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The Effects of Extended-Wear Hydrophilic Contact Lenses on the Human Corneal Epithelium
The Effects of Extended-Wear Hydrophilic Contact Lenses on the Human Corneal Epithelium Michael A. Lemp, M.D., and Joseph B. Gold, M.D. We used wide-field color specular microscopy of the human corneal surface to study the morphologic changes that occur under extended-wear contact lenses. There was a shift in the frequency distribution of surface cells by size to larger cells, suggesting a prolonged residence time on the ocular surface. Other abnormalities included retained desiccated mucin, coarse mucus plaques, and palisading of cells. WIDE-FIELD SPECULAR microscopy to examine the corneal epithelium represents a relatively noninvasive method of studying ocular surface morphology in vivo in a variety of clinical conditions. Lohman, Rao, and Aquavella-" first demonstrated the practicality of this method. Using a method similar to that of F. H. Deutsch, O. N. Sardarvec, C. J. Koester, M. D. Marquandt, and P. Thompson (unpublished data), we described the morphologic characteristics of the normal human cornea by means of color specular microscopy combined with the vital stains, rose bengal and fluorescein. 3,4 Pfister," in a scanning electron microscopic study of the normal rabbit cornea, suggested that small cells represent newly emerged surface cells: as cells remain on the surface they enlarge and flatten; large cells, then, represent older surface cells. We identified three distinct cell populations and studied their frequency distributions in both normal human subjects and in patients with keratoconjunctivitis sicca." Statistically significant differences in cell size
Accepted for publication Nov. 14, 1985. From the Cornea Service, Center for Sight, Georgetown University Medical Center, Washington, D.C. This study was supported in part by grant EY 04361-03 from the National Eye Institute (Dr. Lemp) and in part by a grant from Research to Prevent Blindness, Inc. (Dr. Lemp). Reprint requests to Michael A. Lernp, M.D., Cornea Service, Center for Sight, Georgetown University Medical Center, 3800 Reservoir Road, N.W., Washington, D.C. 20007.
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populations have been identified in these two groups. Soft hydrophilic extended-wear contact lenses have become popular in the past few years. Initial reportst" demonstrated a low incidence of complications with these contact lenses. More recently, however, adverse reactions associated with the use of these contact lenses on an extended-wear basis have been reported. 9-13 These include infectious corneal ulcers, sterile corneal infiltrates, and acute corneal erosions associated with perilimbal chemosis and redness, known as the "tight lens syndrome."!' Careful slit-lamp examination of patients with extended-wear contact lenses demonstrates epithelial abnormalities. 15-17 In this study, we examined a series of patients wearing high-water-content and thinmembrane hydrogel contact lenses on an extended-wear basis in an attempt to detect and analyze the possible epithelial surface alterations.
Subjects and Methods Subjects-We studied surface morphologic characteristics in 24 patients with no history of previous ocular surface disease. These patients were divided into separate groups. Group 1 consisted of 12 patients ranging in age from 23 to 43 years who had worn thin-membrane hydrogel extended-wear contact lenses for an average of 1. 9 years for the correction of myopia. Group 2 included six patients ranging in age from 60 to 82 years who had worn high-watercontent hydrogel lenses for an average of three years for the correction of surgical aphakia. Group 3 included six surgically aphakic patients in the same age range as those in Group 2 but who used spectacles rather than contact lenses for correction. All subjects were asked to read and sign a consent form approved by our institutional review board. Methods-We placed a drop of preservativefree sterile saline solution on the applanating
©AMERICAN JOURNAL OF OPHrHALMOLOGY
101:274-277 MARCH, 1986
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Effects of Contact Lenses om the Corneal Epithelium
Vol. 101, No.3
