Publications by authors named "Srinivas Sadda"

554 Publications

Longitudinal Changes of Fixation Stability and Location within 24 Months in Stargardt Disease: ProgStar Report No. 16: Short title: Longitudinal Changes of Fixation in Stargardt Disease.

Am J Ophthalmol 2021 Jul 20. Epub 2021 Jul 20.

Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.; Department of Ophthalmology, University of Basel, Basel, Switzerland.. Electronic address:

Objective: Stargardt Disease type 1 (STGD1) is the most common macular dystrophy. The assessment of fixation describes an important dimension of visual function but there is limited data on its progression over time. We present longitudinal changes and investigate its usefulness for clinical trials.

Design: International, multicenter, prospective cohort study PARTICIPANTS AND MAIN OUTCOME MEASURES: : A total of 239 individuals with genetically confirmed STGD1 (≥ 1 disease-causing ABCA4 variant). We determined the fixation stability (FS) using the bivariate contour ellipse area (1 SD-BCEA) and fixation location (FL) using the eccentricity of fixation from the fovea during 5 study visits every 6 months.

Results: At baseline, 239 patients (105 males, 44 %) and 459 eyes with a median age of 32 years were included. The baseline mean log BCEA was 0.70 ± 1.41 log deg and the mean FL was 6.25 ± 4.40 deg. Although the mean log BCEA did not monotonically increase from visit to visit, the overall yearly increase in log BCEA was 0.124 log deg (95% CI, 0.063-0.185). The rate of change was not different between the two years but increased faster in eyes without flecks outside of the vascular arcades and depended on baseline log BCEA. FL did not change statistically significantly over time.

Conclusion And Relevance: Fixation parameters are unlikely to be sensitive outcome measures for clinical trials in STGD1 but they may provide useful ancillary information in selected cases to longitudinally describe and understand an eye's visual function.
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http://dx.doi.org/10.1016/j.ajo.2021.07.013DOI Listing
July 2021

Effect of Residual Retinal Fluid on Visual Function in Ranibizumab-Treated Neovascular Age-Related Macular Degeneration: Effect of Retinal Fluid on Vision Outcomes in HARBOR.

Am J Ophthalmol 2021 Jul 18. Epub 2021 Jul 18.

Genentech, Inc., South San Francisco, California, United States.

Purpose: To investigate the relationship between retinal fluid and vision in ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD).

Design: Clinical cohort study using post hoc analysis of clinical trial data.

Methods: Setting: HARBOR (NCT00891735): phase III, randomized, controlled trial.

Population: 917 patients aged ≥50 years with subfoveal nAMD associated with subretinal (SRF) and/or intraretinal fluid (IRF) at baseline, screening, or week 1.

Intervention: Intravitreal ranibizumab 0.5 or 2.0 mg (all treatment arms pooled).

Outcomes: Mean best-corrected visual acuity (BCVA) and BCVA change from baseline at months (M)12/24 evaluated by presence/absence of SRF and/or IRF.

Results: Baseline BCVA was higher with residual versus resolved SRF at M12 (mean [95% confidence interval (CI)], 58.8 letters [57.2 to 60.4] vs 53.5 [52.4 to 54.5]) and M24 (59.3 letters [57.8 to 60.8] vs 53.5 [52.5 to 54.5]). Mean BCVA change (adjusted for baseline) to M12 was greater with residual versus resolved SRF (mean difference [95% CI], +2.4 letters [+0.1 to +4.7]), but lower with residual versus resolved IRF (-3.5 letters [-5.8 to -1.2]). Eyes with residual SRF (no IRF) exhibited the largest mean BCVA gains (M12, +14.1 letters; M24, +13.2), followed by resolved SRF/IRF (M12, +10.6 letters; M24, +10.0), residual SRF/IRF (M12, +7.2 letters; M24, +8.5), and residual IRF only (M12, +5.5 letters; M24, +3.6).

Conclusions: Vision outcomes (adjusted for baseline BCVA) through M24 were better in ranibizumab-treated eyes with residual versus resolved SRF, and worse with residual versus resolved IRF. Presence of residual retinal fluid requires a more complex and nuanced assessment and interpretation in the context of nAMD management.
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http://dx.doi.org/10.1016/j.ajo.2021.06.029DOI Listing
July 2021

Coincident PAMM and AMN and Insights into a Common Pathophysiology: Coincident PAMM and AMN.

Am J Ophthalmol 2021 Jul 17. Epub 2021 Jul 17.

Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States; Greater Los Angeles Veterans Affairs Healthcare Center, Los Angeles, California. Electronic address:

Purpose: To analyze imaging characteristics and the clinical course of patients demonstrating coincident lesions of paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) in the same eye.

Design: Retrospective, observational, case series.

Methods: Lesions from patients presenting with coincident PAMM and AMN in the same eye were evaluated with multimodal imaging including optical coherence tomography (OCT). The association with ocular and systemic findings was also investigated.

Results: Fifteen subjects (17 eyes) were included in the study. Mean age was 44.4±15.3 years old and follow-up period ranged from 1-32 weeks (mean 11.9±11.4 weeks). Mean visual acuity was 0.8±0.6 logMAR (Snellen equivalent 20/126) at baseline and 0.3±0.4 logMAR (Snellen equivalent 20/40) at the last follow-up. PAMM and AMN lesions occurred in the setting of Purtscher's retinopathy (4 eyes, 3 patients), retinal vein occlusion (7 eyes, 7 patients), central retinal artery occlusion (1 eye, 1 patient), and idiopathic retinal vasculitis (1 eye, 1 patient). In 4 eyes (3 patients) an association with other ocular disorders was not identified as evaluated with multimodal imaging. Of the total cohort,11 eyes (64.7%) showed extension of the AMN hyperreflective bands in the Henle's fiber layer (HFL) with a Z-shaped morphology on OCT B-scan.

