SLIViT: a general AI framework for clinical-feature diagnosis from limited 3D biomedical-imaging data.

We present SLIViT, a deep-learning framework that accurately measures disease-related risk factors in volumetric biomedical imaging, such as magnetic resonance imaging (MRI) scans, optical coherence tomography (OCT) scans, and ultrasound videos. To evaluate SLIViT, we applied it to five different datasets of these three different data modalities tackling seven learning tasks (including both classification and regression) and found that it consistently and significantly outperforms domain-specific state-of-the-art models, typically improving performance (ROC AUC or correlation) by 0.1-0.4. Notably, compared to existing approaches, SLIViT can be applied even when only a small number of annotated training samples is available, which is often a constraint in medical applications. When trained on less than 700 annotated volumes, SLIViT obtained accuracy comparable to trained clinical specialists while reducing annotation time by a factor of 5,000 demonstrating its utility to automate and expedite ongoing research and other practical clinical scenarios.

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.

Reticular Pseudodrusen: Interreader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration.

Purpose: To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence. Design: Interreader agreement study. Participants: Twelve readers from 6 reading centers. Methods: All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image. Main Outcome Measures: Interreader agreement, as assessed by Gwet's first-order agreement coefficient (AC1). Results: When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60-0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58-0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30). Conclusions: There was generally substantial or near-substantial-but not near-perfect-agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Endpoints for clinical trials in ophthalmology.

With the identification of novel targets, the number of interventional clinical trials in ophthalmology has increased. Visual acuity has for a long time been considered the gold standard endpoint for clinical trials, but in the recent years it became evident that other endpoints are required for many indications including geographic atrophy and inherited retinal disease. In glaucoma the currently available drugs were approved based on their IOP lowering capacity. Some recent findings do, however, indicate that at the same level of IOP reduction, not all drugs have the same effect on visual field progression. For neuroprotection trials in glaucoma, novel surrogate endpoints are required, which may either include functional or structural parameters or a combination of both. A number of potential surrogate endpoints for ophthalmology clinical trials have been identified, but their validation is complicated and requires solid scientific evidence. In this article we summarize candidates for clinical endpoints in ophthalmology with a focus on retinal disease and glaucoma. Functional and structural biomarkers, as well as quality of life measures are discussed, and their potential to serve as endpoints in pivotal trials is critically evaluated.

OPTIC DISK PIT ASSOCIATED WITH AN UNUSUAL OUTER RETINAL HOLE AND NASAL PERIPHERAL RETINOSCHISIS.

PURPOSE: To document a peculiar case of optic disk pit-associated maculopathy with extensive nasal retinoschisis with lamellar outer retinal hole. METHODS: A 41-year-old woman presented to the eye clinic complaining of new photopsias and enlargement of the blind spot in the left eye. Uncorrected visual acuity was 20/20 in both eyes. Fundus examination of the left eye revealed an anomalous appearing optic nerve with a gray oval depression at the temporal margin of the disk consistent with an optic disk pit. RESULTS: Optical coherence tomography confirmed the presence of the pit and demonstrated outer plexiform layer schisis superonasal to the fovea and extensive inner and outer retinal schisis nasal to the nerve extending to the equator. A large lamellar outer retinal hole was noted nasal to the disk without associated retinal detachment. The vitreous appeared to be attached over the nasal retina. CONCLUSION: Multimodal imaging revealed an unusual optic disk pit-associated retinopathy with dramatically more extensive retinoschisis and a lamellar outer retinal hole nasal to the nerve despite the temporal location of the pit. Although the precise pathophysiologic mechanisms are not fully understood, forces associated with the vitreo-retinal adhesion may have contributed to the distribution of the schisis in this case.

Characterisation of the vascular anterior surface of type 1 macular neovascularisation after anti-VEGF therapy.

BACKGROUND: To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA). METHODS: In consecutive treatment-naïve patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the 'neo-CC'. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated. RESULTS: Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development. CONCLUSIONS: More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration.

