The corneal endothelium: clinical review of endothelial cell health and function.

The endothelial cell is a critical structure within the cornea and is responsible for maintaining corneal clarity through its pump function. Endothelial cells are lost over time naturally but can be injured medically, surgically, or as a part of various dystrophies. Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy. In cases of significant compromise, endothelial cells can be transplanted by various endothelial keratoplasty techniques. The future pipeline is bright for possible endothelial cell regeneration and rehabilitation. This article reviews these topics in depth to provide a comprehensive look at the structure and function of the endothelial cell, etiologies of endothelial cell damage, detailed review of iatrogenic causes of endothelial cell loss, and management strategies.

Increasing Povidone-Iodine Exposure in Endothelial Keratoplasty Tissue Processing and Fungal Infection Impact.

PURPOSE: To evaluate the effect on donor rim cultures and postoperative infections of doubling the povidone-iodine exposure time during corneal tissue recovery before its use in keratoplasty. METHODS: Consecutive donor cornea recoveries were evaluated for positive donor corneal rim cultures and postoperative infections before and after a protocol change of doubling the exposure time of povidone-iodine during donor preparation. RESULTS: In 631 consecutive cornea donor recoveries, 18 (2.9%) had positive fungal rim cultures and 41 (6.5%) had positive bacterial rim cultures. Three (0.48%) developed postoperative fungal infections, and no bacterial infections occurred. After doubling the povidone-iodine exposure time during the recovery process, 725 consecutive corneas were reviewed. Four (0.6%) had positive fungal rim cultures, and 29 (4.0%) had positive bacterial rim cultures. No postoperative fungal or bacterial infections occurred. No noticeable increase in epithelial toxicity developed between the 2 groups. CONCLUSIONS: Increasing the povidone-iodine exposure time during the donor cornea recovery process decreased the rate of positive donor corneal rim fungal cultures (P = 0.001), positive donor corneal rim bacterial cultures (P = 0.04), and postoperative fungal infections (P = 0.06).

Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study.

Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm2), lower screening ECD (-234 [-331 to -137] per 500 cells/mm2), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm2), and operative complications (-324 [-516 to -133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

Descemet Membrane Endothelial Keratoplasty: Safety and Outcomes: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of corneal endothelial dysfunction. METHODS: Literature searches were last conducted in the PubMed and the Cochrane Library databases most recently in May 2017. The searches, which were limited to English-language abstracts, yielded 1085 articles. The panel reviewed the abstracts, and 47 were determined to be relevant to this assessment. RESULTS: After DMEK surgery, the mean best-corrected visual acuity (BCVA) ranged from 20/21 to 20/31, with follow-up ranging from 5.7 to 68 months. At 6 months, 37.6% to 85% of eyes achieved BCVA of 20/25 or better and 17% to 67% achieved BCVA of 20/20 or better. Mean endothelial cell (EC) loss was 33% (range, 25%-47%) at 6 months. Overall change in spherical equivalent was +0.43 diopters (D; range, -1.17 to +1.2 D), with minimal induced astigmatism of +0.03 D (range, -0.03 to +1.11 D). The most common complication was partial graft detachment requiring air injection (mean, 28.8%; range, 0.2%-76%). Intraocular pressure elevation was the second most common complication (range, 0%-22%) after DMEK, followed by primary graft failure (mean, 1.7%; range, 0%-12.5%), secondary graft failure (mean, 2.2%; range, 0%-6.3%), and immune rejection (mean, 1.9%; range, 0%-5.9%). Overall graft survival rates after DMEK ranged from 92% to 100% at last follow-up. Best-corrected visual acuity after Descemet's stripping endothelial keratoplasty (DSEK) ranged from 20/34 to 20/66 at 9 months. The most common complications after DSEK were graft detachment (mean, 14%; range, 0%-82%), endothelial rejection (mean, 10%; range, 0%-45%), and primary graft failure (mean, 5%; range, 0%-29%). Mean EC loss after DSEK was 37% at 6 months. CONCLUSIONS: The evidence reviewed supports DMEK as a safe and effective treatment for endothelial failure. With respect to visual recovery time, visual outcomes, and rejection rates, DMEK seems to be superior to DSEK and to induce less refractive error with similar surgical risks and EC loss compared with DSEK. The rate of air injection and repeat keratoplasty were similar in DMEK and DSEK after the learning curve for DMEK.

