Areas Of Retinal Nonperfusion Research Articles

Systemic microvascular rarefaction is correlated with dysfunction of late endothelial progenitor cells in mild hypertension: a substudy of EXCAVATION-CHN1

BackgroundHypertension often presents with microvascular rarefaction (MVR), which is closely associated with impaired angiogenesis. Early detection of MVR is essential for systemic assessment in patient with hypertension. We aimed to determine the systemic MVR through both optical coherence tomography angiography (OCTA) and intravital capillaroscopy, and to investigate their respective efficacies and related mechanisms associated with late endothelial progenitor cells (LEPCs) dysfunction.MethodsSeventy-one hypertensive and sixty-nine age-match normotensive subjects were included in this study. All subjects received intravital capillaroscopy for skin capillary density (SCD) and OCTA for retinal capillary density (RCD) and non-perfused areas (R-NPA). Subsequently, correlation of LEPCs activities and microvascular rarefaction were examined.ResultsCompared with normotensive subjects, hypertensive patients had significantly lower RCD [(52.9 ± 2.9)% vs. (57.8 ± 1.6)%, P < 0.01] and higher R-NPA [(0.12 ± 0.07) mm2 vs. (0.053 ± 0.020) mm2, P < 0.01]. SCD correlated positively with RCD but negatively with R-NPA [(RCD: OR = 0.40, 95% CI 0.25–0.67, P < 0.01); (R-NPA: OR = 0.39, 95% CI − 0.0029 to 0.0011, P < 0.01)]. The discriminative powers of RCD performed best (AUC 0.79 versus SCD AUC 0.59, P < 0.001) followed by R-NPA (AUC 0.73 versus SCD AUC 0.59, P < 0.001) for systolic blood pressure. Similar pattern is also found for diastolic blood pressure (RCD AUC 0.80 versus SCD AUC 0.54, P < 0.001; R-NPA AUC 0.77 versus SCD AUC 0.54, P < 0.001). Furthermore, LEPCs tube formation was impaired in hypertensive patients (36.8 ± 2.3 vs. 28 ± 3.7, P < 0.01). After multivariate adjustments, positive correlation existed between RCD or R-NPA with LEPCs tube formation (RCD: β = 0.64, 95% CI 0.34–0.91, P < 0.01; R-NPA: β = − 24.67, 95% CI − 43.14 to − 4.63, P < 0.05) but not with SCD (β = 0.082, 95% CI 0.01–0.18, P = 0.085).ConclusionCompared to intravital capillaroscopy, OCTA is a more precise technique for early detection of hypertensive microvascular rarefaction, which is associated with the fall in LEPC-mediated angiogenesis. Both of OCTA and LEPCs function can help identify hypertension-related capillary abnormality.Trail Registration The trial is a substudy of EXCAVATION-CHN1, registered at clinicaltrials.gov as NCT02817204 (June 26, 2016).

Relationship Between Retinal Fractal Dimension and Nonperfusion in Diabetic Retinopathy on Ultrawide-Field Fluorescein Angiography

To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA). Cross-sectional study. Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared. While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P < .001). FD for the entire retina was negatively associated with global nonperfusion area (R=-0.44; P < .001), and this relationship was also present within the 3 concentric retinal zones (posterior: R=-0.31, P= .016; midperiphery: R=-0.35, P= .007; and far periphery: R=-0.31, P= .015). Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.

Arteriovenous crossing associated with branch retinal vein occlusion.

