Immunohistochemical Findings in Retrocorneal Membranes of Eyes with Corneal Decompensation after Complicated Intraocular Surgery.

BACKGROUND: Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. METHODS AND PATIENTS: Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. RESULTS: On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. CONCLUSIONS: In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium.

A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1.

Fuchs Endothelial Corneal Dystrophy (FECD) results from dysfunctional corneal endothelial cells (CECs) and is currently treated by transplantation of the whole cornea or Descemet's membrane. Recent developments in ocular surgery have established Descemet's Stripping Only (DSO), a surgical technique in which a central circle of guttae-dense Descemet's membrane is removed to allow for the migration of CECs onto the smooth stroma, restoring function and vision to the cornea. While this potential treatment option is of high interest in the field of ophthalmic research, no successful ex vivo models of DSO have been established and clinical data is limited. This work presents a novel wound-healing model simulating DSO in human donor corneas. Using this approach to evaluate the efficacy of the human engineered FGF1 (NM141), we found that treatment accelerated healing via stimulation of migration and proliferation of CECs. This finding was confirmed in 11 pairs of human corneas with signs of dystrophy reported by the eye banks in order to verify that these results can be replicated in patients with Fuchs' Dystrophy, as the target population of the DSO procedure.

Pilot Study of Corneal Clearance With the Use of a Rho-Kinase Inhibitor After Descemetorhexis Without Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To investigate corneal clearance time using a topical rho-kinase inhibitor, netarsudil, after descemetorhexis without endothelial keratoplasty (DWEK). METHODS: Twenty eyes from 10 patients with Fuchs endothelial corneal dystrophy had DWEK with cataract surgery. For the first eye of each participant, netarsudil was administered immediately after surgery until corneal clearance. For the second eye, netarsudil was withheld 2 weeks beyond the time for corneal clearance of the first eye and then administered only if corneal edema was still present. Interpatient and intrapatient comparisons were made for pachymetry, endothelial cell count, intraocular pressure, and time to corneal clearance. RESULTS: Intrapatient comparison demonstrated no significant difference in preoperative pachymetry (P value 0.58), endothelial cell counts (P value 0.97), and intraocular pressure (P value 0.46) between eyes treated with netarsudil immediately after DWEK and those with delayed netarsudil use. Average time for corneal clearance in eyes treated with netarsudil immediately after surgery was 4.6 ± 1.7 weeks, which was significantly shorter than eyes not treated with netarsudil immediately at 8 ± 1.9 weeks (P < 0.01). Corneal clearance occurred in eyes between 1 and 2 weeks after addition of netarsudil as a "rescue" drop. Interpatient comparison demonstrated significantly greater endothelial cell counts in eyes treated with netarsudil immediately compared with eyes with a delay in netarsudil use (P = 0.05). CONCLUSIONS: Netarsudil significantly reduces the time to corneal clearance after DWEK. Furthermore, increased endothelial cell counts in eyes with immediate netarsudil use versus delayed netarsudil use suggests that the immediate perioperative period is crucial in cell regeneration and migration.

Cigarette Smoke Triggers Loss of Corneal Endothelial Cells and Disruption of Descemet's Membrane Proteins in Mice.

Purpose: To investigate changes at a molecular level in the mouse corneal endothelium (CE) exposed to chronic cigarette smoke (CS). Methods: Pregnant mice (gestation days 18-20) were placed in a whole-body exposure smoking chamber, and a few days later pups were born. After 3.5 months of CS exposure, a ConfoScan4 scanning microscope was used to examine the corneal endothelial cells (CECs) of CS-exposed and control (Ct) mice. The CE was peeled under a microscope and maintained as four biological replicates (two male and two female) for CS-exposed and Ct mice; each replicate consisted of 16 CEs. The proteome of the CE was investigated through mass spectrometry. Results: The CE images of CS-exposed and Ct mice revealed a difference in the shape of CECs accompanied by a nearly 10% decrease in CEC density (P < 0.00003) following CS exposure. Proteome profiling identified a total of 524 proteins exhibiting statistically significant changes in CE from CS-exposed mice. Importantly, proteins associated with Descemet's membrane (DM), including COL4α1, COL4α2, COL4α3, COL4α4, COL4α5, COL4α6, COL8α1, COL8α2, and FN1, among others, exhibited diminished protein levels in the CE of CS-exposed mice. Conclusions: Our data confirm that exposure to CS results in reduced CEC density accompanied by diminished levels of multiple collagen and extracellular matrix proteins associated with DM.