cone of the wide-field specular microscope. After removal of the extended-wear contact lens, each subject was given one drop of proparacaine followed by one drop each of 2% fluorescein and 1% rose bengal solution. The applanating tip was applied directly to the central corneal surface and 36 color photographs were taken of each eye and processed in the usual manner. Developed transparencies were projected with a calculated magnification of x311, corresponding to that of low-power scanning electron microscopy. We measured cell size and determined the frequency of small, medium, and large cells by means of a fixed-frame analysis with an overlying grid. There was considerable variability in cell shape. The Table lists the average dimensions of cells described as small, medium, and large. The assignment of individual cells to each category was based on cell area regardless of shape. By calculating cellular area and assigning cells to the category with average values most closely corresponding to individual cell area, we found that only a few cells were questionable in regard to category. This objective method minimized subjective judgments on the part of the examiner. Results were compared with the previously reported cell size and population distributions found in normal subjects who did not wear contact lenses (Table).3,5 The uptake of vital dyes, and the observation of abnormal surface characteristics, were noted in each patient. No adverse effects were noted during the course of these studies. Results In both Group 1 and Group 2, there was a distinct shift in superficial cell population to medium and large cells compared with normal (Figure, top left and top right). This was striking in Group 2 where large cells constituted 56.6% of the total compared to our previous findings of 0.4% in normal subjects (Table). In contrast, small cells constituted only 13.7% of the total in Group 2 compared to 32% in normal subjects and 43.7% in Group 2. To study further the significance of these shifts in Group 2, we studied a series of six patients ranging in age from 60 to 85 years who were surgically aphakic but who did not wear contact lenses (Group 3). The percentage of large cells (7%), while greater than that in the
TABLE CELL SIZE POPULATIONS CELLSIZE
Normal corneas (No. = 13) Small cells Medium cells Large cells Group 1 (No. = 12)* Small cells Medium cells Large cells Group 3 (No. = 6)* Small cells Medium cells Large cells Group 4 (No. = 6)* Small cells Medium cells Large cells
DIMENSIONS (11M)
FREQUENCY (%)
15.7 x 12.1 28.1 x 22.7
32.0 67.6
47.2 x 31.1
0.4
17.7 x 14.3 24.2 x 22.0
43.5 44.7 11.8
58.4 x 32.3 20.5 x 12.2 35.2 x 29.1 65.6 x 35.2 18.2 x 15.2 27.3 x 23.2 40.5 x 32.0
13.7 29.7 56.6 35.0 58.0 7.0
*Group 1 ranged in age from 23 to 43 years and had worn contact lenses for myopia for an average of 1.9 years. Group 2 ranged in age from 60 to 82 years and had worn contact lenses for aphakia for an average of three years. Group 4 ranged in age from 60 to 85 years and had worn spectacles rather than contact lenses for aphakia.
normal subjects, was still significantly less than that in Group 2 (Table). Cellular size was significantly increased in both Group 1 and Group 2. The large cells, moreover, appeared to take up more fluorescein than small or medium size cells did. Additional surface abnormalities included sheets of elongated palisading cells in two aphakic patients (Figure, bottom left); white desiccated cells, retained mucus and cellular debris, and coarse mucus plaques (Figure, bottom right) were noted in both groups. Discussion The effects of contact lenses on the corneal epithelium have been well documented in both animal and human studies. In the rabbit, Thoft and Friend" reported decreased adenosine triphosphate and glycogen depletion in the corneal epithelium with hard contact lenses. Francois, Victoria-Troncoso, and D'Haenens" showed increased cellular exfoliation in rabbits with silicone lenses. Bergmanson and Chu 20
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Figure (Lemp and Gold). Top left, Normal corneal surface with small, nonstaining cells predominating. Top right, Large cells with desiccated mucin (white) in Group 2 (aphakic subjects with extended-wear contact lenses). Bottom left, Palisading of cells under an extended-wear contact lens. Bottom right, Coarse mucus plaques (arrow) under an extended-wear contact lens.