Conclusions: Presence of coincident PAMM and AMN suggest a common pathophysiologic etiology. This may be the result of retinal vein impairment and hypoperfusion at the level of the deep retinal capillary plexus possibly leading to injury to the Müller glia or photoreceptors in the HFL.
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http://dx.doi.org/10.1016/j.ajo.2021.07.004DOI Listing
July 2021

Early Postnatal Oxygen Exposure Predicts Choroidal Thinning in Neonates.

Invest Ophthalmol Vis Sci 2021 Jul;62(9):23

Department of Pediatrics, Division of Neonatology and Developmental Biology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States.

Purpose: To evaluate whether choroidal thickness (CT) using arm-mounted optical coherence tomography (OCT) in infants screened for retinopathy of prematurity (ROP) correlates with oxygen exposure in neonates.

Methods: OCT images were obtained in infants screened for ROP in a single level IV neonatal intensive care unit. CT was measured at three different locations: the subfoveal center and 1.5 mm from the fovea center in each direction. Correlation and regression analyses were performed to determine the relationship between clinical factors and CT. Clinical factors included gestational age, birth weight, presence of bronchopulmonary dysplasia (BPD), and fraction of inspired oxygen (FiO2) at defined time points: 30 weeks postmenstrual age (PMA), 36 weeks PMA, and on day of imaging.

Results: Mean subfoveal, nasal, and temporal choroidal thicknesses CT (SFCT, NCT, and TCT, respectively) were 228.0 ± 51.4 µm, 179.7 ± 50.3 µm, and 186.4 ± 43.8 µm, respectively. SFCT was found to be significantly thicker than NCT and TCT (P < 0.0001 and P = 0.0002, respectively), but no significant difference was found between NCT and TCT (P = 0.547). Compared with infants without BPD, infants with BPD had thinner SFCT and NCT (P = 0.01 and P = 0.0008, respectively). Birth weight was positively correlated with SFCT (r = 0.39, P = 0.01) and NCT (r = 0.33, P = 0.045) but not TCT. Gestational age and ROP stage were not significantly associated with CT. SFCT was found to be significantly thinner with higher average FiO2 supplementation levels at 30 weeks PMA (r = -0.51, P = 0.01) but not at 36 weeks PMA. Regression analysis revealed that FiO2 at 30 weeks PMA was an independent predictor of SFCT in infants screened for ROP (P = 0.01).

Conclusions: Early postnatal exposure (<32 weeks PMA) to higher oxygen supplementation in premature neonates statistically predicts choroidal thinning.
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http://dx.doi.org/10.1167/iovs.62.9.23DOI Listing
July 2021

In vivo measurement of the lineal density of red blood cells in human retinal capillaries using high-speed adaptive optics ophthalmoscopy.

Opt Lett 2021 Jul;46(14):3392-3395

We present an automated method for measuring the lineal density of red blood cells (RBCs) in human retinal capillaries using adaptive optics near-confocal ophthalmoscopy (AONCO). The spatiotemporal traces of RBCs flowing in retinal capillaries were extracted from AONCO images, enhanced using the Gabor filter, the vesselness filter, and the Hough transform. A total of 43 capillary segments (each 50 µm long) were analyzed in 12 eyes of 12 subjects, and the measurement error of the automated method was 0.09 cell over 50 µm compared with results obtained by manual counting. Our method provides a tool for assessing RBC spatial distribution in retinal capillaries.
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http://dx.doi.org/10.1364/OL.428538DOI Listing
July 2021

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

Eye (Lond) 2021 Jul 14. Epub 2021 Jul 14.

Doheny Eye Institute, Los Angeles, CA, USA.

Purpose: To evaluate the ability of retro mode illumination imaging for quantifying atrophy compared to confocal color fundus photography (c-CFP), green light fundus autofluorescence (G-FAF), blue light fundus autofluorescence (B-FAF) using the scanning laser ophthalmoscope (SLO) Mirante device by Nidek (Nidek Co., Ltd, Gamogori, Japan).

Methods: Eyes with clinical evidence of geographic atrophy (GA) associated with non-neovascular age-related macular degeneration, evaluated at the Doheny Eye Centers-UCLA and Hospital Sacco Milan, were included in this prospective, cross-sectional study. All eyes were imaged with multiple retinal imaging modalities using the SLO Nidek Mirante device: c-CFP, G-FAF, B-FAF, retro mode illumination deviated-right (RMDR), and deviated-left (RMDL). Masked graders measured the GA lesion on each modality and inter-modality and inter-grader repeatability were assessed.

Results: The mean (SD) area of GA measured 9.76 (3.82) mm, 9.75 (3.91) mm, 9.76 (3.92) mm, 9.82 (3.87) mm, and 9.81 (3.86) mm using c-CFP, G-FAF, B-FAF, RMDR, and RMDL, respectively (p = 0.2). Inter-modality correlation was high (Pearson's r > 0.9 and p < 0.0001). Agreement between graders was excellent for all modalities.

