Endothelial wound healing mechanisms: sloughing & sliding, coalescence, and mitosis Prior to the development of clinical specular microscopy it was believed that the only healing mechanism for the adult human corneal endothelium was the "sloughing and sliding" mechanism whereby damaged endothelial cells sloughed from the endothelium and the adjacent undamaged, or less damaged, cells moved laterally so as to cover the defect left by the sloughed cells. Specular microscopy revealed two additional healing mechanisms. Endothelial cell coalescence (cell fusion), is a mechanism in which the common cell membrane between two cells degenerates to result in a larger cell containing two nuclei and, presumably, all of the cellular organelles of the two individual cells.44,45 Endothelial cell mitosis, once generally believed to be impossible for adult human endothelial cells, has also been demonstrated in the adult human cornea following successful treatment for graft rejection.30 Although considerable effort has been expended since the mid-1980's to induce mitosis by the application of exogenous substances such as growth factors, such efforts have been largely unsuccessful and the trigger for endothelial cell mitosis has been elusive. Aging It is well established that the central endothelium changes as a function of age7,46-62. In most individuals the cell density decreases (or mean cell area increases) from birth to death. From birth to adolescence the cell density decreases rapidly56, though it is not known whether this represents true cell loss or is simply a reflection of the normal enlargement the globe that occurs during this period57. From age 20 through approximately age 50, endothelial cell density seems to be relatively stable. After the age of 60, cell density decreases significantly in most people, although there is a great deal of individual variability. Since at this age the globe does not change in size, this observation seems to represent a true loss of endothelial cells. In younger individuals there is usually no significant difference in endothelial cell density between the two eyes. With increasing age, however, some people display a significant difference between the two eyes that is currently not understood. Changes in the variability of cell size (polymegathism), cell shape (pleomorphism), and other non-size related parameters have been found to correlate with age7,63. Fuch’s Dystrophy Cornea guttate, characteristic for Fuch’s endothelial dystrophy, are focal accumulations of collagen on the posterior surface of Descemet's membrane that apparently are formed by stressed or abnormal endothelial cells; they appear as warts or excrescences of Descemet's membrane and can easily be seen with specular microscopy64. Cornea guttate also occur as a result of aging65,66 and corneal inflammation67.
The progressive morphologic changes of cornea guttate in Fuchs' endothelial dystrophy have been characterized by specular photomicroscopy64. Five specific stages in the development of excrescences can be discerned during the early evolution of the disorder (see figure above). All five stages can occur in a cornea clinically free of edema. Several stages can be observed in the same cornea at a given time, although in most cases the majority of cornea guttate seem to have progressed to the same stage of development. Specular microscopic findings demonstrate that an individual excrescence begins as a tiny structure, much smaller in size than an endothelial cell, and progressively grows. Initially the endothelial cell lying behind the excrescence, as well as neighboring endothelial cells, all appear normal. As the excrescence grows larger, it obscures the view of the endothelial cell lying directly behind it, and the neighboring endothelial cells begin to appear distinctly abnormal. Two types of cornea guttate can be identified in vivo with the specular microscope. One has a smooth, regular posterior surface, whereas the posterior contour of the second is irregular. Ultrastructural studies have identified rounded excrescences and excrescences with a flat, broad posterior surface containing a central depression68,69. The latter umbilicated excrescences tend to be large, generally larger than the rounded excrescences, suggesting that the irregular posterior surface may represent a maturation change and that particular excrescence is long lived. However, one cannot differentiate between the endothelial changes adjacent to the two types of cornea guttate, nor is one able to identify either type of excrescence as a specific contributor to endothelial decompensation. Lattice corneal dystrophy Specular microscopy of patients having Lattice Corneal Dystrophy, an autosomal dominant disease, has shown the presence of linear structures described as branching lines criss-crossing the stroma that are believed to be amaloid deposits or lesions caused by amyloid deposition70-73 as well as a craterform appearance70. Although histologically there are irregularities in the epithelium and in Bowman's zone, no endothelial involvement has been noticed71. Iridocorneal endothelial syndrome The iridocorneal endothelial syndrome(ICE syndrome), believed to be due to a defect of the corneal endothelium74, includes progressive essential iris atrophy, Chandler's syndrome75, and the iris nevus (Cogan-Reese) syndrome76. This spectrum of diseases is characterized by abnormalities of the cornea, the anterior chamber angle, and the iris77. In some cases corneal edema, and in other cases, the growth of a membrane onto the iris are seen. Contraction of the membrane may cause peripheral anterior synechiae with secondary glaucoma and various iris abnormalities74. Ultrastructural studies of cases with advanced corneal edema reveal abnormal cells having a decreased endothelial cell density covering a thickened, multilayered Descemet's membrane78,79. An early report of the specular microscopic appearance of the corneal endothelium in Chandler's syndrome described grossly abnormal cells and suggested that the changes could be confused with cornea guttatae.80 However, a subsequent study indicated that this similarity in specular microscopic findings might be problematic only in advanced cases of the iridocorneal endothelial syndrome and Fuchs' dystrophy, and that the abnormalities observed in the former entity were rather distinctive. In minimally affected corneas the clinical specular microscopic appearance of the endothelium was characterized as a "rounding-up" of the endothelial cells. There was a loss of cellular definition and hexagonal shape, and many pentagonal cells were evident81,82. There was also an increased granularity of the intracellular details, and small, centric dark areas appeared in individual cells. These changes seemed to affect virtually all cells81. Moderately affected corneas are characterized by an increased endothelial cell pleomorphism and an enlargement of the intracellular dark areas. In some instances, these structures extend to the cell margin but do not cross cell boundaries. In markedly affected corneas, a true endothelial mosaic no longer exists. Surprisingly, corneas with this degree of endothelial abnormality often remain clear and dehydrated, permitting excellent visualization and specular microscopy. In early changes of ICE syndrome, specular