Ocular manifestations of liver disease: an important diagnostic aid.

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Methods: Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main Outcome Measures: Vessel and invasion area of vessels in the corneal graft and host beds. Results: This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P = 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P = 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. Conclusions: In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Zone 1 trauma: wound dehiscence compared to primary trauma.

PURPOSE: The study aims to assess if Zone 1 globe injuries hold a favorable prognosis for all situations, including wound dehiscence, or just primary traumatic injuries. METHODS: Retrospective cross-sectional chart review of patients who underwent open globe repair from 1/1/2019 to 12/1/2020 at an urban hospital setting was evaluated for final visual outcomes, associated ocular pathology, long-term complications, and need for further surgeries. RESULTS: Fifty-eight eyes were identified-38 primary trauma and 20 dehisced wounds (11 penetrating keratoplasties, five clear corneal incisions, one laceration, one extracapsular cataract extraction, one radial keratotomy, and one tectonic graft). Dehisced wounds had more posterior segment pathology vs primary trauma, i.e., hemorrhagic choroidal, vitreous hemorrhage, retinal detachment, choroidal effusion (all 20% vs 2.63%, 5.26%, 5.26%, and 0%, respectively), vitreous prolapse (20% vs 2.63%), and uveal prolapse (80% vs 36.84%). Dehisced wounds had more traumatic aphakia (40% vs 0%) and dislocated lenses (15% vs 0%). Primary trauma was more likely to have traumatic cataracts (55.26% vs 10%) or no lens changes (44.74% vs 25%). About 10% dehisced wounds required enucleation (0% primary trauma). Cataract/secondary intraocular lens surgery was performed in 34% of the primary traumas (10% in dehisced wounds). Primary traumas achieved 20/40 vision or better in 44.74% (10% dehisced wounds). About 7.89% of patients with wound dehiscence ended with no light perception (none in primary trauma). CONCLUSION: Zone 1 open globe injuries due to wound dehiscence may exhibit worse prognosis compared to primary trauma open globe injury. More important than the zone of injury may be the source.

Interspecialty Opioid Prescribing Patterns in Ophthalmology Following Declaration of a Public Health Emergency.

Purpose: Previous literature has investigated opioid prescription trends in ophthalmology at large, however, little has been done looking at differences between subspecialties. We evaluate if significant trends exist among subspecialties in opioid prescribing patterns. This study aims to illuminate potential over-usage of opioids in ophthalmology that could compromise patient quality of life. Methods: Medicare data and "National Plan and Provider Enumeration System (NPPES) Downloadable File" were queried for cases of ophthalmologists with nonsuppressed opioid prescription data from 2014 to 2019. Ophthalmologists with no subspecialty code or missing regional, gender, degree, or graduation information were excluded. Chi-squared analysis, analysis of variance, t-tests, and multivariate logistic regression were utilized. Results: Five thousand one hundred forty-three physician records were included in analysis, 450 of which were by cornea subspecialists. Most cornea cases were male, graduated before 2005, and practiced in the South. All subspecialties had a significantly increased likelihood of making opioid claims and higher prescription rates compared with cornea (P < 0.050) besides glaucoma (P = 0.357). Only oculoplastics had significantly increased likelihood of greater total supply of opioids compared with cornea (odds ratio [OR] = 22.195, 95% confidence interval [CI] = 12.209-40.350, P < 0.001), while pediatrics (OR = 4.036, 95% CI = 1.377-11.831, P = 0.011) and neuro-ophthalmology (OR = 4.158, 95% CI = 1.237-13.975, P = 0.021) in addition to oculoplastics (OR = 64.380, 95% CI = 26.306-157.560, P < 0.001) were predicted to have significantly greater opioid beneficiaries. Males, the South/Midwest, and graduating before 2005, all were generally associated with increased likelihood of greater total opioid claims, supply, beneficiaries, and prescription rate (P < 0.050). Conclusion: Subspecialty, demographic, chronological, and regional trends exist for opioid prescribing patterns in ophthalmology.

