A., Fonn, D., and Mertz, G. W. : Effects of cataract surgery on cor neal function. Invest. Ophthalmol. Vis. Sei. 22:343, 1982. 16. Weissman, B. A., Fatt, I., and Rasson, J.: Diffusion of oxygen in human corneas in vivo. Invest. Ophthalmol. Vis. Sei. 20:123, 1981. 17. Poise, K. A.: Tear flow under hydrogel contact lenses. Invest. Ophthalmol. Vis. Sei. 18:409, 1979. 18. Klyce, S. D., and Bernegger, O.: Epithelial hypoxia, lactate production, and stromal edema. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sei. St. Louis, C. V. Mosby, 1978, p. 277. 19. Thoft, R. A., and Mobilia, E. F.: Complica tions with therapeutic extended wear soft contact lenses. Int. Ophthalmol. Clin. 21:197, 1981. 20. White, P. F., and Miller, D.: Corneal edema. Int. Ophthalmol. Clin. 21:3, 1981. 21. Dohlman, C. H.: The function of the corneal epithelium in health and disease. Invest. Ophthal mol. 10:383, 1971. 22. Caldwell, D. R. : The effect of long-term hard lens wear on corneal endothelium. Contact Intraocu lar Lens Med. J. 8:87, 1982. 23. Hirst, L. W., Tseng, S., and Khodadoust, A.: Specular microscopy of hard contact lens wearers. Ophthalmology 90(suppl.):47, 1983. 24. Barr, J. T., and Schoessler, J. P.: Corneal endothelial response to rigid contact lenses. Am. J. Optom. Physiol. Opt. 57:267, 1980. 25. Zantos, S. G., and Holden, B. A.: Transient endothelial changes soon after wearing soft contact lenses. Am. J. Optom. Physiol. Opt. 54:856, 1977. 26. Vannas, A., Holden, B. A., Makitie, J., Ruusuvaara, P., and O'Donnell, J. J. : Specular microsco py and ultrastructure of endothelial blebs. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sei. St. Louis, C. V. Mosby, 1979, p. 143. 27. Miller, D., and Weiss, J.: Corneal endotheli um. Int. Ophthalmol. Clin. 21:39, 1981.
A N D J O H N C. B A E R ,
M.D.
Maryland
Corneal edema developed in seven aphakic eyes of six patients (three men and three women ranging in age from 60 to 88 years) who used daily- or extended-wear hydrophilic and silicone contact lenses. This edema, which developed suddenly, persisted despite discontinuation of contact lens wear and treatment with topical corticosteroids. The onset of the edema occurred in two patterns. In three eyes, edema occurred soon (30 minutes to 30 days) after the contact lens was first worn and persisted during follow-up periods averaging 15 months. In the other four eyes, the edema developed late, after 20 to 66 months. In three of these eyes, edema resolved after follow-up periods averaging seven months. In the fourth eye, it was still present after 18 months. Of the affected eyes in which peripheral endothelial cell densities could be measured, all but one had fewer than 800 cells/mm2. Central cell densities in the five uninvolved fellow eyes averaged 1,964 cells/mm2. Marked polymegathism and cornea guttata were present in all affected and fellow eyes. We believe this condition is a complication of aphakic contact lens wear, distinct from contact-lens-intolerance syndrome and aphakic bullous keratopathy.
Among the corneal complications asso ciated with contact lenses in aphakic eyes are epithelial defects, neovascularization, infectious and sterile ulcers, corneal infil trates, and changes in refractive error. 1 ' 8 Corneal edema has also been report ed.1'5,9,10 Small increases in corneal thick ness may be asymptomatic, 3 but more severe swelling is characterized by de creased vision, pain, photophobia, conjunctival and ciliary injection, and ante rior chamber cells and flare.1,3,4 Corneal edema induced by contact lenses in aphaAccepted for publication July 2, 1984. From the Cornea Service, Department of Ophthal mology, University of Maryland School of Medicine, Baltimore, Maryland. Reprint requests to Verinder S. Nirankari, M . D . , Cornea Service, Department of Ophthalmology, Uni versity of Maryland School of Medicine, 22 S. Greene St., Baltimore, MD 21201.
