Peripheral retinal lesions in diabetic retinopathy on ultra-widefield imaging.

Peripheral retinal imaging plays a crucial role in the diagnosis, management, and prognosis of diabetic retinopathy (DR). Traditional fundus imaging techniques have limited coverage of the retina, resulting in missed peripheral lesions. The advent of ultra-widefield (UWF) imaging has revolutionized the assessment of the peripheral retina. UWF imaging modalities provide comprehensive visualization of the retina, enabling the detection of peripheral lesions without the need for mydriasis. Integration of UWF imaging with other modalities, including fluorescein angiography (FA), indocyanine green angiography, pseudocolor imaging, and fundus autofluorescence, further enhances our understanding of peripheral retinal lesions. UWF imaging has demonstrated improved detection of DR lesions and presumably more accurate management of DR compared to traditional fundus photography and dilated fundus examination. UWF-FA and UWF-optical coherence tomography angiography have emerged as valuable tools for assessing retinal and choroidal vascular abnormalities, nonperfusion areas, neovascularization, and microvascular abnormalities. The presence and increasing extent of predominantly peripheral lesions detected using UWF FA are associated with a higher risk of DR progression and proliferative DR. UWF imaging provides a comprehensive evaluation of DR severity, aiding in more accurate risk stratification and treatment decision-making. Overall, UWF imaging modalities have significantly advanced our understanding of peripheral retinal lesions in DR, facilitating early detection and targeted management for better visual outcomes.

VITELLIFORM LESIONS ASSOCIATED WITH LEPTOCHOROID AND PSEUDODRUSEN.

OBJECTIVE: To characterize clinical and prognostic implications of leptovitelliform maculopathy (LVM), a distinctive phenotype of vitelliform lesion characterized by the coexistence of subretinal drusenoid deposits (SDD) and leptochoroid. DESIGN: Retrospective, cohort study. SUBJECTS: The study compares patients affected by leptovitelliform maculopathy with cohorts displaying a similar phenotypic spectrum. This includes patients with acquired vitelliform lesions (AVL) and those with SDD alone. METHODS: A total of 60 eyes of 60 patients were included, of whom 20 eyes had LVM, 20 eyes had AVL, and the remaining had SDD. Patients older than 50 years with complete medical records and multimodal imaging for at least 6 months of follow-up, including color fundus photograph (CFP) or MultiColor, optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA) were included. MAIN OUTCOME MEASURES: Choroidal vascularity index (CVI); proportion of late-stage complications (macular neovascularization, atrophy). RESULTS: The AVL subgroup exhibited a significantly higher CVI compared to both LVM (p<0.001) and SDD subgroups (p<0.001). The proportion of late-stage complications significantly differed among subgroups (χ2=7.5, p=0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, while the remaining eyes presented a similar proportion of complications, including 20% in AVL after 27.6 months and 20% in SDD after 36.9 months. Kaplan-Meier estimates of survival demonstrated a significant difference in atrophy development between groups (p<0.001), with a median survival of 3.9 years for LVM and 7.1 years for controls. The presence of LVM correlated with a fourfold increase in the likelihood of developing complications. CONCLUSIONS: Leptovitelliform maculopathy, characterized by the association of vitelliform lesions with SDD and leptochoroid, represents a distinct clinical phenotype in the broader spectrum of vitelliform lesions. The importance of a clinical distinction for these lesions is crucial due to a higher propensity for faster progression and an elevated rate of complications, particularly toward atrophic conversion.

Prediction of Long-Term Treatment Outcomes for Diabetic Macular Edema Using a Generative Adversarial Network.

