Publications by authors named "Caroline R Baumal"

126 Publications

Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy.

Ophthalmology 2021 Mar 9. Epub 2021 Mar 9.

Objective: Evaluate clinical characteristics of eyes that developed investigator-determined new-onset exudative age-related macular degeneration (eAMD) during the FILLY trial.

Design: Post-hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).

Subjects: 246 subjects with GA secondary to AMD.

Intervention: Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month (EOM) for 12 months followed by a 6-month off-treatment period.

Main Outcome Measures: Time of onset of new eAMD in the study eye; history of eAMD in the fellow eye; presence of double layer sign (DLS) on structural optical coherence tomography (OCT) in the study eye; changes in retinal anatomy by structural OCT and fluorescein angiography (FA); and changes in visual acuity.

Results: Exudation was reported in 26 study eyes across all treatment groups over 18 months. Mean time to diagnosis of eAMD was 256 days (range: 31 to 555). Overall, a higher proportion of subjects with a history of eAMD in the fellow eye (P=0.016) and a DLS in the study eye at baseline (P=0.0001) developed eAMD. Among study eyes that developed eAMD, 18/26 (69%) had a history of fellow eye eAMD and 19/26 (73.1%) had a DLS at baseline, compared to 72/217 (33%) (P=0.0003) and 70/215 (32.5%) (P<0.0001)respectively, of study eyes that did not develop eAMD. All 21 subjects with structural OCT imaging at the time of eAMD diagnosis had subretinal fluid and/or intraretinal cysts, consistent with exudation. Among 17 subjects who received FA at the time of eAMD diagnosis, 10 had detectable MNV, all occult lesions. Development of eAMD did not appear to have an appreciable impact on visual acuity, and all subjects responded to anti-VEGF therapy.

Conclusions: Intravitreal injections of pegcetacoplan slowed the rate of GA growth and were associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. eAMD appeared to be associated with the presence of baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria.
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http://dx.doi.org/10.1016/j.ophtha.2021.02.025DOI Listing
March 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

Ocular Toxoplasmosis after Exposure to Wild Game.

Ocul Immunol Inflamm 2021 Feb 9:1-6. Epub 2021 Feb 9.

Department of Ophthalmology and Visual Sciences, University of Michigan , Ann Arbor, Michigan, USA.

: To describe eight patients with toxoplasma retinochoroiditis following exposure to wild game. : Retrospective, multicenter case series : Eight men, aged 29 to 71 (mean, 56 years), developed toxoplasmic retinochoroiditis after hunting and/or consuming wild game in the United States, including seven deer and one bear. Five patients developed the disease after eating undercooked game meat, while three developed ocular findings after cleaning hunted animals. Seven patients were healthy prior to exposure. LogMAR visual acuity at presentation was 0.697 ± 0.745, improving to 0.256 ± 0.335 by last follow-up. Disease complications developed in five (62.5%) patients, of which recurrence of retinochoroiditis was the most common. : Contact with wild game is a potential source of primary ocular toxoplasmosis in immunocompetent adults. Hunters and consumers of rare game are at risk of serious ocular disease and appropriate contact precautions and cooking may reduce this complication.
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http://dx.doi.org/10.1080/09273948.2020.1854316DOI Listing
February 2021

Valsalva-Induced Retinal Hemorrhage as a Secondary Effect of COVID-19 Disease.

Asia Pac J Ophthalmol (Phila) 2021 Jan-Feb 01;10(1):125-126

Duke University Eye Center, Durham, NC, USA.

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http://dx.doi.org/10.1097/APO.0000000000000358DOI Listing
February 2021

Choroidal nonperfusion on optical coherence tomography angiography in a case of unilateral posterior segment ocular sarcoidosis misdiagnosed as MEWDS.

Am J Ophthalmol Case Rep 2020 Dec 25;20:100944. Epub 2020 Sep 25.

