Shane Griffin, MD MCR
California Pacific Medical Center, San Francisco, CA
On the third day of the conference, Dr. David Sarraf welcomed the international audience to the 10th annual Pacific Retina Club (PRC) & International Retinal Imaging Society (IntRIS) symposium. As a joint meeting this year, the IntRIS session focused on the latest developments in retinal imaging.
Sessions 1 & 2: Technology Innovations I and II
The first session highlighted cutting-edge technologies for studying retinal pathophysiology in vivo. Dr. Siyu Chen from OHSU discussed OCT split-spectrum amplitude decorrelation optoretinography (SSADOR).1 Excitingly, this technology correlates with and may be more sensitive than microperimetry for tracking photoreceptor dysfunction. Next, Dr. Amani Fawzi presented her work characterizing retinal pericyte loss in diabetic retinopathy.2–4 Impressively, she showed a quantifiable level of pericyte loss leading to increased diabetic macular edema and that this change correlates with renal dysfunction.
Next was the fluorescence lifetime imaging ophthalmoscopy (FLIO) session directed by Dr. Paul Bernstein and Dr. Ruikang Wang. Dr. Chantal Dysli from Universität Bern discussed how she used FLIO to characterize fluorescence lifetimes in geographic atrophy5 and peripapillary atrophy, with alpha mixed, beta intermediate, and gamma zone showing the longest lifetimes. Dr. Bernstein finished the session discussing the clinical utility of FLIO in hydroxychloroquine retinal toxicity.6,7
Session 3: OCTA Imaging
Using wide-field OCTA, Dr. Yali Jia from OHSU demonstrated ambiguities and limitations in identifying areas of subclinical neovascularization using traditional methods in diabetic retinopathy. She showed how wide-field OCTA may help clinicians identify individuals at risk of proliferative disease as well as quantify areas of vascular non-perfusion.8 As OCTA becomes increasingly deployed in clinical settings, the importance of standardized communication regarding its uses and features has become critical. Reporting the results of literature review, expert meetings, and IntRIS member surveys, Dr. Marion Munk from Universität Bern ended the session by describing their consensus regarding OCTA communications.
Session 4: OCT Imaging
Shifting to a discussion of presymptomatic Alzheimer’s disease, Dr. Jane Chan from UCLA built upon her related OCTA findings9 by demonstrating that systemic tau levels are correlated with GCL and IPL retinal thinning. As tau is a key marker for neurodegeneration, this OCT feature may allow for earlier detection of Alzheimer’s disease. Dr. Brandon Lujan next explained the importance of directional OCT for understanding photoreceptor orientation in diverse retinal pathologies.10 His presentation underscored the importance of considering OCT imaging position in clinical image acquisition and interpretation. Finally, Dr. Bailey Freund from Vitreous Retina Macula Consultants of New York showcased new impressive discoveries utilizing Heidelberg’s high resolution (HR) OCT device. He showed how HR allowed vascular flow to be detected in real time, and how this powerful device may soon help us to explain fundamental pathophysiological processes like drusen formation.
Session 5: Inherited Retinal and Pediatric disease
Dr. Irena Tsui from UCLA shared impressive OCTA images from pre-term infants. She described her collaboration with Dr. Christian Altenbach which permitted segmentation of distinct capillary plexuses.11,12 This exciting tool has revealed new insights in retinopathy of prematurity and may potentially allow better understanding of treatment response. Later, Dr. Cynthia Toth from Duke took the stage and honored her late colleague Dr. Joseph Izatt who sadly passed away April 7th, 2024. Dr. Izatt was an OCT inventor and innovator with immeasurable contributions to retinal imaging including pediatric research. Dr. Toth then shared a fascinating body of work in preterm infants analyzing the link between retinal and neurological development. She described the rapid neurological changes taking place during the preterm period and how this evolution correlates with observable changes in the retina.13 Her research shows a biphasic pattern of RNFL development which correlates with infant cognitive and motor development.14,15 These investigations emphasize the potential for retinal biomarkers to help us understand global infant neurodevelopment.
Session 6 & 9: Non-neovascular Age-related Macular degeneration
Dr. Elodie Bousquet from University of Paris Cité, started the session by discussing RPE pump impairment underlying the collapse of drusenoid PEDs leading to subsequent cRORA.16 This process may be related to the important OCT imaging finding of sub RPE hyporeflective spaces shown longitudinally preceding PED collapse. By identifying this non-neovascular fluid, clinicians may avoid unnecessarily treating these lesions with anti-VEGF agents.