Ciliary body metastasis from renal cell carcinoma successfully treated with intravitreal bevacizumab.

PURPOSE: To report an innovative new treatment option for ciliary body tumor metastasis from renal cell carcinoma treated with intravitreal bevacizumab. OBSERVATIONS: A 70-year-old Caucasian man presented with a ciliary body tumor as a result from metastasis from renal cell carcinoma. It was preferable to treat the ciliary body tumor in the least invasive manner possible based on the patient's health, systemic metastasis, and the invasiveness of local resection. The tumor was treated with intravitreal bevacizumab for attempted tumor regression. Complete tumor resolution occurred following three injections. CONCLUSIONS AND IMPORTANCE: There is no consensus on treatment for ciliary body metastases from renal cell carcinoma. Based on the successful result of our patient, intravitreal bevacizumab could be an acceptable treatment option for this type of intraocular tumor. It affords a relatively non-invasive method of tumor regression without undergoing major intraocular surgery.

Safety and Efficacy of Lacrimal Drainage System Plugs for Dry Eye Syndrome: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To review the published literature assessing the efficacy and safety of lacrimal drainage system plug insertion for dry eye in adults. METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on March 9, 2015, without date restrictions and were limited to English language abstracts. The searches retrieved 309 unique citations. The primary authors reviewed the titles and abstracts. Inclusion criteria specified reports that provided original data on plugs for the treatment of dry eyes in at least 25 patients. Fifty-three studies of potential relevance were assigned to full-text review. The 27 studies that met the inclusion criteria underwent data abstraction by the panels. Abstracted data included study characteristics, patient characteristics, plug type, insertion technique, treatment response, and safety information. All studies were observational and rated by a methodologist as level II or III evidence. RESULTS: The plugs included punctal, intracanalicular, and dissolving types. Fifteen studies reported metrics of improvement in dry eye symptoms, ocular-surface status, artificial tear use, contact lens comfort, and tear break-up time. Twenty-five studies included safety data. Plug placement resulted in ≥50% improvement of symptoms, improvement in ocular-surface health, reduction in artificial tear use, and improved contact lens comfort in patients with dry eye. Serious complications from plugs were infrequent. Plug loss was the most commonly reported problem with punctal plugs, occurring on average in 40% of patients. Overall, among all plug types, approximately 9% of patients experienced epiphora and 10% required removal because of irritation from the plugs. Canaliculitis was the most commonly reported problem for intracanalicular plugs and occurred in approximately 8% of patients. Other complications were reported in less than 4% of patients on average and included tearing, discomfort, pyogenic granuloma, and dacryocystitis. CONCLUSIONS: On the basis of level II and III evidence in these studies, plugs improve the signs and symptoms of moderate dry eye that are not improved with topical lubrication, and they are well tolerated. There are no level I studies that describe the efficacy or safety of lacrimal drainage system plugs.

Boston Keratoprosthesis: Outcomes and Complications: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To review the published literature on safety and outcomes of the Boston type I keratoprosthesis (BI-KPro) for the surgical treatment of corneal opacification not amenable to human cadaveric corneal transplantation. METHODS: Searches of peer-reviewed literature were conducted in PubMed and the Cochrane Library in December 2012, July 2013, and January 2014 without date restrictions. The searches were limited to studies published in English and yielded 587 citations. The abstracts of these articles were reviewed, 48 articles were selected for possible clinical relevance, and 22 were determined to be relevant for the assessment objectives. Nine studies were rated as level II evidence and 13 studies were rated as level III evidence. Excluded were level III evidence, case reports, review articles, letters, editorials, and case series with fewer than 25 eyes. RESULTS: In 9 articles, a best-corrected Snellen visual acuity (BCSVA) of 20/200 or better occurred in 45% to 89% of eyes. Five articles described a BCSVA of 20/50 or better in 43% to 69% of eyes, and 4 articles found a BCSVA of 20/40 or better in 11% to 39% of eyes. Retention rates of the BI-KPro ranged from 65% to 100%. Reasons for loss of vision after BI-KPro implantation most commonly included corneal melts resulting from exposure keratopathy, endophthalmitis, and infectious keratitis or corneal ulceration. The 2 most common complications after surgery were retroprosthetic membrane formation (range, 1.0%-65.0%; mean ± standard deviation [SD], 30.0±19.0%) and elevated intraocular pressure (range, 2.4%-64.0%; mean ± SD, 27.5±18.1%). The 2 most common posterior segment complications were endophthalmitis (range, 0%-12.5%; mean ± SD, 4.6±4.6%) and vitritis (range, 0%-14.5%; mean ± SD, 5.6±4.7%). CONCLUSIONS: The reviewed articles on BI-KPro use suggest that the device improves vision in cases of severe corneal opacification that were not amenable to corneal transplantation using human cadaveric keratoplasty techniques. A number of severe anterior and posterior segment complications can develop as follow-up continues, making ongoing close observation paramount for patients undergoing this surgery. These complications include infection, device extrusion, and permanent vision loss.

