Individual recurrence intervals after anti-VEGF therapy for age-related macular degeneration

Abstract

Background: To assess the time interval to recurrent choroidal neovascular membrane (CNV) activity in eyes with neovascular age-related macular degeneration (AMD) after intravitreal anti-VEGF therapy.

Methods: Data from all patients who received intravitreal ranibizumab injections for neovascular AMD at the University of Cologne prior to February 2009 were retrospectively reviewed. Patients were treated on a pro re nata (PRN) basis and eyes with active CNV received three consecutive monthly injections. Recurrence of CNV activity was defined as recurrence of intra- or subretinal fluid on optical coherence tomography (OCT) or leakage on fluorescein angiography (FA) after initial resolution of fluid and leakage following anti-VEGF therapy. All eyes showing at least two documented recurrences of CNV activity during follow-up were included in this analysis. Recurrence intervals were calculated and were deemed to be regular or periodical if the difference between recurrence interval times was less than 50 days.

Results: Twenty-nine eyes of 28 patients met the inclusion criteria. Two to six recurrences were detected per case (mean 2.8 ± 1.1 recurrences). Recurrence intervals ranged from 41 days to 523 days (mean 5.5 ± 3.4 months, median 4.5 months). Twenty-two eyes (76%) showed at least two periodical recurrence intervals. In 12 eyes (41%), all recurrences occurred at regular intervals (2-4 recurrences, mean 2.3 ± 0.6 recurrences). Seven eyes (24%) showed irregular recurrence intervals (2-3 recurrences, mean 2.1 ± 0.4 recurrences). All 11 eyes with a classic CNV lesion component showed at least two periodical recurrence intervals. Eyes with occult CNV lesions showed periodical recurrence intervals in 11 out of 18 cases (61%).

Conclusions: Preliminary data indicate that periodical recurrences of CNV activity may be seen in eyes with neovascular AMD undergoing anti-VEGF therapy. Knowledge of individual recurrence interval times may allow for the development of an individualized treatment plan and prophylactic therapy.

Fig. 1

Recurrence intervals (months) for all cases. One case showed six recurrences (red), two cases five recurrences (green), three cases four recurrences (blue), seven cases three recurrences (yellow) and 16 cases two recurrences (black and white) during follow-up

Fig. 2

Example showing a case with occult CNV and RAP demonstrating five recurrences during a 3-year follow-up (the most recent three out of those five are shown here). The recurrence interval times ranged between 3.9 and 5.7 months. Visual acuity (VA) decreased progressively over time. OCT Optical coherence tomography, FA fluorescein angiography

Fig. 3

Frequency of periodical recurrence interval times in various CNV lesion types