Purpose: The purpose of this study was to analyze optical coherence tomography (OCT) images of generative adversarial networks (GANs) for the prediction of diabetic macular edema after long-term treatment. Methods: Diabetic macular edema (DME) eyes (n = 327) underwent anti-vascular endothelial growth factor (VEGF) treatments every 4 weeks for 52 weeks from a randomized controlled trial (CRTH258B2305, KINGFISHER) were included. OCT B-scan images through the foveal center at weeks 0, 4, 12, and 52, fundus photography, and retinal thickness (RT) maps were collected. GAN models were trained to generate probable OCT images after treatment. Input for each model were comprised of either the baseline B-scan alone or combined with additional OCT, thickness map, or fundus images. Generated OCT B-scan images were compared with real week 52 images. Results: For 30 test images, 28, 29, 15, and 30 gradable OCT images were generated by CycleGAN, UNIT, Pix2PixHD, and RegGAN, respectively. In comparison with the real week 52, these GAN models showed positive predictive value (PPV), sensitivity, specificity, and kappa for residual fluid ranging from 0.500 to 0.889, 0.455 to 1.000, 0.357 to 0.857, and 0.537 to 0.929, respectively. For hard exudate (HE), they were ranging from 0.500 to 1.000, 0.545 to 0.900, 0.600 to 1.000, and 0.642 to 0.894, respectively. Models trained with week 4 and 12 B-scans as additional inputs to the baseline B-scan showed improved performance. Conclusions: GAN models could predict residual fluid and HE after long-term anti-VEGF treatment of DME. Translational Relevance: The implementation of this tool may help identify potential nonresponders after long-term treatment, thereby facilitating management planning for these eyes.

Relationship between macular perfusion and lesion distribution in diabetic retinopathy.

BACKGROUND/OBJECTIVES: To assess the relationship between macular vessel density metrics and foveal avascular zone (FAZ) characteristics on optical coherence tomography angiography (OCTA) and lesion distribution in eyes with diabetic retinopathy (DR). SUBJECTS/METHODS: Patients with DR who underwent both Optos ultrawidefield (UWF) pseudocolor imaging and macular OCTA (Cirrus Angioplex, 6 × 6 mm) were included in this cross-sectional observational study. The distribution of DR lesions was assessed by comparing each of the peripheral ETDRS extended fields (3-7) against their corresponding ETDRS field, hence eyes were defined as either having predominantly peripheral lesions (PPL) or predominantly central lesions (PCL). En face OCTA images from the superficial and deep capillary plexuses (SCP and DCP) were then analysed using Image J software. Perfusion density (PD), vessel length density (VLD), and fractal dimensions (FD) were calculated following binarization and skeletonization of the images. RESULTS: Out of 344 eyes, 116 (33.72%) eyes had PPL and 228 (66.28%) eyes had PCL. For all DRSS levels, VLD, PD, and FD were not significantly different between eyes with PPL and PCL. The FAZ in eyes with PPL, however, was found to be more circular in shape compared to eyes with PCL (p = 0.037). CONCLUSION: Although the presence of PPL has been associated with a higher risk for diabetic retinopathy progression, the macular perfusion is similar in eyes with PPL and PCL. The FAZ is more circular in eyes with PPL, but the clinical relevance of this difference remains to be defined.

Retinal Imaging Findings in Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) represent one of the major causes of progressive and irreversible vision loss in the working-age population. Over the last few decades, advances in retinal imaging have allowed for an improvement in the phenotypic characterization of this group of diseases and have facilitated phenotype-to-genotype correlation studies. As a result, the number of clinical trials targeting IRDs has steadily increased, and commensurate to this, the need for novel reproducible outcome measures and endpoints has grown. This review aims to summarize and describe the clinical presentation, characteristic imaging findings, and imaging endpoint measures that are being used in clinical research on IRDs. For the purpose of this review, IRDs have been divided into four categories: (1) panretinal pigmentary retinopathies affecting rods or cones; (2) macular dystrophies; (3) stationary conditions; (4) hereditary vitreoretinopathies.

Acquired Vitelliform Lesions in Intermediate Age-Related Macular Degeneration: A Cross Sectional Study.