Effect of simulated cataract on the accuracy of artificial intelligence in detecting diabetic retinopathy in color fundus photos.

PURPOSE: Artificial intelligence (AI) is often trained on images without ocular co-morbidities, limiting its generalizability. This study aims to evaluate the accuracy of a convolutional neural network (CNN) applied to color fundus photos (CFPs) with simulated cataracts (SCs) in detecting diabetic retinopathy (DR). METHODS: A database of 3662 CFPs (from Asia Pacific Tele-Ophthalmology Society (APTOS) 2019) was used. Using transfer learning, a CNN was trained to classify the training images as either DR or non-DR. The CNN was then applied to classify the testing images after an SC was applied, using varying degrees of Gaussian blur. RESULTS: Accuracy without SC was 97.0%, sensitivity (Sn) 95.7%, specificity (Sp) 98.3%. For mild SC, accuracy was 93.1%, Sn 91.8%, Sp 94.3%. For moderate SC, accuracy was 62.8%, Sn 31.4%, Sp 95.2%. For severe SC, accuracy was 53.5%, Sn 11.8%, Sp 96.5%. CONCLUSION: SCs significantly impaired AI accuracy. To prepare AI for clinical use, cataracts and other real-world clinical challenges affecting image quality must be accounted for.

Long-time irradiation effect on corrosion behavior of aluminum alloy in pool water of low-power research reactor.

This study conducted an evaluation of the corrosion behavior of an aluminum alloy utilized in the Isfahan Miniature Neutron Source Reactor (MNSR). The component analyzed, dry channel (DC), had been exposed to radiation for 12 years in a water environment within the reactor pool since its installation. To determine the effect of radiation on the corrosion of the LT-21 aluminum alloy used in the DC, different parts of the pipe were sampled and various tests were performed. These tests included mechanical strengths (impact, and micro-hardening), XRD, TEM, SEM-EDS, and potentiodynamic polarization (PDP). The parameters measured included corrosion potential, corrosion rate, changes in microscopic structure, and mechanical properties of the aluminum alloy along the entire length of the DC. The neutron and gamma dose distribution along the height of the DC, which was 540 cm, was calculated to determine the correlation between the dose distribution and observed corrosion. The study found that the corrosion mechanisms were complex and resulted from the simultaneous presence of the DC in the pool water and radiation from the reactor core. The observed results are presented and discussed in this study.

Hepatic regenerative response to long-term consumption of cinnamon-rich diet in aged rats.

Objective: The present study aimed to investigate the impact of cinnamon on liver regeneration in a rat model of partial hepatectomy (PH). Materials and Methods: Thirty-two old male Sprague-Dawley rats (12 weeks old) were randomly divided into two equal groups (n=16). One group was fed with a standard diet (control) while the other group was fed with the same diet containing 1% cinnamon for 41 weeks. Then, all animals were subjected to the PH procedure and their livers were studied on postoperative days 2, 10 and 28. The liver contents of hepatic growth factor (HGF), insulin, malondialdehyde (MDA), nitric oxide metabolites (NOx), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) were evaluated. Also, the serum levels of liver function markers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST), MDA, NOx and SOD activity were measured. Results: The regenerated liver weight was significantly higher in cinnamon-treated animals than the controls on both day 10 and 28 post hepatectomy. The hepatic MDA levels in the cinnamon-treated animals were significantly lower than the control rats. Cinnamon led to a significant increase of SOD on day 2 after hepatectomy in serum and liver content. The basal level of HGF in the liver of cinnamon-consuming rats was significantly higher than in the control rats. Hepatic insulin level was significantly increased relative to baseline and control on day 2 in the cinnamon-consuming rats. Hepatic TNF-α levels dramatically decreased on postoperative days (POD) 2 relative to baseline in the control and cinnamon-treated rats. Conclusion: Long-term cinnamon consumption enhanced liver regeneration outcomes in old rats.

Transforming tree topping waste into flooring: a study on the production and evaluation of oriented strand board finish using urban and garden residues.

