Retinal Vasculitis After Intravitreal Pegcetacoplan: Report From the ASRS Research and Safety in Therapeutics (ReST) Committee.

Purpose: To analyze post-marketing cases of retinal vasculitis after intravitreal pegcetacoplan. Methods: The American Society of Retina Specialists (ASRS) Research and Safety in Therapeutics (ReST) Committee as well as an expert panel performed a retrospective review of cases of retinal vasculitis reported to the ASRS. Clinical and imaging characteristics were reviewed for evidence of retinal vasculitis and analyzed. Results: Fourteen eyes of 13 patients were confirmed to have retinal vasculitis by review of imaging studies. All cases occurred after the first pegcetacoplan injection. Occlusive retinal vasculopathy was confirmed in 11 eyes (79%). Patients presented a median of 10.5 days (range, 8-23 days) after pegcetacoplan injection. All eyes had anterior chamber inflammation, and 12 eyes (86%) had vitritis. Vasculopathy involved retinal veins (100%) more than arteries (73%), and 12 eyes (86%) had retinal hemorrhages. The median visual acuity (VA) was 20/60 (range, 20/30-5/200) at baseline, 20/300 (range, 20/100-no light perception [NLP]) at vasculitis presentation, and 20/200 (range 20/70-NLP) at the last follow-up. Eight eyes (57%) had more than a 3-line decrease in VA, and 6 eyes (43%) had more than a 6-line decrease in VA from baseline to the final follow-up, including 2 eyes that were enucleated. Six eyes (43%) developed signs of anterior segment neovascularization. Conclusions: There is currently no known etiology for vasculitis in this series. Optimum treatment strategies remain unknown. Infectious etiologies should be considered, and corticosteroid treatments may hasten resolution of inflammatory findings. Continued treatment of affected patients with pegcetacoplan should be avoided.

Relentless Placoid Chorioretinitis Responsive to Intravitreal Triamcinolone and Systemic Adalimumab.

PURPOSE: We describe a case of relentless placoid chorioretinitis that was responsive to intravitreal triamcinolone (IVT) and systemic adalimumab, but suboptimally responsive to oral prednisone. METHODS: Interventional case report. RESULTS: A 23-year-old woman presented with macular placoid chorioretinitis in the left eye and visual acuity of finger counting at 3 feet. Despite a 2-week course of 60mg oral prednisone, the choroiditis expanded dramatically in the mid-periphery. She was admitted to the hospital for high-dose intravenous corticosteroids, which stopped progression of disease. After discharge, the patient was started on adalimumab and restarted oral prednisone, however upon resumption of oral prednisone 60mg, the disease started to progress again over the next 2 weeks. An intravitreal injection of triamcinolone (IVT) 2mg was given, which halted progression of the disease for at least 9 weeks, at which time it was felt that the adalimumab started to also have an effect. Visual acuity 9 weeks after IVT had improved to 20/20. The patient was lost to follow-up after this point. CONCLUSION: This is a case of relentless placoid chorioretinitis that continued to progress despite high-dose oral corticosteroids, but which responded to intravitreal triamcinolone and systemic adalimumab. This indicates that intravitreal corticosteroids may represent an alternative treatment option to oral corticosteroids in the short-term management of macula-threatening non-infectious chorioretinitis, particularly in patients with a sub-optimal response to oral corticosteroids.

Pseudoaveraging for denoising of OCT angiography: a deep learning approach for image quality enhancement in healthy and diabetic eyes.

