Publications by authors named "Andre J Witkin"

89 Publications

Occlusive Retinal Vasculitis Following Intravitreal Drug Delivery.

Ocul Immunol Inflamm 2021 Apr 13:1-4. Epub 2021 Apr 13.

Centre for Ophthalmology, University Tuebingen, Tuebingen, Germany.

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http://dx.doi.org/10.1080/09273948.2021.1882243DOI Listing
April 2021

Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration.

JAMA Ophthalmol 2021 Feb 25. Epub 2021 Feb 25.

Retina-Vitreous Associates of Florida, Tampa.

Importance: Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD).

Objective: To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD.

Design, Setting, And Participants: This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020.

Exposures: Treatment with brolucizumab IVI, 6 mg.

Main Outcomes And Measures: Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety.

Results: A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) μm and was 269.8 (66.5) μm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision.

Conclusions And Relevance: In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.7085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907988PMC
February 2021

Retinal Imaging Using a Confocal Scanning Laser Ophthalmoscope-Based High-Magnification Module.

Ophthalmol Retina 2020 Aug 28. Epub 2020 Aug 28.

New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts. Electronic address:

Purpose: To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions.

Design: Observational descriptive study.

Participants: Thirty-two participants with normal and pathologic retina examination results.

Methods: Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae.

Main Outcomes Measures: Description of HMM module-obtained macula images.

Results: From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane.

Conclusions: In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.
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http://dx.doi.org/10.1016/j.oret.2020.08.014DOI Listing
August 2020

The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration.

Int J Retina Vitreous 2020 20;6:39. Epub 2020 Aug 20.

New England Eye Center, Tufts Medical Center, Boston, MA USA.

Background: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA).

Methods: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated.

Results: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate.

Conclusions: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.
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http://dx.doi.org/10.1186/s40942-020-00242-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441632PMC
August 2020

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab.

J Vitreoretin Dis 2020 Jul 1;4(4):269-279. Epub 2020 Jul 1.

Austin Retina Associates, Austin, TX, USA.

Purpose: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration.

Methods: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab.

Results: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied.

Conclusions: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown.
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http://dx.doi.org/10.1177/2474126420930863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418897PMC
July 2020

Akreos AO60 Intraocular Lens Opacification after Retinal Detachment Repair.

Ophthalmol Retina 2020 08 11;4(8):854-856. Epub 2020 Apr 11.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2020.03.030DOI Listing
August 2020

Analyzing Relative Flow Speeds in Diabetic Retinopathy Using Variable Interscan Time Analysis OCT Angiography.

Ophthalmol Retina 2021 Jan 22;5(1):49-59. Epub 2020 Jun 22.

New England Eye Center, Tufts Medical Center, Boston, Massachusetts. Electronic address:

Purpose: Further insight into the flow characteristics of the vascular features associated with diabetic retinopathy (DR) may improve assessment and treatment of disease progression. The variable interscan time analysis (VISTA) algorithm is an extension of OCT angiography (OCTA) that detects relative blood flow speeds, which then can be depicted on a color-coded map. This study used VISTA to analyze relative blood flow speeds in the microvascular changes associated with DR.

Design: Cross-sectional study.

Participants: Thirteen patients with varying severities of DR treated at New England Eye Center, Boston, Massachusetts.

Methods: OCT angiography images centered at the fovea were obtained on a prototype swept-source OCT device, and the VISTA algorithm was applied to visualize relative blood flow speeds.

Main Outcome Measures: Descriptive flow analysis of the retinal vascular features of DR was conducted on the VISTA-generated images.

Results: Twenty-six eyes were included in this study. Of these, 3 eyes had mild nonproliferative DR (NPDR), 6 eyes had moderate NPDR, 4 eyes had severe NPDR, 9 eyes had proliferative DR, and 4 eyes were normal controls. Microaneurysms, intraretinal microvascular abnormalities (IRMAs), and neovascularization appeared to originate from areas of relatively slow blood flow speeds. Microaneurysms showed relatively slower flow, IRMAs showed turbulent, intermediate to slow flow, and venous beading and looping presented with relatively high flow speeds that tapered progressively. Neovascularization of venous origin demonstrated slower flow speeds, whereas that of arterial origin showed relatively high flow speeds. Additionally, increased disease severity was associated with globally slower flow speeds, with particularly slower flow around the foveal avascular zone.

Conclusions: The VISTA algorithm seems to be a useful extension of OCTA that overcomes some of the limitations of normal gray-scale OCTA. It seems to have some potential in providing relevant insight into the pathogenesis of the microvascular changes associated with DR. These findings may assist in improving our understanding of the pathogenic changes that take place in DR.
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http://dx.doi.org/10.1016/j.oret.2020.06.024DOI Listing
January 2021

Bilateral epiretinal membrane formation following intravitreal injections of autologous mesenchymal stem cells.

Retin Cases Brief Rep 2020 Jun 17. Epub 2020 Jun 17.

Tufts Medical Center, Department of Ophthalmology, Boston, MA.

Purpose: The authors describe a case of new bilateral epiretinal membranes and vitreous cells following intravitreal and subTenon's injections of bone marrow-derived stem cells.

Methods: Case report of a 43-year-old man with OPA-1 autosomal dominant optic atrophy who self-enrolled in a stem cell therapy clinical trial and received simultaneous bilateral intravitreal and subTenon's injections of bone marrow-derived stem cells.

Results: Within one month of receiving the injections, the patient developed epiretinal membranes and vitreous cells in both eyes, seen with optical coherence tomography.

