This study evaluates the associations between morphologic features and 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

Study design

This cohort study examined VA and image gradings for 57% of CATT participants who were alive at year 5 of the study period. Eyes with AMD-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Participants were randomly assigned to ranibizumab or bevacizumab, and to 1 of 3 dosing regimens for 2 years. Thereafter, treatment was administered at the ophthalmologists’ discretion.

Outcomes

At year 5 of the trial, 60% of eyes had intraretinal fluid, 38% had subretinal fluid, 36% had subretinal pigment epithelial fluid, and 66% had subretinal hyperreflective material. Mean VA letters was 62 for no pathology in fovea; 61 for CNV, fluid, or hemorrhage; 65 for non-geographic atrophy (GA); 64 for non-fibrotic scar; 53 for GA; and 56 for fibrotic scar.

The incidence or worsening of 8 pathological features between years 2 and 5 in the study were independently associated with greater vision loss—not only from year 2 to 5, but also for vision loss from baseline to year 5. These features included foveal GA, foveal scar, foveal CNV, subretinal hyperreflective material, foveal intraretinal fluid, retinal thinning, CNV lesion area, and GA area.

Limitations

This analysis was limited to 57% of original study participants.

Clinical significance

There has been much debate about whether wet AMD patients are undertreated in a real-world setting and whether this undertreatment contributes to the observed VA decline after 2 years of treatment in studies such as CATT. The present study found evidence to support this idea. For example, 60% of participants had VEGF-driven pathology, such as intraretinal fluid at year 5.

However, some patients experience VA decline despite aggressive treatment. There is occasionally a morphologic explanation, and the present study did identify contributing pathologic features, such as GA or foveal scar. In other cases, however, VA decline occurred without any such findings, leaving the authors to hypothesize that this might be due to a loss of neuroprotective effects induced by anti-VEGF therapy, which may not have been detectable with the imaging modalities used in CATT. Some patients did retain excellent vision between years 2 and 5 despite no additional injections during that time.

Other AMD studies, such as the Seven-Up study and a 2015 paper by Gillies et al in Ophthalmology, have tried to correlate anatomic features at final follow-up with VA. However, those studies were underpowered or dependent on data from only a single time point.

This study confirms that undertreatment of VEGF-driven exudation exists, highlights the need for an effective treatment to limit GA progression, and reveals that the number of anti-VEGF injections needed to achieve an optimal VA result may vary greatly among patients.