Intraocular Deposition of Copper and ERG Findings in a Patient With Progressive Vision Loss From Hypercupremia.

A 46-year-old woman who presented for progressive glare was found to have dense deposition of copper within Descemet's membrane and lens capsule in both eyes (OU). Systemic workup revealed elevated serum copper secondary to multiple myeloma. Following bilateral Descemet stripping automated endothelial keratoplasty and cataract extraction, a green discoloration of the vitreous was noted. The patient was followed for 3 years with serial exams and electroretinograms. Electroretinograms showed declining photopic response amplitude OU, indicative of progressive retinal toxicity from copper. Although retinal toxicity and vitreous copper deposition are common in chalcosis, this appears to be the first case of hypercupremia associated with these findings. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e324-e326.].

Postmortem ultrastructural analysis of a cornea transplanted with Descemet membrane endothelial keratoplasty.

PURPOSE: The aim of this study was to describe the ultrastructure of the host-donor interface in the eye of a recently deceased patient, who had undergone Descemet membrane endothelial keratoplasty. METHODS: The eye was enucleated postmortem, and after standard decontamination, the corneoscleral button was excised, cut into 4 quadrants, and processed for light and transmission electron microscopy evaluation. RESULTS: Transmission electron microscopy revealed close attachment of the donor's Descemet membrane to the host's stroma and projection of stromal collagen fibers into the interfacial matrix, resembling a normal "virgin" corneal architecture. CONCLUSIONS: Ultrastructurally, an attached Descemet membrane endothelial keratoplasty graft closely resembles that of an unoperated, healthy eye with no appreciable adventitious or missing structures.

Factors affecting DSAEK graft lenticle adhesion: an in vitro experimental study.

PURPOSE: The aim of this study was to evaluate different factors that affect Descemet stripping automated endothelial keratoplasty (DSAEK) donor graft lenticle adhesion to the recipient cornea. METHODS: This experimental study included 10 eye bank recipient corneas and 10 donor DSAEK lenticles. Recipient corneas were mounted on an artificial anterior chamber (AC), whereas donor lenticles were placed beneath the host cornea. Using optical coherence tomography and imaging software, the interface gap (IG) between the donor and recipient cornea was quantified to evaluate the effect of variations in AC air fill pressure, AC air fill duration, corneal massage, and corneal venting incisions on DSAEK donor graft lenticle adhesion. RESULTS: Different intraocular pressures (IOP) under air for the same time intervals, do not significantly correlate with the IG; nevertheless, it was noticed that the IG decreases as the IOP increases. With respect to the magnitude of AC IOP, there was no statistically significant difference when comparing 10 mm Hg with 30 mm Hg and assessing IG (P = 0.4). Complete air-fluid exchange resulted in significantly higher IG when compared with AC air bubble of 10 and 30 mm Hg that was sustained for 1 hour (P < 0.05). Furthermore, corneal surface massage did not facilitate DSAEK graft adhesion (P = 0.59). Finally, paracentral venting incisions followed by interface fluid aspiration seemed to significantly decrease the IG (P = 0.014). CONCLUSIONS: Corneal venting incisions and higher AC IOP values seem to facilitate DSAEK donor graft lenticle adhesion to the recipient cornea.

Graft adhesion in descemet membrane endothelial keratoplasty dependent on size of removal of host's descemet membrane.

