conference reporter

Optical Coherence Tomography and Multimodal Diagnostics in Age-Related Macular Degeneration and Geographic Atrophy

by SriniVas R. Sadda, MD, FARVO

Overview

As seen at AAO 2022, multimodal diagnostics promise to usher in a more molecular level analysis paradigm in age-related macular degeneration (AMD) and geographic atrophy (GA). The ability to predict disease progression is of vital importance, and a new treatment era is emerging for patients with these conditions.

Following these presentations, featured expert SriniVas R. Sadda, MD, FARVO, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Sadda’s clinical perspectives on these findings are presented here.

SriniVas R. Sadda, MD, FARVO

Director, Artificial Intelligence & Imaging Research
Doheny Eye Institute
Pasadena, CA
Professor of Ophthalmology
David Geffen School of Medicine at UCLA
Los Angeles, CA

“There were a number of fascinating presentations on multimodal diagnostics at AAO 2022. In fact, some major innovations and advances in imaging were presented that will have real relevance for us as we think about how to treat and approach patients with GA and AMD in the future.”

SriniVas R. Sadda, MD, FARVO

The eye is an optically clear organ, so we are able to access it with a diverse range of imaging approaches involving light. There were a number of fascinating presentations on multimodal diagnostics at AAO 2022. In fact, some major innovations and advances in imaging were presented that will have real relevance for us as we think about how to treat and approach patients with GA and AMD in the future. Optical coherence tomography (OCT) is one of the central technologies that we use in our assessment of patients with retinal diseases, including AMD. And, whether you are considering OCT or newer emerging techniques such as flavoprotein fluorescence (FPF), there is always more for us to learn.

Innovations in OCT continue to emerge and promise to have major impacts. Lejla Vajzovic, MD, gave an update on intraoperative OCT, noting that there continues to be an evolution toward these systems having higher speeds and higher resolutions. This could impact how we approach GA treatment, since next-generation systems may aid with visualizing the blebs that develop in the retina during therapeutic subretinal injections. This is quite important as we contemplate the subretinal delivery of targeted therapies and gene-based therapeutics in AMD and GA.

Home OCT was another topic of great interest at AAO 2022, including in a presentation by Nancy M. Holekamp, MD. It was also one of the topics from "The 2022 Debates," during which Anat Loewenstein, MD, argued that home OCT would be a boon for retinal specialists, while Carl C. Awh, MD, took the opposing view. I think that home OCT will be relevant for GA in the future, even though the immediate application is expected to be in patients with neovascular AMD. Pegcetacoplan and avacincaptad pegol are both complement-targeted therapies that have been shown to slow the rate of GA progression, and both may be associated with an increased incidence of choroidal neovascularization (CNV). Once available, patients would receive injections of these agents in a clinic and then would return to their home. They may need an assessment periodically to monitor for any CNV development, and, while OCT can be done at the office, I think that it would be an exciting development to incorporate home OCT into the treatment armamentarium for our patients. 

Advances in OCT angiography (OCT-A) were highlighted in a presentation by Nadia Khalida Waheed, MD. One of the major applications of OCT-A is certainly in wet AMD, primarily using it to assess for the development of CNV, which, again, is very relevant in the context of GA treatments. Patients can develop CNV with exudation, but it can also sometimes occur without exudation. In the case of the latter, there is no evidence of fluid to be identified or quantified by structural OCT. Thus, OCT-A will play a big role in that scenario. 

OCT-A also allows us to assess the choriocapillaris, which has been reported by a number of groups to be very relevant to GA progression. In fact, during the Charles L. Schepens, MD, Lecture at this year's conference, Philip J. Rosenfeld, MD, PhD, focused on the choriocapillaris in the context of AMD and GA, noting that flow deficits in the choriocapillaris can be quite extensive outside of the GA lesions. Such findings could be an important predictor of GA lesion growth. Dr Rosenfeld suggested that we might be able to predict almost 60% of the enlargement rate based on imaging features on OCT-A and structural OCT, including the attenuation of photoreceptors, which is exciting and will be important as we enter the era of therapeutics for GA. 

