Ординатура / Офтальмология / Английские материалы / Corneal Endothelial Transplant (DSAEK, DMEK & DLEK)_John_2010

Figure 3-2: Slit-lamp photograph displaying post-traumatic arcuate Descemet’s breaks (arrows).

is better in younger donor grafts. Injuries that accumulate with time, such as UV exposure23 and the effects of oxidative species, may play a role in the aging process. Animal studies suggest that intrinsic protective mechanisms, such as catalase, superoxide dismutase, and glutathione peroxidase, lose their activity in older corneas, while generation of reactive oxygen species remain unchecked.24-26 In previous studies, it has also been demonstrated that vitamin E, an antioxidant, is able to significantly increase the survival of treated endothelial cells.27

In humans, the corneal endothelium has a very limited capacity to mitose either in vivo or in vitro. Damage to this monolayer either by aging or disease heals by enlargement and sliding of remaining cells. Even when injured, HCECs appear to be “locked” in G-1 and cannot enter the S phase of mitosis. It is therefore critical to avoid damage to the endothelium during any intraoperative procedure.

Figure 3-3: Photomicrograph of post-traumatic loss of corneal endothelium and iris pigment deposition (arrow).

Ultrastructural Characteristics

Normal HCECs contain large numbers of mitochondria and a large nucleus, indicating their active metabolism. Further, they contain rough and smooth endoplasmic reticula, as well as a well-developed Golgi apparatus, reflecting their high level of protein synthesis. Pinocytotic vesicles and a terminal web of fine fibrils can be seen on cross-sections toward the apical surface of the cells. A circumferential band of actin-containing microfilaments, present at the cell periphery and beneath the plasma membrane, is probably involved in maintaining the endothelial cell shape.28 These filaments may also facilitate cell migration in response to injury. Apical F-actin, for example, dramatically reorganizes in response to transforming growth factor (TGF)-β1, which is known to

enhance endothelial wound healing through migration and cell spreading.5

Endothelial cells interdigitate and contain several junctional complexes at the overlapping apicolateral boundaries that include zonula occludens, macula occludens, macula adherens, but no desmosomes, providing a leaky barrier to the aqueous humor.5,29 Further, gap junctions allow the transport of electrolytes and small molecules between these cells at all levels of the lateral plasma membrane, facilitating cell-to-cell communication.30 The anterior aspect of the endothelium is adjacent to Descemet’s membrane and has no known anchoring microstructures. The posterior aspect (apical) of the endothelium is covered by microvilli and free marginal folds. This creates a high surface area in contact with the aqueous humor, presumably in order to carry out the many metabolic functions of the HCECs, as discussed below.

Pump and Barrier Function

The amount of corneal stromal hydration plays a role in maintaining corneal transparency, as described below.31-33 The mechanism of permitting the passage of nutrients into the cornea, while maintaining a barrier to the free flow of water into the stroma, is described by the pump-leak hypothesis of the endothelium32 (See also Chapter 2, Corneal Physiology). The leak rate of water and nutrients into the cornea is balanced by the pumping rate of endothelial cells. An imbalance would result in corneal swelling, clouding of the cornea and decreased vision.

Normal HCECs maintain corneal transparency by regulating stromal water content. The precise arrangement of stromal collagen bundles, and therefore corneal transparency, is disrupted above or below 78% stromal hydration.31-33 Hydration homeostasis is, in part, achieved by HCEC ionic pumps that counteract the osmosis of water into the stroma. At least two active transport systems seem to contribute to the pumping mechanism of the endothelial cells: Na+/K+-dependent ATPase pumps,34 and functional Na+-HCO3– dependent cotransport.35,36 The Na+/K+- dependent ATPase pumps are present in the basolateral membrane of HCECs. These pumps actively transport Na+ ions from the stroma into the aqueous. Additionally, carbon dioxide that diffuses into the endothelial cytoplasm is converted to HCO3– and water via carbonic anhydrase. HCO3– is then transported into the aqueous across the endothelium, along with Na+ by a cotransport pump, which apparently is the net effect of multiple subservient ionic mechanisms. The combined ionic

pumping creates an osmotic gradient, and therefore a flux of water, across endothelial cells into the aqueous humor.