Mitomycin C-associated scleral stromalysis after pterygium surgery.

PURPOSE: To describe complications after use of mitomycin C (MMC) as a surgical adjuvant in pterygium surgery. METHODS: This is a retrospective chart review of patients presenting to a tertiary referral center over a 7-year period with a diagnosis of scleral stromalysis after previous pterygium removal. RESULTS: Sixteen eyes of 15 patients were identified with scleral stromalysis after pterygium surgery with the use of adjuvant MMC. Three eyes were excluded because of insufficient chart information or previous beta-irradiation treatment. Twelve of 13 eyes underwent surgical treatment for primary pterygium, and 1 eye was treated for recurrent pterygium. Time from initial pterygium surgery to presentation ranged from 1 month to 10 years. Dosage and routes of MMC administration included 0.02% intraoperative application to either the bare sclera or Tenon capsule with a range of 30 seconds to 3 minutes or topical administration 4 times daily for 2 weeks. In some cases, the dose and route of MMC administration were unknown. Four of 13 patients (31%) required a scleral patch graft with 1 patient (8%) requiring multiple patch grafts. CONCLUSIONS: Use of MMC in various forms and concentrations can cause devastating complications including scleral stromalysis. Scleral stromalysis may present anywhere from months to years after application. We suggest that MMC should be used with extreme caution when used as a surgical adjuvant for pterygium surgery. Patients must be urged to continue long-term follow-up after MMC use because of the potential for future anterior segment complications.

Visual outcome after Descemet's stripping automated endothelial keratoplasty in an 8-month-old with congenital hereditary endothelial dystrophy.

Descemet's stripping automated endothelial keratoplasty (DSAEK) has rapidly become the standard of care for endothelial dysfunction of the cornea in adults. There are few reports of DSAEK in children and infants, mainly because most pediatric corneal opacities are full-thickness and therefore not amenable to lamellar procedures but also because of the unique difficulties of performing this procedure in the youngest patients. We report the case of an 8-month-old girl who underwent DSAEK for congenital hereditary endothelial dystrophy. At 24 months' follow-up, her visual acuity was 20/40 in the operated eye. To our knowledge, this is the first report of an objective visual outcome in a child with DSAEK performed in infancy.

Options and adjuvants in surgery for pterygium: a report by the American Academy of Ophthalmology.

