Publications by authors named "Philip J Rosenfeld"

228 Publications

Replacement of polyps with type 1 macular neovascularization in polypoidal choroidal vasculopathy imaged with swept source OCT angiography.

Am J Ophthalmol Case Rep 2021 Jun 11;22:101057. Epub 2021 Mar 11.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: To investigate the morphological changes of polyps in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors using swept source optical coherence tomography angiography (SS-OCTA).

Observations: Following anti-VEGF therapy, polyps were found to evolve into typical type 1 macular neovascularization (MNV) in five eyes. In all of these five eyes, a polypoidal lesion was detected adjacent to a serous or hemorrhagic retinal pigment epithelial detachment (PED).

Conclusions And Importance: Polypoidal lesions in PCV can evolve into typical type 1 MNV. This morphological evolution suggests that these polyps are clusters of tangled vessels that can proliferate into a more typical neovascular pattern, and this evolution may be facilitated by being adjacent to a PED. Since this morphological appearance could be associated with a better prognosis, SS-OCTA might be helpful in identifying cases of transformed polyps that may be associated with a decreased risk for vision loss.
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http://dx.doi.org/10.1016/j.ajoc.2021.101057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995480PMC
June 2021

Widefield optical coherence tomography monitoring of the peri-venular fern-like pattern of paracentral acute middle maculopathy.

Am J Ophthalmol Case Rep 2021 Jun 10;22:101047. Epub 2021 Mar 10.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: To demonstrate the ability of widefield swept source optical coherence tomography (OCT) imaging to monitor peri-venular fern-like patterns of paracentral acute middle maculopathy (PAMM) associated with retinal arterial occlusions.

Observations: The peri-venular fern-like pattern of PAMM was diagnosed on the 12 × 12 mm structural OCT images from three patients. Fluorescein angiography images were unremarkable. Over time, all three patients demonstrated significant improvement in visual acuity with resolution of their peri-venular PAMM.

Conclusions: The peri-venular fern-like pattern of PAMM is usually associated with retinal vein occlusions, but we identified three cases with this pattern in eyes with presumed incomplete retinal arterial occlusions. Our cases support the ischemic cascade theory that begins within the deep capillary plexus and ascends in the retina depending on the severity of the ischemic event. Using the 12 × 12 mm structural OCT images, we are able to demonstrate a wider area of ischemia in PAMM compared with the traditional 6 × 6 mm scans.
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http://dx.doi.org/10.1016/j.ajoc.2021.101047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973291PMC
June 2021

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

Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan.

Am J Ophthalmol 2021 Mar 3. Epub 2021 Mar 3.

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina. Electronic address:

Purpose: To evaluate the effect of select baseline characteristics on geographic atrophy (GA) progression in eyes receiving intravitreal pegcetacoplan or sham.

Design: Phase 2 multicenter, randomized, single-masked, sham-controlled trial.

Methods: Patients with GA received 15 mg pegcetacoplan monthly or every other month (EOM), or sham injection monthly or EOM for 12 months. Primary efficacy endpoint was change in GA lesion size (square root) from baseline. Post hoc analysis evaluated the effects of age; gender; lesion size, focality, and location (extrafoveal vs foveal); pseudodrusen status; best corrected visual acuity (BCVA); and low luminance deficit (LLD) on GA progression at month 12.

Results: Of 246 randomized patients, 192 with 12-month data were included in this analysis. Overall mean (standard deviation) change in lesion size (mm) was 0.26 (0.17) (P < .01), 0.27 (0.27) (P < .05), and 0.36 (0.21) in the monthly pegcetacoplan (n = 67), EOM pegcetacoplan (n = 58), and sham (n = 67) groups, respectively. In univariate analysis, patients with extrafoveal lesions (P < .001), BCVA ≥ 20/60 (P = .001), and larger LLD (P = .002) had greater mean changes in lesion size. Multivariate analysis confirmed significant association of extrafoveal lesions (P = .001) and larger LLD (P = .023) with GA progression. Monthly and EOM pegcetacoplan significantly reduced progression (P < .05) when controlling for these risk factors.