described epithelial edema and premature cell loss in the monkey. Hamano and Hori" reported suppression of basal cell mitoses in rabbits wearing hydrogel contact lenses. Recent studies by Bergmanson, Ruben, and Chu 22 further documented epithelial cell changes associated with contact lens wear in the monkey. Furthermore, specular microscopy of soft contact lenses after wear has demonstrated attached cells with a high reflectivity in addition to debris and mucus.! In patients with keratoconjunctivitis sicca, we recorded a shift in normal epithelial cell distribution, with a greater number of small
cells suggesting accelerated epithelial exfoliation." In the present study, the striking shift to medium and large cells with increased large cell size suggested a delay in the normal corneal exfoliative process. This was particularly evident in Group 3, the older patients wearing high-water-content extended-wear hydrogel contact lenses for aphakia, but was also present in Group 2, the younger group wearing thinmembrane contact lenses for myopia. There is little tear exchange beneath soft hydrophilic contact lenses and the tear film trapped beneath represents a sequestered body of fluid." It was not surprising that the exit
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Effects of Contact Lenses on the Corneal Epithelium
pathway for trapped exfoliative cells and debris was impeded. Our studies suggested a prolonged residence time on the ocular surface of cells that enables them to change from newly emerged small cells to large, flattened cells. Combining these findings with the work of Hamano and Hori" in the rabbit, showing a suppression of basal cell mitosis associated with contact lens wear, we suggest the following hypothesis: Extendedwear contact lenses may cause a delay in epithelial cell turnover characterized by the presence of large, more senescent cells residing on the corneal epithelial surface, thus delaying the emergence and maturation of underlying younger cells. Other findings included trapped surface debris, intraepithelial pseudocysts, and increased uptake of water-soluble dyes, suggesting increased permeability of the surface cells. These studies demonstrated in vivo changes in surface cell populations in the human corneal epithelium under extended-wear contact lenses. The significance of these profound changes in epithelial turnover is not entirely clear.' The sequestration of the tear film beneath any hydrophilic lens worn on an extended basis and the presence of these significant shifts in epithelial cell characteristics suggests a profound alteration in corneal epithelial turnover and a possible build-up of metabolic waste products within this milieu. These changes may playa role in the pathogenesis of some of the clinical problems reported with extendedwear contact lenses.
References 1. Lohman, 1. E., Rao, G. N., and Aquavella, V.: Normal human corneal epithelium. In vivo microscopic observations. Arch. Ophthalmol. 100:991, 1982. 2. - - : In vivo microscopic observations of human corneal epithelial abnormalities. Am. J. Ophthalmol. 93:210, 1982. 3. Lemp, M. A., Guimaraes, R. Q., Mahmood, M. A., Wong,S., and Blackman, H. J.: In vivo surface morphology of the human cornea by color specular microscopy. Cornea 2:295, 1983. 4. Wong,S., Rodrigues, M. M., Blackman, H. J., Guimaraes, R., and Lemp, M. A.: Color specular microscopy of disorders involving the corneal epithelium. Ophthalmology 91:1176, 1984. 5. Pfister, R. R.: The normal surface of the corneal epithelium. A scanning electron microscopic study. Invest. Ophthalmol. 12:654, 1973. 6. Lemp, M. A., Gold, J. B., Wong,S., Mahmood, M., and Guimaraes, R.: An in vivo study of corneal
J.