Functional and anatomic changes between early postoperative recovery and long-term follow-up after combined epiretinal and internal limiting membrane peeling.

OBJECTIVE: To evaluate short- and long-term changes in best-corrected visual acuity (BCVA) and retinal layer thicknesses after combined epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling for macular holes and symptomatic ERMs. DESIGN: Retrospective observational case series. PARTICIPANTS: Patients with ERMs or with macular holes and ERMs treated with combined ERM and ILM peeling. METHODS: Study eyes (n = 36) and healthy fellow eyes (n = 17) were evaluated using the automated segmentation of retinal layers performed by SPECTRALIS software that automatically calculated the average central retinal thickness and the average thickness in each of the individual retinal layers. The analysis was performed at 6-18 months after surgery and after 60 months. MAIN OUTCOME MEASURES: Changes in BCVA and retinal layer thicknesses determined by automated segmentation at the first and last follow-up visits. RESULTS: BCVA improved from a baseline 0.48 ± 0.25 logMAR (20/60 Snellen) to 0.18 ± 0.18 logMAR (20/30 Snellen) at the short-term postoperative examination (p < 0.0001). Between first and last follow-up visit, 5 eyes (14%) were classified as better, 28 (78%) as stable, and 3 (8%) as worse. BCVA of the control fellow eyes remained stable during the follow-up. The thicknesses of retinal layers decreased significantly (p < 0.009). At the last follow-up, the ganglion cell layer was thinner and the inner nuclear layer was thicker in the operated eyes compared with the healthy fellow eyes. CONCLUSION: Combined ERM and ILM peeling may improve BCVA in some patients. However, over a long follow-up period, it can be associated with progressive ganglion cell layer thinning that could affect BCVA stability.

Automated Identification of Incomplete and Complete Retinal Epithelial Pigment and Outer Retinal Atrophy Using Machine Learning.

OBJECTIVE: To assess and validate a deep learning algorithm to automatically detect incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and complete retinal pigment epithelial and outer retinal atrophy (cRORA) in eyes with age-related macular degeneration. DESIGN: In a retrospective machine learning analysis, a deep learning model was trained to jointly classify the presence of iRORA and cRORA within a given B-scan. The algorithm was evaluated using 2 separate and independent datasets. PARTICIPANTS: OCT B-scan volumes from 71 patients with nonneovascular age-related macular degeneration captured at the Doheny-University of California Los Angeles Eye Centers and the following 2 external OCT B-scans testing datasets: (1) University of Pennsylvania, University of Miami, and Case Western Reserve University and (2) Doheny Image Reading Research Laboratory. METHODS: The images were annotated by an experienced grader for the presence of iRORA and cRORA. A Resnet18 model was trained to classify these annotations for each B-scan using OCT volumes collected at the Doheny-University of California Los Angeles Eye Centers. The model was applied to 2 testing datasets to assess out-of-sample model performance. MAIN OUTCOMES MEASURES: Model performance was quantified in terms of area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). Sensitivity, specificity, and positive predictive value were also compared against additional clinician annotators. RESULTS: On an independently collected test set, consisting of 1117 volumes from the general population, the model predicted iRORA and cRORA presence within the entire volume with nearly perfect AUROC performance and AUPRC scores (iRORA, 0.61; 95% confidence interval [CI] [0.45, 0.82]: cRORA, 0.83; 95% CI [0.68, 0.95]). On another independently collected set, consisting of 60 OCT B-scans enriched for iRORA and cRORA lesions, the model performed with AUROC (iRORA: 0.68, 95% CI [0.54, 0.81]; cRORA: 0.84, 95% CI [0.75, 0.94]) and AUPRC (iRORA: 0.70, 95% CI [0.55, 0.86]; cRORA: 0.82, 95% CI [0.70, 0.93]). CONCLUSIONS: A deep learning model can accurately and precisely identify both iRORA and cRORA lesions within the OCT B-scan volume. The model can achieve similar sensitivity compared with human graders, which potentially obviates a laborious and time-consuming annotation process and could be developed into a diagnostic screening tool.

