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.

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.

Evaluating fingerprint-like patterns in the healthy Henle fiber layer using enface OCT imaging.

PURPOSE: Enface OCT may disclose a distinct "fingerprint-like' pattern within the HFL in various macular disorders. This study aims to investigate the frequency and characteristics of this pattern in healthy eyes and identify potential factors influencing its visibility. METHODS: Two, independent masked reading center graders evaluated for the presence and prominence of a fingerprint pattern in the Henle fiber layer (HFL) on enface OCT images from 33 healthy subjects (66 eyes). The prominence of the pattern was rated qualitatively using a 0-3 scale, with 3 indicating the strongest prominence. Tilt angles (relative to the normal/perpendicular at the center) of the retina were measured on horizontal and vertical B-scans, and the retinal curvature was assessed using ImageJ, in order to determine the impact of the incident light angle on the visibility and prominence of the fingerprint pattern. Inter-grader agreement using Cohen's kappa and the frequency and percentage of patterns in the entire enface image and in each quadrant were calculated and compared using the Friedman test with Dunn's post-test. A generalized estimating equation (GEE) was used to analyze the association between these metrics and fingerprint prominence. RESULTS: Substantial inter-grader agreement was observed (Cohen's kappa = 0.71) for assessing the prominence of the fingerprint pattern. Over 70% of eyes exhibited some evidence of the pattern (score ≥1). Significant difference in pattern prominence across quadrants was detected (p < 0.05), with lowest prominence in the temporal quadrant (p < 0.001 for pairwise comparisons against all other quadrants). The GEE analysis to account for the extent of the effect of scan tilt angle and RPE curvature was not able to predict the prominence of the fingerprint pattern, highlighting that angle of incidence (of the scanning laser light) alone could not explain the pattern. CONCLUSIONS: This study confirms that a fingerprint-like pattern within the HFL can also be observed in healthy eyes, challenging the notion that this finding is only manifest in the setting of disease. In addition, the lack of correlation with angle of incident light suggests that the pattern may be related to other intrinsic characteristics of the HFL.

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.

Subretinal hyperreflective material in regions of atrophy and fibrosis in eyes with neovascular age-related macular degeneration.

BACKGROUND: Subretinal hyperreflective material (SHRM) is a significant biomarker for poor visual outcomes in neovascular age-related macular degeneration (nAMD); however, its relationship with fibrosis and atrophy is not well understood. This study aims to evaluate the relationship between SHRM, atrophy, and fibrosis in eyes receiving antivascular endothelial growth factor therapy for nAMD. METHODS: Post-hoc analysis of the 65 patients enrolled in the SEVEN-UP study, a multicenter cross-sectional study of patients originally enrolled in the ANCHOR and MARINA trials of ranibizumab. Color fundus photographs (CFP) were reviewed and manually segmented to define regions of atrophy and fibrosis. SHRM borders on OCT volume scans were manually delineated, and thickness measurements were computed and compared in corresponding regions of atrophy and fibrosis on the CFPs. RESULTS: Of the 65 subjects, 51 eyes showed atrophy and/or fibrosis on CFP and were included in the final analysis. Both atrophy and fibrosis regions exhibited SHRM on OCT. The mean SHRM thickness on OCT was significantly greater in CFP-fibrosis regions (44.19 ± 46.95 µm) compared with CFP-atrophy regions (14.28 ± 13.35 µm; p < 0.001). Additionally, the average maximum height of SHRM in fibrotic regions (268.04 ± 130.05 µm) was significantly thicker than in atrophic regions (121.95 ± 51.17 µm; p < 0.001). CONCLUSIONS: Although atrophy and fibrosis are thought to be different end-stage outcomes in eyes with nAMD, they both demonstrate SHRM on OCT; the main distinction being thickness. Given these similarities, these regions of nAMD-associated atrophy may be better-termed "atrosis" to distinguish these lesions from typical atrophy in the absence of neovascular disease.

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.

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.

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: An Amish Eye Study Analysis.

PURPOSE: To compare the ganglion cell complex (GCC) thickness in eyes with age-related macular degeneration (AMD) vs healthy controls in an elderly Amish population. DESIGN: Prospective cross-sectional study. METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects underwent imaging with the Cirrus HD-OCT (Carl Zeiss Meditec Inc) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each comprising 512 A-scans) over a 6 mm × 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the ganglion cell layer (GCL) and the IPL. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of 6 sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. RESULTS: Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of 1294 subjects had all required imaging studies of sufficient quality and were included in the final analysis. Of these, 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (P < .001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). An independent t test showed that the early AMD (75.03 ± 12.45 µm) and late AMD (61.64 ± 21.18 µm) groups (among which eyes with geographic atrophy [GA] had the lowest thickness, of 58.10 ± 20.27 µm) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant differences in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. CONCLUSIONS: The GCC thickness in AMD eyes is reduced compared to normal eyes; however, the relationship is complex, with the greatest reduction in late AMD eyes (particularly eyes with GA) but no difference between early and intermediate AMD eyes.

Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration: A Nonrandomized Controlled Trial.

Importance: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable. Objective: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD. Design, Setting, and Participants: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023. Intervention: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years. Main Outcomes and Measures: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase. Results: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 µm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants). Conclusions and Relevance: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

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.

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.

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.

Optical Coherence Tomography Features of Macular Hyperpigmented Lesions without Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.