IMPORTANCE: It is essential to devise strategies that improve graft adhesion after Descemet membrane endothelial keratoplasty (DMEK) to reduce the rebubbling rate. OBJECTIVE: To evaluate the influence of the extent of descemetorhexis on graft adhesion properties after DMEK. DESIGN, SETTING, AND PARTICIPANTS: Single-surgeon, retrospective, observational case series conducted in the Department of Ophthalmology, University of Erlangen-Nuremberg, Germany, that reviewed the medical records of 200 consecutive patients undergoing DMEK. Fifty-three eyes of 51 patients undergoing DMEK for Fuchs endothelial dystrophy fulfilling the inclusion criteria were enrolled in this study. Based on intraoperative drawings, postoperative slitlamp examination, and photographs, eyes were divided into 2 groups. The diameter of the descemetorhexis was approximately 10 mm in group A (30 eyes), resulting in a peripheral 1-mm zone of denuded stroma between the graft and the host's Descemet membrane, and approximately 6 mm in group B (23 eyes), resulting in a peripheral 1-mm zone of overlapping between the graft and the host's Descemet membrane. MAIN OUTCOMES AND MEASURES: Graft detachment rate, extent of graft detachment (in clock hours of graft's circumference), and rebubbling rate. RESULTS: Four days after DMEK, the graft detachment rate was 33.3% (10 of 30) in group A and 78.3% (18 of 23) in group B (P = .002). The mean (SD) extent of graft detachment was 0.6 (0.9) and 2.8 (2.5) clock hours in groups A and B, respectively (P < .001), 4 days after surgery. The rebubbling rate was 6.7% (2 of 30) and 30.4% (7 of 23) for groups A and B, respectively (P = .03). CONCLUSIONS AND RELEVANCE: A larger descemetorhexis in DMEK is correlated with better graft adhesion and lower rebubbling rates. Therefore, patients with a larger descemetorhexis require less intensive follow-up.

Ocular manifestations of monoclonal copper-binding immunoglobulin.

The dense accumulation of copper in Descemet membrane and lens capsule is the characteristic manifestation of a circulating monoclonal antibody with strong affinity for copper. The overproduction of this monoclonal immunoglobulin may be associated with either multiple myeloma or a benign monoclonal gammopathy. Despite prolonged exposure to elevated serum copper, no other tissues in the body are adversely affected by this redox metal. We describe the clinical and pathological findings in a 46-year-old woman with this disorder.

Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice.

The corneal endothelium (CE) is a single layer of cells lining the posterior face of the cornea providing metabolic functions essential for maintenance of corneal transparency. Adult CE cells lack regenerative potential, and the number of CE cells decreases throughout life. To determine whether endogenous DNA damage contributes to the age-related spontaneous loss of CE, we characterized CE in Ercc1(-/Δ) mice, which have impaired capacity to repair DNA damage and age prematurely. Eyes from 4.5- to 6-month-old Ercc1(-/Δ) mice, age-matched wild-type (WT) littermates, and old WT mice (24- to 34-month-old) were compared by spectral domain optical coherence tomography and corneal confocal microscopy. Histopathological changes in CE were further identified in paraffin tissue sections, whole-mount immunostaining, and scanning electron and transmission electron microscopy. The CE of old WT mice displayed polymorphism and polymegathism, polyploidy, decreased cell density, increased cell size, increases in Descemet's thickness, and the presence of posterior projections originating from the CE toward the anterior chamber, similar to changes documented for aging human corneas. Similar changes were observed in young adult Ercc1(-/Δ) mice CE, demonstrating spontaneous premature aging of the CE of these DNA repair-deficient mice. CD45(+) immune cells were associated with the posterior surface of CE from Ercc1(-/Δ) mice and the tissue expressed increased IL-1α, Cxcl2, and TNFα, pro-inflammatory proteins associated with senescence-associated secretory phenotype. These data provide strong experimental evidence that DNA damage can promote aging of the CE and that Ercc1(-/Δ) mice offer a rapid and accurate model to study CE pathogenesis and therapy.

Reproducibility of graft preparations in Descemet's membrane endothelial keratoplasty.