OBJECTIVE: To assess the outcomes and safety of current surgical options and adjuvants in the treatment of primary and recurrent pterygium. METHODS: Literature searches of the PubMed and the Cochrane Library databases were last conducted in January 2011 using keywords and were restricted to randomized controlled trials reporting on surgical intervention for pterygium. The searches were limited to articles published in English and yielded 120 citations. Citation abstracts, and if necessary the full text, were reviewed to identify randomized controlled trials that reported recurrence as an outcome measure and had a mean follow-up of at least 6 months. Fifty-one studies comparing bare sclera excision, conjunctival or limbal autograft, intraoperative mitomycin C, postoperative mitomycin C, and amniotic membrane transplantation for primary and recurrent pterygia fit these inclusion criteria. RESULTS: Four studies demonstrated that the conjunctival or limbal autograft procedure is more efficacious than amniotic membrane placement. Use of conjunctival or limbal autografts or mitomycin C during or after pterygium excision reduced recurrence compared with bare sclera excision alone in most studies of primary or recurrent pterygium. The outcomes of conjunctival or limbal autograft were similar to outcomes for intraoperative mitomycin C in the few studies that directly compared the 2 techniques. There is evidence that increased concentration and duration of exposure to intraoperative mitomycin C is associated with increased efficacy. Of the adjuvants studied, only mitomycin C was associated with vision-threatening complications, including scleral thinning, ulceration, and delayed conjunctival epithelialization; there is some evidence of increasing complications with increased concentration and duration of exposure. There is conflicting evidence as to whether increasing age is protective against recurrence, but the morphologic features of the pterygium were shown to affect the recurrence rate. CONCLUSIONS: Evidence indicates that bare sclera excision of pterygium results in a significantly higher recurrence rate than excision accompanied by use of certain adjuvants. Conjunctival or limbal autograft was superior to amniotic membrane graft surgery in reducing the rate of pterygium recurrence. Among other adjuvants, there is evidence that mitomycin C and conjunctival or limbal autografts reduce the recurrence rate after surgical excision of a pterygium. Furthermore, the data indicate that using a combination of conjunctival or limbal autograft with mitomycin C further reduces the recurrence rate after pterygium excision compared with conjunctival or limbal autograft or mitomycin C alone. Additional studies are necessary to determine the long-term effects, optimal route of administration, and dose and duration of treatment for mitomycin C. Factors such as availability of resources, primary or recurrent status of pterygium, age of patient, and surgeon or patient preference may influence the surgeon's choice of adjuvant because there are insufficient data to recommend a specific adjuvant as superior. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Cystic benign melanosis of the conjunctiva.

PURPOSE: To report the clinical and histologic features of cystic benign melanosis. METHODS: This case series reports on the clinical and histopathologic features of 3 patients with enlarging, cystic, brown, pigmented, conjunctival lesions. RESULTS: Slit-lamp examination showed cystic melanotic lesions of bulbar conjunctiva. Histopathologic examination of the biopsy specimens showed epithelial lined cysts in the substantia propria, goblet cells, and secondary pigmentation of basilar keratinocytes. CONCLUSIONS: Cystic benign melanosis, a unique conjunctival lesion, should be differentiated from cystic nevus and primary acquired melanosis.

Relationship Between Fuchs Endothelial Corneal Dystrophy Severity and Glaucoma and/or Ocular Hypertension.

OBJECTIVE To investigate whether Fuchs endothelial corneal dystrophy (FECD) severity is associated with glaucoma and/or ocular hypertension (G/OHTN). METHODS A subset of eyes (n = 1610) from the FECD Genetics Multi-Center Study were examined to estimate the association between FECD severity (grades 0-6 based on guttae confluence) and G/OHTN. Logistic regression models that accounted for the correlation between eyes and adjusted for age, sex, central corneal thickness, intraocular pressure, presence of diabetes, and time of day of the initial evaluation were fit. RESULTS A total of 107 eyes (6.6%) had G/OHTN based on the study definition. The prevalence of G/OHTN in the control group was 6.0%. The prevalence was lower in index cases with an FECD grade of 1 through 3 and family members with a grade of 0 or 1 through 3 (0.0% and 2.1%, respectively) but higher in index cases and family members with a grade of 4 through 6 (11.2% and 8.5%, respectively). Adjusting for covariates, eyes with a grade of 4 through 6 were more likely to have concurrent G/OHTN than eyes with no FECD (index cases vs controls: odds ratio [OR] = 2.10, P = .04; affected vs unaffected family members: OR = 7.06, P = .07). Age (OR = 1.06 per 1-year increase, P < .001) and intraocular pressure (OR = 1.15 per 1-mm Hg increase, P < .001) were also associated with an increased prevalence of G/OHTN. Sex, diabetes, time of day of evaluation, and central corneal thickness were not associated with the prevalence of G/OHTN (P ≥ .15). CONCLUSIONS Glaucoma and/or ocular hypertension occurs more often in eyes with severe FECD compared with unaffected eyes. Therefore, it may be beneficial to monitor for the development of glaucoma in these patients.

Interface fungal keratitis after endothelial keratoplasty: a clinicopathological report.