Oriented strand board (OSB) has become a popular building material for residential construction, but little research has been conducted on its use as a finish floor material. The study investigated the quality and performance of OSB as an alternative to traditional engineered wood products for finish floors. Four types of OSB finish floors using a mixture of garden and urban tree toppings were produced and evaluated, along with different types and levels of resin and mat moisture content. The finish floor panels were subjected to a battery of tests, including concentrated loading, indentation, falling ball impact resistance, abrasion resistance, and surface wettability. The findings showed that urea formaldehyde resin with garden tree toppings performed best in floor surface indentation, abrasion resistance, and falling ball indentation. The phenol formaldehyde resin with garden tree toppings, on the other hand, showed less moisture absorption and swelling during surface wetting tests and better resistance to force application in the concentrated loading test. Our qualitative comparison revealed that OSB finish floor production using 100% garden tree topping strands and 12% urea formaldehyde resin, along with 14% mat moisture content, produced the best results. The study provides valuable insights into the potential use of OSB as a sustainable and cost-effective finish floor material, using waste materials from urban and garden tree toppings.

Antibody-Drug Conjugates and Ocular Toxicity.

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class.

Comparative Analysis of Alternative Calcium Chelators for the Treatment of Calcific Band Keratopathy.

PURPOSE: In this study, we compared clinically relevant biochemical properties of each chelator for pH, osmolarity, and calcium chelation potential. METHODS: In total, 0.2 M K 2 EDTA and K 3 EDTA (BD vacutainer tubes by Becton, Dickinson and Company) and Na 2 EDTA (Sigma Aldrich) solutions were made. The pH of each solution was measured (Mettler Toledo pH meter), and the theoretical osmolarity was calculated. Next, we determined the calcium chelation potential of each EDTA salt by titrating it with 10 µmol of calcium hydroxyapatite or CaCl 2 containing Patton-Reeder colorimetric indicator. Statistical significance was analyzed using analysis of variance. RESULTS: The 0.2 M solutions of Na 2 EDTA, K 2 EDTA, and K 3 EDTA have pH values of 4.43, 5.71, and 9.191 and theoretical osmolarities of 600, 600, and 800 mOsm/L, respectively. Calcium chelation ability was similar among all 3 solutions: 0.94 to 0.98 mol of EDTA was needed to fully chelate 1 mol calcium ions of CaCl 2 ( P = 0.296), 0.100 to 0.108 mol of EDTA for 1 mol calcium ions of the hydroxyapatite aqueous suspension ( P = 0.296), and 0.992 to 0.996 mol for 1 mol calcium ions of hydroxyapatite in acidic solution ( P = 0.178). Compared with the clinical standard of 3% (30 mg/mL) Na 2 EDTA, approximately 3.3% (33 mg/mL) K 2 EDTA and 3.6% (36 mg/mL) K 3 EDTA are needed to chelate an equivalent amount of calcium. CONCLUSIONS: In this article, we provide clinically relevant biochemical properties of 2 alternatives to Na 2 EDTA and demonstrate comparable calcium chelation ability among all 3 solutions. In situations where sterile sources of Na 2 EDTA are unavailable, potassium EDTA may provide a convenient and equally effective method of treatment for band keratopathy.

Vitamin A Deficiency Screening in Patients With Chronic Alcohol-Associated Liver Disease: Implications for Liver Transplant Candidates.

Chronic liver pathologies may lead to vitamin A deficiency (VAD) through impairment of vitamin A absorption, storage, and distribution. VAD can contribute to ocular pathologies, and in the article, we present 2 patients with alcohol-associated cirrhosis admitted for liver transplant presenting with nonhealing central corneal epithelial defects in the eye without other known ocular pathologies. Low serum vitamin A levels were detected in both patients. Vitamin A supplementation eventually helped corneal epithelial healing within days/weeks. We suggest that VAD be screened for in all liver transplant candidates even before ocular symptoms present. This may prevent more severe VAD ocular sequelae.

Female authorship trends and the effect of COVID-19 on cataract and refractive surgery literature.

