Relationship between nonperfusion area from widefield optical coherence tomography angiography and macular vascular parameters in diabetic retinopathy.

PURPOSE: To evaluate the relationship between the nonperfusion area (NPA) from widefield optical coherence tomography angiography (OCTA) and macular vascular parameters in diabetic retinopathy (DR). METHODS: In total, 51 eyes from 51 patients with proliferative DR (PDR) or moderate/severe non-PDR were included. Widefield OCTA using the Zeiss Plex Elite 9000 was performed. A semi-automatic algorithm calculated the percentages of the NPA within the total image. Macular OCTA (3 × 3 mm and 6 × 6 mm area) was scanned using the RTVue-XR Avanti. Vessel density (VD) was automatically separated into the superficial (SCP) and deep capillary plexus (DCP), and foveal avascular zone (FAZ) measurements were computed according to the parafoveal (1-3 mm) and perifoveal (3-6 mm) regions. RESULTS: A negative correlation was found between the average VD of the SCP and DCP obtained 3 × 3 mm and 6 × 6 mm area and the NPA. Multiple regression analysis revealed that the temporal-perifoveal region most negatively correlated with the NPA (r = - 0.55, p < 0.0001). No correlation was found between FAZ measurements and DR severity (area, p = 0.07; perimeter, p = 0.13). CONCLUSION: Diabetic macular nonperfusion was significantly associated with the NPA from widefield OCTA. In particular, the temporal-perifoveal DCP disorder may be a sensitive indicator of wide NPA.

Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells.

Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.

Outcomes of patients with acute Vogt-Koyanagi-Harada disease treated with intravenous corticosteroid pulse followed by the slow tapering of oral corticosteroid therapy.

PURPOSE: To elucidate the intravenous corticosteroid pulse treatment outcomes of patients with acute Vogt-Koyanagi-Harada (VKH) disease and assess the differences between patients with no inflammation worsening and those with persistent or worsening inflammation. Potential factors responsible for eyes with low visual outcomes were also investigated. METHODS: We retrospectively reviewed the clinical records of patients with acute VKH disease who first visited us between 2009 and 2018 and were followed up for > 300 days. Clinical characteristics, treatments, and posttreatment conditions were assessed. Patients were classified into no inflammation worsening (acute-resolved [AR]) and inflammation worsening (chronic-recurrent [CR]) groups based on conditions after 6 months from disease onset. RESULTS: This study included 60 eyes from 30 patients (mean age: 52.7 years). Patients were treated with methylprednisolone pulse followed by the slow tapering of oral prednisolone; 73% of patients developed AR and 27% CR, and the best-corrected visual acuity (BCVA) was ≥ 1.0 in 83% of eyes at 6 months following the introduction of treatment. Although the total prednisolone dose was higher in patients with CR disease, no significant difference was noted in the final BCVA. Among the patients, five eyes had a final BCVA of ≤ 0.5 due to anisometropic amblyopia, diabetic maculopathy, pre-existing macular hole, epiretinal membrane, and ellipsoid zone loss. CONCLUSIONS: Patients with acute VKH disease treated with corticosteroid pulse appear to demonstrate good visual outcomes, including patients with CR; the majority of eyes with low visual outcomes have pre-existing conditions that explain the low vision.

Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation.

AIM: To investigate changes in extracellular matrix (ECM) gene expression in human trabecular meshwork (HTM) cells in response to mechanical fluid flow stimulation. METHODS: HTM cells were grown on a glass plate coated with 0.02% type I collagen (COL) and exposed to shear stress (0, 0.2, 1.0 dyne/cm2) for 12h. Changes in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain reaction. Phosphorylation of Smad2 protein was investigated by Western blotting. RESULTS: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control (P<0.05, <0.05, and <0.01, respectively). The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control (P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not significant. The phosphorylation of Smad2 levels was significantly higher compared to the static control cells. CONCLUSION: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical stimulation. The mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

Recommendations for OCT Angiography Reporting in Retinal Vascular Disease: A Delphi Approach by International Experts.

PURPOSE: To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN: Delphi-based survey. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts. METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of "wide-field (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: "strong consensus" was defined as ≥85% agreement, "consensus" as 80% to 84%, and "near consensus" as 70% to 79%. MAIN OUTCOME MEASURES: Consensus and near consensus on OCTA nomenclature in retinal vascular disease. RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of "no-flow areas," and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS: This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

Outcomes of a 2-year treat-and-extend regimen with aflibercept for diabetic macular edema.