In the second non-neovascular AMD session, Dr. Talisa E de Carlo Forest from University of Colorado discussed her recently published large cohort study identifying imaging biomarkers associated with GA growth rate including non-exudative subretinal fluid and subretinal hyperreflective material, and incomplete RPE atrophy.17 This was followed by Dr. Ruikang Wang from University of Washington and later Dr. Philip Rosenfeld from Bascom Palmer who considered the importance of calcified drusen when studying OCTA signals as these drusen scatter light. In not adequately accounted for, this effect may impact interpretation of adjacent vascular flow.18
Session 7: Vitreoretinal disease
Dr. Andrea Govetto from Humanitas University, Italy started the session by reconsidering the nature of non-operculated peripheral retinal holes. Through wide-field OCT imaging, he was able to demonstrate hypo-reflective lacunae overlying the majority of such holes. Using this imaging data, he proposed a pathophysiological explanation for the development and maintenance of these lesions, as well as potential imaging applications for their monitoring. Dr. Fiammetta Catania also from Humanitas University, Italy then discussed the potential link between choriocapillaris impairment and lamellar macular hole development.19 She discussed fascinating pathophysiological mechanisms by which microvascular abnormalities may lead to a greater predisposition for lamellar hole formation.
Session 8: Retinal vascular disease
From University of Paris Cité, Dr. Valérie Krivosic started the session with her discussion of OCTA findings in macular telangiectasia and how these vascular changes may serve as a biomarker for disease progression.20 Next Dr. Nadia Waheed from New England Eye Center, shared exciting work with Dr. James Fujimoto using variable interscan time analysis OCTA (VISTA) for studying blood flow in microaneurysms in patients with diabetic retinopathy.21 Following the presentation, she and Dr. Bailey Freund proposed hypotheses regarding the relationship between blood flow speed and clinical retinal fluid leakage.
Remembering Ramin Tadayoni, MD, PhD
Dr. Alain Gaudric was welcomed to the stage to remember Dr. Ramin Tadayoni who recently passed away at the age of 54. Dr. Gaudric who trained and was a close colleague of Dr. Tadayoni, shared his reflections on the life and impact of this internationally-recognized physician scientist. “The future was his domain,” said Dr. Gaudric as he highlighted Dr. Tadayoni’s contributions as a “talented teacher, surgeon, and scientist… who always showed courtesy toward colleagues and patients.” Dr. Gaudrics heartfelt memorial ended with his reflection: “he was a very sincere person… and his integrity was total.”
Session 10: Inflammatory and infectious disease
Early in the uveitis session, Dr. Jesse Jung from Eastbay Retina in California discussed his early findings of potential retinal changes in thyroid eye disease patients who have received the IGF-1 targeted therapy, teprotumumab. Subsequently, Dr. Prithi Ramtohul from Aix-Marseille Université, France discussed multi-zonal outer retinopathy and retinal pigment epitheliopathy (MORR) which may represent a distinct entity or an unusual variant of AZOOR.22 He discussed phenotypic patterns of progression of the multiple zones of involvement, as well as peripapillary and far peripheral changes seen distinctly in MORR. Finally, Dr. Ramtohul discussed potential response to treatment in cases of MORR, including with TNF-alpha and intravitreal steroid.
Session 11: Imaging of the Choroid and Related diseases
The choroidal imaging started with Dr. Federica Fossataro from ASST Fatebenefratelli Sacco, Italy who discussed the growing area of retinal vascular abnormalities found in patients with neurofibromatosis type 1 (NF1). She shared a comparison of imaging modalities for detecting these lesions, which are now included in the diagnostic criteria for NF1. Dr. Fossataro concluded that image quality was a key limitation in deploying color fundus, near-infrared, and en face OCT imaging for lesion detection. To complete the session, our host Dr. David Sarraf from UCLA discussed the potential pathophysiological mechanism of RPE pump reversal in diseases in the central serous chorioretinopathy spectrum.23 He proposed an elegantly simple explanation of RPE function like a water wheel that with increased pressure and resistance in pachychoroid states may reverse its direction of action leading to active leakage into the subretinal space.
5th Annual Lawrence A. Yannuzzi Award Lecture
Dr. Cynthia Toth introduced the co-inventor of optical coherence tomography and our esteemed lecturer: Dr. James Fujumoto and he was greeted by a standing ovation. Throughout Dr. Fujimoto’s lecture, he honored his career colleagues including Dr. Joel Schuman, Dr. David Huang, Dr. Eric Swanson, the late Dr. Joseph Izatt, and Dr. Michael Hee. He began his moving lecture by sharing his gratitude towards the clinician retinal specialist who serve patients like his father every day: “I wouldn’t be here without you.” Dr. Fujimoto explained that his father had suffered from a retinal hemorrhage early in his life, and without the treatment his father received from a retinal specialist named Dr. John Bellows, his life would have been very different. He proceeded to recount the history of OCT, key steps in its wide-spread adoption, and new cutting-edge advancements in this area. To conclude he encouraged developing scientists to believe in their translational research which can yield substantial clinical benefits.
