Corneal Transplant Rejection Postvaccination Among Medicare Beneficiaries.

PURPOSE: The purpose of this study was to describe the incidence of corneal graft rejection after COVID and influenza vaccination. METHODS: Patients 65 years or older undergoing penetrating keratoplasty or endothelial keratoplasty any time between 2016 and 2021 followed by COVID or influenza vaccination in 2021 among the 100% Medicare Fee-For-Service database were included. Demographic and ocular history characteristics of patients with (cases) and without graft rejection (controls) were compared using the χ2 test. RESULTS: After COVID (n = 31,398) and influenza (n = 24,290) vaccination, 0.45% (n = 140) and 0.17% (n = 41) patients developed rejection within 90 days, respectively. There was no difference in the rate of graft rejection within 90 days relative to 90 to 180 days after vaccination after both COVID (90 days: 0.45% vs. 180 days: 0.61%, P = 0.37) and influenza (90 days: 0.17% vs. 180 days: 0.29%, P = 0.11) vaccines. For COVID vaccination, patients who underwent penetrating keratoplasty (n = 51, 0.97%; vs. endothelial keratoplasty = 89; 0.34%, P < 0.001), history of rejection up to 1 year before vaccination (n = 13; 1.30% vs. no history = 127, 0.42%; P < 0.001), and having an ocular comorbidity (n = 110, 0.54% vs. no ocular comorbidity = 30, 0.27%; P = 0.001) had higher rates of graft rejections, and most rejections were after 1 year postkeratoplasty (87.14%, n = 122). CONCLUSIONS: The incidence of graft rejection postvaccination is low compared with the overall rates of rejection in the published literature. Most post-COVID vaccination graft rejections were after 1 year postkeratoplasty when corticosteroids are expected to have been tapered to lower doses. Surgeons may counsel patients regarding graft rejection symptoms, but overall low rates may not warrant pretreatment in low-risk keratoplasty patients.

Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study.

PURPOSE: The Zoster Eye Disease Study (ZEDS) is the first randomized clinical trial to study the efficacy of long-term (1 year) suppressive valacyclovir treatment on herpes zoster ophthalmicus (HZO) outcomes. This article details the baseline characteristics of participants. SETTING: The study was set at 95 participating clinical centers in 33 states, Canada, and New Zealand. STUDY POPULATION: Immunocompetent adults with a history of a characteristic HZO unilateral rash and documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, or iritis within the preceding year, enrolled in ZEDS from November 2017 to January 2023. INTERVENTION: Participants were randomized to double-masked oral valacyclovir 1 gm daily versus placebo for 1 year of treatment and followed for 18 months. RESULTS: Five hundred twenty-seven participants were enrolled across 4 strata according to age at HZO onset (younger or older than 60 years) and duration of HZO at enrollment (less or greater than 6 months), with an even distribution of men and women and a median age of 60 years. More participants with recent (57%, 300/527) than chronic HZO and younger than 60 years at HZO onset (54%, 286/527) were enrolled. Most participants were treated acutely with a recommended antiviral regimen (91%, 480/527) and had not been vaccinated against zoster (79%, 418/527). CONCLUSIONS: The broad ZEDS study population enhances the likelihood that ZEDS will provide generalizable high-quality evidence regarding the efficacy and safety of suppressive valacyclovir for HZO immunocompetent adults and whether it should become standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03134196.

Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1): outcome masked, placebo-controlled trial comparing two types of corneal transplant surgeries and effect of rho kinase inhibitors on endothelial cell loss protocol.

BACKGROUND: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial. METHODS: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness. RESULTS: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods. CONCLUSION: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

Prevalence and Economic Burden of Fuchs Endothelial Corneal Dystrophy in the Medicare Population in the United States.

PURPOSE: The aim of this study was to assess the prevalence and economic burden of Fuchs endothelial corneal dystrophy (FECD) in patients older than 65 years in the United States. METHODS: A retrospective analysis of the Medicare data reported to the Vision and Eye Health Surveillance System including patients diagnosed with FECD between 2014 and 2019 was performed. The crude prevalence rate of FECD was assessed and extrapolated to estimate the total case burden in the United States. The prevalence data were further compared between men and women and different racial groups. In addition, the economic burden was computed using inflation-adjusted direct costs of treatment to patients. RESULTS: The Medicare database included 25,432,700 patients older than 65 years. The national prevalence of FECD in this population cohort was calculated to be 1.12% in 2019. In 2019, FECD case burden in Medicare patients older than 65 years was 284,846 and total estimated FECD case count in the country in this age group was 591,226. FECD prevalence was significantly higher in women as compared to men during the 6-year period evaluated in this study. The intergroup comparison revealed that FECD prevalence in the White population was significantly higher than all other racial groups (P < 0.0001). The total inflation-adjusted economic burden of FECD in the United States in 2019 was USD 291.648 million and has increased from USD 243.998 million over the 6-year study period. CONCLUSIONS: The estimated prevalence of FECD in the individuals older than 65 years is 1.12% in the United States. FECD prevalence is significantly higher in women and White population compared with other ethnicities.