PURPOSE: This study aims to define the characteristics of acquired vitelliform lesions (AVLs) in patients with intermediate age-related macular degeneration (iAMD). DESIGN: Retrospective, observational, cross sectional study. SUBJECTS: This study included 217 eyes with AVLs associated with iAMD, and an equivalent number of control patients. METHODS: OCT scans were evaluated for qualitative and quantitative parameters at both the eye and lesion level. Eye-level parameters included the presence of: hyporeflective core drusen, intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits, macular pachyvessels, central retinal thickness, and central choroidal thickness. Lesion-level qualitative parameters included the presence of ellipsoid zone (EZ) and external limiting membrane disruption overlying the AVL, IHRF overlying the AVL, AVL overlying drusen, pachyvessels under the AVL, a solid core within AVL, and AVL location. Lesion-level quantitative characteristics included AVL height and width, AVL distance from the fovea, and sub-AVL choroidal thickness. MAIN OUTCOME MEASURES: The primary outcomes assessed included the frequency of IHRF, the presence of macular pachyvessels, central choroidal thickness, and the dimensions (both height and width) of AVLs. RESULTS: Comparing the AVL and control groups, the frequency of IHRF (AVL: 49.3% vs. control: 26.3%) and macular pachyvessels (37.3% vs. 6.9%) was significantly higher in the AVL case group, and the central choroidal thickness (256.8 ± 88 µm vs. 207.1± 45 µm) was thicker in the AVL group. Acquired vitelliform lesions located over drusen, with overlying IHRF, or situated subfoveally, and AVL lesions with EZ disruption were found to have a greater lesion height and width compared with AVL lesions lacking these characteristics (P value < 0.001 for all). Additionally, a significant negative correlation was observed between the distance from the fovea and AVL height (Spearman rho: -0.19, P = 0.002) and width (Spearman rho: -0.30, P = 0.001). CONCLUSIONS: This study represents the largest reported cohort of AVL lesions associated with iAMD. Novel findings include the higher frequency of pachyvessels in addition to the presence of a thicker choroid in these eyes, as well as the greater height and width of AVL closer to the foveal center. These findings may offer insights into pathophysiologic mechanisms underlying the development of AVL. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Longitudinal Evaluation of the Distribution of Intraretinal Hyper-Reflective Foci in Eyes with Intermediate Age-Related Macular Degeneration.

PURPOSE: Intraretinal hyper-reflective foci (IHRF) are optical coherence tomography (OCT) risk factors for progression of age-related macular degeneration (AMD). In this study we assess the change in the number and distribution of IHRF over two years. METHODS: The axial distribution of IHRF were quantified in eyes with intermediate AMD (iAMD) at baseline and 24 months, using a series of 5 sequential equidistant en face OCT retinal slabs generated between the outer border of the internal limiting membrane (ILM) and the inner border of the retinal pigment epithelium (RPE). Following thresholding and binarization, IHRF were quantified in each retinal slab using ImageJ. The change in IHRF number in each slab between baseline and month 24 was calculated. RESULTS: Fifty-two eyes showed evidence of IHRF at baseline, and all continued to show evidence of IHRF at 24 months (M24). The total average IHRF count/eye increased significantly from 4.67 ± 0.63 at baseline to 11.62 ± 13.86 at M24 (p < 0.001) with a mean increase of 6.94 ± 11.12 (range: - 9 to + 60). Overall, at M24, 76.9% eyes showed an increase in IHRF whereas 15.4% of eyes showed a decrease (3 eyes [5.7%] showed no change). There was a greater number of IHRF and a greater increase in IHRF over M24 in the outer slabs. CONCLUSIONS: IHRF are most common in the outer retinal layers and tend to increase in number over time. The impact of the distribution and frequency of these IHRF on the overall progression of AMD requires further study.

Predictive Factors Influencing the Evolution of Acquired Vitelliform Lesions in Intermediate Age-Related Macular Degeneration Eyes.

