Conclusion
Anti-VEGF therapy has the potential to stabilize vision impairment in up to 90% of predominantly CNV lesions, and the preponderance of the long-term Level 1 evidence favors monthly ranibizumab through 24 months as the gold-standard treatment. Currently, however, the available long-term data is limited, and much of the information we do have beyond 2 years of anti-VEGF treatment comes from the potentially biased studies. Hopefully, data obtained from other trials with planned follow-up longer than 12 months and preferably longer than 24 months will contribute to our understanding of the effects of long-term anti-VEGF treatment. Two-year outcomes of IVAN are anticipated within the next year and may help clarify some of the discrepancies between the observations of CATT and IVAN.
Monthly treatment with ranibizumab or bevacizumab and fixed dosing regimens with aflibercept have yielded the largest relative increases in visual acuity compared with the as-needed treatment regimens. Maintenance of vision improvements during the second year of management requires monthly examinations, and thus far fixed monthly dosing in the second year has provided the most consistent benefits. Suboptimal long-term vision outcomes may be because of the natural progression of the disease, effects of anti-VEGF undertreatment, or drug tachyphylaxis or tolerance.
The long-term cost impact of expensive drugs on our healthcare systems is not trivial, particularly those that require frequent and chronic administration such as ranibizumab and aflibercept. However, systemic safety signals exist when considering the more economical use of intraocular bevacizumab, as does the concern for potential for serious ocular adverse events from improper bevacizumab compounding procedures. It is also unknown whether deleterious cumulative systemic effects that may be associated with pan-VEGF blockade are underreported in these large clinical trials.
The number of patients being diagnosed with and treated for NVAMD will continue to increase as our population ages. The treatment burden of frequent office visits is of mounting concern for many patients, care-givers, and physicians' offices, and discovery of longer acting, more cost-effective therapies with minimal systemic risk will be critical in improving our quality of care for these patients.