Corneal avascularity necessitates oxygen and nutrient delivery from the tear film and the aqueous humor. Vitamins, glucose and amino acids needed by the stroma and epithelium are mainly received from the aqueous humor through a paracellular route. This route requires endothelial cells to be permeable, or “leaky”, to these nutrients. Focal tight junctions, gap junctions, and the interdigitations of the lateral plasma membranes provide the relative permeability to nutrient molecules and water needed for the pump-leak mechanism to work.37,38

Descemet’s Membrane

Descemet’s membrane, the basement membrane of the corneal endothelium, is a thick extracellular matrix that is secreted by endothelial cells. It increases in thickness from 3 μm at birth to around 10 μm in adults. Descemet’s membrane is laid down over time and is divided into a 0.3 μm thin anterior nonbanded zone adjacent to the stroma, an anterior 2-4 μm banded zone, and a posterior amorphous unbanded zone that is more than 4 μm thick.39 The positive correlation of age with the thickness of Descemet’s membrane allows the evaluation of endothelial cell function, which is particularly useful in studying endothelial dystrophies and diseases. An atypical striated collagen deposition in the posterior layer, for example, has been described in Fuchs’ endothelial dystrophy.40 Excessive extracellular matrix can be produced by individual endothelial cells, resulting in focal thickenings of the membrane, called Hassal-Henle bodies that are found in the corneal periphery. If similar structures are found in the central cornea, they are termed corneal guttae. These focal thickenings can increase with age, in Fuchs’ dystrophy, after trauma, and as a result of inflammation. Pigment phagocytosis by the endothelium at the level of guttata can be seen as brownish pigmentation. Further, pseudoguttata can be seen in conditions such as iritis, infections, and inflammation. However, these psudoguttata are usually reversible, as these conditions resolve.

The adult Descemet’s membrane contains collagen type IV and VIII, fibronectin, laminin, dermatan sulfate and heparan sulfate proteoglycans. Descemet’s membrane is tightly adherent to the overlying stroma and reflects its changes. This leads to the observation of Descemet’s folds with swelling of the stroma on slitlamp biomicroscopy. The Descemet’s membrane usually remains intact in bacterial keratitis or corneal ulcers and protrudes as a descemetocele, but exposure to shearing stress tears it easily.

Tears in Descemet’s membrane allow penetration of the aqueous humor into the stroma, and corneal edema from inflammation and secondary loss of the endothelial pump. Although Descemet’s membrane does not regenerate, small defects in the Descemet’s membrane are healed by endothelial cells that migrate over the site of the tear; larger areas of Descemet’s membrane disruption require fibroblasts for the repair process.

Disease States

Endothelial Dystrophies

Congenital Hereditary Endothelial Dystrophy (CHED)

Congenital hereditary endothelial dystrophy (CHED) is a rare disease that presents as a bilaterally symmetric, diffuse corneal edema with Descemet’s membrane thickening in children.41 Although cases consistent with this dystrophy were described under different names in the European literature as early as in 1893,42 it was Maumenee who initially described this dystrophy in the English literature in 1960, suggesting that the disease arises from an abnormality of the endothelium.43 CHED is thought to be caused by a primary dysfunction and degeneration of the corneal endothelial cells, leading to an increase in permeability, accelerated Descemet’s membrane secretion, and stromal edema.44 The corneal thickness is variable, but can reach two to three times the normal thickness, with epithelial microbullae and opacification extending to the limbus without any clear zones.

