Structural and vascular correlates of visual field defects in branch retinal vein occlusion: a multimodal imaging study.

Objective To observe the alterations of macular vascular density and the area of foveal avascular zone (FAZ) in branch retinal vein occlusion (BRVO) eyes. Methods A retrospective case-control study. Forty-five patients with unilateral BRVO and macular edema were enrolled in this study. Optical coherence tomography angiography (OCTA) was performed on the BRVO and fellow eyes. The scanning region in the macular area was 3 mm×3 mm. Macular vascular density and FAZ area in the superficial and deep retinal capillary plexi were measured in all eyes. The values of macular vascular density and FAZ area between BRVO eyes and fellow eyes, affected sector and unaffected sector were compared. Results The mean overall vascular density measured in the entire scan was lower in BRVO eyes compared with fellow eyes in both the superficial and deep capillary plexus (t=14.186, 9.468; P<0.05). The reduce degree of vascular density in the deep capillary plexus (7.65%) was higher than that in the superficial plexus (7.27%). In the superficial plexus, the vascular density was lower in the affected sector and the unaffected sector of the BRVO eyes compared with the corresponding sector in the fellow eyes (t=15.386, 9.435; P<0.05). The FAZ area enlarged in the BRVO eyes compared with the fellow eyes in the superficial capillary plexus and in the deep capillary plexus (t=3.216, 5.119; P<0.05). The degree of enlargement of FAZ area in the deep capillary plexus (0.19 mm2) was higher than that in the superficial plexus (0.11 mm2). Conclusions In eyes with BRVO, quantitative OCTA measurements confirm that vascular density decreased and FAZ area enlarged in the superficial and deep capillary plexi. The reduce degree of vascular density and enlargement degree of FAZ area in the deep capillary plexus are higher than those in the superficial plexus. Key words: Retinal vein occlusion/diagnosis; Regional blood flow; Tomography, optical coherence

To investigate systematically the retinal changes in branch retinal vein occlusion (BRVO) and their natural history. The study comprised 214 consecutive patients with BRVO (144 major BRVO and 72 macular BRVO eyes) seen within 3 months of onset. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography. Initially, retinal hemorrhages were moderate to severe in the perifovea and macula in at least 65% in major and 52% in macular BRVO; at the fovea, it was 51% in major and 36% in macular BRVO. Initially, macular edema was more marked in major BRVO than in macular BRVO (P = 0.007). Major BRVO had a significantly higher rate of development of serous macular detachment (P = 0.002), epiretinal membrane (P = 0.008), serous retinal detachment (P = 0.002), perivenous sheathing (P < 0.0001), optic disk pallor (P < 0.0001), and lipid deposit (P < 0.0001) compared with macular BRVO. Retinal and disk neovascularization was seen only in major BRVO. The time to resolution of BRVO was significantly longer for major BRVO compared with macular BRVO (P = 0.0002). Major and macular BRVOs are two distinct clinical entities. Initial and final fundus findings in the two types differ markedly.

PurposeExamine associations between the vasculature at arteriovenous (AV) crossings and the onset of branch retinal vein occlusion (BRVO).MethodsWe included 78 patients with major BRVO, 35 patients with macular BRVO, and 110 controls without BRVO and determined the vessel positions at AV crossings, where the first- or second-order branches of the retinal veins associate, using a viewing angle of 12 × 12 mm2 in optical coherence tomography angiography (OCTA).ResultsWe reviewed 1349 and 1276 AV crossings in BRVO patients and control subjects, respectively. The proportions of venous overcrossing were 26.5%, 28.6%, and 26.8% at non-causative crossings in BRVO eyes, non-BRVO fellow eyes, and unaffected control eyes, respectively; however, the rate of venous overcrossings at the causative crossings was 45.1%. In OCTA analyses, we divided the branches into macular- or non-macular veins. The rate of venous overcrossing was 52.5% at causative crossings in major BRVO but was 28.6% in macular BRVO. Odds ratios for whether venous overcrossing was a risk factor for BRVO were 3.09 (95% confidence interval [CI], 1.96–4.88) and 0.94 (95% CI, 0.44–2.00) for non-macular veins and macular veins, respectively. The patients with major BRVO caused by venous overcrossing were younger than patients for whom the cause was arterial overcrossing (P < 0.001). The onset of macular BRVO did not differ between crossing patterns at causative crossings (P = 0.60).ConclusionsIn eyes with BRVO, venous overcrossing was a common angiographic feature at causative crossings and might be a risk factor for major BRVO onset.

