Publications by authors named "David Sarraf"

277 Publications

Maculopathy caused by pentosan polysulfate.

CMAJ 2021 May;193(18):E645

Michael G. DeGroote School of Medicine (Rosenberg), McMaster University, Hamilton, Ont.; Stein Eye Institute (Sarraf), David Geffen School of Medicine, University of California Los Angeles; Greater Los Angeles Veterans Administration Healthcare Center (Sarraf), Los Angeles, Calif.; Division of Ophthalmology (Chaudhary), Department of Surgery, and Department of Health Research Methods, Evidence and Impact (HEI) (Chaudhary), McMaster University; St. Joseph's Healthcare Hamilton and McMaster University (Chaudhary), Hamilton, Ont.

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http://dx.doi.org/10.1503/cmaj.201900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112634PMC
May 2021

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

JAMA Ophthalmol 2021 Apr 22. Epub 2021 Apr 22.

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

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

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

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

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

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

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

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

Trial Registration: ClinicalTrials.gov Identifier: NCT01639209.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0803DOI Listing
April 2021

Identification and Characterization of Epivascular Glia using En Face OCT.

Am J Ophthalmol 2021 Mar 24. Epub 2021 Mar 24.

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

Purpose: To describe the clinical features of epivascular glia (EVG) using en face optical coherence tomography (OCT).

Design: Retrospective cross-sectional study.

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

Results: Characteristic hyper-reflective internal limiting membrane (ILM) plaques with dendritic-like radiations were identified with en face OCT and displayed vascular predilection. 161 eyes with EVG (EVG group) and 2315 eyes without EVG (control group) were identified from a total cohort of 1298 patients (or 2476 eyes). The prevalence of EVG was 6.5% (161/2476) of eyes and 9.2% (119/1298) of patients in our cohort. Mean age was 79.3±10.7 years in the EVG group and 55.9±24.6 years in the control group (p<0.01). Advanced posterior vitreous detachment (PVD) stage was more common in the EVG (grade 3: 41.7%, grade 4: 48.6%) versus the control group (grade 3: 18.5%, grade 4: 26.9%, p<0.001). Contractile ERM was present in 44.1% (71/161) of patients with EVG as compared to 18.6% (30/161) in a random age- and gender-matched control cohort without EVG (p<0.001).

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

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

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

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

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

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

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

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

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

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

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

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

Pentosan Polysulfate Maculopathy: Prevalence, Spectrum of Disease, and Choroidal Imaging Analysis Based on Prospective Screening.

Am J Ophthalmol 2021 Feb 27;227:125-138. Epub 2021 Feb 27.

Retinal Disorders and Ophthalmic Genetics, Stein Eye Institute, University of California Los Angeles (D.W., C.G., A.A., F.G., J.Y.J., D.S.), Los Angeles, California, USA; Greater Los Angeles VA Healthcare Center (D.S.), Los Angeles, California, USA. Electronic address:

Purpose: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis.

Design: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed.

Results: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group.

Conclusions: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.
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http://dx.doi.org/10.1016/j.ajo.2021.02.025DOI Listing
February 2021

Functional and structural evolution of paracentral acute middle maculopathy.

Can J Ophthalmol 2021 Feb 8. Epub 2021 Feb 8.

Stein Eye Institute, University of California, Los Angeles, Los Angeles, Calif.

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http://dx.doi.org/10.1016/j.jcjo.2021.01.014DOI Listing
February 2021

Understanding the Mechanisms of Fluid Development in Age-Related Macular Degeneration.

Ophthalmol Retina 2021 02;5(2):105-107

Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, California.

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http://dx.doi.org/10.1016/j.oret.2020.09.016DOI Listing
February 2021

Natural history of incomplete retinal pigment epithelial and outer retinal atrophy in age-related macular degeneration.

Can J Ophthalmol 2021 Feb 1. Epub 2021 Feb 1.

