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Sunness JS. Spontaneous Improvement in Visual Acuity in Age-Related Geographic Atrophy of the Macula. JAMA Ophthalmol. 2014;132(3):356–357. doi:10.1001/jamaophthalmol.2014.21
Geographic atrophy (GA) from age-related macular degeneration (AMD) is generally regarded as a monotonically worsening disorder. Unlike exudative AMD, in which improvements in visual acuity (VA) can occur as fluid resolves and neovascularization involutes, photoreceptor loss causing VA worsening in GA is irreversible. Successful therapy that stops the progression of disease will not restore function to a blind area. However, spontaneous improvement in VA can occur over time in eyes with GA. Microperimetry has shown that improvement is associated with better use of the eccentric retina in eyes that could not place the object of interest on the seeing retina at baseline.1 In a study of patients with bilateral GA followed up for 3 years, 17% improved by 2 or more lines in the worse-seeing eye on this basis, while no better-seeing eyes of the patients improved. The same phenomenon has been observed in the first-affected eye of patients with bilateral disciform scars.2
Recent reports of VA improvement in eyes with advanced macular disease in clinical trials of stem cell–derived retinal pigment epithelial cells3,4 may be misinterpreted as indicating a true treatment effect, while the reason for visual improvement may in fact be related to using the remaining seeing retina more effectively. The data from the National Institutes of Health–funded Wilmer prospective natural history study5 of GA associated with AMD were analyzed for the occurrence of spontaneous VA improvement at the shorter time frames characteristic of clinical trials. This study was approved by the Johns Hopkins University School of Medicine Institutional Review Board. Written informed consent was obtained.
Sixty patients with bilateral GA without exudative AMD who had 2-year follow-up data are included. They were thoroughly described in previous publications.5 A protocol refraction and measurement of best-corrected Early Treatment Diabetic Retinopathy Study VA were performed at baseline and at each annual visit. Descriptive statistics of improvement of VA at 1 and 2 years are provided.
The Table presents the number of patients who had improved VA at the follow-up visit, the amount of this improvement, and the distribution of improvement as a function of baseline VA. The median baseline VA (approximate Snellen equivalent) was 20/44 for the better-seeing eyes and 20/136 for the worse-seeing eyes. At 2 years, no better-seeing eye improved by 10 or more letters, while 5 of the worse-seeing eyes improved by 10 or more letters—3 by 10 to 15 letters and 2 by 20 to 25 letters. All 5 eyes that improved had baseline VA worse than 20/100. At 1-year follow-up from baseline, 3 of these 5 eyes already had improved by 10 or more letters, and no other eyes improved to this extent at 1 year. Despite the improvement in VA, all eyes had further enlargement of GA during follow-up.
Five (10%) of the 48 worse-seeing eyes with baseline VA worse than 20/100 improved by 10 or more letters at 2 years. No better-seeing eye improved by 10 or more letters, although only 10 better-seeing eyes had baseline VA worse than 20/100, so the significance of an eye being the better-seeing vs worse-seeing eye is uncertain. One can anticipate that a small proportion of patients with GA in a clinical trial will have spontaneous improvement in VA. Previous work has suggested that the improvement occurs in eyes without an eccentric preferred retinal locus for fixation at baseline and is associated with better use of the seeing eccentric retina by the time of follow-up.1 These findings suggest that efforts should be made prior to starting a trial to document by microperimetry whether there is an eccentric preferred retinal locus for fixation. If the patient cannot put the object of interest (fixation cross) on the seeing retina, one could consider vision rehabilitation to optimize use of the eccentric retina prior to enrollment in a trial.6
Corresponding Author: Janet S. Sunness, MD, Richard E. Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, 6569 N Charles St, PPW 504, Baltimore, MD 21204 (firstname.lastname@example.org).
Conflict of Interest Disclosures: Dr Sunness has been a consultant to the following companies for design of clinical trials for age-related macular degeneration: Acucela, Alcon, Alexion, BioMarin, Cell Cure, Genentech, GlaxoSmithKline, Neurotech, Novartis, Ophthotech, Pfizer, ReVision, System Analytic, Sucampo, and Velocity Pharm Dev. No other disclosures were reported.
Funding/Support: This work was funded in part by grant R01 EY08552 from the National Institutes of Health.
Role of the Sponsor: The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: Neil M. Bressler, MD, Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, is the JAMA Ophthalmology Editor but was not involved in the review process or the acceptance of the manuscript.
Additional Contributions: Dr Bressler helped with patient recruitment and design of the study, and Carol A. Applegate, COT, Richard E. Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, Baltimore, Maryland, helped with data acquisition. Both received funding from grant R01 EY08552 from the National Institutes of Health for their roles in the study (coinvestigator and study coordinator, respectively).