Safety and Efficacy of Epithelium-Off Corneal Collagen Cross-Linking for the Treatment of Corneal Ectasia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia. METHODS: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies. RESULTS: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare. CONCLUSIONS: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk Factors for Fibrous Ingrowth in Eyes Requiring Primary Keratoplasty.

PURPOSE: The aim of this study was to define risks for corneal transplantation associated with fibrous ingrowth among first-time transplant recipients. METHODS: We performed a retrospective case-control study of patients with a histopathologic diagnosis of fibrous ingrowth between 2002 and 2019. Patients with fibrous ingrowth from a first corneal specimen were included. Those with incomplete records were excluded. A 1:2 case-control ratio was used. Controls were matched using surgical indication, surgery year, transplantation method, sex, and age. RESULTS: Seventy-eight eyes (76 patients) were included and matched with 160 control eyes. The incidence of fibrous ingrowth found on a first corneal transplant was 0.6% per year. The most common keratoplasty indications were pseudophakic corneal edema (n = 25, 32%) and aphakic corneal edema (n = 15, 19%). Cases were more likely to have a history of ocular trauma (odds ratio [OR], 2.94; 95% CI, 1.30-6.30; P = 0.007), uveitis (OR, 2.73; 95% CI, 1.12-6.63; P = 0.022), retinal detachment or previous retinal surgery (OR, 2.40; 95% CI, 1.34-4.30; P = 0.003), glaucoma tube-shunt surgery (OR, 2.70; 95% CI, 1.29-5.65; P = 0.007), aphakia (OR, 3.02; 95% CI, 1.61-5.67; P = 0.0004), or iris derangement (OR, 10.52; 95% CI, 5.45-20.30; P <0.0001). A multivariate logistic regression model using iris derangement, history of ocular trauma, history of uveitis, and history of cataract surgery demonstrated 81% sensitivity and 66% specificity in predicting presence of fibrous ingrowth. CONCLUSIONS: A history of ocular trauma, uveitis, retinal detachment or previous retinal surgery, glaucoma tube-shunt surgery, aphakia, and iris derangement are risks for detecting fibrous ingrowth among first-time keratoplasty recipients. Patients with these conditions should be monitored closely for corneal decompensation.

Disease Endotypes Predict the Severity of Mucous Membrane Pemphigoid.

Mucous membrane pemphigoid is an autoimmune disease with variable clinical presentation and multiple autoantigens. To determine whether disease endotypes could be identified on the basis of the pattern of serum reactivity, the clinical and diagnostic information of 70 patients with mucous membrane pemphigoid was collected, and reactivity to dermal or epidermal antigens, using indirect immunofluorescence, and specific reactivity to bullous pemphigoid (BP) autoantigens BP180 and BP230, collagen VII, and laminin 332 were evaluated. Most patients had lesions at multiple mucosae, with the most prevalent being oropharyngeal (mouth, gingiva, pharynx; 98.6%), followed by ocular (38.6%), nasal (32.9%), genital or anal (31.4%), laryngeal (20%), and esophageal (2.9%) sites and skin (45.7%). Autoantigen profiling identified BP180 (71%) as the most common autoantigen, followed by laminin 332 (21.7%), collagen VII (13%), and BP230 IgG (11.6%). Reactivity to dermal antigens predicted a more severe disease characterized by a higher number of total sites involved, especially high-risk sites, and a decreased response to rituximab. In most cases, identification of dermal indirect immunofluorescence reactivity is an accurate predictor of disease course; however, confirmation of laminin 332 reactivity is important, with dermal indirect immunofluorescence positivity because of an increased risk of solid tumors. In addition, the ocular mucosae should be monitored in patients with IgA on direct immunofluorescence.

Metabolic and proteomic indications of diabetes progression in human aqueous humor.