Retina Disorders and Ophthalmic Genetics, Stein Eye Institute, University of California-Los Angeles, Los Angeles, Calif.; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, Calif.; Greater Los Angeles VA Healthcare Center, Los Angeles, Calif.. Electronic address:

Objective: To assess the time course and risk factors for conversion of incomplete retinal pigment epithelium and outer retina atrophy (iRORA) to complete retinal pigment epithelium and outer retina atrophy (cRORA) in eyes with non-neovascular intermediate age-related macular degeneration (iAMD), using optical coherence tomography (OCT) analysis.

Design: Retrospective survival study.

Participants: Tracked structural Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) volume datasets from 2 retinal specialists at the University of California-Los Angeles were retrospectively screened to identify consecutive participants with non-neovascular iAMD without signs of atrophy or macular neovascularization in either eye at baseline.

Methods: In the first stage of selection, 321 consecutive iAMD eyes were screened for onset of iRORA. Eyes that developed iRORA within the first 24 months were followed for an additional 24 months to assess the rate of conversion to cRORA. A Kaplan-Meier survival curve was formulated to illustrate the conversion from iRORA to cRORA.

Results: Among 321 baseline participants with iAMD, 87 incident iRORA lesions (50 eyes, 42 participants) were included in the conversion analysis. Eighty-one iRORA lesions (93.1%) converted to cRORA within 24 months (median 14 months). Multivariate binary logistic regression analysis indicated that intraretinal hyperreflective foci and extrafoveal iRORA location at baseline were associated with a faster rate of progression to cRORA (model R = 0.816, p < 0.05).

Conclusions: The majority of incident iRORA lesions progress to cRORA within a 24-month period. These findings may be of value in the design of early intervention trials for risk stratification and prognostication but need to be validated with a prospective analysis.
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http://dx.doi.org/10.1016/j.jcjo.2021.01.005DOI Listing
February 2021

Quantitative assessment of choriocapillaris flow deficits in eyes with macular neovascularization.

Graefes Arch Clin Exp Ophthalmol 2021 Jan 8. Epub 2021 Jan 8.

Doheny Eye Institute, Los Angeles, CA, USA.

Purpose: To investigate choriocapillaris flow deficits (CC FD) in a group of eyes with Type 3 macular neovascularization (MNV) versus a group of eyes with Type 1 and/or 2 MNV versus healthy eyes.

Methods: In this cross-sectional, retrospective, multicenter, observational study, consecutive patients with Type 3 MNV, Type 1 and/or 2 MNV, and age-matched controls were included. PLEX Elite optical coherence tomography angiography was performed with a 6 × 6 mm scan pattern centered on the fovea. The CC FD was computed in 4 peripheral 1 × 1 mm squares to allow comparison between equidistant regions unaffected by MNV.

Results: Twenty Type 3, 20 Type 1 and/or 2 MNV [13 (65%) Type 1 MNV, 1 (5%) Type 2 MNV, and 6 (30%) mixed Type 1 and 2 MNV], and 20 age-matched controls were included. The mean impairment in the CC in the 4 peripheral squares was 16.07 ± 7.27% in Type 3 MNV eyes, 11.48 ± 5.59% in Type 1/2 MNV eyes, and 9.64 ± 3.59% in controls. Type 3 MNV displayed a statistically significantly higher CC FD compared with both Type 1/2 MNV (P = 0.031) and controls (P < 0.0001). No significant differences were observed between Type 1/2 MNV and controls (P = 0.223).

Conclusions: CC FD was significantly greater in the peripheral macular regions of eyes with Type 3 MNV compared to eyes with Type 1/2 MNV and normal control eyes. Pathogenic choroidal mechanisms may differ in eyes with different MNV subtypes. Whereas focal CC impairment may drive the development of Type 1/2 MNV, diffuse CC disruption may be more important in eyes with Type 3 MNV.
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http://dx.doi.org/10.1007/s00417-020-05056-1DOI Listing
January 2021

Long-term visual and anatomic outcomes of patients with peripapillary pachychoroid syndrome.

Br J Ophthalmol 2020 Dec 21. Epub 2020 Dec 21.

Stein Eye Institute, University of California Los Angeles, Los Angeles, California, USA.

Background/aims: To analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum.

Methods: This study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed.

Results: Fifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS.

Conclusion: Patients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315550DOI Listing
December 2020

Imaging Features Associated with Progression to Geographic Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 5.