Conclusions: Retro mode imaging demonstrated good agreement for measuring GA compared to other imaging modalities, with a high level of repeatability. Given that retro mode imaging uses infrared light and is comfortable, it may prove to be a useful tool for the assessment of GA in the clinic.
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http://dx.doi.org/10.1038/s41433-021-01670-3DOI Listing
July 2021

Post hoc analysis of ellipsoid zone changes beyond the central subfield in symptomatic vitreomacular adhesion patients from the OASIS trial.

BMJ Open Ophthalmol 2021 21;6(1):e000648. Epub 2021 Jun 21.

Retina, Doheny Eye Institute, Los angeles, California, USA.

Background/aims: OASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.

Methods: 220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.

Results: A total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.

Conclusions: Ocriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.

Trial Registration Number: NCT01429441.
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http://dx.doi.org/10.1136/bmjophth-2020-000648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217951PMC
June 2021

Longitudinal assessment of type 3 macular neovascularization using three-dimensional volume-rendering OCTA.

Can J Ophthalmol 2021 May 28. Epub 2021 May 28.

Vita-Salute San Raffaele University, Milan, Italy; San Raffaele Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Milan, Italy; Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, Calif. Electronic address:

Objective: To investigate the evolution of treatment-naive type 3 macular neovascularization (MNV) undergoing anti-vascular endothelial growth factor (VEGF) treatment through volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA).

Design: Retrospective observational study.

Participants: Patients with type 3 MNV and age-related macular degeneration (AMD).

Methods: Included subjects had three loading injections of an anti-VEGF agent. The OCTA volume data at baseline and follow-up were processed with a previously published algorithm in order to obtain a volume-rendered representation of type 3 MNV. Progressive changes in type 3 lesions were analyzed via 3D OCTA volume rendering.

Results: A total of 14 treatment-naive eyes with type 3 MNV from 11 AMD patients (7 females) were included. At both baseline and follow-up visits, a type 3 MNV complex was identifiable. Each complex was composed of a mean number of 2.5 ± 0.7 vascular branches at baseline and 1.4 ± 0.6 at the follow-up visit (p < 0.0001). The mean changes in central macular thickness and visual acuity were significantly correlated with modifications in the number of type 3 MNV branches (ρ = -0.533, p = 0.049, and ρ = -0.581, and p = 0.040, respectively).

Conclusions: This study demonstrated that type 3 lesions do not disappear completely after loading treatment, as indicated previously by histopathologic studies. Importantly, quantitative volume changes in type 3 lesions are directly associated with treatment response.
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http://dx.doi.org/10.1016/j.jcjo.2021.04.020DOI Listing
May 2021

Therapeutic Margin for Geographic Atrophy: The Race Between Longevity and Disease Progression.

JAMA Ophthalmol 2021 Jul;139(7):751-752

Department of Ophthalmology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.

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http://dx.doi.org/10.1001/jamaophthalmol.2021.1414DOI Listing
July 2021

Automatic Segmentation in Multiple OCT Layers For Stargardt Disease Characterization Via Deep Learning.

Transl Vis Sci Technol 2021 04;10(4):24

Doheny Image Analysis Laboratory, Doheny Eye Institute, Los Angeles, CA, USA.

Purpose: This study sought to perform automated segmentation of 11 retinal layers and Stargardt-associated features on spectral-domain optical coherence tomography (SD-OCT) images and to analyze differences between normal eyes and eyes diagnosed with Stargardt disease.

Methods: Automated segmentation was accomplished through application of the deep learning-shortest path (DL-SP) framework, a shortest path segmentation approach that is enhanced by a deep learning fully convolutional neural network. To compare normal eyes and eyes diagnosed with Stargardt disease, various retinal layer thickness and intensity feature maps associated with the outer retinal layers were generated.

Results: The automated DL-SP approach achieved a mean difference within a subpixel accuracy range for all layers when compared to manually traced layers by expert graders. The algorithm achieved mean and absolute mean differences in border positions for Stargardt features of -0.11 ± 4.17 pixels and 1.92 ± 3.71 pixels, respectively. In several of the feature maps generated, the characteristic Stargardt features of flecks and atrophic-appearing lesions were readily visualized.

Conclusions: To the best of our knowledge, this is the first automated algorithm for 11 retinal layer segmentation on OCT in eyes with Stargardt disease, and, furthermore, the feature differences found between eyes diagnosed with Stargardt disease and normal eyes may inform new insights and the better understanding of retinal characteristic morphologic changes caused by Stargardt disease.

Translational Relevance: The automated algorithm's performance and the feature differences found using the algorithm's segmentation support the future applications of SD-OCT for the quantitative monitoring of Stargardt disease.
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http://dx.doi.org/10.1167/tvst.10.4.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083069PMC
April 2021

Relative Postpartum Retinal Vasoconstriction Detected With Optical Coherence Tomography Angiography.

Transl Vis Sci Technol 2021 02;10(2):40

Doheny Eye Center and UCLA Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.

Purpose: To characterize changes in retinal perfusion during pregnancy and the postpartum period using optical coherence tomography angiography (OCTA).

Methods: A nonmydriatic OCTA camera was used to image healthy women who were pregnant or in the postpartum period along with nonpregnant controls. Perfusion density (PD) and vessel length density (VLD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were evaluated.