This prospective, open-label, single-arm, non-randomized clinical trial, assessed the efficacy of a 2-year treat-and-extend (T&E) regimen involving intravitreal aflibercept injection (IAI), with the longest treatment interval set to 16 weeks, and adjunct focal/grid laser in diabetic macula edema (DME) patients. We examined 40 eyes (40 adults) with fovea-involving DME from 8 Japanese centers between April 2015 and February 2017. Participants received IAI with an induction period featuring monthly injections and a subsequent T&E period featuring 8-16-week injection interval, adjusted based on optical coherence tomography findings. The primary endpoints were mean changes in the best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Thirty patients (75%) completed the 2-year follow-up. The mean BCVA and CST changed from 60.5 ± 15.6 letters and 499.2 ± 105.6 µm at baseline to 66.6 ± 17.1 letters (P = 0.217) and 315.2 ± 79.0 µm (P < 0.001), respectively, after 2 years. The treatment interval was extended to 12 and 16 weeks in 6.7% and 66.7% of patients, respectively, at the end of 2 years. The T&E aflibercept regimen with the longest treatment interval set to 16 weeks, with adjunct focal/grid laser may be a rational 2-year treatment strategy for DME.

Treat-and-extend therapy with aflibercept for diabetic macular edema: a prospective clinical trial.

PURPOSE: To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). STUDY DESIGN: Prospective, open-label, multicenter, single-arm, nonblinded clinical study. METHODS: Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16 weeks and adjunct focal/grid laser for 1 year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1 year. RESULTS: Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0 µm (P < .001), but the mean BCVA gain was limited to 4.3 ± 12.2 letters (P = .782). Subanalysis revealed that eyes that gained ≥ 4 letters (median at week 12) after the initial 3 consecutive IAIs (induction phase) achieved greater vision improvement (13.8 ± 9.5 letters) than did the residual eyes (- 4.3 ± 9.2 letters) at 1 year (P < .001). Treatment intervals were extended to 12 and 16 weeks in 16.1% (5/31) and 45.2% (14/31) of the patients, respectively. The mean IAI number was 7.0 ± 1.1. CONCLUSIONS: The results of this study suggest that although the BCVA improvement might be somewhat less than that of frequent treatment, a T&E aflibercept regimen with the longest treatment interval set to 16 weeks is a realizable rational strategy for DME treatment over 1 year.

Circumpapillary collateral vessel development in iatrogenic central retinal artery occlusion observed using OCT angiography.

PURPOSE: It has been reported that peripapillary loops develop after central retinal artery occlusion (CRAO). Although cilioretinal anastomoses have been shown by fluorescein angiography (FA) and indocyanine green angiography, these examinations cannot confirm the structural continuity between the retinal arteries and the posterior ciliary arteries. In the current report, we followed a patient with iatrogenic CRAO in which circumpapillary collaterals formed and assessed the connection between these two vascular systems using optical coherence tomography angiography (OCTA). OBSERVATION: Iatrogenic CRAO developed in the left eye of a 30-year-old woman during preoperative embolization of a convexity meningioma. FA and OCTA showed complete impairment of the retinal circulation. Two weeks after this event, OCTA images showed flow in the retinal vessels and the beginning of collateral vessel development on the optic disc margin. Six months later, OCTA images showed that these circumpapillary collaterals connected branches of the retinal arteries with the vessels supplying the optic disc, which originate from the posterior ciliary arteries. CONCLUSION AND IMPORTANCE: OCTA aided our understanding of the three-dimensional configuration of the circumpapillary collaterals that developed after iatrogenic CRAO, which included anastomosis of the retinal and posterior ciliary artery systems. OCTA is useful for noninvasively monitoring the status of retinal circulatory dynamics after iatrogenic CRAO.

Association Between Alterations of the Choriocapillaris Microcirculation and Visual Function and Cone Photoreceptors in Patients With Diabetes.