Branch retinal vein occlusion (BRVO) is defined as the focal occlusion of a first or second-order branch of retinal vein, which occurs most frequently at an arteriovenous (AV) crossing. Direct ophthalmoscopy, color fundus photography, and fluorescein angiography facilitate observation of AV crossings parallel to the retinal plane. Optical coherence tomography (OCT), with its high-depth resolution, enables observation of retinal lesions perpendicular to the retinal plane. OCT angiography (OCTA) provides depth-resolved images of the retinal vasculature by segmenting three-dimensional data. In this review, we discuss novel findings related to affected AV crossings associated with BRVO obtained via OCT and OCTA. The high-depth resolution of OCT or OCTA is useful for observation of the narrowed vein and determination of the vessel position of the affected AV crossing. Studies using OCT and OCTA have shown that BRVO caused by a venous overcrossing is more prevalent than previously reported, and that venous narrowing was significantly greater in instances caused by a venous overcrossing than in those caused by an arterial overcrossing. Moreover, OCTA also revealed that the retinal nonperfusion area size was larger in eyes with BRVO caused by a venous overcrossing than in those with BRVO caused by an arterial overcrossing. This contrasts with earlier findings obtained by conventional imaging modalities predating OCT, which showed that an arterial overcrossing was more common than a venous overcrossing at the causative venous occlusion site in eyes with BRVO. This review discusses these findings and their significance in the study of AV crossing associated with BRVO.

Prospective evaluation of intravitreal bevacizumab for ischemic central retinal vein occlusion

BackgroundAlthough previous studies have evaluated the effect of anti-VEGF therapies for central retinal vein occlusion (CRVO) patients, the majority of previous studies have excluded or included a very small number of patients with ischemic CRVO (iCRVO). The aim of our study is to examine the effects of bevacizumab on macular edema secondary to ischemic central retinal vein occlusion, as well as the effects on central choroidal thickness and best-corrected visual acuity.MethodsIn this prospective, interventional case series, iCRVO was defined by the presence of ≥ 10 or more disc diameter areas of retinal nonperfusion by fluorescein angiography (FA) and by the presence of a b/a ratio less than 1.5 by full-field electroretinogram (ffERG). Nine eyes with iCRVO received monthly bevacizumab 0.5 mg injections at baseline and months 1 to 5 for a maximum of six injections. Main outcome measures were visual acuity (Snellen), central foveal thickness, and central choroidal thickness as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT) at baseline and at 6 month following initial intravitreal bevacizumab injection. Pairwise t-tests and the Wilcoxon signed-rank test were conducted to compare the outcome measures.ResultsAfter intravitreal administration of bevacizumab, there was a significant reduction of central foveal thickness from 858 ± 311 μm at baseline to 243 ± 106 μm at the 6-month follow-up, as well as a significant reduction of central choroidal thickness from 282 ± 38 μm at baseline to 227 ± 56 μm at the 6-month follow-up (p = 0.0006, p = 0.0003 respectively). The visual acuity worsened from a median of 1.3 to 1.7 (p = 0.02).ConclusionIn patients with iCRVO, intravitreal bevacizumab led to a reduction of central macular edema and central choroidal thickness, but a worsening of visual acuity. Intravitreal bevacizumab reduces macular edema but is not able to overcome the poor prognosis of iCRVO.

Research progress of optical coherence tomography angiography in retinal vein occlusion

Retinal vein occlusion (RVO) is a vascular disease characterized by intraretinal hemorrhage, edema and hard exudation, which is caused by increased retinal vein pressure. OCT angiography (OCTA) has been widely used in the diagnosis of retinal vascular diseases including RVO by virtue of non-invasive, high resolution and stratified display of superficial, deep retinal vessels and quantification of retinal vessel density and non-perfusion area size. OCTA can provide information of retinal microvascular structure and blood perfusion under the condition of disease, it also can be used to evaluate the effect of treatment and changes of retinal circulation during the course of disease follow-up. Although OCTA cannot replace fundus angiography completely, it has brought us more information about the pathogenesis, disease progression and prognostic factors of RVO. It is believed that with the progress of technology, OCTA will bring us a new chapter in the study of retinal vascular diseases including RVO. Key words: Retinal vein occlusion; Tomography, optical coherence; Review

Intravitreal Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy: Outcomes from the Randomized RECOVERY Trial