277
surface morphologic features in patients with keratoconjunctivitis sicca. Am. J. Ophthalmol. 98:426, 1984. 7. Stark, W. J., Kracher, G. P., Cowan, C. L., Taylor, H. R., Hirst, 1. W., Oyakawa, R. T., and Maumenee, A. E.: Extended-wear contact lenses for aphakic correction. Am. J. Ophthalmol. 88:535, 1979. 8. Stark, W. J., and Martin, N. F.: Extended-wear contact lenses for myopic correction. Arch. Ophthalmol. 99:1963, 1981. 9. Eichenbaum, J. W., Feldstein, M., and Podos, S. M.: Extended-wear aphakic soft contact lenses and corneal ulcers. Br. J. Ophthalmol. 66:663, 1982. 10. Adams, C. P., n.. Cohen, E. J., Laibson, P. R., Galentine, P., and Arentsen, J. J.: Corneal ulcers in patients with cosmetic extended-wear contact lenses. Am. J. Ophthalmol. 96:705, 1983. 11. Hassman, G., and Sugar, J.: Pseudomonas corneal ulcer with extended-wear soft contact lenses for myopia. Arch. Ophthalmol. 101:1549, 1983. 12. Lemp, M. A., Blackman, H. J., Wilson, 1. A., and Leveille, A. 5.: Gram-negative corneal ulcers in elderly aphakic eyes with extended-wear lenses. Ophthalmology 90:60, 1984. 13. Spoor, T. c., Hartel, W. c., Wynn, P., and Spoor, P. K.: Complications of continuous-wear soft contact lenses in a nonreferral population. Arch. Ophthalmol. 102:1312, 1984. 14. McCarey, B. E., and Wilson, 1. A.: pH, osmolarity and temperature effects on the water content of hydrogel contact lenses. Contact Intraocul. Lens Med. J. 8:158, 1982. 15. Humphreys, J. A., Larke, J. R., and Parrish, S. T.: Microepithelial cysts observed in extended contact lens-wearing subjects. Br. J. Ophthalmol. 64:888, 1980. 16. Zantos, S. G.: Cystic formations in corneal epithelium during extended wear of contact lenses. Int. Contact Lens Clin. 10:128, 1983. 17. Margulies, 1. J., and Mannis, M. J.: Dendritic corneal lesions associated with soft contact lens wear. Arch. Ophthalmol. 101:1551, 1983. 18. Thoft, R. A., and Friend, J.: Biochemical aspects of contact lens wear. Am. J. Ophthalmol. 80:139, 1975. 19. Francois, J., Victoria-Troncoso, V., and D'Haenens, J.: Histochemical and microscopical study of the corneal epithelium after wearing different types of contact lenses. Contact Lens J. 9:16, 1980. 20. Bergmanson, J. P. G., and Chu, 1. W.-F.: Corneal response to rigid contact lens wear. Br. J. Ophthalmol. 66:667, 1982. 21. Hamano, H., and Hori, M.: Effect of contact lens wear on the mitoses of corneal epithelial cells. C.L.A.O. J. 9:133, 1983. 22. Bergmanson, J. P. G., Ruben, M., and Chu, 1. W.-F.: Corneal epithelial response of the primate eye to gas-permeable corneal contact lenses. A preliminary report. Cornea 3:109, 1984. 23. Polse, K. A., and Decker, M.: Oxygen tension under a contact lens. Invest. Ophthalmol. Vis. Sci. 18:188, 1979.
Accepted for publication Nov. 14, 1985. From the Cornea Service, Center for Sight, Georgetown University Medical Center, Washington, D.C. This study was supported in part by grant EY 04361-03 from the National Eye Institute (Dr. Lemp) and in part by a grant from Research to Prevent Blindness, Inc. (Dr. Lemp). Reprint requests to Michael A. Lernp, M.D., Cornea Service, Center for Sight, Georgetown University Medical Center, 3800 Reservoir Road, N.W., Washington, D.C. 20007.
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populations have been identified in these two groups. Soft hydrophilic extended-wear contact lenses have become popular in the past few years. Initial reportst" demonstrated a low incidence of complications with these contact lenses. More recently, however, adverse reactions associated with the use of these contact lenses on an extended-wear basis have been reported. 9-13 These include infectious corneal ulcers, sterile corneal infiltrates, and acute corneal erosions associated with perilimbal chemosis and redness, known as the "tight lens syndrome."!' Careful slit-lamp examination of patients with extended-wear contact lenses demonstrates epithelial abnormalities. 15-17 In this study, we examined a series of patients wearing high-water-content and thinmembrane hydrogel contact lenses on an extended-wear basis in an attempt to detect and analyze the possible epithelial surface alterations.