Purpose: The purpose of this study was to investigate the association between the choriocapillaris microcirculation and the visual function and cone photoreceptor structure in patients with diabetes. Methods: Thirteen control subjects and 26 patients with type 2 diabetes were recruited. The patients with diabetes were divided into three groups based on the grade of diabetic retinopathy (DR). The retinal sensitivity (RS) was evaluated using microperimetry. Cone photoreceptor mosaics were imaged using an adaptive optics retinal camera, and the cone heterogeneity packing index (HPi) was calculated. Optical coherence tomography angiography (OCTA) images of the choriocapillaris were obtained using spectral-domain OCTA, and the area of flow deficit (FD) was evaluated. All parameters were evaluated in the foveal and parafoveal areas. Results: The study included four patients with diabetes without retinopathy, 12 patients with nonproliferative diabetic retinopathy (NPDR), and 10 patients with proliferative diabetic retinopathy (PDR). The foveal and parafoveal FDs were correlated significantly (fovea, r = -0.58; P = 0.046 and r = -0.82; P = 0.003; parafovea, r = -0.59; P = 0.044 and r = -0.72; and P = 0.019, respectively) with the RS in patients with NPDR and PDR, but not in control and no diabetic retinopathy (NDR) groups. There were no differences in the foveal HPi among the groups. Conclusions: Impaired choriocapillaris microcirculation is associated with impaired visual function but not cone photoreceptor integrity in eyes with DR.

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.

Topographic analysis of macular choriocapillaris flow deficits in diabetic retinopathy using swept-source optical coherence tomography angiography.

BACKGROUND: The purpose of this study was to investigate the association between diabetic retinopathy (DR) severity and macular choriocapillaris (CC) flow deficit percentage (FD %) in different macular regions using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Diabetic patients with SS-OCTA images were graded by severity and retrospectively assessed. CC FD % was calculated in four different regions of the OCTA image: inner, middle, outer, and full-field region. The generalized estimating equations (GEE) approach for clustered eye data was used to determine effect size and significance of age and disease severity on FD % for each region. RESULTS: 160 eyes from 90 total diabetic patients met inclusion criteria. Out of 90 patients, 33 had no DR, 17 had mild nonproliferative DR (NPDR), 8 had moderate NPDR, 10 had severe NPDR and 22 had proliferative DR. Age and DR severity had a significant positive association with FD % for each region studied with a greater effect in the two centermost regions. The increase in flow deficit percentage per year of age by region was: inner 0.12 (p < 0.001), middle 0.09 (p < 0.001), outer 0.05 (p < 0.001, full-field 0.06 (p < 0.001). The increase in flow deficit percentage per increase in diabetic retinopathy severity stage by region was: inner 0.65 (p < 0.0087), middle 0.56 (p < 0.0012), outer 0.33 (p < 0.045), full-field 0.36 (p < 0.018). CONCLUSIONS: Topographic analysis of the CC FD % in diabetic eyes suggests that CC flow impairment corresponds to DR severity, with all studied regions of the CC significantly affected. There was greater regional impairment due to age and disease severity in the inner and middle regions.

A Proposed Classification of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Following Panretinal Photocoagulation.

Purpose: To investigate the characteristics of intraretinal microvascular abnormalities (IRMAs) before and after panretinal photocoagulation (PRP) for diabetic retinopathy (DR) by using optical coherence tomography angiography (OCTA). Methods: Forty-six eyes of 29 patients with DR were included (26 eyes with severe nonproliferative diabetic retinopathy [SNPDR] and 20 eyes with proliferative diabetic retinopathy [PDR]). En face OCTA images of IRMAs in a 6 × 6-mm area were acquired by using Cirrus 5000 with AngioPlex. The morphological changes in IRMAs were evaluated before and after PRP. The changes in the IRMAs were divided into five subtypes: unchanged; tuft regression; reperfusion; mixed (combined tuft regression/reperfusion); and worsening (new appearance of tuft). Results: Unchanged IRMAs were identified in 15 SNPDR eyes and 2 PDR eyes; all neovascularization (NV) had regressed after PRP. Tufts were more frequently observed in the PDR eyes (15/20, 75%) than in the SNPDR eyes (8/26, 31%) (P = 0.003), and two tufts tended to exceed the inner limiting membrane, which showed progression to NV before PRP. The reperfusion phenomenon was observed in 7/26 SNPDR eyes and 4/20 PDR eyes, including the mixed type, and showed two vascular patterns: abnormal (dilated, tortuous, and twisted) and normal vessels. The worsening type was observed in 1/26 SNPDR eye and 2/20 PDR eyes. Conclusions: OCTA enabled classification of IRMA into more detailed types. The unchanged and reperfusion types suggested that IRMAs had aspects of remodeling. However, IRMAs with tufts were observed in 75% of the PDR eyes, and the tufts had aspects of NV.

