Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Optical Coherence Tomography Angiography Analysis Toolbox: A Repeatable and Reproducible Software Tool for Quantitative Optical Coherence Tomography Angiography Analysis.

BACKGROUND AND OBJECTIVE: The purpose of this article is to demonstrate the optical coherence tomography angiography (OCTA) Analysis Toolkit (OAT), a custom-designed software package, as a repeatable and reproducible tool for computing OCTA metrics across different devices. MATERIALS AND METHODS: Fourteen participants were imaged using three devices. Foveal avascular zone, vessel index, vessel length index, and vessel diameter index were calculated using the OAT. Repeatability and reproducibility were assessed using the coefficient of variation and interclass correlation coefficient (ICC). RESULTS: Analysis of identical images demonstrated perfect levels of repeatability for all metrics (coefficient of variation 0%), which was a consequence of the software being deterministic (ie, producing the same outputs for the same inputs). Foveal avascular zone ICC values were in the excellent-to-good range (ICC > 0.6) for all devices. All values for vessel index (VI), vessel length index, and vessel diameter index fell in the good-to-fair (ICC > 0.4) or excellent-to-good range, except for vessel index analysis in the Cirrus device (ICC = 0.34). CONCLUSIONS: The OAT appears to be a reliable tool that may enable comparison between OCTA data sets acquired on different imaging instruments, thereby facilitating a more consistent approach to OCTA analysis. [Ophthalmic Surg Lasers Imaging Retina 2023;54:114-122.].

BILATERAL EPIRETINAL MEMBRANE FORMATION AFTER INTRAVITREAL INJECTIONS OF AUTOLOGOUS MESENCHYMAL STEM CELLS.

PURPOSE: The authors describe a case of new bilateral epiretinal membranes and vitreous cells after intravitreal and sub-Tenon's injections of bone marrow-derived stem cells. METHODS: A case report of a 43-year-old man with OPA-1 autosomal dominant optic atrophy who self-enrolled in a stem cell therapy clinical trial and received simultaneous bilateral intravitreal and sub-Tenon's injections of bone marrow-derived stem cells. RESULTS: Within one month of receiving the injections, the patient developed epiretinal membranes and vitreous cells in both eyes, seen with optical coherence tomography. CONCLUSION: Stem cell therapy has been gaining popularity as a potential intervention for progressive retinal and optic nerve diseases; however, the mechanism of action of bone marrow-derived stem cells is still not well understood and may result in unintended cell differentiation.

Mean macular intercapillary area in eyes with diabetic macular oedema after anti-vascular endothelial growth factor therapy and its association with treatment response.

BACKGROUND: To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti-vascular endothelial growth factor (VEGF) therapy in initially treatment-naïve eyes with diabetic macular oedema (DME). METHODS: In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea-with the exclusion of foveal avascular zone (FAZ)-in 0.5 mm diameter increments as well as within the intervening rings. RESULTS: In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006). CONCLUSIONS: Absence of significant change in mean ICA after a minimum of three intravitreal anti-VEGF injections, may indicate that, in the short term, anti-VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes.

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

IMPORTANCE: Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). OBJECTIVE: To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. EXPOSURES: Treatment with brolucizumab IVI, 6 mg. MAIN OUTCOMES AND MEASURES: Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. RESULTS: A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) µm and was 269.8 (66.5) µm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. CONCLUSIONS AND RELEVANCE: In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

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

Purpose: To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR). Methods: Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 × 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified. Results: Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r = -0.600, P < 0.0001). The results from the widefield montages showed similar patterns. Conclusions: OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.

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

PURPOSE: To evaluate changes in macular vessel density following intravitreal anti-VEGF injection in patients with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). METHODS: In this retrospective case series, optical coherence tomography angiography (OCTA) images from 55 eyes of 35 patients with either DME (46 eyes) or PDR (9 eyes) were included. Macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP) before and after anti-VEGF treatment was calculated. Longitudinal changes in vessel density following serial anti-VEGF treatment were analyzed in a subset of eyes. RESULTS: Vessel density in the SCP, DCP or TCP was not found to be significantly different after one, two or three intravitreal injections (p > 0.05 for all time points). Subgroup analysis revealed no significant change in the DME and PDR subgroups (all p > 0.05). Multivariate analysis revealed no effect of type of injected anti-VEGF agent or presence of previous treatment on VD measurements (all p > 0.05). There was no correlation between the anatomic response of DME to treatment and VD measurements. CONCLUSIONS: In this study, macular vessel density remained statistically unchanged following up to three intravitreal injections of any anti-VEGF agent. This indicates that there may not be an early effect of anti-VEGF treatment on macular vessel density and its effect on macular perfusion may not be a direct change in microvascular flow.

