Two-Year Risk of Exudation in Eyes with Nonexudative Age-Related Macular Degeneration and Subclinical Neovascularization Detected with Swept Source Optical Coherence Tomography Angiography

Abstract

Purpose: Swept source optical coherence tomography angiography (SS-OCTA) was used to study the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with unilateral nonexudative age-related macular degeneration.

Design: Prospective cohort study.

Methods: Patients were imaged using 3- × 3-mm and 6- × 6-mm SS-OCTA scan patterns. MNV was detected using the outer retina to choriocapillaris en face slab. Prevalence and incidence of subclinical MNV, Kaplan-Meier cumulative estimates for the overall risk of exudation, and the association between neovascular lesion size and the risk of exudation were assessed through 2 years.

Results: From August 2014 through March 2018, 227 patients (154 intermediate and 73 late age-related macular degeneration eyes) underwent SS-OCTA imaging. Thirty eyes (13.2%) had subclinical MNV at first imaging and 12 eyes (8.9%) developed subclinical MNV during follow-up. Of the 191 eyes with >1 visit, 19 developed exudation. Fourteen of these eyes had pre-existing subclinical MNV. The incidence of exudation from the time of first detection of any subclinical MNV was 34.5%. The relative risk of exudation after detection of subclinical MNV was 13.6 times greater (95% confidence interval 4.9-37.7) than in the absence of subclinical MNV (P < .001). There was no significant risk of exudation based on lesion size alone (P = .91).

Conclusions: By 24 months, the risk of exudation was 13.6 times greater for eyes with subclinical MNV detected by SS-OCTA compared with eyes without subclinical MNV. For eyes with subclinical MNV in the absence of symptomatic exudation, we recommend close follow-up without treatment.

FIGURE 1.

Swept source optical coherence tomography angiography (SS-OCTA) 6×6 mm scans of the asymptomatic eye from a patient with exudative AMD in the fellow eye, followed for 27 months without exudation. (A,B,D,E,G,H) SS-OCTA B-scans with color-coded flow, where red represents the retinal microvasculature, pink the outer retina-tochoriocapillaris (ORCC) slab, and green the remainder of the choroid. The pink coloration under the retinal pigment epithelium and above Bruch’s membrane represents the type 1 macular neovascularization. (A,D,G) SS-OCTA B-scans superior to the fovea (dotted line in C,F,I). (B,E,H) SS-OCTA B-scans through the fovea (dashed line in C,F,I). (C,F,I) SS-OCTA en face ORCC slab images, after removal of retinal vessel projection artifacts. (C) SS-OCTA en face ORCC slab image showing a multilobular and multifocal neovascular complex with a total area of 4.70 mm². (D-F) Images obtained 14 months after those in (A-C). (F) SS-OCTA en face ORCC slab image showing a multilobular and multifocal neovascular complex with a total area of 5.11 mm². (G-I) Images obtained 13 months after those in (D-F). (I) SS-OCTA en face ORCC slab image showing a multilobular and multifocal neovascular complex with a total area of 5.90 mm².

FIGURE 2.

Swept source optical coherence tomography angiography (SS-OCTA) 6×6 mm scans of the asymptomatic eye from a patient with exudative AMD in the fellow eye followed up for 28 months without exudation. (A,C,E) SS-OCT B-scan through the fovea with color-coded flow, where red represents the retinal microvasculature, pink the outer retina-to-choriocapillaris (ORCC) slab, and green the remainder of the choroid. The pink coloration under the retinal pigment epithelium and above Bruch’s membrane, which represents the type 1 macular neovascularization. (B,D,F) SS-OCTA en face ORCC slab images, after removal of retinal vessel projection artifacts. The dashed line represents the B-scan contained in (A,C,E). (B) SS-OCTA en face ORCC slab image showing a wreath-shaped neovascular complex with a total area of 7.10 mm². (C, D)Images obtained 14 months after those in (A, B). (D) SS-OCTA en face ORCC slab image showing a wreath-shaped neovascular complex with a total area of 7.39 mm². (E, F) Images obtained 14 months after those in (C, D). (F) SS-OCTA en face ORCC slab image showing a wreath-shaped neovascular complex with a total area of 7.91 mm².