Effects of enhanced depth imaging and en face averaging on optical coherence tomography angiography image quantification.

PURPOSE: To examine the effects of enhanced depth imaging (EDI) and en face averaging on global vascular measurements of optical coherence tomography angiography (OCTA) images. METHODS: All eyes were imaged with 3 mm × 3 mm fields centered at the fovea using the Carl Zeiss Cirrus 5000 spectral-domain OCTA, with and without EDI, and the Zeiss PLEX Elite 9000 swept-source OCTA. Vessel area density (VAD), vessel length (VL), and vessel diameter index (VDI) were calculated for the superficial capillary plexus (SCP) en face angiograms. For the choriocapillaris (CC), VAD and the number, total area, and average size of flow voids were calculated. These metrics were compared between SD- and SS-OCTA images, with and without en face averaging and EDI. RESULTS: Both averaging and EDI had a significant effect on quantitative metrics. EDI images trended toward a decrease in SCP VAD. In the CC, EDI decreased average flow void size. Averaging increased CC VAD while decreasing number of flow voids, total flow void area, and average flow void size. With both averaging and EDI, SD-OCTA was not able to visualize as many CC flow voids, particularly of a smaller size, compared with SS-OCTA. CONCLUSIONS: Averaging and EDI affect quantitative metrics from SCP and CC OCTA images. EDI resulted in a trend toward decreased VAD in SCP images. Averaging had a major effect on CC imaging. Even with the combination of EDI and en face averaging, SD-OCTA images do not appear to approximate SS-OCTA images in terms of quantitative metrics. This has implications for clinical and research use of SD-OCTA for retinal imaging.

Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography.

Purpose: We aimed to observe longitudinal changes in retinal blood flow (RBF) and structural transformations in capillaries using Doppler optical coherence tomography (DOCT) and optical coherence tomography angiography (OCTA) in a feline retinal blood occlusion (RVO) model. Methods: RVO was induced by argon green laser photocoagulation (PC) in six eyes of six cats. RBF was measured at a first-order retinal artery and vein by a DOCT flowmeter, and structural changes in the capillaries around the occluded vessels (12 × 12 and 3 × 3 mm) were assessed by OCTA before (at baseline); immediately after PC; and on days 1, 4, 7, and 14 thereafter. Systemic and ocular parameters were monitored during the observation period. Results: There were no significant differences in any systemic or ocular parameters before and after PC. Arterial RBF increased significantly on day 1 (160.6 ± 8.6% vs. baseline, P < 0.001) and decreased below baseline after day 1 through 14. Venous RBF decreased immediately after PC (17.4 ± 9.6% vs. baseline, P = 0.001) and then gradually increased afterwards, but did not return to baseline. OCTA showed dilatation of retinal venules immediately after PC to day 1. Collateral vessels began to form on day 4, had matured by day 7, and were pruned on day 14, which formed as mature as normal retinal venule diameters. Conclusions: With increasing arterial RBF within 1 day after inducing RVO, venules gradually expanded to form collateral vessels, suggesting that collateral vessels originate from existing capillary networks, not neovascularization.

Global Analysis of Macular Choriocapillaris Perfusion in Dry Age-Related Macular Degeneration using Swept-Source Optical Coherence Tomography Angiography.

Purpose: Swept-source optical coherence tomography angiography (SS-OCTA) was used to investigate if the clinical stage of dry age-related macular degeneration (AMD) was correlated with global and regional macular choriocapillaris (CC) perfusion. Methods: In this retrospective, cross-sectional study, 6 × 6-mm SS-OCTA images from eyes with early, intermediate, and advanced dry AMD (56 eyes, 41 patients) were analyzed using algorithms described in the literature to assess regional flow deficit percentage (FD%) and average flow deficit size. Regions were defined by concentric areas centered on the fovea: a 1-mm-diameter area, 3-mm-diameter ring, 5-mm-diameter area, 5-mm-diameter ring, and 6 × 6-mm whole image. Data were modeled using the generalized estimating equations approach. Results: The relationship between age and CC FD% and average flow deficit size was statistically significant (P ≤ 0.05) in all regions of analysis by linear modeling. The relationship between dry AMD stage and FD% was statistically significant by linear modeling in the 5-mm ring, and between dry AMD stage and average flow deficit size in the 3-mm ring, 5-mm area, 5-mm ring, and 6 × 6-mm whole image. Conclusions: Linear modeling suggests a statistically significant relationship between dry AMD stage and CC perfusion, most prominent in the more peripheral regions of the macula.