BACKGROUND: This study aimed to develop a deep learning (DL) algorithm that enhances the quality of a single-frame enface OCTA scan to make it comparable to 4-frame averaged scan without the need for the repeated acquisitions required for averaging. METHODS: Each of the healthy eyes and eyes from diabetic subjects that were prospectively enrolled in this cross-sectional study underwent four repeated 6 × 6 mm macular scans (PLEX Elite 9000 SS-OCT), and the repeated scans of each eye were co-registered to produce 4-frame averages. This prospective dataset of original (single-frame) enface scans and their corresponding averaged scans was divided into a training dataset and a validation dataset. In the training dataset, a DL algorithm (named pseudoaveraging) was trained using original scans as input and 4-frame averages as target. In the validation dataset, the pseudoaveraging algorithm was applied to single-frame scans to produce pseudoaveraged scans, and the single-frame and its corresponding averaged and pseudoaveraged scans were all qualitatively compared. In a separate retrospectively collected dataset of single-frame scans from eyes of diabetic subjects, the DL algorithm was applied, and the produced pseudoaveraged scan was qualitatively compared against its corresponding original. RESULTS: This study included 39 eyes that comprised the prospective dataset (split into 5 eyes for training and 34 eyes for validating the DL algorithm), and 105 eyes that comprised the retrospective test dataset. Of the total 144 study eyes, 58% had any level of diabetic retinopathy (with and without diabetic macular edema), and the rest were from healthy eyes or eyes of diabetic subjects but without diabetic retinopathy and without macular edema. Grading results in the validation dataset showed that the pseudoaveraged enface scan ranked best in overall scan quality, background noise reduction, and visibility of microaneurysms (p < 0.05). Averaged scan ranked best for motion artifact reduction (p < 0.05). Grading results in the test dataset showed that pseudoaveraging resulted in enhanced small vessels, reduction of background noise, and motion artifact in 100%, 82%, and 98% of scans, respectively. Rates of false-positive/-negative perfusion were zero. CONCLUSION: Pseudoaveraging is a feasible DL approach to more efficiently improve enface OCTA scan quality without introducing notable image artifacts.

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.

MULTISCALE CORRELATION OF MICROVASCULAR CHANGES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH RETINAL SENSITIVITY IN DIABETIC RETINOPATHY.

PURPOSE: To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography and retinal sensitivity measured by microperimetry across diabetic retinopathy severity. METHODS: Diabetic patients and nondiabetic controls underwent optical coherence tomography angiography imaging and microperimetry testing. Pearson's correlation was used to assess associations between average sensitivity and skeletonized vessel density (SVD) or foveal avascular zone area centrally. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements. RESULTS: Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the foveal avascular zone areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this seemed to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities. CONCLUSION: This study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.

Brolucizumab-associated intraocular inflammation in eyes without retinal vasculitis.

PURPOSE: To analyze a series of eyes with brolucizumab-associated intraocular inflammation (IOI) without retinal vasculitis reported to the American Society of Retina Specialists (ASRS). METHODS: The ASRS Research and Safety in Therapeutics (ReST) Committee analyzed clinical characteristics from submitted reports of IOI after brolucizumab. Eyes with retinal vasculitis or that received intraocular antibiotics were excluded. RESULTS: Forty-nine eyes of 45 patients were collected. Mean visual acuity (VA) at baseline was 20/49 (range 20/20 - 5/200). Patients presented with IOI a mean of 24 (range 3-63) days after most recent brolucizumab injection; 61% presented for an unscheduled visit while 39% presented at routine follow-up. Mean VA at IOI presentation was 20/67 (range 20/20 - 3/200). Most common symptoms were floaters (78%) and blurry vision (76%). Pain (20%) and redness (16%) were less common; 3 (6%) eyes were asymptomatic. IOI was anterior only in 18%, posterior only in 31%, and both anterior and posterior in 51% of eyes. Treatment included topical steroids alone in 67% eyes, while 10% eyes received no treatment. Mean VA at last follow-up was 20/56 (range 20/20 - 1/200). Three (6%) eyes lost 3 or more lines and 1 (2%) eye lost 6 or more lines. CONCLUSIONS: Brolucizumab-associated IOI without retinal vasculitis typically presented with a delayed onset of a few weeks. Often, visual acuity decline was relatively mild. Most symptoms resolved and nearly all had a return to baseline VA, but a small percentage of patients had a significant decrease in VA at last follow-up.

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

PURPOSE: To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions. DESIGN: Observational descriptive study. PARTICIPANTS: Thirty-two participants with normal and pathologic retina examination results. METHODS: Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae. MAIN OUTCOMES MEASURES: Description of HMM module-obtained macula images. RESULTS: From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane. CONCLUSIONS: In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.