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

BACKGROUND AND OBJECTIVE: To assess variability in vessel density (VD) measurements across three optical coherence tomography angiography (OCTA) devices to identify a methodology that offers the least amount of variation in VD, and to assess the effect of averaging of multiple scans on VD variability. PATIENTS AND METHODS: Fifteen eyes of eight healthy individuals were imaged consecutively on three OCTA devices. Segmentations at the superficial, deep, and full retinal layers were generated. Repeat scans for each retinal layer were registered and averaged to generate one OCTA image. Two different automated thresholding techniques were used to calculate vessel area density (VAD) from binarized images and vessel skeleton density (VSD) from skeletonized images. Vessel length, a linear measure of the combined lengths of vessels, was calculated. Foveal avascular zone (FAZ) area was measured. RESULTS: All three OCTA devices were significantly different (P < .0001). This finding remained after averaging images (P < .0001). VSD was more repeatable within a device but less reproducible across devices. Conversely, VAD demonstrated less repeatability but greater reproducibility. Differences in VSD between devices were systematic and attributable to differences in resolution. Vessel length, unaffected by resolution, demonstrated no significant differences between the devices (P > .107). There was no significant difference in FAZ area across devices (P = .51). After averaging images, VD was significantly different from the single images for each device and plexus (P < .05) but remained within 1% of the value of a single scan. CONCLUSIONS: OCTA devices show variability in VD for healthy individuals. With greater repeatability, VSD appeared useful for following a patient on one device. VAD and vessel length seemed ideal for comparing vessel parameters between OCTA devices. After averaging multiple scans, VSD remained within 1% of a single scan, for which clinical significance remains to be determined. Caution is advised when comparing quantitative analyses across OCTA devices. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S17.].

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

PURPOSE: To compare foveal vascular anatomy between patients with and without disorganization of retinal inner layers (DRILs) after resolved diabetic macular edema using optical coherence tomography angiography (OCTA). METHODS: Twenty-four eyes of 21 age- and sex-matched patients with resolved diabetic macular edema were included in this retrospective, cross-sectional study. All eyes were imaged with enhanced high-definition line or cross-line structural B scans and 3 × 3-mm OCTA scans. Optical coherence tomography B scans were analyzed for the presence of DRIL, and based on this, eyes were classified as either DRIL present or DRIL absent. The foveal avascular zone area on OCTA was compared between patients with and without DRIL. The foveal avascular zone area was correlated with visual acuity. RESULTS: Nine eyes with DRIL and resolved diabetic macular edema were compared with 15 control eyes without DRIL and resolved diabetic macular edema. Area of ischemia on OCTA scans corresponded to the area of DRIL as determined on OCT B scans. The foveal avascular zone area in full retina as well as superficial and deep retinal plexuses OCTA slabs were significantly larger in patients with DRIL as compared to those without DRIL (P = 0.005, P < 0.001, and P = 0.004, respectively). The larger foveal avascular zone in full retinal segmentation (r = 0.72, P = 0.03) and superficial plexus (r = 0.74, P = 0.02) were positively correlated with lower visual acuity. CONCLUSION: Optical coherence tomography angiography can visualize retinal ischemia in patients with and without DRIL. Correspondence of impaired blood flow with DRIL suggests that retinal ischemia and loss of normal vasculature contributes to DRIL.

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

PURPOSE: To expand understanding of presentation, diagnosis, and outcomes of hemorrhagic occlusive retinal vasculitis (HORV). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-six eyes of 23 patients. METHODS: The American Society of Cataract and Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) formed a joint task force to define clinical characteristics of HORV and to study its prevalence, cause, treatment, and outcomes. An online registry was established on both societies' web sites. Surveys were e-mailed to members of both societies soliciting cases of suspected HORV. A literature search was performed to uncover additional cases. MAIN OUTCOME MEASURES: Historical data including intraoperative characteristics, images, treatment regimens, and visual and anatomic outcomes. RESULTS: Characteristic findings of HORV included unremarkable postoperative day 1 undilated examination, delayed-onset painless vision loss, mild anterior chamber and vitreous inflammation, sectoral retinal hemorrhages in areas of ischemia, and predilection for venules and peripheral involvement. Based on predetermined diagnostic criteria, 36 eyes of 23 patients were diagnosed with HORV. All eyes received intraocular vancomycin via intracameral bolus (33/36), via intravitreal injection (1/36), or through the irrigation bottle (2/36). Patients sought treatment with HORV 1 to 21 days after surgery or intravitreal injection. Visual results usually were poor: 22 of 36 eyes (61%) had 20/200 or worse visual acuity and 8 of 36 eyes (22%) had no light perception (NLP). Neovascular glaucoma developed in 20 of 36 eyes (56%). Seven eyes received additional intravitreal vancomycin after surgery; 5 of these 7 eyes had NLP visual acuity at the most recent examination. Three eyes received intravitreal corticosteroids and had final visual acuities of 20/40, 20/70, and hand movements. CONCLUSIONS: Hemorrhagic occlusive retinal vasculitis is a rare, potentially devastating condition that can develop after cataract surgery or intraocular injection. All cases in this series were associated with intraocular vancomycin. Disease course and findings suggest that HORV is caused by a delayed hypersensitivity reaction to vancomycin. Early treatment with corticosteroids likely is beneficial. Subsequently, anti-vascular endothelial growth factor injections and panretinal photocoagulation are important to prevent neovascular glaucoma, a common complication. Avoidance of additional intravitreal vancomycin is recommended if HORV is suspected.