Two inheritance forms of CHED are recognized. A more common autosomal recessive (AR) form, which is present at birth or within the first few weeks, is stationary, and it is associated with a nystagmus that is due to the severe visual loss. The cornea has a bluish-white ground-glass appearance and a uniform thickening of the Descemet’s membrane. The endothelium is typically difficult to observe, but if seen, it is atrophic, irregular or absent. Despite the severe corneal edema, symptoms of discomfort, epiphora or photophobia are absent in this form of CHED. In contrast, the autosomal dominant (AD) inheritance form presents later during the first or second year of life and it is slowly progressive without any nystagmus. The cornea has a diffuse, blue-gray, ground-glass appearance. Vision tends to be better than the AR form and the patients complain of photophobia and epiphora before the onset of corneal clouding.45 The primary abnormality in the AD form of CHED is thought to be a dysfunction of the corneal endothelium during or after the fifth month of gestation. Recent genetic studies have mapped the gene locus of CHED to chromosome 20 (AD CHED: 20p11.2-q11.2; AR

CHED: 20p13) with the autosomal recessive form being genetically distinct from the autosomal dominant form of CHED.46-48 Reports of similar pathology49 and the possible genetic allelism of AD CHED with PPMD suggest that AD CHED may represent an earlier and more severe spectrum of the posterior dystrophies.36,50

It is important to rule out congenital glaucoma, as with any other form of congenital corneal clouding, although congenial glaucoma has been reported in association with CHED.51 While congenital glaucoma results from abnormal neural crest cell migration, it is thought that CHED results from abnormal neural crest cell differentiation.52 Additional ocular abnormalities are usually absent, but corneal amyloidosis53,54 and hearing deficiency44 have been reported in association with CHED. Due to the early presentation of CHED in the amblyogenic period, penetrating keratoplasty is indicated in these patients. Despite the high rejection rates in this age group, good results have been reported.51,55 Schaumberg et al have reported in a recent multicenter retrospective study of penetrating keratoplasty for CHED that 69% of grafts remained clear after 70 months.56 The 2-year survival for first grafts was reported at 71%. It has been postulated that poor results are related to the early age of onset of the disease or the severity of the disease requiring penetrating keratoplasty.57

Posterior Polymorphous Dystrophy (PPMD)

Posterior polymorphous dystrophy (PPMD) is a bilateral, asymptomatic, generally nonprogressive disease that has an autosomal dominant inheritance. PPMD, even within the same families, has a variable clinical spectrum and is easily overlooked.58 It occurs typically in the second and third decade of life, although presentation as a cloudy cornea in newborn infants has been reported.59 The clinical appearance that is characterized by grouped vesicular or annular opacities, geographic-shaped discrete gray lesions, or broad bands with scalloped edges, is produced by a thick collagenous layer, deposited by epithelioid cells that projects into the anterior chamber (Figure 3-5). Descemet’s membrane can be irregular or have a nodular appearance, and endothelial guttae can be seen. Further, peripheral anterior synechiae (PAS) have been reported in as high as 27% of PPMD patients.60 Although most patients are asymptomatic, stromal edema can occur. It is important to distinguish PPMD from CHED, since corneal edema in PPMD patients, unlike in CHED, may resolve. In case of persistent stromal edema, penetrating keratoplasty is indicated, but the presence of PAS, visible without gonioscopy in association with an increased intraocular pressure should be considered a relative contraindication.

Figure 3-5: Slit-lamp photograph of posterior polymorphous dystrophy with vacuoles (arrows).

Following grafting, recurrence of PPMD has been reported.61,62

Histologically, PPMD is characterized by epithelioid cells that form multiple layers and overgrow normal cells. Unlike the normal endothelium, these cells have desmosomal junctions and microvilli. Immunohistochemical studies indicate the transformation of endothelial cells into epithelioid cells.63 However, recently Cockerham et al. reported that the epithelioid-cell like endothelium does represent a simple transformation from endothelium to surface epithelium.49 They demonstrated the strong expression of the PPMD endothelium for cytokeratin 7, which is not expressed on the surface epithelium.