Conclusion: Stem cell therapy has been gaining popularity as a potential intervention for progressive retinal and optic nerve diseases; however, the mechanism of action of bone marrow-derived stem cells is still not well understood and may result in unintended cell differentiation.
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http://dx.doi.org/10.1097/ICB.0000000000001032DOI Listing
June 2020

Visual and anatomic outcomes of sustained single agent anti-VEGF treatment versus double anti-VEGF switching in the treatment of persistent diabetic macular edema.

Int J Retina Vitreous 2020 8;6:17. Epub 2020 Jun 8.

New England Eye Center, Tufts Medical Center, Tufts University, Boston, MA USA.

Background: To compare the anatomical and visual outcomes in eyes with persistent diabetic macular edema (DME) after initial anti-VEGF therapy that were retreated continuously with the same anti-VEGF drug versus those that underwent two successive cycles of medication change in anti-VEGF drugs (double anti-VEGF switch).

Methods: Retrospective review of eyes with persistent DME after 3 initial consecutive monthly anti-VEGF injections. This cohort was divided into two groups: Group 1 continued to receive the same initial anti-VEGF drug for at least 18 months while group 2 eyes were switched to different anti-VEGF medications twice. Group 1 was further subdivided into: Group 1A composed of eyes with less than 20% reduction in central subfield thickness (CRT) at month 3; and group 1B eyes with greater than or equal to 20% reduction in CRT. The percentage of eyes that achieved greater than 10 letters visual acuity (VA) gain or loss was recorded as the primary end point (through month 18 in group 1 and month 6 after 2nd switch in group 2).

Results: Group 1A, 1B and group 2 were composed of 24, 18, and 14 eyes respectively. 34.7%, 56.2% and 36.3% of eyes achieved > 10 letters gain, while 4.3%, 6.2% and 27.2% of eyes lost > 10 letters in groups 1A, 1B, and 2, respectively. Analysis of the visual acuity (VA) letter change in this time interval revealed no significant difference between all groups (p = 0.11). Mean VA and CRT measurements at the primary endpoint in all groups were 0.5, 0.39, and 0.47 logMAR (p = 0.44), and 369.7, 279.9, 321 µm, (p = 0.01) respectively.

Conclusions: There was no difference in the visual outcomes between the two treatment strategies in eyes with persistent DME after 3 consecutive anti-VEGF injections. This may indicate that anti-VEGF switching-even if it is done twice-may have comparable clinical outcomes to sustained treatment with one agent.
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http://dx.doi.org/10.1186/s40942-020-00220-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278067PMC
June 2020

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography.

Eye Vis (Lond) 2020 1;7:29. Epub 2020 Jun 1.

Department of Ophthalmology, New England Eye Center, Tufts Medical Center, 800 Washington Street, Box 450, Boston, MA 02111 USA.

Background: To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities (IRMAs) in response to anti-vascular endothelial growth factor (anti-VEGF) treatment, documented by optical coherence tomography angiography (OCTA) in diabetic eyes.

Methods: In this retrospective study, IRMAs were evaluated with multimodal imaging (fundus photography, fluorescein angiography, OCTA) in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR) and compared to diabetic control eyes with similar diabetic retinopathy (DR) severity that did not receive anti-VEGF therapy. The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline, then after anti-VEGF therapy in treated eyes or after observation in control eyes. Characterization of interval changes in an IRMA were based on the following parameters: branching, vessel caliber and area of adjacent capillary non-perfusion.

Results: The treated group included 45 IRMA foci from 15 eyes of 11 patients, while the control group included 27 IRMA foci from 15 eyes of 14 patients. Following anti-VEGF treatment, enface OCTA demonstrated that 14 foci of IRMA (31%) demonstrated regression with normalization of appearance of the capillary bed, 20 IRMAs (44%) remained unchanged, six IRMAs (13%) progressed with enlargement or development of new IRMAs and five IRMAs (11%) demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out. In the control group, 17 IRMA (63%) remained stable, 8 IRMAs (29.6%) progressed and 2 experienced total obliteration (7.4%). The difference in rank order between the two groups was statistically significant ( = 0.022).

Conclusions: In eyes with DR status post anti-VEGF therapy, foci of IRMAs have a variable course demonstrating one of four possible outcomes: regression, stability, progression or complete obliteration. In contrast, none of the untreated control diabetic eyes demonstrated regression of IRMAs, consistent with known progression of DR severity in high risk eyes. Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.
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http://dx.doi.org/10.1186/s40662-020-00195-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262762PMC
June 2020

Repeatability and Reproducibility of Photoreceptor Density Measurement in the Macula Using the Spectralis High Magnification Module.

Ophthalmol Retina 2020 11 1;4(11):1083-1092. Epub 2020 May 1.

New England Eye Center, Tufts Medical Center, Boston, Massachusetts. Electronic address:

Purpose: To evaluate the repeatability and reproducibility of photoreceptor density assessment with manual cell counting in healthy participants imaged with the Heidelberg Spectralis High Magnification Module (HMM).

Design: Precision study, evaluation of diagnostic test or technology.

Participants: Eleven eyes of 8 participants.

Methods: Images were acquired using the Spectralis HMM by a single operator during 2 separate imaging sessions. The 3 highest-quality images of each eye from each session were selected for analysis and coregistered. For a subset of participants, a second operator acquired images in 1 session, and images with the best quality were selected for analysis. Photoreceptor densities were obtained by manual counts in squares of 0.0625 mm located in the parafovea. Repeatability (intragrader and intrasession) and reproducibility (interoperator, intergrader, and intersession) were assessed by calculating the intraclass correlation coefficient (ICC) from linear mixed effects models. Bland-Altman plots, coefficients of repeatability, and Pearson correlation results were reported.