Diabetes mellitus is a multiorgan systemic disease impacting numerous ocular structures that results in significant ocular morbidity and often results in more frequent corneal and glaucoma surgeries for affected individuals. We hypothesize that the systemic metabolic and proteomic derangement observed in the progression of diabetes influences the composition of the aqueous humor (AH), which ultimately impacts the anterior segment health of the eye. To identify changes associated with diabetes progression, we mapped the metabolite profile and proteome of AH samples from patients with varying severities of type II diabetes (T2DM). Patients were classified as nondiabetic (ND or control), non-insulin-dependent diabetic without advanced features of disease (NAD-ni), insulin-dependent diabetic without advanced features (NAD-i), or diabetic with advanced features (AD). AH samples collected from the anterior chamber during elective ophthalmic surgery were evaluated for metabolite and protein expression changes associated with diabetic severity via gas chromatography/mass spectrometry and ultra-high performance liquid chromatography tandem mass spectrometry, respectively. Metabolic and proteomic pathway analyses were conducted utilizing MetaboAnalyst 4.0 and Ingenuity Pathway Analysis. A total of 14 control, 12 NAD-ni, 4 NAD-I, and 14 AD samples were included for analysis. Elevated levels of several branched amino acids (e.g., valine, leucine, isoleucine), and lipid metabolites (e.g., palmitate) were found only with increasing diabetic severity (i.e., the AD group). Similar proteomic trends were noted in amino acid and fatty acid metabolism and the unfolded protein/stress response. These results represent the first report of both metabolomic and proteomic evaluation of aqueous humor. Diabetes results in metabolic and proteomic perturbations detectable in the AH, and unique changes become manifest as T2DM severity worsens. Changes in AH composition may serve as an indicator of disease severity, risk assessment of anterior segment cells and structures, and potential future therapies.

Solubilized ubiquinol for preserving corneal function.

Defective cellular metabolism, impaired mitochondrial function, and increased cell death are major problems that adversely affect donor tissues during hypothermic preservation prior to transplantation. These problems are thought to arise from accumulated reactive oxygen species (ROS) inside cells. Oxidative stress acting on the cells of organs and tissues preserved in hypothermic conditions before surgery, as is the case for cornea transplantation, is thought to be a major reason behind cell death prior to surgery and decreased graft survival after transplantation. We have recently discovered that ubiquinol - the reduced and active form of coenzyme Q10 and a powerful antioxidant - significantly enhances mitochondrial function and reduces apoptosis in human donor corneal endothelial cells. However, ubiquinol is highly lipophilic, underscoring the need for an aqueous-based formulation of this molecule. Herein, we report a highly dispersible and stable formulation comprising a complex of ubiquinol and gamma cyclodextrin (γ-CD) for use in aqueous-phase ophthalmic products. Docking studies showed that γ-CD has the strongest binding affinity with ubiquinol compared to α- or ß-CD. Complexed ubiquinol showed significantly higher stability compared to free ubiquinol in different aqueous ophthalmic products including Optisol-GS® corneal storage medium, balanced salt solution for intraocular irrigation, and topical Refresh® artificial tear eye drops. Greater ROS scavenging activity was noted in a cell model with high basal metabolism and ROS generation (A549) and in HCEC-B4G12 human corneal endothelial cells after treatment with ubiquinol/γ-CD compared to free ubiquinol. Furthermore, complexed ubiquinol was more effective at lowering ROS, and at far lower concentrations, compared to free ubiquinol. Complexed ubiquinol inhibited lipid peroxidation and protected HCEC-B4G12 cells against erastin-induced ferroptosis. No evidence of cellular toxicity was detected in HCEC-B4G12 cells after treatment with complexed ubiquinol. Using a vertical diffusion system, a topically applied inclusion complex of γ-CD and a lipophilic dye (coumarin-6) demonstrated transcorneal penetrance in porcine corneas and the capacity for the γ-CD vehicle to deliver drug to the corneal endothelium. Using the same model, topically applied ubiquinol/γ-CD complex penetrated the entire thickness of human donor corneas with markedly greater ubiquinol retention in the endothelium compared to free ubiquinol. Lastly, the penetrance of ubiquinol/γ-CD complex was assayed using human donor corneas preserved for 7 days in Optisol-GS® per standard industry practices, and demonstrated higher amounts of ubiquinol retained in the corneal endothelium compared to free ubiquinol. In summary, ubiquinol complexed with γ-CD is a highly stable composition that can be incorporated into a variety of aqueous-phase products for ophthalmic use including donor corneal storage media and topical eye drops to scavenge ROS and protect corneal endothelial cells against oxidative damage.

Mitophagy: An Emerging Target in Ocular Pathology.

Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases. In this article, we review mitochondrial homeostasis in detail, focusing on the balance of mitochondrial dynamics including the processes of fission and fusion, and provide a description of the mechanisms involved in mitophagy. Furthermore, this article reviews investigations of ocular diseases with impaired mitophagy, including Fuchs endothelial corneal dystrophy, primary open-angle glaucoma, diabetic retinopathy, and age-related macular degeneration, as well as several primary mitochondrial diseases with ocular phenotypes that display impaired mitophagy, including mitochondrial encephalopathy lactic acidosis stroke, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. The results of various studies using cell culture, animal, and human tissue models are presented and reflect a growing awareness of mitophagy impairment as an important feature of ophthalmic disease pathology. As this review indicates, it is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction.

Optimizing Visualization of Descemet Membrane Endothelial Keratoplasty Tissue: Assessing the Impact of Trypan Blue Exposure on Stain Duration and Corneal Endothelial Cell Function.

PURPOSE: To assess how trypan blue staining affects Descemet membrane endothelial keratoplasty (DMEK) graft visibility and corneal endothelial cell (CEC) mitochondrial respiration. METHODS: DMEK grafts (n = 20) were stained with trypan blue 0.06% for 1, 3, 5, or 10 minutes. Each graft was injected into an artificial anterior chamber. Surgery was simulated with tapping and sweeping motions on the corneal surface and injections of balanced salt solution (BSS). Graft visibility was assessed at 5, 10, 20, and 30 minutes. Effects of trypan blue on mitochondrial respiration were assessed using primary CECs cultured from donor corneas (n = 43). Treatment wells exposed to trypan blue 0.06% (1, 5, or 30 minutes) and donor-matched control wells to methylene blue 1% (1 minute) or BSS (1, 5, or 30 minutes) were assayed for key respiration parameters. RESULTS: After 5 minutes of surgical manipulation, grafts stained for 5 minutes were significantly more visible than grafts stained for 1 or 3 minutes; there was no added benefit of staining for 10 minutes. After 10 minutes of surgical manipulation, grafts stained for 3 minutes were more visible than grafts stained for 1 minute, without additional benefits of staining ≥5 minutes. No visibility differences were observed after ≥20 minutes of surgical manipulation. CEC mitochondrial respiration did not change significantly following trypan blue exposure for all intervals tested compared to BSS. CONCLUSIONS: Staining DMEK grafts with trypan blue for 3 to 5 minutes optimizes visibility during surgical manipulation without mitochondrial impairment. Corneal surgeons learning DMEK will benefit from optimizing this critical step.

Intraoperative fibrin formation during Descemet membrane endothelial keratoplasty.

PURPOSE: To describe Descemet membrane endothelial keratoplasty (DMEK) cases complicated by spontaneous intraoperative fibrin formation. METHODS: DMEK surgeries performed at two centers using a standardized technique were reviewed retrospectively for the occurrence of intraoperative fibrin formation. Cases were assessed for recipient medical history, donor age, best spectacle-corrected visual acuity (BSCVA), intraoperative unscrolling time, 6-month endothelial cell loss (ECL), and the course of the mate donor cornea. RESULTS: In this review of 868 cases of standardized DMEK surgery with surgical peripheral iridotomy, 32 eyes of 29 patients (3.7%) were complicated by the formation of intraoperative fibrin formation, including 3 patients that developed fibrin in both eyes. Three of the 32 grafts failed (9.4%). None of the mate corneas transplanted (n = 27) developed complications related to fibrin. The donor age ranged from 51 to 75 years and recipient age ranged from 49 to 82 years (median, 66 years). Unscrolling time ranged from 1 to 105 min (median, 15 min). Nine eyes required one rebubble procedure. No eyes had vision-limiting comorbidities, and the 6-month BSCVA was ≥20/40 in all eyes. Six-month ECL ranged from 19% to 73% (median, 44%). CONCLUSIONS: We conclude that fibrin formation during DMEK surgery is an uncommon but important complication that can make graft manipulation more difficult, and may have deleterious effects on endothelial cell density and graft survival.

Transcorneal Cryotherapy and Descemet Membrane Endothelial Keratoplasty to Treat Epithelial Downgrowth and Corneal Decompensation After Cataract Surgery.