Conclusions: Extrafoveal lesions and larger LLD are potential risk factors for GA progression. Pegcetacoplan treatment significantly controlled GA progression even after accounting for these risk factors.
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http://dx.doi.org/10.1016/j.ajo.2021.02.031DOI Listing
March 2021

A Novel Method to Detect and Monitor Retinal Vasculitis Using Swept-Source OCT Angiography.

Ophthalmol Retina 2021 Feb 19. Epub 2021 Feb 19.

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

Purpose: To introduce a novel method for assessment of retinal vasculitis using swept-source OCT angiography (SS-OCTA).

Design: Retrospective case series.

Participants: Patients with retinal vasculitis.

Methods: The subjects were identified among the clinic population and imaged with 12 × 12-mm SS-OCTA scans centered on the fovea. A custom retina segmentation superimposed the color retinal thickness map on a modified en face flow scan. Findings from en face flow scans were correlated with localized perivascular retinal thickening on B-scans. Results from SS-OCTA were compared with fluorescein angiography (FA) to examine the proportion of perivascular thickening to retinal vascular leakage or staining.

Results: Twenty-one patients with retinal vasculitis underwent same-day FA and SS-OCTA. Visible retinal vascular leakage/staining on FA corresponded to increased perivascular retinal thickness on SS-OCTA in 17 patients. Five patients had a second examination with same-day FA and SS-OCTA after treatment of the vasculitis. Three of those 5 patients showed improved retinal vascular leakage/staining on post-treatment FA and decreased perivascular retinal thickness on SS-OCTA scans.

Conclusions: Swept-source OCT angiography detects structural retinal thickening secondary to inflammatory retinal vascular leakage. Further studies are required to confirm whether SS-OCTA may serve as a semiquantitative alternative to FA to diagnose and monitor the response to treatment in patients with retinal vasculitis.
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http://dx.doi.org/10.1016/j.oret.2021.02.007DOI Listing
February 2021

Persistent Hyper-Transmission Defects on En Face OCT Imaging as a Stand-Alone Precursor for the Future Formation of Geographic Atrophy.

Ophthalmol Retina 2021 Feb 18. Epub 2021 Feb 18.

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

The presence of persistent choroidal hyper-transmission defects on custom en face OCT images can be used as a stand-alone precursor for the progression of drusen to geographic atrophy in age-related macular degeneration.
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http://dx.doi.org/10.1016/j.oret.2021.02.004DOI Listing
February 2021

Correlations Between Choriocapillaris and Choroidal Measurements and the Growth of Geographic Atrophy Using Swept Source OCTImaging.

Am J Ophthalmol 2020 Dec 24;224:321-331. Epub 2020 Dec 24.

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

Purpose: Correlations among enlargement rates (ERs) of geographic atrophy (GA) and choriocapillaris (CC) flow deficits (FDs), mean choroidal thickness (MCT), and choroidal vascularity index (CVI) were investigated using swept source-optical coherence tomography (SS-OCT) in age-related macular degeneration (AMD).

Design: A retrospective review of prospective, observational case series.

Methods: Eyes with GA from AMD were imaged with SS-OCT using 6 × 6-mm scan pattern. GA lesions were identified and measured using customized en face structural images, and annual square root ERs of GA were calculated. At baseline, choriocapillaris FDs from different regions outside the GA were measured, and MCT and CVI from the entire scan area were measured. All measurements were performed using previously published and validated algorithms.

Results: A total of 38 eyes from 27 patients were included. The CC FDs within each region around GA lesions were highly correlated with ERs of GA (all P < .005). CVI inside the GA region was correlated with the ERs (P = .03), whereas other choroidal measurements had no significant correlation with the ERs of GA (P > .06).

Conclusions: Statistically significant correlations were found between the ERs of GA and CC percentage of FD (FD%) from the entire scan region outside the GA and not just the region immediately adjacent to the GA. These results suggest that abnormal CC perfusion throughout the macula contributes to disease progression in eyes with GA. CVI inside the GA region could also be a potential indicator for the growth of GA.
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http://dx.doi.org/10.1016/j.ajo.2020.12.015DOI 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

The Extent of Retinal Involvement of Canthaxanthin Crystalline Retinopathy Demonstrated by Multimodal Imaging.