microscopic photographs reveal distinct demarkation between abnormal and normal endothelial cells near the peripheral anterior synechiae44,83. Many abnormally shaped cells with bright intracellular structures were observed. Moreover, the normal endothelial cells adjacent to the demarkation line have a higher endothelial cell count of 5464 cells/mm˛ 88 or 5350 cells/mm˛ .44 Specular microscopy of apparently uninvolved fellow eyes of these patients often show a degree of endothelial cell pleomorphism and polymegathism that is inconsistent with the patient's age81,84. Posterior polymorphous dystrophy The clinical manifestations of posterior polymorphous dystrophy are similar to those of iridocorneal endothelial syndrome so that the diagnosis is complicated. Many of the features of iridocorneal endothelial dystrophy have been reported in cases of posterior polymorphous dystrophy69,85-90. Posterior polymorphous dystrophy is generally regarded to be an inherited, often bilateral abnormality of the posterior, non-banded layer of Descemet's membrane, that may be the result of an abnormality of the corneal endothelium at the time of birth69. Unlike iridocorneal endothelial dystrophy, posterior polymorphous dystrophy is generally non-progressive and only occasionally associated with corneal decompensation or glaucoma69.
These two dystrophies can generally be distinguished by specular microscopy . The dark structures seen in posterior polymorphous dystrophy have a thick dark border and lie anterior to recognizable endothelial cells that have an undistorted appearance and are almost always larger than normal, while the dark structures seen in iridocorneal endothelial dystrophy have a thin dark edge and lie within the endothelium. The endothelial cells adjacent to the dark structure have a distorted appearance and are commonly smaller than normal91,92. Specular microscopy has also been useful in distinguishing posterior polymorphous dystrophy from other problems causing posterior corneal opacities. The parallel "rail track" (straight) borders from old Descemet's tears can be distinguished from the "snail tracks" (irregular) seen in posterior polymorphous dystrophy93,94 as well as from the posterior corneal vesicles seen in this condition95. Keratoconus Specular microscopy of keratoconic corneas has demonstrated the presence of endothelial abnormalities96. There appears to be an increase in cellular pleomorphism, a finding that is particularly unusual in view of the relative youth of the population studied. Many cells considerably smaller than normal are distributed throughout the endothelial population. Indeed, after clinically scanning the photomicrographs the investigators were left with the distinct impression that there are two populations of cells, one larger and the other considerably smaller than normal. The most striking abnormality in keratoconus is directional enlargement of many endothelial cells96. The long axis of these cells seems orientated toward the apex of the cone, and the cells themselves appear to have been stretched by the ectatic process. This observation is consistent with the current concept of acute corneal hydrops, wherein stretching of the endothelium and Descemet's membrane is presumed to result ultimately in the rupture of both structures, allowing aqueous humor to enter the corneal stroma. Specular photographs also reveal that many endothelial cells contain a dark structure, which in all instances is completely contained within the cell. Invariably there is a normal-appearing area between the dark structure and the cell boundary, and the latter is normal. These intracellular dark structures seem to occur less frequently in larger endothelial cells. They are consistent in appearance with blebs or vacuoles seen with the electron microscope97, but their role in the pathogenesis of keratoconus is not presently understood. In most cases of acute ectasia of the cornea (or corneal hydrops) dehydration of the cornea ultimately occurs. It is presumed that with time the endothelial cells adjacent to the area of rupture enlarge, fill in the defect, and ultimately effect regeneration of Descemet's membrane. Corneas with a history of acute hydrops are reported to contain a localized area of endothelium in which the cells are seven to ten times larger than normal96,98. In other areas of this cornea the endothelial cells were normal both in size and in morphologic appearance. This suggests that the endothelium and Descemet's membrane ruptured in the area of enlarged cells and that the dramatic increase in the size of these cells reflects the changes necessary to repair the affected site, an interpretation that is consistent with the current understanding of acute corneal hydrops and its resolution. Glaucoma Persistently elevated intraocular pressure is believed to result in the gradual loss of endothelial cells and a progressive loss in endothelial function99 This is reflected in the decreasing levels of intraocular pressure at which the cornea becomes edematous in many glaucoma patients as their disease progresses99. For example, at one point in the course of the disease there was no evidence of corneal edema at intraocular pressure levels of 40 to 50 mm Hg. Two years later, however, the cornea was noted to be edematous when the intraocular pressure exceeded 25 mm Hg. In contrast, in In Vitro experiments, as long as normal aqueous flow is maintained, no morphological changes have been seen even when the pressure is elevated above normal100. This seems to indicate that the loss of endothelial is not the direct result of high pressure per se, but is due to some metabolic disturbance, such as prolonged low oxygen concentration in the aqueous humor. Specular microscopic studies in patients with unilateral glaucoma or with a history of unilateral attacks of glaucomatocyclitic crisis often show a lower endothelial cell density in the eye afflicted with glaucoma101-103. If the pressure is medically controlled, cell loss is reduced101. Intraocular inflammation
Experimental studies have demonstrated that during an episode of an acute anterior uveitis mononuclear inflammatory cells penetrate the apical junctional complexes of corneal endothelial cells and infiltrate themselves between endothelial cells as well as between endothelial cells and Descemet's membrane(Fig. H). Endothelial cells appear to suffer little intracellular damage as a result of the inflammatory cell invasion104, although in the most advanced cases the inflammatory cells dislodge individual endothelial cells and cause them to float free in the aqueous humor.105 Cataract extraction Following conventional cataract extraction (not using phacoemulsification) some degree of endothelial cell loss generally occurs. Numerous investigators have reported their findings106-115, and the data show a degree of variability. In uncomplicated cases mean cell loss varies from approximately 6 per cent to 17 per cent, but individual cases range from virtually no cell loss to levels that exceed 40 per cent. Even the latter degree of endothelial cell loss is consistent with corneal transparency during the period of observation, at least in some cases. Intraoperative and postoperative complications are generally associated with a greater mean cell loss than that encountered