PURPOSE: Epithelial downgrowth is a vision-threatening complication of intraocular surgery or penetrating ocular trauma, and although various therapeutic interventions have been performed to treat this disease, success has been limited. We present a case of corneal decompensation secondary to epithelial downgrowth after uncomplicated clear corneal cataract surgery in the left eye, treated successfully with sequential transcorneal cryotherapy to destroy epithelial cell nests followed by Descemet membrane endothelial keratoplasty (DMEK) to restore corneal clarity and vision. METHODS: We applied a transcorneal cryotherapy probe using a double freeze-thaw technique at -80°C to the entire cornea, with care taken to spare the limbus except at the superior temporal quadrant overlying the clear corneal incision where treatment was applied intentionally. The same procedure was performed 2 weeks later to ensure complete ablation of epithelial nest cells. Uncomplicated DMEK surgery using standard technique was performed 1 week later to restore corneal clarity. RESULTS: Visual acuity at presentation was 20/40. Endothelial cell densities were 2138 cells/mm (22% loss) and 1720 cells/mm (37% loss) at 3- and 12-months after DMEK, respectively. Two years after surgery, the best-corrected visual acuity remained 20/20 and the patient had no evidence of recurrence or limbal stem cell deficiency. CONCLUSIONS: The use of sequential cryotherapy as a targeted intervention to destroy invasive corneal epithelial cells followed by staged DMEK surgery to replace damaged corneal endothelium was, in this case, an effective treatment for endothelial decompensation secondary to epithelial downgrowth and may be a potential alternative for the management of this disease.

The effects of diabetes mellitus on the corneal endothelium: A review.

The corneal endothelium plays a critical role in maintaining corneal clarity. There is an expected decline in cell density with age and disease, and maintaining the health of this cell layer is important as corneal endothelial cells generally are amitotic in vivo. Diabetes mellitus is a highly prevalent disease that damages the corneal endothelium. Diabetes causes structural and functional impairments in the corneal endothelium that decrease cellular reserve in response to stress. These effects have implications to consider for diabetic patients undergoing anterior segment surgery, and for corneal surgeons who use diabetic donor tissue and treat diabetic patients. In this review, we discuss the specifics of how diabetes mellitus impacts the corneal endothelium including alterations in cell morphology, cell density, ultrastructure, pump and barrier function, cataract surgery outcomes, and corneal transplant outcomes with attention to the use of diabetic donor tissue and diabetic transplant recipients.

Evaluation of interferon alpha 2b as adjunctive therapy for conjunctival melanoma.

PURPOSE: Interferon alpha 2b (IFN-α2b) has been used as an adjunctive agent to treat conjunctival melanoma (CM), however its efficacy is unproved due to a paucity of data. We present 5 cases of incompletely excised CM lesions to inform clinical decision making regarding the adjunctive use of IFN-α2b. OBSERVATIONS: We identified all biopsy proven CM cases treated between 1997 and 2017 at the University of Iowa. Of these, we analyzed cases in which topical IFN-α2b drops were prescribed after the initial excision to treat surgical margins that were positive for primary acquired melanosis [PAM] with or without atypia or invasive CM. We noted the origin of CM (nevus, PAM, or de novo), presence and location of margins positive for residual melanoma, duration of IFN-α2b treatment, recurrences, time to recurrence, and outcome at last follow-up. Topical IFN-α2b drops (1 million IU/mL 4 times daily for 3-6 months) were used as adjunctive therapy in 5 cases following incomplete surgical excision of CM. The preceding lesion was PAM in 4 cases and compound nevus in 1 case. In 2 cases, margins were positive for PAM with atypia and both resulted in remission of melanoma at 54 and 33 months, respectively. However, in 3 cases, margins were positive for invasive melanoma and all 3 developed recurrence of melanoma despite IFN-α2b use. CONCLUSIONS AND IMPORTANCE: There are limited data regarding the efficacy of IFN-α2b as adjunctive therapy for incomplete excision of CM lesions. In this series, adjunctive topical IFN-α2b did not prevent recurrence in cases with surgical margins positive for invasive melanoma. Our results indicate that caution should be exercised when considering adjunctive IFN-α2b to treat CM lesions not excised completely.

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 for corneal decompensation due to iridoschisis.

PURPOSE: To report a case of bilateral iridoschisis with cataracts and corneal decompensation in a patient who underwent cataract extraction and superficial iridectomy followed by Descemet membrane endothelial keratoplasty (DMEK). OBSERVATIONS: A 58-year-old man with previously diagnosed iridoschisis, cataracts, and diabetes mellitus experienced progressive vision loss bilaterally due to corneal decompensation. Slit lamp examination revealed iridoschisis with iris fibrils contacting the corneal endothelium, stromal edema, and mild guttate changes bilaterally. Corneal findings were more severe in the right eye, including the presence of bullous keratopathy at the time of presentation. Cataract extraction with intraocular lens implantation and superficial iridectomy were performed in the right eye, followed by DMEK. These same procedures were performed subsequently in the left eye. Postoperatively, the patient had significant improvement in visual acuity and corneal edema. CONCLUSIONS AND IMPORTANCE: DMEK can be performed safely and successfully after staged cataract surgery with superficial iridectomy in eyes with endothelial decompensation caused by iridoschisis.