Choriocapillaris Flow Deficit in Tubercular Serpiginous-Like Choroiditis with and without Paradoxical Worsening.

PURPOSE: The aim is to analyze automated quantification of choriocapillaris flow deficit (CCFD) on swept-source (SS)-optical coherence tomography angiography (OCTA) in tubercular serpiginous-like choroiditis (TBSLC). METHODS: In this prospective study, automated CCFD calculations were performed on SS-OCTA and compared with CCFD areas on indocyanine green angiography (ICGA). Patients were divided into two groups based on the occurrence of paradoxical worsening (PW). RESULTS: Twenty-nine eyes (29 subjects; 18 males; mean age: 33±12 years) were included. The mean CCFD at baseline was 34.9 ± 4.3% on OCTA in eyes without PW and 35.4 ± 5.0% on SS-OCTA with PW (p = .77). At 4 and 12 weeks, CCFD on SS-OCTA improved to 30.6 ± 3.9% and 28.0 ± 4.2% (p < .001) without PW, respectively, and increased to 42.9 ± 4.4% and 48.8 ± 4.1% (p < .001) with PW, respectively. The SS-OCTA CCFD correlated well with ICGA (r = 0.48; p < .001). CONCLUSIONS: Automated quantitative serial assessment of CCFD on SS-OCTA can serve as a useful biomarker of disease activity in eyes with TBSLC.

Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study.

Objective: To evaluate the optical coherence tomography (OCT)-based risk factors for progression to late age-related macular degeneration (AMD) in a population-based study of elderly Amish. Methods: A total of 1332 eyes of 666 consecutive subjects who completed a 2-year follow-up visit were included in this multicenter, prospective, longitudinal, observational study. Imaging features were correlated with 2-year incidence of late AMD development. Odds ratios for imaging features were estimated from logistic regression. Baseline OCT images were reviewed for the presence of drusen volume ≥0.03 mm3 in the central 3 mm ring, intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDD), and drusenoid pigment epithelium detachment (PED). Subfoveal choroidal thickness, drusen area, and drusen volume within 3 and 5 mm circles centered on the fovea were also assessed. Results: Twenty-one (1.5%) of 1332 eyes progressed to late AMD by 2 years. The mean age of the study subjects was 65 ± 10.17 (±SD) years and 410 subjects were female. Univariate logistic regression showed that drusen area and volume in both 3 mm and 5 mm circles, subfoveal choroidal thickness, drusen volume ≥ 0.03 mm3 in the 3 mm ring, SDD, IHRF, and hDC were all associated with an increased risk for development of late AMD. The multivariate regression model identified that drusen volume in the 3 mm ring (OR: 2.59, p = 0.049) and presence of IHRF (OR: 57.06, p < 0.001) remained as independent and significant risk factors for progression to late AMD. Conclusions: This population-based study confirms previous findings from clinic-based studies that high central drusen volume and IHRF are associated with an increased risk of progression to late AMD. These findings may be of value in risk-stratifying patients in clinical practice or identifying subjects for early intervention clinical trials.

Clinical and Morphologic Characteristics of Perivenular Fernlike Leakage on Ultrawide-field Fluorescein Angiography.