Main Outcome Measures: Intragrader, intrasession, intersession, interoperator, and intergrader ICC estimates and their 95% confidence intervals for photoreceptor density measurements in the parafovea.

Results: Twenty-four eyes of 13 healthy participants were imaged initially. Of these, 11 eyes (45.83%) of 8 participants that had at least 3 acceptable images in each session were included in this study. Mean parafoveal photoreceptor density was 14 988 cells/mm (standard deviation, 1403.15 cells/mm). Intragrader ICC was 0.84 (95% confidence interval, 0.57-0.95), intrasession ICC was 0.69 (95% confidence interval, 0.17-0.86), intersession ICC was 0.88 (95% confidence interval, 0.53-0.96), interoperator ICC was 0.70 (95% confidence interval, 0-0.95), and intergrader ICC was 0.22 (95% confidence interval, 0-0.71).

Conclusions: Images obtained with the HMM allow for photoreceptor mosaic visualization in the macular area, mainly in the parafovea. Although densities obtained are in accordance with other reported methods in the literature, variability within and between images of the apparent cell mosaic were observed, and this study did not demonstrate high repeatability or reproducibility for quantitative assessments using the manual counting method.
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http://dx.doi.org/10.1016/j.oret.2020.04.021DOI Listing
November 2020

Repeatability and reproducibility of vessel density measurements on optical coherence tomography angiography in diabetic retinopathy.

Graefes Arch Clin Exp Ophthalmol 2020 Aug 4;258(8):1687-1695. Epub 2020 May 4.

New England Eye Center, Tufts Medical Center, Boston, MA, USA.

Purpose: Understanding the precision of measurements on and across optical coherence tomography angiography (OCTA) devices is critical for tracking meaningful change in disease. The purpose of this study is to investigate the repeatability and reproducibility of vessel area density and vessel skeleton density measurements from various commercial OCTA devices in diabetic eyes.

Methods: Patients were imaged three consecutive times each on three different OCTA devices. En face OCTA images of the superficial capillary plexus, deep capillary plexus, and full retinal layer were exported for analysis. Vessel area density and vessel skeleton density were calculated. The coefficient of repeatability (CoR) was calculated to assess the repeatability of these measurements, and linear mixed models were utilized to assess the reproducibility of these measurements.

Results: Forty-four eyes from 27 diabetic patients were imaged. Normalized CoR values ranged between 3.44 and 6.65% when calculated for vessel area density and between 1.35 and 23.39% when calculated for vessel skeleton density. When stratified by disease severity, the swept-source OCTA device consistently produced the smallest CoR values for vessel area density in the full retinal layer. Vessel area density measurements were repeatable across the two spectral-domain devices in the full retinal layer when all severities were combined, as well as in diabetic patients without retinopathy, mild nonproliferative diabetic retinopathy (NPDR), and moderate NPDR.

Conclusion: Vessel area density measured in the full retinal layer may be a more precise measure than vessel skeleton density to follow diabetic retinopathy patients both on the same device and across devices.
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http://dx.doi.org/10.1007/s00417-020-04716-6DOI Listing
August 2020

Topographic analysis of macular choriocapillaris flow deficits in diabetic retinopathy using swept-source optical coherence tomography angiography.

Int J Retina Vitreous 2020 19;6. Epub 2020 Mar 19.

1New England Eye Center, Tufts Medical Center, 260 Tremont St, Boston, MA 02116 USA.

Background: The purpose of this study was to investigate the association between diabetic retinopathy (DR) severity and macular choriocapillaris (CC) flow deficit percentage (FD %) in different macular regions using swept-source optical coherence tomography angiography (SS-OCTA).

Methods: Diabetic patients with SS-OCTA images were graded by severity and retrospectively assessed. CC FD % was calculated in four different regions of the OCTA image: inner, middle, outer, and full-field region. The generalized estimating equations (GEE) approach for clustered eye data was used to determine effect size and significance of age and disease severity on FD % for each region.

Results: 160 eyes from 90 total diabetic patients met inclusion criteria. Out of 90 patients, 33 had no DR, 17 had mild nonproliferative DR (NPDR), 8 had moderate NPDR, 10 had severe NPDR and 22 had proliferative DR. Age and DR severity had a significant positive association with FD % for each region studied with a greater effect in the two centermost regions. The increase in flow deficit percentage per year of age by region was: inner 0.12 (p < 0.001), middle 0.09 (p < 0.001), outer 0.05 (p < 0.001, full-field 0.06 (p < 0.001). The increase in flow deficit percentage per increase in diabetic retinopathy severity stage by region was: inner 0.65 (p < 0.0087), middle 0.56 (p < 0.0012), outer 0.33 (p < 0.045), full-field 0.36 (p < 0.018).

Conclusions: Topographic analysis of the CC FD % in diabetic eyes suggests that CC flow impairment corresponds to DR severity, with all studied regions of the CC significantly affected. There was greater regional impairment due to age and disease severity in the inner and middle regions.
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http://dx.doi.org/10.1186/s40942-020-00209-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081691PMC
March 2020

Effects of enhanced depth imaging and en face averaging on optical coherence tomography angiography image quantification.

Graefes Arch Clin Exp Ophthalmol 2020 May 4;258(5):979-986. Epub 2020 Feb 4.

New England Eye Center, Tufts Medical Center, Boston, MA, USA.

Purpose: To examine the effects of enhanced depth imaging (EDI) and en face averaging on global vascular measurements of optical coherence tomography angiography (OCTA) images.