MICROBIOLOGIC SPECTRUM AND VISUAL OUTCOMES OF ACUTE-ONSET ENDOPHTHALMITIS UNDERGOING THERAPEUTIC PARS PLANA VITRECTOMY.

PURPOSE: To report the clinical presentation, microbiologic spectrum, and visual outcomes associated with acute-onset infectious endophthalmitis undergoing therapeutic pars plana vitrectomy. METHODS: Multicenter interventional retrospective noncomparative consecutive case series. Billing records were reviewed to identify all charts for patients undergoing pars plana vitrectomy within 14 days of diagnosis of acute-onset infectious endophthalmitis over a 4-year period at 5 large tertiary referral retina practices. Statistical analysis was performed to assess for factors associated with visual outcomes. RESULTS: Seventy patients were identified. The most common clinical setting was postcataract surgery (n = 20). Only 3 patients (4.3%) presented with 20/400 or better visual acuity (VA). Although most of the patients initially underwent vitreous tap and intravitreal antibiotic injection (n = 47, 67.1%), all patients eventually underwent pars plana vitrectomy within 14 days of presentation with 68.5% (48/70) of patients undergoing pars plana vitrectomy within 48 hours of presentation. Positive intraocular cultures were obtained in 56 patients (80%). The most common identified organism was Streptococcus sp (n = 19). Visual acuity at last follow-up was 20/400 or better in 19 patients (27.1%). Three patients underwent evisceration or enucleation (4.3%). Last recorded postoperative VA (mean LogMAR 1.99 ± 0.94, Snellen VA equivalent finger count) improved from presenting VA (mean LogMAR 2.37 ± 0.38, Snellen VA hand motions) (P ≤ 0.001). There was no statistically significant correlation between the underlying etiology or the timing of surgery with this VA outcome. CONCLUSION: Although less than one-third of patients achieved 20/400 or better VA, this VA often improved significantly from presenting VA.

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.

OBJECTIVE: To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). DESIGN: Retrospective, consecutive, interventional case series. PARTICIPANTS: Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. METHODS: Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. RESULTS: Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks' follow-up. CONCLUSIONS: Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

Retinal Capillary Network and Foveal Avascular Zone in Eyes with Vein Occlusion and Fellow Eyes Analyzed With Optical Coherence Tomography Angiography.

PURPOSE: To evaluate the perifoveolar retinal capillary network at different depths and to quantify the foveal avascular zone (FAZ) in eyes with retinal vein occlusion (RVO) compared with their fellow eyes and healthy controls using spectral-domain optical coherence tomography angiography (SD-OCTA). METHODS: We prospectively recruited 23 patients with RVO including 15 eyes with central RVO (CRVO) and 8 eyes with branch RVO (BRVO), their fellow eyes, and 8 age-matched healthy controls (8 eyes) for imaging on prototype OCTA software within RTVue-XR Avanti. The 3 × 3 mm and 6 × 6 mm en face angiograms of superficial and deep retinal capillary plexuses were segmented. Perifoveolar retinal capillary network was analyzed and FAZ was quantified. RESULTS: Decrease in vascular perfusion at the deep plexus was observed in all eyes with CRVO (8/8, 100%) and BRVO (6/6, 100%) without cystoid macular edema, and in 8 of 15 (53%) and 2 of 8 (25%) of the fellow eyes, respectively. Vascular tortuosity was observed in 13 of 15 (87%) CRVO and 5 of 8 (63%) BRVO eyes. Collaterals were seen in 10 of 15 (67%) CRVO and 5 of 8 (63%) BRVO eyes. Mean FAZ area was larger in eyes with RVO than their fellow eyes (1.13 ± 0.25 mm2 versus 0.58 ± 0.28 mm2; P = 0.007) and controls (1.13 ± 0.25 mm2 versus 0.30 ± 0.09 mm2; P < 0.0001), and in fellow eyes of RVO patients when compared to controls (0.58 ± 0.28 mm2 versus 0.30 ± 0.09 mm2; P = 0.01). CONCLUSIONS: Spectral-domain OCTA reveals abnormalities at different levels of perifoveolar retinal capillary network and is able to quantify the FAZ in RVO. Longitudinal studies may be considered to evaluate the clinical utility of OCTA in RVO and other retinal vascular diseases.