kic eyes has been considered to be rapid ly reversible after discontinuation of con tact lens wear. 3 ' 5 ' 9 We retrospectively studied seven apha kic eyes (six patients) that were corrected with daily- or extended-wear contact lenses and later developed acute corneal edema. All the patients were referred here when the edema persisted despite discontinuation of the contact lens wear and conventional medical management. S U B J E C T S AND M E T H O D S
The six patients (three men and three women) had an average age of 71 years (range, 60 to 88 years) at the time of cataract extraction. Two right eyes and five left eyes had undergone five intracapsular extractions, one planned extracapsular extraction, and one unplanned extracapsular extraction. Visual acuity on
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referral ranged from 20/80 to counting fingers, with five of the seven eyes having visual acuities of 20/200 or worse. Four eyes had undergone uncomplicat ed cataract extractions. In the other three eyes, the surgical complications included retinal detachment, vitreous strands in the wound, unplanned extracapsular ex traction with vitreous loss, and vitreous herniation into the anterior chamber, touching the posterior corneal surface, after neodymium-YAG laser posterior capsulotomy. At the time corneal edema developed, two patients (three affected eyes) were wearing daily-wear soft contact lenses (Softens) and two were wearing extendedwear contact lenses (Sauflon). The other two patients had previously worn extended-wear contact lenses but had switched to silicone daily-wear lenses (Silsoft) because of contact lens intoler ance despite good fits. The onset of edema occurred in two patterns, early and late. Three of the affected patients (three eyes) developed edema early, within 30 days of being fitted for contact lenses. One of these patients was fitted postoperatively with a high-water-content extended-wear lens (Sauflon) and developed corneal edema within 48 hours. Each of the two other patients who had been fitted previously with extended-wear lenses that .were dis continued because of lens intolerance was later fitted with a silicone daily-wear lens (Silsoft). Corneal edema recurred within 30 minutes in one patient and was noted at a four-week follow-up visit in the other. In the other four eyes, symptoms of corneal decompensation developed long after the original fitting of the contact lenses. The onset of symptoms was sud den, as in the first three eyes, but the lenses had been fitted an average of 50 months previously (range, 20 to 66 months).
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Before symptoms developed, contact lenses had been tolerated with good visu al acuity and no evidence of edema. No patient had evidence of tight-fitting con tact lenses or any clinical signs of stromal or epithelial edema. Pachymetry readings were not performed. In all cases, the patients had been examined regularly by the referring ophthalmologist. Initial management of the edema had consisted of discontinuation of the contact lens and conventional medical management (in cluding topical corticosteroid eyedrops). In the three eyes in which edema de veloped early, it failed to resolve during follow-up periods averaging 15 months. Best corrected visual acuities at the last measurement were 20/80, 20/200, and 20/400. In three of the four eyes in which edema developed late, it took an average of seven months to resolve. These pa tients were monitored for an average of nine months after referral (range, eight to 12 months). Visual acuity in these three eyes ranged from 20/20 to 20/40 at the -most recent examinations. In the fourth eye with late edema, the edema did not resolve during an 18month follow-up period. This patient had a history of glaucoma, and had had in creased intraocular pressure at the time the edema developed but this was later controlled by medical therapy. None of the patients had undergone endothelial cell counts before using con tact lenses but each did undergo corneal wide-field specular microscopy here. Be cause of the edema, central endothelial cell counts were not initially possible in any of the affected eyes but peripheral endothelial cell counts were obtained in five of the seven affected eyes. In all but one of these, the cell density was less than 800 cells/mm 2 (range, 347 to 2,000 cells/mm 2 ). Marked polymegathism and cornea guttata were present in all eyes. Of the affected eyes measured, the
