Rediscovering AMD with Swept-Source OCT Imaging: The 2022 Charles L. Schepens, MD, Lecture.

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross-sectional and en face imaging strategies. DESIGN: Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30, 2022 PARTICIPANTS: Patients with AMD METHODS: Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD. MAIN OUTCOME MEASURES: SS-OCTA imaging of AMD at different stages of disease progression. RESULTS: Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-naïve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid. CONCLUSIONS: Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

Spectral-Domain and Swept-Source OCT Angiographic Scans Yield Similar Drusen Measurements When Processed with the Same Algorithm.

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P < 0.001). Conclusions: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Impact of Carotid Endarterectomy on Choriocapillaris Perfusion.

Purpose: The impact of carotid endarterectomy (CEA) on choriocapillaris (CC) perfusion was investigated using swept-source optical coherence tomography angiography (SS-OCTA) imaging before and after surgery in patients with clinically significant carotid artery stenosis (CAS). Methods: In this prospective observational study, patients with clinically significant CAS undergoing unilateral CEA had SS-OCTA imaging performed in both eyes before and within 1 week after surgery. The percent CC flow deficits (CC FD%) and CC thickness were assessed using previously validated algorithms. Multivariable regression analysis was conducted to evaluate the impact of variables on the change in CC measurements. Results: A total of 112 eyes from 56 patients with an average age of 72.6 ± 6.9 years were enrolled. At baseline, significantly higher CC FD% and thinner CC thickness were observed on the surgical side (eyes ipsilateral to the side of CEA) versus the nonsurgical side (eyes contralateral to the side of CEA) (P = 0.001 and P = 0.03, respectively). Following CEA, a significant reduction in CC FD% and a significant increase in CC thickness were detected on the surgical as compared with the nonsurgical side (P = 0.008 and P = 0.01, respectively). Smoking status positively affected CC FD% change (coefficient of variation [CV] = 0.84, P = 0.01) on the surgical side and negatively affected CC thickness change on both the surgical side (CV = -0.382, P = 0.009) and the nonsurgical side (CV = -0.321, P = 0.04). The degree of stenosis demonstrated a positive influence on CC FD% change (CV = 0.040, P = 0.02) on the surgical side. Conclusions: Unilateral CEA on the side of clinically significant CAS increases carotid blood flow, which further results in improved CC perfusion.

Bilateral Hypotony Maculopathy Associated With Ipilimumab and Nivolumab Therapy Unresponsive to Corticosteroid Treatment.

In rare instances, immunotherapy associated with hypotony and uveitis has been documented. We report the case of a 72-year-old man treated with 2 months of ipilimumab and nivolumab for metastatic melanoma who developed bilateral hypotony maculopathy and serous choroidal detachments without prominent initial uveitis. Despite treatment with topical, periocular, and intraocular corticosteroid injection, hypotony persisted 18 months after immunotherapy cessation. The patient's unresponsiveness to corticosteroids indicates the need to further explore the mechanism behind immune checkpoint inhibitor-associated hypotony. We hypothesize that immunotherapy significantly decreased aqueous humor production through ciliary body inflammation, disruption, or shutdown. [Ophthalmic Surg Lasers Imaging Retina 2023;54:301-304.].

Decreased Macular Choriocapillaris Perfusion in Eyes With Macular Reticular Pseudodrusen Imaged With Swept-Source OCT Angiography.

Purpose: To determine if macular reticular pseudodrusen (RPD) were associated with markers of impaired macular choroidal perfusion, we investigated measurements of macular choriocapillaris (CC) flow deficits (FDs), CC thickness, and mean choroidal thickness (MCT) in eyes with macular RPD compared with normal eyes and eyes with soft drusen. Methods: Eyes with intermediate age-related macular degeneration (iAMD) and normal eyes underwent 6 × 6 mm swept-source optical coherence tomography angiography (SS-OCTA) imaging to diagnose macular RPD, occupying over 25% of the fovea-centered 5 mm diameter circle, and measure outer retinal layer (ORL) thickness, CC FDs, CC thickness, MCT, and choroidal vascularity index (CVI) using previously published strategies within the same fovea-centered 5 mm circle. Results: Ninety eyes were included; 30 normal eyes, 30 eyes with soft drusen, and 30 eyes with macular RPD. The RPD eyes showed higher macular CC FDs than normal eyes (P < 0.001) and soft drusen eyes (P = 0.019). Macular CC thickness was decreased in RPD eyes compared with normal eyes (P < 0.001) and soft drusen eyes (P = 0.016). Macular MCT in RPD eyes was thinner than normal eyes (P = 0.005) and soft drusen eyes (P < 0.001). No statistically and clinically significant differences were found in the ORL thickness and CVI measurements between RPD eyes and the other two groups (all P > 0.05). Conclusions: Eyes with macular RPD had decreased macular CC perfusion, decreased CC thickness, and decreased MCT measurements compared with normal and soft drusen eyes, suggesting that RPD may result from impaired choroidal perfusion.

Automated segmentation and quantification of calcified drusen in 3D swept source OCT imaging.

Qualitative and quantitative assessments of calcified drusen are clinically important for determining the risk of disease progression in age-related macular degeneration (AMD). This paper reports the development of an automated algorithm to segment and quantify calcified drusen on swept-source optical coherence tomography (SS-OCT) images. The algorithm leverages the higher scattering property of calcified drusen compared with soft drusen. Calcified drusen have a higher optical attenuation coefficient (OAC), which results in a choroidal hypotransmission defect (hypoTD) below the calcified drusen. We show that it is possible to automatically segment calcified drusen from 3D SS-OCT scans by combining the OAC within drusen and the hypoTDs under drusen. We also propose a correction method for the segmentation of the retina pigment epithelium (RPE) overlying calcified drusen by automatically correcting the RPE by an amount of the OAC peak width along each A-line, leading to more accurate segmentation and quantification of drusen in general, and the calcified drusen in particular. A total of 29 eyes with nonexudative AMD and calcified drusen imaged with SS-OCT using the 6 × 6 mm2 scanning pattern were used in this study to test the performance of the proposed automated method. We demonstrated that the method achieved good agreement with the human expert graders in identifying the area of calcified drusen (Dice similarity coefficient: 68.27 ± 11.09%, correlation coefficient of the area measurements: r = 0.9422, the mean bias of the area measurements = 0.04781 mm2).