in uncomplicated cases107,113. It has been reported that post-operative endothelial cell loss is somewhat less in extracapsular than intracapsular procedures116-118. Phacoemulsification and other procedures in which the cataract is fragmented by an ultrasonic probe and in which the lens fragments are then irrigated and aspirated from the eye can damage the endothelium. Here, the endothelial damage has been attributed to mechanical injury caused by anterior chamber instrumentation and/or anterior chamber manipulation of a hard lens nucleus, to the ultrasonic vibration, to heat generated by the ultrasonic tip, and to prolonged intraocular irrigation119-121. This procedure is more likely to injure the endothelium if Fuchs' dystrophy or similar dystrophic changes are present122. In early studies, cataract extraction performed by phacoemulsification or a similar method generally resulted in greater endothelial cell loss (30 to 40%) than more conventional forms of extraction110,111,114,123. Using currently available apparatus and viscoelastic materials, cell loss has been reduced to 15% or less in intracapsular procedures. There is specular microscopic evidence that, following cataract extraction, endothelial damage is greatest in the superior part of the cornea, adjacent to the incision, in the area of maximal manipulation117,124-127. The inferior portion of the cornea is least affected and shows the least endothelial cell loss. Central endothelial cell counts are between the other two but this may be more a mathematical average of endothelial cell density than an indicator of overall uniform density. This vertical disparity in endothelial cell density occurs following cataract extraction by conventional techniques or by phacoemulsification, and it has been observed in cases both with and without implantation of an intraocular lens. No such regional differences in endothelial density have been documented in cataractous eyes prior to lens extraction. Time does not appear to alter the vertical cell disparity caused by surgical trauma. Intraocular lens implantation During intraocular lens implantation, even momentary contact between an acrylic intraocular lens and the corneal endothelium produces significant endothelial damage and cell loss128-131 due to the strong adhesive force between the methacrylate lens and the endothelial cell membrane. Separation of these two surfaces causes the cell membrane to be torn from endothelial cells, irreversibly damaging the cells. Scanning electron microscopy of the surface of an intraocular lens after contact with the endothelium demonstrates that cell membrane material adheres to the lens surface. Other substances such as glass and stainless steel also produce endothelial damage on contact, but the natural crystalline lens of the eye appears to cause little or no damage when it is touched to the endothelium for short periods. Similarly, contact between the corneal endothelium and hydrophilic contact lens material (hydroxymethyl methacrylate) produces minimal endothelial cell damage129. This type of damage to the endothelium can be reduced if the hydrophobic surface of the typical intraocular lens is coated with a hydrophilic material132,132. Some commercial suppliers of intraocular lenses have utilized this approach and coated their lenses directly. However, the use of hyaluronic acid or other viscoelastic material has become a routine part of the cataract extraction procedure and seems to provide a substantial measure of protection for the endothelium. Placement of the viscoelastic material on the surface of the implant prior to its insertion seems to reduce endothelial damage. The introduction of the viscoelastic material into the anterior chamber of the endothelium creates a deep chamber, minimizing the potential for contact during surgery. The introduction of a bubble of air into the anterior chamber is another practical and effective way of attaining this result108,133,134.
Specular microscopic data support the conclusion that the lens implantation procedure is more traumatic to the endothelium than is an uneventful, conventional cataract extraction without lens implantation106-112,114,125,134,135. The implantation of an anterior chamber lens appears to be more traumatic than that of a posterior chamber lens118,136-140. Nonetheless, currently available implants and surgical techniques have reduced this to an acceptable level of surgical risk. Intraocular lens implantation has become a routine part of cataract extraction and is well justified by the visual rehabilitation provided by the device. Penetrating keratoplasty Specular microscopy on successful corneal grafts indicate that substantial endothelial cell loss occurs during or immediately after surgery. In many instances there also may be a progressive and sustained cell loss for a considerable period thereafter. Although there is a critical endothelial cell density below which corneal deturgescence cannot be maintained and irreversible edema occurs, early specular microscopy studies showed that a surprisingly low endothelial cell density can maintain the cornea in a dehydrated, transparent state8. Endothelial changes resulting from or occurring after penetrating keratoplasty also have been studied8,48,114,141-153, although it is apparent that such studies are limited to successful, transparent corneal grafts. Giant endothelial cells, indicating extensive cell loss, have been observed while in other instances little or no endothelial cell loss is seen. The variability in endothelial cell loss is great, ranging from 5 to 80% following penetrating keratoplasty. Because a grafted cornea can remain transparent and support 20/20 vision with less than 20 percent of its normal endothelial cell density8,143, specular microscopy is needed to accurately distinguish between a clear corneal transplant with extensive cell loss and one with virtually no cell loss. Endothelial cell loss occurs faster in a transplanted cornea than in the unoperated cornea after intraocular surgery, suggesting a greater vulnerability in the grafted endothelium. There is also evidence that the endothelium of a corneal graft remains in a state of transition for a considerable length of time post-operatively, seeming to reflect a prolonged healing process. Cell density may decrease, and mean cell area increases with time150,154-156. These changes are progressive and may continue for months and perhaps for years after surgery. Should progressive cell loss continue to occur this would explain the sudden decompensation of some grafted corneas years after successful corneal transplantation surgery. Sato's study confirmed that there is considerable endothelial cell loss following successful keratoplasty48. He found that mean endothelial cell size in a corneal graft was about three times that of endothelial cells of normal individuals in their seventh decade of life and concluded that cell loss was due to surgical trauma and postoperative inflammation and that recovery took place largely by expansion of the surviving cells. Sato also demonstrated in transparent grafts that, although the transplanted cornea recovered excellent deturgescence capabilities, a small but statistically significant increase in corneal thickness (in comparison with normal corneas) persisted. The correlation between graft thickness and endothelial cell size or endothelial cell pleomorphism was not significant. However, the transfer coefficient of fluorescein from the aqueous humor to the cornea was significantly greater in cases of uneventful keratoplasty than in normal corneas, indicating a persistent increase in the endothelial permeability of successful corneal grafts. Thus, endothelial function of the clear graft is not completely normal. The correlation between graft thickness and endothelial permeability (as measured by the transfer coefficient of fluorescein) is statistically significant48,157, suggesting that endothelial permeability, rather than the size or pleomorphism of endothelial cells, is the major factor that determines the thickness of a clear corneal graft. The specular microscopic data on corneal grafts in patients having ketatoconus who showed evidence of a severe allograft rejection episode revealed a significantly decreased endothelial cell density as compared to similar patients that showed no evidence of an allograft rejection (15% vs. 7%, p=.01)158.