Ophthalmol Retina 2020 Dec 22. Epub 2020 Dec 22.

Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Purpose: To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural OCT.

Design: Consensus meeting.

Participants: International group that included those with expertise in imaging and AMD basic science and histology, and those with Reading Center experience in AMD clinical trials.

Methods: As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA, risk of progression to GA, or both. Attendees undertook premeeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histologic features. Each of these different features were then discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees to refine the consensus definitions and descriptions further.

Results: Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypotransmission or hypertransmission), features frequently seen in eyes with atrophy (e.g., refractile drusen), and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits).

Conclusions: An international consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.
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http://dx.doi.org/10.1016/j.oret.2020.12.009DOI Listing
December 2020

Optical coherence tomography angiography analysis of the retina in patients recovered from COVID-19: a case-control study.

Can J Ophthalmol 2021 02 14;56(1):24-30. Epub 2020 Nov 14.

Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA.

Objective: To quantify the density of the macular microvasculature and the area of the foveal avascular zone (FAZ) in patients recovered from coronavirus disease 2019 (COVID-19) using optical coherence tomography angiography (OCTA) analysis.

Methods: In a comparative cross-sectional, observational study, patients recovered from COVID-19 were included in this study. All included subjects exhibited a reverse transcription-polymerase chain reaction-confirmed diagnosis of COVID-19. Spectral domain macular OCTA was performed at least 2 weeks after recovery from systemic COVID-19. Vessel density (VD) of the superficial (SCP) and deep retinal capillary plexus (DCP) and the area of the FAZ were measured in COVID-19 recovered patients versus age-matched normal controls.

Results: Thirty-one recovered COVID-19 patients and 23 healthy normal controls were studied. Mean quality scan index was 7.64 ± 0.66 in the COVID cases and 8.34 ± 0.71 in the normal controls (p = 0.001). Mean SCP VD and DCP VD of the COVID cohort were significantly lower than the SCP VD and DCP VD of the control group in the foveal and parafoveal regions. FAZ area was greater in the COVID cohort, but this difference was not statistically significant. In addition, in the COVID cohort, VD of the SCP was lower in patients with a history of COVID-19 hospitalization versus those without such a history, but this did not reach statistical significance.

Conclusions: Patients recovered from COVID-19 displayed alterations in the retinal microvasculature, including a significantly lower VD in the SCP and DCP. Patients with coronavirus infection may be at risk of retinal vascular complications.
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http://dx.doi.org/10.1016/j.jcjo.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666612PMC
February 2021

Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum.

JAMA Ophthalmol 2021 01;139(1):113-118

Cornea Society, Fairfax, Virginia.

In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities. Furthermore, the emerging role of artificial intelligence in ophthalmic imaging was reviewed. This article summarizes the presentations, discussion, and future directions.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.4994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005310PMC
January 2021

Spontaneous macular hole closure after posterior vitreous detachment in an eye with hyperreflective OCT stress line.

Am J Ophthalmol Case Rep 2020 Dec 29;20:100950. Epub 2020 Sep 29.

Retina Disorders and Ophthalmic Genetics, Stein Eye Institute, University of California-Los Angeles, Los Angeles, CA, USA.

Purpose: The aim of this report is to describe a patient who presented with a central hyper-reflective line (HRL) with spectral domain-optical coherence tomography (SD-OCT) after posterior vitreous detachment that evolved to full thickness macular hole (FTMH) with subsequent spontaneous resolution.

Observations: A 59-year-old patient presented with a history of photopsia and floaters followed by the development of a central scotoma in the right eye (OD). The left eye (OS) was normal. On examination, visual acuity (VA) was 20/20- OD and 20/20 OS. Retinal examination OD was remarkable for a retinal tear, and SD-OCT demonstrated a central HRL. The patient underwent laser retinopexy to barricade the retinal tear. Sequential SD-OCT of the macula was performed and the patient eventually developed a small FTMH 8 months after the baseline presentation. VA was correspondingly reduced to 20/80 OD. Upon return after 4 months, the hole was completely resolved with improvement of VA to 20/20 OD.

