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Postoperative Corneal Edema
AMERICAN JOURNAL OF OPHTHALMOLOGY® FRANK W. N E W E L L , Publisher and Editor-in-Chief Tribune Tower, Suite 1415, 435 North Michigan Ave., Chicago, Illinois 60611 EDITORIAL BOARD Thomas M. Aaberg, Milwaukee Mathea R. Allansmith, Boston Douglas R. Anderson, Miami Charles J. Campbell, New York Ronald E. Carr, New York Claes H. Dohlman, Boston Fred Ederer, Bethesda Eugene Helveston, Indianapolis
Frederick A. Jakobiec, New York Herbert E. Kaufman, Neu; Orleans Steven G. Kramer, San Francisco Irving H. Leopold, Irvine Robert Machemer, Durham A. Edward Maumenee, Baltimore Irene H. Maumenee, Baltimore Edward W. D. Norton, Miami G. Richard O'Connor, Son Francisco Arnall Patz, Baltimore
Deborah Pavan-Langston, Boston Stephen J. Ryan, Los Angeles David Shoch, Chicago Hruce E. Spivey, San Francisco Bradley R. Straatsma, Los Angeles H. Stanley Thompson, Iowa City Gunter K. von Noorden, Houston George O. Waring, Atfonta
Published monthly by the Ophthalmic Publishing Company Tribune Tower, Suite 1415, 435 North Michigan Avenue, Chicago, Illinois 60611 Directors: A. EDWARD MAUMENEE, President; DAVID SHOCH, Vice President; FRANK W. NEWELL, Secretary and Treasurer; EDWARD W. D. NORTON, BRUCE E. SPIVEY, BRADLEY R. STRAATSMA
previous ocular surgery, trauma, inflam mation, or corneal dystrophies that may compromise corneal function. Corneal Mimimizing postoperative corneal ede guttata, increased corneal thickness, and ma has been a subject of great interest a decreased endothelial cell count all to ophthalmologists in recent years. Al alert the clinician to a cornea with bor though microsurgical advances have derline function that should b e treated made intraocular surgery more successful with caution. during the last decade, they have also In preparation for surgery, the com placed more stress on the cornea. The monly used skin disinfectants containing maintenance of normal corneal thickness povidine iodine (with detergent), tinc depends on an intact epithelium and on ture of iodine, chlorhexidine, hexachlorothe barrier and metabolic pump functions phene, or ethyl alcohol must b e applied of the corneal endothelium. Thus, post with care because these solutions can operative corneal edema can be mini cause corneal de-epitheu'alization and mized by avoiding unnecessary physio anterior stromal edema if a drop inadvert logic, pharmacologie, and mechanical ently reaches the tear film during prepa trauma to both the epithelium and t h e ration of the skin. 1 Povidine iodine solu endothelium during preoperative and tion (without detergent) is significantly surgical procedures. less toxic to the cornea and provides Preoperatively, a complete history will excellent antimicrobial protection. disclose conditions such as glaucoma, Effective control of the pupillary aper ture during and after surgery often r e quires the use of mydriatic eyedrops that Reprint requests to Henry F. Edelhauser, may be toxic to the cornea. Topical phenylPh. D., Department of Physiology, Medical College ephrine HCI is only minimally toxic to the of Wisconsin, 8701 Watertown Plank Rd., Milwau epithelium but it may cause significant kee, WI 53226. POSTOPERATIVE C O R N E A L EDEMA
552
VOL. 95, NO. 4 drug-induced edema and reversible dis ruption of the corneal endothelium if ad ministered after the epithelium is re moved. 2 We noted a similar pattern with cyclopentolate HC1 but not with atro pine, tropicamide, or homatropine. Using phenylephrine and cyclopentolate should be avoided, therefore, in eyes in which the epithelium has been removed (a com mon occurrence during vitrectomy or after corneal transplantation when the donor epithelium is poor). As intraocular surgical techniques have developed, the need to use intraocular irrigating solutions in greater quantities for longer times has increased. An irrigat ing solution containing calcium, magnesi um, and an acid citrate buffer system, such as Balanced Salt Solution, can be infused into the eye without corneal toxicity for at least an hour. For longer periods, a bicarbonated buffered salt so lution enriched with glucose and glutathione (BSS Plus) is advisable. 3 More re cently a solution containing additional glucose (Glucose Fortified Balanced Salt Solution) has been shown to minimize posterior subcapsular lens opacification and corneal swelling in diabetic rabbits during vitrectomy. 4 A preliminary study with this solution in diabetic patients to determine its efficacy in humans is under way. The p H and osmotic tolerance of the corneal endothelium must also be consid ered when intracameral solutions are used during surgery. The cornea tol erates p H changes within the range of 6.8 to 8.2 and variations in osmolality from 200 to 450 mOsm. 5 ' 6 The irrigating solu tions we recommend fall well within these limits. Intracameral epinephrine (1:1,000), 1 mg/ml, diluted 1:10 with BSS formulated with a weak buffer system permits pupillary dilation during intraoc ular surgery and maintains the p H within the tolerance of the cornea. However, preparations with a greater buffer capaci