Glaucoma-associated corneal endothelial cell damage: A review.

The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function, but preservation of these cells is paramount as they have limited regenerative capacity. Glaucoma is a prevalent disease, and damage to the corneal endothelium may be caused by the disease process itself as well as by its treatment. The mechanisms involved in glaucoma-associated damage to the corneal endothelium need further investigation. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity and visual acuity in all glaucoma patients, including those undergoing corneal transplant. We will discuss a range of identified factors that may impact corneal endothelial cell health in glaucoma, including intraocular pressure, glaucoma medications, surgical glaucoma management, mechanical forces, and alterations in the aqueous environment.

Scleral Contact Lenses in an Academic Oculoplastics Clinic: Epidemiology and Emerging Considerations.

PURPOSE: To describe the role and efficacy of scleral contact lenses (SCLs) in the treatment of progressive keratopathy in patients who have undergone periocular surgical procedures, to investigate the financial impact of these surgical interventions, and to demonstrate the role of oculoplastic surgery in improving scleral contact lens fit. METHODS: A retrospective medical record review was performed to identify patients who both received SCLs and were examined by the oculoplastics service at the University of Iowa between January 1990 and December 2015. Inclusion criteria also required a minimum of 12 months of patient follow up after being fit with a SCL. The indication for SCL use, as well as clinical outcomes and cumulative relative value units (RVUs) of prior oculoplastic treatments and SCL therapy were recorded for each patient. RESULTS: Six hundred and fifty-nine patients were fitted with SCLs at the authors' institution during the 25-year study period, 43 of whom were examined by the oculoplastics service for reasons related to their SCL. Patients who were fitted for SCLs before (27 patients) or after (16 patients) evaluation in the oculoplastics clinic presented with a variety of corneal and periocular pathology. Corneal indications for SCLs in patients seen secondarily in the oculoplastics clinic included decreased corneal sensation (from CN V palsy or neurotrophic keratopathy), decreased corneal healing from limbal stem cell deficiency, exposure keratopathy, and keratoconjunctivitis sicca secondary to Sjogren's syndrome or orbital radiation. Indications for oculoplastic clinic evaluation in current scleral lens patients included lagophthalmos, trichiasis, epiphora, cicatricial changes in the eyelids or fornices, and eyelid or eyebrow malposition affecting SCL centration. In all 27 patients, surgical intervention resulted in improved SCL centration. Sixteen patients (5 with CN VII palsy, 4 with CN V and CN VII palsy, 4 with neurotrophic keratitis, and 3 with cicatricial entropion) had progressive corneal decompensation despite primary oculoplastics procedures to protect the cornea and ultimately benefitted from SCL treatment secondarily. Fourteen of these 16 patients demonstrated an improved visual acuity of 1 line or more using SCLs. Procedures performed before referral for SCLs included tarsorrhaphies, gold weights, ectropion repair with lateral tarsal strip, retraction repair with spacer grafts, full-thickness skin grafts, cheek lifts, and punctal occlusion. The total RVUs of these procedures performed per patient were tabulated. The RVU range was 10.47-33.96 with an average of 19.5 RVUs (standard deviation = 9.4 RVUs) per patient. CONCLUSIONS: Scleral contact lenses may offer a useful alternative to stabilize the ocular surface, improve vision, and minimize the financial impact and morbidity of multiple periocular procedures in select patients with progressive keratopathy of varying etiologies. The therapeutic indications and utilization of SCLs are likely to increase in oculoplastic practices with optometric support, particularly in academic settings. Surgical correction of eyelid and eyebrow malposition, as well as epiphora, may also be useful adjunctive procedures to optimize SCL fit.

Incidence of Cystoid Macular Edema After Descemet Membrane Endothelial Keratoplasty as a Staged and Solitary Procedure.