PURPOSE: To analyze the spectrum of the perivenular fernlike leakage on ultrawide-field fluorescein angiography (UWFA) and discuss its potential implications in the current understanding of the retinal venous outflow. DESIGN: Retrospective, observational case series. PARTICIPANTS: Eyes presenting with fernlike patterns of dye leakage on UWFA were included in this study. METHODS: Analysis of the clinical characteristics and multimodal imaging findings using UWFA and wide-angle swept-source OCT-angiography (SS-OCTA). MAIN OUTCOME MEASURES: The disease spectrum, anatomic origin, and clinical implications of this fernlike leakage. RESULTS: Multimodal retinal images from 40 eyes of 29 patients with fernlike leakage on UWFA were studied. The underlying etiologies included a wide range of inflammatory disorders, including pars planitis (18 eyes) and central retinal vein occlusion (2 eyes). On UWFA, the fernlike leakage originated from the retinal capillaries and venules directly adjacent to the veins and spared the periarterial zone. This perivenular fernlike leakage involved the far periphery in all cases and progressed more diffusely and centripetally in cases with more severe intraocular inflammation. On wide-angle SS-OCTA, the impairment of deep capillary plexus (DCP) flow signals precisely colocalized with the perivenular fernlike leakages identified on UWFA. CONCLUSIONS: The fernlike leakage on UWFA refers to the distinctive perivenular dye leakage that originates from the retinal capillaries and venules. Multimodal imaging correlation suggests that the predominant impairment is at the level of the DCP. The axial symmetry of the fernlike leakage with the veins and sparing of the periarterial zone may support the dominant venous role of the DCP.

Differences in Long-Term Progression of Atrophy between Neovascular and Nonneovascular Age-Related Macular Degeneration.

PURPOSE: To compare the enlargement rates of geographic atrophy (GA) over 5 years of follow-up with those of macular atrophy (MA) associated with macular neovascularization (MNV). DESIGN: Retrospective, longitudinal, comparative case series. PARTICIPANTS: Consecutive series of patients with age-related macular degeneration and GA (dry) or with MA and MNV. METHODS: Atrophic regions detected on serial registered fundus autofluorescence images were semiautomatically delineated, and the measurements of these areas were recorded every 6 ± 3 months for the first 2 years of follow-up and at yearly intervals for up to 5 years. MAIN OUTCOME MEASURES: Annual raw and square root-transformed rates of atrophy growth. RESULTS: The study included 117 eyes of 95 patients (61 in the GA cohort and 56 in the MA cohort); 100% and 38.5% of the eyes completed 2 and 5 years of follow-up, respectively. The mean size of lesions at baseline was similar between the 2 groups (raw: 1.74 vs. 1.53 mm2, P = 0.56; square root-transformed: 1.17 vs. 1.02 mm, P = 0.26). The overall enlargement rates were greater for the GA cohort (raw: 1.72 vs. 1.32 mm2/year, P = 0.002; square root-transformed: 0.41 vs. 0.33 mm/year, P = 0.03), and so was the area of atrophy growth at 5 years (raw: +8.06 vs. +4.55 mm2, P = 0.001; square root-transformed: +1.93 vs. +1.38 mm, P = 0.02). The estimated square root-transformed area was also significantly greater for the GA cohort at 2 years (1.84 vs. 1.67 mm, P = 0.01). CONCLUSIONS: The presence of MNV was associated with a slower rate of expansion, resulting in overall smaller areas of atrophy over time. These findings support the hypothesis that MNV may protect against the progression of atrophy.

Diagnosing Persistent Hypertransmission Defects on En Face OCT Imaging of Age-Related Macular Degeneration.

PURPOSE: A training exercise was performed to study the ability of graders to reliably identify precursor lesions to geographic atrophy (GA), known as persistent choroidal hypertransmission defects (hyperTDs), using en face OCT images from eyes with nonexudative age-related macular degeneration (AMD). DESIGN: Intergrader agreement study. PARTICIPANTS: Eleven graders participated in this exercise. METHODS: Formal training on how to identify persistent hyperTDs on en face OCT images was provided to the graders. A persistent hyperTD was defined as a bright lesion having a greatest linear dimension (GLD) of at least 250 µm. Training consisted of a tutorial session followed by the grading of 3 pretest exercises, each consisting of 3 cases. After all graders scored 100% on the pretest exercises, they performed a final exercise consisting of 30 en face OCT images from 29 eyes with nonexudative AMD containing 107 hyperTDs that each grader needed to evaluate. The cases contained a variety of AMD-related atrophic lesions. MAIN OUTCOME MEASURES: The sensitivity, positive predictive value (PPV), and modified accuracy were assessed for each grader. RESULTS: A total of 1177 hyperTDs from 30 en face OCT images were reviewed by the graders. The mean sensitivity, PPV, and modified accuracy for all the graders were calculated to be 99.0%, 99.2%, and 98.2%, respectively. There was a 97% agreement observed between all the graders (first-order agreement coefficient [AC1] = 0.97). Internal graders from the Bascom Palmer Eye Institute had a slightly higher agreement compared with the external graders (AC1 = 0.98 vs. AC1 = 0.96). The hyperTDs most often incorrectly identified included the following features: (1) hyperTDs containing hypotransmission defect cores, (2) single hyperTDs that were incorrectly graded as 2 separate lesions, and (3) hyperTDs with borderline GLDs that were close to 250 µm. CONCLUSIONS: The accurate detection of persistent hyperTDs on en face OCT images by graders demonstrates the feasibility of using this OCT biomarker to identify disease progression in eyes with nonexudative AMD, especially when used as a clinical trial end point in studies designed to test new therapies that may slow disease progression from intermediate AMD to GA.

