Swept-source OCT angiography aids detection of dry AMD

Reviewed by Dr Philip J. Rosenfeld.

Non-exudative macular neovascularisation (MNV) is asymptomatic, but it is important to identify MNV lesions because they seem to be a precursor for the development of exudative disease, according to Dr Philip J. Rosenfeld, professor of ophthalmology at Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine in Florida, United States. Treatment-naive MNV is now recognised as a state of age-related macular degeneration (AMD) that can be accurately detected with swept-source optical coherence tomography angiography (SS-OCTA).

Dr Rosenfeld discussed the detection, natural history and management of treatment-naive MNV in a presentation at the 2021 Ohio Ophthalmological Society virtual annual meeting. “A double-layer sign (DLS) or shallow, irregular retinal pigment epithelial elevation (SIRE) on the structural OCT B-scan is a characteristic feature of these lesions,” said Dr Rosenfeld.

“Finding these lesions in eyes with dry AMD is important because they have a high risk of conversion to exudative AMD. So far, we have not been able to predict which eyes are likely to progress to exudation based on anatomic changes. Therefore, close follow-up and at-home monitoring [are] crucial in these patients to prevent vision loss.”

Dr Rosenfeld highlighted his message about monitoring with a case history involving a patient who presented in January 2020 with large drusen and 20/40 visual acuity (VA). Routine SS-OCT showed structural elevation of the retinal pigment epithelium (RPE) consistent with drusen in the right eye, but no evidence of exudation.

Non-exudative MNV was detected with SS-OCTA imaging, where the areas of confluent drusen corresponded to a DLS seen on individual B-scans. Segmentation of RPE-Bruch’s membrane on the SS-OCTA angiographic flow map showed that the patient had three independent neovascular complexes.

The patient was counselled to return for follow-up in March 2020, but because of the COVID-19 pandemic, she cancelled that appointment. A re-scheduled visit in April was also cancelled. In May, 4 months after her January appointment, she presented to the emergency department because of sudden vision loss in the right eye.

Examination showed count fingers VA and identified a massive sub-macular haemorrhage along with exudation. “This situation could have been prevented by home monitoring and even better by home OCT monitoring that could have showed exudation developing long before the haemorrhage occurred,” Dr Rosenfeld said.

Detecting MNV on OCTA

Dr Rosenfeld credited the ability to detect MNV to Dr Ruikang Wang of the University of Washington in Seattle, United States, who developed an optical microangiography algorithm that enables flow detection in OCT images. Using specific segmentation strategies, clinicians can identify subclinical MNV lesions using a number of different slab configurations with different boundaries.

For the purposes of his study, Dr Rosenfeld used a slab extending from the outer retina (OR) to the choriocapillaris (CC), which is termed the ORCC slab. He noted that the presence of subclinical MNV had been described in the 1990s in eyes that had undergone indocyanine green angiography (ICGA). The ability to identify these lesions equally well using non-invasive SS-OCTA imaging was demonstrated by Dr Rosenfeld and his colleagues in a study of patients with asymptomatic, intermediate AMD in one eye and exudative NV AMD in the fellow eye.¹

Subsequently, Dr Rosenfeld and his colleagues went on to investigate the prevalence and natural history of non-exudative MNV in dry AMD. For this study, they included patients with dry AMD in one eye and a fellow eye with exudative AMD. In the eyes with dry AMD, they found a 14-fold increased risk of developing exudation within 2 years among eyes with non-exudative MNV compared with eyes that did not have subclinical MNV.²

Overall, if the fellow eye had exudative AMD, the prevalence of a non-exudative MNV in an eye with dry AMD was 13%. The prevalence was similar in eyes with either intermediate AMD or geographic atrophy.

Follow-up of eyes with non-exudative MNV showed that the lesions can grow without becoming exudative. Anti-vascular endothelial growth factor (VEGF) treatment was administered when symptomatic fluid developed in association with a decrease in vision; the treatment was effective in resolving the fluid and improving VA, but there were no obvious effects on lesion morphology for type 1 MNV, which comprised 93% of the lesions.

Search for changes that predict exudation

Studies conducted to find possible biomarkers to predict exudative conversion have so far shown no association with size or growth of the MNV prior to exudation or with changes in the volume of pigment epithelial detachments associated with the MNV prior to exudation, choriocapillaris flow deficits or the surrounding choroidal vasculature.³ “Additional potential predictors we are looking at include flow velocity within the MNV or in the choriocapillaris around the MNV and changes in choroidal blood flow,” Dr Rosenfeld noted.

He explained that in the Phase 2 FILLY study investigating pegcetacoplan for the treatment of geographic atrophy, the adverse event analysis showed that new-onset exudation developed in a dose-dependent fashion, occurring in 21% of eyes treated monthly with the investigational agent, in 9% of eyes receiving treatment every other month, and in only one eye (1.2%) in the sham-treated control group.⁴ A post hoc review of images obtained at baseline showed that the DLS was present in 73% of eyes that developed exudative AMD versus 32% that did not develop exudation.⁵

“These eyes with the DLS had subclinical neovascularisation, but we were not prepared to capture these eyes at baseline,” Dr Rosenfeld explained. “Now, in the Phase 3 trials investigating pegcetacoplan, DLS at baseline is being identified and these eyes are being followed carefully for the development of exudation that will be treated with anti-VEGF therapy.”

However, Dr Rosenfeld added that the take-home message from FILLY “is that the VA outcome was just as good in eyes that developed exudation compared with those that did not because they were treated promptly with, and responded very well to, anti-VEGF therapy.”

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Philip J. Rosenfeld, MD, PhD

E: prosenfeld@med.miami.edu

This article is based on Dr Rosenfeld’s presentation at the 2021 Ohio Ophthalmological Society virtual annual meeting. Dr Rosenfeld receives research support from and is a consultant to Carl Zeiss Meditec and is chairman of the steering committee of the Advanced Retina Imaging Network, which is a global consortium of clinical researchers and the Zeiss Medical Technology business group.

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References

1. Roisman L, Zhang Q, Wang RK, et al. Optical coherence tomography angiography of asymptomatic neovascularization in intermediate age-related macular degeneration. Ophthalmology. 2016;123:1309-1319.

2. Yang J, Zhang Q, Motulsky EH, et al. Two-year risk of exudation in eyes with nonexudative age-related macular degeneration and subclinical neovascularization detected with swept source optical coherence tomography angiography. Am J Ophthalmol. 2019;208:1-11.

3. Shen M, Zhang Q, Yang J, et al. Swept-source oct angiographic characteristics of treatment-naive nonexudative macular neovascularization in amd prior to exudation. Invest Ophthalmol Vis Sci. 2021;62:14.

4. Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to age-related macular degeneration: a randomized phase 2 trial. Ophthalmology. 2020;127:186-195.

5. Wykoff CC, Rosenfeld PJ, Waheed NK, et al. Characterizing new-onset exudation in the randomized phase 2 FILLY trial of complement inhibitor pegcetacoplan for geographic atrophy. Ophthalmology. Published online 10 March 2021.

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