Results: A total of 16, 15, and 13 eyes from nonpregnant, pregnant, and healthy postpartum subjects, respectively, were evaluated. When compared to controls, there were significant increases in ICP PD during the second and third trimester of pregnancy, along with significant decreases in both PD and VLD in SCP, ICP, and DCP up to 14 weeks postpartum.

Conclusions: During pregnancy, vascular changes consistent with retinal vasodilation were noted in the ICP. During the postpartum period, changes in retinal vasculature suggest relative vasoconstriction involving all three layers when compared to both the pregnant and nonpregnant states.

Translational Relevance: Detecting postpartum changes in retinal vasculature could offer important insights into postpartum physiology throughout the body.
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http://dx.doi.org/10.1167/tvst.10.2.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910633PMC
February 2021

Prevalence of Focal Inner, Middle, and Combined Retinal Thinning in Diabetic Patients and Its Relationship With Systemic and Ocular Parameters.

Transl Vis Sci Technol 2021 02;10(2):26

Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Purpose: To determine the prevalence of focal inner, middle, and combined inner/middle retinal thinning (FIRT, FMRT, and FCRT, respectively) in different stages of diabetic retinopathy (DR) without diabetic macular edema and to assess the relationship between such findings with ocular and systemic parameters.

Methods: This was a cross-sectional, comparative study comprising healthy participants and diabetic patients with different stages of DR. Forty-nine horizontal macular B-scans from the selected eye were obtained using spectral-domain optical coherence tomography (SD-OCT) and analyzed for the presence of FIRT, FMRT, or FCRT and any relationship with systemic and ocular parameters. Focal retinal thinning (FRT) was subjectively defined as any evidence of inner and/or middle retinal thinning.

Results: A total of 190 participants (52 healthy participants and 138 diabetic patients) were included. A higher prevalence of FRT was observed in eyes with advanced DR versus healthy eyes and versus diabetic eyes with no DR or mild DR. FIRT and FCRT were significantly greater in eyes with proliferative DR treated with pan-retinal photocoagulation, and FMRT was significantly more common in eyes with severe nonproliferative DR. FRT was significantly more common in patients with coronary artery disease and was positively correlated with diabetes duration, serum creatinine, and glycosylated hemoglobin and negatively correlated with age, estimated glomerular filtration rate, and visual acuity.

Conclusions: FRT occurs in all stages of DR and is increasingly prevalent with increasing severity of DR.

Translational Relevance: OCT identification of FRT may provide a surrogate biomarker of retinal and systemic disease in diabetic patients.
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http://dx.doi.org/10.1167/tvst.10.2.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900871PMC
February 2021

The Progression of Stargardt Disease Using Volumetric Hill of Vision Analyses Over 24 Months: ProgStar Report No.15.

Am J Ophthalmol 2021 May 2;230:123-133. Epub 2021 May 2.

Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; Departments of Ophthalmology, University of Basel, Basel, Switzerland. Electronic address:

Purpose: To report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical trials investigating the efficacy on retinal sensitivity.

Methods: Design: International, multicenter, prospective cohort study with 5 study visits every 6 months over 24 months.

Participants: A total of 233 individuals with genetically confirmed STGD1 (≥1 disease-causing ABCA4 variant).

Main Outcome Measures: The total volume (V) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of V over time and its correlation with the ABCA4 genotype and baseline features.

Results: At baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average V of 0.91 decibel-steradian (dB-sr) and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity [95% confidence interval] was 0.077 [0.064, 0.090] dB-sr/y for V and 0.87 [0.72, 1.02] dB/year for MS. The progression rate of V depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline V; P < .001) and exhibited a difference in the first vs second year of follow-up (0.065 dB-sr/year vs 0.089 dB-sr/year, respectively; P < .001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (P < .001), whereas a significant association with the genotype was not detected (P = .7).

Conclusion: In STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.
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http://dx.doi.org/10.1016/j.ajo.2021.04.015DOI Listing
May 2021

Comparison between Widefield Optical Coherence Tomography Devices in Eyes with High Myopia.

Diagnostics (Basel) 2021 Apr 6;11(4). Epub 2021 Apr 6.

Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco", Sacco Hospital, University of Milan, via G.B Grassi 74, 20157 Milan, Italy.

Background: To compare four different optical coherence tomography (OCT) devices for visualization of retinal and subretinal layers in highly myopic eyes.

Methods: In this prospective, observational, cross-sectional study, consecutive patients with high myopia and control subjects were imaged by four OCT devices: Spectralis OCT2, PlexElite 2.0 100 kHz, PlexElite 2.0 200 kHz and the Canon Xephilio OCT-S1. The acquisition protocol for comparison consisted of single vertical and horizontal line scans centered on the fovea. Comparison between the devices in the extent of visible retina, presence of conjugate image or mirror artifacts, visibility of the sclerochoroidal interface and retrobulbar tissue.

Results: 30 eyes with high myopia and 30 control subjects were analyzed. The visualized RPE length was significantly different between the OCT devices with Xephilio OCT-S1 imaging the largest extent ( < 0.0001). The proportion of eyes with conjugate image artifact was significantly higher with the Spectralis OCT ( < 0.0001), and lower with the PlexElite 200 kHz ( < 0.0001). No difference in visibility of the sclerochoroidal interface was noted among instruments. The retrobulbar tissue was visible in a higher proportion of eyes using swept-source PlexElite 100 kHz and 200 kHz ( < 0.007) compared to the other devices.

