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To evaluate aspects of construct validity of the Michigan Retinal Degeneration Questionnaire (MRDQ) and the Michigan Vision-related Anxiety Questionnaire (MVAQ).Subjects with a clinical diagnosis of an inherited retinal disease (IRD) were recruited prospectively and three tests were used to assess construct validity: the ability to distinguish different IRD phenotypes; test a priori hypothesis of an association between vision-related anxiety and vision-related disabilities; and correlate MRDQ and MVAQ with the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and the Impact of Vision Impairment (IVI). One-way ANOVA was used to compare different phenotypes for mean domain scores for MRDQ/MVAQ. Pearson's correlations were performed between; Cone-function Anxiety and Central Vision controlling for better eye visual acuity, Rod-function anxiety and Scotopic Function controlling for visual field area (III4e and IV4e), and scores of MRDQ/MVAQ, NEI VFQ-25, and IVI.The study sample consisted of 146 patients evenly divided between males and females, and mean age was 50 years. The one-way ANOVA test was significant for distinguishing IRD phenotypes in 6 domains of MRDQ/MVAQ. Cone-function Anxiety correlated with Central Vision controlling for visual acuity, Rod-function anxiety correlated with Scotopic Function controlling for visual field area, all domains in MRDQ/MVAQ had significant correlations with NEI VFQ-25 and IVI composite scores.MRDQ and MVAQ domenstrate aspects of construct-validity set forth by the U.S. Food and Drug Administration. The study futher supports the use of both patient-reported outcome measures in IRD clinical trials and natural history studies.

No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate the safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients.This was a prospective, phase 1b, single-center, randomized, double-masked, vehicle-controlled, parallel-group study.This study was designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function (clinicaltrials.gov NCT02855450). A total of 60 open-angle glaucoma patients were randomized 40:20 to receive either 180 μg/mL rhNGF or vehicle control eye drops in both eyes, 3 times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed by adverse events, and tolerability, as assessed by patient-reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field, electroretinograpy (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12 and 32 weeks total).Of the 60 randomized patients, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with a low level of symptom burden mainly eliciting periocular ache (in 52% of treated group and 5% of placebo group) and only 3 patients (7.5%) discontinuing treatment because of discomfort, of whom 1 patient (2.5%) prematurely withdrew from the study. There were no statistically significant differences in global indices of Humphrey visual field and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed nonsignificant trends toward significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies.Use of rhNGF is safe and tolerable in a topical 180-μg/mL formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and the trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.