Visual acuity has long dominated age-related macular degeneration (AMD) trials. But anyone who treats AMD knows that letters on a chart do not fully describe the lived experience of the disease. Patients may struggle with reading, mobility, independence, low-light vision, distortion, scotomas, and psychosocial well-being – sometimes even when best-corrected visual acuity appears relatively preserved.
A new systematic review in Ophthalmology Science asks how well randomized controlled trials in AMD have captured that patient perspective. Nicolas S. Bodmer, Melisa Guezelguen, Leyla Huber, and colleagues reviewed the use and reporting of vision-related patient-reported outcome measures (PROMs) in AMD RCTs, focusing especially on whether baseline PROM data were reported in enough detail to interpret trial findings.
The rationale is timely. AMD remains a leading cause of irreversible vision loss, with an estimated 8.06 million people affected by AMD-related visual impairment in 2021 and projections rising to 21.34 million by 2050. Yet high-contrast visual acuity, still the dominant endpoint in many trials and regulatory pathways, can miss deficits in contrast sensitivity, low-luminance vision, dark adaptation, metamorphopsia, and everyday function.
The study authors searched MEDLINE, Embase, Web of Science Core Collection, and Scopus from inception to September 27, 2023, with a targeted update for 2024 and 2025 publications. Eligible studies were randomized controlled trials enrolling at least 20 people with AMD and reporting both baseline visual acuity and baseline vision-related PROM data. The review was conducted according to PRISMA 2020 and registered prospectively on PROSPERO.
From 7,356 records, 38 RCTs met inclusion criteria. The included trials spanned 2001 to 2024, ranged from small single-center studies to multinational phase 3 programs, and covered early AMD, intermediate AMD, neovascular AMD, geographic atrophy, mixed populations, and unspecified AMD stages.
Across these trials, the authors identified 11 distinct vision-related PROM instruments. The National Eye Institute Visual Function Questionnaire (NEI VFQ) family dominated, appearing in 30 of 38 studies, with the NEI VFQ-25 the most commonly used version. Other instruments, including the Impact of Vision Impairment questionnaire, Night Vision Questionnaire-10, and Melbourne Low-Vision Activities of Daily Living Index, appeared far less often.
Baseline patient-reported function varied by AMD stage. Early and intermediate AMD cohorts generally reported higher NEI VFQ-25 composite scores, ranging from 75.34 to 89.13, while neovascular AMD trials showed lower and more heterogeneous scores, from 59.1 to 77.9. The lowest standard NEI VFQ-25 scores appeared in low-vision and rehabilitation cohorts.
But the major message is not simply which questionnaire was used – it is how inconsistently PROMs were reported. Many trials presented only composite scores or selected subscales, and subscale or domain-level baseline reporting was available for only a minority. Baseline PROM results were not stratified by ethnicity, geography, language, country, or economic setting, limiting interpretation across populations.
A particularly important ophthalmic issue was laterality. AMD interventions are often delivered to one study eye, whereas PROMs capture person-level, often binocular, experience. Yet only 13 percent of studies reported both better- and worse-seeing eye acuity, and binocular function was rarely reported.
The study authors propose an AMD-specific minimum reporting set for future RCTs, including exact PROM version, language, administration mode, scoring, missing-data handling, study-eye and fellow-eye status, better- and worse-seeing eye definitions, binocular visual function, and baseline and follow-up PROM distributions.
For clinicians, researchers, and trialists, the message is that patient-reported outcomes can enrich AMD trials, but only if they are measured and reported with enough context to be meaningful. Better PROM reporting would not replace visual acuity, the review suggests – it would help explain what visual acuity cannot.