Conclusions: In highly myopic eyes, the four OCT devices demonstrated significant differences in the extent of the retina imaged, in the prevalence of conjugate image artifact, and in the visualization of the retrobulbar tissue.
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http://dx.doi.org/10.3390/diagnostics11040658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067388PMC
April 2021

Topography of choriocapillaris flow deficit predicts development of neovascularization or atrophy in age-related macular degeneration.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 26. Epub 2021 Apr 26.

Doheny Eye Institute, University of California at Los Angeles, Los Angeles, CA, USA.

Purpose: To evaluate the relationship between choriocapillaris (CC), flow deficits (FD), and structural optical coherence tomography (OCT) biomarkers, and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy (cRORA) or macular neovascularization (MNV).

Methods: Consecutive patients with iAMD were sequentially reviewed to define three equal sized groups: progressed to MNV, progressed to cRORA, or remained stable over 12 months of follow-up. Odds ratios for progression to cRORA and MNV were estimated by logistic regression for intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDDs), high central drusen volume, fellow eye with late AMD, and peripheral and central CC FD.

Results: Thirty iAMD eyes from 30 patients were enrolled into each group. The CC FD was greater in the peripheral sectors of the macula of eyes which progressed to cRORA compared to the other two groups (P < 0.0001). The central CC FD was also significantly impaired in eyes that progressed to cRORA or MNV compared to eyes that did not progress (P = 0.001 and P = 0.02, respectively). CC FD in the peripheral macula was significantly and independently associated with the development of cRORA, while CC FD in the center was significantly and independently associated with the development of MNV.

Conclusions: While the CC is diffusely impaired throughout the macula in iAMD eyes that progress to cRORA, it is relatively spared in the more peripheral macula among eyes which progress to MNV. These differential findings may have implications for the pathophysiology of the different late-stage manifestations of AMD.
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http://dx.doi.org/10.1007/s00417-021-05167-3DOI Listing
April 2021

Postoperative Photoreceptor Integrity Following Pneumatic Retinopexy vs Pars Plana Vitrectomy for Retinal Detachment Repair: A Post Hoc Optical Coherence Tomography Analysis From the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial.

JAMA Ophthalmol 2021 Jun;139(6):620-627

Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, England.

Importance: Pneumatic retinopexy (PnR) is associated with superior visual acuity and reduced vertical metamorphopsia compared with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). It is important to determine postoperative photoreceptor integrity with both surgical techniques.

Objective: To compare photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months postoperatively.

Design, Setting, And Participants: Post hoc analysis of the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Primary RRDs with specific criteria were included. Data were analyzed between April and August 2020.

Intervention: Randomization to PnR vs PPV stratified by macular status.

Main Outcomes And Measures: Difference in proportion of patients with discontinuity of the ellipsoid zone (EZ) and external limiting membrane (ELM) between groups assessed independently by 2 masked graders at an external masked image reading center.

Results: A total of 150 participants completed the 12-month follow-up visit. A total of 145 patients (72 PPV and 73 PnR) had gradable spectral-domain optical coherence tomography at 12 months. Analysis of the central 3-mm (foveal) scans found that 24% (n = 17 of 72) vs 7% (n = 5 of 73) displayed EZ discontinuity (difference, 17%; odds ratio [OR], 4.204; 95% CI, 1.458-12.116; P = .005) and 20% (n = 14 of 71) vs 6% (n = 4 of 73) displayed ELM discontinuity (difference, 14%; OR, 4.237; 95% CI, 1.321-13.587; P = .01) in the PPV and PnR groups, respectively. Analysis of the 6-mm (foveal and nonfoveal) scans revealed that EZ and ELM discontinuity was greater in the PPV vs PnR groups (EZ, 32% [n = 23 of 72] vs 11% [n = 8 of 73]; difference, 21%; OR, 3.814; 95% CI, 1.573-9.249; P = .002; ELM, 32% [n = 23 of 71] vs 18% [n = 13 of 73]; difference, 14%; OR, 2.211; 95% CI, 1.015-4.819; P = .04).

Conclusions And Relevance: Discontinuity of the EZ and ELM was more common at 12 months postoperatively following PPV vs PnR for RRD repair. The findings of this post hoc analysis suggest that less discontinuity of the EZ and ELM may provide an anatomic basis for the previously reported superior functional outcomes with PnR, although the analysis does not prove a cause-and-effect relationship.

Trial Registration: ClinicalTrials.gov Identifier: NCT01639209.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209566PMC
June 2021

Non-ICGA treatment criteria for Suboptimal Anti-VEGF Response for Polypoidal Choroidal Vasculopathy: APOIS PCV Workgroup Report 2.

Ophthalmol Retina 2021 Apr 16. Epub 2021 Apr 16.

Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong Hong Kong Eye Hospital, Hong Kong.

Purpose: To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment.

Design: Clinical study evaluating diagnostic accuracy.

Participants: Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments.

Methods: In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN).

Main Outcome Measures: Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA.

Results: In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN.

Conclusions: In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.
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http://dx.doi.org/10.1016/j.oret.2021.04.002DOI Listing
April 2021

Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-β induced retinal pigmented epithelium degeneration.

Signal Transduct Target Ther 2021 Apr 14;6(1):149. Epub 2021 Apr 14.

Center for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, VA, USA.