Evaluate the impact of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) on retinal nonperfusion (RNP) in eyes with proliferative diabetic retinopathy (PDR). Prospective, randomized clinical trial. Eyes with treatment-naïve PDR and extensive RNP without diabetic macular edema. Patients were randomized 1:1 to intravitreal 2 mg aflibercept every 4 weeks (monthly) or every 12 weeks (quarterly). The primary outcome measure was change in total RNP area (in square millimeters) from baseline to year 1. Secondary outcomes included ischemic index (ISI), diabetic retinopathy severity scale (DRSS) scores, visual acuity, central retinal thickness, and adverse events. The mean and 95% confidence interval were calculated for each outcome. Through 1 year, the monthly (n= 20) and quarterly (n= 20) cohorts received 11.0 and 3.95 mean aflibercept injections, and DRSS scores improved 2 steps or more in 74% and 67% of patients, respectively. Among all patients through 1 year, mean total area of RNP increased from 235 mm2 to 266 mm2 (P= 0.18) and ISI increased from 25.8% to 31.9% (P= 0.004). Retinal nonperfusion outcomes favored monthly dosing. Mean total RNP increased from 207 mm2 at baseline to 268 mm2 (P= 0.01) at 1 year in the quarterly cohort and remained stable at 264 mm2 at baseline and 1 year (P= 0.70) in the monthly cohort (P= 0.05, monthly vs. quarterly cohorts). Although many eyes demonstrated increased areas of RNP longitudinally (n= 24 [66.7%]), this was more common with quarterly dosing (n= 14 [77.8%]), and a proportion of eyes (n= 12 [33.3%]) demonstrated localized areas of apparent reperfusion of nonperfused retina, more commonly in the monthly cohort (n= 8 [44.4%]). Widespread evidence of retinal reperfusion with aflibercept dosing of PDR eyes with extensive RNP was not identified, and therefore the primary outcome of the current study was not met. Nevertheless, zones of apparent reperfusion were detected in some patients, and a dose response was identified with a reduction of RNP progression with monthly compared to quarterly dosing.

The Relationship Between Retinal Vessel Oxygenation and Spatial Distribution of Retinal Nonperfusion in Retinal Vascular Diseases.

We study the relationship between retinal vessel oxygenation and the spatial distribution of retinal nonperfusion using ultrawide field angiography in eyes with retinal vascular diseases. This prospective single center study recruited 57 eligible eyes from 44 patients with retinal vascular diseases. Retinal oximetry measurements were obtained using the Oxymap T1 device to determine the arteriovenous (AV) difference. Retinal nonperfusion was measured from ultrawide field angiography images taken with the Optos 200TX system and superimposing the images with the concentric rings template to determine the area and distribution of retinal nonperfusion. Seven (12.3%) eyes had a diagnosis of a branch or hemiretinal vein occlusion, 24 (42.1%) with central retinal vein occlusion and 26 (45.6%) with diabetic retinopathy (11 [19.3%] nonproliferative and 15 [26.3%] proliferative diabetic retinopathy). The correlation between the total area of retinal nonperfusion with the AV difference controlling for age was not statistically significant (R = -0.103, P = 0.449). However, when analyzing the correlation of AV difference with the area of retinal nonperfusion in the posterior pole controlling for age and peripheral nonperfusion, this was significant (R = -0.295, P = 0.029). This was not significant for the area of retinal nonperfusion in the periphery while controlling for posterior pole nonperfusion and age (R = 0.124, P = 0.368). Retinal nonperfusion has a negative correlation with AV difference measured on retinal oximetry. This correlation is significant in the posterior pole, but not in the peripheral retina.

