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 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.

Reproducibility and agreement of four anterior segment-optical coherence tomography devices for anterior chamber angle measurements.

PURPOSE: To compare the reproducibility and agreement of anterior chamber angle (ACA) parameters and metrics obtained by four different anterior segment-optical coherence tomography (AS-OCT) devices. METHODS: In this prospective study, 30 eyes from 15 normal subjects underwent anterior segment angle scanning using the Spectralis, Cirrus, and Optovue spectral domain optical coherence tomography (SD-OCT), as well as the Visante time-domain optical coherence tomography (TD-OCT). For each eye, the scan line was performed perpendicularly on the inferior (270°) angle, and the inferior ACA image was acquired 2 times. Inter-instrument and intra-instrument, as well as inter-observer and intra-observer reproducibility of anterior chamber angle metrics, Schwalbe's line (SL) to scleral spur (SS) distance (TM-Span), angle opening distance (AOD), and trabecular iris space area (TISA) measurements, were evaluated by intraclass correlation coefficients (ICCs) and Bland-Altman plots with limits of agreement (LoA). RESULTS: For this cohort of 30 eyes of 15 normal subjects, the mean TM-Span, AOD, and TISA were 0.966 ± 0.198 mm, 0.750 ± 0.205 mm, and 0.286 ± 0.090 mm2 from the Spectralis; 0.929 ± 0.113 mm, 0.717 ± 0.120 mm, and 0.267 ± 0.095 mm2 from the Cirrus; 0.923 ± 0.191 mm, 0.683 ± 0.161 mm, and 0.265 ± 0.072 mm2 from the Optovue; and 0.970 ± 0.070 mm, 0.705 ± 0.150 mm, and 0.279 ± 0.065 mm2 from the Visante. The intra-instrument (ICCs > 0.838), intra-grader (ICCs > 0.910), and inter-grader (ICCs > 0.869) agreement were good. Agreement between the four instruments was also good with ICCs from 0.901 to 0.967 for TM-Span, 0.887 to 0.941 for AOD, and 0.923 to 0.961 for TISA. CONCLUSIONS: Consistent and reproducible ACA measurements could be obtained from multiple AS-OCT devices including both SD- and TD-OCT instruments. These findings have relevance when considering multiple imaging devices in future studies.

CHOROIDAL VASCULARITY INDEX AND CHOROIDAL THICKNESS IN EYES WITH RETICULAR PSEUDODRUSEN.

PURPOSE: To evaluate choroidal vascularity index (CVI), choroidal thickness, choroidal volume, and choroidal intensity in subjects with nonneovascular age-related macular degeneration (NNVAMD) with and without reticular pseudodrusen (RPD). METHODS: We included 60 eyes of 35 subjects with NNVAMD (including 30 eyes of 18 subjects with RPD) and 30 eyes of 17 age-matched healthy individuals from the ongoing Amish Eye study. The choroid was segmented from dense volume spectral domain optical coherence tomography scans and choroidal thickness (microns), choroidal intensity (log units), and choroidal volume (mm) from the entire macula (6 × 6 mm) were computed. A central horizontal B-scan was binarized and the luminal and stromal portions of the choroid were segmented. Choroidal vascularity index (%) was calculated as the ratio of luminal area to total choroid area. Choroidal parameters were compared between the groups by pairwise comparisons using the Student's t-test. RESULTS: The CVI was significantly lower in healthy eyes compared to those with RPD (53.43 ± 8.51 vs. 54.76 ± 4.83, P < 0.001). The CVI was also significantly lower in NNVAMD eyes without RPD compared to those with RPD (50.09 ± 7.51 vs. 54.76 ± 4.83, P = 0.006). There was no difference in CVI between healthy eyes and NNVAMD eyes without RPD (P = 0.84). Choroidal thickness and choroidal volume were significantly higher in NNVAMD without RPD (P < 0.05); and significantly lower in NNVAMD with RPD (P < 0.05) when compared with normal eyes. Choroidal intensity was significantly higher in NNVAMD with RPD when compared with normal eyes (P = 0.02) and NNVAMD eyes without RPD (P = 0.001). CONCLUSION: Multiple choroidal parameters reflecting the status of the choroidal vasculature and stroma seem to be altered in eyes with RPD compared with both normal eyes and NNVAMD eyes without RPD. These findings may provide insights into the pathophysiology of RPD.

AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

PURPOSE: To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). METHODS: The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. RESULTS: Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. CONCLUSION: The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.

QUANTIFICATION OF INTRARETINAL HARD EXUDATES IN EYES WITH DIABETIC RETINOPATHY BY OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the reproducibility of intraretinal hard exudate (HE) quantification from spectral domain optical coherence tomography (SD-OCT) images of eyes with diabetic retinopathy (DR). METHODS: Cases with diabetic macular edema were enrolled. The area of HE obtained by B-scan segmentation was compared with the area obtained by en face segmentation. RESULTS: The mean ± SD for the HE area was 1.78 ± 1.37 mm with B-scan segmentation and 0.72 ± 0.82 mm with the automated en face analysis tool; the absolute difference was 1.01 ± 0.64 mm. There was excellent correlation in total HE area between the two methods (r = 0.95, P < 0.0001). The HE volume was 0.06 ± 0.07 mm. The correlation between HE volume and en face HE area was high (r = 0.95, P < 0.001). Intergrader reproducibility yielded excellent agreement with an intraclass correlation coefficient value of 0.99 (95% CI 0.994-0.999) for the en face approach and 0.99 (95% CI 0.977-0.997) for manual segmentation. CONCLUSION: Quantification of HE in eyes with diabetic retinopathy can be performed reliably using en face segmentation and, though the en face results are consistently lower, correlates well with HE measurements obtained by exhaustive segmentation of all B-scans in dense volume optical coherence tomography (OCT).

Proposal of a simple optical coherence tomography-based scoring system for progression of age-related macular degeneration.

PURPOSE: To develop a simple, clinically practical, optical coherence tomography (OCT)-based scoring system for early age-related macular degeneration (AMD) to prognosticate risk for progression to late AMD. METHODS: We retrospectively reviewed OCT images (512 × 128 macular cube, Cirrus) from 138 patients diagnosed of early AMD in at least one eye and follow-up of at least 12 months. For patients with early AMD in both eyes, only the right eye was chosen as the study eye for longitudinal assessment. Scans were graded on four SD-OCT criteria associated with disease progression in previous studies: drusen volume within a central 3-mm circle ≥0.03 mm3, intraretinal hyperreflective foci (HRF), hyporeflective foci (hRF) within a drusenoid lesion (DL), and subretinal drusenoid deposits (SDD). Each criterion was assigned one point. For risk assessment of the study eye, the baseline status of the fellow eye was also considered, and thus these four features were also assessed in the fellow eye. The number of risk factors were summed for both eyes, yielding a total score (TS) of 0 to 8 for each patient. A fellow eye with evident choroidal neovascularization (CNV) or atrophy automatically received 4 points. Scores were then grouped into four categories to facilitate comparative analysis: I. (TS of 0, 1, 2), II. (TS of 3, 4), III. (TS of 5, 6) and IV. (TS of 7, 8). Correlation of baseline category assignment with progression to late AMD (defined as the presence of atrophy or CNV on OCT) by the last follow-up visit was evaluated with logistic regression analysis. RESULTS: The rate of progression to late AMD was 39.9% (55/138). Progression rates by category (I to IV) were 0, 14.3, 47.5, and 73.3%, respectively. Logistic regression analysis showed risk of progression to late AMD was 3.0 times (95% CI: 1.2-7.9) higher for an eye assigned to category IV than for an eye in category III and 16.4 (95% CI: 4.7-58.8) times higher than for an eye in category II. CONCLUSIONS: A simple scoring system relevant to prognosis for early AMD, and practical for use in a busy clinic, can be developed using SD-OCT criteria alone.

