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.

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.

Choroidal Changes After Anti-VEGF Therapy in AMD Eyes With Different Types of Macular Neovascularization Using Swept-Source OCT Angiography.

Purpose: Choroidal changes before and after anti-VEGF therapy were investigated in eyes with exudative AMD to determine if there was a difference between eyes with macular neovascularization (MNV) that arises from the choroid (type 1 or 2) versus the retinal circulation (type 3). Methods: Patients with treatment-naïve AMD were imaged with swept-source optical coherence tomography angiography using a 12 × 12-mm scan pattern. The mean choroidal thickness and choroidal vascularity index (CVI) were measured within 5-mm and 11-mm fovea-centered circles before, at the onset of, and after anti-VEGF therapy. Results: Forty-one eyes of 37 patients were included; 24 eyes with type 1 MNV, 4 eyes with type 2 MNV, and 13 eyes with type 3 MNV. Within the 5-mm and 11-mm circles, the mean choroidal thickness and CVI measurements increased from pretreatment to the onset of exudation (P ≤ 0.03). The mean choroidal thickness and CVI measurements decreased from the onset of exudation to after treatment (P < 0.001). No significant changes in mean choroidal thickness or CVI were observed when comparing measurements before or after treatment (P ≥ 0.38). No significant differences in mean choroidal thickness or CVI measurements were observed between eyes with type 1 or 2 MNV and type 3 MNV. Conclusions: In treatment-naïve AMD eyes with MNV, the choroidal thickness and vascularity increased at the onset of exudation and then decreased after anti-VEGF therapy. This finding suggests that these choroidal changes develop in response to the proangiogenic milieu before treatment and in response to treatment, regardless of the site of origin for the MNV.

Monitoring Delayed Toxoplasmosis-Related Branch Retinal Artery Occlusion Using Widefield en face Optical Coherence Tomography and Multimodal Imaging.

Ocular toxoplasmosis has a known, rare association with acute retinal artery occlusion (RAO). We describe a 21-year-old male who presented with acute focal toxoplasmosis chorioretinitis in the right eye treated with intravitreal clindamycin, intravitreal dexamethasone, and adjunct oral therapy for vision-threatening retinitis with subsequent quiescence. Nine months from his initial presentation, the patient presented with a branch RAO adjacent to an inactive retinal scar in the right eye. Widefield en face structural swept-source optical coherence tomography (SS-OCT) centered on the middle retina showed paracentral acute middle maculopathy (PAMM) in an arteriolar distribution. The patient was started on 81 mg of aspirin daily. Six months later, the en face structural SS-OCT and corresponding B-scans showed resolution of PAMM. Along with a review of the literature on toxoplasmosis-related RAOs, we present the first case of delayed-onset RAO in ocular toxoplasmosis.

Comparison between B-Scan and En Face Images for Incomplete and Complete Retinal Pigment Epithelium and Outer Retinal Atrophy.

PURPOSE: To evaluate and compare the detection of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) assessed on OCT B-scans versus persistent choroidal hypertransmission defects (hyperTDs) assessed by en face choroidal OCT images. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Patients with late atrophic age-related macular degeneration imaged on the same day using both Spectralis OCT and Cirrus OCT. MAIN OUTCOME MEASURE: Agreement between the B-scan and en face OCT for the detection of hyperTDs, cRORA, and iRORA. METHODS: Two independent graders examined en face OCT and structural OCT to determine the presence and location of hyperTDs, iRORA, and cRORA. RESULTS: A total of 239 iRORA and cRORA lesions were detected on the B-scans, and 249 hyperTD lesions were identified on the en face OCT images. There was no significant difference (P = 0.88) in the number of lesions. There was no significant difference in the 134 cRORA lesions identified on B-scans and the 131 hyperTDs detected on en face OCT images (P = 0.13). A total of 105 iRORA lesions were identified by B-scan assessment; however, 50 of these iRORA lesions met the criteria for persistent hyperTDs on en face OCT images (P < 0.001). When considering the topographic correspondence between B-scan and en face OCT detected lesions, the mean percentage of agreement between B-scan detection of cRORA lesions with en face OCT detection was 97.6 % (P = 0.13). CONCLUSIONS: We observed high overall agreement between cRORA lesions identified on B-scans and persistent hyperTDs identified on en face OCT. However, en face imaging was able to detect iRORA lesions that had a greatest linear dimension ≥ 250 µm in a nonhorizontal en face dimension. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Impact of Cataracts on the Measurement of Macular Choriocapillaris Flow Deficits Using Swept-Source OCT Angiography.