PURPOSE: In this study, we identify risk factors that predict the progression of acquired vitelliform lesions (AVLs) over time. DESIGN: Retrospective cohort study. SUBJECTS: One hundred sixty-three eyes of 132 patients with a diagnosis of intermediate age-related macular degeneration (iAMD) with AVL. METHODS: This retrospective study evaluated consecutive eyes with AMD from a retina clinic population and included 1181 patients and 2362 eyes. After excluding cases with associated geographic atrophy, macular neovascularization (MNV), vitreomacular traction, and those with <2 years of follow-up data, the final analysis cohort consisted of 163 eyes (132 patients) with ≥1 AVL. The first available visit in which an AVL was evident was considered the baseline visit, and follow-up data were collected from a visit 2 years (± 3 months) later. Progression outcomes at the follow-up visit were classified into 6 categories: resorbed, collapsed, MNV, stable, increasing, and decreasing. Subsequently, we analyzed the baseline characteristics for each category and calculated odds ratios (ORs) to predict these various outcomes. MAIN OUTCOME MEASURES: The study focused on identifying predictive factors influencing the evolution of AVL in iAMD eyes. RESULTS: In total, 163 eyes with AVL had follow-up data at 2 years. The collapsed group demonstrated a significantly greater baseline AVL height and width compared with other groups (P < 0.001). With regard to qualitative parameters, subretinal drusenoid deposits (SDDs) and intraretinal hyperreflective foci (IHRF) at the eye level, AVL located over drusen, and IHRF and external limiting membrane disruption over AVL were significantly more prevalent in the collapsed group compared with other groups (P < 0.05 for all comparisons). Odds ratios for progressing to atrophy after 2 years of follow-up, compared with the resorbed group, were significant for SDD (OR, 2.82; P = 0.048) and AVL height (OR, 1.016; P = 0.006). CONCLUSIONS: The presence of SDDs and greater AVL height significantly increases the risk of developing atrophy at the location of AVL after 2 years of follow-up. These findings may be of value in risk prognostication and defining patient populations for inclusion in future early intervention trials aimed at preventing progression to atrophy. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

En Face and Volumetric Comparison of Hypertransmission Defects Evaluated by Cirrus and Spectralis Optical Coherence Tomography.

PURPOSE: To evaluate and compare en face and 3-dimensional (3-D) properties of hypertransmission defects (HTDs) between different optical coherence tomography (OCT) devices using OCT volumes and reconstructed en face images. SETTINGS: Comparative diagnostic evaluation study. METHODS: Thirty eyes with dry age-related macular degeneration (AMD) that underwent dense OCT macular volume scans with both the Spectralis (97 B-scans/volume; 2910 B-scans in total) and Cirrus OCT (128 B-scans/volume; 3840 B-scans in total) from the Amish Eye Study cohort were included in this analysis. HTD regions were labeled on each B-scan and reconstructed into en face and 3-D volume images. Properties of HTD volume were compared between the 2 devices. RESULTS: The qualitative score of en face images for HTD was higher for the Cirrus compared to the Spectralis (P < .01). The quality of Spectralis en face images improved after preprocessing and reconstruction. The 2-D HTD area on en face obtained from 2-D projections of 3-D volume did not differ between devices (P = .478, ICC = 0.998; Jaccard index 0.721 ± 0.086). There was no difference in the number, volume, PALs, and surface areas of HTDs between devices in the volumetric analysis (all P ≥ .090). The signal intensity of HTD normalized by the mean choroidal signal intensity did not differ between devices (P = .861). CONCLUSIONS: The visualization of HTD on en face images from Spectralis OCT could be enhanced through image processing. The equivalence in 3-D HTD parameters between the 2 devices suggests interchangeability for assessing these lesions in AMD.

Topographic analysis of local OCT biomarkers which predict progression to atrophy in age-related macular degeneration.