ASSESSMENT OF RETINAL BLOOD FLOW IN DIABETIC RETINOPATHY USING DOPPLER FOURIER-DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate retinal blood flow measurements in normal eyes and eyes with varying levels of diabetic retinopathy (DR) using Doppler Fourier-domain optical coherence tomography (FD-OCT). METHODS: Twenty-two eyes of 19 subjects, 10 with severe nonproliferative DR (NPDR) and 12 with proliferative DR (PDR), were compared with 44 eyes of 40 healthy control subjects. All eyes were scanned by RTvue FD-OCT. Color disk photographs and cube/volume scans of the optic nerve head were obtained. Doppler OCT scans and accessory imaging data were imported into Doppler OCT of Retinal Circulation grading software to calculate TRBF and vascular parameters (e.g., venous and arterial cross-sectional area). Measurements were compared between cases and controls using independent t-tests. RESULTS: Mean TRBF was 44.98 ± 9.80 (range: 30.18-64.58) µL/minute for normal eyes, 35.80 ± 10.48 (range: 20.69-49.56) µL/minute for eyes with severe NPDR, and 34.79 ± 10.61 (range: 16.77-48.9) µL/minute for eyes with PDR. Mean TRBF was significantly lower in eyes with severe NPDR (P = 0.01) and PDR (P = 0.003) than in normal eyes. CONCLUSION: Total retinal blood flow was significantly lower in eyes with severe NPDR and PDR compared with normal eyes. Retinal blood flow determined by Doppler OCT may be a useful parameter for evaluating patients with DR.

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. METHODS: Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. RESULTS: A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. CONCLUSION: Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration.

Heritability of Choroidal Thickness in the Amish.

PURPOSE: To evaluate the heritability of choroidal thickness and its relationship to age-related macular degeneration (AMD). DESIGN: Cohort study. PARTICIPANTS: Six hundred eighty-nine individuals from Amish families with early or intermediate AMD. METHODS: Ocular coherence tomography was used to quantify choroidal thickness, and fundus photography was used to classify eyes into categories using a modified Clinical Age-Related Maculopathy Staging (CARMS) system. Repeatability and heritability of choroidal thickness and its phenotypic and genetic correlations with the AMD phenotype (CARMS category) were estimated using a generalized linear mixed model (GLMM) approach that accounted for relatedness, repeated measures (left and right eyes), and the effects of age, gender, and refraction. MAIN OUTCOME MEASURES: Heritability of choroidal thickness and its phenotypic and genetic correlation with the AMD phenotype (CARMS category). RESULTS: Phenotypic correlation between choroidal thickness and CARMS category was moderate (Spearman's rank correlation, rs = -0.24; n = 1313 eyes) and significant (GLMM posterior mean, -4.27; 95% credible interval [CI], -7.88 to -0.79; P = 0.02) after controlling for relatedness, age, gender, and refraction. Eyes with advanced AMD had thinner choroids than eyes without AMD (posterior mean, -73.8; 95% CI, -94.7 to -54.6; P < 0.001; n = 1178 eyes). Choroidal thickness was highly repeatable within individuals (repeatability, 0.78; 95% CI, 0.68 to 0.89) and moderately heritable (heritability, 0.40; 95% CI, 0.14 to 0.51), but did not show significant genetic correlation with CARMS category, although the effect size was moderate (genetic correlation, -0.18; 95% CI, -0.49 to 0.16). Choroidal thickness also varied with age, gender, and refraction. The CARMS category showed moderate heritability (heritability, 0.49; 95% CI, 0.26 to 0.72). CONCLUSIONS: We quantify the heritability of choroidal thickness for the first time, highlighting a heritable, quantitative trait that is measurable in all individuals regardless of AMD affection status, and moderately phenotypically correlated with AMD severity. Choroidal thickness therefore may capture variation not captured by the CARMS system. However, because the genetic correlation between choroidal thickness and AMD severity was not significant in our data set, genes associated with the 2 traits may not overlap substantially. Future studies should therefore test for genetic variation associated with choroidal thickness to determine the overlap in genetic basis with AMD.

Outer retinal tubulation as a predictor of the enlargement amount of geographic atrophy in age-related macular degeneration.