Subjects and Methods Subjects-We studied surface morphologic characteristics in 24 patients with no history of previous ocular surface disease. These patients were divided into separate groups. Group 1 consisted of 12 patients ranging in age from 23 to 43 years who had worn thin-membrane hydrogel extended-wear contact lenses for an average of 1. 9 years for the correction of myopia. Group 2 included six patients ranging in age from 60 to 82 years who had worn high-watercontent hydrogel lenses for an average of three years for the correction of surgical aphakia. Group 3 included six surgically aphakic patients in the same age range as those in Group 2 but who used spectacles rather than contact lenses for correction. All subjects were asked to read and sign a consent form approved by our institutional review board. Methods-We placed a drop of preservativefree sterile saline solution on the applanating
©AMERICAN JOURNAL OF OPHrHALMOLOGY
101:274-277 MARCH, 1986
275
Effects of Contact Lenses om the Corneal Epithelium
Vol. 101, No.3
cone of the wide-field specular microscope. After removal of the extended-wear contact lens, each subject was given one drop of proparacaine followed by one drop each of 2% fluorescein and 1% rose bengal solution. The applanating tip was applied directly to the central corneal surface and 36 color photographs were taken of each eye and processed in the usual manner. Developed transparencies were projected with a calculated magnification of x311, corresponding to that of low-power scanning electron microscopy. We measured cell size and determined the frequency of small, medium, and large cells by means of a fixed-frame analysis with an overlying grid. There was considerable variability in cell shape. The Table lists the average dimensions of cells described as small, medium, and large. The assignment of individual cells to each category was based on cell area regardless of shape. By calculating cellular area and assigning cells to the category with average values most closely corresponding to individual cell area, we found that only a few cells were questionable in regard to category. This objective method minimized subjective judgments on the part of the examiner. Results were compared with the previously reported cell size and population distributions found in normal subjects who did not wear contact lenses (Table).3,5 The uptake of vital dyes, and the observation of abnormal surface characteristics, were noted in each patient. No adverse effects were noted during the course of these studies. Results In both Group 1 and Group 2, there was a distinct shift in superficial cell population to medium and large cells compared with normal (Figure, top left and top right). This was striking in Group 2 where large cells constituted 56.6% of the total compared to our previous findings of 0.4% in normal subjects (Table). In contrast, small cells constituted only 13.7% of the total in Group 2 compared to 32% in normal subjects and 43.7% in Group 2. To study further the significance of these shifts in Group 2, we studied a series of six patients ranging in age from 60 to 85 years who were surgically aphakic but who did not wear contact lenses (Group 3). The percentage of large cells (7%), while greater than that in the
TABLE CELL SIZE POPULATIONS CELLSIZE
Normal corneas (No. = 13) Small cells Medium cells Large cells Group 1 (No. = 12)* Small cells Medium cells Large cells Group 3 (No. = 6)* Small cells Medium cells Large cells Group 4 (No. = 6)* Small cells Medium cells Large cells
DIMENSIONS (11M)
FREQUENCY (%)
15.7 x 12.1 28.1 x 22.7
32.0 67.6
47.2 x 31.1
0.4
17.7 x 14.3 24.2 x 22.0
43.5 44.7 11.8
58.4 x 32.3 20.5 x 12.2 35.2 x 29.1 65.6 x 35.2 18.2 x 15.2 27.3 x 23.2 40.5 x 32.0
13.7 29.7 56.6 35.0 58.0 7.0
*Group 1 ranged in age from 23 to 43 years and had worn contact lenses for myopia for an average of 1.9 years. Group 2 ranged in age from 60 to 82 years and had worn contact lenses for aphakia for an average of three years. Group 4 ranged in age from 60 to 85 years and had worn spectacles rather than contact lenses for aphakia.
