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Corneal Endothelial Cell Counts After Molteno Implantation
Corneal Endothelial Cell Counts After Molteno Implantation Mark L. McDermott, M.D., Ronald P. Swendris, M.D., Dong H. Shin, M.D., Mark S. juzych, M.D., and John W. Cowden, M.D.
Implantation of a Molteno drainage shunt has been shown to be effective in advanced glaucoma. Foreign substances within the anterior chamber have been known to cause progressive endothelial cell loss. We undertook a study to evaluate the endothelial effects of an indwelling Molteno drainage shunt. Nineteen patients who underwent uneventful implantation of a Molteno drainage shunt for advanced aphakic or pseudophakic glaucoma were followed up. Serial endothelial cell counts were obtained in a masked fashion. During follow-up periods ranging from 5.4 to 25.7 months, endothelial cell loss averaged two cells per square millimeter per postoperative month with a 95% confidence interval of positive seven cells to negative ten cells per square millimeter per postoperative month. No clinically significant progressive trend in endothelial cell loss was seen in patients undergoing uncomplicated Molteno drainage procedures. Larger sample sizes with longer follow-up will be necessary to establish whether a Molteno drainage shunt causes clinically remarkable endothelial cell loss. PLACEMENT of a drainage shunt in patients with uncontrolled glaucoma is now accepted practice."! With the increased scope of patients eligible for the implantation of such a device, the long-term safety of these devices for the
Accepted for publication Oct. 2, 1992. From the Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan. This study was presented in part as a poster at the Association for Research in Vision and Ophthalmology Annual Meeting, Sarasota, Florida, May 7, 1992. Reprint requests to Mark L. McDermott, M.D., Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, 4717 St. Antoine, Detroit, MI 48201.
©AMERICAN JOURNAL OF OPHTIiALMOLOGY
115:93-96,
corneal endothelium is not well known. The placement of a silicone tube within the anterior chamber has the potential for multiple endothelial side effects. The active reciprocation of aqueous humor through the silicone tube during the cardiac cycle may create a fluid jet that may impinge on the corneal endothelium during diastole. Additionally, the placement of the tube close to the corneal endothelium may set up a vicious cycle of intermittent corneal endothelial wounding followed by inflammation and corneal endothelial migration to cover the defect followed by rewounding. In this situation the potential exists for ongoing cell loss. The important factor in this hypothesis would be intermittent tube touch. With constant tube touch there may be scarring and fibrosis which, while initially causing a greater reduction in cell count, will result in a stable fixed tubecorneal attachment with no further cell loss. With intermittent tube touch, which can occur when the patient rubs the eye, the potential exists for repeated endothelial wounding and progressive cell loss. Additionally, intermittent tube-uveal touch may cause chronic low-grade inflammation, resulting in endothelial damage. Finally there may be foreign body inflammation secondary to the silicone tube itself. The purpose of our study, therefore, was to assess the endothelial cell counts in patients who had uneventful placement of a Molteno drainage shunt.
Patients and Methods Nineteen patients in whom aphakic or pseudophakic glaucoma was diagnosed were entered into the study. The patients all underwent identical Molteno drainage shunt implantation procedures by the same surgeon (D.H.S.). Briefly, this procedure consisted of preparation of a
JANUARY,
1993
93
94
January, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
10-mm cord length superotemporal or inferonasal fornix-based conjunctival flap including Tenon's capsule with a radial relaxation wing on one side. After blunt dissection of the flap as far posteriorly as possible, a single plate Molteno shunt was inserted into the subtenon's space with the anterior border of the plate no closer than 10 mm from the corneoscleral limbus. The length of the silicone tube was estimated and cut beveled end up at a length to permit its extension 2 to 3 mm into the anterior chamber.' To limit postoperative hypotony, a 9-0 nylon releasable internal ligature was tied tightly around the silicone tube 1.5 mm from its beveled end within the anterior chamber. A paracentesis track was prepared by using a 23-gauge butterfly needle 2 mm from the corneal periphery. The tube with the attached ligature was passed through the paracentesis track into the anterior chamber. Close attention was paid to ensure that the tube lay as far from the cornea as possible without touching the iris. The external portion of the tube was covered with a 5 x 7 -rnm scleral patch graft, which was sutured to the recipient sclera with multiple interrupted 9-0 nylon sutures. The conjunctival peritomy was closed over the site with interrupted 9-0 nylon sutures. Postoperative medications included topical corticosteroids, antibiotics, and cycloplegics. The internal ligature around the silicone tube was lysed with an argon laser (50-J..I.m spot size, O.l-second duration, 1.0-W power) if the intraocular pressure was judged to be clinically unacceptable." During routine scheduled follow-up visits the patients underwent specular microscopy (x 40 cone) of the central endothelium in the operated-on eye. Enlarged negatives were projected on a viewbox and the cells were traced and counted in a masked fashion by the same examiner (M.L.M.). For each patient a rate of cell change per month was calculated from the change in cell counts between successive visits and the elapsed time between visits. For patients examined more than two times a cell change per postoperative month was determined by the quotient of the difference in cell number between the present visit and the most recent previous visit over the elapsed time between visits. For the mean cell change per postoperative month the values determined after each visit were averaged. Although attempts were made to schedule equal intervals between microscopy, the duration between visits was primarily a function of the patient's ability to travel.