Session 12: Neovascular Age-related Macular degeneration
To start the 12th session, Dr. Riccardo Sacconi from University Vita-Salute, Italy discussed type 3 macular neovascularization (MNV) as a predictor of atrophy development and progression. This long-term follow up of previous results24 showed that the presence of subretinal fluid is a long-term negative predictor of final BCVA in type 3 MNV. Independent predictors of long-term geographic atrophy progression included baseline level of atrophy, reticular pseudodrusen, subretinal hyper-reflective material, and nascent GA as well as total number of injections received. He suggested that this last point may encourage clinicians to extend treatment intervals earlier to PRN dosing in certain clinical circumstances. To complete the session. Dr. Gemmy Cheung from Singapore National Eye Centre, discussed a new terminology framework for defining, detecting, and quantifying fibrosis in neovascular AMD. She shared the evaluation of expert opinions which will subsequently be sent to InTRS members before standardized nomenclature recommendations are made.
Session 13 & 14: Members-in-Training
During the first members-in training session sponsored by Dr. Elodie Bousquet, Dr. Alessandro Feo from UCLA reviewed the important link between ischemic perivascular lesions and cardiovascular disease.25,26 This presentation led to an expanded discussion of how ocular biomarkers may serve as surrogate markers of systemic health including those traditionally associated with age-related macular degeneration.27 In the final session and sponsored by Dr. Philip Rosenfeld, Dr. Allessandro Berni from Bascom Palmer discussed an exciting method for quantifying the total burden of retinal hyperreflective foci. As these lesions have been linked to higher risk in AMD28, such quantification schemes may provide valuable prognostic information regarding disease progression as well as better stratify patients in clinical trials.
Meeting Adjourned
At the end of the three-day meeting in Los Angeles, Dr. David Sarraf made his closing remarks.
1. Chen S, Ni S, Jiménez-Villar A, et al. Optical coherence tomography split-spectrum amplitude-decorrelation optoretinography. Opt Lett. 2023;48:3921. doi:10.1364/OL.492178
2. Huang BB, Fukuyama H, Burns SA, Fawzi AA. Imaging the Retinal Vascular Mural Cells In Vivo: Elucidating the Timeline of Their Loss in Diabetic Retinopathy. ATVB. 2024;44:465-476. doi:10.1161/ATVBAHA.123.320169
3. Huang BB, Fukuyama H, Konopek N, et al. Retinal Pericyte Density Declines Before the Onset of Clinically-apparent Diabetic Retinopathy while Increased Non-perfusion Drives Leakage. Investigative Ophthalmology & Visual Science. 2023;64:3839-3839.
4. Decker N, Huang BB, Fukuyama H, et al. Retinal Pericyte Loss is Correlated with Capillary Non-perfusion in Preclinical Stages of Diabetic Retinopathy. Investigative Ophthalmology & Visual Science. 2023;64:1061-1061.
5. Lincke JB, Dysli C, Jaggi D, et al. LONGITUDINAL FOVEAL FLUORESCENCE LIFETIME CHARACTERISTICS IN GEOGRAPHIC ATROPHY USING FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY. Retina. 2021;41:2391-2398. doi:10.1097/IAE.0000000000003222
6. Sauer L, Vitale AS, Modersitzki NK, Bernstein PS. Fluorescence lifetime imaging ophthalmoscopy: autofluorescence imaging and beyond. Eye. 2021;35:93-109. doi:10.1038/s41433-020-01287-y
7. Sauer L, Calvo CM, Vitale AS, et al. Imaging of Hydroxychloroquine Toxicity with Fluorescence Lifetime Imaging Ophthalmoscopy. Ophthalmology Retina. 2019;3:814-825. doi:10.1016/j.oret.2019.04.025
8. Hormel TT, Liang GB, Wei X, et al. Visualizing features with wide-field volumetric OCT angiography. Opt Express. 2024;32:10329-10347. doi:10.1364/OE.510640
9. Corradetti G, Oncel D, Kadomoto S, et al. Choriocapillaris and Retinal Vascular Alterations in Presymptomatic Alzheimer’s Disease. Invest Ophthalmol Vis Sci. 2024;65:47. doi:10.1167/iovs.65.1.47
10. Lujan BJ, Griffin S, Makhijani VS, et al. Directional Optical Coherence Tomography Imaging of Macular Pathology. Retina. Published online March 22, 2024. doi:10.1097/IAE.0000000000004105
11. Kothari N, Huang M, Lin F, et al. Optical Coherence Tomography Angiography in Neonates with Retinopathy of Prematurity. Investigative Ophthalmology & Visual Science. 2019;60:4556-4556.