Branch Retinal Vein Occlusion: Treatment Outcomes According to the Retinal Nonperfusion Area, Clinical Subtype, and Crossing Pattern

This prospective study examined 58 eyes with branch retinal vein occlusion (BRVO) to investigate the effects of the nonperfusion area (NPA), clinical subtype, and crossing pattern on the 2-year outcomes of ranibizumab therapy for the macular edema (ME). All eyes received three initial monthly injections, followed by additional pro re nata (PRN) injections. The final best corrected visual acuity (BCVA) and ranibizumab injection number were not associated with the macular NPA or total NPA at baseline or month 12, and they showed no significant differences between the clinical subtypes. However, the incidence of neovascular changes was higher in the major BRVO group than in the macular BRVO group (P = 0.030). Twelve and 19 of the 34 eyes with major BRVO exhibited arterial overcrossing and venous overcrossing, respectively. At baseline, the total NPA did not differ according to the crossing pattern, however, the total NPA was significantly larger in the venous overcrossing group at month 12 (P = 0.047). At month 24, the incidence of neovascular changes was higher in the venous overcrossing group (P = 0.030). Following ranibizumab therapy for BRVO-associated ME, the clinical subtype and the arteriovenous crossing pattern may be associated with neovascular changes.

Retinal Nonperfusion Characteristics on Ultra-Widefield Angiography in Eyes With Severe Nonproliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy

Threshold of retinal nonperfusion for the development of proliferative diabetic retinopathy (PDR) is unclear. To identify a threshold of retinal nonperfusion for the presence of retinal neovascularization and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy (NPDR), PDR, neovascularization of the optic disc (NVD), and retinal neovascularization elsewhere (NVE). This cross-sectional image analysis study was performed between September 24, 2018, and October 24, 2018, at a multicenter national study in the United Kingdom. Baseline images were obtained from 2 completed randomized clinical trials (Ranibizumab for Diabetic Macular Edema Panretinal Photocoagulation [RDP] study and Clinical Efficacy of Intravitreal Aflibercept vs Panretinal Photocoagulation for Best Corrected Visual Acuity in Patients With Proliferative Diabetic Retinopathy at 52 Weeks [CLARITY] study). The RDP study recruited eyes with severe NPDR between April 1, 2014, and December 31, 2015, and the CLARITY study recruited eyes with PDR between August 22, 2014, and November 20, 2015. Ultra-widefield angiography images of eyes with no prior panretinal photocoagulation treatment were included. The total area of retinal nonperfusion, the area of posterior pole retinal nonperfusion, and the area of peripheral retinal nonperfusion were measured. A total of 92 patients (92 eyes) were included in the study: 59 in the PDR group (mean [SD] age, 42 [15] years; 20 female [33.9%]) and 33 in the NPDR group (mean [SD] age, 63 [10] years; 3 female [9.1%]). Forty eyes had NVE and 19 had NVD with or without NVE. We identified a retinal nonperfusion threshold of 118.3 disc areas (DA) with a specificity of 84.9% (95% CI, 68.1% to 94.9%) for PDR. The median area of retinal nonperfusion was 67.8 DA (95% CI, 44.2 to 107.3 DA) in the NPDR eyes and 147.9 DA (95% CI, 127.4 to 173.5 DA) for eyes with proliferative changes, with a difference of 69.0 DA (95% CI, 42.2 to 97.7 DA; P < .001). No difference was found in the median area of posterior nonperfusion between NPDR and PDR, with a difference of 0 DA (95% CI, -6.7 to 5.2 DA; P = .56). As for peripheral nonperfusion, NPDR eyes measured 64.1 DA and PDR eyes measured 130.6 DA, with a difference of 70.8 DA (95% CI, 48.4 to 94.9 DA; P < .001). Eyes with NVD had the largest total area of retinal nonperfusion, with a difference of 65.1 DA (95% CI, 28.6 to 95.8 DA; P < .001) compared with eyes with only NVE. These findings suggest eyes with at least 107.3 DA of nonperfusion are at risk of proliferative disease, and eyes with NVD have the largest area of retinal nonperfusion.

Evaluation of retinal nonperfusion in branch retinal vein occlusion using wide-field optical coherence tomography angiography.