Results Follow-up ranged from 5.4 to 25.7 months with a mean of 10.0 ± 6.7 months (mean ± standard deviation). Twelve (63%) patients underwent three or more endothelial cell counts at an average of 6.0 ± 4.4 months between counts. The Figure shows endothelial cell counts plotted as a function of time for each patient. On inspection, all curves were essentially flat, indicating a stable cell count. A mean endothelial cell loss of approximately two cells per square millimeter per postoperative month was seen for all patients. The 95 % confidence interval for this cell change ranged from a positive 6.7 to a negative 10.2 cells per square millimeter per postoperative month. Discussion Our rate of cell loss of two cells per square millimeter per postoperative month lies between that reported for uncomplicated extracapsular cataract extraction and the age-dependent loss of endothelial cells in normal individuals who have never had ocular surgery. In a series of 101 patients undergoing uncomplicated extracapsular cataract extraction with a one-year follow-up, Bates, Hiorns, and Cheng' showed an average rate of cell loss of five cells per square millimeter per postoperative month. In assessing the age-related loss of endothelial cells, data from Vee and associates" permit an estimate of 1.3 cells per square millimeter per month of life to be calculated. The observed interposition of our study's rate of cell loss per postoperative month between that seen in cataract extraction and that related to aging is expected because the initial surgical trauma associated with the Molteno implant placement is probably less than that associated with cataract extraction or trabeculectomy. Implantation of a Molteno device is by and large an extraocular procedure. The only intraocular portion is preparation of a paracentesis track for silicone tube placement. Postoperative complications such as flat anterior chamber, degree of inflammatory response, and tube-corneal touch will surely result in most of the cell loss. With meticulous surgical technique, appropriate safeguards against postoperative hypotony.' and careful postoperative follow-up, endothelial cell loss from these factors can be minimized.
Corneal Endothelial Cells and Molteno Implant
Vol. 115, No.1
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Figure (McDermott and associates). Composite plot of endothelial cell number vs months after Molteno implantation for all 19 patients. The numbers adjacent to the open circles indicate the patient numbers.
o
In contrast to the results described here, there have been reports suggesting a decreased survival rate of corneal grafts in eyes containing Molteno shunts.P In these eyes, however, it would be difficult to attribute endothelial cell loss to the device because most corneal transplants undergo a 60% reduction in central endothelial cell count during the first two postoperative years.' Consequently, it would be difficult to distinguish cell attrition caused by the Molteno device from the cell loss that occurs in the natural course after a corneal transplant. Nevertheless, it is possible that given the reduced reserve of endothelial cells in corneas after keratoplasty, even a small increase in cell attrition of the order of two cells per square millimeter per postoperative month may result in increased rates of corneal decompensation. There is also the possibility that the full-thickness trephination and grafting may alter anterior segment support, resulting in a flaccid anterior segment that would promote tubeendothelial touch and an accelerated rate of cell loss. Additionally, a flaccid anterior segment may promote or tube-uveal touch with attendant inflammation. Besides direct trauma to the endothelium, inflammation alone may affect the endothelium. These effects include neutrophil-generated hydrolases, free radicals, and phagocytic activity. Trauma to the iris may result in generation of prostaglandins, some of which may affect endothelial sodium/potassium adenosine triphosphatase activity. One prostaglandin product;I2 R hydroxyicosatetraenoic acid, has been shown to cause corneal swelling in humans by an in vitro corneal perfusion apparatus." Chronic inflammation has been shown to reduce sodium/potassium adenosine triphosphatase pump site density and increase corneal endothelial permeability in a rabbit uveitis model.!"
