Abstract - Quantitative Analysis of Retinal Layer Thickness Surrounding Geographic Atrophy Lesions Using OCT

We are excited to share our latest abstract, published in the IOVS Journal (June 2024). This study explores the spatial distribution of retinal layer thickness surrounding Geographic Atrophy (GA) lesions using OCT. Leveraging our advanced AI-based OCT segmentation, we provide a quantitative framework to understand structural changes and identify potential biomarkers for GA progression. Dive into the findings below!

‍

Introduction 

Geographic atrophy (GA) is a debilitating manifestation of advanced age-related macular degeneration (AMD), defined by the degeneration of retinal pigment epithelium (RPE) and photoreceptors (PR). 

‍

Optical coherence tomography (OCT) has become an invaluable tool for imaging retinal structures because it allows atrophy to be studied in three dimensions, providing detailed and quantitative information on the loss and morphological change of specific retinal layers. We previously showed a strong correlation between the atrophic lesion measured by means of fundus autofluorescence (FAF) and the structural loss of RPE and PR in OCT. 

The Classification of Atrophy Meetings (CAM) group proposed consensus criteria based on OCT-defined changes in the different retinal layers and the choroid to classify atrophy secondary to AMD¹. Based on this classification, GA has been categorised as a subset of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA). As a continuum of morphological changes occurs from the early to late stages of AMD, further information about the layers and other anatomical features assessed by means of OCT may offer a deeper understanding of the evolution of the disease.

In this scenario, we present a comprehensive analysis of the retinal layer thickness surrounding RORA lesions using OCT A-scans.

‍

Methods

In collaboration with Dr. Robyn Guymer and Dr. Zhichao Wu (Centre for Eye Research Australia, we analysed data (500,000 A-scans) from participants (N=18) of the LEAD trial who developed complete RORA lesions. The Myoid Zone (MZ), Ellipsoid zone + outer photoreceptor segment + interdigitation zone (EZ+OPR+IZ), RPE, and the choroids (CC+CS) were automatically segmented with our OCT segmentation device (Figure 1). The thickness was measured in staggered distance bands from the lesion edge and drusen material edge (0 mm to 1 mm distance at 0.1 mm intervals) (Figure 2), excluding lesion areas for drusen and vice-versa. Linear mixed-effects models were used to compare the layer thickness to the distance from the lesion edge, with patient ID used as a random effect, controlled from distance from fovea.

‍

‍

‍

‍

‍

Results

We showed a distinct spatial distribution of photoreceptor, RPE, and CC+CS thickness loss outside the lesion boundaries (Figure 3). MZ and EZ+OPR+IZ increase in thickness further from the RORA lesion edge, showing a steeper decline closer to the lesion edge (all bins, p<0.01). RPE is the thinnest close to the lesion edge but is the thickest at around 0.2 mm from the lesion (all bins, p<0.01). From the drusen edge, RPE is thinnest the furthest from the lesion (all bins, p<0.01). CC+CS was the thickest furthest from the lesion edge, while it was the thinnest furthest from the drusen material edge (all bins, p<0.01).

‍

‍

Conclusions

When investigating the layer thickness in response to the proximity to the lesion, we showed a distinct spatial distribution of PR, RPE, and CC+CS thickness loss outside the lesion boundaries. This behaviour might be related to further RORA lesion spreading and may help identify early biomarkers for disease progression, in line with recent findings ^2,3. Our approach contributes to the growing knowledge concerning RORA and establishes a quantitative framework for characterising structural changes surrounding lesions. 

‍

Want to explore how our platform can transform your R&D initiatives and enhance patient outcomes? Request a demo, and see our technology in action! We are here to enable the right decisions sooner in Healthcare.

‍

‍

This article was written by Romina Lasagni Vitar, PhD, and is based on the research work of Joseph Blair, PhD

References

1. Sadda SR, Guymer R, Holz FG, et al. Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3. Ophthalmology. 2018;125:537-548. doi:10.1016/j.ophtha.2017.09.028

2. Yordi S, Cakir Y, Kalra G, et al. Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration. J Pers Med. 2024;14:543. doi:10.3390/jpm14050543

3. Lally D, Abbruscato A, Yordi S, et al. Elamipretide-Mediated Visual Function Improvements Are Associated With Ellipsoid Zone Integrity in Patients With Geographic Atrophy. Investigative Ophthalmology & Visual Science. 2023;64:2261.