As with CHED, the pathogenesis of PPMD is thought to be due to a dysfunction of the corneal endothelium and an aberrant differentiation of neural crest cells.46 PPMD is mapped to chromosome 20q11.64 In addition, recently a missense mutation was reported on chromosome 1q34.3- p32.65 The mutated gene codes for the alpha 2 chain of collagen VIII that is the predominant collagen in the anterior banded zone of the Descemet’s membrane. Moreover, mutations in the TCF8 gene have recently been implicated in PPMD, causing ectopic expression of COL4A3 by corneal endothelial cells.66

Iridocorneal Endothelial (ICE) Syndrome

Iridocorneal endothelial (ICE) syndrome describes a spectrum of disorders that are distinguished by a spectrum of nonfamilial iris abnormalities, including pigmented iris nodules, full-thickness holes and stromal matting and effacement (Figures 3-6 to 3-8).67-70 These disorders are further characterized by varying degrees of unilateral secondary angle closure glaucoma, abnormal corneal

Figure 3-6: Iris atrophy in Iridocorneal Endothelial (ICE) syndrome.

Figure 3-7: Ectropion uveae (arrow) in Iridocorneal Endothelial (ICE) syndrome.

Figure 3-8: Early Iridocorneal Endothelial (ICE) syndrome with iridoschisis (arrow).

endothelium with corneal edema, and peripheral anterior synechiae (PAS), although rare bilateral cases have been published recently.71-73 The diagnosis of ICE syndrome should be considered when two of the three main clinical

features (endothelial abnormality, typical iris changes and PAS) are found. There are three subdivisions of ICE syndrome: Iris nevus74 or Cogan-Reese75 syndrome, Chandler syndrome, 76 and essential iris atrophy.

Essential iris atrophy typically presents in young adults with a predelication for females. Patients present with blurry vision or coincidental findings of iris changes, which can extend from a slightly eccentric pupil, to severe corectopia, and partial or full thickness iris holes, caused by stretching or ischemia. In advanced cases that are associated with glaucoma and corneal edema, patients complain of pain. The pathophysiology of this disorder appears to involve an abnormal clone of endothelial cells that has the ultrastructural findings of epithelial cells, but retains its characteristics and lineage.77,78 Early in the disease process, these cells are interspersed with groups of normal endothelial cells, while replacing them slowly. The abnormal endothelial cells produce an abnormal basement membrane that grows along with endothelial cells on the trabecular meshwork and the iris, and is referred to as the “glass membrane”.79,80 The contraction of this membrane results in iris stretching, and results in atrophy and corectopia on the opposite side.67 Further, secondary angle closure glaucoma develops due to the progressive formation of PAS or the membrane overgrowth of the angle. Slit-lamp biomicroscopy does not always demonstrate a beaten-metal appearance that is typically seen in Chandler syndrome. On specular microscopy, however, typical ICEcells with an irregular shape, altered density, and loss of the hexagonal conformation are apparent in the affected eye.81 In cases with severe corneal edema, interfering with the use of specular microscopy, confocal microscopy has been used successfully.82,83

Chandler syndrome typically presents with severe corneal edema and ipsilateral glaucoma due to membrane formation and PAS in the angle.76 Although iris changes and nodules rarely occur in Chandler syndrome, no holes are formed. The corneal edema presents due to an abnormal endothelium that has a fine beaten-metal appearance and resembles Fuchs’ endothelial dystrophy, although looking finer than guttata in Fuchs’ dystrophy. Differentiating this disorder from PPMD is also important. In contrast to Chandler syndrome, PPMD is familial, bilateral and does not present with the typical iris findings. The progressive nature of this disorder eventually leads to corneal decompensation. As with the other ICE syndrome subtypes, specular and confocal microscopy are useful diagnostic tools that demonstrate endothelial changes.

