Outer Retinal Layer Thickening Precedes Neovascularization in AMD

Age Related Macular Degeneration. Indocyanine Green Retinal Angiogram Of Choroidal Neovascularization Under Infrared Light. (Photo By BSIP/UIG Via Getty Images)
Researchers identified changes on OCT imaging associated with disease progression.

Outer retinal layer thickening precedes exudative macular neovascularization development by approximately 8 months, according to research results published in the American Journal of Ophthalmology. 

Researchers conducted a retrospective, multicenter study in order to evaluate outer retinal layer thickness change in consecutive optical coherence tomography (OCT) scans in the second eyes of patients already being treated for age-related macular degeneration (AMD). The patients in this study developed exudative macular neovascularization, and the investigators sought to identify a parameter that might predict the development of this condition. 

Participants were identified through the Fight Retinal Blindness database from 3 different eye centers. Consecutive patients with neovascular (nAMD) in one eye, diagnosed between 2015 and 2018, were included; the second eye was designated as the “study eye.” 

At each study visit, 5 values for outer retinal layer thickness were collected: central, superior, temporal, inferior, and nasal. Investigators also collected data on the difference between outer retinal layer thickness in sectors that developed exudative macular neovascularization and those that did not, as well as the presence of drusen in each sector and the presence of a double layer sign. 

The final cohort included 47 eyes from 47 patients (18 men; mean age, 77.2±9.8 years). Within this group, 68% of eyes ultimately developed type 1 macular neovascularization, 13% developed type 2, and 19% developed type 3. Mean follow-up duration was 747±41 days, and the mean time from last visit to exudation was 52±25 days. 

Exudative macular neovascularization development occurred in all ocular sectors at a similar rate with evenly distributed drusen, although drusen that affected the center and inferior sectors were “present in a significantly higher number of eyes” that eventually developed exudative macular neovascularization. 

Double layer signs were present in 6.4% of eyes at baseline. At the final visit, the same sign was present in 21.5% of eyes, with a statistically significant difference from baseline. 

Automatic outer retinal layer thickness measurements were successful in 71% of b-scans; manual correction was required in the remaining scans. 

At baseline, mean outer retinal layer thickness was similar between sectors that developed and did not develop exudative macular neovascularization (85.2±8.2 vs 86.8±5.7 µm). A significantly thicker central sector was noted compared with other sectors in both groups. 

Across the entire cohort, mean outer retinal layer thickness significantly increased, from 85.2±8.2 µm at baseline to 91.0±14.9 µm at the final visit (mean thickness change of 5.9±10.4 µm). Within sectors that did not develop exudative macular neovascularization, there was no significant increase in thickness (mean change, -2.8±3.6 µm). 

The outer retinal layer was significantly thicker at the final visit in sectors that did vs did not develop exudative macular neovascularization. 

Results of a longitudinal analysis found that the predicted outer retinal thickness layer remained steady until 256 days before the occurrence of exudative macular neovascularization (1.2 µm, 1.4% increase from baseline), while predicted outer retinal layer thickness increased 3.6 µm (4.2% increase from baseline) by 55 prior to detection of exudative macular neovascularization. There was a subsequent increase to 9.5 µm (increase of 11.1% from baseline) within the 30 days before exudative macular neovascularization. 

Results of a subanalysis by macular neovascularization type found that outer retinal layer thickness changes differed over time based on macular neovascularization subtype. 

Study limitations include the enrollment only of second eyes in patients who already had nAMD in 1 eye, variable timing between visits, and a lack of a control group of eyes. 

“We found that the development of exudative [macular neovascularization] was preceded by thickening of the [outer retinal layer] in the area that subsequently developed it approximately 8 months before it developed,” researchers report. 

“Given the simplicity of its assessment, we believe that [outer retinal layer] thickness could serve as a surrogate measurement to predict the time of conversion to exudative AMD and to ensure timely treatment to optimize outcomes.”


Invernizzi A, Parrulli S, Monteduro D, et al. Outer retinal layer thickening predicts the onset of exudative neovascular age related macular degeneration: outer retinal thickening predicts neovascular AMD. Am J Ophthalmol. Published online May 28, 2021. doi:10.1016/j.ajo.2021.05.015