Novel imaging techniques that are in development were also a part of the excitement at AAO 2022. For example, Rishi P. Singh, MD, discussed the use of FPF, a noninvasive imaging technology that essentially measures oxidative stress in the eye. FPF has the potential to be a functional biomarker for oxidative damage from mitochondrial dysfunction in retinal diseases. Further, Sunil K. Srivastava, MD, gave an excellent presentation on ellipsoid zone preservation in patients with AMD who are treated with subcutaneous elamipretide, a drug that is currently being studied for its potential to improve mitochondrial function. Both of these presentations highlighted the importance of mitochondria in retinal diseases, including AMD and GA. 

In summary, in addition to OCT and OCT-A, I think that other novel technologies such as FPF and fluorescence lifetime imaging ophthalmoscopy, which can assess metabolic processes that are linked to the visual cycle, are going to be the wave of the future, enabling us to characterize the ongoing pathology of GA at the molecular level. Such advances will nicely complement the new era of targeted treatment.

References

Awh CC. Home OCT is going to be the bane of retina specialists. Section VI: the 2022 debates. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Chen AX, Conti TF, Hom GL, et al. Functional imaging of mitochondria in retinal diseases using flavoprotein fluorescence. Eye (Lond). 2021;35(1):74-92. doi:10.1038/s41433-020-1110-y

Chu Z, Wang L, Zhou X, et al. Automatic geographic atrophy segmentation using optical attenuation in OCT scans with deep learning. Biomed Opt Express. 2022;13(3):1328-1343. doi:10.1364/BOE.449314

Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390. doi:10.1016/j.ophtha.2017.08.038

Guymer R, Wu Z. Age-related macular degeneration (AMD): more than meets the eye. The role of multimodal imaging in today's management of AMD—a review. Clin Exp Ophthalmol. 2020;48(7):983-995. doi:10.1111/ceo.13837

Holekamp NM. Home OCT. Section IX: imaging. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Loewenstein A. Home OCT is going to be a boon for retinal specialists. Section VI: the 2022 debates. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Mathis T, Holz FG, Sivaprasad S, et al. Characterisation of macular neovascularisation subtypes in age-related macular degeneration to optimise treatment outcomes. Eye (Lond). 2022 Sep 14. doi:10.1038/s41433-022-02231-y

Rosenfeld PJ. Rediscovering AMD with swept source OCT imaging. The Charles L Schepens MD Lecture. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Salehi MA, Mohammadi S, Gouravani M, Rezagholi F, Arevalo JF. Retinal and choroidal changes in AMD: a systematic review and meta-analysis of spectral-domain optical coherence tomography studies. Surv Ophthalmol. 2022 Jul 29;S0039-6257(22)00096-0. doi:10.1016/j.survophthal.2022.07.006

Shi Y, Zhang Q, Zhou H, et al. Correlations between choriocapillaris and choroidal measurements and the growth of geographic atrophy using swept source OCT imaging. Am J Ophthalmol. 2021;224:321-331. doi:10.1016/j.ajo.2020.12.015

Singh RP. Mitochondrial imaging insights into retinal diseases. Section IX: imaging. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Srivastava SK. Ellipsoid zone preservation in patients with age-related macular degeneration treated with subcutaneous elamipretide. Section X: late breaking developments, part II. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Vajzovic L. Update on intraoperative OCT. Section IX: imaging. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

Velaga SB, Nittala MG, Hariri A, Sadda SR. Correlation between fundus autofluorescence and en face OCT measurements of geographic atrophy. Ophthalmol Retina. 2022;6(8):676-683. doi:10.1016/j.oret.2022.03.017

Waheed NK. Update on OCT angiography. Section IX: imaging. Session presented at: 2022 Annual Meeting of the American Academy of Ophthalmology (AAO 2022); September 30-October 3, 2022; Chicago, IL.

You QS, Camino A, Wang J, et al. Geographic atrophy progression is associated with choriocapillaris flow deficits measured with optical coherence tomographic angiography. Invest Ophthalmol Vis Sci. 2021;62(15):28. doi:10.1167/iovs.62.15.28


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