Specular microscopy has been proven to be of value in following high risk patients since early evidence of graft rejection can be seen. During rejection episodes one sees intercellular bright bodies and black inflammatory cells and generally recognizable keratic precipitates on the endothelial surface159-161. Although adult human endothelial cells do not normally undergo mitosis, this has been reported in a 35 year old grafted cornea that rejected but that was successfully treated with corticosteroid.30 Many investigators have used specular microscopy to observe and evaluate the endothelium of donor corneas prior to their use for penetrating keratoplasty.62,114,141,162-167 Special chambers that permit evaluation of the endothelium of an excised cornea stored in culture medium and that allow inspection of donor endothelium in the intact globe have been constructed. These techniques provide for more detailed and more accurate evaluation of the suitability of donor material for keratoplasty than does observation with the slit-lamp biomicroscope alone, and have become routinely used in many eye banks. Correlation has been demonstrated between endothelial cell loss (i.e., increased endothelial cell size) and morphology and the time between death and enucleation (within the conventionally accepted limits), or time between enucleation and surgery (again within the conventionally accepted limits).141,150,168,169 Evidence has been presented that fewer endothelial cells are lost when the corneal grafting procedure is performed in an aphakic eye than when the procedure is performed in a phakic eye.145 This finding was attributed to the deeper anterior chamber and the absence of endothelial trauma from the lens-iris diaphragm in the aphakic eye. However, it has not been confirmed by subsequent studies114,146, and needs further research. Intraocular irrigating solutions Closed intraocular surgery (e.g., phacoemulsification, vitrectomy) requires the introduction into the eye of a large volume of an irrigating solution over a relatively prolonged time period. Several corneal perfusion studies have demonstrated that endothelial structure and function is best maintained when solutions that resemble aqueous humor in composition are used.170-172 Irrigating solutions not satisfying the basal metabolic requirements of the corneal endothelium can rapidly produce adverse endothelial changes and corneal edema. In vitro perfusion experiments demonstrate that these endothelial changes and the resultant corneal swelling are caused by many commercially available intraocular irrigating solutions that are deficient in some essential component. Vitreocorneal contact Persistent corneal edema, resulting from contact of formed vitreous humor with the corneal endothelium, can occur months to years after uneventful intracapsular cataract extraction, but the precise mechanism of corneal decompensation is not known.173-176 Since corneal dehydration is controlled primarily by the endothelium, it is assumed that vitreous contact mechanically injures the endothelium and interferes with its physiologic function. Experimental evidence suggests that contact of solid, collagenous elements of the vitreous humor with the endothelium interferes with transport of fluid out of the cornea.177 However, contact between formed vitreous humor and the corneal endothelium is not invariably followed by corneal edema, and in those cases in which the phenomenon is encountered the cornea may tolerate vitreous contact and remain clear and dehydrated for extended periods before edema is observed. Specular microscopic studies tend to support these concepts.178,179 Several types of morphologic abnormalities are observed in the endothelium of corneas in the early stages of decompensation as a result of vitreous contact. Some endothelial cells are markedly enlarged and grossly abnormal in shape. Others contain abnormal bright or dark structures within their cell boundaries. Abnormal cell intersections and side length distribution are encountered, and the central guttate excrescences of Fuchs' dystrophy are often seen. Removal of vitreous humor from the anterior chamber by closed vitrectomy, with the elimination of vitreous contact, may result in substantial improvement in the state of corneal hydration and in some cases in the elimination of clinically significant corneal edema.178-181 Surprisingly, those endothelial changes seen in edematous corneas prior to vitrectomy appear to persist following vitrectomy and corneal deturgescence. Despite the seeming irreversibility of the endothelial changes, clinical reversal of corneal edema may occur on occassion in cases of moderately prolonged vitreous contact. Cases in which closed vitrectomy does not produce complete reversal of corneal edema are those with Fuchs' dystrophy and those with the most bizarre endothelium. Apparently the progressive endothelial changes wrought by vitreous contact can reach a stage of functional irreversibility. If specular photomicroscopy shows that endothelial cell abnormalities are not pronounced, the data available indicate that closed vitrectomy can be a useful procedure for the treatment of corneal decompensation secondary to vitreous contact. Epithelialization of the anterior chamber The endothelial surface of the cornea has been photographed in vivo with the specular microscope during varying stages of epithelization of the anterior chamber in an effort to define clinical signs that would permit a definite diagnosis to be made in the absence of histopathologic verification.182-184 The findings vary somewhat, which is not surprising since evaluation of the corneal endothelium in this entity is laborious and demanding. Even in the most cooperative of patients, cellular structures may be difficult to detect and, when seen, they often cannot be distinctly focused. Smith and Parrett reported a sharply defined border between normal corneal endothelial cells and the area of epithelial downgrowth.182 In contrast, in the region occupied by the clinically observed endothelial demarcation line, Laing and coworkers observed enlarged, abnormally shaped endothelial cells inferiorly blending into an acellular, structureless area superiorly.183 By