EDITORIAL
553
ty may decrease the p H to 4.0, resulting in endothelial damage and corneal ede ma. 7 Viscous aqueous substitutes, such as 1% sodium hyaluronate (Healon), 20% chondroitin sulfate, and methylcellulose have been used to minimize the endothe lial cell trauma that occurs with intraocu lar lens insertion. Sodium hyaluronate and methylcellulose are iso-osmotic and have a physiologic p H , whereas 20% chondroitin sulfate is hyperosmolar (656 mOsm) and may cause mild anterior subcapsular cataracts in monkeys as well as a reversible decrease in corneal thick ness during corneal endothelial perfu sion. Its reformulation to a more isoosmotic solution would subject the cornea and lens to less osmotic stress. It should be noted that all three of these substances are relatively viscous and can cause sharp increases in intraocular pressure one to six hours after anterior segment usage if they are not washed out. 8 A sharp in crease in intraocular pressure may be associated with a reversible disruption of the normal endothelial ultrastructure. 9 The presence of preservatives in prepa rations applied topically or introduced intracamerally must also be considered if corneal edema is to b e minimized. Pre servatives such as sodium bisulfate 7 (the antioxidant for epinephrine), thimerosal, 10 and chlorhexidene 11 can induce endotheli al barrier breakdown if they come in direct contact with the corneal endotheli um. Damage to the endothelial barrier allows the rate of leakage to exceed the metabolic p u m p rate, resulting in stromal edema. Advances in microsurgical techniques have also been accompanied by a new interest in minimizing iatrogenic corneal trauma, especially in cataract surgery. Intracapsular extraction, planned extracapsular extraction, and posterior cham ber phacoemulsification appear to cause roughly the same amount of endothelial
554
AMERICAN JOURNAL OF OPHTHALMOLOGY
cell loss. Anterior chamber phacoemulsification, however, appears to cause a greater endothelial cell loss. Although insertion of an intraocular lens is associat ed with a greater endothelial cell loss, improved surgical techniques, lens de sign, and patient selection have reduced endothelial cell loss. As intraocular surgery continues to evolve and diversify, we must be alert to the many, often subtle, causes of corneal edema. This challenge requires a knowl edge of corneal physiology and pharma cology as well as continuous improve ment in our surgical techniques. S C O T T M. M A C R A E H E N R Y F. E D E L H A U S E R
REFERENCES
1. Mac Rae, S. M., Edelhauser, H. F., and Brown, B. A.: The corneal toxicity of surgical scrubs. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. St. Louis, C. V. Mosby. In press. 2. Edelhauser, H. F., Hine, J. Ε., Pederson, H., Van Horn, D. L., and Schultz, R. O.: The effect of phenylephrine on the cornea. Arch. Ophthalmol. 97:937, 1979. 3. Edelhauser, H. F., Gonnering, R., and Van
APRIL, 1983
Hom, D. L.: Intraocular irrigating solutions. Arch. Ophthalmol. 96:516, 1978. 4. Haimann, M. H., Abrams, G. W., Edelhauser, H. F., and Hatchell, D. L. : The effects of intraoc ular irrigating solutions on lens clarity in normal and diabetic rabbits. Am. J. Ophthalmol. 94:594, 1982. 5. Gonnering, R., Edelhauser, H. F., Van Horn, D. L., and Durant, W.: The pH tolerance of rabbit and human corneal endothelium. Invest. Ophthal mol. Vis. Sci. 18:373, 1979. 6. Edelhauser, H. F., Hanneken, A. M., Peder son, H. J., and Van Horn, D. L.: Osmotic tolerance of the rabbit and human corneal endothelium. Arch. Ophthalmol. 99:1281, 1981. 7. Edelhauser, H. F., Hyndiuk, R. A., Zeeb, A., and Schultz, R. O. : Corneal edema and the intraocu lar use of epinephrine. Am. J. Ophthalmol. 93:327, 1982. 8. Mac Rae, S. M., Edelhauser, H. F., Hyndiuk, R. A., Burd, E. M., and Schultz, R. O.: The effects of sodium hyaluronate, chondroitin sulfate, and methylcellulose on the corneal endothelium and intraocular pressure. Am. J. Ophthalmol. 95:332, 1983. 9. Svedbergh, B. : Effects of artificial intraocular pressure elevation on the corneal endothelium in the Vervet monkey. Acta Ophthalmal. 53:839, 1959. 10. Van Horn, D. L., Edelhauser, H. F.,Pradonovich, G., Eiferman, R., and Pederson H. J.: Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium. Invest. Ophthal mol. Vis. Sci. 16:273, 1977. 11. Green, K., Livingston, V., Bowman, K., and Hull, D. S.: Chlorhexidine effects on the corneal epithelium and endothelium. Arch. Ophthalmol. 98:1273, 1980.