Patients with iris nevus74 or Cogan-Reese syndrome75 present with unilateral iris nodules, diffuse iris nevi, heterochromia, loss of iris surface architecture, PAS,

glaucoma and occasionally corneal edema. Patients essentially have a diffuse endothelialization of the iris with multiple pigmented nodules that are produced by the contracting endothelial basement membrane. The membrane extends from the posterior surface of the cornea, over the angle, and onto the iris surface. Endothelial changes, typical for Chandler syndrome, and iris holes are typically not seen in this disorder.

Although the etiology of ICE syndrome is still unknown, the spectrum of disorders included in this syndrome has been attributed to an embryologic ectopia of the epithelium, delayed expression of the neural crest development, or an inflammatory disease. The presence of a normal Descemet’s membrane under the posterior collagenous layer indicates a postnatal onset of the etiology.79,80 Immunohistochemical studies indicating the coexpression of cytokeratin (epithelium) and vimentin (endothelium) in ICE cells suggests that metaplasia of endothelial cells is the more likely etiology.78,84,85 Although the stimulus for this metaplasia is unknown, studies using PCR have detected the herpes simplex virus in a large number of patients with ICE syndrome, indicating a possible role for this virus.86

Medical treatment has been proven ineffective in ICE syndrome, although corneal edema in Chandler syndrome can initially be treated successfully with hypertonic saline solution. The initial mild form of glaucoma also responds to aqueous suppressants. However, once medical therapy fails and the cornea decompensates, penetrating keratoplasty is needed and, in contrast to essential iris atrophy,87 good results have especially been reported with Chandler syndrome.68,88-90 Eventually, filtering surgery is also required due to the progressive closure of the angle. The use of antifibrotic agents and drainage implants has lead to only variable success.91-94 Trabeculectomy with mitomycin-C is therefore the initial approach, followed by implantation of drainage devices.

Fuchs’ Endothelial Dystrophy

Fuchs’ endothelial dystrophy was initially described by Fuchs in 1910 as a combination of epithelial and stromal edema in older patients.95 Fuchs’ endothelial dystrophy manifests itself as bilateral, albeit asymmetric, central corneal guttae, corneal edema and reduced vision (Figures 3-9 to 3-11).96,97 It is the most common endothelial dystrophy and is usually seen beyond the fifth decade of life, although Biswas et al recently reported several families with early onset of this dystrophy in their third and forth decades of life.65 Fuchs’ endothelial dystrophy is, despite its dominant inheritance form, more common and progressive in women.98 It may also present in a sporadic form and is thought to be a primary disorder of the endothelium.

Figure 3-9: Fuchs’ dystrophy with fixed Descemet’s folds and diffuse corneal stromal and epithelial edema.

Figure 3-10: Specular microscopic view of Fuchs’ corneal dystrophy with guttae adjacent to normal hexagonal endothelial cells.

Figure 3-11: Photomicrograph of endothelial guttae (arrows) in Fuchs’ corneal endothelial dystrophy.

However, according to recent findings, subtypes could be the result of abnormal basement membrane assembly rather than a primary defect.99 Late-onset Fuchs’ endothelial dystrophy has recently been linked to chromosome 13pTel13q12.13.100 It is thought that a gradual transformation of

the endothelium into fibroblast-like cells results in the deposition of collagen fibrils and basement membrane as well as thickening of the Descemet’s membrane. Recent reports investigated whether the loss of endothelial cells is due to apoptotic cells death.101,102 While apoptosis was detected in all corneal layers, it remains unclear whether apoptosis is the cause of endothelial cell death or is it secondary to corneal edema.

Clinically, corneal stromal edema starts centrally and spreads peripherally. This is associated with spreading of corneal guttae towards the periphery, or a central coalescence of corneal guttae with a beaten-metal appearance. Initially, an increase in endothelial pump function delays the edema. Eventually, the pump function is, however, insufficient and with progression of stromal edema, epithelial edema develops. Epithelial edema, usually starting with the central corneal thickness exceeding 650 μm,103 presents with microcystic edema and continues to bullous keratopathy. Finally, rupture of bullae causes pain and foreign body sensation. This can initially be managed medically, but ultimately requires corneal transplantation.