Differences in minimal disease knowledge of keratoconus patients: results from an international survey.

BACKGROUND/AIMS: The objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition. METHODS: We recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of 'minimal keratoconus knowledge' (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient. RESULTS: Our findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score. CONCLUSIONS: Our study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus.

Trends and Surgeon Variations in Early Regrafts After Endothelial Keratoplasty: Analysis of the National Medicare Data Set.

PURPOSE: The aims of this study were to determine national-level trends in early regraft rates and examine patient-level and surgeon-level characteristics associated with early regrafts. METHODS: This was a retrospective, cohort study. We identified beneficiaries aged 65 years or older in the 2011 to 2020 Medicare carrier claims data set who underwent Endothelial keratoplasty (EK) and subsequently underwent an early regraft. The incidence of early regraft for each year was calculated and patient-level and surgeon-level characteristics associated with regrafts were examined using a multivariable regression model. RESULTS: Of 114,383 EK procedures, 4119 (3.60%) were followed by an early regraft, with no significant variations in the rates between years ( P = 0.59). Factors associated with higher odds of early regraft were Black compared with White race (OR 1.151; 95% confidence interval (CI) 1.018-1.302) and the highest quartile of income versus the lowest quartile (OR 1.120; 95% CI 1.002-1.252). Factors associated with lower odds were female sex (OR 0.889; 95% CI 0.840-0.942), receiving surgery in a hospital-based outpatient department versus an ambulatory center (OR 0.813; 95% CI 0.740-0.894), and having a surgeon with the highest quartile of annual EK volume versus the lowest (OR 0.726; 95% CI 0.545-0.967). Early regraft rates among surgeons ranged from 0% to 58.8% with a median [interquartile range] of 3.13 [0-6.15]. CONCLUSIONS: We found no significant increases in the early regraft rates over the past decade in the United States. Patient male sex and Black race, ambulatory surgery center-based location of the surgery, and low surgeon EK volume were associated with early regrafts. Substantial surgeon variability in regraft rates may indicate opportunities for improvement through development of best practices on perioperative management and patient counseling.

Herpetic Eye Disease After SARS-CoV-2 Vaccination: A CDC-VAERS Database Analysis.

PURPOSE: The aim of this study was to evaluate the cases of herpes simplex and zoster ophthalmicus after SARS-CoV-2 vaccination and assess the clinical presentations in patients. METHODS: A retrospective analysis of cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) between December 11, 2020, and July 1, 2022. Patients diagnosed with herpes simplex ophthalmicus (HSO) and herpes zoster ophthalmicus (HZO) after vaccination with BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) were included in the study. We performed a descriptive analysis of patient demographics, history, and ophthalmic and systemic clinical presentations. The correlations between vaccine type and continuous variables were assessed by the one-way analysis of variance test. In addition, we used the Pearson χ 2 test to assess the association between 3 vaccines and categorical variables. A post hoc analysis was performed between HSO and HZO onset intervals after vaccination, dose, and vaccine type. The 30-day risk analysis was also performed for HSO and HZO onset postvaccination using the reverse Kaplan-Meier analysis. RESULTS: A total of 1180 cases of HZO (983, 83.30%) and HSO (180, 15.25%) were reported. The mean age of patients with HZO and HSO was 59.02 ± 19.05 and 52.68 ± 17.83 years, respectively. Most of the cases of HZO (795, 80.87%) and HSO (131, 72.78%) were reported in patients who received BNT162b2. In the cohort, 63.28% and 65.56% diagnosed with HZO and HSO were women. About one third of HZO (36.52%) and HSO (35.56%) cases were reported after the first dose. More than half of the cases of HZO (61.34%) and HSO (64.45%) were reported within the first 2 weeks after vaccination. The estimated crude reporting rate (per million doses) in the United States was 0.25, 0.22, and 0.47 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The onset interval for HZO was significantly shorter in patients who received BNT162b2 (20.51 ± 56.20 days, P = 0.030) compared with patients who received mRNA-1273 (36.56 ± 108.67 days) and Ad26.COV2.S (39.66 ± 60.15 days) vaccines. The 30-day risk analysis showed a significantly higher risk of HZO after BNT162b2 than the other 2 vaccines ( P = 0.011). CONCLUSIONS: The low crude reporting rate suggests that HZO and HSO after SARS-CoV-2 vaccination occur rarely. This study provides insights into the possible temporal association between reported HSO and HZO after SARS-CoV-2 vaccines; however, further investigations are required to delineate the possible underlying immunological mechanisms.