The authors report two cases of interface fungal keratitis following Descemet's stripping automated endothelial keratoplasty (DSAEK). Two patients developed culture-proven interface keratitis with Candida albicans and Candida glabrata following DSAEK. Both patients presented with white interface opacities at approximately 1 month after uncomplicated DSAEK. Adjunct confocal microscopy identified fungal elements prior to surgical therapy. A penetrating keratoplasty was performed in both cases after failed medical therapy with fungal elements confirmed by corneal histopathology. Interface fungal keratitis must be recognized as a potential complication of endothelial keratoplasty. Surgeons should consider corneal donor rim cultures on all endothelial keratopathy cases and confocal microscopy on cases with new interface opacities in the early postoperative period. These measures may lead to early identification and treatment of fungal interface infections.

Deep anterior lamellar keratoplasty as an alternative to penetrating keratoplasty a report by the american academy of ophthalmology.

OBJECTIVE: To review the published literature on deep anterior lamellar keratoplasty (DALK) to compare DALK with penetrating keratoplasty (PK) for the outcomes of best spectacle-corrected visual acuity (BSCVA), refractive error, immune graft rejection, and graft survival. METHODS: Searches of the peer-reviewed literature were conducted in the PubMed and the Cochrane Library databases. The searches were limited to citations starting in 1997, and the most recent search was in May 2009. The searches yielded 1024 citations in English-language journals. The abstracts of these articles were reviewed, and 162 articles were selected for possible clinical relevance, of which 55 were determined to be relevant to the assessment objective. RESULTS: Eleven DALK/PK comparative studies (level II and level III evidence) were identified that compared the results of DALK and PK procedures directly; they included 481 DALK eyes and 501 PK eyes. Of those studies reporting vision and refractive data, there was no significant difference in BSCVA between the 2 groups in 9 of the studies. There was no significant difference in spheroequivalent refraction in 6 of the studies, nor was there a significant difference in postoperative astigmatism in 9 of the studies, although the range of astigmatism was often large for both groups. Endothelial cell density (ECD) stabilized within 6 months after surgery in DALK eyes. Endothelial cell density values were higher in the DALK groups in all studies at study completion, and, in general, the ECD differences between DALK and PK groups were significant at all time points at 6 months or longer after surgery for all of the studies reporting data. CONCLUSIONS: On the basis of level II evidence in 1 study and level III evidence in 10 studies, DALK is equivalent to PK for the outcome measure of BSCVA, particularly if the surgical technique yields minimal residual host stromal thickness. There is no advantage to DALK for refractive error outcomes. Although improved graft survival in DALK has yet to be demonstrated, postoperative data indicate that DALK is superior to PK for preservation of ECD. Endothelial immune graft rejection cannot occur after DALK, which may simplify long-term management of DALK eyes compared with PK eyes. As an extraocular procedure, DALK has important theoretic safety advantages, and it is a good option for visual rehabilitation of corneal disease in patients whose endothelium is not compromised.

Retrospective review of graft dislocation rate associated with descemet stripping automated endothelial keratoplasty after primary failed penetrating keratoplasty.

PURPOSE: To report the rate of graft dislocation in patients who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) after a previous penetrating keratoplasty (PKP). METHODS: Institutional review board-approved, multicenter, retrospective chart review. Inclusion criteria included: prior failed PKP and subsequent DSAEK. The primary outcomes measured in this study were the presence of a graft dislocation, rate of rebubble, and graft attachment. Additional variables included: presence of a prior glaucoma drainage device, graft-to-host size disparity, number of sutures remaining in PKP, and stripping of the Descemet membrane at the time of DSAEK surgery. RESULTS: Ninety patients (97 eyes) were included in the study. In 31% (30 of 97), the endothelial graft dislocated after surgery. All 30 cases required a rebubble except 1, which reattached spontaneously. Ninety-eight percent (95 of 97) of all grafts remained attached for the duration of the follow-up period. Only 2 eyes (2.2%) required repeat graft. Endothelial grafts dislocated in 67% of patients with glaucoma draining devices. The dislocation rate for grafts larger than the host was 12 of 49 (24%), equal to the host was 3 of 17 (18%), and smaller than the host was 8 of 19 (42%). Dislocations occurred in 5 of 21 (24%) of grafts with sutures remaining and 22 of 76 (29%) of those with all sutures out. Five of 12 (42%) cases of grafts performed without stripping the Descemet had dislocations. CONCLUSIONS: The graft dislocation rate in DSAEK procedures after PKP is comparable to that after primary DSAEK cases. Donor grafts that are smaller than the host PKP and the presence of prior glaucoma drainage devices are risk factors for higher rates of graft dislocation.

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.