PURPOSE: To define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that location in eyes with age-related macular degeneration (AMD). METHODS: In this retrospective case-control study, patients with dry AMD who had evidence of cRORA and OCT data available for 4 years (48 ± 4 months) prior to the first visit with evidence of cRORA were included. The visit 4 years prior to the development of cRORA was defined as the baseline visit, and the region on the OCT B-scans of future cRORA development was termed the case region. A region in the same eye at the same distance from the foveal center as the case region that did not progress to cRORA was selected as the control region. OCT B-scans at the baseline visit through both the case and control regions were evaluated for the presence of soft and cuticular drusen, drusen with hyporeflective cores (hcD), drusenoid pigment epithelial detachments (PED), subretinal drusenoid deposits (SDD), thick and thin double-layer signs (DLS), intraretinal hyperreflective foci (IHRF), and acquired vitelliform lesions (AVL). RESULTS: A total of 57 eyes of 41 patients with dry AMD and evidence of cRORA were included. Mean time from the baseline visit to the first visit with cRORA was 44.7 ± 6.5 months. The presence of soft drusen, drusenoid PED, AVL, thin DLS, and IHRF at the baseline visit was all associated with a significantly increased risk of cRORA at that location. Multivariable logistic regression revealed that IHRF (OR, 8.559; p < 0.001), drusenoid PED (OR, 7.148; p = 0.001), and a thin DLS (OR, 3.483; p = 0.021) were independent predictors of development of cRORA at that location. CONCLUSIONS: IHRF, drusenoid PED, and thin DLS are all local risk factors for the development of cRORA at that same location. These findings would support the inclusion of these features within a more granular staging system defining specific steps in the progression from early AMD to atrophy.

Risk factors for development of hyper-reflective foci overlying drusen in eyes with intermediate age-related macular degeneration.

AIMS: The aim of this study is to assess baseline characteristics of drusen preceding the development of intraretinal hyper-reflective foci (IHRF) in eyes with intermediate age-related macular degeneration (AMD). METHODS: In this retrospective case-control study, longitudinal optical coherence tomography (OCT) volume data from eyes with intermediate AMD in a retina clinic population were screened. All drusen that developed overlying IHRF were marked. A random number generator was used to select for further grading three drusen that did not develop IHRF. RESULTS: Ninety eyes (from 72 patients), including 140 drusen with overlying IHRF and 270 IHRF- drusen, were analysed. Greater drusen height, basal drusen width and overlying ellipsoid zone (EZ) and external limiting membrane disruption were associated with a significantly greater risk for IHRF development (p≤0.001). Regression analysis revealed EZ disruption increased these odds by 4.1 (p≤0.001). Each 10-µm increase in drusen height and width increased the odds by 34% (p≤0.001) and 3% (p: 0.005), respectively. Each 100-µm increase in distance from the fovea decreased the odds by 10% (p: 0.013). CONCLUSIONS: The presence of overlying EZ disruption and a greater drusen height substantially increased the risk for IHRF development, whereas drusen further from the fovea indicated reduced risk. Given the importance of IHRF as a biomarker for AMD progression, these findings may be of value in defining patient populations for future early intervention trials.

Choriocapillaris and Retinal Vascular Alterations in Presymptomatic Alzheimer's Disease.

Purpose: To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF) Aß42/tau ratios. Methods: Swept-source OCTA scans were collected using the Zeiss PLEX Elite 9000 and analyzed on 23 cognitively healthy (CH) subjects who had previously undergone CSF analysis. Thirteen subjects had a pathological Aß42/tau (PAT) ratio of <2.7132, indicative of presymptomatic Alzheimer's disease (AD), and 10 had a normal Aß42/tau (NAT) ratio of ≥2.7132. OCTA en face images of the superficial vascular complex (SVC) and deep vascular complex were binarized and skeletonized to quantify the perfusion density (PD), vessel length density (VLD), and fractal dimension (FrD). The foveal avascular zone (FAZ) area was calculated using the SVC slab. Choriocapillaris flow deficits (CCFDs) were computed from the en face OCTA slab of the CC. The above parameters were compared between CH-PATs and CH-NATs. Results: Compared to CH-NATs, CH-PATs showed significantly decreased PD, VLD, and FrD in the SVC, with a significantly increased FAZ area and CCFDs. Conclusions: Swept-source OCTA analysis of the SVC and CC suggests a significant vascular loss at the CH stage of pre-AD that might be an indicator of a neurodegenerative process initiated by the impaired clearance of Aß42 in the blood vessel wall and by phosphorylated tau accumulation in the perivascular spaces, a process that most likely mirrors that in the brain. If confirmed in larger longitudinal studies, OCTA retinal and inner choroidal metrics may be important biomarkers for assessing presymptomatic AD.