Ophthalmic Surg Lasers Imaging Retina 2020 12;51(12):727-731

Limited information is known about the extent of canthaxanthin crystalline retinopathy on the retinal layers. The authors describe a 51-year-old woman who was taking canthaxanthin for tanning purposes for 7 years. Three years after cessation of this agent, she presented with asymmetric crystalline retinopathy affecting both eyes. She was lost to follow-up, and upon returning 4 years later, the crystalline retinopathy persisted but the number of crystals had decreased. Using swept-source optical coherence tomography, the authors showed that the crystalline retinopathy affected all retinal layers. In addition, retinal pigmented epithelial detachments were present suggesting persistent damage caused by the canthaxanthin. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:727-731.].
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http://dx.doi.org/10.3928/23258160-20201202-08DOI Listing
December 2020

Comparison Between Graders in Detection of Diabetic Neovascularization With Swept Source Optical Coherence Tomography Angiography and Fluorescein Angiography.

Am J Ophthalmol 2020 Dec 11;224:292-300. Epub 2020 Dec 11.

Bascom Palmer Eye Institute, Miami, Florida, USA. Electronic address:

Purpose: We compared the ability of ophthalmologists to identify neovascularization (NV) in patients with proliferative diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA).

Design: Retrospective study comparing diagnostic instruments.

Methods: Eyes with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy and a high suspicion of NV based on clinical examination were imaged using SS-OCTA and FA at the same visit. Two separate grading sets consisting of scrambled, anonymized SS-OCTA and FA images were created. The ground truth for presence of NV was established by consensus of 2 graders with OCTA experience who did not participate in the subsequent assessment of NV in this study. The 2 anonymized image sets were graded for presence or absence of NV by 12 other graders that included 2 residents, 6 vitreoretinal fellows, and 4 vitreoretinal attending physicians. The percentage of correct grading of NV using SS-OCTA and FA was assessed for each grader and across grader training levels.

Results: Forty-seven eyes from 24 patients were included in this study. Overall, the mean percentage of correct NV grading was 87.8% using SS-OCTA with B-scans and 86.2% using FA (P = .92). Assessing each grader individually, there was no statistically significant asymmetry in correct grading using SS-OCTA and FA.

Conclusions: Ophthalmologists across training levels were able to identify diabetic NV with equal accuracy using SS-OCTA and FA. Based on these results, SS-OCTA may be an appropriate standalone modality for diagnosing diabetic NV.
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http://dx.doi.org/10.1016/j.ajo.2020.11.020DOI Listing
December 2020

Reply to Comment on: Is this a 737 Max Moment for Brolucizumab?

Am J Ophthalmol 2021 03 10;223:446-447. Epub 2020 Nov 10.

Charlotte, North Carolina.

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http://dx.doi.org/10.1016/j.ajo.2020.06.034DOI Listing
March 2021

Dose-Response Relationship between Intravitreal Injections and Retinal Nerve Fiber Layer Thinning in Age-Related Macular Degeneration.

Ophthalmol Retina 2020 Oct 10. Epub 2020 Oct 10.

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

Purpose: To determine if multiple intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors for unilateral exudative age-related macular degeneration (eAMD) are associated with thinning of the retinal nerve fiber layer (RNFL), we compared RNFL thickness measurements from the injected eye with that of the fellow eye with nonexudative age-related macular degeneration (neAMD).

Design: Retrospective, cross-sectional study.

Participants: Patients undergoing anti-VEGF therapy for unilateral eAMD.

Methods: Patients receiving anti-VEGF therapy secondary to eAMD in 1 eye with neAMD in their fellow eye were identified. Patients with a known diagnosis of glaucoma were excluded. Spectral domain OCT measurements of the peripapillary RNFL thickness from both eyes were performed and compared. The differences in the RNFL thickness measurements between eyes were correlated with the number of injections and the duration of therapy.

Main Outcome Measures: Correlation between the number of anti-VEGF injections and peripapillary RNFL thinning.

Results: A total of 108 eyes of 54 patients were evaluated in this study. The average peripapillary RNFL thickness measurements of the injected eye and fellow eye were 87.3 ± 9.6 μm and 89.0 ± 7.5 μm, respectively (P = 0.055). The RNFL thickness difference (fellow eye minus injected eye) was significantly correlated with the number of injections (r = 0.40, P = 0.002) and months of injections (r = 0.38, P = 0.005). The relationship between the difference in the RNFL thickness and the number of injections had a nonlinear dose-response relationship that became apparent after approximately 30 injections and 50 months of injections.