PURPOSE: To assess the reproducibility of manual graft preparation and evaluate the incidence rate and nature of structural anomalies of Descemet's membrane (DM) preventing successful graft preparation in DM endothelial keratoplasty (DMEK). DESIGN: Prospective, single-center, nonrandomized, consecutive case series. PARTICIPANTS: We analyzed 350 corneoscleral buttons from donors aged 18-95 years stored in Optisol-GS or Dulbecco's modified Eagle's medium and used for DMEK surgery in 343 consecutive patients with Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy. METHODS: Residual endothelial cell-DM complexes obtained after successful DM stripping for DMEK and whole donor corneas obtained after unsuccessful DM stripping were examined by transmission electron microscopy and immunohistochemistry. MAIN OUTCOME MEASURES: Accuracy of the cleavage plane between DM and corneal stroma and structural abnormalities of the DM-stroma interface. RESULTS: Uneventful manual separation without any disruption of DM was achieved in 335 of 350 donor corneas (95.7%) by use of a previously established bimanual submerged preparation technique. Correspondingly, the peeled DM specimens revealed a regular and smooth cleavage plane exposing the amorphous interfacial matrix on their anterior surface. Although 8 of 350 donor corneas (2.3%) showed focal adhesions of DM to the corneal stroma and developed isolated tears during stripping, preparation of the graft could be successfully completed. However, 7 of the 350 donor corneas (2.0%) showed extremely strong adhesion and multiple tears of DM, preventing successful preparation of the graft. These specimens revealed either ultrastructural (peg-like interlockings) or biochemical abnormalities (increased staining intensities for adhesive glycoproteins) along the DM-stroma interface. CONCLUSIONS: Using an appropriate technique, manual preparation of grafts for DMEK with reproducible tissue qualities is possible in the vast majority (98%) of donor corneas. Although a relatively rare phenomenon, interindividual variations in DM structure and composition may be responsible for failure of graft preparation in about 2% of donor corneas. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Retrocorneal membrane formation after Baerveldt shunt implantation for iridocorneal endothelial syndrome.

PURPOSE: Retrocorneal membranes can occur after trauma or surgery and remain as a therapeutic problem in graft failure after penetrating keratoplasty. We report for the first time the finding of a retrocorneal membrane in Descemet stripping automated endothelial keratoplasty (DSAEK) in a young woman who underwent Baerveldt shunt implantation for iridocorneal endothelial (ICE) syndrome. METHODS: Clinical examination, preoperative and postoperative slit lamp-adapted optical coherence tomography of the anterior segment, and immunohistochemical staining and electron microscopic analysis of the stripped Descemet membrane were performed. RESULTS: A 25-year-old woman presented with decline of visual acuity because of the formation of a retrocorneal membrane after Baerveldt shunt implantation for ICE syndrome. Visual acuity improved after DSAEK from 20/200 to 20/63, whereas intraocular pressure did not change in the 6-month postoperative follow-up. Histological and ultrastructural analysis showed a massive retrocorneal membrane. Immunohistopositivity for α-smooth muscle actin, cytokeratin 7, and pan-cytokeratin suggests a metaplastic endothelial origin of this membrane. CONCLUSIONS: The exact origin of the retrocorneal membrane found in this case in ICE syndrome after Baerveldt shunt implantation cannot be clarified, but DSAEK is an effective treatment to improve visual acuity in this situation.

Facilitated diffusion of VEGF165 through descemet's membrane with sucrose octasulfate.

Vascular endothelial growth factor A (VEGF-A) is a promoter of neovascularization and thus a popular therapeutic target for diseases involving excessive growth of blood vessels. In this study, we explored the potential of the disaccharide sucrose octasulfate (SOS) to alter VEGF165 diffusion through Descemet's membrane. Descemet's membranes were isolated from bovine eyes and used as a barrier between two chambers of a diffusion apparatus to measure VEGF transport. Diffusion studies revealed a dramatic increase in VEGF165 transport in the presence of SOS, with little diffusion of VEGF165 across the membrane over a 10-h time course in the absence of SOS. Diffusion studies with VEGF121, a non-heparin binding variant of VEGF, showed robust diffusion with or without SOS. To determine a possible mechanism, we measured the ability of SOS to inhibit VEGF interactions with extracellular matrix (ECM), using cell-free and cell surface binding assays. Binding studies showed SOS had no effect on VEGF165 binding to either heparin-coated plates or endothelial cell surfaces at less than mg/ml concentrations. In contrast, we show that SOS inhibited VEGF165 binding to fibronectin in a dose dependent manner and dramatically accelerated the rate of release of VEGF165 from fibronectin. SOS also inhibited the binding of VEGF165 to fibronectin-rich ECM deposited by vascular smooth muscle cells. These results suggest that fibronectin-rich extracellular matrices serve as barriers to VEGF165 diffusion by providing a network of binding sites that can trap and sequester the protein. Since the content of Descemet's membrane is typical of many basement membranes it is possible that they serve throughout the body as formidable barriers to VEGF165 diffusion and tightly regulate its bioavailability and distribution within tissues.