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

PURPOSE: Further insight into the flow characteristics of the vascular features associated with diabetic retinopathy (DR) may improve assessment and treatment of disease progression. The variable interscan time analysis (VISTA) algorithm is an extension of OCT angiography (OCTA) that detects relative blood flow speeds, which then can be depicted on a color-coded map. This study used VISTA to analyze relative blood flow speeds in the microvascular changes associated with DR. DESIGN: Cross-sectional study. PARTICIPANTS: Thirteen patients with varying severities of DR treated at New England Eye Center, Boston, Massachusetts. METHODS: OCT angiography images centered at the fovea were obtained on a prototype swept-source OCT device, and the VISTA algorithm was applied to visualize relative blood flow speeds. MAIN OUTCOME MEASURES: Descriptive flow analysis of the retinal vascular features of DR was conducted on the VISTA-generated images. RESULTS: Twenty-six eyes were included in this study. Of these, 3 eyes had mild nonproliferative DR (NPDR), 6 eyes had moderate NPDR, 4 eyes had severe NPDR, 9 eyes had proliferative DR, and 4 eyes were normal controls. Microaneurysms, intraretinal microvascular abnormalities (IRMAs), and neovascularization appeared to originate from areas of relatively slow blood flow speeds. Microaneurysms showed relatively slower flow, IRMAs showed turbulent, intermediate to slow flow, and venous beading and looping presented with relatively high flow speeds that tapered progressively. Neovascularization of venous origin demonstrated slower flow speeds, whereas that of arterial origin showed relatively high flow speeds. Additionally, increased disease severity was associated with globally slower flow speeds, with particularly slower flow around the foveal avascular zone. CONCLUSIONS: The VISTA algorithm seems to be a useful extension of OCTA that overcomes some of the limitations of normal gray-scale OCTA. It seems to have some potential in providing relevant insight into the pathogenesis of the microvascular changes associated with DR. These findings may assist in improving our understanding of the pathogenic changes that take place in DR.

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

BACKGROUND: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA). METHODS: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated. RESULTS: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate. CONCLUSIONS: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab.

PURPOSE: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration. METHODS: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab. RESULTS: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied. CONCLUSIONS: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown.

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

BACKGROUND: To compare the anatomical and visual outcomes in eyes with persistent diabetic macular edema (DME) after initial anti-VEGF therapy that were retreated continuously with the same anti-VEGF drug versus those that underwent two successive cycles of medication change in anti-VEGF drugs (double anti-VEGF switch). METHODS: Retrospective review of eyes with persistent DME after 3 initial consecutive monthly anti-VEGF injections. This cohort was divided into two groups: Group 1 continued to receive the same initial anti-VEGF drug for at least 18 months while group 2 eyes were switched to different anti-VEGF medications twice. Group 1 was further subdivided into: Group 1A composed of eyes with less than 20% reduction in central subfield thickness (CRT) at month 3; and group 1B eyes with greater than or equal to 20% reduction in CRT. The percentage of eyes that achieved greater than 10 letters visual acuity (VA) gain or loss was recorded as the primary end point (through month 18 in group 1 and month 6 after 2nd switch in group 2). RESULTS: Group 1A, 1B and group 2 were composed of 24, 18, and 14 eyes respectively. 34.7%, 56.2% and 36.3% of eyes achieved > 10 letters gain, while 4.3%, 6.2% and 27.2% of eyes lost > 10 letters in groups 1A, 1B, and 2, respectively. Analysis of the visual acuity (VA) letter change in this time interval revealed no significant difference between all groups (p = 0.11). Mean VA and CRT measurements at the primary endpoint in all groups were 0.5, 0.39, and 0.47 logMAR (p = 0.44), and 369.7, 279.9, 321 µm, (p = 0.01) respectively. CONCLUSIONS: There was no difference in the visual outcomes between the two treatment strategies in eyes with persistent DME after 3 consecutive anti-VEGF injections. This may indicate that anti-VEGF switching-even if it is done twice-may have comparable clinical outcomes to sustained treatment with one agent.

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

BACKGROUND: To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities (IRMAs) in response to anti-vascular endothelial growth factor (anti-VEGF) treatment, documented by optical coherence tomography angiography (OCTA) in diabetic eyes. METHODS: In this retrospective study, IRMAs were evaluated with multimodal imaging (fundus photography, fluorescein angiography, OCTA) in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR) and compared to diabetic control eyes with similar diabetic retinopathy (DR) severity that did not receive anti-VEGF therapy. The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline, then after anti-VEGF therapy in treated eyes or after observation in control eyes. Characterization of interval changes in an IRMA were based on the following parameters: branching, vessel caliber and area of adjacent capillary non-perfusion. RESULTS: The treated group included 45 IRMA foci from 15 eyes of 11 patients, while the control group included 27 IRMA foci from 15 eyes of 14 patients. Following anti-VEGF treatment, enface OCTA demonstrated that 14 foci of IRMA (31%) demonstrated regression with normalization of appearance of the capillary bed, 20 IRMAs (44%) remained unchanged, six IRMAs (13%) progressed with enlargement or development of new IRMAs and five IRMAs (11%) demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out. In the control group, 17 IRMA (63%) remained stable, 8 IRMAs (29.6%) progressed and 2 experienced total obliteration (7.4%). The difference in rank order between the two groups was statistically significant (p = 0.022). CONCLUSIONS: In eyes with DR status post anti-VEGF therapy, foci of IRMAs have a variable course demonstrating one of four possible outcomes: regression, stability, progression or complete obliteration. In contrast, none of the untreated control diabetic eyes demonstrated regression of IRMAs, consistent with known progression of DR severity in high risk eyes. Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.