MULTIMODAL IMAGING OF CRB1 RETINITIS PIGMENTOSA WITH A PERIPHERAL RETINAL TUMOR.

PURPOSE: To report the multimodal imaging findings of a patient with gene- crumbs 1 -associated retinitis pigmentosa (RP) characterized by preservation of para-arteriolar retinal pigment epithelium and a peripheral retinal tumor. METHODS: A 27-year-old woman was referred to our center because of progressive decreased vision in both eyes with a diagnosis of gene- crumbs 1 -associated RP. Fundus examination was remarkable for attenuated retinal vessels and bone spicule migration that was bilateral and symmetric. In addition, an elevated yellow-white mass with dilated retinal vessels was noted in the superotemporal midperiphery of the retina in the left eye without any associated exudation. RESULTS: Diffuse retinal pigment epithelium mottling was present but spared the area along the retinal arterioles. Swept-source optical coherence tomography showed diffuse outer retinal atrophy. Optical coherence tomography angiography of the peripheral lesion illustrated extensive vascularity and a possible retinal feeder vessel communicating with the tumor at its inferior margin. The phenotype of the lesion showed overlap with a vasoproliferative tumor or an astrocytic hamartoma. Over a period of 5 years of follow-up, the peripheral tumor was unchanged. No significant progression of the peripheral retinal degeneration was evidenced by autofluorescent imaging over this time period although the central acuity continued to decrease. CONCLUSION: Gene- crumbs 1 -associated RP may be characterized by preservation of the para-arteriolar retinal pigment epithelium and slow progression and may also feature a benign peripheral retinal tumor.

MULTIMODAL IMAGING OF A CHOROIDAL NEVUS WITH CAVERNS IN THE SETTING OF PACHYCHOROID DISEASE.

PURPOSE: To describe the multimodal imaging findings of extensive choroidal caverns within a choroidal nevus in an eye with pachychoroid spectrum disease. METHODS: A 69-year-old woman was referred with a known history of branch retinal vein occlusion in the right eye and choroidal nevus in the left eye. Fundus examination of both eyes revealed subretinal yellow deposits, suggestive of pachydrusen. Retinal venous collaterals were noted in the temporal macular of the right eye. A lightly pigmented choroidal lesion with nearly confluent overlying drusen and retinal pigment epithelial alterations, consistent with chronic choroidal nevus, was noted in the macula of the left eye. RESULTS: Optical coherence tomography B-scans revealed thickened choroid (pachychoroid) with subfoveal choroidal thickness of 504 µ m and 580 µ m with large hyporeflective spaces suggestive of pachyvessels in both eyes. In the region of the choroidal nevus, the choroidal vascular spaces appeared comparatively large and were classified as "caverns" measuring up to 480 µ m in diameter. Optical coherence tomography angiography and indocyanine green angiography demonstrated the absence of flow within the caverns. Indocyanine green angiography further illustrated choroidal vascular hyperpermeability with patchy hyperfluorescent areas in both eyes. Wide-field swept-source optical coherence tomography showed mild posterior scleral bowing, a feature occasionally documented with choroidal nevus, and highlighted greater hyporeflectivity and hypertransmission on optical coherence tomography within the caverns compared with the noncavernous choroidal vessels. CONCLUSION: Choroidal caverns can occur within choroidal nevus in the setting of pachychoroid disease.

