In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques.

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes - 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruchs membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates

Vertical Macular Asymmetry Measures Derived From SD-OCT for Detection of Early Glaucoma.

PurposeTo test the hypothesis that vertical asymmetry in macular ganglion cell/inner plexiform layer (GCIPL) thickness can improve detection of early glaucoma.MethodsSixty-nine normal eyes and 101 glaucoma eyes had macular imaging with spectral-domain optical coherence tomography (OCT; 200 × 200 cube). The resulting GCIPL thickness matrix was grouped into a 20 × 20 superpixel array and superior superpixels were compared to their inferior counterparts. A global asymmetry index (AI) was defined as the grand mean of the asymmetry ratios. To measure local asymmetry, the corresponding thickness measurements of three rows above and below the horizontal raphe were compared individually and in combinations. Global and local AIs were compared to the best-performing GCIPL thickness parameters with area under the receiver operating curves (AUC) and sensitivity/specificities.ResultsAge or axial length did not influence AIs in normal subjects (P ≥ 0.08). Global and local AIs were significantly higher in the glaucoma group compared to normal eyes. Minimum (AUC = 0.962, 95% confidence interval [CI]: 0.936-0.989) and inferotemporal thickness (AUC = 0.944, 95% CI: 0.910-0.977; P = 0.122) performed best for detection of early glaucoma. The AUC for global AI was 0.851 (95% CI: 0.792-0.909) compared to 0.916 (95% CI: 0.874-0.958) for the best local AI. Combining minimum or inferotemporal GCIPL thickness and the best local AI led to higher partial AUCs (0.088 and 0.085, 90% specificity, P = 0.120 and 0.130, respectively) than GCIPL thickness measures.ConclusionsMacular vertical thickness asymmetry measures did not perform better than sectoral or minimum GCIPL thickness for detection of early glaucoma. Combining local asymmetry parameters with the best sectoral GCIPL thickness measures enhanced this task

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities

To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND-)

Correlation between retinal function and microstructural foveal changes in intermediate age related macular degeneration

Purpose: To assess foveal microstructural changes influencing retinal sensitivity (RS) and fixation stability using microperimeter MP-1 in intermediate age-related macular degeneration (AMD). Methods: In this cross-sectional study, 22 eyes of 22 patients (mean age: 75 ± 9.02 years) with intermediate AMD were enrolled. Retinal sensitivity and bivariate contour ellipse area (BCEA) were obtained by microperimetry MP-1 (Humphrey 10-2 68-loci grid) under mesopic conditions. Drusen type, drusenoid pigment epithelial detachment, hyperreflective foci (HF), integrity of external limiting membrane (ELM), inner ellipsoid zone (ISel), RPE/Bruch’s mem- brane complex (RPE/B) and subfoveal choroidal thickness were analyzed in the foveal region and compared with RS and BCEA. Spearman’s rank correlation coefficient was used to evaluate the relationship between variables. Logistic regression analysis was also used to assess morphological predictor influencing RS or BCEA. Results: RS was strongly and inversely related with the presence of HF (r = −0.66, P = 0.001), integrity of ELM (r = −0.70, P < 0.001), ellipsoid zone (r = −0.45, P = 0.03). Instead, BCEA is positively related to the ellipsoid zone integrity (r = 0.45, P = 0.03). Logistic regression analysis confirmed that disruption of ISel influenced fixation stability (ExpB: 9.69, P = 0.04) but not RS. Instead, the presence of HF and disruption of ELM predicted RS reduction (ExpB: 0.55, P = 0.02 and ExpB: 0.29, P = 0.04, respectively). Conclusions: The integrity of ELM and the presence of HF are both predictors of RS. The ELM status may be con- sidered a new biomarker of retinal function together with HF. Instead, the integrity of ISel band seems to be a more selective predictor of BCEA than RS