PREVALENCE AND PERSISTENCE OF HYPERTRANSMISSION DEFECTS OF VARIOUS SIZES IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the prevalence and rate of persistence over 2 years of various-sized hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration. METHODS: Retrospective analysis of optical coherence tomography data from consecutive intermediate age-related macular degeneration patients. Choroidal en face optical coherence tomography images were evaluated for the presence and number of hyperTDs of three different sizes based on greatest linear dimension (small, 63-124 µ m; medium, 125-249 µ m; large, ≥250 µ m) at baseline and at the 2-year follow-up. Interreader agreement was determined by Gwet's agreement coefficient. Disagreements between graders were resolved by the senior investigator to yield a single consensus for all cases. RESULTS: From 273 intermediate age-related macular degeneration eyes (247 patients), 72 and 76 hyperTD lesions were independently identified by two graders at baseline and overall agreement coefficient was 0.89 (95% CI, 0.86-0.93). After adjudication by the senior grader, the final consensus yielded 78 hyperTD lesions from 46 eyes (16.8%) of 42 patients (17.0%) in this study cohort. Among eyes with follow-up optical coherence tomography, 32 of 45 hyperTD lesions (71.1%) persisted. The rates of persistence were 100.0%, 72.7%, and 53.3% in large, medium, and small hyperTD sizes, respectively. CONCLUSION: HyperTDs were present in a significant proportion of intermediate age-related macular degeneration eyes. Acceptable interreader agreement was demonstrated in identifying hyperTD. Larger hyperTD lesions were more likely to persist over 2 years.

Assessment of intraretinal hyperreflective foci using multimodal imaging in eyes with age-related macular degeneration.

PURPOSE: This study aimed to investigate the correspondence between intraretinal hyperreflective foci (IHRF) identified on optical coherence tomography (OCT) B-scans with hyperpigmentation on colour fundus photography (CFP) or hyperreflectivity on infrared reflectance (IR) images in eyes with age-related macular degeneration (AMD). METHODS: Flash CFP, IR images and OCT B-scans obtained at the same visit were evaluated. Individual IHRF identified on OCT B-scans were assessed for the qualitative presence or absence of a hypotransmission tail into the choroid. The corresponding IR image obtained at the time of OCT acquisition was analysed for the presence or absence of hyperreflectivity in this region. The IR images were manually registered to the CFP image, and CFP images were inspected for the presence or absence of hyperpigmentation at the location of IHRF. RESULTS: From 122 eyes, a total of 494 IHRF were evaluated. For the primary analysis of qualitative presence or absence of hyperpigmentation on CFP and hyperreflectivity on IR at the locations corresponding to IHRF on OCT, 301 (61.0%) of the IHRFs demonstrated evidence of hyperpigmentation on CFP, while only 115 (23.3%) showed evidence of hyperreflectivity on IR. The qualitative determination of the presence or absence of an abnormality on CFP or IR were significantly different (p < 0.0001). 327 (66.2%) of the IHRF showed hypotransmission, and 80.4% of these IHRF showed hyperpigmentation on CFP, though only 23.9% (p < 0.0001) demonstrated hyperreflectivity on IR. CONCLUSIONS: Less than two-thirds of IHRF evident on OCT manifest as hyperpigmentation on colour photos, though IHRF with posterior shadowing are more likely to be evident as pigment. IR imaging appears to be even more poorly sensitive for visualizing IHRF.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

Atrophic Lesions Associated with Age-Related Macular Degeneration: High-Resolution versus Standard OCT.