To characterize wide-field optical coherence tomography angiography (OCTA) features of retinal nonperfusion in eyes with branch retinal vein occlusion (BRVO). Automated scanning of five 12×12-mm areas of swept-source OCTA and wide-field fluorescein angiography (FA) images was performed in a consecutive case series of 27 eyes in 27 patients with BRVO in this institutional cross-sectional study. The correlation between the areas of retinal nonperfusion detected by both examinations was assessed. Panoramic images obtained in five 12×12-mm OCTA scans in eyes with retinal nonperfusion were binarized or skeletonized, and the associations between vascular parameters such as vascular density (VD) and vascular length (VL) with the wide-field FA characteristics were evaluated. The mean area of retinal nonperfusion in the OCTA images was 81.0±66.8mm2 (range, 0.0-188.8). The mean areas of retinal nonperfusion in FA and the total FA images were, respectively, 84.7±72.5mm2 (range, 0.0-221.9) and 184.1±167.7mm2 (range, 0.0-515.0). The mean VD was 27.6±3.5% (range, 19.6-33.7), and the mean VL was 12.4±8.5% (range, 5.4-31.3). Separate regression analyses of the areas of retinal nonperfusion in FA (p=0.0004, R2 =0.4627) and the total FA (p=0.0008, R2 =0.4214) images showed a significant association with the VL. OCTA images based on wide-field technologies can quantitatively evaluate retinal nonperfusion in eyes with BRVO.

One year efficacy of intravitreal injection with ranibizumb for macular edema secondary to ischemic and non-ischemic central retinal vein occlusion

Objective To compare the one year efficacy of intravitreal injection with ranibizumb for macular edema (ME) secondary to ischemic and non-ischemic central retinal vein occlusion (CRVO). Methods A total of 88 patients (88 eyes) with ME secondary to CRVO were enrolled in this retrospective study. The best corrected visual acuity (BCVA) was detected by the Early Treatment Diabetic Retinopathy Study Chart. The optical coherence tomography was used to measure the foveal retinal thickness (CRT) and macular edema volume. The patients were divided into non-ischemic group and ischemic group, 44 eyes of 44 patients in each group. There was no significant differences in age (t=0.650, P=0.517) and gender (χ2=0.436, P=0.509) between the two groups. Compared with the ischemic group, the CRT was significantly decreased in the non-ischemic group (t=−2.291, P=0.024), and the edema volume in the macular area was significantly reduced (t=−2.342,P=0.022). All eyes were treated with continuous intravitreal injection of ranibizumab three times, and repeated injections were performed as needed. The patients without obvious ME regression after treatment were combined with triamcinolone acetonide injection. The patients with peripheral retinal non-perfusion area were combined with peripheral retinal laser photocoagulation. The follow-up was 1 year. The number of injections was counted. The changes of BCVA, CRT and edema volume in the macular area were compared between the two groups. Results During the 1-year follow-up period, 88 eyes were injected 1 to 10 times, with the mean of 4.51±2.33. The number of injections in the ischemic group and non-ischemic group were 4.55±1.59 and 4.48±2.91, respectively. There was no significant difference in the average number of injections between the two groups (t=0.136, P=0.892). The number of acetonide injections and laser treatment in the ischemic group was significantly higher than that in the non-ischemic group (t=3.729, 9.512; P<0.001). At the last follow-up, compared with the ischemic group, the BCVA was increased (t=8.128), the CRT was decreased (t=−7.029) and the edema volume in the macular area was decreased (t=−7.213) in the non-ischemic group (P<0.001). Conclusion Compared with ME secondary to ischemic CRVO, intravitreal injection of ranibizumab for ME secondary to non-ischemic CRVO has the better outcome of vision improvement and edema regression as well as less frequent of acetonide injections and laser treatment. Key words: Retinal vein occlusion/complications; Macular edema/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use

Retinal flow density by optical coherence tomography angiography is useful for detection of nonperfused areas in diabetic retinopathy.