Prechoroidal cleft thickness correlates with disease activity in neovascular age-related macular degeneration.

PURPOSE: The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch's membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). METHODS: In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity. RESULTS: Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size. CONCLUSION: Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

Multimodal Imaging Comparison of Polypoidal Choroidal Vasculopathy Between Asian and Caucasian Populations.

PURPOSE: Differences in multimodal imaging features between Asian and Caucasian eyes may contribute to our understanding of the etiology of the polypoidal choroidal vasculopathy (PCV). The purpose of this study was to compare the multimodal imaging features of Asian and Caucasian eyes with PCV. DESIGN: Cross-sectional, retrospective, multicenter, observational case series. METHODS: Consecutive treatment-naïve patients diagnosed with PCV based on indocyanine green angiography in accordance with published guidelines. Demographic and multimodal imaging findings based on color fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography were graded. RESULTS: A total of 250 participants with PCV (128 Asian vs 122 Caucasian participants) were included. Asian participants presented with lower best-corrected visual acuity (mean ± SD: 0.7 ± 0.6 logMAR vs 0.4 ± 0.3 logMAR; P < .001) compared with Caucasian participants. More Asian eyes had subretinal hemorrhage (mean ± SD: 53.9% vs 24.6%; P < .001) and larger areas of hemorrhage (mean ± SD: 7.5 ± 15.2 mm2 vs 1.3 ± 3.3 mm2; P < .001). More Asian eyes had pachyvessels (84.4% vs 28.7%; P < .001), choroidal vascular hyperpermeability (70.3% vs 17.2%; P < .001), and widespread polypoidal lesions (19.5% vs 8.2%; P = .005), and Caucasian eyes had more drusen (79.5% vs 49.2%; P = .02). CONCLUSIONS: Multimodal imaging analysis revealed ethnic differences in disease characteristics of PCV, suggesting pathophysiologic mechanism of the disease vary based on ethnicity.

Retro mode illumination for detecting and quantifying the area of geographic atrophy in non-neovascular age-related macular degeneration.

PURPOSE: To evaluate the ability of retro mode illumination imaging for quantifying atrophy compared to confocal color fundus photography (c-CFP), green light fundus autofluorescence (G-FAF), blue light fundus autofluorescence (B-FAF) using the scanning laser ophthalmoscope (SLO) Mirante device by Nidek (Nidek Co., Ltd, Gamogori, Japan). METHODS: Eyes with clinical evidence of geographic atrophy (GA) associated with non-neovascular age-related macular degeneration, evaluated at the Doheny Eye Centers-UCLA and Hospital Sacco Milan, were included in this prospective, cross-sectional study. All eyes were imaged with multiple retinal imaging modalities using the SLO Nidek Mirante device: c-CFP, G-FAF, B-FAF, retro mode illumination deviated-right (RMDR), and deviated-left (RMDL). Masked graders measured the GA lesion on each modality and inter-modality and inter-grader repeatability were assessed. RESULTS: The mean (SD) area of GA measured 9.76 (3.82) mm2, 9.75 (3.91) mm2, 9.76 (3.92) mm2, 9.82 (3.87) mm2, and 9.81 (3.86) mm2 using c-CFP, G-FAF, B-FAF, RMDR, and RMDL, respectively (p = 0.2). Inter-modality correlation was high (Pearson's r > 0.9 and p < 0.0001). Agreement between graders was excellent for all modalities. CONCLUSIONS: Retro mode imaging demonstrated good agreement for measuring GA compared to other imaging modalities, with a high level of repeatability. Given that retro mode imaging uses infrared light and is comfortable, it may prove to be a useful tool for the assessment of GA in the clinic.

OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement: Classification of Atrophy Meetings Report 6.

PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 µm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 µm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.