Purpose: The impact of cataracts on the measurement of macular choriocapillaris flow deficits (CC FDs) was assessed by comparing the quantitative results before and after cataract surgery using an image quality algorithm developed for swept-source optical coherence tomography angiography (SS-OCTA) scans and a validated strategy for quantifying the CC FDs. Methods: SS-OCTA image quality scores and CC FDs measurements within the fovea-centered 1-mm, 3-mm, and 5-mm diameter circles were compared before and after cataract surgery. CC FDs changes in a modified Early Treatment Diabetic Retinopathy Study (ETDRS) grid were further investigated. Results: Twenty-four eyes were studied. Overall image quality in all three circles was observed to improve significantly following the removal of cataracts (all P < 0.05). Although there was good repeatability in the measurements of CC FDs at both visits (intraclass correlation coefficients were over 0.95), significant decreases in CC FD measurements were observed after surgery within the 1-mm circle (P < 0.001) and the 3-mm circle (P = 0.011), but no changes were observed within the 5-mm circle (P = 0.509) or any of the quadrant sectors of the modified ETDRS grid (all P > 0.05). Conclusions: The presence of cataracts resulted in worse image quality and increased CC FD measurements within the fovea-centered 1-mm and 3-mm circles, with the 1-mm circle being impacted the most. Translational Relevance: The impaired detection of CC perfusion deficits within the central macula of cataract eyes needs to be appreciated when imaging the CC in phakic eyes, especially in clinical trials.

Assessments of early patellofemoral joint osteoarthritis features after anterior cruciate ligament reconstruction: a cross-sectional study.

BACKGROUND: Persistent anterior knee pain and subsequent patellofemoral joint (PFJ) osteoarthritis (OA) are common symptoms after anterior cruciate ligament reconstruction (ACLR). Quadriceps weakness and atrophy is also common after ACLR. This can be contributed by arthrogenic muscle inhibition and disuse, caused by joint swelling, pain, and inflammation after surgery. With quadriceps atrophy and weakness are associated with PFJ pain, this can cause further disuse exacerbating muscle atrophy. Herein, this study aims to identify early changes in musculoskeletal, functional and quality of health parameters for knee OA after 5 years of ACLR. METHODS: Patients treated with arthroscopically assisted single-bundle ACLR using hamstrings graft for more than 5 years were identified and recruited from our clinic registry. Those with persistent anterior knee pain were invited back for our follow-up study. For all participants, basic clinical demography and standard knee X-ray were taken. Likewise, clinical history, symptomatology, and physical examination were performed to confirm isolated PFJ pain. Outcome measures including leg quadriceps quality using ultrasound, functional performance using pressure mat and pain using self-reported questionnaires (KOOS, Kujala and IKDC) were assessed. Interobserver reproducibility was assessed by two reviewers. RESULTS: A total of 19 patients with unilateral injury who had undergone ACLR 5-years ago with persistent anterior knee pain participated in this present study. Toward the muscle quality, thinner vastus medialis and more stiffness in vastus lateralis were found in post-ACLR knees (p < 0.05). Functionally, patients with more anterior knee pain tended to shift more of their body weight towards the non-injured limb with increasing knee flexion. In accordance, rectus femoris muscle stiffness in the ACLR knee was significantly correlated with pain (p < 0.05). CONCLUSION: In this study, it was found that patients having higher degree of anterior knee pain were associated with higher vastus medialis muscle stiffness and thinner vastus lateralis muscle thickness. Similarly, patients with more anterior knee pain tended to shift more of their body weight towards the non-injured limb leading to an abnormal PFJ loading. Taken together, this current study helped to indicate that persistent quadriceps muscle weakness is potential contributing factor to the early development of PFJ pain.

Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits.