Conclusion: Vitreomacular traction (VMT) may lead to foveal dehiscence. This instability can be detected with SD-OCT as a vertical hyperreflective stress line that is a risk factor for progression to a FTMH. With release of VMT, FTMH can spontaneously close.
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http://dx.doi.org/10.1016/j.ajoc.2020.100950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644851PMC
December 2020

Nodular Epiretinal Gliosis in the Fovea.

Ophthalmol Retina 2020 Nov 13. Epub 2020 Nov 13.

Doheny Eye Institute, University of California at Los Angeles, Los Angeles, California; Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2020.11.001DOI Listing
November 2020

Meticulous multimodal analysis of aflibercept therapy for submacular vascularized pigment epithelial detachment associated with neovascular AMD in a prospective case series, the EVEN study.

Am J Ophthalmol Case Rep 2020 Dec 18;20:100916. Epub 2020 Sep 18.

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

Purpose: This prospective case series investigates the visual and anatomical outcomes including detailed volumetrics of eyes with vascularized pigment epithelial detachments (PED) treated with aflibercept in eyes with neovascular age-related macular degeneration (nAMD) through meticulous analysis in a reading center setting.

Methods: We conducted a single-arm multicenter, prospective, open-labeled, interventional case series, comparing visual and anatomic outcomes at 12 months with baseline for intense aflibercept therapy. Eyes with submacular vascularized PED due to AMD received 2.0 mG of intravitreal aflibercept at baseline and then monthly for 6 months. During the subsequent 6 months, mandatory aflibercept therapy was given for every other month, while additional aflibercept injections were allowed between mandatory injections if necessary, at 4 weeks after last injection, contingent on pre-defined visual and anatomic re-treatment criteria. Standardized ETDRS vision measurement, anterior and posterior segment examination, and high-density spectral-domain optical coherence tomography scans were obtained at baseline and monthly, while fundus photography and fluorescein angiography were obtained at baseline, 3,6, and 12 months. Indocyanine-green angiography was obtained at baseline and 3 months. Meticulous multidimensional assessment of the scanned multimodal serial images was then performed by Doheny Image Reading Center.

Results: Of 36 eyes and patients with mean age of 80, mean baseline and 12-month-ETDRS BCVA was 59 ± 8.9 letters (20/66), and 65 ± 27 letters (20/50), respectively; (6.5 letters improvement, p = 0.02). Significant reductions from baseline to month-12 were noted for multiple anatomic measures, including PED maximum height, entire lesion and central 1-mm subfield of PED mean thickness and volume, and mean subretinal hyperreflective material (SHRM) thickness and volume, also entire lesion of retinal thickness, retinal volume, and mean subretinal fluid (SRF) thickness (mean reductions in magnitude ranging from 37.5 to 91.7%, all p < 0.001). FA measurements also showed significant decrease from baseline to month-12, including area and greatest linear diameter (GLD) of fibrovascular PED, area and GLD of NV area and leakage (mean reductions in magnitude from 41.9 to 87.7%, p value from 0.002 to <0.001). This case series shows that while majority of reductions in SRF volume occurred during first month from baseline, majority of reduction in retinal, PED, and SHRM volumes occurred during first 2 months after onset of anti-VEGF injections. RPE tears developed in 5 eyes (13.9%) correlating with eyes with large PED height and volume at baseline (mean height >800 μm, mean volume >4 mm). Geographic atrophy (GA) was noted in only 1 eye at baseline, but in 16 eyes (44.4%) by 12 months.

Conclusions And Importance: Significant improvement in vision and anatomic measures including volumetrics of vPED were noted at 12 months after aflibercept therapy. Besides substantial PED height, large PED volume at baseline also correlated with RPE tears in 13.9% of eyes with vPED after anti-VEGF therapy. Reduction in SHRM correlated directly with decrease in PED, and more than 40% of study eyes developed GA by 12 months following intense anti-VEGF therapy.
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http://dx.doi.org/10.1016/j.ajoc.2020.100916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527713PMC
December 2020

Comparison of vitreoretinal disorders in fellow eyes of lamellar macular holes versus epiretinal membrane foveoschisis.

Graefes Arch Clin Exp Ophthalmol 2020 Dec 3;258(12):2611-2619. Epub 2020 Oct 3.