12. Falavarjani KG, Iafe NA, Velez FG, et al. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEA IN CHILDREN BORN PRETERM. Retina. 2017;37:2289-2294. doi:10.1097/IAE.0000000000001471
13. Shen LL, Mangalesh S, McGeehan B, et al. Birth Weight Is a Significant Predictor of Retinal Nerve Fiber Layer Thickness at 36 Weeks Postmenstrual Age in Preterm Infants. American Journal of Ophthalmology. 2021;222:41-53. doi:10.1016/j.ajo.2020.08.043
14. Shen LL, Mangalesh S, McGeehan B, et al. Biphasic change in retinal nerve fibre layer thickness from 30 to 60 weeks postmenstrual age in preterm infants. Br J Ophthalmol. 2023;107:1680. doi:10.1136/bjo-2022-321621
15. Toth C, Shimony JS, McGeehan B, et al. Preterm infant retinal microanatomy from bedside optical coherence tomography imaging relative to injury score on brain MRI. Investigative Ophthalmology & Visual Science. 2020;61:2776-2776.
16. Balaratnasingam C, Yannuzzi LA, Curcio CA, et al. Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments. Invest Ophthalmol Vis Sci. 2016;57:5479. doi:10.1167/iovs.16-19816
17. De Carlo Forest TE, Gill Z, Lisker-Cervantes A, et al. Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate. American Journal of Ophthalmology. 2024;264:168-177. doi:10.1016/j.ajo.2024.03.023
18. Lu J, Cheng Y, Li J, et al. Automated segmentation and quantification of calcified drusen in 3D swept source OCT imaging. Biomed Opt Express. 2023;14:1292. doi:10.1364/BOE.485999
19. Crincoli E, Parolini B, Catania F, et al. Prediction of functional and anatomical progression in lamellar macular holes. Ophthalmology Science. Published online April 2024:100529. doi:10.1016/j.xops.2024.100529
20. Krivosic V, Lavia C, Aubineau A, et al. OCT of Outer Retinal Hyperreflectivity, Neovascularization, and Pigment in Macular Telangiectasia Type 2. Ophthalmology Retina. 2021;5:562-570. doi:10.1016/j.oret.2020.09.012
21. Hwang Y, Won J, Yaghy A, et al. Retinal blood flow speed quantification at the capillary level using temporal autocorrelation fitting OCTA [Invited]. Biomed Opt Express. 2023;14:2658-2677. doi:10.1364/BOE.488103
22. Ramtohul P, Marchese A, Introini U, et al. MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR? Retina. 2023;43:1890-1903. doi:10.1097/IAE.0000000000003927
23. Fossataro F, Fossataro C, Abraham N, et al. Pathogenesis of Central Serous ChorioRetinopathy and the Link between Choroidal Hyperpermeability and RPE Pump Reversal. American Journal of Ophthalmology. Published online May 2024:S0002939424001818. doi:10.1016/j.ajo.2024.04.025
24. Sacconi R, Battista M, Borrelli E, et al. OCT-A characterisation of recurrent type 3 macular neovascularisation. Br J Ophthalmol. 2021;105:222-226. doi:10.1136/bjophthalmol-2020-316054
25. Bousquet E, Santina A, Abraham N, et al. Detection of Paracentral Acute Middle Maculopathy Can Prevent Blindness and Death. Retina. 2023;43:1827-1832. doi:10.1097/IAE.0000000000003939
26. Madala S, Adabifirouzjaei F, Lando L, et al. Retinal Ischemic Perivascular Lesions, a Biomarker of Cardiovascular Disease. Ophthalmology Retina. 2022;6:865-867. doi:10.1016/j.oret.2022.05.005
27. Drakopoulos M, Zhang KX, Zhang DL, et al. Independence of Ocular Biomarkers of Cardiac Risk in Macular Degeneration. Ophthalmology Retina. Published online November 2023:S2468653023005791. doi:10.1016/j.oret.2023.11.003
28. Vallino V, Berni A, Coletto A, et al. Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD. Graefes Arch Clin Exp Ophthalmol. Published online April 30, 2024. doi:10.1007/s00417-024-06497-8