PURPOSE: Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA). DESIGN: Prospective cross-sectional study. METHODS: Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1-mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and outer retinal layer (ORL) thickness were assessed. RESULTS: In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r = -0.393, P < .001), LL-BCVA (r = -0.534, P < .001), and the LLVAD (r = 0.439, P < .001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA, and LLVADs (all P < .05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2 = 0.24, P < .05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2 = 0.44, P < .01); and central CC FD% and ORL thickness were associated with LLVAD (R2 = 0.24, P < .01). CONCLUSIONS: The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.

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.

Longitudinal quantification of choriocapillaris flow deficits in persistent placoid maculopathy: a case report.

BACKGROUND: Persistent placoid maculopathy (PPM) is a rare idiopathic chorioretinopathy characterized by choriocapillaris (CC) hypoperfusion. In a case of PPM, we quantified CC flow deficits (FDs) over time and observed an increase in CC perfusion as the visual acuity and outer photoreceptor anatomy improved. CASE PRESENTATION: A 58-year-old man was diagnosed with PPM in both eyes based on the patient's clinical presentation and imaging. He presented with sudden-onset central scotomas in both eyes for about two months. On referral, the best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/100 in the left eye. Plaque-like yellowish macular lesions were observed bilaterally and autofluorescence imaging showed bilateral hyperautofluorescent lesions. Fluorescein angiography (FA) revealed early-phase hyper-fluorescent staining that intensified in the late phases, while indocyanine green angiography (ICGA) displayed persistent hypofluorescence in both eyes. Foveal centered swept source optical coherence tomography (SS-OCT) B-scans showed bilateral focal deposits on the level of retinal pigment epithelium (RPE) and disruption of outer photoreceptor bands. The CC FDs were quantified on SS-OCT angiography (SS-OCTA) images using a previously published algorithm that was validated. The CC FD% was 12.52% in the right eye and 14.64% in the left eye within a 5 mm circle centered on the fovea. After 5 months of steroid treatment, BCVA remained 20/20 in the right eye and improved to 20/25 in the left eye. On OCT imaging, the outer photoreceptor bands fully recovered in both eyes, while some focal deposits remained along the RPE in the left eye. The CC perfusion in both eyes improved, with CC FD% decreasing from 12.52% to 9.16% in the right eye and from 14.64% to 9.34% in the left eye. CONCLUSIONS: Significant impairment of macular CC perfusion was detected after the onset of PPM. Improvement in central macular CC perfusion corresponded with improvements in BCVA and outer retinal anatomy. Our findings suggest that imaging and quantification of CC FDs could serve as a valuable imaging strategy for diagnosing PPM and for following disease progression.

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).

Onset and Progression of Persistent Choroidal Hypertransmission Defects in Intermediate Age-Related Macular Degeneration: A Novel Clinical Trial Endpoint.

PURPOSE: The appearance and growth of persistent choroidal hypertransmission defects (hyperTDs) detected on en face swept-source optical coherence tomography (SS-OCT) images from eyes with intermediate age-related macular degeneration (iAMD) were studied to determine if they could serve as novel clinical trial endpoints. DESIGN: Post hoc subgroup analysis of a prospective study. METHODS: Subjects with iAMD underwent 6 × 6 mm SS-OCT angiography imaging at their baseline and follow-up visits. The drusen volumes were obtained using a validated SS-OCT algorithm. Two graders independently evaluated all en face structural images for the presence of persistent hyperTDs. The number and area of all hyperTDs along with drusen volume were obtained from all SS-OCT angiography scans. Eyes were censored from further follow-up once exudative AMD developed. RESULTS: A total of 171 eyes from 121 patients with iAMD were included. Sixty-eight eyes developed at least 1 hyperTD. Within 1 year after developing a hyperTD, 25% of eyes developed new hyperTDs for an average of 0.44 additional hyperTDs. Over 2 years, as hyperTDs appeared, enlarged, and merged, the average area growth rate was 0.220 mm/yr using the square-root transformation strategy. A clinical trial design using the onset and enlargement of these hyperTDs for the study of disease progression in eyes with iAMD is proposed. CONCLUSIONS: The appearance and growth of persistent choroidal hyperTDs in eyes with iAMD can be easily detected and measured using en face OCT imaging and can serve as novel clinical trial endpoints for the study of therapies that may slow disease progression from iAMD to late AMD.

