Wet AMD Lesion Components May Affect Retinal Sensitivity During Anti-VEGF Treatment


The biggest predictors of retinal sensitivity loss during 2 years of anti-VEGF treatment included RPE atrophy, Type 2 MNV, cystoid intraretinal spaces, and the presence of SRT.

Henrik Bygglin | Silmaasema

Henrik Bygglin

Credit: Silmaasema

New research identified the effects of exudative age-related macular degeneration (wet AMD) lesion components on retinal sensitivity during anti-vascular endothelial growth factor (anti-VEGF) treatment.1

The 2-year analysis showed the most powerful predictors of retinal sensitivity loss primarily occurred in the loci of retinal pigment epithelial (RPE) atrophy, areas of hemorrhage, arena of macular neovascularization (MNV), intraretinal cysts, and subretinal tissue (SRT); on the other hand, type 1 MNV, (PED), and neuroepithelial detachment (NED) had lesser effects on retinal sensitivity loss.

“Our results are in line with earlier studies in showing a clear improvement of retinal sensitivity with anti-VEGF treatment within the first year of treatment, but not during the second year,” wrote the investigative team, led by Henrik Bygglin from the department of ophthalmology at Helsinki University Central Hospital. “As such, with the 2-year follow-up, our results represent one of the longest time spans among similar studies.”

The exact mechanisms of functional improvement or deterioration resulting from anti-VEGF treatment are not completely understood, particularly in the long term.2 Few studies have prospectively analyzed the retinal sensitivity and optical coherence tomography (OCT) structure relationship during anti-VEGF treatment in treatment-naive wet AMD eyes, according to the investigative team. As visual acuity (VA) results generally decrease over time, the team indicated an analysis of data from a longer follow-up could elucidate the functional outcome of long-term anti-VEGF treatments.

The analysis investigated which wet AMD lesion characteristics affect and predict the retinal sensitivity over 2-year prospective follow-up of treatment-naive patients treated with bevacizumab using a pro-re-nata protocol between May 2008 - April 2012. Fluorescein (FA) and indocyanine green angiographies (ICGA) were performed at baseline and at 1 and 2 years. Of 43 patients completing the 2-year follow, 24 had reliable microperimetries, good quality OCTs, and angiographies available at baseline and at 1 and 2 years.

Microperimetries were automatically aligned with the OCTs and manually aligned with the angiographies and autofluorescence images by aligning the major vessels. Under each stimulus site of the microperimetry, the thickness of the neuroretina, RPE, NED, SRT, and cystoid spaces were identified and manually measured; the areas of MNV type I and II, ICG plaque, hemorrhage, and RPE atrophy were identified using the aligned angiographies and autofluorescence images. Multivariate mixed linear model analysis designed for repeated measurements were used to estimate the effects of lesion components on retinal sensitivity during the pro re nata treatment.

Upon analysis, investigators found the mean retinal sensitivity increased during the first year (10.1 dB at baseline to 11.9 dB at 1 year; P = .021, Wilcoxon signed ranks). However, it remained the same during the second year (median, 11.5 dB; P = .301). In addition, the mean VA increased only during the first year (median, 72.0 ETDRS letters to 77.5 letters at 1 year; P = .006) and remained 77.0 letters at 2 years (P = .808).

At baseline, the lesion components most affecting the retinal sensitivity were RPE atrophy, presence of hemorrhage, intraretinal cysts, type 2 MNV, intraretinal cysts, and subretinal tissues (all P <.0001). Meanwhile, the presence of RPE elevation, type 1 MNV, and NED had moderate effects, while the effect of retinal thickening was less prominent.

Moreover, the baseline characteristics predicting deteriorated sensitivity at 1 year were RPE atrophy, the area of type 2 MNV, intraretinal cysts, hemorrhage, occult choroidal neovascularization (CNV), and retinal thickening >350 µm. Older age predicted less increase in function, while NED and RPE elevation had small effects. At the 2-year mark, the analysis showed the predictive values of the baseline lesion components remained mostly unchanged.

“The lesion components detected after 1 year of treatment predicting worse function at 2 years were quite similar,” investigators wrote. “The combined area of CNV lesion in FA at 1 year remained a significant predictor, hemorrhage was not present in any of the study eyes at this point of treatment and, in contrast to the baseline characteristics, SRT became a somewhat significant predictor of further deterioration.”


  1. Bygglin H, Immonen I, Luoma A, Hautamäki A. Exudative age-related macular degeneration lesion components predicting microperimetric retinal sensitivity during anti-vascular endothelial growth factor treatment [published online ahead of print, 2023 May 25]. Acta Ophthalmol. 2023;10.1111/aos.15707. doi:10.1111/aos.15707
  2. Sharma, S., Toth, C.A., Daniel, E., Grunwald, J.E., Maguire, M.G., Ying, G.S. et al. (2016) Macular morphology and visual acuity in the second year of the comparison of age-related macular degeneration treatments trials. Ophthalmology, 123(4), 865–875.
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