PURPOSE: To determine the prognostic value of outer retinal tubulation (ORT) in the enlargement amount of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). DESIGN: Cohort study. PARTICIPANTS: One hundred eight fellow untreated eyes of 143 patients with GA resulting from AMD enrolled in the MAHALO study (clinicaltrials.gov identifier, NCT01229215) who completely satisfied the study term and had gradable spectral-domain optical coherence tomography (OCT) images obtained at both baseline and month 18 visits. METHODS: The MAHALO study enrolled 143 subjects into a phase 1b/2 multicenter, randomized, single-masked, sham-injection controlled clinical trial of the safety, tolerability, and evidence of activity of lampalizumab in patients with GA associated with AMD. Spectral-domain optical coherence tomography images were obtained at multiple time points in both eyes, although only the baseline and month 18 data of the fellow (nonstudy) eyes were considered in this exploratory analysis. The Cirrus HD-OCT review software was used for automatic segmentation and measurement of GA areas, with manual correction of segmentation errors by certified OCT graders. Baseline OCT images also were assessed for the presence of ORT. The enlargement amount of GA in eyes with ORT was compared with that of eyes without ORT. MAIN OUTCOME MEASURES: Comparison of the enlargement amount of GA in eyes with and without ORT. RESULTS: Twenty-four of these 108 eyes demonstrated evidence of ORT. The amount of enlargement of GA in eyes with ORT was significantly slower than that of eyes without ORT (1.85±0.78 vs. 2.67±1.61; P = 0.001). This difference remained significant when considering subgroups with unifocal or multifocal GA lesions, because eyes with ORT in both subgroups had a slower enlargement amount of GA than eyes without ORT (2.91±1.70 vs. 2.08±0.88 [P = 0.01], in eyes with multifocal GA lesions; and 2.24±1.40 vs. 1.63±0.57 [P = 0.02], in eyes with unifocal GA lesions). CONCLUSIONS: In eyes with ORT, GA lesions seem to enlarge at a significantly slower rate than those of eyes without ORT. The presence of ORT may need to be accounted for in longitudinal studies of GA.

Risk factors for proliferative diabetic retinopathy in a Latino American population.

PURPOSE: To assess the personal and demographic risk factors for proliferative diabetic retinopathy in Latino Americans in Los Angeles County. METHODS: In this prospective, non-interventional, cross-sectional case control study, seven hundred and twenty-nine subjects from Los Angeles County University of Southern California Medical Center (LAC + USC), Los Angeles, CA, were enrolled. All patients were recruited prospectively from the LAC + USC Medical Center and affiliated clinics between June 2008 and June 2011. Complete personal data and results from systemic and ophthalmic examinations were collected for all enrolled subjects. Laboratory tests such as glycosylated hemoglobin, creatinine levels, and cholesterol levels were collected prospectively by drawing blood at the time of each patient's clinic visit. The main outcome measures were age, gender, type of diabetes mellitus (DM I or II) duration of diabetes mellitus, history of hypertension, history of insulin use, height, weight, and body mass index, smoking history, glycosylated hemoglobin, creatinine levels, and cholesterol levels. RESULTS: The mean age of subjects with no diabetic retinopathy was 56.38 years (SD, 10.16), whereas that of patients with proliferative diabetic retinopathy was 57.43 years (SD, 9.63). Parameters that conferred a statistically significant increased risk for proliferative diabetic retinopathy in the multivariate model included gender (men were at higher risk: odds ratio [OR], 4.11; 95% confidence interval [CI], 2.56-6.58), insulin use (OR, 1.85; 95% CI, 1.13-3.03), history of hypertension (OR, 1.64; 95% CI, 1.02-2.63), and duration (>25 years vs. 10-15 years) of diabetes (OR, 22.00; 95% CI, 9.76-49.60). CONCLUSION: In this case-control study in a Latino population, duration of diabetes and male gender were the strongest risk factor for the development of proliferative diabetic retinopathy followed by insulin use and hypertension. Interestingly, smoking and glycosylated hemoglobin levels did not confer additional significant risk in this cohort.

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.

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.

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.

Long-Term Effects of Intravitreal Ranibizumab Compared With Panretinal Photocoagulation on Optical Coherence Tomography Measured Choroidal Thickness and Vascularity.