Conclusions: The difference in RNFL thickness measurements between injected eyes and uninjected fellow eyes was largely within the reported normal limits for interocular differences between healthy eyes. Nevertheless, there was a dose-response relationship between RNFL thinning and number of injections among patients receiving a greater number of injections, suggesting that anti-VEGF injections may have a modest effect on the RNFL thickness after several years of therapy in eyes requiring more anti-VEGF injections; however, we cannot exclude that the RNFL thinning may be secondary to active age-related macular degeneration (AMD) disease progression in both eyes.
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http://dx.doi.org/10.1016/j.oret.2020.10.004DOI Listing
October 2020

Reply.

Ophthalmol Retina 2020 10;4(10):e11-e12

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

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http://dx.doi.org/10.1016/j.oret.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531339PMC
October 2020

Developing a potential retinal OCT biomarker for local growth of geographic atrophy.

Biomed Opt Express 2020 Sep 20;11(9):5181-5196. Epub 2020 Aug 20.

Department of Electrical Engineering and Computer Science, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Geographic atrophy (GA), the advanced stage of age-related macular degeneration, is a leading cause of blindness. GA lesions are characterized by anisotropic growth and the ability to predict growth patterns would be valuable in assessing potential therapeutics. In this study, we propose an OCT-based marker of local GA growth rate based on an axial projection of the OCT volume in the Henle fiber layer (HFL) and outer nuclear layer (ONL). We analyze the association between our proposed metric and local GA growth rates in a small longitudinal cohort of patients with AMD. These methods can potentially be used to identify risk markers, stratify patients, or assess response in future therapeutic studies.
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http://dx.doi.org/10.1364/BOE.399506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510858PMC
September 2020

Prediction of age-related macular degeneration disease using a sequential deep learning approach on longitudinal SD-OCT imaging biomarkers.

Sci Rep 2020 09 22;10(1):15434. Epub 2020 Sep 22.

Department of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA.

We propose a hybrid sequential prediction model called "Deep Sequence", integrating radiomics-engineered imaging features, demographic, and visual factors, with a recursive neural network (RNN) model in the same platform to predict the risk of exudation within a future time-frame in non-exudative AMD eyes. The proposed model provides scores associated with risk of exudation in the short term (within 3 months) and long term (within 21 months), handling challenges related to variability of OCT scan characteristics and the size of the training cohort. We used a retrospective clinical trial dataset that includes 671 AMD fellow eyes with 13,954 observations before any signs of exudation for training and validation in a tenfold cross validation setting. Deep Sequence achieved high performance for the prediction of exudation within 3 months (0.96 ± 0.02 AUCROC) and within 21 months (0.97 ± 0.02 AUCROC) on cross-validation. Training the proposed model on this clinical trial dataset and testing it on an external real-world clinical dataset showed high performance for the prediction within 3-months (0.82 AUCROC) but a clear decrease in performance for the prediction within 21-months (0.68 AUCROC). While performance differences at longer time intervals may be derived from dataset differences, we believe that the high performance and generalizability achieved in short-term predictions may have a high clinical impact allowing for optimal patient follow-up, adding the possibility of more frequent, detailed screening and tailored treatments for those patients with imminent risk of exudation.
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http://dx.doi.org/10.1038/s41598-020-72359-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508843PMC
September 2020

Guidelines for Imaging the Choriocapillaris Using OCT Angiography.

Am J Ophthalmol 2021 02 4;222:92-101. Epub 2020 Sep 4.

Department of Bioengineering, University of Washington, Seattle, Washington, USA; Department of Ophthalmology, University of Washington, Seattle, Washington, USA. Electronic address:

Purpose: To provide guidance on how to appropriately quantitate various choriocapillaris (CC) parameters with optical coherence tomography angiography (OCTA).

Design: Evidence-based perspective.

Methods: Review of literature and experience of authors.