Vascular Response to Sildenafil Citrate in Aging and Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) - the leading cause of vision loss in the elderly - share many risks factors as atherosclerosis, which exhibits loss of vascular compliance resulting from aging and oxidative stress. Here, we attempt to explore choroidal and retinal vascular compliance in patients with AMD by evaluating dynamic vascular changes using live ocular imaging following treatment with oral sildenafil citrate, a phosphodiesterase type 5 (PDE5) inhibitor and potent vasodilator. Enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A) were performed on 46 eyes of 23 subjects, including 15 patients with non-exudative AMD in one eye and exudative AMD in the fellow eye, and 8 age-matched control subjects. Choroidal thickness, choroidal vascularity, and retinal vessel density were measured across the central macula at 1 and 3 hours after a 100 mg oral dose of sildenafil citrate. Baseline choroidal thickness was 172.1 ± 60.0 μm in non-exudative AMD eyes, 196.4 ± 89.8 μm in exudative AMD eyes, and 207.4 ± 77.7 μm in control eyes, with no difference between the 3 groups (P = 0.116). After sildenafil, choroidal thickness increased by 6.0% to 9.0% at 1 and 3 hours in all groups (P = 0.001-0.014). Eyes from older subjects were associated with choroidal thinning at baseline (P = 0.005) and showed less choroidal expansion at 1 hour and 3 hours after sildenafil (P = 0.001) regardless of AMD status (P = 0.666). The choroidal thickening appeared to be primarily attributed to expansion of the stroma rather than luminal component. Retinal vascular density remained unchanged after sildenafil in all 3 groups (P = 0.281-0.587). Together, our studies suggest that vascular response of the choroid to sildenafil decreases with age, but is not affected by the presence of non-exudative or exudative AMD, providing insight into changes in vessel compliance in aging and AMD

Optical Coherence Tomography Interpretation for Glaucoma

Structural glaucomatous changes occur more frequently in the earlier stages of glaucoma than functional defects so we should give special care on oct (optical coherence tomography) importance as the best current method. RNFL change detection are more useful in early glaucoma, GCC in moderate to advanced glaucoma while visual field test is more useful in advanced stages but overall using a combination of RNFL, ONH and macular measurement modalities is recommended for glaucoma evaluation because each of these parameters may be affected earlier than the others so, taking into account the findings from the RNFL, ONH and macula enhances early diagnosis of glaucoma

Microperimetric evaluation in patients with adult-onset foveomacular vitelliform dystrophy

INTRODUCTION: To compare mean best-corrected visual acuity (BCVA), retinal sensitivity (RS), and bivariate contour ellipse area (BCEA) in patients with adult-onset foveomacular vitelliform dystrophy (AOFVD) and healthy subjects (HSs), reporting also functional disease-related changes in the different stages of the AOFVD disease. MATERIALS AND METHODS: In this observational cross-sectional study, a total of 19 patients (30 eyes; 12 female and 7 male) with AOFVD were enrolled, and 30 patients (30 eyes; 16 female and 14 male) were recruited as age-matched control group (74.36 ± 9.17 years vs. 71.83 ± 6.99 years respectively, P= 0.11). All patients underwent a complete ophthalmologic examination, fundus autofluorescence and fluorescein angiography, spectral-domain optical coherence tomography and microperimetry (MP)-1 analysis. The data collection included mean BCVA, mean RS measured by means of MP-1, BCEA, and central retinal thickness. RESULTS: All the functional parameters (BCVA, RS, and BCEA) were significantly worse in AOFVD group than HS. Subgroup analysis showed that the most significant functional changes, quantified by mean BCVA, RS, and BCEA, were in the atrophic stage (P = 0.03, P= 0.01, and P= 0.001, respectively). All the functional parameters were well correlated in the different stages. CONCLUSIONS: This study further confirms the good visual prognosis in the AOFVD eyes. Fixation stability measurement using BCEA demonstrates good evaluation of visual performance integrating traditional functional parameters. It may also serve for further rehabilitative purposes in atrophic eyes

Automated Retinal Layer Segmentation Using Spectral Domain Optical Coherence Tomography: Evaluation of Inter-Session Repeatability and Agreement between Devices