Another source of inflammation can be of a foreign-body type in response to the silicone tube. A histopathologic study of the Molteno implant has shown, however, that no appreciable inflammatory reaction is induced by the Molteno plate and the silicone tube entering into the anterior chamber. 11 Furthermore, solid silicone prostheses have been thought to be well tolerated in other areas of the body. More likely, the causes of inflammation center on tube-uveal touch or endothelial wounding. Both of these causes can be minimized with proper tube placement. Nevertheless a lowgrade inflammatory response may exist and this may be enough to shorten graft survival either directly via the previously mentioned mechanisms or by accelerating the afferent and efferent limbs of the immune response, resulting in graft rejection. The range of endothelial cell change per postoperative month does include spread into a positive cell change. Since the human endothelium has little mitotic potential, the positive cell change is most likely representative of sampling differences between successive examinations, as well as variability in central endothelial counting. Sampling differences are especially important in patients with low cell counts. In those patients a maximum possible number of cells was traced and counted." Nevertheless in those patients the number of cells counted was necessarily small. Possibly the sampling difference could mask a larger net cell loss in some patients. A more sensitive technique may be to perform regional specular microscopy in the area of the silicone tube. In our patients, however, the placement of the silicone tube was in the far periphery, and specular microscopy in these areas is technically difficult because of the corneal positioning to allow applanation with the specular microscope cone and the presence of peripheral cor-
96
AMERICAN JOURNAL OF OPHTHALMOLOGY
neal arcus, which limits visualization of the endothelium.
References 1. Minckler, D. S., Heuer, D. K., Hasty, B., Baerveldt, G., Cutting, R. c., and Barlow, W. E.: Clinical experience with the single-plate Molteno implant in complicated glaucomas. Ophthalmology 95:1181, 1988. 2. Melamed, S., and Fiore, P. M.: Molteno implant surgery in refractive glaucoma. Surv. OphthalmoI. 34:441,1990. 3. Freedman, J., and Rubin, B.: Molteno implants as a treatment for refractory glaucoma in black patients. Arch. OphthalmoI. 109:1417, 1991. 4. Shin, D. H., Swendris, R. P., and Sa lot, L. A.: Molteno implantation with a laser-releasable intracameral ligature to limit postoperative pressure fluctuations. AAO abstracts. Ophthalmology 98 (suppI. ):24 7, 1991. 5. Bates, A. K., Hiorns, R. W., and Cheng, H.: Modelling of changes in the corneal endothelium after cataract surgery and penetrating keratoplasty. Br. J. OphthalmoI. 76:32, 1992. 6. Yee, R. W., Matsuda, M., Schultz, R.O., and Edelhauser, H. F.: Changes in the normal corneal endothelial cellular pattern as a function of age. Curro Eye Res. 4:671, 1985.
January, 1993
7. Stewart, D. H., Swendris, R. P., Shin, D. H., Cowden, J. W., and Siegel, M. J.: Outcome of Molteno implantation for glaucoma associated with penetrating keratoplasty. ARVO abstracts. Supplement to Invest. OphthalmoI. Vis. Sci. Philadelphia, J. B. Lippincott, 1992, p. 1273. 8. O'Day, D. G., Stulting, R. D., Lynch, M. G., and Brown, R. H.: Graft survival and intraocular pressure control after Molteno valve implantation for postkeratoplasty glaucoma. ARVO abstracts. Supplement to Invest. OphthalmoI. Vis. Sci. Philadelphia, J. B. Lippincott, 1992, p. 1273. 9. Edelhauser, H. F., Holley, G. P., Geroski, D. H., and Williams, K. K.: A comparison of 12(R) HErE and ouabain reversibility and additive effects on corneal endothelial Na/K ATPase and swelling. ARVO abstracts. Supplement to Invest. OphthalmoI. Vis. Sci. Philadelphia, J. B. Lippincott, 1991, p. 1177. 10. MacDonald, J. M., Geroski, D. H., and Edelhauser, H. F.: Effect of inflammation on corneal endothelial pump and barrier. Curr. Eye Res. 6:1125, 1987. 11. Rubin, B., Chan, c.. Burnier, M., Munion, L., and Freedman, J.: Histopathologic study of the Molteno glaucoma implant in three patients. Am. J. OphthalmoI. 110:371, 1990. 12. Cheng, H., Jacobs, P. M., McPherson, K., and Noble, M. J.: Precision of cell density estimates and endothelial cell loss with age. Arch. OphthalmoI. 103:1478, 1985.