Results: Accurate and reliable quantification of CC using OCTA requires that CC can be visualized and that the measurements of various CC parameters are validated. For accurate visualization, the selected CC slab must be physiologically sound, must produce images consistent with histology, and must yield qualitatively similar images when viewing repeats of the same scan or scans of different sizes. For accurate quantification, the measured intercapillary distances (ICDs) should be consistent with known measurements using histology and adaptive optics and/or OCTA, the selected CC parameters must be physiologically and physically meaningful based on the resolution of the instrument and the density of the scans, the selected algorithm for CC binarization must be appropriate and generate meaningful results, and the CC measurements calculated from multiple scans of the same and different sizes should be quantitatively similar. If the Phansalkar local thresholding method is used, then its parameters must be optimized for CC based on the OCTA instrument and scan patterns used. It is recommended that the window radius used in the Phansalkar method should be related to the expected average ICD in normal eyes.

Conclusions: Quantitative analysis of CC using commercially available OCTA instruments is complicated, and researchers need to tailor their strategies based on the instrument, scan patterns, anatomy, and thresholding strategies to achieve accurate and reliable measurements.
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http://dx.doi.org/10.1016/j.ajo.2020.08.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930158PMC
February 2021

Validation of a Compensation Strategy Used to Detect Choriocapillaris Flow Deficits Under Drusen With Swept Source OCT Angiography.

Am J Ophthalmol 2020 12 2;220:115-127. Epub 2020 Jul 2.

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

Purpose: A compensation strategy that was developed to measure the choriocapillaris (CC) flow deficits (FDs) under drusen was tested in eyes with large drusen from age-related macular degeneration (AMD) before and after the drusen spontaneously resolved without evidence of disease progression.

Design: Prospective, observational consecutive case series.

Methods: Patients with AMD were enrolled in a prospective swept-source optical coherence tomography (SS-OCT) imaging study. Consecutive eyes with large drusen were followed, and eyes that underwent spontaneous collapse of drusen without evidence of disease progression were identified retrospectively. The drusen-resolved regions were manually outlined. CC FDs were measured using a previously published compensation strategy that adjusted for the decreased signal intensity underlying drusen. Both the percentage of FDs (FD%) and the mean FD sizes (MFDSs) were measured before and after drusen resolution.

Results: Resolution of drusen was identified in 8 eyes from 8 patients. The average interval between the 2 visits was 7.8 months. The average drusen volumes measured between visits were 0.23 and 0.04 mm, respectively. After the drusen resolved, the average follow-up time without evidence of disease progression was 10.1 months. When the 2 visits were compared, there were no statistically significant differences in any of the CC parameters within the drusen resolved regions once the compensation strategy was applied (all P values >.22).

Conclusions: In this naturally occurring experiment in which drusen collapsed without evidence of disease progression, the CC parameters were similar once our compensation strategy was applied both before and after the drusen resolved.
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http://dx.doi.org/10.1016/j.ajo.2020.06.033DOI Listing
December 2020

Eliminating Visual Acuity and Dilated Fundus Examinations Improves Cost Efficiency of Performing Optical Coherence Tomogrpahy-Guided Intravitreal Injections.

Am J Ophthalmol 2020 11 2;219:222-230. Epub 2020 Jul 2.

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

Purpose: The clinic efficiency and cost savings achieved by eliminating formal visual acuity (VA) and dilated fundus examinations (DFEs) were assessed for established patients receiving optical coherence tomography (OCT)-guided intravitreal injections.

Design: Comparative cost analysis.

Methods: Two different treatment models were evaluated. The first model included patients undergoing routine VA assessment, DFEs, OCT imaging, and intravitreal injections. The second model eliminated the routine VA assessment and DFE while using OCT imaging through an undilated pupil followed by the intravitreal injection. The 2 models incorporated both bevacizumab and aflibercept. The number of patients per clinic day, the cost per visit, and the daily revenues were compared between the 2 models.

Results: Optimized schedules with and without VA assessments and DFEs allowed for 48 and 96 patients to be injected per day, respectively. Excluding drug costs, the cost per encounter for the visits with and without a DFE were $39.33 and $22.63, respectively. Including the drug costs, the costs per encounter for the visits with and without a DFE were $85.55 and $68.85 for bevacizumab and $1787.58 and $17770.88 for aflibercept, respectively. Once the reimbursements for each visit type were included, the clinics that eliminated the VA and DFEs were more cost efficient.