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

Purpose: To report a case of presumed ocular sarcoidosis initially presenting with features of multiple evanescent white dot syndrome (MEWDS) with atypical optical coherence tomography angiography (OCTA) findings.

Observations: A 23 year-old woman presented with a unilateral central scotoma, photophobia, and decreased visual acuity after a viral illness. Examination of the right eye revealed multiple round white macular spots and stippled granularity at the fovea. Multimodal imaging with fluorescein angiography (FA), indocyanine green angiography (ICG), fundus autofluorescence (FAF), and optical coherence tomography (OCT) was consistent with a diagnosis of MEWDS. However, OCTA demonstrated choriocapillaris (CC) flow deficits, which is not typical for MEWDS. The clinical course was initially consistent with MEWDS, with spontaneous recovery of symptoms over ensuing months. The patient presented five months later with floaters and a central scotoma. Examination showed panuveitis, and systemic evaluation revealed an elevated angiotensin converting enzyme (ACE) and hilar lymphadenopathy on chest x-ray consistent with presumed sarcoidosis.

Conclusions And Importance: A case of MEWDS atypically demonstrated CC flow deficits on OCTA and subsequently presented as uveitis secondary to presumed sarcoidosis. Atypical features in MEWDS may be a sign of another disorder masquerading early on as MEWDS and ought to prompt further investigation.
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http://dx.doi.org/10.1016/j.ajoc.2020.100944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528049PMC
December 2020

Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion after Brolucizumab Treatment.

Ophthalmol Retina 2020 Sep 29. Epub 2020 Sep 29.

York Teaching Hospital NHS Foundation Trust, University of York, York, United Kingdom.

Purpose: Recent reports have described a spectrum of uncommon findings of intraocular inflammation (IOI), retinal vasculitis, or retinal vascular occlusion in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. We present guidance on the clinical presentation of this spectrum and propose recommendations for management of these events.

Design: PubMed literature review and expert opinion panel.

Participants: A working group of international medical experts and Novartis medical personnel.

Methods: The working group deliberated on the clinical presentations and used a 3-pronged approach to develop management recommendations based on (1) critical appraisal of scientific literature; (2) clinical insights from the HAWK and HARRIER trials, postmarketing reports, and assessments from an independent Safety Review Committee (SRC); and (3) their clinical experience.

Main Outcome Measures: Management recommendations for a spectrum of ocular inflammatory events after treatment with brolucizumab or other anti-vascular endothelial growth factors (VEGFs).

Results: Based on insights gained from the available information and the expertise of the contributors, recommendations were proposed for ocular examinations, imaging modalities, and treatment strategies for management of this spectrum of events. Patients should be educated to promptly report any relevant or persistent symptoms after IVI to facilitate timely intervention. Patients diagnosed with IOI should be evaluated for concomitant retinal vasculitis or retinal vascular occlusive events. Clinical examination can be augmented with multimodal imaging techniques, including widefield imaging, fluorescein angiography (with peripheral sweeps), and OCT. Once confirmed, the ongoing brolucizumab treatment should be suspended and intensive treatment with potent corticosteroids (topical, subtenon, intravitreal, or systemic) is recommended, which may be supplemented with other treatment strategies depending on the severity. Based on the clinical outcome of these events, individualized treatment with locally available standard of care should be considered for the underlying nAMD.

Conclusions: These recommendations emphasize the need for early diagnosis, prompt and timely intervention, intensive treatment, and frequent monitoring to minimize the risk of progression of these events. The proposed recommendations may facilitate a consistent management approach of this spectrum of ocular inflammatory events should they arise in nAMD after treatment with brolucizumab or other anti-VEGFs.
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http://dx.doi.org/10.1016/j.oret.2020.09.020DOI Listing
September 2020

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

Using the Pathophysiology of Dry AMD to Guide Binarization of the Choriocapillaris on OCTA: A Model.

Transl Vis Sci Technol 2020 07 29;9(8):44. Epub 2020 Jul 29.