PURPOSE: To evaluate whether gender barriers persist specifically in the cataract and refractive surgery (CRS) literature. In addition, no literature exists investigating the long-term effect of COVID-19 on female authorship in ophthalmology past 2020. SETTING: Scopus 2015 to 2022. DESIGN: Retrospective data review. METHODS: Articles published in the Journal of Refractive Surgery and the Journal of Cataract & Refractive Surgery were recorded from January 2015 to February 2022 from Scopus. Articles with only 1 author or where gender could not be identified were excluded. The first author (FA) gender, senior author (SA) gender, affiliated country, type of literature, and number of citations were collected. Pearson chi-squared tests with phi coefficients and multivariate logistic regression were performed. RESULTS: 3153 articles were included in analysis. There were 910 works with female FAs and 648 with female SAs. Gender did not predict publishing in one journal over the other (P > .050). Women made up less than 30% of authorship of all types of literature, except for prospective/observational studies as FA (31.3%). Compared with before 2020, female FAs from 2020 onward were associated with increased retrospective analysis (phi = 0.072, P = .030) and letters/editorials (phi = 0.134, P < .001) but decreased case reports (phi = 0.087, P = .009) and "others" (phi = -0.164, P < .001). Similar associations were observed for female SAs. Females were more likely to publish in Asian countries. Female SAs predicted an increased likelihood of female FAs (odds ratio, 1.401, 95% CI, 1.165-1.684, P < .001). CONCLUSIONS: Gender disparities exist in authorship of the CRS literature. COVID-19 has altered the types of literature published by women, but men still publish most of all types of CRS research.

Povidone-Iodine Adverse Effects and Alternatives for Ocular Procedures.

Purpose: Povidone-iodine (PVI), also known as Betadine, is a widely used antiseptic agent used in several fields of medicine. In ophthalmology, it is applied as a preoperative antiseptic to prevent infectious complications that can result from surgical procedures. PVI's safety and efficacy have been extensively studied and represented in the literature; however, the incidence of adverse effects has been reported in conjunction. The aim of this paper is to compile information regarding PVIs use, safety profile, adverse effects, and possible alternatives through a review of the existing literature. Methods: Literature was compiled utilizing the database PubMed and Google Scholar using specified keywords with a total of 86 reviewed articles, after excluding search results that did not meet the inclusion criteria. Results: While the allergic potential to PVI is a highly contested topic, there are several nonallergic adverse effects of PVI that should not be overlooked. These effects include chemical burn, cytotoxic effects, and general patient discomfort. In light of these adverse effects, alternatives to PVI may be considered. However, there has been little research identifying feasible alternatives in preoperative intraocular procedures. Alternatives including chlorhexidine, polyhexamethylene biguanide (polyhexanide), and octenidine were identified as potential substitutes for PVI. Conclusions: Further study is needed to provide robust evidence regarding the efficacy profiles of these alternatives in comparison with PVI and to demonstrate comparable tolerance to PVI in intraocular procedures.

Association between obesity and age-related cataract: an updated systematic review and dose-response meta-analysis of prospective cohort studies.

Objective: There are inconsistent findings on the association between obesity and age-related cataract (ARC). This systematic review was done to summarize available findings on the association between obesity [defined by body mass index (BMI)] and ARC by performing a dose-response meta-analysis on eligible prospective cohort studies. Methods: We performed a systematic search in PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until June 2022 to identify eligible publications. Results: In total, 16 studies with a total sample size of 1,607,125 participants were included. Among all of these studies, there were 103,897 cases of ARC. In the follow-up periods ranging between 4 and 28 years, 4,870 cases of nuclear cataract, 1,611 cases of cortical cataract, and 1,603 cases of posterior subcapsular cataracts (PSC) were detected. By comparing the highest and lowest categories of BMI, we found that higher BMI was associated with an increased risk of ARC (RR: 1.18, 95% CI: 1.09-1.28) and PSC (RR: 1.44, 95% CI: 1.08-1.90). In the dose-response analysis, each 5 kg/m2 increase in BMI was associated with a 6 and 27% increased risk of ARC (RR: 1.06, 95% CI: 1.01-1.12) and PSC (RR: 1.27, 95% CI: 1.14-1.41), respectively. In addition, we found a positive association for cortical cataract among high-quality studies, in which higher BMI was associated with a 20% increased risk of cortical cataract (RR: 1.20, 95% CI: 1.02-1.42). In terms of nuclear cataract, we found no significant association either in the comparison between the highest and lowest categories of BMI or in the dose-response meta-analysis. Conclusion: Obesity (defined by BMI) was associated with an increased risk of ARC, PSC, and cortical cataract in adults. However, such a positive association was not seen for nuclear cataract. PROSPERO registration: CRD42022357132.