Comparing size measurement of colorectal polyps using a novel virtual scale endoscope, endoscopic ruler or forceps: A preclinical randomized trial.

Background and study aims Accurate polyp size measurement is important for guideline conforming choice of polypectomy techniques and subsequent surveillance interval assignments. Some endoscopic tools (biopsy forceps [BF] or endoscopic rulers [ER]) exist to help with visual size estimation. A virtual scale endoscope (VSE) has been developed that allows superimposing a virtual measurement scale during live endoscopies. Our aim was to evaluate the performance of VSE when compared to ER and BF-based measurement. Methods We conducted a preclinical randomized trial to evaluate the relative accuracy of size measurement of simulated colorectal polyps when using: VSE, ER, and BF. Six endoscopists performed 60 measurements randomized at a 1:1:1 ratio using each method. Primary outcome was relative accuracy in polyp size measurement. Secondary outcomes included misclassification of sizes at the 5-, 10-, and 20-mm thresholds. Results A total of 360 measurements were performed. The relative accuracy of BF, ER, and VSE was 78.9 % (95 %CI = 76.2-81.5), 78.4 % (95 %CI = 76.0-80.8), and 82.7 % (95 %CI = 80.8-84.8). VSE had significantly higher accuracy compared to BF ( P  = 0.02) and ER ( P  = 0.006). VSE misclassified a lower percentage of polyps > 5 mm as ≤ 5 mm (9.4 %) compared to BF (15.7 %) and ER (20.9 %). VSE misclassified a lower percentage of ≥ 20 mm polyps as < 20 mm (8.3 %) compared with BF (66.7 %) and ER (75.0 %). Of polyps ≥10mm, 25.6 %, 25.5 %, and 22.5 % were misclassified as <10 mm with ER, BF, and VSE, respectively. Conclusions VSE had significantly higher relative accuracy in measuring polyps compared to ER or BF assisted measurement. VSE improves correct classification of polyps at clinically important size thresholds.

Detection of Nonexudative Macular Neovascularization on Structural OCT Images Using Vision Transformers.

Purpose: A deep learning model was developed to detect nonexudative macular neovascularization (neMNV) using OCT B-scans. Design: Retrospective review of a prospective, observational study. Participants: Normal control eyes and patients with age-related macular degeneration (AMD) with and without neMNV. Methods: Swept-source OCT angiography (SS-OCTA) imaging (PLEX Elite 9000, Carl Zeiss Meditec, Inc) was performed using the 6 × 6-mm scan pattern. Individual B-scans were annotated to distinguish between drusen and the double-layer sign (DLS) associated with the neMNV. The machine learning model was tested on a dataset graded by humans, and model performance was compared with the human graders. Main Outcome Measures: Intersection over Union (IoU) score was measured to evaluate segmentation network performance. Area under the receiver operating characteristic curve values, sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were measured to assess the performance of the final classification performance. Chance-corrected agreement between the algorithm and the human grader determinations was measured with Cohen's kappa. Results: A total of 251 eyes from 210 patients, including 182 eyes with DLS and 115 eyes with drusen, were used for model training. Of 125 500 B-scans, 6879 B-scans were manually annotated. A vision transformer segmentation model was built to extract DLS and drusen from B-scans. The extracted prediction masks from all B-scans in a volume were projected to an en face image, and an eye-level projection map was obtained for each eye. A binary classification algorithm was established to identify eyes with neMNV from the projection map. The algorithm achieved 82%, 90%, 79%, and 91% sensitivity, specificity, PPV, and NPV, respectively, on a separate test set of 100 eyes that were evaluated by human graders in a previous study. The area under the curve value was calculated as 0.91 (95% confidence interval, 0.85-0.98). The results of the algorithm showed excellent agreement with the senior human grader (kappa = 0.83, P < 0.001) and moderate agreement with the junior grader consensus (kappa = 0.54, P < 0.001). Conclusions: Our network (code is available at https://github.com/uw-biomedical-ml/double_layer_vit) was able to detect the presence of neMNV from structural B-scans alone by applying a purely transformer-based model.

Multimodal Imaging, OCT B-Scan Localization, and En Face OCT Detection of Macular Hyperpigmentation in Eyes with Intermediate Age-Related Macular Degeneration.