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

Especially since the incorporation of swept laser sources, optical coherence tomography angiography (OCTA) has enabled quantification of choriocapillaris perfusion. A critical step in this process is binarization, which makes angiographic images quantifiable in terms of perfusion metrics. It remains challenging to have confidence that choriocapillaris perfusion metrics reflect the reality of pathophysiologic flow, largely because choice of binarization method can result in significantly different perfusion metric outcomes. This commentary discusses a proof-of-concept case involving comparative assessment of binarization methods for a set of dry age-related macular degeneration OCTA data. One of these methods was deemed preferable based on superior agreement with suspected physiologic and pathophysiologic characteristics, thus demonstrating the principle that, in the absence of gold standards for measurement of choriocapillaris perfusion, the best available approximations of pathophysiology may be used to guide choice of binarization method.
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http://dx.doi.org/10.1167/tvst.9.8.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422830PMC
July 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

High-Speed, Ultrahigh-Resolution Spectral-Domain OCT with Extended Imaging Range Using Reference Arm Length Matching.

Transl Vis Sci Technol 2020 06 8;9(7):12. Epub 2020 Jun 8.

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

Purpose: To develop high-speed, extended-range, ultrahigh-resolution spectral-domain optical coherence tomography (UHR SD-OCT) and demonstrate scan protocols for clinical retinal imaging.

Methods: A UHR SD-OCT operating at 840-nm with 150-nm bandwidths was developed. The axial imaging range was extended by dynamically matching reference arm length to the retinal contour during acquisition. Two scan protocols were demonstrated for imaging healthy participants and patients with dry age-related macular degeneration. A high-definition raster protocol with intra-B-scan reference arm length matching (ReALM) was used for high-quality cross-sectional imaging. A cube volume scan using horizontal and vertical rasters with inter-B-scan ReALM and software motion correction was used for en face and cross-sectional imaging. Linear OCT signal display enhanced visualization of outer retinal features.

Results: UHR SD-OCT was demonstrated at 128- and 250-kHz A-scan rates with 2.7 µm axial resolution and a 1.2-mm, 6-dB imaging range in the eye. Dynamic ReALM was used to maintain the retina within the 6-dB imaging range over wider fields of view. Outer retinal features, including the rod and cone interdigitation zones, retinal pigment epithelium, and Bruch's membrane were visualized and alterations observed in age-related macular degeneration eyes.

Conclusions: Technological advances and dynamic ReALM improve the imaging performance and clinical usability of UHR SD-OCT.

Translational Relevance: These advances should simplify clinical imaging workflow, reduce imaging session times, and improve yield of high quality images. Improved visualization of photoreceptors, retinal pigment epithelium, and Bruch's membrane may facilitate diagnosis and monitoring of age-related macular degeneration and other retinal diseases.
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http://dx.doi.org/10.1167/tvst.9.7.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414734PMC
June 2020

Update on Anti-Vascular Endothelial Growth Factor Safety for Retinopathy of Prematurity.

Asia Pac J Ophthalmol (Phila) 2020 Jul-Aug;9(4):358-368

Department of Ophthalmology, New England Eye Center, Tufts University School of Medicine, Boston, MA.

Retinopathy of prematurity (ROP) is a neovascular retinal disorder that occurs in infants born prematurely. Nowadays, ROP constitutes a leading cause of childhood blindness worldwide and for decades the standard of care has involved peripheral retinal ablation. However, this type of treatment requires the use of specialized equipment by well-trained physicians, has been associated with poor structural and visual outcomes in some preterm infants, and despite its adequate application, some cases of ROP may continue to progress. Therefore, the need for simpler and more efficient strategies made anti-vascular endothelial growth factor (anti-VEGF) medications an appealing option for treatment. Recently, the use of anti-VEGF agents for ROP has increased worldwide; nevertheless, this practice remains off-label, and there is a lack of information regarding its safety profile and the possibility of unfavorable long-term outcomes causes the utmost concern. This review updates the recent evidence regarding the systemic and ocular safety of anti-VEGF treatment for ROP.
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http://dx.doi.org/10.1097/APO.0000000000000302DOI Listing
January 2021

Striving for Parity in 2020-Raising Awareness and Effecting Change.