FIGURE 3.

Swept-source optical coherence tomography angiography (SS-OCTA) 6×6mm scans of the asymptomatic eye from a patient with exudative AMD in the fellow eye followed up for 36 months in which exudation developed requiring aflibercept therapy after 24 months of observation. (A,C,E)SS-OCTA B-scan through the fovea with color-coded flow, where red represents the retinal microvasculature, pink the outer retina-to-choriocapillaris (ORCC) slab, and green the remainder of the choroid. The pink coloration under the retinal pigment epithelium and above Bruch’s membrane, which represents the type 1 macular neovascularization. (B,D,F) SS-OCTA en face ORCC slab image, after removal of retinal vessel projection artifacts. The dashed line represents the B-scan contained in (A,C,E). (B) SS-OCTA en face ORCC slab image showing a multilobular neovascular complex with a total area of 2.42 mm². (C, D) Images obtained 3 months after those in (A, B). (C) SS-OCTA B-scan with color-coded flow through the fovea showing subretinal fluid through the fovea. (D) SS-OCTA en face ORCC slab image showing a neovascular lesion with an area of 2.88 mm². (E, F) Images obtained 12 months after those in (C, D). (E) SS-OCTA B-scan with color-coded flow through the fovea showing resolved subretinal fluid after eight anti-VEGF injections. (F) SS-OCTA en face ORCC slab image showing a neovascular lesion with an area of 2.75 mm². After anti-VEGF therapy, no significant change in the configuration of the MNV was appreciated.

FIGURE 4.

Swept source optical coherence tomography angiography (SS-OCTA) 6×6 mm scans of the asymptomatic eye from a patient with exudative AMD in the fellow eye followed up for 25 months in which exudation developed requiring anti-VEGF therapy after 14 months of observation. (A,C,E,G) SS-OCTA B-scan through the fovea with color-coded flow, where red represents the retinal microvasculature, pink the outer retina-to-choriocapillaris (ORCC) slab, and green for the remainder of the choroid. The pink coloration under the retinal pigment epithelium and above Bruch’s membrane, which represents the type 1 macular neovascularization. (B,D,F,H) SS-OCTA en face ORCC slab image, after removal of retinal vessel projection artifacts. The dashed line represents the B-scan contained in (A,C,E,G).(B) SS-OCTA en face ORCC slab image showing a multilobular neovascular complex with a total area of 0.69 mm². (C, D) Images obtained 13 months after those in (A, B). (D) SS-OCTA en face ORCC slab image showing a neovascular lesion with an area of 2.97 mm². Because of the patient was symptomatic with subretinal fluid presented two months after those in (C, D), the patient received anti-VEGF therapy in the ER, so the SS-OCTA imaging was not performed on the day of injection. (E, F) Images obtained one month after the first injection. (E) SS-OCTA B-scan with color-coded flow through the fovea showing the treated type 1 macular neovascularization. (F) SS-OCTA en face ORCC slab image showing a neovascular lesion with an area of 2.51 mm². (G, H) Images obtained 9 months after those in (E, F). (G) SS-OCTA B-scan with color-coded flow through the fovea showing decreased RPE elevation after five anti-VEGF injections. (H) SS-OCTA en face ORCC slab image showing a neovascular lesion with a total area of 3.21 mm².

FIGURE 5.