Conclusion: Eliminating both VA assessments and DFEs for patients undergoing OCT-guided retreatment with intravitreal injections resulted in decreased exposure times between patients and clinic staff, decreased cost per encounter, and increased patient volumes per clinic day, resulting in improved clinic efficiency and safety while seeing more patients in a clinic day.
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http://dx.doi.org/10.1016/j.ajo.2020.06.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329678PMC
November 2020

Longitudinal Angiographic Evidence That Intraretinal Microvascular Abnormalities Can Evolve into Neovascularization.

Ophthalmol Retina 2020 12 13;4(12):1146-1150. Epub 2020 Jun 13.

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

Purpose: The hallmark of proliferative diabetic retinopathy (PDR) is retinal neovascularization. Tortuous intraretinal vascular segments known as intraretinal microvascular abnormalities (IRMAs) are a known risk factor for neovascularization (NV), but whether IRMA represents a biomarker or a vascular precursor lesion to NV has not been demonstrated. The purpose of this study was to determine whether IRMA may evolve directly into NV.

Design: Retrospective analysis of prospective, observational case series.

Participants: Patients with treatment-naïve PDR.

Methods: Patients were imaged longitudinally with fluorescein angiography (FA) and swept-source (SS) OCT angiography (OCTA) before and after panretinal photocoagulation (PRP).

Main Outcome Measures: Presence and colocalization of IRMA and NV on serial FA and SS OCTA.

Results: Two PDR patients showed multiple NV and IRMA lesions at baseline examination. Three months after PRP, FA demonstrated profuse leakage from 3 new NV lesions in one patient and 1 new NV lesion in another patient. Multimodal imaging showed that these 4 lesions were IRMAs at baseline. Swept-source OCTA performed before PRP and 1 week, 1 month, and 3 months after PRP confirmed that the precursor IRMA lesions were intraretinal tortuous vascular lesions at baseline and that they developed into preretinal NV with contiguous intraretinal components. NV was found to develop and adhere to the posterior hyaloid even in areas of pre-existing hyaloidal detachment.

Conclusions: Diabetic retinal NV can develop from IRMA. Early identification of IRMAs may be an accurate means of predicting progression to PDR, and frequent monitoring of IRMAs with SS OCTA may facilitate early diagnosis of PDR.
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http://dx.doi.org/10.1016/j.oret.2020.06.010DOI Listing
December 2020

Is This a 737 Max Moment for Brolucizumab?

Am J Ophthalmol 2020 08 25;216:A7-A8. Epub 2020 May 25.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA.

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http://dx.doi.org/10.1016/j.ajo.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263271PMC
August 2020

A Comparison Study of Polypoidal Choroidal Vasculopathy Imaged with Indocyanine Green Angiography and Swept-Source Optical Coherence Tomography Angiography.

Am J Ophthalmol 2020 09 21;217:240-251. Epub 2020 May 21.

Department of Ophthalmology, Kyung Hee University Medical Center, Kyung Hee University, Seoul, South Korea. Electronic address:

Purpose: Indocyanine green angiography (ICGA) was compared with swept-source optical coherence tomography angiography (SS-OCTA) for the detection of polypoidal choroidal vasculopathy (PCV).

Design: Retrospective, cross-sectional.

Methods: Patients with treatment-naïve PCV based on ICGA imaging underwent same-day SS-OCTA imaging at Kyung Hee University Medical Center between April 2017 and November 2018. ICGA and SS-OCTA images were graded independently. SS-OCTA images were graded using both flow and structural information. Images were graded for the number of polypoidal lesions and the total lesion area, which included both the polypoidal lesions and the branching vascular networks (BVNs).

Results: A total of 31 eyes from 30 patients were enrolled. Polypoidal lesions were identified in all eyes using both modalities, and there was agreement on the number of polypoidal lesions in 17 eyes (55%). In 12 eyes (39%), SS-OCTA graders identified a greater number of polypoidal lesions, and in 2 eyes (6%) ICGA graders identified more lesions. There was no significant difference in the lesion area measurements (standard deviation = 1.09, P = .08). The lesion with the largest difference in area measurements resulted from focal areas of atrophy, misdiagnosed as polypoidal lesions on ICGA, and a low-lying serous retinal pigment epithelial detachment erroneously identified as part of the BVN by ICGA graders. SS-OCTA imaging correctly diagnosed the focal areas of atrophy and the serous retinal pigment epitheial detachment.