Frederick A. Jakobiec, New York Herbert E. Kaufman, Neu; Orleans Steven G. Kramer, San Francisco Irving H. Leopold, Irvine Robert Machemer, Durham A. Edward Maumenee, Baltimore Irene H. Maumenee, Baltimore Edward W. D. Norton, Miami G. Richard O'Connor, Son Francisco Arnall Patz, Baltimore
Deborah Pavan-Langston, Boston Stephen J. Ryan, Los Angeles David Shoch, Chicago Hruce E. Spivey, San Francisco Bradley R. Straatsma, Los Angeles H. Stanley Thompson, Iowa City Gunter K. von Noorden, Houston George O. Waring, Atfonta
Published monthly by the Ophthalmic Publishing Company Tribune Tower, Suite 1415, 435 North Michigan Avenue, Chicago, Illinois 60611 Directors: A. EDWARD MAUMENEE, President; DAVID SHOCH, Vice President; FRANK W. NEWELL, Secretary and Treasurer; EDWARD W. D. NORTON, BRUCE E. SPIVEY, BRADLEY R. STRAATSMA
previous ocular surgery, trauma, inflam mation, or corneal dystrophies that may compromise corneal function. Corneal Mimimizing postoperative corneal ede guttata, increased corneal thickness, and ma has been a subject of great interest a decreased endothelial cell count all to ophthalmologists in recent years. Al alert the clinician to a cornea with bor though microsurgical advances have derline function that should b e treated made intraocular surgery more successful with caution. during the last decade, they have also In preparation for surgery, the com placed more stress on the cornea. The monly used skin disinfectants containing maintenance of normal corneal thickness povidine iodine (with detergent), tinc depends on an intact epithelium and on ture of iodine, chlorhexidine, hexachlorothe barrier and metabolic pump functions phene, or ethyl alcohol must b e applied of the corneal endothelium. Thus, post with care because these solutions can operative corneal edema can be mini cause corneal de-epitheu'alization and mized by avoiding unnecessary physio anterior stromal edema if a drop inadvert logic, pharmacologie, and mechanical ently reaches the tear film during prepa trauma to both the epithelium and t h e ration of the skin. 1 Povidine iodine solu endothelium during preoperative and tion (without detergent) is significantly surgical procedures. less toxic to the cornea and provides Preoperatively, a complete history will excellent antimicrobial protection. disclose conditions such as glaucoma, Effective control of the pupillary aper ture during and after surgery often r e quires the use of mydriatic eyedrops that Reprint requests to Henry F. Edelhauser, may be toxic to the cornea. Topical phenylPh. D., Department of Physiology, Medical College ephrine HCI is only minimally toxic to the of Wisconsin, 8701 Watertown Plank Rd., Milwau epithelium but it may cause significant kee, WI 53226. POSTOPERATIVE C O R N E A L EDEMA
552
VOL. 95, NO. 4 drug-induced edema and reversible dis ruption of the corneal endothelium if ad ministered after the epithelium is re moved. 2 We noted a similar pattern with cyclopentolate HC1 but not with atro pine, tropicamide, or homatropine. Using phenylephrine and cyclopentolate should be avoided, therefore, in eyes in which the epithelium has been removed (a com mon occurrence during vitrectomy or after corneal transplantation when the donor epithelium is poor). As intraocular surgical techniques have developed, the need to use intraocular irrigating solutions in greater quantities for longer times has increased. An irrigat ing solution containing calcium, magnesi um, and an acid citrate buffer system, such as Balanced Salt Solution, can be infused into the eye without corneal toxicity for at least an hour. For longer periods, a bicarbonated buffered salt so lution enriched with glucose and glutathione (BSS Plus) is advisable. 3 More re cently a solution containing additional glucose (Glucose Fortified Balanced Salt Solution) has been shown to minimize posterior subcapsular lens opacification and corneal swelling in diabetic rabbits during vitrectomy. 4 A preliminary study with this solution in diabetic patients to determine its efficacy in humans is under way. The p H and osmotic tolerance of the corneal endothelium must also be consid ered when intracameral solutions are used during surgery. The cornea tol erates p H changes within the range of 6.8 to 8.2 and variations in osmolality from 200 to 450 mOsm. 5 ' 6 The irrigating solu tions we recommend fall well within these limits. Intracameral epinephrine (1:1,000), 1 mg/ml, diluted 1:10 with BSS formulated with a weak buffer system permits pupillary dilation during intraoc ular surgery and maintains the p H within the tolerance of the cornea. However, preparations with a greater buffer capaci