Nonfibrillar amyloid-β oligomers (AβOs) are a major component of drusen, the sub-retinal pigmented epithelium (RPE) extracellular deposits characteristic of age-related macular degeneration (AMD), a common cause of global blindness. We report that AβOs induce RPE degeneration, a clinical hallmark of geographic atrophy (GA), a vision-threatening late stage of AMD that is currently untreatable. We demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7, an upstream mediator of NLRP3 inflammasome activation, is required for AβO-induced RPE degeneration. Two classes of small molecule inflammasome inhibitors-nucleoside reverse transcriptase inhibitors (NRTIs) and their antiretrovirally inert modified analog Kamuvudines-both inhibit AβOs-induced RPE degeneration. These findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.
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http://dx.doi.org/10.1038/s41392-021-00537-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044134PMC
April 2021

Ocular Imaging for Enhancing the Understanding, Assessment, and Management of Age-Related Macular Degeneration.

Adv Exp Med Biol 2021 ;1256:33-66

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA, USA.

Age-related macular degeneration (AMD) is a progressive neuro-retinal disease and the leading cause of central vision loss among elderly individuals in the developed countries. Modern ocular imaging technologies constitute an essential component of the evaluation of these patients and have contributed extensively to our understanding of the disease. A challenge with any review of ocular imaging technologies is the rapid pace of progress and evolution of these instruments. Nonetheless, for proper and optimal use of these technologies, it is essential for the user to understand the technical principles underlying the imaging modality and their role in assessing the disease in various settings. Indeed, AMD, like many other retinal diseases, benefits from a multimodal imaging approach to optimally characterize the disease. In this chapter, we will review the various imaging technologies currently used in the assessment and management of AMD.
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http://dx.doi.org/10.1007/978-3-030-66014-7_2DOI Listing
April 2021

Retinal vascular bed area on ultra-wide field fluorescein angiography indicates the severity of diabetic retinopathy.

Br J Ophthalmol 2021 Apr 7. Epub 2021 Apr 7.

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA, USA

Aims: To quantify retinal vascular bed area (RVBA) in square millimetres on stereographically projected ultra-wide field (UWF) fluorescein angiography (FA) in eyes with diabetic retinopathy (DR).

Methods: A prospective, observational study. Baseline Optos 200Tx UWF FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center to adjust for peripheral distortion. The early-phase FA frame was used to extract the retinal vasculature as a mask for calculating RVBA. The pixels of the retinal vasculature were automatically computed in square millimetres using manufacturer-provided software.

Results: Eighteen of 80 diabetic eyes were excluded because image quality and contrast were insufficient for automatic extraction of the retinal vasculature from the background fluorescence. The remaining 62 eyes were included in the final analysis. In comparison with age-matched and sex-matched normal controls, eyes with DR had a higher global RVBA for the entire retina (p<0.001), and RVBA correlated with DR severity (p<0.001), with a higher RVBA in eyes with proliferative DR (66.1±16.2 mm) than in those with non-proliferative DR (56.2±16.6 mm) or in normal controls (37.2±9.9 mm). This tendency was also present in the posterior retina and mid-periphery but absent in the far-periphery. RVBA did not correlate with retinal ischaemia (p>0.05).

Conclusions: Eyes with DR harboured a larger global RVBA for the entire retina than normal controls, and RVBA appeared to indicate DR severity. However, this biomarker was not observed to be a good indicator of retinal ischaemia.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317488DOI Listing
April 2021

Multimodal imaging in a case of best vitelliform macular dystrophy.

Eur J Ophthalmol 2021 Apr 7:11206721211008779. Epub 2021 Apr 7.

Doheny Eye Institute, Los Angeles, CA, USA.

We describe a case of Best Vitelliform Macular Dystrophy using the Mirante device by Nidek, a multi-modal confocal scanning laser ophthalmoscopy (SLO) system equipped with Retro Mode Illumination, a relatively new retinal imaging modality.
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http://dx.doi.org/10.1177/11206721211008779DOI Listing
April 2021

Clinical Update on Metamorphopsia: Epidemiology, Diagnosis and Imaging.

Curr Eye Res 2021 May 17:1-15. Epub 2021 May 17.

NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.

: To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function.: A literature search of electronic databases was performed: Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed.: It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.
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http://dx.doi.org/10.1080/02713683.2021.1912779DOI Listing
May 2021

Identification and Characterization of Epivascular Glia Using En Face Optical Coherence Tomography.

Am J Ophthalmol 2021 Mar 24;229:108-119. Epub 2021 Mar 24.

Division of Retinal Disorders and Ophthalmic Genetics, Stein Eye Institute, University of California Los Angeles, Los Angeles, California, USA; Department of Ophthalmology, Greater Los Angeles VA Healthcare Center, Los Angeles, California, USA. Electronic address:

Purpose: The purpose of this study was to describe the clinical features of epivascular glia (EVG) using en face optical coherence tomography (OCT).

Design: Retrospective cross-sectional study.

Methods: Single-institution en face OCT images were reviewed. Eyes displaying EVG were captured with manual internal limiting membrane (ILM) segmentation and analyzed with customized segmentation . A random age- and sex-matched control group was selected to determine relative epiretinal membrane (ERM) prevalence.