Conclusions: SS-OCTA imaging was comparable to ICGA for the diagnosis of treatment-naïve PCV. However, SS-OCTA might be better than ICGA in correctly identifying both polypoidal lesions and BVNs in treatment-naïve PCV.
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http://dx.doi.org/10.1016/j.ajo.2020.05.017DOI Listing
September 2020

Longitudinal Swept-Source OCT Angiography of Juxtapapillary Retinal Capillary Hemangioblastoma.

Ophthalmol Retina 2020 09 8;4(9):956-958. Epub 2020 May 8.

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.2020.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484327PMC
September 2020

Nonexudative Macular Neovascularization - A Systematic Review of Prevalence, Natural History, and Recent Insights from OCT Angiography.

Ophthalmol Retina 2020 07 13;4(7):651-661. Epub 2020 Mar 13.

Department of Ophthalmology, Centro Hospitalar e Universitário de São João, Porto, Portugal; Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. Electronic address:

Purpose: To review the available literature on the prevalence, incidence, natural history, and exudative conversion rates of subclinical (treatment-naïve) nonexudative macular neovascularization (MNV) in patients with age-related macular degeneration (AMD).

Clinical Relevance: Nonexudative MNV is now known to be more prevalent in patients with AMD than initially thought and is bringing new insights into both the natural history and management of this very prevalent disease.

Methods: We conducted a literature search on PubMed, Scopus, and Web of Science, along with a manual search, from January 2014 to June 2019. We included studies that used optical coherence tomography angiography (OCTA) as a primary diagnostic tool to evaluate subclinical (treatment-naïve), nonexudative, neovascular AMD.

Results: Of the 258 screened articles, 12 were included. The prevalence of subclinical nonexudative neovascular AMD in the fellow eyes of patients with unilateral exudative AMD ranged from 6.25% to 27%. Although these lesions were not associated with a significant decrease in visual acuity, the presence of nonexudative MNV seems to be an important predictor of exudative disease. Incidence of exudation in the reviewed studies ranged from 20% to 80% (follow-up 6 months to 2 years). There is some evidence that nonexudative MNV may slow down the growth of adjacent geographic atrophy (GA). As long as exudation does not occur, it appears that subclinical nonexudative MNV is not responsible for the deterioration of visual function.

Conclusions: Nonexudative MNV is an asymptomatic condition. Although nonexudative MNV seems to be a precursor for the formation of exudative neovascular AMD, there is evidence suggesting a protective effect in slowing the progression of GA. Early detection of nonexudative MNV before exudation develops should result in better monitoring of patients who are at high risk of conversion to exudative AMD. Though no controlled clinical trial has been performed to provide definitive recommendations, the authors of the studies included in this review agree that nonexudative lesions should not be treated until symptomatic exudation develops. Moreover, the existence of a nonexudative form of neovascular AMD would suggest that the term "neovascular AMD" should be preceded by either "exudative" or "nonexudative" when describing this neovascular stage of AMD.
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http://dx.doi.org/10.1016/j.oret.2020.02.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354220PMC
July 2020

Wide field swept source OCT angiography of multifocal retinal and choroidal occlusions from embolic triamcinolone acetonide.

Am J Ophthalmol Case Rep 2020 Jun 14;18:100704. Epub 2020 Apr 14.

Bascom Palmer Eye Institute, Miami, FL, USA.

Purpose: Multifocal retinal arterial occlusions and choroidal infarctions due to embolic triamcinolone acetonide (TA) administered during a septoplasty were imaged using swept source OCT angiography (SS-OCTA) to demonstrate the utility of this imaging modality for the diagnosis and longitudinal follow-up of retinal and choroidal vascular diseases.

Observations: A 37-year-old man presented with vision loss in his left eye upon awakening from a left-sided septoplasty during which TA was injected. Examination of the left eye demonstrated retinal whitening in the macula, white material in the distal lumen of retinal arterioles, and multifocal hypopigmented choroidal lesions. SS-OCTA imaging showed the absence of detectable flow in areas of retinal and choroidal whitening. Corresponding B-scans demonstrated hyperreflective material, thought to be embolic TA, within the retinal vessels and inner choroid.