focusing more deeply in the seemingly structureless area superiorly, these investigators were able to visualize poorly defined structures that suggested multilayered epithelial cells. However, neither epithelial nor endothelial cells could be identified with certainty in the region above the demarcation line seen with the slit-lamp biomicroscope. A more recent study has provided improved resolution of the epithelial cells at the junction between epithelial downgrowth and the endothelial cells.185 In the patients examined by Laing and coworkers,183 the diagnosis was later verified histopathologically. When the endothelium was successfully visualized with the specular microscope, it was usually abnormal. Considerable cell loss seemed to have occurred, as evidenced by the large size of the remaining cells. Whether this cell loss results from a traumatic insult prior to surgery and contributes to the subsequent epithelial invasion of the anterior chamber or, alternatively, whether it is produced by the advancing layer of epithelium, is not clear. The specular photomicrographs show only that endothelial cells are present but are large and abnormal-appearing when the clinically visible demarcation line is well above the photographed region. When epithelialization was moderately advanced, cellular structures were seen that did not have the morphologic appearance of endothelial cells. Presumably these were epithelial cells, but this is not certain. In the most advanced cases, no distinct cell boundaries could be seen. Only a disorganized, amorphous, membranous layer containing some formed structures was visualized. Again, the presumption is that this is a thickened, multilayered epithelial membrane whose structure does not permit satisfactory resolution by the specular microscope. The problem of endothelial resolution was encountered in clear corneas that were free of significant edema as measured with the corneal pachymeter. Thus, the inability to see endothelial structures distinctly with the specular microscope suggests either that the endothelium is disorganized or that more than a single layer of cells is present. The invading epithelium also produces an irregular layer of fibrillar material along the epithelial-Descemet's membrane interface186 that may contribute to the gray appearance of the involved cornea and to the difficulty encountered in obtaining a clear image of the structures in the zone of specular reflection. Blunt trauma Blunt trauma to the cornea can damage the endothelium. Bourne and coworkers59 have reported their findings on a 16-year-old boy who had suffered a BB injury of the right eye 2 years previously. Clinically, both corneas were clear and free of edema; evidence of prior endothelial damage was revealed only by clinical specular microscopy. The endothelial cells on the right were enlarged and the central endothelial cell density was only 47 per cent of that of the opposite, normal left eye. Although it is suspected that in such instances the residual endothelial cells might be more susceptible to subsequent trauma than normal cells, no additional cell loss was documented following cataract extraction by phacoemulsification in this particular case. The impact of small, nonpenetrating foreign bodies on the cornea may give rise to clinically apparent gray rings on the corneal endothelium.187,188 Reproduction of these rings in experimental animals reveals that they consist of swollen or disrupted endothelial cells. The center of each ring corresponds to the epithelial impact site of the foreign body, with the least disruption of the endothelium occurring here. Specular microscopic studies confirm that posterior annular keratopathy, occurring after blunt corneal trauma in humans, represents a contusion injury and consists of disrupted and swollen endothelial cells.127 The damaged cells may still be evident many days after the clinically visible endothelial rings disappear and, indeed, permanent cell loss may occur. As might be expected, the degree of endothelial cell loss appears to be related to the severity of the injury; a measurable decrease in cell density occurs only in the more severely injured corneas. Contact lens wear Both acute and chronic endothelial changes are seen with the specular microscope following contact lens wear. Within minutes of application of a contact lens, small dark endothelial blebs occur that disappear quickly if the lens is removed.189,190 These endothelial blebs reach a maximum size in 20-30 minutes from the time the contact lens is placed on the cornea and then gradually decrease in size. Similar blebs occur during prolonged lid closure, such as during sleep,191 and possibly represent the effects of hypoxia or lactate accumulation. Long term wear of either hard or soft contact lenses results in an increased polymegathism192-203 that is not reversed upon cessation of lens wear202,203 although some recovery towards normal might exist.204 The degree of polymegathism increases as the period of time the lenses are worn increases.194,196-199,203 The degree of increase in polymegathism depends upon the type of lenses worn. An interesting finding has been the observation of small clusters of small cells possibly due to mitosis occurring as a result of contact lens wear.196,205 Diabetes Early studies using fixed-frame analysis showed no differences in endothelial cell density between normal and diabetic patients.28,206 More recent studies using the more accurate computer assisted variable-frame analysis has revealed increased polymegathism and pleomorphism and decreased percent hexagonality in diabetic corneas.35,207-210 In Type I diabetes the cell density significantly decreased with age.208 However, there was no difference in corneal thickness nor endothelial permeability to fluorescein.209,211 |
References: 30. Laing R, Neubauer L, Oak S, Kayne H, Leibowitz H. Evidence for mitosis in the adult corneal endothelium. Ophthalmol. 1984;10:1129. 44. Neubauer L, Laing R, Leibowitz H, Oak S. Coalescense of endothelial cells in the traumatized cornea. I: Experimental observation in cryopreserved tissue. Arch Ophthalmol. 1983;101:1787. 45. Laing R, Neubauer L, Leibowitz H, Oak S. Coalescence of endothelial cells in the traumatized cornea II. Clinical observations. Arch of Ophthalmol. 1983;101:1712. 46. Bourne W, Kaufman H. Specular microscopy of the human corneal endothelium in vivo. Amer J Ophthalmol. 1976;81:319. 47. McCarey B. Noncontact specular microscopy: A macrophotography technique and some endothelial cell findings. Ophthalmology. 1979;86:1848. 48. Sato T. Studies on the endothelium of the corneal graft. Jpn J Ophthalmol. 1978;22:114. 49. Blatt H, Rao G, Aquavella J. Endothelial cell density in relation to morphology. Invest Ophthalmol. 1979;18:856. 50. Laule A, Cable M, Hoffman C, Hanna C. Endothelial cell population changes of human cornea during life. Arch Ophthalmol. 1978;96:2031. 51. Sturrock G, Sherrard E, Rice N. Specular microscopy of the corneal endothelium. Br J Ophthalmol. 1978;62:809. 52. Majima Y, Nogawa HY E 53. Olsen T. Non-contact specular microscopy of human corneal endothelium. Acta Ophthalmol. 1979;57:986. 54. Hoffer K, Kraft M. Normal endothelial cell count range. Ophthalmology. 1980;87:861. 