PURPOSE: To compare the incidence of visually significant postoperative cystoid macular edema (CME) in pseudophakic eyes after Descemet membrane endothelial keratoplasty (DMEK) performed after recent versus remote cataract surgery. METHODS: A retrospective chart review was performed of all consecutive eyes that underwent DMEK without concurrent cataract surgery at the University of Iowa between October 2012 and December 2014. The DMEK procedures were classified as staged if performed between 2 weeks and 6 months after cataract surgery and solitary if performed more than 6 months after cataract surgery. Possible confounders, including a history of diabetes in the recipient, were tracked. Macular optical coherence tomography was performed to detect CME 1 month after DMEK if the best-corrected visual acuity was ≤20/30 with a clear cornea with no other reason for visual compromise. RESULTS: A total of 173 eyes from 140 patients were included in the statistical analysis. Staged DMEK was performed in 88 eyes (50.8%) and solitary DMEK in 85 eyes (49.2%). The incidence of CME was 8.0% (7 of 88 eyes) in the staged DMEK group and 7.1% (6 of 85 eyes) in the solitary DMEK group (P = 0.823). The incidence of CME did not differ significantly between the staged and solitary DMEK groups regardless of the recipient diabetic status. All cases of CME resolved within 6 months on topical therapy. CONCLUSIONS: The incidence of postoperative CME after DMEK is similar in the setting of recent or remote cataract surgery.

Boston type 1 keratoprosthesis for primary congenital glaucoma.

BACKGROUND/AIMS: To evaluate the Boston type 1 keratoprosthesis (KPro-1) in treatment of eyes with primary congenital glaucoma. METHODS: A retrospective review was performed of every eye with congenital glaucoma that was treated with a KPro-1 at a tertiary eye care centre between 1 January 2008 and 1 July 2014. The main outcome measures were visual outcome, prosthesis retention and postoperative complications. RESULTS: Six eyes of six patients met the inclusion criteria. This included two paediatric patients, aged 6 months and 6 years, and four adults who were 27-33 years of age. Preoperatively, the best corrected visual acuity (BCVA) was worse than 20/400 in every eye. Three eyes had hand motions and one eye had light perception vision. After a mean follow-up period of 31 months (range 16-51 months), three eyes (50.0%) had a BCVA that was ≥20/400. Overall, the BCVA improved in four eyes (66.7%), and remained the same in two eyes (33.3%). The device was retained in six eyes (83.3%). One or more complications occurred in five eyes (83.3%) and included sterile corneal ulceration (three eyes), retroprosthetic membrane formation (three eyes), progressive glaucomatous optic neuropathy (two eyes), device extrusion (one eye) and an epiretinal membrane (one eye). CONCLUSIONS: The Boston KPro-1 has an excellent prognosis for retention in eyes with congenital glaucoma. The visual prognosis remains guarded due to the high prevalence of pre-existing ocular comorbidity and the common occurrence of sight-threatening postoperative complications.

Boston Type 1 Keratoprosthesis for Iridocorneal Endothelial Syndromes.

PURPOSE: To evaluate the outcome of the Boston type 1 keratoprosthesis (KPro-1) in eyes with iridocorneal endothelial syndromes and failed keratoplasties. METHODS: A retrospective review was performed of every eye with a history of iridocorneal endothelial syndrome and a failed corneal transplant that was treated with a KPro-1 at a tertiary eye care center between January 1, 2008, and July 1, 2014. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications. RESULTS: Four eyes met the inclusion criteria. Two eyes had essential iris atrophy and 2 eyes had Chandler syndrome. All 4 eyes had failed corneal transplants and successful glaucoma drainage devices. The mean patient age at the time of KPro-1 surgery was 68.3 years (range, 60-80 years). The mean postoperative follow-up duration was 47 months (range, 27-69 months). Preoperatively, the best-corrected visual acuity (BCVA) was worse than 20/200 in all 4 eyes, including 2 eyes that had hand motions vision. After KPro-1, all 4 eyes initially obtained a BCVA of ≥20/70. At the most recent examination, the BCVA was still ≥20/100 in 3 eyes. The KPro-1 device was retained in all 4 eyes. Postoperative complications included glaucoma progression (1 eye), a retroprosthetic membrane (1 eye), and sterile vitritis (1 eye). CONCLUSIONS: The Boston KPro-1 may offer a better prognosis than repeat traditional keratoplasty in reestablishing corneal clarity in eyes with iridocorneal endothelial syndromes. Despite anatomic success, visual rehabilitation may be compromised by preexisting glaucomatous optic neuropathy and its postoperative progression.