Conclusions: Wide field SS-OCTA was sufficient for the diagnosis and longitudinal evaluation of retinal and choroidal occlusions without the need for dye-based angiography.
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http://dx.doi.org/10.1016/j.ajoc.2020.100704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170946PMC
June 2020

A2E Distribution in RPE Granules in Human Eyes.

Molecules 2020 Mar 20;25(6). Epub 2020 Mar 20.

Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

A2E (retinylidene-retinylethanolamine) is a major fluorophore in the RPE (retinal pigment epithelium). To identify and characterize A2E-rich RPE lipofuscin, we fractionated RPE granules from human donor eyes into five fractions (F1-F5 in ascending order of density) by discontinuous sucrose density gradient centrifugation. The dry weight of each fraction was measured and A2E was quantified by liquid chromatography/mass spectrometry (LC/MS) using a synthetic A2E homolog as a standard. Autofluorescence emission was characterized by a customer-built spectro-fluorometer system. A significant A2E level was detected in every fraction, and the highest level was found in F1, a low-density fraction that makes up half of the total weight of all RPE granules, contains 67% of all A2E, and emits 75% of projected autofluorescence by all RPE granules. This group of RPE granules, not described previously, is therefore the most abundant RPE lipofuscin granule population. A progressive decrease in autofluorescence was observed from F2 to F4, whereas no autofluorescence emission was detected from the heavily pigmented F5. The identification of a novel and major RPE lipofuscin population could have significant implications in our understanding of A2E and lipofuscin in human RPE.
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http://dx.doi.org/10.3390/molecules25061413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144568PMC
March 2020

Reply.

Ophthalmology 2020 04;127(4):e26

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

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http://dx.doi.org/10.1016/j.ophtha.2019.11.023DOI Listing
April 2020

Quantification of Choriocapillaris with Phansalkar Local Thresholding: Pitfalls to Avoid.

Am J Ophthalmol 2020 05 12;213:161-176. Epub 2020 Feb 12.

Department of Bioengineering, University of Washington, Seattle, Washington, USA; Department of Ophthalmology, University of Washington, Seattle, Washington, USA. Electronic address:

Purpose: To demonstrate the proper use of the Phansalkar local thresholding method (Phansalkar method) in choriocapillaris (CC) quantification with optical coherence tomography angiography (OCTA).

Design: Retrospective, observational case series.

Methods: Swept source OCTA imaging was performed using 3×3 mm and 6×6 mm scanning patterns. The CC slab was extracted after semiautomatic segmentation of the retinal pigment epithelium/Bruch membrane complex. Retinal projection artifacts were removed before further analysis, and CC OCTA images from drusen eyes were compensated using a previously published strategy. CC flow deficits (FDs) were segmented with 2 previously published algorithms: the fuzzy C-means approach (FCM method) and the Phansalkar method. With the Phansalkar method, different parameters were tested and a local window radius of 1 to 15 pixels was used. FD density, mean FD size, and FD number were calculated for comparison.

Results: Six normal eyes from 6 subjects and 6 eyes with drusen secondary to age-related macular degeneration from 6 subjects were analyzed. With both 3×3 mm and 6×6 mm scans from all eyes, the FD metrics were highly dependent on the selection of the local window radius when using the Phansalkar method. Larger window radii resulted in higher FD density values. FD number increased with the increase in the window radius but then decreased, with an inflection point at about 1 to 2 intercapillary distances. Mean FD size decreased then increased with increasing window radii.

Conclusions: Multiple parameters, especially the local window radius, should be optimized before using the Phansalkar method for the quantification of CC FDs with OCTA imaging. It is recommended that the proper use of the Phansalkar method should include the selection of the window radius that is related to the expected intercapillary distance in normal eyes.
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http://dx.doi.org/10.1016/j.ajo.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214221PMC
May 2020

Anti-Vascular Endothelial Growth Factor Therapy for Choroidal Rupture-Associated Choroidal Neovascularization.

Ophthalmol Retina 2020 02 21;4(2):226-228. Epub 2019 Sep 21.

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.2019.09.008DOI Listing
February 2020