Retina Division, Stein Eye Institute, University of California Los Angeles, 100 Stein Plaza, Los Angeles, CA, USA.

Purpose: To evaluate and compare the rate and characteristics of vitreoretinal disorders in fellow eyes of lamellar macular holes (LMH) versus epiretinal membrane foveoschisis (ERMF).

Methods: Included patients in this retrospective study were divided into two groups based on spectral-domain optical coherence tomography (SD-OCT) features of their primary eye: LMH (group A) and ERMF (group B).

Results: Ninety-four patients were enrolled: 59 (62.8%) in group A and 35 (37.2%) in group B. Fellow eyes in group A had a higher rate of retinal detachment (8/59 [13.6%] vs. 0/35 [0%], P = 0.024), and full-thickness macular hole (FTMH) (11/59 [18.6%] vs. 2/35 [5.7%], P = 0.079), compared with fellow eyes in group B. In group A, 4/59 patients (6.8%) showed a bilateral LMH while none from group B had a LMH in their fellow eye (0/35 [0%]), P = 0.293. Additionally, epiretinal proliferation was noted in 30/59 (50.8%) fellow eyes in group A versus 3/35 (8.6%) fellow eyes in group B, P < 0.001. Longitudinal data were available for 80/94 patients. Over a mean follow-up of 37.4 ± 29.9 months, 1/48 (2.1%) fellow eyes from group A developed a FTMH and 2/48 (4.2%) developed a LMH, while no FTMH or LMH occurred in fellow eyes of group B.

Conclusions: Fellow eyes of LMH showed a high rate of macular and peripheral vitreoretinal disorders. In addition, epiretinal proliferation was detected in a higher number of fellow eyes of LMH versus ERMF. These findings suggest a bilateral process in eyes of patients with LMH.
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http://dx.doi.org/10.1007/s00417-020-04950-yDOI Listing
December 2020

PAMM and the ischemic cascade associated with radiation retinopathy.

Am J Ophthalmol Case Rep 2020 Dec 8;20:100918. Epub 2020 Sep 8.

Stein Eye Institute, Department of Ophthalmology, University of California, David Geffen School of Medicine, Los Angeles (UCLA), CA, USA.

Purpose: To report a case of paracentral acute middle maculopathy (PAMM) and evidence of the ischemic cascade documented with spectral domain optical coherence tomography (SD-OCT) following radiation treatment of a choroidal melanoma.

Observations: A healthy young patient was evaluated for an asymptomatic choroidal nevus in the left eye. Fundus examination was remarkable for a choroidal melanocytic lesion that measured 1.8 mm in thickness by initial B-scan ultrasound. Clinical examination 6 months later showed growth of the tumor at several margins with new subretinal fluid, and a B-scan measured thickness of 1.9 mm. The lesion was diagnosed as a small choroidal melanoma and treated with gamma knife radiation with a dose of 3000 cGy. Sixteen months later, examination showed signs of radiation retinopathy including cotton wool spots and PAMM via SD-OCT and OCT angiography and evidence of the ischemic cascade (i.e., alternating zones of middle and combined middle and inner retinal layer infarction).

Conclusions: Radiation retinopathy can include signs of microvascular damage and ischemia including lesions such as cotton wool spots and PAMM. A case is presented in this report of radiation retinopathy with OCT evidence of PAMM and the ischemic cascade.
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http://dx.doi.org/10.1016/j.ajoc.2020.100918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495006PMC
December 2020

Multimodal Imaging of CRB1 Retinitis Pigmentosa with a Peripheral Retinal Tumor.

Retin Cases Brief Rep 2020 Sep 21. Epub 2020 Sep 21.

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California, United States.

Purpose: To report the multimodal imaging findings of a patient with CRB1-associated retinitis pigmentosa (RP) characterized by preservation of para-arteriolar retinal pigment epithelium and a peripheral retinal tumor.

Methods: Case report.

Patient: A 27 year-old woman was referred to our center due to progressive decreased vision in both eyes with a diagnosis of CRB1-associated RP. Fundus examination was remarkable for attenuated retinal vessels and bone spicule migration that was bilateral and symmetric. In addition, an elevated yellow-white mass with dilated retinal vessels was noted in the superotemporal mid-periphery of the retina in the left eye without any associated exudation.