Purpose: Multimodal imaging was used to identify and characterize the cause of hyperpigmentation seen on color fundus images (CFIs) of eyes with intermediate age-related macular degeneration (iAMD). Design: Retrospective review of a prospective study. Participants: Patients with iAMD. Methods: Color fundus images with macular hyperpigmentation were compared with same-day images obtained using fundus autofluorescence (FAF), near infrared reflectance (NIR), and swept-source (SS) OCT imaging. Two SS OCT en face slabs were generated: a retinal slab to identify hyperreflective foci within the retina and a slab from beneath the retinal pigment epithelium (RPE; the sub-RPE slab) that was used to detect regions that cause decreased light transmission into the choroid, also known as hypotransmission defects. All images were registered to allow for qualitative comparisons by 2 independent graders. Main Outcome Measures: Comparison between foci of macular hyperpigmentation seen on CFIs with the detection of these regions on FAF, NIR, and SS OCT en face images. Results: Compared with CFIs, FAF imaging seemed to be the least sensitive method for the detection of hyperpigmentation, whereas NIR and SS OCT imaging reliably detected these hyperpigmented areas. Although NIR imaging detected most of the hyperpigmentation seen in CFIs, SS OCT imaging detected all the areas of hyperpigmentation and anatomically localized these areas by using both en face and B-scan images. En face OCT slabs of the retina and sub-RPE region were registered to the CFIs, and areas of hyperpigmentation were shown to correspond to hyperreflective foci in the retina and regions of thickened RPE seen on OCT B-scans. Although both hyperpigmentation and early atrophic lesions appeared bright on NIR imaging, en face SS OCT imaging was able to distinguish these lesions because hyperpigmentary changes appeared dark and early atrophic lesions appeared bright on the sub-RPE slab. Conclusions: En face OCT imaging in conjunction with OCT B-scans were able to identify and localize the hyperpigmentation seen in CFIs reliably. This hyperpigmentation was not only associated with intraretinal hyperreflective foci, but also corresponded to areas with a thickened RPE.

Multimodal Imaging and En Face OCT Detection of Calcified Drusen in Eyes with Age-Related Macular Degeneration.

Purpose: En face OCT imaging was investigated as a method for the detection and monitoring of calcified drusen in eyes with nonexudative age-related macular degeneration (AMD). Design: Retrospective case series of a prospective study. Participants: Patients with nonexudative AMD. Methods: A retrospective review was performed of same-day color fundus (CF), fundus autofluorescence (FAF), near-infrared (NIR), and en face swept-source (SS) OCT images to identify eyes with nonexudative AMD and calcified drusen. The appearance and progression of these lesions were compared using the different imaging methods. Main Outcome Measures: Comparison between the presence of calcified drusen observed on CF images with the detection of these lesions on FAF, NIR, and en face SS OCT images. Results: Two hundred twenty eyes from 139 patients with nonexudative AMD were studied, with 42.7% of eyes containing calcified drusen either at baseline or during follow-up visits. On the en face SS OCT images, calcified drusen appeared as dark focal lesions referred to as choroidal hypotransmission defects (hypoTDs) that were detected in the choroid using a sub-retinal pigment epithelium (RPE) slab. The corresponding B-scans showed drusen with heterogenous internal reflectivity, hyporeflective cores, and hyperreflective caps. In most calcified drusen, choroidal hypertransmission defects (hyperTDs) were observed to develop over time around the periphery of the hypoTDs, giving them the appearance of a donut lesion on the en face SS OCT images. These donut lesions were associated with significant attenuation of the overlying retina, and the corresponding FAF images showed hypoautofluorescence at the location of these lesions. The donut lesions fulfilled the requirement for a persistent hyperTD, which is synonymous with complete RPE and outer retinal atrophy (cRORA). Six eyes displayed regression of the calcified drusen without cRORA developing. B-scans at the location of these regressed calcified drusen showed deposits along the RPE, with outer retinal thinning in the regions where the calcified lesions previously existed. Conclusions: En face OCT imaging is a useful method for the detection and monitoring of calcified drusen and can be used to document the evolution of these drusen as they form donut lesions or foci of cRORA.

Depth-resolved visualization and automated quantification of hyperreflective foci on OCT scans using optical attenuation coefficients.