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three highest cell densities were in eyes with late onset of symptoms (range, 595 to 2,000 cells/mm 2 ); the two lowest cell densities were in eyes with early symp toms (range, 347 to 446 cells/mm 2 ). One patient (No. 6) underwent paracentral cell density measurement after the bilateral corneal edema had re solved. At that time the measurements were R.E.: 600 cells/mm 2 and L.E.: 1,000 cells/mm 2 . In the five unaffected fellow eyes, one of which was aphakic, the central cell densities averaged 1,964 cells/mm 2 with a range of 1,537 to 2,200 cells/mm 2 . Marked polymegathism and cornea guttata were also present in these eyes
(Table). We have selected two representative case histories for more detailed discus sion. CASE REPORTS Case 1—This 76-year-old man had undergone bi lateral uncomplicated intracapsular cataract extrac tion. Two months later, extended-wear aphakic soft contact lenses (Sauflon) were fitted, producing a visual acuity of 20/25 in both eyes. Within 48 hours, corneal edema developed bilaterally. The contact lenses were discontinued, and treatment was begun with topical fluorometholone and 5% sodium chlo ride every three hours. During the next two days, the right cornea cleared but edema persisted in the left. The patient was then referred here. Examination at that time showed a visual acuitv of R.E.: 20/20 and L.E.: 20/400. The right corneal stroma appeared to be thickened and there were fine, pigmented cornea guttata centrally. The left corneal epithelium was grossly edematous with be dewing and bullae formation, and the stroma was milky. Cornea guttata were again noted centrally. Intraocular pressure by pneumotonometry was R. E. : 18 mm Hg and L.E.: 15 mm Hg. The administration of topical fluorometholone was increased to every hour in the left eye for the next three weeks. There was no change in the edema and administration was gradually decreased to four times daily. At a followup examination seven weeks later, there was little change in the edema and the fluorometholone was discontinued and topical treatment with 5% sodium chloride was started again. During the next ten months, central bedewing and edema persisted in the left eye and stromal scarring developed in the center of the edematous area. The right cornea remained clear, and its thickness was grossly normal. Endothelial cell density measured by
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specular microscopy was R.E.: 1,537 cells/mm 2 cen trally and L.E.: 446 cells/mm 2 peripherally. Best corrected visual acuitv when last measured was R.E.: 20/25 and L.E.: 20/80-2. Case 2—This 60-year-old woman had undergone bilateral uncomplicated intracapsular cataract extrac tions. Postoperatively, daily-wear soft contact lenses (Soflens) were fitted for aphakic correction. She tolerated contact lenses well, with a visual acuity of 20/20 in both eyes and no clinical evidence of corneal edema. Sixty-six months later, the patient noted a sudden decrease in visual acuity bilaterally but more pronounced in the left eye and went to her ophthal mologist. The contact lenses were discontinued, and the patient began using a topical dexamethasoneantibiotic combination and 5% sodium chloride four times daily. A week later, this was changed to 1% prednisolone acetate and 5% sodium chloride four times daily. The edema did not resolve during the next month and the patient was referred here. At that time, her visual acuity with spectacle correction was R.E.: 20/80 and L.E.: 20/200. A slit-lamp examina tion showed central edema with stromal thickening. Epithelial bedewing was present bilaterally but worse in the left eye. Central cornea gutatta were present in both eyes. Intraocular pressure was R. E.: 17 mm Hg and L.E.: 18 mm Hg. By specular mi croscopy, the peripheral endothelial cell density was R.E.: 2,000 cells/mm 2 and L.E.: 595 cells/min 2 with polymegathism and cornea guttata bilaterally The edema completely resolved after seven months in the right eye and after eight months in the left eye. Visual acuity was 20/20 in both eyes. Paracentral specular microscopy showed cell densities of R.E.: 600 cells/mm 2 and L.E.: 1,000 cells/mm 2 . DISCUSSION
In our six patients (seven eyes), the edema persisted for periods ranging from five to 18 months, in marked contrast to the readily reversible edema previously observed in healthy9'11,12 and aphakic eyes.3"5·9 The course of the edema followed two patterns. Those eyes that developed edema early had lower endothelial cell densities and the edema did not resolve during an average follow-up period of 15 months. Endothelial densities were high er in the eyes with late edema and the edema eventually resolved after an aver age follow-up period of seven months in all but one eye. In three patients, there was a clear temporal relationship between contact lens fitting and the onset of corneal
(yrs) eye surgery complications
1,785
2,000
1,537
2,000
2,200
Xot possible
*Had previously worn extended-wear lenses but switched because of intolerance. Peripheral cell densities; central specular microscopy was not possible in any of the affected eyes.