Methods: All eyes were imaged with 3 mm × 3 mm fields centered at the fovea using the Carl Zeiss Cirrus 5000 spectral-domain OCTA, with and without EDI, and the Zeiss PLEX Elite 9000 swept-source OCTA. Vessel area density (VAD), vessel length (VL), and vessel diameter index (VDI) were calculated for the superficial capillary plexus (SCP) en face angiograms. For the choriocapillaris (CC), VAD and the number, total area, and average size of flow voids were calculated. These metrics were compared between SD- and SS-OCTA images, with and without en face averaging and EDI.

Results: Both averaging and EDI had a significant effect on quantitative metrics. EDI images trended toward a decrease in SCP VAD. In the CC, EDI decreased average flow void size. Averaging increased CC VAD while decreasing number of flow voids, total flow void area, and average flow void size. With both averaging and EDI, SD-OCTA was not able to visualize as many CC flow voids, particularly of a smaller size, compared with SS-OCTA.

Conclusions: Averaging and EDI affect quantitative metrics from SCP and CC OCTA images. EDI resulted in a trend toward decreased VAD in SCP images. Averaging had a major effect on CC imaging. Even with the combination of EDI and en face averaging, SD-OCTA images do not appear to approximate SS-OCTA images in terms of quantitative metrics. This has implications for clinical and research use of SD-OCTA for retinal imaging.
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http://dx.doi.org/10.1007/s00417-020-04610-1DOI Listing
May 2020

Global Analysis of Macular Choriocapillaris Perfusion in Dry Age-Related Macular Degeneration using Swept-Source Optical Coherence Tomography Angiography.

Invest Ophthalmol Vis Sci 2019 12;60(15):4985-4990

New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States.

Purpose: Swept-source optical coherence tomography angiography (SS-OCTA) was used to investigate if the clinical stage of dry age-related macular degeneration (AMD) was correlated with global and regional macular choriocapillaris (CC) perfusion.

Methods: In this retrospective, cross-sectional study, 6 × 6-mm SS-OCTA images from eyes with early, intermediate, and advanced dry AMD (56 eyes, 41 patients) were analyzed using algorithms described in the literature to assess regional flow deficit percentage (FD%) and average flow deficit size. Regions were defined by concentric areas centered on the fovea: a 1-mm-diameter area, 3-mm-diameter ring, 5-mm-diameter area, 5-mm-diameter ring, and 6 × 6-mm whole image. Data were modeled using the generalized estimating equations approach.

Results: The relationship between age and CC FD% and average flow deficit size was statistically significant (P ≤ 0.05) in all regions of analysis by linear modeling. The relationship between dry AMD stage and FD% was statistically significant by linear modeling in the 5-mm ring, and between dry AMD stage and average flow deficit size in the 3-mm ring, 5-mm area, 5-mm ring, and 6 × 6-mm whole image.

Conclusions: Linear modeling suggests a statistically significant relationship between dry AMD stage and CC perfusion, most prominent in the more peripheral regions of the macula.
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http://dx.doi.org/10.1167/iovs.19-27861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890395PMC
December 2019

Retinal Nonperfusion Relationship to Arteries or Veins Observed on Widefield Optical Coherence Tomography Angiography in Diabetic Retinopathy.

Invest Ophthalmol Vis Sci 2019 10;60(13):4310-4318

New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States.

Purpose: To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR).

Methods: Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 × 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified.

Results: Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r = -0.600, P < 0.0001). The results from the widefield montages showed similar patterns.

Conclusions: OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.
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http://dx.doi.org/10.1167/iovs.19-26653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996665PMC
October 2019

Short-term eplerenone for treatment of chronic central serous chorioretinopathy; a prospective study.

Int J Retina Vitreous 2019 9;5:39. Epub 2019 Sep 9.

1New England Eye Center, Tufts Medical Center, 800 Washington Street, Box 450, Boston, MA 02111 USA.

Background: Increased mineralocorticoid activity is one of the plausible causes of chronic central serous chorioretinopathy (CSCR) and mineralocorticoid inhibitors such as eplerenone have been investigated as its potential therapy. This study investigates the short-term safety and efficacy of oral eplerenone in patients with chronic CSCR.

Patients And Methods: Prospective study of 13 eyes of 13 patients with the diagnosis of chronic CSCR. All patients received eplerenone 50 mg/day for 4 weeks. Enhanced depth imaging optical coherence tomography (OCT) was obtained. Best corrected visual acuity (BCVA), and OCT parameters including sub retinal fluid (SRF), choroidal thickness (CT) and central macular thickness (CMT), were measured manually.

Results: The mean SRF height decreased slightly at 1-month follow-up as compared to baseline, but the change was not statistically significant (94.18 ± 17.53 vs. 113.15 ± 18.69; p = 0.08). Subfoveal CT and CMT was significantly reduced as compared to baseline (6.6% [p = 0.002] and 7.05% [p = 0.04], respectively). The BCVA did not change significantly (20/28 vs. 20/30 [p = 0.16]).

Conclusion: This study suggests that oral eplerenone may be used as a safe and potentially effective treatment in chronic CSCR, however there are minimal short-term effects on subretinal fluid or visual acuity therefore therapeutic trials longer than one month are necessary to test its benefits. Clinicaltrials.gov identification number: NCT01822561. Registered 3/25/13, https://clinicaltrials.gov/ct2/show/study/NCT01822561.
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http://dx.doi.org/10.1186/s40942-019-0190-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734298PMC
September 2019

SPATIAL DISTRIBUTION OF CHORIOCAPILLARIS IMPAIRMENT IN EYES WITH CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Quantitative OCT Angiography Study.

Retina 2020 Mar;40(3):428-445

Department of Electrical Engineering and Computer Science, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts.