Swept source optical coherence tomography angiography (SS-OCTA) 3×3 mm scans of the asymptomatic eye from a patient with exudative AMD in the fellow eye followed up for 26 months in which exudation developed requiring anti-VEGF therapy after 9 months of observation. (A,C,E,G) SS-OCTA B-scan through the fovea with color-coded flow, where red represents the retinal microvasculature, pink the outer retina-tochoriocapillaris (ORCC) slab, and green the remainder of the choroid. The pink coloration under the retinal pigment epithelium and above Bruch’s membrane, which represents the type 1 macular neovascularization. (B,D,F,H) SS-OCTA en face ORCC slab image, after removal of retinal vessel projection artifacts. The dashed line represents the B-scan contained in (A,C,E,G). (B) SS-OCTA en face ORCC slab image showing a small lesion with a total area of 0.06 mm²(arrow). (C, D) Images obtained 9 months after those in (A, B). (C) SS-OCTA B-scan with color-coded flow through the fovea and subretinal fluid presented. (D) SS-OCTA en face ORCC slab image showing increased neovascular lesion with an area of 0.18 mm². The patient was symptomatic at this visit and intravitreal aflibercept was injected. (E, F) Images obtained 1 month after the first injection. (E) SS-OCTA B-scan with color-coded flow through the fovea showing subretinal fluid resolved. (F) SS-OCTA en face ORCC slab image showing a decreased neovascular lesion size with an area of 0.04 mm². (G, H) Images obtained 16 months after those in (E, F). (G) SS-OCTA B-scan with color-coded flow through the fovea still showing the type1 neovascularization after nine anti-VEGF injections. (H) SS-OCTA en face ORCC slab image showing a neovascular lesion extends to an area of 0.11 mm².

FIGURE 6.

Swept source optical coherence tomography angiography (SS-OCTA) 6×6 mm scans of the asymptomatic eye from a patient with non-exudative AMD in one eye and exudative AMD in the fellow eye followed up for 21 months in which exudation from both of the two neovascular foci developed after 5 months of observation. (A,B,C,E,F,G,I,J,K,M,N,O) SS-OCTA B-scans with color-coded flow represented as red for the retinal microvasculature, pink for the outer retina-to-choriocapillaris (ORCC) slab, and green for the remainder of the choroid. The pink coloration under the retinal pigment epithelium and above Bruch’s membrane represents the type 1 macular neovascularization. (A,E,I,M) SS-OCTA B-scans of the first neovascular foci superior to the fovea (dotted line in D,H,L,P). (B,F,J,N) through the second neovascular foci in the foveal (short dashed line in D,H,L,P), (C,G,K,O) through the second neovascular foci inferior to the foveal (long dashed line in D,H,L,P), (D) SS-OCTA en face ORCC slab image showing MNV with a total area of 5.32 mm². (E-H) Images obtained 5 months after those in (A-D). (E,F) B-scans of the both of the neovascular foci appears to be associated with new onset exudation. (H) SS-OCTA en face ORCC slab image showing the MNV with a total area of 6.61 mm². The patient was symptomatic at that visit and intravitreal aflibercept was given. (I-L) Images obtained 1 month after the exudation, those in (E-H). (L) SS-OCTA en face ORCC slab image showing the MNV with a total area of 4.19 mm². (M-P) Images obtained 15 months after those in (I-L) after ten anti-VEGF injections. (P) SS-OCTA en face ORCC slab image showing the MNV with a total area of 5.49 mm².

FIGURE 7.

Kaplan-Meier analysis showing the cumulative proportion of eyes treated with anti-vascular endothelial growth factor (VEGF) therapy from the time of the first swept source optical coherence tomography angiography (SS-OCTA). For eyes with subclinical macular neovascularization (MNV) at the time of first SS-OCTA imaging, the incidence of exudation was 21.1% by 12 months and 34.5% by 24 months. For eyes without subclinical MNV at the time of first SS-OCTA imaging, the incidence of exudation was 3.6% by 12 months and 6.3% by 24 months.

FIGURE 8.

Kaplan-Meier analysis of the cumulative proportion of eyes treated with anti-vascular endothelial growth factor (VEGF) therapy from the time the subclinical macular neovascularization (MNV) was first detected. The overall incidence of exudation from detection of any subclinical MNV was 24.2% by 12 months and 34.5% by 24 months.