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The National Eye Institute (NEI) hosted a workshop on November 19, 2014, as part of the Audacious Goals Initiative (AGI), an NEI-led effort to rapidly expand therapies for eye diseases through coordinated research funding. The central audacious goal aims to demonstrate by 2025 the restoration of usable vision in humans through the regeneration of neurons and neural connections in the eye and visual system. This workshop focused on identifying promising strategies for optic nerve regeneration. Its principal objective was to solicit input on future AGI-related funding announcements, and specifically to ask, where are we now in our scientific progress, and what progress should we reach for in the coming years? A full report was generated as a white paper posted on the NEI Web site; this report summarizes the discussion and outcomes from the meeting and serves as guidance for future funding of research that focuses on optic nerve regeneration.

Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell-based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell-derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell-derived RPE, bone marrow- or umbilical cord-derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells-derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called "precompetitive space." The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell-based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community.

Purpose: Both the long form visual functioning scale (LFVFS(39)) and visual functioning scale (VFS) are measures of visual functioning (VF) that represent the Rasch-scaled versions of the NEI-VFQ(39) and the Indian vision function questionnaire (IND-VFQ), respectively. The objectives of this study were to investigate if the 15-item LFVFS(39) and 13-item VFS of the IND-VFQ meet the assumptions of the Rasch model and measure the same construct, VF, in an Indian visually impaired (VI) population., Methods: Data from 120 VI adults administered both instruments concurrently, were fitted to the Rasch measurement model to demonstrate that each instrument satisfies the assumptions of the model (including unidimensionality by principal components analysis); and both instruments can be cocalibrated onto a single underlying continuum of VF., Results: Both instruments required category reorganization for optimal rating scale functioning and possessed similar measurement precision (person separation = 2.76). Separate analysis of each instrument (eigenvalues, 2.3 and 1.9 for LFVFS(39) and VFS of IND-VFQ, respectively) and the pooled 28-item analyses (eigenvalue, 2.8) satisfied the assumptions of the Rasch model, including unidimensionality. Furthermore, all items fit in the separate and pooled analyses. Separate item and person measures for each instrument correlated strongly with estimates from the pooled data (r > 0.9 for all, P < 0.0001). CONCLUSIONS; Both the LFVFS(39) and VFS of the IND-VFQ measure the same construct, VF, and with equal measurement precision in an Indian VI population. Both instruments can be calibrated onto a single metric, thereby, enabling a comparison of their measurement range of VF.

Purpose: Patient-reported measures of visual function are increasingly incorporated into clinical trials of new treatments for age-related macular degeneration (AMD). Limited information is available regarding the associations between distance visual acuity (VA), reading speed, or contrast sensitivity and the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) subscales judged relevant to these measures. This study's objective was to evaluate such associations along with questions on restricted activity days., Methods: This cross-sectional study was conducted in patients with clinical diagnoses of neovascular AMD. Patient-reported outcome measures included the NEI VFQ-25 and restricted activity days. Clinical assessments included best-corrected visual acuity (BCVA), reading speed, and contrast sensitivity. The better-seeing eye was defined based on the BCVA of each patient. Psychometric properties of the NEI VFQ-25 were examined; analyses a priori focused on the Near Activities, Distance Activities, and Vision-Specific Dependency subscales., Results: The final study group included 92 participants (mean age, 78 years). Cronbach's α for the subscales ranged from 0.67 to 0.92. The NEI VFQ-25 overall composite, Near Activities, Distance Activities, and Vision-Specific Dependency scores were correlated with BCVA (r = -0.48 to -0.54, all P < 0.0001), reading speed (r = 0.43 to 0.56, all P < 0.0001), and contrast sensitivity (r = -0.39 to -0.46, all P < 0.001) of the better-seeing eye and with restricted activity days (r = -0.52 to -0.55, all P < 0.0001)., Conclusions: This study provides additional evidence supporting the validity of the NEI VFQ-25 in neovascular AMD patients by demonstrating correlations with a spectrum of vision measurements and a daily function measure.

Purpose: To evaluate the psychometric characteristics of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with age-related macular degeneration (AMD) who participated in two clinical trials., Methods: A secondary analysis of data from two randomized clinical trials was performed. NEI VFQ-25 data were collected from 1134 of 1146 patients with subfoveal choroidal neovascularization due to AMD with minimally classic or occult with no classic types and predominantly classic type. The NEI VFQ-25 was administered at baseline and months 1, 2, 3, 6, 9, and 12, and the SF-36 Health survey was administered at baseline and months 6 and 12. Visual acuity assessments were completed monthly throughout the studies. Internal consistency reliability and construct validity were examined., Results: The average age was 77 years (SD = 7.5; range, 52-96) with 59% women. At baseline, internal consistency reliability was 0.96 for the NEI VFQ-25 total score and ranged from 0.62 (ocular pain) to 0.91 (near activities) for the subscales. NEI VFQ-25 total and subscale scores correlated significantly with SF-36 scores (P < 0.05), and total, near activities, distance activities, and dependency scores correlated significantly with best corrected visual acuity (BCVA) in the better (P < 0.0001) and worse seeing eye (P < 0.0001). Mean NEI VFQ-25 total and subscale scores, except for ocular pain and general health, varied by BCVA group (P < 0.001), with higher impairment scores seen in the lower visual acuity groups., Conclusions: The NEI VFQ-25 demonstrated good reliability and construct validity as a measure of vision-related functioning outcomes in patients with AMD.