Purpose: To develop an optical coherence tomography angiography (OCTA)-based framework for quantitatively analyzing the spatial distribution of choriocapillaris (CC) impairment around choroidal neovascularization (CNV) secondary to age-related macular degeneration.

Methods: In a retrospective, cross-sectional study, 400-kHz swept-source OCTA images from 7 eyes of 6 patients with CNV secondary to age-related macular degeneration were quantitatively analyzed using custom software. A lesion-centered zonal OCTA analysis technique-which portioned the field-of-view into zones relative to CNV boundaries-was developed to quantify the spatial dependence of CC flow deficits.

Results: Quantitative, lesion-centered zonal analysis of CC OCTA images revealed highest flow-deficit percentages near CNV boundaries, decreasing in zones farther from the boundaries. Optical coherence tomography angiography using shorter (1.5 ms) interscan times revealed more severe flow deficits than OCTA using longer (3.0 ms) interscan times; however, spatial trends were similar for both interscan times. A detailed description of the OCTA processing steps and parameters was provided so as to elucidate their influence on quantitative measurements.

Conclusion: Impairment of the CC, assessed by flow-deficit percentages, was most prominent closest to CNV boundaries. The lesion-centered zonal analysis technique enabled quantitative CC measurements relative to focal lesions. Understanding how processing steps, imaging/processing parameters, and artifacts can affect quantitative CC measurements is important for longitudinal, OCTA-based studies of disease progression, and treatment response.
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http://dx.doi.org/10.1097/IAE.0000000000002556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015807PMC
March 2020

Potentially Novel Acute Retinopathy Similar to Multiple Evanescent White Dot Syndrome in Patients With Pseudoxanthoma Elasticum.

Authors:
Andre J Witkin

JAMA Ophthalmol 2019 Aug 8. Epub 2019 Aug 8.

Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.2884DOI Listing
August 2019

Controlling for Artifacts in Widefield Optical Coherence Tomography Angiography Measurements of Non-Perfusion Area.

Sci Rep 2019 06 24;9(1):9096. Epub 2019 Jun 24.

Department of Electrical Engineering and Computer Science, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

The recent clinical adoption of optical coherence tomography (OCT) angiography (OCTA) has enabled non-invasive, volumetric visualization of ocular vasculature at micron-scale resolutions. Initially limited to 3 mm × 3 mm and 6 mm × 6 mm fields-of-view (FOV), commercial OCTA systems now offer 12 mm × 12 mm, or larger, imaging fields. While larger FOVs promise a more complete visualization of retinal disease, they also introduce new challenges to the accurate and reliable interpretation of OCTA data. In particular, because of vignetting, wide-field imaging increases occurrence of low-OCT-signal artifacts, which leads to thresholding and/or segmentation artifacts, complicating OCTA analysis. This study presents theoretical and case-based descriptions of the causes and effects of low-OCT-signal artifacts. Through these descriptions, we demonstrate that OCTA data interpretation can be ambiguous if performed without consulting corresponding OCT data. Furthermore, using wide-field non-perfusion analysis in diabetic retinopathy as a model widefield OCTA usage-case, we show how qualitative and quantitative analysis can be confounded by low-OCT-signal artifacts. Based on these results, we suggest methods and best-practices for preventing and managing low-OCT-signal artifacts, thereby reducing errors in OCTA quantitative analysis of non-perfusion and improving reproducibility. These methods promise to be especially important for longitudinal studies detecting progression and response to therapy.
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http://dx.doi.org/10.1038/s41598-019-43958-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591294PMC
June 2019

Optical coherence tomography angiography analysis of macular vessel density before and after anti-VEGF therapy in eyes with diabetic retinopathy.

Int Ophthalmol 2019 Oct 22;39(10):2361-2371. Epub 2019 May 22.

New England Eye Center, Tufts Medical Center, Boston, MA, USA.

Purpose: To evaluate changes in macular vessel density following intravitreal anti-VEGF injection in patients with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR).

Methods: In this retrospective case series, optical coherence tomography angiography (OCTA) images from 55 eyes of 35 patients with either DME (46 eyes) or PDR (9 eyes) were included. Macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP) before and after anti-VEGF treatment was calculated. Longitudinal changes in vessel density following serial anti-VEGF treatment were analyzed in a subset of eyes.

Results: Vessel density in the SCP, DCP or TCP was not found to be significantly different after one, two or three intravitreal injections (p > 0.05 for all time points). Subgroup analysis revealed no significant change in the DME and PDR subgroups (all p > 0.05). Multivariate analysis revealed no effect of type of injected anti-VEGF agent or presence of previous treatment on VD measurements (all p > 0.05). There was no correlation between the anatomic response of DME to treatment and VD measurements.

Conclusions: In this study, macular vessel density remained statistically unchanged following up to three intravitreal injections of any anti-VEGF agent. This indicates that there may not be an early effect of anti-VEGF treatment on macular vessel density and its effect on macular perfusion may not be a direct change in microvascular flow.
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http://dx.doi.org/10.1007/s10792-019-01076-xDOI Listing
October 2019

Analyzing Relative Blood Flow Speeds in Choroidal Neovascularization Using Variable Interscan Time Analysis OCT Angiography.

Ophthalmol Retina 2018 04 31;2(4):306-319. Epub 2017 Oct 31.

New England Eye Center, Tufts Medical Center, Boston, Massachusetts. Electronic address:

Purpose: Longitudinally visualizing relative blood flow speeds within choroidal neovascularization (CNV) may provide valuable information regarding the evolution of CNV and the response to vascular endothelial growth factor (VEGF) inhibitors.

Design: Retrospective, longitudinal case series conducted at the New England Eye Center.

Participants: Patients with either treatment-naïve or previously treated CNV secondary to neovascular age-related macular degeneration.