Characterization of the cleavage plane in DESCemet's membrane endothelial keratoplasty.

PURPOSE: To define the cleavage plane between Descemet's membrane (DM) and posterior corneal stroma in Descemet's membrane endothelial keratoplasty (DMEK) concerning its ultrastructural and immunohistochemical characteristics. DESIGN: Observational, consecutive case series. PARTICIPANTS: Fifteen corneoscleral buttons from donors 71.5±4.3 years of age stored in Optisol-GS and used for DMEK surgery in 15 consecutive patients. METHODS: Endothelial cell-DM complexes (EDMs) and corresponding corneoscleral rims were investigated by transmission electron microscopy and immunohistochemistry using a panel of antibodies against adhesive matrix proteins. MAIN OUTCOME MEASURES: Ultrastructural and immunohistochemical characteristics of interface and cleavage plane between DM and posterior stroma. RESULTS: Connection between DM and corneal stroma was mediated predominantly by amorphous material of the interfacial matrix and projecting stromal collagen fibers. After DM stripping, the cleavage plane was located consistently between interfacial matrix and posterior stromal collagen lamellae, providing a largely smooth anterior EDM surface exposing the interfacial zone. Interindividual variations in amount and composition of the interfacial matrix resulted in variable degrees of EDM surface irregularities and variable staining patterns for adhesive matrix proteins such as fibronectin, vitronectin, amyloid P, osteonectin/secreted protein acidic and rich in cysteine (SPARC), fibulin-1, fibulin-2, fibulin-3, fibrillin-1, and keratoepithelin. CONCLUSIONS: The findings provide evidence for the existence of a physiologic cleavage plane between the interfacial matrix, the anteriormost adhesive zone of DM, and the corneal stroma, suggesting a relatively weak attachment that can be disconnected by mechanical forces. Interindividual variations in structure and composition of the interfacial matrix may provide an explanation for the variable attachment of EDM grafts to the recipients' corneal stroma and thus may affect the postoperative clinical outcome. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Oxidative stress, mitochondrial dysfunction and calcium overload in human lamina cribrosa cells from glaucoma donors.

PURPOSE: Oxidative stress is implicit in the pathological changes associated with glaucoma. The purpose of this study was to compare levels of oxidative stress in glial fibrillary acid-negative protein (GFAP) lamina cribrosa (LC) cells obtained from the optic nerve head (ONH) region of 5 normal (NLC) and 4 glaucomatous (GLC) human donor eyes and to also examine mitochondrial function and calcium homeostasis in this region of the ONH. METHODS: Intracellular reactive oxygen species (ROS) production was examined by a thiobarbituric acid reactive substances (TBARS) assay which measures malondialdehyde (MDA), a naturally occurring product of lipid peroxidation and is used as an indicator of oxidative stress. Mitochondrial membrane potential (MMP) and intracellular calcium ([Ca(2+)](i)) levels were evaluated by flow cytometry using the JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetrabenzimidazolecarbocyanine iodide) and fluo-4/AM probes respectively. Anti-oxidant and Ca(2+) transport system gene and protein expression were determined by real time polymerase chain reaction (RT-PCR) using gene-specific primer/probe sets and western immunoblotting, respectively. RESULTS: Intracellular ROS production was increased in GLC compared to NLC (27.19 ± 7.05 µM MDA versus 14.59 ± 0.82 µM MDA, p < 0.05). Expression of the anti-oxidants Aldo-keto reductase family 1 member C1 (AKR1C1) and Glutamate cysteine ligase catalytic subunit (GCLC) were significantly lower in GLC (p = 0.02) compared to NLC control. MMP was lower in GLC (57.5 ± 6.8%) compared to NLC (41.8 ± 5.3%). [Ca(2+)](i) levels were found to be higher (p < 0.001) in GLC cells compared to NLC. Expression of the plasma membrane Ca(2+)/ATPase (PMCA) and the sodium-calcium (NCX) exchangers were lower, while intracellular sarco-endoplasmic reticulum Ca(2+)/ATPase 3 (SERCA) expression was significantly higher in GLC compared to NLC. Subjection of NLC cells to oxidative stress (200 µM H(2)0(2)) reduced expression of Na(+)/Ca2(+) exchanger 1 (NCX 1), plasma membrane Ca2+ ATPase 1 (PMCA 1), and PMCA 4 as determined by RT-PCR. CONCLUSIONS: Our data finds evidence of oxidative stress, mitochondrial dysfunction and impaired calcium extrusion in GLC cells compared to NLC cells and suggests their importance in the pathological changes occurring at the ONH in glaucoma. Future therapies may target reducing oxidative stress and / or [Ca(2+)](i).