Visualization of Changes in the Choriocapillaris, Choroidal Vessels, and Retinal Morphology After Focal Laser Photocoagulation Using OCT Angiography.

PURPOSE: To utilize optical coherence tomography (OCT) and OCT angiography (OCTA) to describe alterations in the retinal and choriocapillaris vasculature following remote laser photocoagulation. Lesions are classified on the basis of choriocapillaris alteration as evaluated on en face OCTA. METHODS: This was a retrospective, cross-sectional study analyzing 28 laser photocoagulation scars from 8 patients treated for diabetic macular edema. All eyes were analyzed using a combination of OCTA, en face and cross-sectional OCT, and fundus photography. Two masked readers scored images for alterations at the level of the retinal pigment epithelium (RPE), choroid, and choriocapillaris. Laser photocoagulation lesions were classified as deep if choriocapillaris alteration was present on OCTA; lesions were classified as superficial if no choriocapillaris alteration was present on OCTA. RESULTS: Optical coherence tomography angiography was found to be useful for evaluation of choriocapillaris alteration underlying regions of laser scarring. Of the 28 analyzed laser scars, 13 were classified as superficial and 15 were classified as deep. CONCLUSIONS: Optical coherence tomography angiography can be used to visualize choriocapillaris alterations associated with focal laser photocoagulation treatment.

Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source Optical Coherence Tomography Angiography Compared to Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. DESIGN: Comparative analysis of diagnostic instruments. METHODS: Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant. RESULTS: Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm × 3 mm OCTA were 0.949 ± 1.168 mm(2) and 0.340 ± 0.301 mm(2), respectively (P = .001). For the 6 mm × 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 ± 1.284 mm(2) and 0.604 ± 0.597 mm(2), respectively (P = .0019). The field of view did not significantly affect the measured CNV area (P = .19 and P = .18 for SS OCT and SD OCT, respectively). CONCLUSION: SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature.

Distinguishing Diabetic Macular Edema From Capillary Nonperfusion Using Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To describe the appearance of diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and distinguish it from capillary nonperfusion. PATIENTS AND METHODS: Patients with DME were recruited for OCTA imaging. Eyes with confounding retinal diseases were excluded. Using 3 mm × 3 mm OCT angiograms segmented into the superficial and deep inner retinal vascular plexuses, two graders described the appearance of DME and confirmed the diagnosis with structural OCT and fluorescein angiography. RESULTS: DME was evaluated in 17 eyes of 12 patients. The cystoid spaces in DME appeared completely devoid of flow on the OCT angiograms and were oblong in shape with smooth borders that did not follow the distribution of surrounding capillaries, whereas areas of capillary nonperfusion were a greyer hue and had irregular borders. CONCLUSIONS: The cystoid spaces in DME can be differentiated from capillary nonperfusion using OCTA. OCTA may help to guide treatment decisions in the future.

Evaluation of Preretinal Neovascularization in Proliferative Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To describe a method for visualizing preretinal neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA) and report the findings in the surrounding vasculature. PATIENTS AND METHODS: Patients with PDR diagnosed on clinical examination who received OCTA scans using the RTVue XR Avanti (Optovue, Fremont, CA) were evaluated. To visualize preretinal neovascularization, OCT angiograms were segmented to project vasculature above the internal limiting membrane (ILM). OCT angiograms were segmented between the ILM and Bruch's membrane to show adjacent retinal vasculature. RESULTS: Thirteen eyes were determined to have preretinal neovascularization in the posterior pole based on OCTA. One OCT angiogram was not of sufficient quality and thus was eliminated from further study. Eleven eyes (92%) had neovascularization adjacent to retinal capillary nonperfusion and six (50%) were adjacent to intraretinal microvascular abnormalities (IRMAs). CONCLUSION: OCTA provided high-resolution, depth-resolved blood flow information, allowing for visualization of preretinal neovascularization, IRMA, and adjacent capillary nonperfusion.