OBJECTIVE: The objective of this study was to determine whether high-resolution OCT (HR-OCT) could enhance the identification and classification of atrophic features in age-related macular degeneration (AMD) compared with standard resolution OCT. DESIGN: Prospective, observational, cross-sectional study. SUBJECTS: The study included 60 eyes from 60 patients > 60 years of age with a diagnosis of AMD. METHODS: The participants underwent volume OCT scanning using HR-OCT and standard resolution OCT devices. Trained graders reviewed and graded the scans, identifying specific regions of interest for subsequent analysis. MAIN OUTCOME MEASURES: The study focused on identifying and classifying complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA), incomplete RORA (iRORA), and other nonatrophic AMD features. Additionally, qualitative and quantitative features associated with atrophy were assessed. RESULTS: The agreement among readers for classifying atrophic lesions was substantial to perfect for both HR-OCT (0.88) and standard resolution OCT(0.82). However, HR-OCT showed a higher accuracy in identifying iRORA lesions compared with standard OCT. Qualitative assessment of features demonstrated higher agreement for HR-OCT, particularly in identifying external limiting membrane (ELM) (0.95) and ellipsoid zone (EZ) disruption (0.94). Quantitative measurements of features such as hypertransmission defects, RPE attenuation/disruption, EZ disruption width, and ELM disruption width showed excellent interreader agreement with HR-OCT (> 0.90 for all features) but only moderate agreement with standard OCT (0.51-0.60). CONCLUSIONS: The study results suggest that HR-OCT improves the accuracy and reliability of classifying and quantifying atrophic lesions associated with AMD compared with standard resolution OCT. The quantitative findings in particular may have implications for future research and clinical practice, especially with the availability of therapeutic agents for treating geographic atrophy and the development of commercially available HR-OCT devices. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of slab selection on the relationship between choriocapillaris flow deficits and enlargement rate of geographic atrophy.

OBJECTIVE: To evaluate the effect of changing slab position on the correlation between choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) and yearly enlargement rate (yER) of GA. METHODS: OCT and OCTA images obtained on Cirrus HD-OCT device were collected from patients with GA. Each patient underwent OCTA scan at baseline and two OCT scans, one at baseline and one after at least 12 months. GA was delineated on en-face fundus image to calculate yER. OCTA images were generated from three 10 µm thick slabs 11, 21 and 31 µm posterior to RPE-fit line. 100 µm-wide concentric rings were generated around GA to calculate FD% in each ring which was correlated with yER. RESULTS: For the 11-21 µm slab, FD% was not significantly correlated with yER for any of the rings (p > 0.05). For the 21-31 and 31-41 µm slab, FD% of rings located in the 600 µm region around GA was significantly correlated with yER (p < 0.05). However, in all slab locations, there was no significant correlation between yER and CC FD% of rings located beyond the 600 µm region (p > 0.05). CONCLUSIONS: Slab selection for quantification of CC FD% may have a significant impact on quantitative results in eyes with GA.

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.

Longitudinal evaluation of the distribution of intraretinal hyper-reflective foci in eyes with intermediate age-related macular degeneration.

Purpose: Intraretinal hyper-reflective foci (IHRF) are optical coherence tomography (OCT) risk factors for progression of age-related macular degeneration (AMD). In this study we assess the change in the number and distribution of IHRF over two years. Methods: The axial distribution of IHRF were quantified in eyes with intermediate AMD (iAMD) at baseline and 24 months, using a series of 5 sequential equidistant en face OCT retinal slabs generated between the outer border of the internal limiting membrane (ILM) and the inner border of the retinal pigment epithelium (RPE). Following thresholding and binarization, IHRF were quantified in each retinal slab using ImageJ. The change in IHRF number in each slab between baseline and month 24 was calculated. Results: Fifty-two eyes showed evidence of IHRF at baseline, and all continued to show evidence of IHRF at 24 months (M24). The total average IHRF count/eye increased significantly from 4.67 ± 0.63 at baseline to 11.62 ± 13.86 at M24 (p<0.001) with a mean increase of 6.94 ± 11.12 (range: - 9 to + 60). Overall, at M24, 76.9% eyes showed an increase in IHRF whereas 15.4% of eyes showed a decrease (4 eyes [7.6%] showed no change). There was a greater number of IHRF and a greater increase in IHRF over M24 in the outer slabs. Conclusions: IHRF are most common in the outer retinal layers and tend to increase in number over time. The impact of the distribution and frequency of these IHRF on the overall progression of AMD requires further study.