Purpose: Compare choroidal changes in ranibizumab versus panretinal photocoagulation (PRP)-treated eyes with proliferative diabetic retinopathy (PDR). Methods: DRCR Retina Network Protocol S post hoc analysis evaluated optical coherence tomography change in choroidal thickness (subfoveal and 3mm superior and inferior to the fovea) through five years; choroidal vascularity index (CVI) was assessed at baseline and one year. Mixed linear models for choroidal change included adjustments for the baseline choroidal value and age. Results: This study included 328 eyes (158 ranibizumab and 170 PRP) from 256 participants (88 ranibizumab and 95 PRP eyes at five years). Mean change in choroidal thickness from baseline to five years at the fovea was -12 µm in ranibizumab versus -8 µm in PRP (difference [95% confidence interval]: -4 [-18 to 10], P = 0.57), superior was -14 µm versus -19 µm (difference: 5 [-8 to 17], P = 0.45) and inferior was -26 µm versus -32 µm [difference: 5 (-9 to 20), P = 0.45]; change at all three points within the ranibizumab group, and the superior and inferior points for PRP, were statistically significant (P < .05). Mean change in CVI at one year was -0.02% in ranibizumab versus -0.95% in PRP (difference: 0.93 [-0.35 to 2.21], P = 0.14). Conclusions: In patients with PDR, treatment with ranibizumab versus PRP did not result in statistically significant differences in five-year choroidal thickness or one-year CVI change. Both groups had significant decreases in choroidal thickness at five years. Translational Relevance: Ranibizumab treatment for PDR did not statistically significantly affect choroidal thickness or vascularity differently than PRP.

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.

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.

Ethnic Variation in Diabetic Retinopathy Lesion Distribution on Ultra-widefield Imaging.

PURPOSE: To evaluate whether the distribution of diabetic retinopathy (DR) lesions differs among various ethnicities. DESIGN: Multi-center, retrospective cohort study. METHODS: We accrued a cohort of 226 eyes with DR consisting of 51 East Asian eyes, 102 South Asian eyes, 30 Caucasian eyes, and 43 Latino eyes, all evaluated with ultrawide field pseudocolor images. Images were manually annotated for DR lesions and were classified as having predominantly peripheral lesions (PPL) or predominantly central lesions (PCL) using 4 quantitative methods. The percent distribution of PCL to PPL was compared among different ethnicities. RESULTS: Using a single-field lesion frequency-based method, East Asian eyes more frequently demonstrated a PPL distribution (86.3%), whereas South Asian eyes more frequently demonstrated a PCL distribution (64.7%). These findings were also observed when considering only the subset of treatment-naïve eyes. Furthermore, in treatment-naïve eyes without proliferative DR, the percent distribution of PPL to PCL in East Asian eyes was significantly different when compared to other ethnicities (P < .0001 South Asian, P = .035 Caucasian, P = .0003 Latino). The majority of patients (60%-78%) in all ethnic groups had moderate nonproliferative diabetic retinopathy(NPDR), and the same difference between East Asian and South Asian eyes was observed in this subgroup. CONCLUSIONS: The distribution of DR lesions appears to vary among different ethnicities. DR lesions tend to be distributed more peripherally in East Asian eyes compared to other ethnic groups, particularly South Asian eyes, which tend to have more central disease. The prognostic implications of these ethnic differences in DR lesion distribution require further investigation.

Measuring retinal sensitivity with the microperimeter in patients with diabetes.

PURPOSE: To evaluate the retinal sensitivity and fixation characteristics in participants with diabetes mellitus, using the microperimeter (MP-1) and to correlate the MP-1 values with the severity of diabetic retinopathy (DR). METHODS: We performed complete ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, indirect ophthalmoscopy, and microperimetry (central 20° of macula) on 210 eyes of 160 participants. Participants included healthy individuals, individuals with diabetes but no retinopathy, and individuals with different stages of DR. RESULTS: The mean age of participants was (mean ± SD) 49.83 ± 7.43 years for healthy individuals, 53.20 ± 5.7 years for participants with diabetes but no retinopathy, and 55.39 ± 7.81 years for participants with DR. Retinal sensitivity was significantly (P = 0.001) decreased with severity of DR. The mean foveal sensitivity (retinal sensitivity in the central 2°) was 16.68 ± 2.13 dB in healthy individuals, 14.73 ± 3.64 dB in participants with diabetes but no DR, and 11.60 ± 5.76 dB in participants with DR. There was significant loss of retinal sensitivity in participants with diabetes but no retinopathy when compared with healthy individuals. Participants with severe nonproliferative DR showed more significant loss of retinal sensitivity in the central 20° than those with other stages of DR. CONCLUSION: The MP-1 is a useful tool to quantify retinal sensitivity in DR. Using the MP-1, we can detect early loss of retinal sensitivity in patients with diabetes but no retinopathy. Patients with severe nonproliferative DR will have less retinal sensitivity than those with other stages of DR. Scotoma mapping using the MP-1 provides details of functional vision in patients with DR.