Fluorescein angiography (FA) has been conventionally used for detection of retinal nonperfused area (NPA) in diabetic retinopathy (DR) in spite of its qualitative evaluation. Optical coherence tomography angiography (OCTA) has been recently reported to be useful for the quantification of retinal vascular disorder in DR. In this study, we examined whether retinal flow density (FD) measurement in OCTA was useful for NPA detection in DR. The study included 41 eyes from 29 patients with DR who underwent FA and OCTA. Regions surrounded by arteries or veins were extracted in the OCTA image, and the FDs in each region were measured by Image J. Furthermore, each region was classified as NPA or perfused area (PA) in FA. The receiver operating characteristic (ROC) curve was prepared by logistic regression analysis of the FD. The AUC (area under the ROC curve) and cutoff value of FD were also calculated. Two hundred fifty-two regions were analyzed and classified into 38 NPA regions and 214 PA regions using FA. FD of each capillary plexus in NPA was significantly smaller than in PA (p< 0.0001). The AUC of total capillary plexus layers (TCP), superficial capillary plexus layer (SCP), and deep capillary plexus layer (DCP) was 0.975, 0.974, and 0.971, respectively. All areas, where the FD was more than the cutoff value (0.07 in TCP), were diagnosed with PA. Three areas with intraretinal microvascular abnormalities (IRMA) were diagnosed as PA despite being below the cutoff value. FD measurement in OCTA is useful for NPA detection in DR.

Mechanistic Evaluation of Panretinal Photocoagulation Versus Aflibercept in Proliferative Diabetic Retinopathy: CLARITY Substudy.

PurposeThe purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy.MethodsThis is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA).ResultsThe AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, −0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45).ConclusionsIntravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks.

Activated Protein C for Ischemic Central Retinal Vein Occlusion: One-Year Results

Intravitreally administered activated protein C in 10 eyes with ischemic central retinal vein occlusion significantly improved macular edema; in 5 eyes, the reperfusion of the retinal nonperfused areas exceeded 50% of baseline.

A new perspective for analyzing clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome.

We aimed to analyze the clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Furthermore, we aimed to correlate the number and location of retinal aneurysms with the size of retinal non-perfusion area and neovascularization. Six patients with IRVAN syndrome (1 male and 5 females, age 5-38years) were enrolled in this study. Fundus fluorescein angiography (FFA) was used to determine the total number of retinal aneurysms, number of aneurysms within the first branch of the retinal artery, minimum distance between the non-perfusion margin and the optic disc, and the number of retinal aneurysms in each quadrant, as well as the type of neovascularization. The size of the non-perfusion area was positively correlated with the total number of retinal aneurysms, the number of aneurysms within the first branch of the retinal artery, and the number of retinal aneurysms in each quadrant (P < 0.05). During the 5-year follow-up, one patient exhibited a dynamic change in the number and location of retinal aneurysms. In IRVAN syndrome, the number and location of retinal aneurysms correlate with the size of retinal non-perfusion area and type of neovascularization.

Effects of ripasudil, a ROCK inhibitor, on retinal edema and nonperfusion area in a retinal vein occlusion murine model

Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are used to treat glaucoma patients and have protective effects on ischemic states. However, it is poorly understood how the ROCK pathway affects the pathological signs of retinal vein occlusion (RVO). In this study, we evaluated the effects of ripasudil, a ROCK inhibitor, on a murine RVO model. In vivo, RVO was induced by retinal vein laser irradiation in mice, and evaluated with ripasudil. In vitro, the effects of ripasudil were examined on tight junction protein integrity in human retinal microvascular endothelial cells (HRMECs). Moreover, we investigated the expression level of the phosphorylated myosin phosphatase target protein (MYPT)-1 after administration of ripasudil. Ripasudil significantly prevented deterioration, such as retinal edema, reduced the size of the nonperfusion area, and improved retinal blood flow. Ripasudil treatment inhibited disintegration of ZO-1 in HRMECs. Administration of ripasudil suppressed retinal phosphorylation of MYPT-1 in a murine RVO model. These findings indicate that ripasudil might be as a possible therapeutic agent for RVO.

