Artificial Intelligence Recognizes Deteriorating Photoreceptors

Summary: Novel artificial intelligence software can provide a precise assessment of the progression of geographic atrophy. The technology can also determine the integrity of photoreceptors and detect progressive degenerative changes beyond the main lessons associated with GA.

Source: University of Bonn

A software based on artificial intelligence (AI), which was developed by researchers at the Eye Clinic of the University Hospital Bonn, Stanford University and University of Utah, enables the precise assessment of the progression of geographic atrophy (GA), a disease of the light sensitive retina caused by age-related macular degeneration (AMD). This innovative approach permits the fully automated measurement of the main atrophic lesions using data from optical coherence tomography, which provides three-dimensional visualization of the structure of the retina. In addition, the research team can precisely determine the integrity of light sensitive cells of the entire central retina and also detect progressive degenerative changes of the so-called photoreceptors beyond the main lesions. The findings will be used to assess the effectiveness of new innovative therapeutic approaches. The study has now been published in the journal “JAMA Ophthalmology”.

There is no effective treatment for geographic atrophy, one of the most common causes of blindness in industrialized nations. The disease damages cells of the retina and causes them to die. The main lesions, areas of degenerated retina, also known as “geographic atrophy”, expand as the disease progresses and result in blind spots in the affected person’s visual field. A major challenge for evaluating therapies is that these lesions progress slowly, which means that intervention studies require a long follow-up period. “When evaluating therapeutic approaches, we have so far concentrated primarily on the main lesions of the disease. However, in addition to central visual field loss, patients also suffer from symptoms such as a reduced light sensitivity in the surrounding retina,” explains Prof. Dr. Frank G. Holz, Director of the Eye Clinic at the University Hospital Bonn. “Preserving the microstructure of the retina outside the main lesions would therefore already be an important achievement, which could be used to verify the effectiveness of future therapeutic approaches.”

Integrity of light sensitive cells predicts disease progression

The researchers were furthermore able to show that the integrity of light sensitive cells outside areas of geographic atrophy is a predictor of the future progression of the disease. “It may therefore be possible to slow down the progression of the main atrophic lesions by using therapeutic approaches that protect the surrounding light sensitive cells,” says Prof. Monika Fleckenstein of the Moran Eye Center at the University of Utah in the USA, initiator of the Bonn-based natural history study on geographic atrophy, on which the current publication is based.

This shows the retina
Image of the central retina in a patient with geographic atrophy – serves as a reference for optical coherence tomography (OCT). Image is credited to University Eye Hospital Bonn.

“Research in ophthalmology is increasingly data-driven. The fully automated, precise analysis of the finest, microstructural changes in optical coherence tomography data using AI represents an important step towards personalized medicine for patients with age-related macular degeneration,” explains lead author Dr. Maximilian Pfau from the Eye Clinic at the University Hospital Bonn, who is currently working as a fellow of the German Research Foundation (DFG) and postdoctoral fellow at Stanford University in the Department of Biomedical Data Science. “It would also be useful to re-evaluate older treatment studies with the new methods in order to assess possible effects on photoreceptor integrity.”

About this artificial intelligence research article

University of Bonn
Maximilian Pfau – University of Bonn
Image Source:
The image is credited to University Eye Hospital Bonn.

Original Research: Closed access
“Progression of Photoreceptor Degeneration in Geographic Atrophy Secondary to Age-Related Macular Degeneration” by Maximilian Pfau, Leon von der Emde, Luis de Sisternes, Joelle A. Hallak, Theodore Leng, Steffen Schmitz-Valckenberg, Frank G. Holz, Monika Fleckenstein, Daniel L. Rubin, MD. JAMA Ophthalmology.


Progression of Photoreceptor Degeneration in Geographic Atrophy Secondary to Age-Related Macular Degeneration

Sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

To quantify photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, to evaluate its association with future GA progression, and to characterize its spatio-temporal progression.

Design, Setting, and Participants
Monocenter cohort study (Directional Spread in Geographic Atrophy [NCT02051998]) and analysis of data from a normative data study at a tertiary referral center. One hundred fifty-eight eyes of 89 patients with a mean (SD) age of 77.7 (7.1) years, median area of GA of 8.87 mm2 (IQR, 4.09-15.60), and median follow-up of 1.1 years (IQR, 0.52-1.7 years), as well as 93 normal eyes from 93 participants.

Longitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30° × 25°) were segmented with a deep-learning pipeline and standardized in a pointwise manner with age-adjusted normal data (z scores). Outer nuclear layer (ONL), photoreceptor inner segment (IS), and outer segment (OS) thickness were quantified along evenly spaced contour lines surrounding GA lesions. Linear mixed models were applied to assess the association between photoreceptor-related imaging features and GA progression rates and characterize the pattern of photoreceptor degeneration over time.

Main Outcomes and Measures
Association of ONL thinning with follow-up time (after adjusting for age, retinal topography [z score], and distance to the GA boundary).

The study included 158 eyes of 89 patients (51 women and 38 men) with a mean (SD) age of 77.7 (7.1) years. The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; 95% CI, 0.80-0.85; compared with manual markings) and revealed a marked interpatient variability in photoreceptor degeneration. The ellipsoid zone (EZ) loss-to-GA boundary distance and OS thickness were prognostic for future progression rates. Outer nuclear layer and IS thinning over time was significant even when adjusting for age and proximity to the GA boundary (estimates of −0.16 μm/y; 95% CI, −0.30 to −0.02; and −0.17 μm/y; 95% CI, −0.26 to −0.09).

Conclusions and Relevance
Distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Macula-wide photoreceptor laminae thinning represents a potential candidate end point to monitor treatment effects beyond mere GA lesion size progression.

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