JAMA Ophthalmol 2020 08;138(8):817-818

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

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http://dx.doi.org/10.1001/jamaophthalmol.2020.2261DOI Listing
August 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

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

Wet age-related macular degeneration: treatment advances to reduce the injection burden.

Am J Manag Care 2020 05;26(5 Suppl):S103-S111

Tufts University School of Medicine and New England Eye Center, Boston, MA. Email:

The burden of age-related macular degeneration (AMD), a leading cause of vision loss in the elderly population, is poised to increase dramatically as the baby boomer generation ages. Fortunately, the prognosis of neovascular AMD has improved dramatically since anti-vascular endothelial growth factor (VEGF) agents reached the market 15 years ago. In large-scale clinical trials, anti-VEGF utilization maintained visual acuity in more than 90% of patients. However, providing anti-VEGF treatment requires the specialized expertise of retina specialists and is labor intensive and costly. Further, results in clinical practice do not always measure up to those obtained in rigorous phase 3 trials. Undertreatment and the burden on patients and caregivers from frequent anti-VEGF injections contribute to suboptimal visual acuity results in the real world. As a consequence, retinal specialists are focused on finding effective strategies to extend the dosing interval. These include individualized optical coherence tomography-guided dosing regimens, longer acting new agents with similar or new mechanisms of action, and sustained release delivery devices. With the recent approval of brolucizumab, the neovascular AMD armamentarium has expanded to 4 anti-VEGF agents, and more are in development. Understanding the treatment landscape is a key issue in managed care due to the substantial cost of anti-VEGF medications. The goal of this article is to provide managed care clinicians with an up-to-date assessment of currently available agents, followed by a preview of some investigational agents that could alter the future treatment landscape. These agents include abicipar pegol, faricimab, the ranibizumab port delivery system, an intravitreal bevacizumab formulation, and anti-VEGF biosimilars.
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http://dx.doi.org/10.37765/ajmc.2020.43435DOI Listing
May 2020

Wide-field optical coherence tomography angiography for the detection of proliferative diabetic retinopathy.

Graefes Arch Clin Exp Ophthalmol 2020 Sep 30;258(9):1901-1909. Epub 2020 May 30.

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

Purpose: To compare the ability of wide-field optical coherence tomography angiography (WF-OCTA) to that of ultra-wide field fluorescein angiography (UWF-FA) and ultra-wide-field color fundus photography (UWF-CP) to detect retinal neovascularization (NV) in eyes with proliferative diabetic retinopathy (PDR).

Methods: In this cross-sectional study, naïve patients with active PDR underwent UWF-FA and UWF-CP using the Optos 200Tx and WF-OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000. NV was defined on OCTA when the co-registered B-scan with flow overlay of the vitreoretinal interface (VRI) segmentation showed extraretinal proliferation. Three masked readers examined the UWF-FA, UWF-CP, and WF-OCTA independently for the presence of NV. Statistical analysis was performed to compare the diagnostic accuracy of the 3 wide-field imaging modalities using OCT B-scan as the reference standard.

Results: In 82 eyes with PDR, neovascularization of the disc (NVD) was detected in 13 eyes by UWF-CP, 35 eyes with UWF-FA, and 37 eyes with OCTA using the VRI slab. Upon review of the 2500 OCT B-scans with superimposed flow overlay of each eye, NVD was confirmed in 37 eyes. The sensitivity and specificity of NVD detection were 35.1% and 97.8%, respectively for UWF-CP; 94.6% and 100%, respectively, for UWF-FA; and 100% and 100% for WF-OCTA. One hundred ninety-six foci of neovascularization elsewhere (NVE) were identified with the OCT B-scan with superimposed flow overlay. UWF-CP analysis was able to detect 62 foci of NVE of the 196 confirmed by B-scan (31.6% detection rate). An additional 11 foci of NVE seen on UWF-CP were not confirmed by B-Scan (15% false positive rate). There were 182 foci of NVE identified by UWF-FA (detection rate 91.3%), while WF-OCTA detected 196 retinal NVEs (detection rate 100%). The rate of false positives for both UWF-FA and WF-OCTA was low (< 2%).