Fellow eye
347
Persistent
—
R.E.: 2,000; L.E.: 595
793
Cell density (cells/mm2) Affected eye 446
Persistent
Persistent
Resolved in 5 mos
Status of edema
Xot possible
20/400
20/80-2
H.M.
20/40
Persistent
R.E.: 20/80; L.E.: 20/200 R.E.: 20/20; L.E.: 20/20 Resolved (R.E.; 7 mos; L. E.: 8 mos) 20/400
20/200
20/400
20/400
CF.
20/200
8
14
15
15
18
12
Final
66 mos
30 min
30 days
Softens Daily-wear
48 hrs
Silsoft* Daily-wear
F, 60 Both Intracapsular Xone
48 mos
Silsoft* Daily-wear
M, 74 Left Extracapsular Unplanned extracapsular and vitreous loss
F, 88 Right Extracapsular Vitreous against cornea after YAG laser capsulotomy
Patient 6
20 mos
M, 76 Left Intracapsular Xone
Patient 5
Patient 4
Sauflon Extended-wear
F, 63 Left Intracapsular Xone
M, 66 Left Intracapsular Retinal detachment; vitreous strands to wound requiring YAG laser
Patient 3
Softens Daily-wear
Patient 2
Patient 1
Sauflon Extended-wear
Contact lens Brand Type Time worn before edema Length of follow-up (mos) Visual acuity Initial
Sex, age Affected Cataract Surgical
Clinical Data
TABLE SUMMARY O F CLINICAL DATA
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sa O > Z
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PERSISTENT CORNEAL EDEMA
edema. The patients had had clear corne as with no clinical evidence of stromal or epithelial edema at the time of fitting. Shortly after beginning to wear the con tact lenses, all three had a sudden onset of edema associated with decreased vi sion. Other associated symptoms includ ed pain, photophobia, and conjunctival and ciliary injection, all of which are found in the lens-intolerance syn drome. 1 · 3,4 In these patients, however, the corneal edema never resolved despite earlier reports of rapid resolution of contact-lens-induced edema in aphakic patients after the patients stopped wear ing the contact lenses.3"5'9 The other four eyes suddenly devel oped corneal edema long after beginning contact lens wear. These patients had had good visual acuities and no clinical evi dence of epithelial or stromal edema. The signs and symptoms were similar to those in the first three patients: the patients reported a sudden onset of pain and de creased visual acuity; examinations showed corneal edema and a pattern compatible with lens-intolerance syn drome. However, as in the first three patients, the edema persisted for eight to 18 months. These four eyes also differed from eyes with aphakic bullous keratopathy in that the edema and accompanying symptoms occurred suddenly, and in three of the four eyes the edema completely resolved. These three eyes have remained free of edema without medication. In contrast, aphakic bullous keratopathy generally oc curs as a chronic, progressive corneal edema with increased stromal thicken ing, a fine epithelial edema, bullae forma tion, and a gradual decrease in visual acuity. The edema is irreversible. 13 The two patterns of onset may repre sent part of a spectrum of contact-lensinduced edema, depending on preexist ing function of the corneal endothelium. If the healthy cornea is stressed by con
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tact lens wear, it can become edematous, but the normal deturgescent state is rap idly restored by discontinuation of the contact lens and medical therapy, if need ed. A cornea that has suffered endothelial cell loss may be susceptible to more se vere or more refractory edema. When endothelial cell function is severely com promised, contact lens wear may lead to corneal decompensation with develop ment of persistent or permanent edema. The concept of a spectrum of corneal edema is supported by the work of Binder and Woodward 3 who measured endotheli al cell counts in 70 eyes before fitting myopic or aphakic contact lenses. They used low-, medium-, and high-watercontent extended-wear lenses. Of the 12 aphakic eyes that had developed corneal edema with low- and medium-watercontent contact lenses, eight developed edema even after being switched to the high-water-content lenses. Of the pa tients who developed the lens-intoler ance syndrome, all but one had fewer than 1,200 cells/mm 2 . All but one also had increased baseline corneal thickness before the contact lens was fitted. How ever, none of these patients had corneal edema that persisted after discontinua tion of the contact lens. These patients appear to form a group between our patients who developed persistent edema and asymptomatic contact lens wearers. The work of Poise, Holden, and Swee ney 9 also suggested that the rate of reso lution of corneal edema may depend on endothelial function. They fitted 12 pa tients with unilateral aphakia with highplus extended-wear contact lenses, and noted bilateral corneal swelling after six hours during which the eyes were kept closed. The patients were then permitted to open their eyes. Corneal thickness was measured hourly. The aphakic eyes, which had approximately 10% endotheli al cell loss, showed slower resolution of the corneal swelling.