Results: Diffuse retinal pigment epithelium mottling was present but spared the area along the retinal arterioles. Swept-source optical coherence tomography (OCT) showed diffuse outer retinal atrophy. OCT angiography (OCTA) of the peripheral lesion illustrated extensive vascularity and a possible retinal feeder vessel communicating with the tumor at its inferior margin. The phenotype of the lesion showed overlap with a vasoproliferative tumor or an astrocytic hamartoma. Over a period of 5 years of follow-up, the peripheral tumor was unchanged. No significant progression of the peripheral retinal degeneration was evidenced by autofluorescent imaging over this time period although the central acuity continued to decrease.

Discussion: CRB1-associated RP may be characterized by preservation of para-arteriolar retinal pigment epithelium and slow progression, and may also feature a benign peripheral retinal tumor.
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http://dx.doi.org/10.1097/ICB.0000000000001058DOI Listing
September 2020

The Expanded Clinical Spectrum of Coxsackie Retinopathy.

Ophthalmic Surg Lasers Imaging Retina 2020 09;51(9):529-532

The authors present two cases of coxsackie retinopathy that presented with the classic findings of acute outer retinal disruption that evolved to an outer retinal scar. In these two cases, the classic lesions displayed an extramacular distribution. The authors provide detailed multimodal imaging in both cases highlighting the nature of the lesions. It is important to consider coxsackie virus infection in the differential diagnosis of extramacular lesions with outer retinal disruption. The term "unilateral acute idiopathic maculopathy" should be replaced with "coxsackie retinopathy" to better align with the expanded clinical spectrum and the known etiology of this disorder. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:529-532.].
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http://dx.doi.org/10.3928/23258160-20200831-08DOI Listing
September 2020

BRANCH RETINAL ARTERY OCCLUSION WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY PRESUMABLY RELATED TO HEAVY CANNABIS USE.

Retin Cases Brief Rep 2020 Sep 16. Epub 2020 Sep 16.

Stein Eye Institute, University of California-Los Angeles School of Medicine, Los Angeles.

Purpose: To report a case of branch retinal artery occlusion associated with paracentral acute middle maculopathy on spectral domain-optical coherence tomography (SD-OCT) presumably related to heavy cannabis consumption.

Methods: Retrospective case report. SD-OCT, fluorescein angiography and OCT angiography were performed.

Results: A 21-year-old healthy man described the acute onset of superior visual field loss in his right eye. He admitted smoking approximately 15 grams daily of cannabis for several weeks during COVID-19 confinement. Ophthalmoscopic examination of the right eye showed inferotemporal retinal whitening. SD-OCT illustrated evidence of the ischemic cascade with diffuse hyperreflectivity of the inner and middle retinal layers within the central region of the retinal infarct and paracentral acute middle maculopathy at the border of the infarct. Optical coherence tomography angiography demonstrated predominant flow signal loss at the level of the deep retinal capillary plexus. Fluorescein angiography and complete systemic workup were unremarkable.

Conclusion: Branch retinal artery occlusion and paracentral acute middle maculopathy may be related to heavy cannabis use as the result of transient arterial vasospasm.
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http://dx.doi.org/10.1097/ICB.0000000000001051DOI Listing
September 2020

Non-neovascular age-related macular degeneration with subretinal fluid.

Br J Ophthalmol 2020 Sep 12. Epub 2020 Sep 12.

Ophthalmology, University of Bonn, Bonn, Germany.

Purpose: To evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes.

Methods: This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes.

Results: Forty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy.

Conclusion: Non-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317326DOI Listing
September 2020

Multimodal Imaging Features and Clinical Relevance of Subretinal Lipid Globules.

Am J Ophthalmol 2021 02 9;222:112-125. Epub 2020 Sep 9.

Unit of Macula, Oftalvist Clinic, Valencia, SP.

Purpose: To describe the presence of subretinal lipid globules (SLG), analyze the multimodal imaging features inherent in their optical properties, and provide a means to distinguish them from other retinal structures and clinical signs.