EDITORIAL
553
ty may decrease the p H to 4.0, resulting in endothelial damage and corneal ede ma. 7 Viscous aqueous substitutes, such as 1% sodium hyaluronate (Healon), 20% chondroitin sulfate, and methylcellulose have been used to minimize the endothe lial cell trauma that occurs with intraocu lar lens insertion. Sodium hyaluronate and methylcellulose are iso-osmotic and have a physiologic p H , whereas 20% chondroitin sulfate is hyperosmolar (656 mOsm) and may cause mild anterior subcapsular cataracts in monkeys as well as a reversible decrease in corneal thick ness during corneal endothelial perfu sion. Its reformulation to a more isoosmotic solution would subject the cornea and lens to less osmotic stress. It should be noted that all three of these substances are relatively viscous and can cause sharp increases in intraocular pressure one to six hours after anterior segment usage if they are not washed out. 8 A sharp in crease in intraocular pressure may be associated with a reversible disruption of the normal endothelial ultrastructure. 9 The presence of preservatives in prepa rations applied topically or introduced intracamerally must also be considered if corneal edema is to b e minimized. Pre servatives such as sodium bisulfate 7 (the antioxidant for epinephrine), thimerosal, 10 and chlorhexidene 11 can induce endotheli al barrier breakdown if they come in direct contact with the corneal endotheli um. Damage to the endothelial barrier allows the rate of leakage to exceed the metabolic p u m p rate, resulting in stromal edema. Advances in microsurgical techniques have also been accompanied by a new interest in minimizing iatrogenic corneal trauma, especially in cataract surgery. Intracapsular extraction, planned extracapsular extraction, and posterior cham ber phacoemulsification appear to cause roughly the same amount of endothelial
554
AMERICAN JOURNAL OF OPHTHALMOLOGY
cell loss. Anterior chamber phacoemulsification, however, appears to cause a greater endothelial cell loss. Although insertion of an intraocular lens is associat ed with a greater endothelial cell loss, improved surgical techniques, lens de sign, and patient selection have reduced endothelial cell loss. As intraocular surgery continues to evolve and diversify, we must be alert to the many, often subtle, causes of corneal edema. This challenge requires a knowl edge of corneal physiology and pharma cology as well as continuous improve ment in our surgical techniques. S C O T T M. M A C R A E H E N R Y F. E D E L H A U S E R
REFERENCES
1. Mac Rae, S. M., Edelhauser, H. F., and Brown, B. A.: The corneal toxicity of surgical scrubs. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. St. Louis, C. V. Mosby. In press. 2. Edelhauser, H. F., Hine, J. Ε., Pederson, H., Van Horn, D. L., and Schultz, R. O.: The effect of phenylephrine on the cornea. Arch. Ophthalmol. 97:937, 1979. 3. Edelhauser, H. F., Gonnering, R., and Van
APRIL, 1983
Hom, D. L.: Intraocular irrigating solutions. Arch. Ophthalmol. 96:516, 1978. 4. Haimann, M. H., Abrams, G. W., Edelhauser, H. F., and Hatchell, D. L. : The effects of intraoc ular irrigating solutions on lens clarity in normal and diabetic rabbits. Am. J. Ophthalmol. 94:594, 1982. 5. Gonnering, R., Edelhauser, H. F., Van Horn, D. L., and Durant, W.: The pH tolerance of rabbit and human corneal endothelium. Invest. Ophthal mol. Vis. Sci. 18:373, 1979. 6. Edelhauser, H. F., Hanneken, A. M., Peder son, H. J., and Van Horn, D. L.: Osmotic tolerance of the rabbit and human corneal endothelium. Arch. Ophthalmol. 99:1281, 1981. 7. Edelhauser, H. F., Hyndiuk, R. A., Zeeb, A., and Schultz, R. O. : Corneal edema and the intraocu lar use of epinephrine. Am. J. Ophthalmol. 93:327, 1982. 8. Mac Rae, S. M., Edelhauser, H. F., Hyndiuk, R. A., Burd, E. M., and Schultz, R. O.: The effects of sodium hyaluronate, chondroitin sulfate, and methylcellulose on the corneal endothelium and intraocular pressure. Am. J. Ophthalmol. 95:332, 1983. 9. Svedbergh, B. : Effects of artificial intraocular pressure elevation on the corneal endothelium in the Vervet monkey. Acta Ophthalmal. 53:839, 1959. 10. Van Horn, D. L., Edelhauser, H. F.,Pradonovich, G., Eiferman, R., and Pederson H. J.: Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium. Invest. Ophthal mol. Vis. Sci. 16:273, 1977. 11. Green, K., Livingston, V., Bowman, K., and Hull, D. S.: Chlorhexidine effects on the corneal epithelium and endothelium. Arch. Ophthalmol. 98:1273, 1980.