Research Article: Progression of subclinical choroidal neovascularization in age-related macular degeneration

Date Published: June 4, 2019

Publisher: Public Library of Science

Author(s): Michael J. Heiferman, Amani A. Fawzi, Demetrios G. Vavvas.


To use optical coherence tomography angiography (OCTA) to study longitudinal subclinical choroidal neovascularization (CNV) changes and their correlation with progression to exudation in age-related macular degeneration (AMD).

This study included a total of 34 patients with unilateral neovascular AMD who were evaluated prospectively using OCTA to detect subclinical CNV in their fellow eye. Eyes with baseline subclinical CNV were followed with serial OCTA for a minimum of one year (15.2±3.27 months) to monitor the development of exudation.

Of the 34 fellow eyes studied, five were found to have baseline subclinical CNV. One of the five cases of baseline subclinical CNV converted to exudative AMD during the follow up period. The average surface area of baseline subclinical CNV on OCTA was 0.131±0.096 mm2 which progressed to 0.136±0.104 mm2 at the final follow up (P = 0.539). Geographic atrophy grew at a rate of 0.82±1.20mm2/year in four eyes without subclinical CNV and 0.02mm2/year in one eye with subclinical CNV.

The rate of conversion to exudative AMD in eyes with subclinical CNV of 20% in our study is similar to previous reports and suggests the importance of vigilance in these eyes. The lower growth rate of geographic atrophy may suggest a protective effect of subclinical CNV that deserves further study.

Partial Text

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in developed countries.[1] Early and intermediate AMD are defined by the presence of drusen; eyes with this feature can be further stratified by the size and number of drusen to determine their risk of progression to late AMD.[2] Late AMD is defined by the presence of choroidal neovascularization or geographic atrophy involving the center of the macula. While most patients with AMD have early or intermediate AMD, severe vision loss is most often related to late AMD.[3] Despite this potential morbidity, the mechanism for progression to late AMD remains unknown.

Thirty-four previously identified patients were included in this study, including five fellow eyes previously found to have subclinical CNV (14.7%). Subclinical CNV patients were followed for an average time period of 15.2±3.27 months. Patients without subclinical CNV were followed for an average time period of 12.4±5.47 months. Of the five eyes with subclinical CNV, one developed exudative AMD requiring anti-VEGF therapy initiation (20%, Fig 2). None of the twenty-nine eyes without subclinical CNV developed exudative AMD. The average surface area of subclinical CNV was 0.131±0.096 mm2 at baseline and 0.136±0.104 mm2 at the final follow up (P = 0.539, Table 1, Fig 3). The average flow area of subclinical CNV was 0.103±0.074 mm2 at baseline and 0.110±0.074 mm2 at the final follow up OCTA (P = 0.355). The single case of subclinical CNV that converted to exudative AMD increased in surface area from 0.139 mm2 at baseline to 0.164 mm2 at the final follow up OCTA.

In the present study, longitudinal monitoring of subclinical CNV revealed a rate of progression to exudative AMD of 20% in our cohort. The rate of conversion of subclinical CNV to exudative AMD has been studied by multiple groups (Table 2). de Oliveira Dias et al. identified 23 eyes with subclinical CNV and found progression to type 1 CNV in five eyes over twelve-months (21.7%).[10] Capuano et al. followed 19 eyes with subclinical CNV and found progression to exudative AMD that required anti-VEGF therapy in five eyes over a six-month period (26%).[7] Carnevali et al. identified 15 eyes with subclinical CNV and found progression to exudative AMD in one eye over a twelve-month period (6.6%). Yanagi et al. followed 8 eyes with subclinical CNV and 10 with polypoidal choroidal vasculopathy and estimated an annual incidence of exudation of 18.1%.[15] We observed a conversion rate of 20%, consistent with the majority of reported rates, and higher compared to Carnevali et al. who observed a rate of 6.6% over one year.[9] The differences may be explained by study design, since Carnevali et al. defined quiescent CNV as treatment-naïve CNV that remained non-exudative during 6-months of follow-up. In their cohort, eyes that converted to exudative AMD prior to 6-month follow-up were excluded from further analysis, which explains their lower rate of conversion. Interestingly, the study by Capuano et al. which had the highest rate of conversion (26% over six months) only evaluated subclinical CNV in eyes with geographic atrophy, which may have led to overestimation of the rate of conversion, given their focus on eyes with late AMD.




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