Phase IV Multicenter, Prospective, Open-Label Clinical Trial of Cenegermin (rhNGF) for Stage 1 Neurotrophic Keratopathy (DEFENDO).

INTRODUCTION: Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK. METHODS: This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up. RESULTS: Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1-94.9%; P < 0.001) at week 8; 95.2% (95% CI 76.2-99.9%; P < 0.001) of those patients remained healed at the end of the 24-week follow-up (week 32). At week 8, 91.2% (95% CI 76.3-98.1%; P < 0.001) of patients experienced improved corneal sensitivity; this improvement was observed in 82.1% (95% CI 63.1-93.9%; P < 0.001) of patients at week 32. Mean best-corrected distance visual acuity change from baseline at week 8 was - 0.10 logMAR (standard deviation [SD], 0.15; 95% CI - 0.16 to - 0.05; P < 0.001) and at week 32 was - 0.05 logMAR (SD, 0.16; 95% CI - 0.11 to 0.01; P = 0.122). At weeks 8 and 32, 15.2% (95% CI 5.1-31.9%; P < 0.001) and 10.7% (95% CI 2.3-28.2%; P < 0.001) of patients, respectively, had a 15-letter gain from baseline. At least one adverse event (AE) was reported by 73.0% and 45.7% of patients during the treatment and follow-up periods, respectively. The most common treatment-related, treatment-emergent AEs were eye pain (37.8%), blurred vision (10.8%), and eyelid pain (8.1%); these were mostly mild or moderate and were only reported during the treatment period. CONCLUSIONS: These results support the potential use of cenegermin for treating patients with stage 1 NK, and future confirmatory studies would be beneficial to elaborate on these findings. TRIAL REGISTRATION: DEFENDO; NCT04485546.

Evaluation of Research Productivity Among Academic Cornea, External Diseases, and Refractive Surgery Ophthalmologists Using the Relative Citation Ratio.

PURPOSE: The purpose of this study was to provide relative citation ratio (RCR) benchmark data for cornea and external diseases specialists. DESIGN: This is a cross-sectional bibliometric analysis. SUBJECTS: Subjects included were fellowship-trained cornea and external diseases faculty at Accreditation Council for Graduate Medical Education-accredited institutions in the United States. METHODS: Academic specialists were indexed using the National Institutes of Health iCite Web site. Publication count, mean RCR score, and weighted RCR score were obtained between October 2022 and January 2023 by examining PubMed-listed publications from 1980 to 2022. Data were compared by sex, career duration, academic rank, and acquisition of a Doctor of Philosophy. MAIN OUTCOME MEASURES: The main outcome measures were publication count, mean RCR value, and weighted RCR value. RESULTS: The cohort included 602 specialists from 112 Accreditation Council for Graduate Medical Education-accredited institutions. These clinician-scientists produced highly impactful research with a median publication count of 15 (interquartile ranges 4-41), median RCR of 1.4 (interquartile ranges 0.91-1.88), and median-weighted RCR of 20.28 (5.3-66.69). Both academic rank and career length were associated with greater publication count and RCR values. Male sex was also associated with greater publications counts and RCR scores compared with female faculty. Acquisition of a Doctor of Philosophy was associated with greater publication counts and weighted RCR scores but no difference in mean RCR scores. CONCLUSIONS: Academic cornea and external diseases specialists conduct high-impact research, with a median RCR of 1.4, exceeding the NIH standard value of 1. These data provide RCR benchmark data for the field to inform self, institutional, and departmental evaluations. These results also highlight a significant gender disparity in the field necessitating efforts to increase female representation and ensure equal opportunities.

Corneal Epithelial Thickness in Sjogren's Disease: A Pilot Study.

Purpose: This study was to assess corneal epithelial thickness (CET) in patients with Sjogren's disease (SjD). Methods: A retrospective chart review was conducted of SjD patients from September 2021 to January 2022. Patient demographics, unanesthetized Schirmer's test, serologic markers, and symptoms as measured by the Ocular Surface Disease Index (OSDI) were reviewed. Epithelial thickness from both eyes was measured using anterior segment OCT at the central 3mm and concentric 5mm, 7mm, and 9mm zones for the superior, temporal, inferior, and nasal corneal quadrants. Associations between corneal epithelial thickness with patient demographics, clinical characteristics, and symptoms were evaluated using regression models. Results: Fifteen SjD patients (100% female) were included with a mean age of 58.4 years. Patients with Sjogren's disease had a significantly thinner superior corneal epithelium compared to the inferior epithelium (mean 47.7mm vs 53.1mm, p = 0.001). The epithelial thickness mean standard deviation (MSD) was significantly inversely correlated with the unanesthetized Schirmer test (r=-0.39, p = 0.005), suggesting that an overall variability of CET correlates with decreased aqueous tear production. SS-A, SS-B, ANA, and RF positivity were not associated with any measures of CET. Conclusion: This pilot study suggests that there is significant superior versus inferior thinning of corneal epithelium in Sjogren's patients. There was a significant correlation between variability of corneal epithelial thickness and decreased tear production in Sjogren's patients. Further larger studies are needed to understand the relationship of CET with objective and subjective measurements of ocular surface disease.