The primary histologic features of Fuchs’ corneal dystrophy are multiple excrescences and a diffuse thickening of the Descemet’s membrane, associated with decrease in endothelial cell density and an increase in cell size. The abnormal portions of the Descemet’s membrane consist of banded collagen and multiple layers of basement membrane material. In addition, the repeated epithelial edema causes abnormalities of the Bowman’s layer with occasional breaks and a fibrovascular pannus in the endstage of the disease.

The course of this dystrophy can further be accelerated after intraocular surgery, specifically cataract extraction. A cell count of less than 1000 cells/mm2 or corneal thickness greater than 640 μm are considered major risk factors for corneal decompensation after cataract surgery.38,104,105 While specular microscopy is of use in diagnosis and follow-up in earlier stages, confocal microscopy can help in the diagnosis of Fuchs’ dystrophy in advanced cases with severe edema.106-108 Medically, corneal edema can initially be managed with hypertonic saline solution or ointment, dehydration of the cornea with a blow dryer, and reduction of intraocular pressure. Bandage contact lenses may be beneficial in the treatment of painful bullae or recurrent erosions. However, penetrating keratoplasty is the treatment of choice in patients with severe vision loss, although endothelial grafting [See also Section 9, Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)] is being advocated with increasing frequency over the last years and might become the treatment of choice in the future.109,110

Mesenchymal Dysgenesis

Mesenchymal dysgenesis, including endothelial dysgenesis, is due to an abnormal migration of neural crest cells. The conditions, previously called Axenfeld anomaly and syndrome or Rieger anomaly and syndrome, have now been grouped under the term Axenfeld-Rieger syndrome.111,112 This syndrome now represents a spectrum of disorders that is characterized by an anterior displacement of Schwalbe’s line, called posterior embryotoxon, iris strands, iris hypoplasia, limbal dermoids, and glaucoma in 50% of patients (Figures 3-12 to 3-14).111 In addition, patients have associated facial (maxillary hypoplasia, hypertelorism, telecanthus, prominent lower lip), cranial (mental retardation, empty sella syndrome) and dental abnormalities (hypodontia, microdontia). Corneal abnormalities associated with Axenfeld-Rieger syndrome

Figure 3-12: Slit-lamp photograph showing Axenfeld-Rieger syndrome with iridocorneal adhesion (arrow).

Figure 3-13: Axenfeld-Rieger syndrome with prominent anteriorly displaced Schwalbe’s line (arrow).

Figure 3-14: Photomicrograph of Axenfeld-Rieger syndrome with anteriorly displaced Schwalbe’s line (green arrow) and iris processes adherent to the cornea (white arrow).

present as pleomorphism of the endothelium, attenuated Descemet’s membrane, and posterior embryotoxon (present in 10-15% of normal eyes). The inheritance pattern is dominant in 75% of cases, while sporadic cases have been reported. The forkhead genes FOXC1, located in chromosome 6p25, are responsible for many of the congenital defects of the anterior segment.113 In addition, mutations in the PITX2 gene (4q25, RIEG1), and chromosome 13q14/RIEG2, can cause this syndrome.114-117 Further, Reneker et al have recently demonstrated the critical role of the endothelial formation on the anterior segment development in a murine transgenic model.118