Conclusion: WF-OCTA can identify NV that is not evident in UWF-CP and represents a faster and safer alternative to UWF-FA for surveillance of PDR with comparable diagnostic accuracy.
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http://dx.doi.org/10.1007/s00417-020-04773-xDOI Listing
September 2020

Henle fibre layer haemorrhage: clinical features and pathogenesis.

Br J Ophthalmol 2021 Mar 6;105(3):374-380. Epub 2020 May 6.

Retina Department, Vitreous Retina Macula Consultants of New York, New York, New York, USA.

Background: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented.

Methods: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented.

Results: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up.

Conclusion: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315443DOI Listing
March 2021

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

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

Ophthalmology 2020 10 25;127(10):1345-1359. Epub 2020 Apr 25.

Bascom Palmer Eye Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.

Purpose: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration.

Design: Retrospective case series.

Participants: Fifteen eyes from 12 patients identified from 10 United States centers.

Methods: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings.

Main Outcome Measures: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies.

Results: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033).

Conclusions: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.
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http://dx.doi.org/10.1016/j.ophtha.2020.04.017DOI Listing
October 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

Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

Ophthalmology 2020 05 14;127(5):616-636. Epub 2019 Nov 14.

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

Purpose: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data.

Design: Consensus meeting.

Participants: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists.

Methods: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components.

Main Outcome Measures: A consensus classification of neovascular AMD.

Results: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated.

Conclusions: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.
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http://dx.doi.org/10.1016/j.ophtha.2019.11.004DOI 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

DISTINGUISHING INTRARETINAL MICROVASCULAR ABNORMALITIES FROM RETINAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Retina 2020 Sep;40(9):1686-1695

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

Purpose: With the increasing prevalence of diabetes, fast, noninvasive identification of proliferative diabetic retinopathy (PDR) becomes essential. This study evaluated the utility of optical coherence tomography angiography (OCTA) to characterize intraretinal microvascular abnormalities (IRMA) and retinal neovascularization (NV).

Methods: Patients with severe non-PDR or PDR were imaged with fluorescein angiography and widefield swept-source OCTA (Zeiss Plex Elite 9000; Carl Zeiss Meditec, Dublin, CA). Regions suspicious for IRMA or retinal NV were identified and the OCTA, including flow overlay on the co-registered structural optical coherence tomography, and fluorescein angiography images were graded by two masked readers.

Results: Ninety-six foci of irregular vasculature were analyzed, comprised of 70 IRMA and 26 retinal NV lesions from 14 eyes. Compared with fluorescein angiography, OCTA with flow overlay demonstrated specificity of 99% and sensitivity of 92% in identifying IRMA and NV. Neovascularization differed from IRMA on OCTA by demonstrating supraretinal flow breaching the internal limiting membrane and posterior hyaloid (P < 0.001). Intraretinal microvascular abnormalities were distinguished from NV by outpouching of the internal limiting membrane (P = 0.035). Vascular flow was reduced in the presence of fibrosis.

Conclusion: Optical coherence tomography angiography, through flow overlay, has utility to image and differentiate IRMA and NV, which are key features distinguishing severe non-PDR and PDR, respectively. Noninvasive widefield OCTA may be a useful tool to diagnose high-risk diabetic retinopathy eyes.
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http://dx.doi.org/10.1097/IAE.0000000000002671DOI Listing
September 2020

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