Methods: Optical coherence tomography angiography (OCTA) was performed using a 400-kHz, 1050-nm swept-source OCT system with a 5-repeat B-scan protocol. Variable interscan time analysis (VISTA) was used to compute relative flow speeds from pairs of B-scans having 1.5- and 3.0-ms separations; VISTA signals then were mapped to a color space for display.

Main Outcome Measures: Quantitative outcomes included OCTA-based area and volume measurements of CNV at initial and follow-up visits. Qualitative outcomes included VISTA OCTA analysis of relative blood flow speeds, along with analysis of contraction, expansion, densification, and rarefication of CNV.

Results: Seven eyes of 6 patients (4 women and 2 men) with neovascular age-related macular degeneration were evaluated. Two eyes were treatment naïve at the initial visit. Choroidal neovascularization in all eyes at each visit showed relatively higher flow speeds in the trunk, central, and larger vessels and lower flow speed in the small vessels, which generally were located at the periphery of the CNV complex. Overall, the CNV appeared to expand over time despite retention of good visual acuity in all patients. In the treatment-naïve patients, slower-flow-speed vessels contracted with treatment, whereas the larger vessels with higher flow speed remained constant.

Conclusions: Variable interscan time analysis OCTA allows for longitudinal observations of relative blood flow speeds in CNV treated with anti-VEGF intravitreal injections. A common finding in this study is that the main trunk and larger vessels seem to have relatively faster blood flow speeds compared with the lesions' peripheral vasculature. Moreover, an overall growth of chronically treated CNV was seen despite retention of good visual acuity. The VISTA framework may prove useful for developing clinical end points, as well as for studying hemodynamics, disease pathogenesis, and treatment response.
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http://dx.doi.org/10.1016/j.oret.2017.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532791PMC
April 2018

Quantifying Microvascular Changes Using OCT Angiography in Diabetic Eyes without Clinical Evidence of Retinopathy.

Ophthalmol Retina 2018 May 7;2(5):418-427. Epub 2017 Nov 7.

New England Eye Center, Tufts Medical Center, Boston, Massachusetts.

Objective: To compare quantitative OCT angiography (OCTA) parameters of macular ischemia in diabetic eyes without retinopathy with those in healthy nondiabetic controls.

Design: Cross-sectional study from August 2014 through June 2017.

Subjects: Thirty-nine eyes of 39 diabetic patients without clinical evidence of diabetic retinopathy and 40 eyes of 40 healthy nondiabetic subjects.

Methods: Subjects underwent OCTA imaging using prototype AngioVue software (RTVue XR Avanti). Analyses of the foveal avascular zone (FAZ) and vasculature surrounding the FAZ were performed on the automatically generated en face OCTA images of the superficial and deep retinal vasculatures using vessel-based and FAZ-based metrics.

Main Outcome Measures: Comparison of measurements made in the superficial and deep retinal capillary plexuses of diabetic eyes and normal eyes.

Results: FAZ-based analysis revealed statistically significant differences between diabetic and normal eyes in FAZ area (superficial and deep layers), perimeter (superficial layer), major axis length (superficial layer), and minor axis layer (superficial and deep layers). Vessel-based analysis revealed statistically significant differences in the binarized flow index (superficial and deep layers), both including and excluding the FAZ area.

Conclusions: Quantitative OCTA parameters reveal subclinical macular ischemia at both the superficial and deep retinal capillary plexuses in diabetic eyes that do not manifest clinical retinopathy. Vessel-based and FAZ-based metrics applied to OCTA images may serve as effective tools for screening and disease monitoring in patients with diabetes without clinical evidence of retinopathy.
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http://dx.doi.org/10.1016/j.oret.2017.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391050PMC
May 2018

QUANTIFICATION OF RETINAL CAPILLARY NONPERFUSION IN DIABETICS USING WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Retina 2020 Mar;40(3):412-420

Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts.

Purpose: To combine advances in high-speed, wide-field optical coherence tomography angiography (OCTA) with image processing methods for semiautomatic quantitative analysis of capillary nonperfusion in patients with diabetic retinopathy (DR).

Methods: Sixty-eight diabetic patients (73 eyes), either without retinopathy or with different degrees of retinopathy, were prospectively recruited for volumetric swept-source OCTA imaging using 12 mm × 12 mm fields centered at the fovea. A custom, semiautomatic software algorithm was used to quantify areas of capillary nonperfusion.

Results: The mean percentage of nonperfused area was 0.1% (95% confidence interval: 0.0-0.4) in the eyes without DR; 2.1% (95% confidence interval: 1.2-3.7) in the nonproliferative DR eyes (mild, moderate, and severe), and 8.5% (95% confidence interval: 5.0-14.3) in the proliferative DR eyes. The percentage of nonperfused area increased in a statistically significant manner from eyes without DR, to eyes with nonproliferative DR, to eyes with proliferative DR.

Conclusion: Capillary nonperfusion area in the posterior retina increases with increasing DR severity as measured by swept-source OCTA. Quantitative analysis of retinal nonperfusion on wide-field OCTA may be useful for early detection and monitoring of disease in patients with diabetes and DR.
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http://dx.doi.org/10.1097/IAE.0000000000002403DOI Listing
March 2020

Parafoveal Retinal Vessel Density Assessment by Optical Coherence Tomography Angiography in Healthy Eyes.

Ophthalmic Surg Lasers Imaging Retina 2018 10;49(10):S5-S17

Background And Objective: To assess variability in vessel density (VD) measurements across three optical coherence tomography angiography (OCTA) devices to identify a methodology that offers the least amount of variation in VD, and to assess the effect of averaging of multiple scans on VD variability.

