AAO 2023: Retina Subspecialty Day – Complement Inhibition Debate

Prashant Tailor, MD
Mayo Clinic, Rochester, MN

For the debate on Current Complement Inhibition Therapy for Geographic Atrophy is Acceptable, we had Dr. Chakravarthy (Pro) and Dr. Spaide (Con).

Dr. Chakravarthy argued in favor of current complement inhibition therapy for geographic atrophy (GA), highlighting several points:

1. The rationale for targeting the complement pathway is strong, given extensive genetic and pathological evidence.
2. Phase 3 trials have shown a reduction in the rate of GA growth, although not necessarily in functional improvement.
3. Discrepancies between GA expansion and functional benefit can be addressed with more sophisticated measures of visual function (microperimetry) and by considering lesion proximity to the fovea.
4. Large data sets reveal a reduction in the risk of progression to severe visual loss with complement inhibition therapy, suggesting the potential for more personalized and precise treatments.

Dr. Spaide, however, presented a contrary view, arguing that current complement inhibition therapies are not acceptable because:

1. Despite reducing the rate of GA growth, they have not demonstrated a functional benefit in patients. Clinical trials have shown that treated patients did not perform better on visual function tests compared to untreated patients.
2. The reduction in GA growth is very small when quantified and may not be clinically meaningful.
3. Given the lack of functional benefit, the quality-adjusted life years (QALYs) for the treatment could be considered low, making it difficult to justify the cost, especially in the context of the potential risks like endophthalmitis, inflammation, and increased choroidal neovascularization.

In summary, Dr. Chakravarthy’s argument was centered on the genetic and clinical evidence supporting complement inhibition and the potential for personalized medicine, while Dr. Spaide questions the clinical significance and cost-effectiveness of such treatments in the absence of demonstrated functional benefits. The audience agreed with Dr. Spaide by a vote of 80% to 20%.