Design: Retrospective cohort study.

Methods: The clinical data and multimodal imaging features of 39 patients (49 eyes) showing SLG were evaluated. Patients underwent color fundus photography, near-infrared reflectance (NIR), spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) and OCT angiography. In vitro phantom models were used to model OCT optical properties of water, mineral oil, and intralipid droplets and to investigate the optical mechanisms producing hypertransmission tails beneath SLG.

Results: The SLG were not visible in color fundus photographs or in NIR images. With both SD- and SS-OCT B-scans, SLG appeared as 31-157 μm, round, hyporeflective structures demonstrating a characteristic hypertransmission tail previously described with lipid globules found in the choroid and in neovascular membranes. Similarly, with en face OCT, SLG appeared as small, round, hyporeflective structures. SLG were encountered most often in eyes with neovascular age-related macular degeneration (AMD) that had type 1 macular neovascularization (MNV) (91.1%). Of those eyes, 93.3% were receiving intravitreal antivascular endothelial growth factor (VEGF) therapy (median of 15 injections) with a mean follow-up of 52.6 months. The number of prior injections positively correlated with the number of SLG. The detection of MNV preceded the presence of SLG in 66.7% of cases. En face OCT showed that, in many eyes (49%), SLG appeared in clusters of >10. In 38.8% of eyes, SLG were found overlying type 1 MNV, and in 44.9% of eyes, often those with more numerous SLG, the SLG were located near the lesion border. In 2 eyes with AMD followed for nonexudative type 1 MNV, SLG were detected prior to the detection of other imaging signs of exudation. SLG were observed in several other exudative macular diseases. Phantom models demonstrated that the hypertransmission tail beneath SLG is related to a lensing effect produced by these hyporeflective spherical structures.

Conclusions: SLG are a newly recognized OCT feature frequently seen in eyes receiving intravitreal anti-VEGF therapy for type 1 MNV due to AMD. OCT B-scans show SLG as small, round, hyporeflective structures with a characteristic hypertransmission tail. This OCT signature is influenced by the OCT focal plane, and it relates to reduced signal attenuation through oil and a lensing effect created by a higher refractive index compared to surrounding tissue.
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http://dx.doi.org/10.1016/j.ajo.2020.09.003DOI Listing
February 2021

Choriocapillaris Flow Deficits and Treatment-Naïve Macular Neovascularization Secondary to Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2020 09;61(11):11

Retina Disorders and Ophthalmic Genetics, Stein Eye Institute, University of California-Los Angeles, Los Angeles, California, United States.

Purpose: To evaluate choriocapillaris (CC) flow deficits (FD) in eyes with treatment-naïve macular neovascularization (MNV) and to compare CC FD around exudative versus nonexudative MNV.

Methods: Treatment-naïve eyes with a diagnosis of either exudative or nonexudative AMD and type 1 MNV were included. Normal control eyes were age-matched to each AMD eye one to one. En face optical coherence tomography angiograms were analyzed for percentage of CC FD (FD%) in two concentric 500 µm rings, ring 1 and ring 2, surrounding the dark halo around MNV. The mean CC FD% in ring 1 and ring 2 was evaluated for each eye. A secondary analysis was similarly carried out to investigate the differences in CC FD% in exudative versus nonexudative treatment-naïve MNV.

Results: Twenty-three eyes with treatment-naïve MNV were age matched with 23 normal controls. The mean CC FD% was significantly greater in both rings in the MNV versus the normal control group (P < 0.05) and was significantly greater in the inner ring, closer to the lesion, than the outer ring. The mean FD% was also greater in both rings in the exudative versus the nonexudative MNV group, but this difference did not reach statistical significance.

Conclusions: The CC FD% was greater in the area surrounding MNV versus age-matched normal controls and in the ring closer to the MNV lesion. Further, CC FD was greater in eyes with exudative versus nonexudative MNV in both rings surrounding the associated dark halo, although this difference was not statistically significant.
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http://dx.doi.org/10.1167/iovs.61.11.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488611PMC
September 2020

Paracentral acute middle maculopathy and the organization of the retinal capillary plexuses.

Prog Retin Eye Res 2021 Mar 9;81:100884. Epub 2020 Aug 9.