Implantation of a Molteno drainage shunt has been shown to be effective in advanced glaucoma. Foreign substances within the anterior chamber have been known to cause progressive endothelial cell loss. We undertook a study to evaluate the endothelial effects of an indwelling Molteno drainage shunt. Nineteen patients who underwent uneventful implantation of a Molteno drainage shunt for advanced aphakic or pseudophakic glaucoma were followed up. Serial endothelial cell counts were obtained in a masked fashion. During follow-up periods ranging from 5.4 to 25.7 months, endothelial cell loss averaged two cells per square millimeter per postoperative month with a 95% confidence interval of positive seven cells to negative ten cells per square millimeter per postoperative month. No clinically significant progressive trend in endothelial cell loss was seen in patients undergoing uncomplicated Molteno drainage procedures. Larger sample sizes with longer follow-up will be necessary to establish whether a Molteno drainage shunt causes clinically remarkable endothelial cell loss. PLACEMENT of a drainage shunt in patients with uncontrolled glaucoma is now accepted practice."! With the increased scope of patients eligible for the implantation of such a device, the long-term safety of these devices for the
Accepted for publication Oct. 2, 1992. From the Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan. This study was presented in part as a poster at the Association for Research in Vision and Ophthalmology Annual Meeting, Sarasota, Florida, May 7, 1992. Reprint requests to Mark L. McDermott, M.D., Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, 4717 St. Antoine, Detroit, MI 48201.
©AMERICAN JOURNAL OF OPHTIiALMOLOGY
115:93-96,
corneal endothelium is not well known. The placement of a silicone tube within the anterior chamber has the potential for multiple endothelial side effects. The active reciprocation of aqueous humor through the silicone tube during the cardiac cycle may create a fluid jet that may impinge on the corneal endothelium during diastole. Additionally, the placement of the tube close to the corneal endothelium may set up a vicious cycle of intermittent corneal endothelial wounding followed by inflammation and corneal endothelial migration to cover the defect followed by rewounding. In this situation the potential exists for ongoing cell loss. The important factor in this hypothesis would be intermittent tube touch. With constant tube touch there may be scarring and fibrosis which, while initially causing a greater reduction in cell count, will result in a stable fixed tubecorneal attachment with no further cell loss. With intermittent tube touch, which can occur when the patient rubs the eye, the potential exists for repeated endothelial wounding and progressive cell loss. Additionally, intermittent tube-uveal touch may cause chronic low-grade inflammation, resulting in endothelial damage. Finally there may be foreign body inflammation secondary to the silicone tube itself. The purpose of our study, therefore, was to assess the endothelial cell counts in patients who had uneventful placement of a Molteno drainage shunt.
Patients and Methods Nineteen patients in whom aphakic or pseudophakic glaucoma was diagnosed were entered into the study. The patients all underwent identical Molteno drainage shunt implantation procedures by the same surgeon (D.H.S.). Briefly, this procedure consisted of preparation of a
JANUARY,
1993
93
94
January, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
10-mm cord length superotemporal or inferonasal fornix-based conjunctival flap including Tenon's capsule with a radial relaxation wing on one side. After blunt dissection of the flap as far posteriorly as possible, a single plate Molteno shunt was inserted into the subtenon's space with the anterior border of the plate no closer than 10 mm from the corneoscleral limbus. The length of the silicone tube was estimated and cut beveled end up at a length to permit its extension 2 to 3 mm into the anterior chamber.' To limit postoperative hypotony, a 9-0 nylon releasable internal ligature was tied tightly around the silicone tube 1.5 mm from its beveled end within the anterior chamber. A paracentesis track was prepared by using a 23-gauge butterfly needle 2 mm from the corneal periphery. The tube with the attached ligature was passed through the paracentesis track into the anterior chamber. Close attention was paid to ensure that the tube lay as far from the cornea as possible without touching the iris. The external portion of the tube was covered with a 5 x 7 -rnm scleral patch graft, which was sutured to the recipient sclera with multiple interrupted 9-0 nylon sutures. The conjunctival peritomy was closed over the site with interrupted 9-0 nylon sutures. Postoperative medications included topical corticosteroids, antibiotics, and cycloplegics. The internal ligature around the silicone tube was lysed with an argon laser (50-J..I.m spot size, O.l-second duration, 1.0-W power) if the intraocular pressure was judged to be clinically unacceptable." During routine scheduled follow-up visits the patients underwent specular microscopy (x 40 cone) of the central endothelium in the operated-on eye. Enlarged negatives were projected on a viewbox and the cells were traced and counted in a masked fashion by the same examiner (M.L.M.). For each patient a rate of cell change per month was calculated from the change in cell counts between successive visits and the elapsed time between visits. For patients examined more than two times a cell change per postoperative month was determined by the quotient of the difference in cell number between the present visit and the most recent previous visit over the elapsed time between visits. For the mean cell change per postoperative month the values determined after each visit were averaged. Although attempts were made to schedule equal intervals between microscopy, the duration between visits was primarily a function of the patient's ability to travel.
