Clinical and Functional Characteristics of Secondary Geographic Atrophy Against the Background of Exudative Age-Related Macular Degeneration

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Abstract

Background. Studies demonstrate the need for long-term follow-up of patients with wet age-related macular degeneration (AMD) treated with inhibitors of angiogenesis to monitor long-term vision outcomes and assess the safety of antiangiogenic therapy in relation to the risk of secondary geographic atrophy. 

Aims — to determine the characteristic clinical and functional signs of secondary GA that developed against the background of wet AMD. 

Methods. In 22 patients (25 eyes) with wet AMD and 18 healthy subjects comparable in age and sex standard ophthalmological and instrumental studies were performed and photopic electroretinograms (ERGs) were recorded according to ISCEV standards, flicker-ERGs, multifocal ERGs and electrooculogram. 

Results. The appearance of the area of secondary atrophy against the background of wet AMD in eyes treated with inhibitors of angiogenesis is clinically indistinguishable from areas of geographic atrophy that developed as an outcome of dry AMD. The ERG-signs of secondary atrophy are described, which are similar to the biomarkers of primary atrophy and specifically differ from them. Secondary atrophy is characterized by the dependence of the increase in the b/a ratio on the atrophic area, reducing of the 8.3 Hz-flicker-ERG amplitude in the absence of 24 Hz-flicker ERG changes. In eyes with secondary atrophy, a significant decrease in the density of the multifocal ERG P1-peak was shown not only in the first hexagon but also in the parafoveal zone. The electrooculography results showed a sharper dark trough’s decrease in with an increase in Arden’s ratio in patients with secondary atrophya on the background of wet AMD, in contrast to the previously described changes in primary geographic atrophy. 

Conclusion. Comparison of the change in the b/a ratio with secondary atrophy area in patients with wet AMD may have clinical implications for assessing retinal dysfunction and predicting visual function. Secondary atrophy is associated with a pronounced inhibition of photoreceptor activity with better preservation of cone bipolar cells. The ERG and electrooculography data taking together indicate a more significant dysfunction of the retinal pigment epithelium in GA against the background of wet AMD and the associated deterioration of photoreceptor function than the changes characterizing primary geographic atrophy.

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About the authors

Vladimir V. Neroev

Helmholtz National Medical Research Center of Eye Diseases

Email: sekr@igb.ru
ORCID iD: 0000-0002-8480-0894
SPIN-code: 5214-4134

MD, PhD, Professor, Academician of the RAS

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

Marina V. Zueva

Helmholtz National Medical Research Center of Eye Diseases

Email: visionlab@yandex.ru
ORCID iD: 0000-0002-0161-5010
SPIN-code: 8838-3997

PhD in Biology, Professor

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

Natalia V. Neroeva

Helmholtz National Medical Research Center of Eye Diseases

Email: nneroeva@gmail.com
ORCID iD: 0000-0003-1038-2746

MD, PhD

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

Ludmila A. Katargina

Helmholtz National Medical Research Center of Eye Diseases

Email: katargina@igb.ru
ORCID iD: 0000-0002-4857-0374

MD, PhD, Professor

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

Oksana A. Losanova

Helmholtz National Medical Research Center of Eye Diseases

Author for correspondence.
Email: oksana_losanova@mail.ru
ORCID iD: 0000-0002-7356-7919
SPIN-code: 9329-0609

PhD Student

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

Marina V. Ryabina

Helmholtz National Medical Research Center of Eye Diseases

Email: mryabina@yandex.ru
ORCID iD: 0000-0001-7961-8695
SPIN-code: 6928-5676

MD, PhD, Senior Researcher

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

Irina V. Tsapenko

Helmholtz National Medical Research Center of Eye Diseases

Email: sunvision@mail.ru
ORCID iD: 0000-0002-0148-8517

PhD in Biology, Senior Researcher

Russian Federation, 14/19, Sadovaya Chernogryazskaya str., 105062, Moscow

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Supplementary files

Supplementary Files
Action
1. Fig. 1. Snapshot in InfraRed mode. OCT, horizontal slice. Fibrovascular detachment of the pigment epithelium, uneven hyperreflectivity of the RPE layer, hyperreflective contents under the RPE

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2. Fig. 2. Snapshot in InfraRed mode. OCT, vertical slice. Atrophic scar in the macula. Increased reflectivity under the retina due to RPE atrophy

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3. Fig. 3. A snapshot for autofluorescence: A - alternation of hypo- and hyperfluorescence, indicating damage to RPE. Small foci of hypofluorescence with clear contours, corresponding to secondary atrophy, without capture of fovea; B - a large round-shaped focus of hypofluorescence with the capture of fovea

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