Results: Characteristic hyper-reflective ILM plaques with dendrite-like radiations were identified using en face OCT and displayed vascular predilection. A total of 161 eyes with EVG (the EVG group) and 2,315 eyes without EVG (control group) were identified from a total cohort of 1,298 patients (or 2,476 eyes). The prevalence of EVG was 161 of 2,476 eyes (6.5%) and 119 of 1,298 patients (9.2%) in the cohort. Mean age was 79.3 ± 10.7 years old in the EVG group and 55.9 ± 24.6 years old in the control group (P <.001). An advanced posterior vitreous detachment (PVD) stage was more common in the EVG group (grade 3: 41.7%; grade 4: 48.6%) than in the control group (grade 3: 18.5%; grade 4: 26.9%; P <.001). Contractile ERM was present in 71 of 161 eyes (44.1%) with EVG compared to 30 of 161 eyes (18.6%) in a random age- and sex-matched control cohort without EVG (P <.001).

Conclusions: EVG previously described with histopathology and scanning electron microscopy can be identified using en face OCT. In this study, these lesions were associated with older age, pseudophakia, and advanced PVD, supporting the role of Müller cell activation through ILM breaks triggered by PVD, a pathogenic mechanism proposed by previous studies.
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http://dx.doi.org/10.1016/j.ajo.2021.03.014DOI Listing
March 2021

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

Ophthalmol Retina 2021 Mar 23. Epub 2021 Mar 23.

GRADE Reading Center and Department of Ophthalmology, University of Bonn, Bonn, Germany; Utah Retinal Reading Center, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. Electronic address:

Purpose: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD).

Design: Interreader agreement study.

Participants: Twelve readers from 6 reading centers.

Methods: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy.

Main Outcome Measures: Interreader agreement based on Gwet's first-order agreement coefficient (AC) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features.

Results: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC = 0.63-0.87), except for RPE attenuation (AC = 0.46) and disruption (AC = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 μm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 μm or more for a more severe atrophic grade (AC = 0.68; P = 0.013).

Conclusions: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.
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http://dx.doi.org/10.1016/j.oret.2021.03.008DOI Listing
March 2021

Multimodal Imaging of Fundus Flecks and Macular Atrophy in Stargardt Disease.

Ophthalmology 2021 04;128(4):608

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California.

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http://dx.doi.org/10.1016/j.ophtha.2020.10.011DOI Listing
April 2021

Automated identification of clinical features from sparsely annotated 3-dimensional medical imaging.

NPJ Digit Med 2021 Mar 8;4(1):44. Epub 2021 Mar 8.

Department of Computer Science, University of California, Los Angeles, CA, USA.

One of the core challenges in applying machine learning and artificial intelligence to medicine is the limited availability of annotated medical data. Unlike in other applications of machine learning, where an abundance of labeled data is available, the labeling and annotation of medical data and images require a major effort of manual work by expert clinicians who do not have the time to annotate manually. In this work, we propose a new deep learning technique (SLIVER-net), to predict clinical features from 3-dimensional volumes using a limited number of manually annotated examples. SLIVER-net is based on transfer learning, where we borrow information about the structure and parameters of the network from publicly available large datasets. Since public volume data are scarce, we use 2D images and account for the 3-dimensional structure using a novel deep learning method which tiles the volume scans, and then adds layers that leverage the 3D structure. In order to illustrate its utility, we apply SLIVER-net to predict risk factors for progression of age-related macular degeneration (AMD), a leading cause of blindness, from optical coherence tomography (OCT) volumes acquired from multiple sites. SLIVER-net successfully predicts these factors despite being trained with a relatively small number of annotated volumes (hundreds) and only dozens of positive training examples. Our empirical evaluation demonstrates that SLIVER-net significantly outperforms standard state-of-the-art deep learning techniques used for medical volumes, and its performance is generalizable as it was validated on an external testing set. In a direct comparison with a clinician panel, we find that SLIVER-net also outperforms junior specialists, and identifies AMD progression risk factors similarly to expert retina specialists.
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http://dx.doi.org/10.1038/s41746-021-00411-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940637PMC
March 2021

Optical Coherence Tomography Angiography of the Choriocapillaris in Age-Related Macular Degeneration.

J Clin Med 2021 Feb 13;10(4). Epub 2021 Feb 13.

Department of Ophthalmology, Stein Eye Institute, University of California, Los Angeles, CA 90095, USA.

The advent of optical coherence tomography angiography (OCTA) has allowed for remarkable advancements in our understanding of the role of the choriocapillaris in age-related macular degeneration (AMD). As a relatively new imaging modality, techniques to analyze and quantify choriocapillaris images are still evolving. Quantification of the choriocapillaris requires careful consideration of many factors, including the type of OCTA device, segmentation of the choriocapillaris slab, image processing techniques, and thresholding method. OCTA imaging shows that the choriocapillaris is impaired in intermediate non-neovascular AMD, and the severity of impairment may predict the advancement of disease. In advanced atrophic AMD, the choriocapillaris is severely impaired underneath the area of geographic atrophy, and the level of impairment surrounding the lesion predicts the rate of atrophy enlargement. Macular neovascularization can be readily identified and classified using OCTA, but it is still unclear if neovascularization features with OCTA can predict the lesion's level of activity. The choriocapillaris surrounding macular neovascularization is impaired while the more peripheral choriocapillaris is spared, implying that choriocapillaris disruption may drive neovascularization growth. With continued innovation in OCTA image acquisition and analysis methods, advancement in clinical applications and pathophysiologic discoveries in AMD are set to follow.
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http://dx.doi.org/10.3390/jcm10040751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918036PMC
February 2021

Comparison of Spectralis and Cirrus optical coherence tomography for the detection of incomplete and complete retinal pigment epithelium and outer retinal atrophy.