normal subjects, was still significantly less than that in Group 2 (Table). Cellular size was significantly increased in both Group 1 and Group 2. The large cells, moreover, appeared to take up more fluorescein than small or medium size cells did. Additional surface abnormalities included sheets of elongated palisading cells in two aphakic patients (Figure, bottom left); white desiccated cells, retained mucus and cellular debris, and coarse mucus plaques (Figure, bottom right) were noted in both groups. Discussion The effects of contact lenses on the corneal epithelium have been well documented in both animal and human studies. In the rabbit, Thoft and Friend" reported decreased adenosine triphosphate and glycogen depletion in the corneal epithelium with hard contact lenses. Francois, Victoria-Troncoso, and D'Haenens" showed increased cellular exfoliation in rabbits with silicone lenses. Bergmanson and Chu 20
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MARCH,1986
Figure (Lemp and Gold). Top left, Normal corneal surface with small, nonstaining cells predominating. Top right, Large cells with desiccated mucin (white) in Group 2 (aphakic subjects with extended-wear contact lenses). Bottom left, Palisading of cells under an extended-wear contact lens. Bottom right, Coarse mucus plaques (arrow) under an extended-wear contact lens.
described epithelial edema and premature cell loss in the monkey. Hamano and Hori" reported suppression of basal cell mitoses in rabbits wearing hydrogel contact lenses. Recent studies by Bergmanson, Ruben, and Chu 22 further documented epithelial cell changes associated with contact lens wear in the monkey. Furthermore, specular microscopy of soft contact lenses after wear has demonstrated attached cells with a high reflectivity in addition to debris and mucus.! In patients with keratoconjunctivitis sicca, we recorded a shift in normal epithelial cell distribution, with a greater number of small
cells suggesting accelerated epithelial exfoliation." In the present study, the striking shift to medium and large cells with increased large cell size suggested a delay in the normal corneal exfoliative process. This was particularly evident in Group 3, the older patients wearing high-water-content extended-wear hydrogel contact lenses for aphakia, but was also present in Group 2, the younger group wearing thinmembrane contact lenses for myopia. There is little tear exchange beneath soft hydrophilic contact lenses and the tear film trapped beneath represents a sequestered body of fluid." It was not surprising that the exit
Vol. 101, No.3
Effects of Contact Lenses on the Corneal Epithelium
pathway for trapped exfoliative cells and debris was impeded. Our studies suggested a prolonged residence time on the ocular surface of cells that enables them to change from newly emerged small cells to large, flattened cells. Combining these findings with the work of Hamano and Hori" in the rabbit, showing a suppression of basal cell mitosis associated with contact lens wear, we suggest the following hypothesis: Extendedwear contact lenses may cause a delay in epithelial cell turnover characterized by the presence of large, more senescent cells residing on the corneal epithelial surface, thus delaying the emergence and maturation of underlying younger cells. Other findings included trapped surface debris, intraepithelial pseudocysts, and increased uptake of water-soluble dyes, suggesting increased permeability of the surface cells. These studies demonstrated in vivo changes in surface cell populations in the human corneal epithelium under extended-wear contact lenses. The significance of these profound changes in epithelial turnover is not entirely clear.' The sequestration of the tear film beneath any hydrophilic lens worn on an extended basis and the presence of these significant shifts in epithelial cell characteristics suggests a profound alteration in corneal epithelial turnover and a possible build-up of metabolic waste products within this milieu. These changes may playa role in the pathogenesis of some of the clinical problems reported with extendedwear contact lenses.
References 1. Lohman, 1. E., Rao, G. N., and Aquavella, V.: Normal human corneal epithelium. In vivo microscopic observations. Arch. Ophthalmol. 100:991, 1982. 2. - - : In vivo microscopic observations of human corneal epithelial abnormalities. Am. J. Ophthalmol. 93:210, 1982. 3. Lemp, M. A., Guimaraes, R. Q., Mahmood, M. A., Wong,S., and Blackman, H. J.: In vivo surface morphology of the human cornea by color specular microscopy. Cornea 2:295, 1983. 4. Wong,S., Rodrigues, M. M., Blackman, H. J., Guimaraes, R., and Lemp, M. A.: Color specular microscopy of disorders involving the corneal epithelium. Ophthalmology 91:1176, 1984. 5. Pfister, R. R.: The normal surface of the corneal epithelium. A scanning electron microscopic study. Invest. Ophthalmol. 12:654, 1973. 6. Lemp, M. A., Gold, J. B., Wong,S., Mahmood, M., and Guimaraes, R.: An in vivo study of corneal
J.