An automated depth-resolved algorithm using optical attenuation coefficients (OACs) was developed to visualize, localize, and quantify hyperreflective foci (HRF) seen on OCT imaging that are associated with macular hyperpigmentation and represent an increased risk of disease progression in age related macular degeneration. To achieve this, we first transformed the OCT scans to linear representation, which were then contrasted by OACs. HRF were visualized and localized within the entire scan by differentiating HRF within the retina from HRF along the retinal pigment epithelium (RPE). The total pigment burden was quantified using the en face sum projection of an OAC slab between the inner limiting membrane (ILM) to Bruch's membrane (BM). The manual total pigment burden measurements were also obtained by combining manual outlines of HRF in the B-scans with the total area of hypotransmission defects outlined on sub-RPE slabs, which was used as the reference to compare with those obtained from the automated algorithm. 6×6 mm swept-source OCT scans were collected from a total of 49 eyes from 42 patients with macular HRF. We demonstrate that the algorithm was able to automatically distinguish between HRF within the retina and HRF along the RPE. In 24 test eyes, the total pigment burden measurements by the automated algorithm were compared with measurements obtained from manual segmentations. A significant correlation was found between the total pigment area measurements from the automated and manual segmentations (P < 0.001). The proposed automated algorithm based on OACs should be useful in studying eye diseases involving HRF.

Recurrent, bilateral endogenous Candida endophthalmitis with multiple focal chorioretinal lesions: management with pars plana vitrectomy and focal endolaser.

PURPOSE: Bilateral endogenous Candida endophthalmitis (ECE) treatment usually involves administering systemic and intravitreal antifungal medications. In advanced cases with vitreous seeding, pars plana vitrectomy (PPV) is considered. The use of focal endolaser treatment to chorioretinal lesions has not been reported. We present a case of bilateral recurrent ECE treated with PPV and endolaser to elevated focal lesions. CASE: A 45-year-old diabetic male presented with decreased visual acuity in both eyes (20/50 right eye, 20/150 left eye) and was found to have bilateral ECE with moderate vitritis and chorioretinal lesions. The initial treatment consisted of multiple intravitreal voriconazole injections to both eyes as well as systemic antifungal therapy. Resolution of ECE occurred after three months, but one year later despite therapy recurred bilaterally. Patient underwent PPV with endolaser to the elevated chorioretinal lesions in both eyes. One year later, his vision improved to 20/40 in both eyes, focal lesions were flat and resolved along with the ECE. CONCLUSION: Advanced or recurrent ECE that is refractive to intravitreal antifungal therapy may be treated with PPV. Endolaser therapy to the chorioretinal lesions is an additional local option that can resolve the activity of ECE.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY DETECTION OF BRUCH MEMBRANE AND CHORIOCAPILLARIS ABNORMALITIES IN SORSBY MACULAR DYSTROPHY.

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) was used to analyze Bruch membrane (BM) and choriocapillaris (CC) abnormalities in undiagnosed family members with Sorsby macular dystrophy (SMD). METHODS: In a family with SMD ( TIMP3 Tyr191Cys), SS-OCTA imaging was performed using the 6 × 6 mm scan patter and previously validated algorithms to detect abnormalities in BM and the CC, as well as the presence of reticular pseudodrusen and macular neovascularization. Genetic analyses were performed for TIMP3 mutations. RESULTS: Of eight family members, two were previously diagnosed with SMD and six were asymptomatic. SS-OCTA imaging of the 33-year-old proband revealed type 1 macular neovascularization in the left eye and bilateral reticular pseudodrusen, thickening of BM, CC thinning, and increases in CC flow deficits. A TIMP3 mutation was confirmed. His niece, despite having no clinical evidence of SMD, showed BM thickening and CC thinning on SS-OCTA. A TIMP3 mutation was confirmed. The proband's younger nephew and niece also carried the TIMP3 mutation without clinical evidence of SMD. Two additional members had normal examinations, unremarkable SS-OCTA findings, and no TIMP3 mutation. CONCLUSION: Swept-source optical coherence tomography angiography imaging can detect BM and CC abnormalities in vivo in subjects unaware of their TIMP3 status in a family with SMD.