Long-term follow-up of a supradescemetic keratoprosthesis in rabbits: an immunofluorescence study.

OBJECTIVE: To evaluate the long-term clinical and immunohistological outcome of two different non-penetrating keratoprosthesis (KPro) implanted in non-injured rabbit corneas. MATERIALS AND METHODS: Three rabbits underwent implantation of a pHEMA-MMA(34) synthetic cornea in the supradescemetic space, and PMMA synthetic corneas in the supradescemetic space and within the central stroma. Animals were followed for at least 24 months before euthanasia. Periodic evaluation was performed with slit-lamp examination and photography. At the end of the follow-up, histological examination including hematoxylin eosin staining and immunocharacterization against collagen IV, alpha smooth muscle actin (α-SMA) and macrophages was performed. RESULTS: The pHEMA-MMA(34) implant was not extruded, and remained transparent until the end of follow-up. This material did not induce any cell infiltration, corneal scarring or tissue remodeling in the surrounding stroma as shown by immunofluorescence. In contrast, synthetic corneas made of PMMA-induced myofibroblast differentiation, stromal remodeling and macrophage infiltration. This reaction was even more significant in the rabbit with the PMMA implant within the corneal stroma. CONCLUSION: pHEMA-MMA(34) was clinically biocompatible, and did not induce any inflammatory reaction or scarring when implanted in the supradescemetic space. This material showed more promising biocompatibility results than for PMMA, whether implanted within the central cornea stroma or in the supradescemetic space.

Copper deposition in a variant of multiple myeloma: pathologic changes in the cornea and the lens capsule.

PURPOSE: To report the pathologic changes in the cornea and the lens capsule resulting from copper deposition in a variant of multiple myeloma. METHODS: Case report. RESULTS: Light microscopy of the cornea revealed endothelial cell attenuation with diffuse copper deposition in the central Descemet membrane, which showed thinning, whereas copper banding was seen in the midperipheral and peripheral cornea where the Descemet membrane was normal in thickness. Copper deposition was confirmed by x-ray microanalysis. The anterior lens capsule showed subepithelial copper deposits. Thickening, multilayering, and splitting of the lens capsule were also noted. CONCLUSIONS: We report the pattern of deposition of copper in the Descemet membrane of the cornea and the anterior lens capsule in multiple myeloma, associated with hypercupremia. Descemet membrane thinning and regional differences in copper deposition were noted. Also, thickening and splitting of the lens capsule are a novel observation.

Clinicopathologic findings in failed descemet stripping automated endothelial keratoplasty.

OBJECTIVE: To evaluate the clinical features of and histologic findings from failed Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective observational case series evaluated 47 consecutive corneal specimens from 42 patients who underwent either penetrating keratoplasty or repeated DSAEK for failed DSAEK. Clinical information was obtained for the cases. Sections of the specimens were examined using light microscopy. Immunohistochemical staining was performed for cytokeratins AE1/AE3 and for the myogenic marker smooth-muscle actin when indicated. Transmission electron microscopic examination was performed in some cases. RESULTS: Graft survival ranged from 0.5 to 34 months. Histologic examination showed that 94% of the specimens (44 of 47) had endothelial cell loss. Residual host Descemet membrane (19%; 9 of 47), fibrocellular tissue (19%; 9 of 47), epithelial implantation (15%; 7 of 47), and fungal infection (4%; 2 of 47) were also identified. Immunohistochemical stains were positive for AE1/AE3 in the epithelial implantations and for smooth-muscle actin in cells in the fibrocellular proliferations. CONCLUSIONS: The principal cause of failed DSAEK is endothelial cell loss. Residual host Descemet membrane, fibrocellular tissue at the edge of the lenticule, and epithelial implantation are common histologic findings. Fungal infection may occur in the setting of DSAEK.