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surface morphologic features in patients with keratoconjunctivitis sicca. Am. J. Ophthalmol. 98:426, 1984. 7. Stark, W. J., Kracher, G. P., Cowan, C. L., Taylor, H. R., Hirst, 1. W., Oyakawa, R. T., and Maumenee, A. E.: Extended-wear contact lenses for aphakic correction. Am. J. Ophthalmol. 88:535, 1979. 8. Stark, W. J., and Martin, N. F.: Extended-wear contact lenses for myopic correction. Arch. Ophthalmol. 99:1963, 1981. 9. Eichenbaum, J. W., Feldstein, M., and Podos, S. M.: Extended-wear aphakic soft contact lenses and corneal ulcers. Br. J. Ophthalmol. 66:663, 1982. 10. Adams, C. P., n.. Cohen, E. J., Laibson, P. R., Galentine, P., and Arentsen, J. J.: Corneal ulcers in patients with cosmetic extended-wear contact lenses. Am. J. Ophthalmol. 96:705, 1983. 11. Hassman, G., and Sugar, J.: Pseudomonas corneal ulcer with extended-wear soft contact lenses for myopia. Arch. Ophthalmol. 101:1549, 1983. 12. Lemp, M. A., Blackman, H. J., Wilson, 1. A., and Leveille, A. 5.: Gram-negative corneal ulcers in elderly aphakic eyes with extended-wear lenses. Ophthalmology 90:60, 1984. 13. Spoor, T. c., Hartel, W. c., Wynn, P., and Spoor, P. K.: Complications of continuous-wear soft contact lenses in a nonreferral population. Arch. Ophthalmol. 102:1312, 1984. 14. McCarey, B. E., and Wilson, 1. A.: pH, osmolarity and temperature effects on the water content of hydrogel contact lenses. Contact Intraocul. Lens Med. J. 8:158, 1982. 15. Humphreys, J. A., Larke, J. R., and Parrish, S. T.: Microepithelial cysts observed in extended contact lens-wearing subjects. Br. J. Ophthalmol. 64:888, 1980. 16. Zantos, S. G.: Cystic formations in corneal epithelium during extended wear of contact lenses. Int. Contact Lens Clin. 10:128, 1983. 17. Margulies, 1. J., and Mannis, M. J.: Dendritic corneal lesions associated with soft contact lens wear. Arch. Ophthalmol. 101:1551, 1983. 18. Thoft, R. A., and Friend, J.: Biochemical aspects of contact lens wear. Am. J. Ophthalmol. 80:139, 1975. 19. Francois, J., Victoria-Troncoso, V., and D'Haenens, J.: Histochemical and microscopical study of the corneal epithelium after wearing different types of contact lenses. Contact Lens J. 9:16, 1980. 20. Bergmanson, J. P. G., and Chu, 1. W.-F.: Corneal response to rigid contact lens wear. Br. J. Ophthalmol. 66:667, 1982. 21. Hamano, H., and Hori, M.: Effect of contact lens wear on the mitoses of corneal epithelial cells. C.L.A.O. J. 9:133, 1983. 22. Bergmanson, J. P. G., Ruben, M., and Chu, 1. W.-F.: Corneal epithelial response of the primate eye to gas-permeable corneal contact lenses. A preliminary report. Cornea 3:109, 1984. 23. Polse, K. A., and Decker, M.: Oxygen tension under a contact lens. Invest. Ophthalmol. Vis. Sci. 18:188, 1979.