55. Stefansson A, Muller O, Sundmacher R. Non-contact specular microscopy of the normal corneal endothelium. A statistical evaluation of morphometric parameters. Graefe's Arch Clin Exp Ophthalmol. 1982;218:200. 56. Sherrard E, Novakovic P, Speedwell L. Age-related changes of the corneal endothelium and stroma as seen in vivo by specular microscop y. Eye. 1987;1:197. 57. Murphy C, Alvarado J, Juster R, and Maglio M. Prenatal and postnatal cellularity of the human corneal endothelium. A quantitative histological st udy. Invest Ophthalmol Vis Sci. 1984;25:312. 58. Matsuda M, Yee R, and Edelhauser H. Comparison of the corneal endothelium in an American and a Japanese population. Arch Ophthalmol. 1985;103:68. 59. Bourne W, McCarey B, Kaufman H. Clinical specular microscopy. Trans Amer Acad Ophthalmol and Otolary. 1976;81:743. 60. Hiles D, Biglan A, and Fetherolf E. Central endothelial cell counts in children. Amer Intraocular Implant Society J of Ophthalmol. 1979;5:292. 61. Mishima S. Clinical investigations on the corneal endothelium. Am J Ophthalmol. 1982;93:1. 62. Stocker F. The Endothelium of the Cornea and Its Clinical Implications. Springfield, MA: Charles C. Thomas; 1971. 63. OHara K, Tsuru T, and Inoda S. Morphometric parameters of the corneal endothelial cells. Acta Ophthalmol Japan. 1987;91:1073. 64. Laing R, Leibowitz H, Chang R, Theodore J, Oak S. The endothelial mosaic in Fuchs dystrophy. A qualitative evaluation with specular microscope. Arch Ophthalmol. 1981;99:80. 65. Goar E. Dystrophy of the corneal endothelium (cornea guttata) with a report of a histological examination. Amer J Ophthalmol. 1934;17:215. 66. Lorenzetti D, Uotila M, Parikh N, Kaufman H. Central cornea guttata. Incidence in the general population. Amer J Ophthalmol. 1967;64:115. 67. Waring G, Font R, Rodrigues M, Mulberger R. Alterations of Descemet's membrane in intersitial keratitis. Amer J Ophthalmol. 1976;81:773. 68. Polack F. The posterior corneal surface in Fuchs' dystrophy. Scanning electron microscopic study. Invest Ophthalmol. 1974;13:913. 69. Waring G, Rodrigues M, Laibson P. Corneal dystrophies II. Endothelial dystrophies. Surv Ophthalmol. 1978;23:147. 70. Takahashi N, Sasaki K, Nakaizumi H, and Koniski F. Specular microscopic findings of lattice corneal dystrophy. Int Ophthalmol. 1987;10:47. 71. Mayer D. Lattice Dystrophy in Clinical Wide-field Specular Microscopy. London: Bailliere Tindall; 1984:68-69. 72. Sugai M, Kobayaski H, Tochikubo T, Komoto. Specular microscopic features of lattice dystrophy of the cornea. Jpn J Ophthalmol. 1985;39:186. 73. Smith M, Zimmerman L. Amyloid in corneal dystrophies. Arch Ophthalmol. 1968;79:407. 74. Campbell D, Shields M, Smith T. The corneal endothelium in the spectrum of essential iris atrophy. Amer J Ophthalmol. 1978;86:317. 75. Hirst L, Green W, Luckenback M, Cruz Z, Stark W. Epithelial characteristics of the endothelium in Chandler's syndrome. Inv Ophthalmol Vis Sci. 1983;24:603. 76. Yanoff M. Iridocorneal endothelial syndrome; Unification of a disease spectrum. Surv Ophthalmol. 1979;24:1-2. 77. Shields M. Progressive essential iris atrophy, Chandler's syndrome and the iris nevus (Cogan-Reese) syndrome. A spectrum of diseases. Surv Ophthalmol. 1979;24:3. 78. Quigley H, Forster R. Histopathology of cornea and iris in Chandler's syndrome. Arch Ophthalmol. 1978;96:1878. 79. Shields M, McCracken J, Klintworth G, Campbell D. Corneal edema in essential iris atrophy. Ophthalmology. 1979; 86:1533. 80. Hetherington J, Jr. The spectrum of Chandler's syndrome. Ophthalmology. 1978;85:240. 81. Hirst L, Quigley H, Stark W, Shields M. Specular microscopy of iridocorneal endothelial syndrome. Amer J Ophthalmol. 1980;89:11. 82. Setala K, Vannas A. Corneal endothelial cells in essential iris atrophy. Acta Ophthalmol. 1979;57:1020. 83. Bourne W. Partial corneal involvement in the iridocorneal endothelial syndrome. Am J Ophthalmol. 1982;94:774. 84. Bourne W, and Brubaker R. Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome . Amer J Ophthalmol. 1992;114:171. 85. Cibis G, Krachmer J, Phelphs C, and Weingeist T. The clinical spectrum of posterior polymorphous dystrophy. Arch Ophthalmol. 1977;95:1529. 86. Waring G, Bourne W, Edelhauser H, Kenyon K. The corneal endothelium. Normal and pathologic structure and function. Ophthalmology. 1982;89:531. 87. Boruchoff S, Kuwabara T. Electron microscopy of posterior polymorphous degeneration. Am J Ophthalmol. 1971;72:879. 88. Cibis G, Krachmer J, Phelps C, Weingeist T. Iridocorneal adhesions in posterior polymorphous dystrophy. Ophthalmology. 1976;81:770. 89. Rodrigues M, Phelps C, Krachmer J, Cibis G, Weingeist T. Glaucoma due to endothelialization of the anterior chamber angle. A comparison of posterior polymorphous dystrophy of the cornea and Chandler's syndrome. Arch Ophthalmol. 1980;98:688. 90. Presberg S, Quigley H, Foster R, Green W. Posterior polymorphous corneal dystrophy. Cornea. 1986;4:239. 91. Laganowski H, Sherrard E, Kerr Muir M, and Buckley R. Distinguishing features of the iridocorneal endothelial syndrome and posterior polymorphous dystrophy. The value of endothelial specular microscopy. Br J Ophthalmol. 1991;75:212. 92. Laganowski H, Sherrard E, and Kerr Muir M. The posterior corneal surface in posterior polymorphous dystrophy. A specular microscopical study. Cornea. 1991;10(3):224. 93. Brooks A, Grant G, and Gillies W. Differentiation of posterior polymorphous dystrophy from other posterior corneal opacities by specular microscopy. Ophthalomology. 1989;96:1639. 94. Cibis G, Tripathi R. The differential diagnosis of Descemet's tears (Haab's striae) and posterior polymorphous dystrophy bauds. A clinico-pathologic study. Ophthalmology. 1982;89:614. 95. Hirst L, Waring G. Clinical specular microscopy of posterior polymorphous endothelial dystrophy. Am J Ophthalmol. 1983;95:143. 96. Laing R, Sandstrom M, Berrospi A, and Leibowitz H. The human corneal endothelium in keratoconus. A specular microscopic study. Arch Ophthalmol. 1979;97:1867. 97. Jakus M. Further observations on the fine structure of the cornea. Invest Ophthalmol. 1962;1:202. 98. Skuta G, Sugar J, and Erickson E. Corneal endothelial cell measurements in megalcornea. Am J Ophthalmol. 1983;101:51. 99. Irvine A. The role of the endothelium in bullous keratopathy. Arch Ophthalmol. 1956;56:338. 100. Mortensen A, Sperling S. Human corneal endothelial cell density after an in vitro immitation of elevated intraocular pressure . Acta Ophthalmol. 1982;60:475. 101. Vannas A, Setala K, Ruusuvaara P. Endothelial cells in capsular glaucoma. Acta Ophthalmol. 1977;55:951. 102. Setala K, Vannas A. Endothelial cells in glaucomato-cyclitic crisis. Adv Ophthalmol. 1978;36:218. 103. Bigar F, Witmer R. Corneal endothelial changes in primary acute angle-closure glaucoma. Ophthalmology. 1982;89:596. 104. Olsen T. Changes in the corneal endothelium after acute anterior uveitis as seen with the specular microsco pe. Acta Ophthalmol. 1980;58:250. 105. Inomata H, Smelser G. Fine structural alterations of corneal endothelium during experimental uveitis. Invest Ophthalmol. 1970;9:272. 106. Bourne W, Kaufman H. Endothelial damage associated with intraocular lenses. Amer J Ophthalmol. 1976;81:482. 107. Forstot S, Blackwell W, Jaffe N, Kaufman H. The effect of intraocular lens implantation on the corneal endothelium. Trans Amer Acad Ophthalmol and Otolaryngol. 1977;83:195. 