Results Follow-up ranged from 5.4 to 25.7 months with a mean of 10.0 ± 6.7 months (mean ± standard deviation). Twelve (63%) patients underwent three or more endothelial cell counts at an average of 6.0 ± 4.4 months between counts. The Figure shows endothelial cell counts plotted as a function of time for each patient. On inspection, all curves were essentially flat, indicating a stable cell count. A mean endothelial cell loss of approximately two cells per square millimeter per postoperative month was seen for all patients. The 95 % confidence interval for this cell change ranged from a positive 6.7 to a negative 10.2 cells per square millimeter per postoperative month. Discussion Our rate of cell loss of two cells per square millimeter per postoperative month lies between that reported for uncomplicated extracapsular cataract extraction and the age-dependent loss of endothelial cells in normal individuals who have never had ocular surgery. In a series of 101 patients undergoing uncomplicated extracapsular cataract extraction with a one-year follow-up, Bates, Hiorns, and Cheng' showed an average rate of cell loss of five cells per square millimeter per postoperative month. In assessing the age-related loss of endothelial cells, data from Vee and associates" permit an estimate of 1.3 cells per square millimeter per month of life to be calculated. The observed interposition of our study's rate of cell loss per postoperative month between that seen in cataract extraction and that related to aging is expected because the initial surgical trauma associated with the Molteno implant placement is probably less than that associated with cataract extraction or trabeculectomy. Implantation of a Molteno device is by and large an extraocular procedure. The only intraocular portion is preparation of a paracentesis track for silicone tube placement. Postoperative complications such as flat anterior chamber, degree of inflammatory response, and tube-corneal touch will surely result in most of the cell loss. With meticulous surgical technique, appropriate safeguards against postoperative hypotony.' and careful postoperative follow-up, endothelial cell loss from these factors can be minimized.
Corneal Endothelial Cells and Molteno Implant
Vol. 115, No.1
....
350ll N
E E
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Z
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.....
. ....
,~
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• 0----..."
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Figure (McDermott and associates). Composite plot of endothelial cell number vs months after Molteno implantation for all 19 patients. The numbers adjacent to the open circles indicate the patient numbers.
o
In contrast to the results described here, there have been reports suggesting a decreased survival rate of corneal grafts in eyes containing Molteno shunts.P In these eyes, however, it would be difficult to attribute endothelial cell loss to the device because most corneal transplants undergo a 60% reduction in central endothelial cell count during the first two postoperative years.' Consequently, it would be difficult to distinguish cell attrition caused by the Molteno device from the cell loss that occurs in the natural course after a corneal transplant. Nevertheless, it is possible that given the reduced reserve of endothelial cells in corneas after keratoplasty, even a small increase in cell attrition of the order of two cells per square millimeter per postoperative month may result in increased rates of corneal decompensation. There is also the possibility that the full-thickness trephination and grafting may alter anterior segment support, resulting in a flaccid anterior segment that would promote tubeendothelial touch and an accelerated rate of cell loss. Additionally, a flaccid anterior segment may promote or tube-uveal touch with attendant inflammation. Besides direct trauma to the endothelium, inflammation alone may affect the endothelium. These effects include neutrophil-generated hydrolases, free radicals, and phagocytic activity. Trauma to the iris may result in generation of prostaglandins, some of which may affect endothelial sodium/potassium adenosine triphosphatase activity. One prostaglandin product;I2 R hydroxyicosatetraenoic acid, has been shown to cause corneal swelling in humans by an in vitro corneal perfusion apparatus." Chronic inflammation has been shown to reduce sodium/potassium adenosine triphosphatase pump site density and increase corneal endothelial permeability in a rabbit uveitis model.!"