Retina Disorders and Ophthalmic Genetics, Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, United States; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Greater Los Angeles VA Healthcare Center, Los Angeles, CA, United States. Electronic address:

The retinal capillary vasculature serves the formidable role of supplying the metabolically active inner and middle retina. In the parafoveal region, the retinal capillary plexuses (RCP) are organized in a system of three capillary layers of varying retinal depths: the superficial capillary plexus (SCP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). While the dynamic flow through these plexuses is complex and not completely understood, current research points to a hybrid model that includes both parallel and in series components in which blood flows in a predominantly serial direction between the superficial vascular complex (SVC) and deep vascular complex (DVC). Each capillary plexus autoregulates independently, so that under most conditions the retinal vasculature supplies adequate blood flow and oxygen saturation at varying depths despite diverse environmental stressors. When the flow in the deep vascular complex (i.e. ICP and DCP) fails, an ischemic lesion referred to as Paracentral Acute Middle Maculopathy (PAMM) can be identified. PAMM is an optical coherence tomography (OCT) finding defined by the presence of a hyperreflective band at the level of the inner nuclear layer (INL) that indicates INL infarction caused by globally impaired perfusion through the retinal capillary system leading to hypoperfusion of the DVC or specifically the DCP. Patients present with an acute onset paracentral scotoma and typically experience a permanent visual defect. Lesions can be caused by a diverse set of local retinal vascular diseases and systemic disorders. PAMM is a manifestation of the retinal ischemic cascade in which the mildest forms of ischemia develop at the venular end of the DCP, i.e. perivenular PAMM, while more severe forms progress horizontally to diffusely involve the INL, and the most severe forms progress vertically to infarct the inner retina. Management is targeted toward the identification and treatment of related vasculopathic and systemic risk factors.
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http://dx.doi.org/10.1016/j.preteyeres.2020.100884DOI Listing
March 2021

Macular microvascular changes after intravitreal bevacizumab injection in diabetic macular edema.

Can J Ophthalmol 2021 Feb 6;56(1):57-65. Epub 2020 Aug 6.

Stein Eye Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Greater Los Angeles VA Healthcare Center, Los Angeles, CA, USA.

Objective: To evaluate the changes in retinal capillary plexus and the choriocapillaris after a single intravitreal injection of bevacizumab in eyes with diabetic macular edema using optical coherence tomography angiography (OCTA).

Design: Prospective interventional case series.

Participants: Patients having diabetes with centre-involving diabetic macular edema.

Methods: In this prospective interventional case series, eyes with centre-involving diabetic macular edema were enrolled. Vascular density (VD), vascular diameter index (VDI), vascular length density (VLD), foveal avascular zone (FAZ) area, and foveal density (FD)-300 were measured using en face OCTA images before and 1 month after administration of intravitreal bevacizumab. VD and VDI measurements were performed in the superficial capillary plexus (SCP) and deep retinal capillary plexus (DCP) and in the choriocapillaris. Additionally, capillary nonperfusion area (CNPA) was detected automatically based on vessel distance map in 4 concentric rings around the foveal centre. The segmentation error was manually corrected, and the measurements were performed by 2 expert graders.

Results: Twenty-three eyes of 19 patients with a mean age of 62.76 ± 6.88 years were included. There were no significant changes in the FAZ area, FD-300, or in the VD of the foveal and parafoveal SCP and DCP. Also, VLD and VDI of the SCP and DCP remained unchanged. The change in the CNPA was not statistically significant. The VD of choriocapillaris increased significantly after injections (p = 0.005).

Conclusions: FAZ area and VD of the retinal capillary plexus remained stable in the short-term period after intravitreal bevacizumab. In addition, the choriocapillaris blood flow improved after bevacizumab injection.
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http://dx.doi.org/10.1016/j.jcjo.2020.07.004DOI Listing
February 2021

Beware of What Lurks Beneath: Nonexudative Macular Neovascularization.

Ophthalmol Retina 2020 07;4(7):649-650

Stein Eye Institute, University of California, Los Angeles, California; VA Greater Los Angeles Healthcare System, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2020.04.003DOI Listing
July 2020