Peters anomaly is a rare, central, corneal opacity that presents at birth, with sixty to eighty percent of cases being bilateral.119 In general, a central leukoma is present that is associated with defects of the endothelium, Descemet’s membrane, or stroma, and can be associated with iridocorneal adhesions (Figures 3-15 and 3-16). The peripheral cornea is usually unaffected. Most cases are sporadic, although both dominant and recessive inheritance patterns have been described. Peters anomaly can be caused by mutations in the PAX6 gene (11p13), PITX2 gene (4q25-26), CYP1B1 gene (2p22-21),120 and the FOXC1 gene (6p25). Additional ocular findings include, cataract, keratolenticular touch, microcornea, aniridia, buphthalmos, glaucoma, and persistent fetal vasculature. In sixty percent of cases, systemic malformations have been described that include heart defect, hearing loss, external ear abnormalities, CNS deficits, developmental delays, spinal defects, gastrointestinal and genitourinary defects, facial clefts, and skeletal abnormalities.121 The lenticular abnormalities demonstrate a stalk-like connection to the posterior cornea, suggesting an incomplete separation of

Figure 3-15: Central leukoma of Peters anomaly (arrow).

Figure 3-16: Photomicrograph of Peters anomaly with iridocorneal adhesion; note the absence of corneal endothelium.

the lens vesicle. This could be due to incomplete migration of neural crest cells, resulting in endothelial and stromal defects. Alternatively, a subluxation of the lens in utero could interrupt the migration of the endothelium. The prognosis for keratoplasty is typically poor and is highest for the first graft, while decreasing significantly with subsequent surgery.122

Diabetes

Corneal changes in diabetes mellitus (DM) present as basement membrane changes, punctate epithelial erosions, vertical Descemet’s folds (Waite-Beetham lines), and decreased corneal sensation. Further, patients have an altered endothelial cell morphology and function that differ from retinal vasculopathy.123 There is no thickening of Descemet’s membrane and the degree of endothelial abnormality does not correlate with the duration of disease or level of glycemic control.124,125 While some studies have shown similar cell areas in diabetics and nondiabetic patients, other studies have demonstrated an increased

polymegathism and polymorphism in diabetic patients.123,125-128 Moreover, the central corneal thickness in diabetics is increased in most studies.123,126,129 Abnormal aldose reductase activity in the endothelium has been implicated in the decrease in cell density and increased cell size seen in diabetics.130 Patients with DM also demonstrate a decreased ability to maintain stromal hydration that is due to endothelial pump dysfunction. This may be related to polyhydroxy alcohols and lysine cross-linking, which could explain the slow recovery from post-operative corneal edema.131-134

Toxic Anterior Segment Syndrome (TASS)

Toxic anterior segment syndrome (TASS) is a rare complication of intraocular surgery that has only recently been recognized.135 TASS is an acute sterile inflammation resulting from inadvertent introduction of noxious agents in the anterior segment, e.g., endotoxins, medications, residual viscoelastic agents, preservatives, or an altered osmolarity or pH.136-139 Permanent corneal endothelial damage can occur in severe cases of TASS. Furthermore, cystoid macular edema, glaucoma and iris atrophy can result.

Clinical signs of TASS include immediate postoperative corneal edema that can extend from limbus-to-limbus, a fixed pupil, high intraocular pressure, and anterior segment inflammation. Patients usually complain of decreased visual acuity and pain. Mild to moderate forms of TASS can be treated successfully with hourly topical and oral steroids, together with nonsteroidal anti-inflammatory agents every 6 hours.136,138 In general, most cases of TASS resolve within weeks with aggressive treatment but more serious cases require endothelial replacement [See also Section 9, Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)].

Future Directions

The authors believe future advances will come from the field of cell biology. In rabbits, the endothelium is capable of robust, mitotic self-repair but this feature is lacking in human corneal endothelium. However, there is a recent report of BrdU activity in the periphery of human corneas, which is a characteristic marker of mitotic activity. In the future, it may be possible to “unlock” the potential of these cells to replicate by finding a biochemical key. Another possibility is the use of stem cells or genetic engineering (perhaps via a viral vector) to stimulate or replace diseased or damaged cells. Hopefully, not too far in the future, we may be able to decrease the need for corneal transplantation

by increasing our understanding of the basic science of the corneal endothelium.

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