108. Hirst L, Snip R, Stark W, Maumanee A. Quantitative corneal endothelial evaluation in intraocular lens implantation and cataract surgery. Am J Ophthalmol. 1977;84:775. 109. Cheng H, Sturrock G, Rubinstein B, Bulpitt C. Endothelial cell loss and corneal thickness after intracapsular extraction and iris clip lens implantation. A randomized controlled trial (interim report). Br J Ophthalmol. 1977;61:785. 110. Sugar A, Fetherolf E, Lin L, Ostbaum S, and Galin M. Endothelial cell loss from intraocular lens insertion. Ophthalmol. 1978;85:394. 111. Sugar J, Mitchelson J, and Kraff M. Endothelial trauma and cell loss from intraocular lens insertion. Arch Ophthalmol. 1978; 96:449. 112. Drews R, Waltman S. Endothelial cell loss in intraocular lens placement. Amer Introc Implant Soc J. 1978;4:14. 113. Bourne W, Kaufman H. Cataract extraction and the corneal endothelium. Amer J Ophthalmol. 1976;82:44. 114. Abbott R, Forster R. Clinical specular microscopy and intraocular surgery. Arch Ophthalmol. 1979;97:1476. 115. Kraff M, Sanders D, Lieberman H. Specular microscopy in cataract and intraocular lens patients. A report of 564 cases. Arch Ophthalmol. 1980;98:1782. 116. Liesegang T, Bourne W, Ilstrup D. Short and long-term endothelial cell loss associated with cataract extraction and intraocular lens implantation. Am J Ophthalmol. 1984;97:32. 117. Schultz R, Glasser D, Matsuda M, Yee R, and Edelhauser H. Response of the corneal endothelium to cataract surgery. Arch Ophthalmol. 1986;104:1164. 118. Martin N, Stark W, Maumenee A. Continuing corneal endothelial loss in intracapsular surgery with and without Binkhorst four-loop lenses. A long-term specular microscopy study. Ophthalmic Surg. 1987;18:867. 119. Binder P, Sternberg H, Wickman M, Worthen D. Corneal endothelial damage associated with phacoemulsification. Amer J Ophthalmol. 1976;82:48. 120. Polack F, Sugar A. The phacoemulsification procedure. II. Corneal endothelial changes. Invest Ophthalmol. 1976;15:458. 121. McCarey B, Polack F, and Marshall E. The phacoemulsification procedure. I. The effect of intraocular irrigating solutions on the corneal endothelium. Invest Ophthalmol. 1976;15:449. 122. Polack F, Sugar A. The phacoemulsification procedure. III. Corneal complications. Invest Ophthalmol vis Sci. 1977;16:39. 123. Irvine A, Kratz R, O'Donnell J. Endothelial damage with phacoemulsification and intraocular lens implantation. Arch Ophthalmol. 1978;96:1023. 124. Hoffer K. Vertical endothelial cell disparity. Amer J Ophthalmol. 1979;87:344. 125. Galin M, Lin L, Fetherolf E, Ostbaum S, Sugar A. Time analysis of corneal endothelial cell density after cataract extraction. Amer J Ophthalmol. 1979;88:93. 126. Inaba M, Matsuda M, Shiozaki Y, and Kosai H. Regional specular microscopy of endothelial cell loss after intracapsular cataract extraction. A preliminary report. Acta Ophthalmologica. 1985;63:232. 127. Azen S, Hurt A, Steel D, et al. Effects of the shearing posterior chamber intraocular lens on the corneal endothelium. Am J Ophthalmol. 1983;95:798. 128. Kaufman H, Katz J, Valenti J, Sheets J, Goldberg E. Corneal endothelial damage with intraocular lenses. Contact adhesion between surgical materials and tissue. Science. 1977;198:525. 129. Kaufman H, Katz J. Endothelial damage from intraocular lens insertion. Invest Ophthalmol. 1976;15:996. 130. Kirk S, Burde R, and Waltman S. Minimizing corneal endothelial damage due to intraocular lens contact. Invest Ophthalmol Vis Sci. 1977;16:1053. 131. Tsubota KM et al. ask Dr. Tsubota for this reference; 1995. 132. Katz J, Kaufman H, Goldberg E, Sheets J. Prevention of endothelial damage from intraocular lens insertion. Trans Amer Acad Ophthalmol Otolaryngol. 1977;83:204. 133. Bourne W, Brubaker R, O'Fallon W. Use of air to decrease endothelial cell loss during intraocular lens implantation. Arch Ophthalmol. 1979;97:1473. 134. Binkhorst C, Nygaard P, Loones L. Specular microscopy of the corneal endothelium and lens implant surgery. Amer J Ophthalmol. 1978;85:597. 135. Rao G, Stevens R, Harris J, Aquavella J. Long term changes in corneal endothelium following intraocular lens implantation. Ophthalmology. 1981;88:386. 136. Kraff M, Sanders D, Lieberman H. Monitoring for continuing endothelial cell loss with cataract extraction and intraocular lens implantation. Ophthalmology. 1982;89:30. 137. Team OC. Long-term corneal endothelial cell loss after cataract surgery. Results of a randomized control tria l. Arch Ophthalmol. 1986;104:1170. 138. Apple D, Mamalis N, Loftfield Ke. Complications of intraocular lenses. A histological and histopathological review. Surv Ophthalmol. 1984;29:1. 139. Glasser D, Matsuda M, Gager We. Corneal endothelial morphology after anterior chamber lens implantation. Arch Ophtalmol. 1985;103:1347. 140. Numa A, Nakamura J, Takashima M, and Kani K. Long-term corneal endothelial changes after intraocular lens implantation. Anterior vs. posterior chamber lenses. Jpn J Ophthalmol. 1993;37:78. 141. Bron A, Brown N. Endothelium of the corneal graft. Trans Ophthalmol Soc UK. 1974;94:863. 142. Ruben M, Colebrook E, Guillon M. Keratoconus, keratoplasty thickness and endothelial morphology. Brit J Ophthalmol. 1979;63:790. 143. Bourne W, Kaufman H. The endothelium of clear corneal transplants. Arch Ophthalmol. 1976;94:1730. 144. Rao G, Shaw E, Arthur E, Aquavella J. Morphological appearance of the healing corneal endothelium. Arch Ophthalmol. 1978;96:2027. 145. Bourne W, O'Fallon W. Endothelial cell loss during penetrating keratoplasty. Amer J Ophthalmol. 1978;85:760. 146. Rao G, Stevens R, Mandelberg A, Aquavella J. Morphological variations in graft endothelium. Arch Ophthalmol. 1980;98:1403. 147. Berg C, Binder P, Kahn M. Distribution of cell areas in normal and transplanted corneas. Exp Eye Res. 1980;31:623. 148. Olsen T. Post-operative changes in the endothelial cell density of corneal grafts. Acta Ophthalmologica. 1981;59:863. 149. Olson R, Levensen J. Migration of donor endothelium in keratoplasty. Amer J Ophthalmol. 1977;84:711. 150. Culbertson W, Abbott R, Foster R. Endothelial cell loss in penetrating keratoplasty. Ophthalmol. 1982;89:600. 151. Ruusuvaara P. Endothelial cell densities in donor and recipient tissue after keratoplasty. Acta Ophthalmologica. 1980;58:267. 152. Bourne W. Chronic endothelial cell loss in transplanted corneas. Cornea. 1983;2:289. 153. Matsuda M, Bourne W. Long-term morphologic changes in the endothelium of transplanted corneas. Arch Ophthalmol. 1985;103:1343. 154. Bourne W. One year observation of transplanted human corneal endothelium. Ophthalmology. 1980;87:673. 155. Bourne W. Morphologic and functional evaluation of the endothelium of transplanted human corneas. Trans Am Ophthalmol Soc. 1983;81:403. 156. Matsuda M, Suda T, Manabe R. Long-term observations of the graft endothelium with different postoperative courses. Jpn J Ophthalmol. 1983;27:556. 157. Ota Y. Endothelial permeability of fluorescein in corneal grafts and bullous keratopathy. Jpn J Ophthalmol. 1975;19:286. 158. Musch D, Schwartz A, Fitzgerald-Shelton K, Sugar A, and Meyer R. The effect of allograft rejection after penetrating keratoplasty on central endothelial cell density. Am J Ophthalmol. 1991;111:739. 159. Khodadoust A. The allograft rejection reaction. The leading cause of late failure of clinical corneal grafts in corneal graft failure.Jones B, ed. . Amsterdam: Associated Scientific Publishers; 1973. Ciba Foundation Symposium No. 15. 