PURPOSE: To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD). METHODS: We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium + basal lamina (RPE + BL) band reflectivity, RPE + BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption. RESULTS: 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE + BL band. RPE + BL band reflectivity was increased in 37 (76%) of the lesions. RPE + BL band thickening, however, was not correlated with RPE + BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE + BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs. CONCLUSIONS: Thickening and/or hyperreflectivity of the RPE + BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD.

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.

OCT outcomes as biomarkers for disease status, visual function, and prognosis in diabetic macular edema.

OBJECTIVE: To evaluate disorganization of retinal inner layers (DRIL), as detected on spectral-domain optical coherence tomography (OCT) images, as a biomarker for diabetic macular edema (DME) activity, visual function, and prognosis in eyes with DME. DESIGN: Longitudinal prospective. METHODS: Post hoc correlation analyses were performed on data from a phase 2 clinical trial. Seventy-one eyes of 71 patients with treatment-naive DME received either suprachoroidally administered CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension) combined with intravitreal aflibercept or intravitreal aflibercept with a sham suprachoroidal injection procedure. DRIL area, maximum horizontal extent of DRIL, ellipsoid zone (EZ) integrity, and the presence and location of subretinal (SRF) and intraretinal fluid (IRF) were evaluated at baseline and week 24 by certified reading centre graders. RESULTS: At baseline, the area and maximum horizontal extent of DRIL were negatively correlated with best-corrected visual acuity (BCVA; r = -0.25, p = 0.05 and r = -0.32, p =0.01, respectively). Mean baseline BCVA progressively worsened with each ordinal drop in EZ integrity, improved with the presence of SRF, and was invariant to the presence of IRF. DRIL area and maximum extent were significantly decreased at week 24 (-3.0 mm2 [p < 0.001] and -775.8 mm [p < 0.001], respectively. At week 24, decreases in the area and maximum horizontal extent of DRIL were positively correlated with increases in BCVA (r = -0.40, p = 0.003 and r = -0.30, p = 0.04). Improvements in BCVA at week 24 were no different between patients showing improvement in EZ, SRF, or IRF and those showing no improvement or worsening from baseline. CONCLUSIONS: DRIL area and DRIL maximum horizontal extent were demonstrated to be novel biomarkers for macular edema status, visual function, and prognosis in eyes with treatment-naive DME.

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.

Relationship between the distribution of intra-retinal hyper-reflective foci and the progression of intermediate age-related macular degeneration.

PURPOSE: To assess the relationship between the distribution of intra-retinal hyper-reflective foci (IHRF) on optical coherence tomography (OCT) and progression of intermediate age-related macular degeneration (iAMD) over 2 years. METHODS: Cirrus OCT volumes of the macula of subjects enrolled in the Amish Eye Study with 2 years of follow-up were evaluated for the presence of iAMD and IHRF at baseline. The IHRF were counted in a series of 5 sequential en face slabs from outer to inner retina. The number of IHRF in each slab at baseline and the change in IHRF from baseline to year 2 were correlated with progression to late AMD at 2 years. RESULTS: Among 120 eyes from 71 patients with iAMD, 52 eyes (43.3%) of 42 patients had evidence of both iAMD and IHRF at baseline. Twenty-three eyes (19.0%) showed progression to late AMD after 2 years. The total IHRF count increased from 243 at baseline to 604 at 2 years, with a significant increase in the IHRF number in each slab, except for the innermost slab 5 which had no IHRF at baseline or follow-up. The IHRF count increased from 121 to 340 in eyes that showed progression to late AMD. The presence of IHRF in the outermost retinal slabs 1 and 2 was independently associated with a significant risk of progression to late AMD. A greater increase in IHRF count over 2 years in these same slabs 1 and 2 was also associated with a higher risk of conversion to late AMD. CONCLUSIONS: The risk of progression to late AMD appears to be significantly associated with the distribution and extent of IHRF in the outermost retinal layers. This observation may point to significant pathophysiologic differences of IHRF in inner versus outer layers of the retina.

The relationship of diabetic retinopathy severity scales with frequency and surface area of diabetic retinopathy lesions.

PURPOSE: To assess the relationship between qualitative diabetic retinopathy (DR) scales with the precise numbers and surface area of DR lesions within the Early Treatment Diabetic Retinopathy Study (ETDRS) standard seven field (S7F) region on ultrawide-field (UWF) color fundus images. METHODS: In this study, we collected UWF images from adult patients with diabetes. Poor-quality images and eyes with any pathology precluding assessment of DR severity were excluded. The DR lesions were manually segmented. DR severity was graded according to the International Clinical Diabetic Retinopathy (ICDR) and AA protocol by two masked graders within the ETDRS S7F. These lesions' numbers and surface area were computed and correlated against the DR scores using the Kruskal-Wallis H test. Cohen's Kappa was performed to determine the agreement between two graders. RESULTS: One thousand five hundred and twenty eyes of 869 patients (294 females, 756 right eyes) with a mean age of 58.7 years were included. 47.4% were graded as no DR, 2.2% as mild non-proliferative DR (NPDR), 24.0% as moderate NPDR, 6.3% as severe NPDR, and 20.1% as proliferative DR (PDR). The area and number of DR lesions generally increased as the ICDR level increased up to severe NPDR, but decreased from severe NPDR to PDR. There was perfect intergrader agreement on the DR severity. CONCLUSION: A quantitative approach reveals that DR lesions' number and area generally correlate with ICDR-based categorical DR severity levels with an increasing trend in the number and area of DR lesions from mild to severe NPDR and a decrease from severe NPDR to PDR.