334
AMERICAN JOURNAL OF OPHTHALMOLOGY
Hypoxia seems to be the major factor causing contact-lens-induced edema.12'14'15 The corneal epithelium's primary source of oxygen is through the tear film16 and, therefore, its access to atmospheric oxy gen is blocked by the contact lens. With a contact lens in place, most of the oxygen reaches the epithelium by diffusion through the contact lens because there is little exchange of tear film under the eyes. 17 Oxygen flux through a soft contact lens is a function of permeability of the lens and its thickness. 14 Closed eyelids also reduce the available supply of oxy gen. 9 ' 14 In patients with normal ocular findings who experienced contact-lensassociated 9 · 11 or experimentally induced 12 corneal edema, there was regression of the edema when the hypoxic state was corrected. The corneal endothelial cells can ob tain an adequate supply of oxygen from the aqueous alone 16 ; how, then, does en dothelial dysfunction increase the likeli hood of corneal edema in eyes with epi thelial hypoxia? As oxygen tension in the outer cornea decreases, the epithelium depends increasingly on anaerobic me tabolism and lactic acid production in creases; osmotic forces tend to draw more water into the cornea. 18 The hypoxic epithelium's effectiveness as a waterimpermeable barrier is reduced. 1 9 The tear film adjacent to the epithelium may become more hypotonie than normal be cause the contact lens tends to reduce evaporation. 20 This also increases osmotic flow of water into the cornea. This se quence of events has been proposed as a mechanism for corneal edema associated with soft contact lenses.15·18"20 Because the endothelium seems to be the site at which water is actively pumped out of the cornea, 21 it is reasonable to assume that superimposed endothelial dysfunction could seriously compromise the cornea's ability to maintain proper hydration. We believe that this hypothesis may explain
SEPTEMBER, 1984
the sequence of events that occurred in the three patients who had early edema. A similar sequence of events could be proposed for the eyes with late edema. Although endothelial function in these eyes was apparently sufficient to maintain a clear cornea when contact lens wear was first begun, normal senile attrition could exhaust the remaining endothelial re serve, resulting in corneal edema. Addi tionally, several reports suggest that the wearing of a contact lens can cause endo thelial damage. In a group of asympto matic patients with hard contact lenses, Caldwell 22 correlated length of contact lens wear with decreases in endothelial cell density. The study group had signifi cantly lower endothelial cell densities than did a group of age- and sex-matched controls. Hirst, Tseng, and Khodadoust 23 reported an increase in endothelial cell size, with a coefficient of skewness and kurtosis demonstrating a dramatic altera tion in cell area distribution. Endothelial blebs have been observed clinically in eyes with both hard 24 and soft15·25 contact lenses. Vannas and associates 26 histologically demonstrated endothelial blebs after short-term soft contact lens use in freshly enucleated eyes and in cadaver eyes that were still being perfused. It has been proposed that alterations in corneal metabolism induced by the con tact lens cause these endothelial chang es.15·22,24 Mechanical forces may also play a role. Miller and Weiss 27 demonstrated histologically that suction from a contact lens can cause both reversible and irre versible endothelial damage in freshly enucleated cow eyes. We believe, there fore, that metabolic or mechanical altera tions of the corneal endothelium, or both, may contribute to corneal edema induced by contact lenses. REFERENCES