160. Polack F. Clinical and pathological aspects of the corneal graft reation. Trans of the American Academy of Ophthalmology and Otolaryngology. 1973;77:486. 161. Hirst L. Specular microscopy of endothelial graft rejection. Las Vegas; 1982. Symposium on Endothelium. International Cornea Society. 162. Bigar F, Schimmelpfenning B, Giesler R. Routine evaluation of endothelium in human donor corneas. Albrecht von Graefes Arch Klin Exp Ophthalmol. 1976;200:195. 163. Schimmelpfenning B, Bigar F, Witmer R, Hurzeler R. Endothelial changes in human donor corneas. Albrecht von Graefes Arch Klin Exp Ophthalmol. 1976;200:201. 164. Bigar F, Schimmelpfennig B, and Hurzeler R. Cornea guttata in donor material. Arch Ophthalmol. 1978;96:653. 165. Bourne W. Examination and photography of donor corneal endothelium. Arch Ophthalmol. 1976;94:1799. 166. McCarey B, McNeil J. Specular microscopic evaluation of donor corneal endothelium. Ann Ophthalmol. 1977;l 9:1279. 167. Matsuda M, Yee R, Glasser D, Geroski D, Edelhauser H. Specular microscopic evaluation of donor corneal endothelium. Arch Ophthalmol. 1986;104:259. 168. Ruusuvaara P. The fate of preserved and transplanted human corneal endothelium. Acta Ophthalmol. 1980;58:440. 169. Binder P. Eye banking and corneal preservation. In: Transactions of the New Orleans Academy of Ophthalmology. St. Louis: C.V. Mosby; 1980. Symposium on Medical and Surgical Diseases of the Cornea. 170. Edelhauser H, Van Horn D, Hyndiuk R, Schultz R. Intraocular irrigating solutions. Their effect on the corneal endothelium. Arch Ophthalmol. 1975;93:648. 171. Edelhauser H, Van Horn D, Schultz R, and Hyndiuk R. Comparative toxicity of intraocular irrigating solutions on the corneal endothelium. Amer J Ophthalmol. 1976;81:473. 172. Edelhauser H, Gonnering R, Van Horn D. Intraocular irrigating solutions. A comparative study of BSS Plus and lactated Ringer's solution. Arch Ophthalmol. 1978;96:516. 173. Leahy B. Bullous keratitis from vitreous contact. Arch Ophthalmol. 1951;46:22. 174. Chandler P. Complications after cataract extraction. Clinical aspects. Trans Amer Acad Ophthalmol Otolaryngol. 1954;58:382. 175. Goar E. Postoperative hyaloid adhesions to the cornea. Amer J Ophthalmol. 1958;45:99. 176. Jaffe N. Cataract Surgery and Its Complications, 2Nd Ed. St. Louis: C.V. Mosby Co.; 1976:256. 177. Fischbarg J, Stuart J. The effect of vitreous humor on fluid transport by rabbit corneal endothelium. Invest Ophthalmol. 1975;14:497. 178. Leibowitz H, Laing R, Chang R, Theodore J, Oak S. Corneal edema secondary to vitreocorneal touch. Arch Ophthalmol. 1981; 99:417. 179. Homer P, Peyman G, Sugar J. Automated vitrectomy in eyes with vitreocorneal touch associated with corneal dysfunction. Amer J Ophthalmol. 1980;89:500. 180. Snip R, Kenyon K, Green W. Retrocorneal fibrous membrane in the vitreous touch syndrome. Amer J Ophthalmol. 1975;79:233. 181. Wilkinson C, Rowsey J. Closed vitrectomy for the vitreous touch syndrome. Amer J Ophthalmol. 1980;90:304. 182. Smith R, Parrett C. Specular microscopy of epithelial downgrowth. Arch Ophthalmol. 1978;96:1222. 183. Laing R, Sandstrom M, Leibowitz H, Berrospi A. Epithelialization of the anterior chamber. Clinical investigation with the specular microscope. Arch Ophthalmol. 1979;97:1870. 184. Zavala E, Binder P. The pathologic findings of epithelial ingrowth. Arch Ophthalmol. 1980; 98:2007. 185. Holliday J, Buller C, and Bourne W. Specular microscopy and fluorophotometry in the diagnosis of epithelial downgrowth after a sutureless cataract operation. Amer J Ophthalmol. 1993;116:238. 186. Jensen P, Minckler D, Chandler J. Epithelial ingrowth. Arch Ophthalmol. 1977;95:837. 187. Cibis G, Weingeist T, Krachmer J. Traumatic corneal endothelial rings. Arch Ophthalmol. 1978;96:485. 188. Forstot S, Gasset A. Transient traumatic posterior annular keratopathy of Payrau. Arch Ophthalmol. 1974;92:527. 189. Zantos S, Holden B. Transient endothelial changes soon after wearing soft contact lenses. Am J Optom Physiol Optics. 1977;54:865. 190. Barr J, Schoessler J. Corneal endothelial response to rigid contact lenses. Amer J Optom Physiol Opt. 1980;57:267. 191. Khodadoust A, and Hirst L. Diurnal variation in corneal endothelial morphology. Ophthalmology. 1984;91:1125. 192. Holden B, Sweeney D, Vannas Ae. Effects of long-term extended contact lens wear on the human cornea. Invest Ophthalmol Vis Sci. 1985;26:1489. 193. Holden B, Sweeney D, Vannus A, et al. Contact lens-induced endothelial polymegathism. Invest Ophthalmol Vis Sci (suppl). 1985;26:275. 194. Schoessler J, Woloschak M. Corneal endothelium in veteran PMMA contact lens wearers. Int Contact Lens Clinics. 1981;8:19. 195. Schoessler J. Corneal endothelial polymegathism associated with extended wear. Int Contact Lens Clinics. 1982;10:148. 196. Hirst L, Auer C, Cohn J, Tseng S, Khodadoust A. Specular microscopy of hard contact lens wearers. Ophthalmology. 1984; 91:1147. 197. Stocker E, Schoessler J. Corneal endothelial polymegathism induced by PMMA contact lens wear. Invest Ophthalmol Vis Sci. 1985;26:857. 198. MacRae S, Matsuda M, Yee R. The effect of long-term hard contact lens wear on the corneal endothelium. CLAO J. 1985;11:322. 199. MacRae S, Matsuda M, Shellans S, Rich L. The effects of hard and soft contact lenses on the corneal endothelium. Am J Ophthalmol. 1986;102:50. 200. Lass J, Dutt R, Spurney R, Stocker E, Wolff C, Glavan I. Morphologic and fluorophotometric analysis of the corneal endothelium in hard and soft contact lens wearers. CLAO J. 1988;14:105. 201. Carlson K, Bourne W, Brubaker R. Effect of long term contact lens wear on corneal endothelial cell morphology and function. Invest Ophthalmol Vis Sci. 1988;29:185. 202. MacRae S, Matsuda M, and Shellans S. Corneal endothelial changes associated with contact lens wear. CLAO J. 1989;15:82. 203. MacRae S, Matsuda M, and Phillips D. The long-term effects of polymethylmethacrylate contact lens wear on the corneal endothelium. Ophthalmology. 1994;101:365. 204. Yamaguchi K, Hirst L, Enger C, Rosenfeld J, Vogelpohl W. Specular microscopy of hard contact lens wearers. II. Ophthalmology. 1989;96:1176. 205. Tsubota K, Yamada Me. Extended wear soft contact lenses induce corneal epithelial changes. Ophthalmology (suppl). 1992;99:128 (abstract). 206. Busted N, Olsen T, Schmitz O. Clinical observations on the corneal thickness and the corneal endothelium in diabetes mellitus. Br J Ophthalmol. 1981;65:687. 207. Aaberg T. Correlation between corneal endothelial morphology and function. Amer J Ophthalmol. 1984;98:510. 208. Schultz R, Matsuda M, Yee R, Edelhauser H, Schultz K. Corneal endothelial changes in type I and type II diabetes mellitus. Am J Ophthalmol. 1984;98:401. 209. Keoleian G, Pack J, Hodge D, Trocme S, Bourne W. Structural and functional studies of the corneal endothelium in diabetes mellitus. Amer J of Ophthalmol. 1992;113:64. 210. Lass J, Spurney R, Dutt R, et al. A morphologic and fluorophotometric analysis of the corneal endothelium in type I diabetes mellitus and cystic fibrosis. Amer J Ophthal. 1985;100:783. 211. Watsky M, McDermott M, Edelhauser H. In vitro corneal endothelial permeability in rabbit and human. The effects of age, cataract surgery and diabetes. Exp Eye Res. 1989;49:751. |