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.

Accuracy and Reliability in Differentiating Retinal Arteries and Veins Using Widefield En Face OCT Angiography.

PURPOSE: To evaluate the accuracy and reliability in differentiating retinal arteries from veins using widefield optical coherence tomography angiography (OCTA). METHODS: Ten healthy eyes and 12 eyes from diabetic patients were included. Foveal-centered swept-source OCTA images (12 × 12 mm) were obtained using the PLEX Elite 9000. Vessels were graded as arteries or veins by two independent, masked readers. Arteriovenous crossings were also evaluated in healthy eyes. The vessel identification gold standard was defined using color fundus photographs (CFP) for normal eyes and both CFP and fluorescein angiography for diabetic eyes. Grading accuracy was compared to the gold standard and reliability between readers assessed. RESULTS: The study evaluated 538 vessels (119 first order, 110 second, 309 third) in healthy eyes and 645 vessels (184 first order, 159 second, 302 third). In healthy eyes, the average accuracies identifying all, first-, second-, and third-order vessels were 98.61%, 99.16%, 100%, and 98.06%, respectively. Cohen's κ between graders in all vessels was 0.948. In diabetic eyes, the average accuracies identifying vessels were 96.90%, 99.46%, 97.77%, and 94.85%, respectively. Cohen's κ between graders for all vessels was 0.888. For crossing identification, the average accuracy and Cohen's κ were low (60.71% and 0.659, respectively). CONCLUSIONS: En face OCTA allows for accurate and reliable artery and vein identification; for small branches and crossings, identification by en face OCTA alone may be less accurate and reliable. TRANSLATIONAL RELEVANCE: Arteries and veins can be differentiated on OCTA, assisting in clinically identifying pathology as arterial or venous side.

A Case of Progressive Diabetic Retinopathy Related to Pregnancy Followed on Optical Coherence Tomography Angiography.

A 27-year-old woman with type 2 diabetes mellitus had mild diabetic retinopathy (DR) during the early gestation period. Optical coherence tomography angiography (OCTA) showed microaneurysms and small capillary nonperfusion with little change until before delivery. The patient later developed pregnancy-induced hypertension, which continued after delivery, and the DR worsened markedly. OCTA showed onset and recovery of paracentral acute middle maculopathy. Macular edema (ME) also developed, and OCTA showed irregular dilation in the radial peripapillary capillaries. After starting antihypertensive therapy, the capillary dilation and ME decreased. OCTA enables close follow-up of DR related to pregnancy during the perinatal period. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:393-397.].

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.

Effect of ripasudil on diabetic macular edema.

The current study aimed to address whether ripasudil, a Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor developed to treat glaucoma and ocular hypertension (OH), improves diabetic macular edema (DME) since it is known that ROCK upregulates vascular endothelial growth factor. We retrospectively investigated the foveal thickness (FT) measured by spectral-domain optical coherence tomography, visual acuity (VA), and intraocular pressure (IOP) in 12 eyes with DME that received ripasudil treatment for primary open-angle glaucoma or OH and compared them with 14 eyes that received no treatment. One month after ripasudil therapy, the mean FT decreased significantly from 439 ± 72 µm to 395 ± 62 µm (P = 0.003); this change was significantly different from that in the controls, in which the mean FT increased by 1 ± 39 µm (P = 0.01). Ripasudil also caused a significant decrease in IOP from 17.3 ± 5.2 mmHg to 14.6 ± 4.0 mmHg (P = 0.02); this change was significantly greater than that in the controls, in which IOP changed by 0.0 ± 1.6 mmHg (P < 0.008). There was no significant difference in the VA changes between groups. Our results suggested that ripasudil may have positive effects on both IOP and DME.