Retina 2021 Feb 24. Epub 2021 Feb 24.

Doheny Eye Institute, University of California at Los Angeles, Los Angeles, California, USA. Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States. Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco", Sacco Hospital, University of Milan, Milan, Italy. Institute for Computational Biology and Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States. Department of Ophthalmology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States.

Purpose: To evaluate and compare the detection of incomplete and complete retinal pigment epithelial and outer retinal atrophy (iRORA and cRORA) using Spectralis and Cirrus optical coherence tomography (OCT) devices.

Methods: Subjects with late age-related macular degeneration (AMD) were imaged on the same day with Spectralis and Cirrus OCT. Two masked, independent and experienced retina specialist graders evaluated each case for the presence of cRORA and iRORA lesions.

Results: A significantly higher number of lesions were observed using Spectralis compared with Cirrus (239 vs 226 and 223 vs 209). Higher number of iRORA lesions were identified with Spectralis (105 vs 90 and 96 vs 82) and no significant difference was observed between devices for cRORA lesions (134 vs 136 and 128 vs 126). When considering the presence or absence of iRORA or cRORA, the agreement between devices for both graders was excellent for cRORA and good for iRORA.

Conclusions: Spectralis and Cirrus OCT identified a similar number of cRORA lesions, though more iRORA lesions could be detected with Spectralis OCT. These findings may have implications for developing acquisition protocols for trials based on the intended atrophy targets and highlight the importance of using a consistent OCT instrument across a study.
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http://dx.doi.org/10.1097/IAE.0000000000003158DOI Listing
February 2021

Multimodal imaging of a choroidal nevus with caverns in the setting of pachychoroid disease.

Retin Cases Brief Rep 2021 Feb 26. Epub 2021 Feb 26.

Doheny Eye Institute, Los Angeles, California, United States. Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States. Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco", Sacco Hospital, University of Milan, Milan, Italy. Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA Vitreous Retina Macula Consultants of New York, New York, New York. Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY USA.

Purpose: To describe the multimodal imaging findings of extensive choroidal caverns within a choroidal nevus in an eye with pachychoroid spectrum disease.

Methods: A 69 year-old woman was referred with a known history of branch retinal vein occlusion (BRVO) in the right eye and choroidal nevus in the left eye. Fundus examination of both eyes (OU) revealed subretinal yellow deposits, suggestive of pachydrusen. Retinal venous collaterals were noted in the temporal macular of the right eye. A lightly pigmented choroidal lesion with nearly confluent overlying drusen and retinal pigment epithelial (RPE) alterations, consistent with chronic choroidal nevus, was noted in the macula of the left eye.

Results: Optical coherence tomography B-scans revealed thickened choroid (pachychoroid) with subfoveal choroidal thickness of 504 and 580 µm with large hyporeflective spaces suggestive of pachyvessels OU. In the region of the choroidal nevus, the choroidal vascular spaces appeared comparatively large and were classified as "caverns", measuring up to 480 µm in diameter. OCT angiography (OCTA) and indocyanine green angiography (ICGA) demonstrated absence of flow within the caverns. ICGA further illustrated choroidal vascular hyperpermeability with patchy hyperfluorescent areas OU. Widefield swept source OCT showed mild posterior scleral bowing, a feature occasionally documented with choroidal nevus, and highlighted greater hyporeflectivity and hypertransmission on OCT within the caverns compared to the non-cavernous choroidal vessels.

Conclusion: Choroidal caverns can occur within choroidal nevus in the setting of pachychoroid disease.
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http://dx.doi.org/10.1097/ICB.0000000000001138DOI Listing
February 2021

The effect of intravitreal recombinant tissue plasminogen activator injection on diabetic tractional fibrovascular membranes: Proposed criteria using optical coherence tomography.

Eur J Ophthalmol 2021 Mar 2:1120672121998224. Epub 2021 Mar 2.

Stein Eye Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.

Purpose: To evaluate the effect of intravitreal recombinant tissue plasminogen activator (tPA) on diabetic tractional fibrovascular membranes (FVM) using proposed optical coherence tomography (OCT) criteria.

Methods: This prospective, interventional case series enrolled eyes with tractional retinal detachment who were candidates for pars plana vitrectomy. OCT images were obtained to evaluate the border of the attached-detached retina and overlying FVP at baseline and 1 week post-intravitreal tPA injection using the follow-up scan acquisition protocol. Two independent graders assessed retinal detachment (RD) height, FVM height, and retinal thickness at the site of membrane attachment.

Results: Thirteen eyes from 13 individuals were included. Assessment of RD height, FVM height, and retinal thickness at membrane attachment point were feasible at both visits in 10/13 (77%), 10/13 (77%), and 8/13 (62%) of eyes, respectively. There was excellent agreement between the two graders for all measurements (all ICC > 0.94). Release of the retina-membrane attachment point was not observed in any eyes. No statistically significant change was found in any of the measured parameters.

Conclusions: Excellent agreement was achieved between the graders for quantitative assessment of diabetic FVM using our proposed OCT criteria. We did not observe a significant change in the FVM measurements, 1-week after intravitreal tPA injection.
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http://dx.doi.org/10.1177/1120672121998224DOI Listing
March 2021
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