1. Binder, P. S.: Complications associated with extended wear of soft contact lenses. Ophthalmology 86:1093, 1979.
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PERSISTENT CORNEAL EDEMA
2. Nesbum, A. B. : Prolonged-wear contact lenses in aphakia. Ophthalmology 85:73, 1978. 3. Binder, P. S., and Woodward, C : Extendedwear Hydrocurve and Sauflon lenses. Am. J. Oph thalmol. 90:309, 1980. 4. Stark, W. J., Kracher, G. P., Cowan, C. L., Taylor, H. R., Hirst, L. W., Oyakawa, R. T., and Maumenee, A. E.: Extended-wear contact lenses and intraocular lenses for aphakic correction. Am. J. Ophthalmol. 88:535, 1979. 5. Gasset, A. R., Lobo, L., and Houde, W.: Permanent wear of soft contact lenses in aphakic eyes. Am. J. Ophthalmol. 83:115, 1977. 6. Farris, R. L.: Complications associated with aphakic contact lenses. Ophthalmology 86:1120, 1979. 7. Kersley, H. J., Kerr, C , and Pierse, D.: Hydrophilic lenses for "continuous" wear in aphakia. Definitive fitting and the problems that occur. Br. J. Ophthalmol. 61:38, 1977. 8. Cooper, R. L., and Constable, I. J.: Infective keratitis in soft contact lens wearers. Br. J. Ophthal mol. 61:250, 1977. 9. Poise, K. A., Holden, B. A., and Sweeney, D.: Corneal edema accompanying aphakic extended lens wear. Arch. Ophthalmol. 101:1038, 1983. 10. Holden, B. A., Mertz, G. W., and Guillon, M.: Corneal swelling response of the aphakic eye. Invest. Ophthalmol. Vis. Sei. 19:1394, 1980. 11. Binder, P. S., and Worthen, D. M.: Clinical evaluation of continuous-wear hydrophilic lenses. Am. J. Ophthalmol. 83:549, 1977. 12. Poise, K. A., and Mandell, R. B.: Etiology of corneal striae accompanying hydrogel lens wear. Invest. Ophthalmol. 15:553, 1976. 13. Gunderson, T. : Surgical treatment of bullous keratopathy. Arch. Ophthalmol. 64:124, 1960. 14. Poise, K. A., and Decker, M.: Oxygen tension under a contact lens. Invest. Ophthalmol. Vis. Sei. 18:188, 1979.
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15. Holden, B. A., Poise, K. A., Fonn, D., and Mertz, G. W. : Effects of cataract surgery on cor neal function. Invest. Ophthalmol. Vis. Sei. 22:343, 1982. 16. Weissman, B. A., Fatt, I., and Rasson, J.: Diffusion of oxygen in human corneas in vivo. Invest. Ophthalmol. Vis. Sei. 20:123, 1981. 17. Poise, K. A.: Tear flow under hydrogel contact lenses. Invest. Ophthalmol. Vis. Sei. 18:409, 1979. 18. Klyce, S. D., and Bernegger, O.: Epithelial hypoxia, lactate production, and stromal edema. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sei. St. Louis, C. V. Mosby, 1978, p. 277. 19. Thoft, R. A., and Mobilia, E. F.: Complica tions with therapeutic extended wear soft contact lenses. Int. Ophthalmol. Clin. 21:197, 1981. 20. White, P. F., and Miller, D.: Corneal edema. Int. Ophthalmol. Clin. 21:3, 1981. 21. Dohlman, C. H.: The function of the corneal epithelium in health and disease. Invest. Ophthal mol. 10:383, 1971. 22. Caldwell, D. R. : The effect of long-term hard lens wear on corneal endothelium. Contact Intraocu lar Lens Med. J. 8:87, 1982. 23. Hirst, L. W., Tseng, S., and Khodadoust, A.: Specular microscopy of hard contact lens wearers. Ophthalmology 90(suppl.):47, 1983. 24. Barr, J. T., and Schoessler, J. P.: Corneal endothelial response to rigid contact lenses. Am. J. Optom. Physiol. Opt. 57:267, 1980. 25. Zantos, S. G., and Holden, B. A.: Transient endothelial changes soon after wearing soft contact lenses. Am. J. Optom. Physiol. Opt. 54:856, 1977. 26. Vannas, A., Holden, B. A., Makitie, J., Ruusuvaara, P., and O'Donnell, J. J. : Specular microsco py and ultrastructure of endothelial blebs. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sei. St. Louis, C. V. Mosby, 1979, p. 143. 27. Miller, D., and Weiss, J.: Corneal endotheli um. Int. Ophthalmol. Clin. 21:39, 1981.