Patients And Methods: Fifteen eyes of eight healthy individuals were imaged consecutively on three OCTA devices. Segmentations at the superficial, deep, and full retinal layers were generated. Repeat scans for each retinal layer were registered and averaged to generate one OCTA image. Two different automated thresholding techniques were used to calculate vessel area density (VAD) from binarized images and vessel skeleton density (VSD) from skeletonized images. Vessel length, a linear measure of the combined lengths of vessels, was calculated. Foveal avascular zone (FAZ) area was measured.

Results: All three OCTA devices were significantly different (P < .0001). This finding remained after averaging images (P < .0001). VSD was more repeatable within a device but less reproducible across devices. Conversely, VAD demonstrated less repeatability but greater reproducibility. Differences in VSD between devices were systematic and attributable to differences in resolution. Vessel length, unaffected by resolution, demonstrated no significant differences between the devices (P > .107). There was no significant difference in FAZ area across devices (P = .51). After averaging images, VD was significantly different from the single images for each device and plexus (P < .05) but remained within 1% of the value of a single scan.

Conclusions: OCTA devices show variability in VD for healthy individuals. With greater repeatability, VSD appeared useful for following a patient on one device. VAD and vessel length seemed ideal for comparing vessel parameters between OCTA devices. After averaging multiple scans, VSD remained within 1% of a single scan, for which clinical significance remains to be determined. Caution is advised when comparing quantitative analyses across OCTA devices. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S17.].
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http://dx.doi.org/10.3928/23258160-20180814-02DOI Listing
October 2018

VISUALIZATION OF CHOROIDAL NEOVASCULARIZATION USING TWO COMMERCIALLY AVAILABLE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DEVICES.

Retina 2019 Sep;39(9):1682-1692

New England Eye Center, Tufts Medical Center, Boston, Massachusetts.

Purpose: To compare the sensitivity of detection and the measured size of choroidal neovascularization (CNV) on two commercially available spectral domain optical coherence tomography angiography (OCTA) devices, the Optovue RTVue XR Avanti with AngioVue and the Zeiss Cirrus HD-OCT with AngioPlex.

Methods: Patients with CNV lesions were imaged consecutively on both OCTA devices on the same day of their visit. 3 × 3 mm and 6 × 6 mm scans centered at the fovea were obtained. Two independent masked readers evaluated the OCTA images for CNV identification and its area measurements.

Results: No significant differences were observed between the 2 OCTA devices in CNV area measurements on their 3 × 3 mm and 6 × 6 mm scans. However, there was suboptimal performance of their automated segmentation algorithms as compared to manually adjusted segmentation for visualizing CNV lesions.

Conclusion: There was no significant difference in the size of the CNV lesion as measured on either commercially available spectral domain OCTA device. Both devices were comparable in their detection of CNV lesions on manual adjustment of segmentation lines. However, their automated segmentation algorithms need improvement to allow for accurate measurement of CNV lesions for routine clinical application.
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http://dx.doi.org/10.1097/IAE.0000000000002241DOI Listing
September 2019

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO DETECT MACULAR CAPILLARY ISCHEMIA IN PATIENTS WITH INNER RETINAL CHANGES AFTER RESOLVED DIABETIC MACULAR EDEMA.

Retina 2018 Dec;38(12):2277-2284

New England Eye Center, Tufts Medical Center, Boston, Massachusetts.

Purpose: To compare foveal vascular anatomy between patients with and without disorganization of retinal inner layers (DRILs) after resolved diabetic macular edema using optical coherence tomography angiography (OCTA).

Methods: Twenty-four eyes of 21 age- and sex-matched patients with resolved diabetic macular edema were included in this retrospective, cross-sectional study. All eyes were imaged with enhanced high-definition line or cross-line structural B scans and 3 × 3-mm OCTA scans. Optical coherence tomography B scans were analyzed for the presence of DRIL, and based on this, eyes were classified as either DRIL present or DRIL absent. The foveal avascular zone area on OCTA was compared between patients with and without DRIL. The foveal avascular zone area was correlated with visual acuity.

Results: Nine eyes with DRIL and resolved diabetic macular edema were compared with 15 control eyes without DRIL and resolved diabetic macular edema. Area of ischemia on OCTA scans corresponded to the area of DRIL as determined on OCT B scans. The foveal avascular zone area in full retina as well as superficial and deep retinal plexuses OCTA slabs were significantly larger in patients with DRIL as compared to those without DRIL (P = 0.005, P < 0.001, and P = 0.004, respectively). The larger foveal avascular zone in full retinal segmentation (r = 0.72, P = 0.03) and superficial plexus (r = 0.74, P = 0.02) were positively correlated with lower visual acuity.

Conclusion: Optical coherence tomography angiography can visualize retinal ischemia in patients with and without DRIL. Correspondence of impaired blood flow with DRIL suggests that retinal ischemia and loss of normal vasculature contributes to DRIL.
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http://dx.doi.org/10.1097/IAE.0000000000001902DOI Listing
December 2018

Optical coherence tomography angiography artifacts in retinal pigment epithelial detachment.

Can J Ophthalmol 2017 Aug 15;52(4):419-424. Epub 2017 Mar 15.

New England Eye Center and Tufts Medical Center, Tufts University, Boston, Massachusetts. Electronic address:

Objective: To describe optical coherence tomography angiography (OCTA) reflectance artifacts secondary to retinal pigment epithelial detachment (RPED).

Design: Retrospective review.