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

PURPOSE: Understanding the precision of measurements on and across optical coherence tomography angiography (OCTA) devices is critical for tracking meaningful change in disease. The purpose of this study is to investigate the repeatability and reproducibility of vessel area density and vessel skeleton density measurements from various commercial OCTA devices in diabetic eyes. METHODS: Patients were imaged three consecutive times each on three different OCTA devices. En face OCTA images of the superficial capillary plexus, deep capillary plexus, and full retinal layer were exported for analysis. Vessel area density and vessel skeleton density were calculated. The coefficient of repeatability (CoR) was calculated to assess the repeatability of these measurements, and linear mixed models were utilized to assess the reproducibility of these measurements. RESULTS: Forty-four eyes from 27 diabetic patients were imaged. Normalized CoR values ranged between 3.44 and 6.65% when calculated for vessel area density and between 1.35 and 23.39% when calculated for vessel skeleton density. When stratified by disease severity, the swept-source OCTA device consistently produced the smallest CoR values for vessel area density in the full retinal layer. Vessel area density measurements were repeatable across the two spectral-domain devices in the full retinal layer when all severities were combined, as well as in diabetic patients without retinopathy, mild nonproliferative diabetic retinopathy (NPDR), and moderate NPDR. CONCLUSION: Vessel area density measured in the full retinal layer may be a more precise measure than vessel skeleton density to follow diabetic retinopathy patients both on the same device and across devices.

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

PURPOSE: To evaluate the repeatability and reproducibility of photoreceptor density assessment with manual cell counting in healthy participants imaged with the Heidelberg Spectralis High Magnification Module (HMM). DESIGN: Precision study, evaluation of diagnostic test or technology. PARTICIPANTS: Eleven eyes of 8 participants. METHODS: Images were acquired using the Spectralis HMM by a single operator during 2 separate imaging sessions. The 3 highest-quality images of each eye from each session were selected for analysis and coregistered. For a subset of participants, a second operator acquired images in 1 session, and images with the best quality were selected for analysis. Photoreceptor densities were obtained by manual counts in squares of 0.0625 mm2 located in the parafovea. Repeatability (intragrader and intrasession) and reproducibility (interoperator, intergrader, and intersession) were assessed by calculating the intraclass correlation coefficient (ICC) from linear mixed effects models. Bland-Altman plots, coefficients of repeatability, and Pearson correlation results were reported. MAIN OUTCOME MEASURES: Intragrader, intrasession, intersession, interoperator, and intergrader ICC estimates and their 95% confidence intervals for photoreceptor density measurements in the parafovea. RESULTS: Twenty-four eyes of 13 healthy participants were imaged initially. Of these, 11 eyes (45.83%) of 8 participants that had at least 3 acceptable images in each session were included in this study. Mean parafoveal photoreceptor density was 14 988 cells/mm2 (standard deviation, 1403.15 cells/mm2). Intragrader ICC was 0.84 (95% confidence interval, 0.57-0.95), intrasession ICC was 0.69 (95% confidence interval, 0.17-0.86), intersession ICC was 0.88 (95% confidence interval, 0.53-0.96), interoperator ICC was 0.70 (95% confidence interval, 0-0.95), and intergrader ICC was 0.22 (95% confidence interval, 0-0.71). CONCLUSIONS: Images obtained with the HMM allow for photoreceptor mosaic visualization in the macular area, mainly in the parafovea. Although densities obtained are in accordance with other reported methods in the literature, variability within and between images of the apparent cell mosaic were observed, and this study did not demonstrate high repeatability or reproducibility for quantitative assessments using the manual counting method.