Study identifies new predictors of success for anti-VEGF treatment

Investigators used data from the Comparison of Age-related Macular Degeneration Treatment Trials (CATT) to evaluate baseline predictors of visual acuity (VA) outcomes one year after treatment with ranibizumab or bevacizumab for wet AMD. The data confirmed results from previous trials of ranibizumab, showing older age, better baseline VA and larger choroidal neovascularization (CNV) area predict poorer visual prognosis. It also identified two new predictors independently associated with outcomes - greater total foveal thickness and retinal pigment epithelium (RPE) elevation. These VA predictors did not differ between patients given ranibizumab or bevacizumab or between dosing regimens.

The authors conclude that the presence of these variables should not be used to justify reduced interest in treatment because all subgroups experienced some visual benefit. Instead, use the predictors to adjust patient expectations. Even the oldest patients or those with larger lesions experienced some improvement in vision.

The prospectively collected clinical data and central grading of images performed for the CATT trial showed that one-year after treatment, older age, larger area of CNV, and elevation of RPE were associated with worse VA (all P < 0.005), less gain in VA (all P < 0.02), and a lower proportion gaining ≥ 3 lines (all P < 0.04). Better baseline VA was associated with better VA at one year, less gain in VA, and a lower proportion gaining ≥ 3 lines (all P < 0.0001). Predominantly or minimally classic lesions were associated with worse VA than occult lesions (66 vs. 69 letters; P = 0.0003). RAP lesions were associated with more gain in VA (10 vs. 7 letters; P = 0.03) and a higher proportion gaining ≥ 3 lines. Geographic atrophy was associated with worse VA (64 vs. 68 letters; P = 0.02). Eyes with total foveal thickness in the second quartile (325 to 425 µm) had the best VA (P = 0.01) and were most likely to gain ≥ 3 lines (P = 0.004).

The authors note that the association with elevated RPE was unexpected. An elevation in RPE anywhere in the macula was one of the OCT factors most strongly associated with vision outcomes. Elevation in RPE was common (85 percent) and independently associated with worse VA, lower mean increase in VA score, and a lower proportion with ≥3 lines gained in VA. They speculate that eyes without RPE elevation at baseline had unimpaired RPE function and thus were more likely to have VA improvement than the majority of eyes with RPE elevation. Eyes with RPE elevation include those with sub-RPE hemorrhage, neovascularization or fibrosis, or drusen alone, features that could signal abnormal RPE functional activity and may have consequently adversely affected VA. In the MARINA and ANCHOR studies, increased RPE abnormalities observed on color photographs were strongly associated with VA loss. Together, these findings suggest that RPE function may play an important role in the VA response to anti-VEGF treatment.