Another source of inflammation can be of a foreign-body type in response to the silicone tube. A histopathologic study of the Molteno implant has shown, however, that no appreciable inflammatory reaction is induced by the Molteno plate and the silicone tube entering into the anterior chamber. 11 Furthermore, solid silicone prostheses have been thought to be well tolerated in other areas of the body. More likely, the causes of inflammation center on tube-uveal touch or endothelial wounding. Both of these causes can be minimized with proper tube placement. Nevertheless a lowgrade inflammatory response may exist and this may be enough to shorten graft survival either directly via the previously mentioned mechanisms or by accelerating the afferent and efferent limbs of the immune response, resulting in graft rejection. The range of endothelial cell change per postoperative month does include spread into a positive cell change. Since the human endothelium has little mitotic potential, the positive cell change is most likely representative of sampling differences between successive examinations, as well as variability in central endothelial counting. Sampling differences are especially important in patients with low cell counts. In those patients a maximum possible number of cells was traced and counted." Nevertheless in those patients the number of cells counted was necessarily small. Possibly the sampling difference could mask a larger net cell loss in some patients. A more sensitive technique may be to perform regional specular microscopy in the area of the silicone tube. In our patients, however, the placement of the silicone tube was in the far periphery, and specular microscopy in these areas is technically difficult because of the corneal positioning to allow applanation with the specular microscope cone and the presence of peripheral cor-
96
AMERICAN JOURNAL OF OPHTHALMOLOGY
neal arcus, which limits visualization of the endothelium.
References 1. Minckler, D. S., Heuer, D. K., Hasty, B., Baerveldt, G., Cutting, R. c., and Barlow, W. E.: Clinical experience with the single-plate Molteno implant in complicated glaucomas. Ophthalmology 95:1181, 1988. 2. Melamed, S., and Fiore, P. M.: Molteno implant surgery in refractive glaucoma. Surv. OphthalmoI. 34:441,1990. 3. Freedman, J., and Rubin, B.: Molteno implants as a treatment for refractory glaucoma in black patients. Arch. OphthalmoI. 109:1417, 1991. 4. Shin, D. H., Swendris, R. P., and Sa lot, L. A.: Molteno implantation with a laser-releasable intracameral ligature to limit postoperative pressure fluctuations. AAO abstracts. Ophthalmology 98 (suppI. ):24 7, 1991. 5. Bates, A. K., Hiorns, R. W., and Cheng, H.: Modelling of changes in the corneal endothelium after cataract surgery and penetrating keratoplasty. Br. J. OphthalmoI. 76:32, 1992. 6. Yee, R. W., Matsuda, M., Schultz, R.O., and Edelhauser, H. F.: Changes in the normal corneal endothelial cellular pattern as a function of age. Curro Eye Res. 4:671, 1985.
January, 1993
7. Stewart, D. H., Swendris, R. P., Shin, D. H., Cowden, J. W., and Siegel, M. J.: Outcome of Molteno implantation for glaucoma associated with penetrating keratoplasty. ARVO abstracts. Supplement to Invest. OphthalmoI. Vis. Sci. Philadelphia, J. B. Lippincott, 1992, p. 1273. 8. O'Day, D. G., Stulting, R. D., Lynch, M. G., and Brown, R. H.: Graft survival and intraocular pressure control after Molteno valve implantation for postkeratoplasty glaucoma. ARVO abstracts. Supplement to Invest. OphthalmoI. Vis. Sci. Philadelphia, J. B. Lippincott, 1992, p. 1273. 9. Edelhauser, H. F., Holley, G. P., Geroski, D. H., and Williams, K. K.: A comparison of 12(R) HErE and ouabain reversibility and additive effects on corneal endothelial Na/K ATPase and swelling. ARVO abstracts. Supplement to Invest. OphthalmoI. Vis. Sci. Philadelphia, J. B. Lippincott, 1991, p. 1177. 10. MacDonald, J. M., Geroski, D. H., and Edelhauser, H. F.: Effect of inflammation on corneal endothelial pump and barrier. Curr. Eye Res. 6:1125, 1987. 11. Rubin, B., Chan, c.. Burnier, M., Munion, L., and Freedman, J.: Histopathologic study of the Molteno glaucoma implant in three patients. Am. J. OphthalmoI. 110:371, 1990. 12. Cheng, H., Jacobs, P. M., McPherson, K., and Noble, M. J.: Precision of cell density estimates and endothelial cell loss with age. Arch. OphthalmoI. 103:1478, 1985.