Predictors of intraocular pressure reduction after femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery: a prospective trial.

PURPOSE: To evaluate the association between postoperative intraocular pressure (IOP) reduction and phacoemulsification parameters in patients who underwent both conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a prospective multicenter comparative study that enrolled 90 participants who underwent cataract surgery at the University of Maryland Medical System and the Wilmer Eye Institute. Patients underwent FLACS in one eye and CPS in the fellow eye. IOP was measured prior to surgery and monitored through six months postoperatively. Demographic, clinical, biometric, and intraoperative variables including cumulative dissipated energy (CDE), aspiration time, and phacoemulsification time were analyzed for any significant association with postoperative IOP. Postoperative IOP reduction was the primary outcome variable. A secondary goal of the study was to determine differences in postoperative IOP reduction between CPS and FLACS cohorts. RESULTS: In total, 157 non-glaucomatous eyes were included. Using multivariable analysis, we found preoperative IOP to be consistently associated with postoperative IOP reduction in the entire cohort. At the 6-month follow-up visit, there was a 12.4% reduction in IOP (-2.2 ± 3.4 mm Hg) seen, with no statistically significant difference between FLACS and CPS (12.3% ± 19.4% vs 12.5% ± 19.3%, respectively, p = 0.32). FLACS reduced the CDE required for phacoemulsification (6.6 ± 4.4%-seconds vs 8.6 ± 6.9%-seconds, respectively, p < 0.05). CDE was a predictor of IOP response at 6 months, but subgroup analysis revealed that this trend was driven by seven eyes requiring high CDE, and for the majority of eyes, CDE did not influence the size of the decrease. The seven eyes experiencing highest CDE were less likely to show IOP reduction at 6 months. CONCLUSION: Both FLACS and CPS resulted in similar and significant IOP reductions through 6 months after surgery. Preoperative IOP was significantly associated with IOP reduction, and CDE generally did not influence the size of the decrease.

Vaccine-associated corneal graft rejection following SARS-CoV-2 vaccination: a CDC-VAERS database analysis.

PURPOSE: To evaluate the cases of corneal graft rejection following SARS-CoV-2 vaccination reported to Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. METHODS: A descriptive analysis of the demographics, clinical history and presentation was performed. We evaluated the correlation between the vaccines and duration of vaccine-associated graft rejection (VAR) onset following vaccination using a one-way analysis of variance test. A post hoc analysis was performed between VAR onset-interval following vaccination dose and vaccine type. Finally, a 30-day cumulative incidence analysis was performed to assess the risk of VAR in short term following different doses, vaccines and type of corneal transplantation. RESULTS: A total of 55 eyes of 46 patients were diagnosed with VAR following vaccination with BNT162b2 (73.91%) and mRNA-1273 (26.09%). The mean age of the patients was 62.76±15.83 years, and 28 (60.87%) were female. The patients diagnosed with VAR had undergone penetrating keratoplasty (61.82%), Descemet membrane endothelial keratoplasty (12.73%), descemet stripping endothelial keratoplasty (18.18%), anterior lamellar keratoplasty (3.64%) and corneal limbal allograft transplantation (1.82%). The mean time for VAR since penetrating and endothelial keratoplasty was 8.42±9.23 years and 4.18±4.40 years, respectively. 45.65% of the cases of VAR were reported after the second dose of vaccine. The duration of VAR onset was significantly shorter after the second dose compared with the first and booster doses (p=0.0165) and in patients who underwent endothelial keratoplasty compared with penetrating keratoplasty (p=0.041). CONCLUSIONS: This study outlines a possible temporal relationship between corneal graft rejection and SARS-CoV-2 vaccination. An earlier onset of VAR was observed in patients who had a history of endothelial keratoplasty and following the second dose of vaccination.

Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes.

ABSTRACT: Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.

Indications for keratoplasty in management of corneal ectasia.

PURPOSE OF REVIEW: The current review aims to describe recent advancements in treatment of corneal ectasias and its effect on indications for corneal transplantation. RECENT FINDINGS: The majority of patients affected by ectatic corneal disease use contact lenses to correct resulting astigmatism. Patients who are intolerant of contact lenses or cannot achieve acceptable vision through conservative measures could consider keratoplasty. However, continuing advancements in both nonsurgical and surgical treatments are either reducing or delaying the need for keratoplasty in patients affected by ectatic corneal disease. SUMMARY: Corneal transplantation has been the mainstay of treatment for patients with advanced ectatic corneal disease. In the past decade, numerous improvements have been occurred to make contact lenses not only more effective for visual correction, but also more comfortable. Although corneal cross-linking is the only proven treatment known to prevent progression of disease, several other therapies show early potential for those in which cross-linking is contraindicated. Patients now have access to a wider range of therapies before considering keratoplasty.

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.