Characteristics of Neovascularization in Early Stages of Proliferative Diabetic Retinopathy by Optical Coherence Tomography Angiography

To classify retinal neovascularization in untreated early stages of proliferative diabetic retinopathy (PDR) based on optical coherence tomography angiography (OCTA). A cross-sectional study. Thirty-five eyes were included. They underwent color fundus photography, fluorescein angiography (FA), and OCTA examinations. Neovascularizations elsewhere (NVEs), neovascularizations at the disc (NVDs), and intraretinal microvascular abnormalities (IRMAs) were scanned by OCTA. The origin and morphology of NVE/NVD/IRMA on OCTA were evaluated. Retinal nonperfusion areas (NPAs) were measured using ImageJ software. In 35 eyes successfully imaged, 75 NVEs, 35 NVDs, and 12 IRMAs were captured. Three proposed subtypes of NVE were identified based on the origins and morphologic features. Type 1 (32 of 75, 42.67%) originated from the venous side, in a tree-like shape. Type 2 (30 of 75, 40.00%) originated from capillary networks, with an octopus-like appearance. Type 3 (13 of 75, 17.33%) originated from the IRMAs, having a sea fan shape. NVD originated from the retinal artery, from the retinal vein, or from the choroid, and arose from the bending vessels near the rim of the optic disc. IRMA originated from and drained into retinal venules, extending into the retina. The initial layer and affiliated NPA were significantly different in the 3 subtypes of NVEs (all P < .01). OCTA allowed identification of the origins and morphologic patterns of neovascularization in PDR. The new classification of retinal neovascularization may be useful to better understand pathophysiological mechanisms and to guide efficient therapeutic strategies.

Analysis of Retinal Nonperfusion Area and Ganglion Cell Layer Thickness in Branch Retinal Vein Occlusion by OCT-Angiography

Analysis of Retinal Nonperfusion Area and Ganglion Cell Layer Thickness in Branch Retinal Vein Occlusion by OCT-Angiography

Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial

To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). Phase I/II prospective, randomized, controlled clinical trial. Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 μm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P= 0.20) and mean CRT improved 302 and 152 μm (P= 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P= 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P= 0.30). In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone.

A case of proliferative diabetic retinopathy in which scintillating particles appeared in the intravitreal cavity after laser photocoagulation

BackgroundTo report a case of proliferative diabetic retinopathy (PDR) exhibiting the appearance of scintillating particles presumed to be crystallin inside the intravitreal cavity after laser photocoagulation.Case presentationA 56-year-old male patient presented at our outpatient clinic after becoming aware of decreased vision in his right eye. Ocular examination performed at the patient’s initial visit revealed a massive preretinal macular hemorrhage due to PDR in his right eye. Fundus fluorescein angiography revealed extensive retinal non-perfusion areas and neovascularization in both eyes. However, no opacity was observed in the intravitreal cavity of his left eye. Vitreous surgery was performed on the patient’s right eye after ultrasonic phacoemulsification aspiration and intraocular lens implantation. Post surgery, the corrected VA in that eye improved from 0.1 to 1.0. In correlation with the treatment performed on the patient’s right eye, we began panretinal photocoagulation on his left eye. Examination performed prior to the patient’s third session of panretinal photocoagulation revealed a large number of scintillating particles in the posterior vitreous gel in front of the retina. Examination via slit-lamp microscopy revealed that the particles were of varied hues, and closely resembled a ‘Christmas tree’ cataract. No posterior vitreous detachment was observed, and since these particles were situated as if captured in the posterior vitreous gel, no eye-movement-associated mobility of the particles was observed. Since the cloudiness was not severe enough to interfere with photocoagulation, additional photocoagulation was performed, and the patient is currently under observation. Six months have now passed since the fourth photocoagulation procedure was performed, and there has been no change in the state of the particles. Optical coherence tomography imaging revealed no change before and after the panretinal photocoagulation. The corrected VA in his left eye has remained at 1.0 during the postoperative follow-up period.ConclusionsWe speculate that the production of crystallin in the retina in this case was triggered by the photocoagulation procedure performed for diabetic retinopathy.