Retinal and intra-retinal layer thicknesses are routinely generated from optical coherence tomography (OCT) images, but on-board software capabilities and image scaling assumptions are not consistent across devices. This study evaluates the device-independent Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) for automated intra-retinal layer segmentation and image scaling for three OCT systems. Healthy participants (n = 25) underwent macular volume scans using a Cirrus HD-OCT (Zeiss), 3D-OCT 1000 (Topcon), and a non-commercial long-wavelength (1040nm) OCT on two occasions. Mean thickness of 10 intra-retinal layers was measured in three ETDRS subfields (fovea, inner ring and outer ring) using the Iowa Reference Algorithms. Where available, total retinal thicknesses were measured using on-board software. Measured axial eye length (AEL)-dependent scaling was used throughout, with a comparison made to the system-specific fixed-AEL scaling. Inter-session repeatability and agreement between OCT systems and segmentation methods was assessed. Inter-session coefficient of repeatability (CoR) for the foveal subfield total retinal thickness was 3.43μm, 4.76μm, and 5.98μm for the Zeiss, Topcon, and long-wavelength images respectively. For the commercial software, CoR was 4.63μm (Zeiss) and 7.63μm (Topcon). The Iowa Reference Algorithms demonstrated higher repeatability than the on-board software and, in addition, reliably segmented all 10 intra-retinal layers. With fixed-AEL scaling, the algorithm produced significantly different thickness values for the three OCT devices (P<0.05), with these discrepancies generally characterized by an overall offset (bias) and correlations with axial eye length for the foveal subfield and outer ring (P<0.05). This correlation was reduced to an insignificant level in all cases when AEL-dependent scaling was used. Overall, the Iowa Reference Algorithms are viable for clinical and research use in healthy eyes imaged with these devices, however ocular biometry is required for accurate quantification of OCT images

Choroidal Haller's and Sattler's Layer Thickness Measurement Using 3-Dimensional 1060-nm Optical Coherence Tomography

Objectives: To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller's and Sattler's layer thickness in healthy eyes Methods: Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36°x36° field of view. Haller's and Sattler's layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller's and Sattler's layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidalsublayers. Results: The coefficients of repeatability for Sattler's and Haller's layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean±SD healthy central submacular field thickness for Sattler's and Haller's was 87±56 µm and 141±50 µm, respectively, with a significant relationship for AL (P<.001). Conclusions: Automated Sattler's and Haller's thickness segmentation generates rapid 3D measurements with a repeatability correspondingto reported manual segmentation. Sublayers in healthy eyes thinnedsignificantly with increasing AL. In the presence of the thinned Sattler's layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss.Macular Vision Research FoundationMedical University of ViennaEuropean Union (project FUN OCT (FP7 HEALTH, contract no. 201880))European Union (FAMOS (FP7 ICT 317744))European Union (FWF-NFN ‘Photoacoustic imaging in biology and Medicine’, Oesterreichische Nationalbank Jubilaumsfonds projekt (14294))National Institutes of Health (U.S.) (NIH R01-EY011289-27)Deutsche Forschungsgemeinschaft (DFG-GSC80-SAOT)Deutsche Forschungsgemeinschaft (DFG-GSC80-SAOT, DFG-HO-1791/11-1)Carl Zeiss Meditec, Inc.FEMTOLASERS (Firm)Christian Doppler Societ

Visual analytics methods for retinal layers in optical coherence tomography data

Optical coherence tomography is an important imaging technology for the early detection of ocular diseases. Yet, identifying substructural defects in the 3D retinal images is challenging. We therefore present novel visual analytics methods for the exploration of small and localized retinal alterations. Our methods reduce the data complexity and ensure the visibility of relevant information. The results of two cross-sectional studies show that our methods improve the detection of retinal defects, contributing to a deeper understanding of the retinal condition at an early stage of disease.Die optische Kohärenztomographie ist ein wichtiges Bildgebungsverfahren zur Früherkennung von Augenerkrankungen. Die Identifizierung von substrukturellen Defekten in den 3D-Netzhautbildern ist jedoch eine Herausforderung. Wir stellen daher neue Visual-Analytics-Methoden zur Exploration von kleinen und lokalen Netzhautveränderungen vor. Unsere Methoden reduzieren die Datenkomplexität und gewährleisten die Sichtbarkeit relevanter Informationen. Die Ergebnisse zweier Querschnittsstudien zeigen, dass unsere Methoden die Erkennung von Netzhautdefekten in frühen Krankheitsstadien verbessern