Methods: Four eyes from 4 subjects were included. Three presented with RPED and 1 eye was a normal control. Two eyes diagnosed with RPED and the normal eye were evaluated using en face OCTA centred at the fovea acquired using the RTVue XR Avanti (Optovue Inc). In the third eye with RPED, OCTA imaging was performed using a CIRRUS 5000 prototype modified to do OCTA imaging on a spectral domain OCT platform provided by Carl Zeiss Meditec, Inc. The segmented OCTA angiograms were overlaid to determine if the flow patterns seen at the edge of the RPEDs were due to reflectance from the inner retinal vessels, also known as "decorrelation tails."

Results: OCTA projection artifacts were noted when segmentation lines intersected with the boundary of the RPED. The overlaid segmented OCTA from the 3 RPED eyes imaged using each system revealed the same vasculature pattern at the edges of the RPED as that of the inner retina, demonstrating the "decorrelation tails" artifact, which caused the RPED to appear as a bright ring on the segmented OCTA.

Conclusions: OCTA images are susceptible to various known artifacts. This series describes the impact of the projection artifact seen at the edges of an RPED that simulates appearance of flow but is actually due to reflectance of the inner retinal vasculature on the RPED.
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http://dx.doi.org/10.1016/j.jcjo.2016.12.012DOI Listing
August 2017

Visualization of changes in the foveal avascular zone in both observed and treated diabetic macular edema using optical coherence tomography angiography.

Int J Retina Vitreous 2017 19;3:19. Epub 2017 Jun 19.

New England Eye Center, Tufts Medical Center, Tufts University, 800 Washington Street, Box 450, Boston, MA 02111 USA.

Background: Central vision loss in diabetic retinopathy is commonly related to diabetic macular edema (DME). The objective of this study was to describe changes between consecutive visits on optical coherence tomography angiography (OCTA) of the foveal avascular zone (FAZ) in eyes with DME.

Methods: 20 eyes from 14 patients with DME were imaged on 2 successive clinic visits separated by at least 1 month. The mean interval between visits was 3.2 months. The only intervention used was intravitreal anti-VEGF in 11 eyes; the others were observed over time without treatment. Two different readers measured FAZ area using a pseudo-automated tool in comparison to a manual tracing tool. Qualitative changes in the appearance of the vasculature surrounding the FAZ were also recorded. The retinal capillary plexus was segmented into deep and superficial plexuses, and FAZ measurements were done on the superficial, deep, and summated plexuses.

Results: Pseudo-automated and manual measurements of FAZ area decreased significantly ( < 0.05) between visits in the deep, superficial, and summated plexuses. Qualitative analysis of vasculature surrounding the FAZ showed that most of the vascular changes (65%) over time were visible in the deep plexus, compared to 30 and 20% in the superficial and summated plexuses, respectively.

Conclusions: The most significant differences in FAZ size over time were in the summated plexus ( < 0.001), while changes in FAZ appearance were most prominent in the deep plexus. Absolute decrease in FAZ size over visits was largest in the deep plexus. Our results demonstrate that OCTA can effectively be used to measure FAZ area in patients with DME, visualize qualitative changes in retinal vasculature, and visualize the segmentation levels at which these changes can be best appreciated. However, larger studies are needed to evaluate the reproducibility of manual and pseudo-automated measuring techniques.
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http://dx.doi.org/10.1186/s40942-017-0074-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474852PMC
June 2017

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes.

Ophthalmology 2017 05 19;124(5):583-595. Epub 2017 Jan 19.

Retina Consultants of Houston, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas.

Purpose: To expand understanding of presentation, diagnosis, and outcomes of hemorrhagic occlusive retinal vasculitis (HORV).

Design: Retrospective case series.

Participants: Thirty-six eyes of 23 patients.

Methods: The American Society of Cataract and Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) formed a joint task force to define clinical characteristics of HORV and to study its prevalence, cause, treatment, and outcomes. An online registry was established on both societies' web sites. Surveys were e-mailed to members of both societies soliciting cases of suspected HORV. A literature search was performed to uncover additional cases.

Main Outcome Measures: Historical data including intraoperative characteristics, images, treatment regimens, and visual and anatomic outcomes.

Results: Characteristic findings of HORV included unremarkable postoperative day 1 undilated examination, delayed-onset painless vision loss, mild anterior chamber and vitreous inflammation, sectoral retinal hemorrhages in areas of ischemia, and predilection for venules and peripheral involvement. Based on predetermined diagnostic criteria, 36 eyes of 23 patients were diagnosed with HORV. All eyes received intraocular vancomycin via intracameral bolus (33/36), via intravitreal injection (1/36), or through the irrigation bottle (2/36). Patients sought treatment with HORV 1 to 21 days after surgery or intravitreal injection. Visual results usually were poor: 22 of 36 eyes (61%) had 20/200 or worse visual acuity and 8 of 36 eyes (22%) had no light perception (NLP). Neovascular glaucoma developed in 20 of 36 eyes (56%). Seven eyes received additional intravitreal vancomycin after surgery; 5 of these 7 eyes had NLP visual acuity at the most recent examination. Three eyes received intravitreal corticosteroids and had final visual acuities of 20/40, 20/70, and hand movements.

Conclusions: Hemorrhagic occlusive retinal vasculitis is a rare, potentially devastating condition that can develop after cataract surgery or intraocular injection. All cases in this series were associated with intraocular vancomycin. Disease course and findings suggest that HORV is caused by a delayed hypersensitivity reaction to vancomycin. Early treatment with corticosteroids likely is beneficial. Subsequently, anti-vascular endothelial growth factor injections and panretinal photocoagulation are important to prevent neovascular glaucoma, a common complication. Avoidance of additional intravitreal vancomycin is recommended if HORV is suspected.
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http://dx.doi.org/10.1016/j.ophtha.2016.11.042DOI Listing
May 2017