Updates in diagnostics, treatments, and correlations between oral and ocular manifestations of Sjogren's syndrome.

Sjogren's syndrome (SS) is characterized as an autoimmune disorder targeting secretory glands, including the lacrimal and salivary glands, causing dry eye and dry mouth predominantly in women over the age of 40. In this review, we summarize recent advancements in SS diagnostics, treatments, and our understanding of correlations between oral and ocular manifestations of SS. Google Scholar and PubMed databases were utilized to search peer-reviewed papers since 2016 on SS diagnosis, treatment, and correlations between oral and ocular manifestations. For diagnostics, we discuss the updated SS classification criteria by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR), new biomarkers, and compare studies of current diagnostic methods with alternative technologies. For treatments, we discuss topical, systemic, and surgical treatment developments in the management of oral and ocular symptoms of SS as there is still no cure for the disorder. Finally, we report studies that directly suggest correlations between the ocular surface disease and oral disease in SS, as well as shared abnormalities in the microbiome and cytokine expression that may be correlated. We conclude by stating limitations to our review as well as paths moving forward. Elucidating correlations between oral and ocular manifestations may be the key to furthering our understanding of SS pathogenesis as well as defining new standards for diagnosis and treatment.

Semi-experimental assessment of neutron equivalent dose and secondary cancer risk for off-field organs in glioma patients undergoing 18-MV radiotherapy.

Neutron contamination as a source of out-of-field dose in radiotherapy is still of concern. High-energy treatment photons have the potential to overcome the binding energy of neutrons inside the nuclei. Fast neutrons emitting from the accelerator head can directly reach the patient's bed. Considering that modern radiotherapy techniques can increase patient survival, concerns about unwanted doses and the lifetime risk of fatal cancer remain strong or even more prominent, especially in young adult patients. The current study addressed these concerns by quantifying the dose and risk of fatal cancer due to photo-neutrons for glioma patients undergoing 18-MV radiotherapy. In this study, an NRD model rem-meter detector was used to measure neutron ambient dose equivalent, H*(10), at the patient table. Then, the neutron equivalent dose received by each organ was estimated concerning the depth of each organ and by applying depth dose corrections to the measured H*(10). Finally, the effective dose and risk of secondary cancer were determined using NCRP 116 coefficients. Evidence revealed that among all organs, the breast (0.62 mSv/Gy) and gonads (0.58 mSv/Gy) are at risk of photoneutrons more than the other organs in such treatments. The neutron effective dose in the 18-MV conventional radiotherapy of the brain was 13.36 mSv. Among all organs, gonads (6.96 mSv), thyroid (1.86 mSv), and breasts (1.86 mSv) had more contribution to the effective dose, respectively. The total secondary cancer risk was estimated as 281.4 cases (per 1 million persons). The highest risk was related to the breast and gonads with 74.4 and, 34.8 cases per 1 million persons, respectively. Therefore, it is recommended that to prevent late complications (secondary cancer and genetic effects), these organs should be shielded from photoneutrons. This procedure not only improves the quality of the patient's personal life but also the healthy childbearing in the community.

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial.

PURPOSE: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. DESIGN: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. PARTICIPANTS: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. METHODS: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. MAIN OUTCOME MEASURE: The 52-week endothelial immune rejection rate. RESULTS: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis. CONCLUSIONS: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.