Three-Dimensional Enhanced Imaging of Vitreoretinal Interface in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography.

PURPOSE: To analyze the vitreoretinal interface in diabetic eyes using 3-dimensional wide-field volumes acquired using high-speed, long-wavelength swept-source optical coherence tomography (SSOCT). DESIGN: Prospective cross-sectional study. METHODS: Fifty-six diabetic patients (88 eyes) and 11 healthy nondiabetic controls (22 eyes) were recruited. Up to 8 SSOCT volumes were acquired for each eye. A registration algorithm removed motion artifacts and merged multiple SSOCT volumes to improve signal. Vitreous visualization was enhanced using vitreous windowing method. RESULTS: Of 88 diabetic eyes, 20 eyes had no retinopathy, 21 eyes had nonproliferative diabetic retinopathy (NPDR) without macular edema, 20 eyes had proliferative diabetic retinopathy (PDR) without macular edema, and 27 eyes had diabetic macular edema (DME) with either NPDR or PDR. Thick posterior hyaloid relative to healthy nondiabetic controls was observed in 0 of 20 (0%) diabetic eyes without retinopathy, 4 of 21 (19%) eyes with NPDR, 11 of 20 (55%) eyes with PDR, and 11 of 27 (41%) eyes with DME (P = .0001). Vitreoschisis was observed in 6 of 22 (27%) healthy nondiabetic eyes, 9 of 20 (45%) diabetic eyes without retinopathy, 10 of 21 (48%) eyes with NPDR, 13 of 20 (65%) eyes with PDR, and 17 of 27 (63%) eyes with DME (P = .007). While no healthy nondiabetic controls and diabetic eyes without retinopathy had adhesions/pegs between detached posterior hyaloid and retina, 1 of 21 (4%), 11 of 20 (55%), and 11 of 27 (41%) eyes with NPDR, PDR, and DME, respectively, demonstrated this feature (P = .0001). CONCLUSION: SSOCT with motion-correction and vitreous windowing provides wide-field 3-dimensional information of vitreoretinal interface in diabetic eyes. This may be useful in assessing progression of retinopathy, planning diabetic vitreous surgery, and predicting treatment outcomes.

CHARACTERIZING THE EFFECT OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY ON TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To use optical coherence tomography angiography (OCTA) to characterize the effects of anti-VEGF injections on treatment-naive choroidal neovascularization (CNV). METHODS: From August 2014 to May 2015, treatment-naive eyes with CNV were scanned using a prototype OCTA system on a commercially available SD-OCT device (Optovue Inc, Fremont, CA). Optical coherence tomography angiography scans were obtained before anti-VEGF injection and at follow-up visits. The CNV area and greatest linear dimension (GLD) were measured along with the maximum retinal pigment epithelial detachment (RPED) height. Changes in subretinal and/or intraretinal fluid were also assessed. RESULTS: Six eyes of six patients with treatment-naive CNV were included. Diagnoses included neovascular age-related macular degeneration, idiopathic polypoidal choroidal vasculopathy, CNV secondary to central serous chorioretinopathy and multifocal choroiditis, and macular telangiectasia Type 2 with subretinal neovascularization. After treatment, all patients with fluid on OCT initially showed a decrease in the amount of fluid. Five of six patients demonstrated decreases in CNV GLD and area with an average reduction of 23.6% and 29.8% respectively. CONCLUSION: Both CNV greatest linear dimension and area measured using OCTA decreased after anti-VEGF treatment in most patients. Optical coherence tomography angiography may be a useful tool for monitoring and quantifying the response of CNV to treatment.

Visualization of the Retinal Vasculature Using Wide-Field Montage Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To evaluate the technique of wide-field montage optical coherence tomography angiography (OCTA) for improved visualization of the retinal vasculature in the posterior pole. PATIENTS AND METHODS: In this prospective case series, five eyes (three healthy and two diseased) of three patients were imaged using a novel technique to create wide-field montage OCTA images by combining nine 3 × 3-mm OCTA scans from the prototype AngioVue software of the RTVue XR (Optovue, Fremont, CA). Features seen on montage OCTA were compared to those visualized on fluorescein angiography (FA) and single-scan 8 × 8-mm OCTA. RESULTS: The montage OCTA showed the retinal vasculature in the greatest detail. The technique successfully detected vascular abnormalities seen on FA, and in some instances, montage OCTA visualized pathology that was not detected by FA and 8 × 8-mm OCTA. CONCLUSION: Wide-field montage OCTA imaging is a noninvasive, high-resolution technique to improve visualization of the retinal vasculature in the posterior pole.