Purpose: My aim was to evaluate the effect of intravitreal bevacizumab and to determine the concentrations of inflammatory cytokines in patients with macular edema due to branch retinal vein occlusion (BRVO), according to the site of the occlusion. Methods: In a prospective interventional case series, 46 eyes of patients with macular edema due to major (n = 30) or macular BRVO (n = 16) were included. The patients were treated primarily with intravitreal bevacizumab (1.25 mg/0.05 ml) and completed 12 months of follow-up. Reinjections were performed if optical coherence tomography showed persistent or recurrent macular edema. Aqueous humor samples were collected at the time of initial intravitreal injection. Multiplex bead assays were used for the measurement of cytokines. Results: The visual acuity and central macular thickness were improved significantly in patients with major and macular BRVO at 12 months. During 12 months, the eyes with major BRVO received a mean of 3.8 intravitreal injections, whereas those with macular BRVO received a mean of 1.9 intravitreal injections (p = 0.009). Significantly increased concentrations of IL-6, IL-8 and MCP-1 were observed in the aqueous humor of BRVO patients compared with control samples. Higher concentrations of IL-6, VEGF, PDGF-AA and MCP-1 were measured in the aqueous humor of patients with major BRVO compared with macular BRVO at baseline (p < 0.05). Conclusion: Intravitreal bevacizumab was similarly effective for improving macular edema in patients with major and macular BRVO. However, macular BRVO required fewer injections and had lower cytokine levels in the aqueous humor than major BRVO.

To analyze the correlation of superficial and deep capillary plexuses using optical coherence tomography (OCT) angiography with visual acuity in eyes with retinal vein occlusion (RVO). We retrospectively reviewed the medical records of 33 patients with retinal vein occlusion (RVO; branch retinal vein occlusion in 21 patients, central retinal vein occlusion in 12 patients) and included 33 healthy subjects as a control group, who were evaluated by OCT angiography. The OCT angiography was performed on a 3 mm × 3-mm region centered on the fovea and parafoveal area. The foveal avascular zone (FAZ), and foveal and parafoveal vascular density (VD) in superficial and deep vascular plexuses were analyzed using OCT angiography. The area of superficial and deep FAZ in eyes with RVO were larger than those in fellow eyes and control eyes (P = 0.034, P = 0.018). The superficial and deep parafoveal VDs in eyes with RVO were significantly lower than those in fellow eyes and control eyes (P = 0.001, P< 0.001). The area of superficial FAZ was negatively correlated with best-corrected visual acuity, and the superficial and deep parafoveal VDs were positively correlated with best-corrected visual acuity. Eighteen of the total 21 eyes with branch retinal vein occlusion (85.7%) showed a high concordance rate with respect to the location of branch retinal vein occlusion and the lowest parafoveal VD area. The multivariate analysis showed that the deep parafoveal VD was associated with best-corrected visual acuity. The OCT angiography allows to detect FAZ enlargement, increased parafoveal capillary nonperfusion, and decreased parafoveal VD in eyes with RVO. The area of superficial FAZ and the parafoveal VD are correlated with best-corrected visual acuity in eyes with RVO.

We non-invasively evaluated macular non-perfused areas (m-NPAs) of branch retinal vein occlusion (BRVO) using optical coherence tomography (OCT) angiography and the Humphrey visual field analyser 10-2 programme (HFA 10-2). We enrolled 30 patients (30 eyes) with macular oedema secondary to BRVO. OCT angiography was used to photograph the macula at 6 × 6-mm; sizes of m-NPAs in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured in four areas. For HFA 10-2, we divided the actual measurement threshold of 68 points into four areas and calculated the mean central visual field sensitivity (CVFS). The correlation between the mean m-NPA and mean CVFS (dB) in each area was examined. There was a strong correlation between the m-NPA of each region detected in SCP and DCP, and the mean CVFS of each corresponding area (SCP: r = − 0.83, r = − 0.64, r = − 0.73, and r = − 0.79; DCP: r = − 0.82, r = − 0.71, r = − 0.71, and r = − 0.70), p values were < 0.001 for all. m-NPAs were associated with decreased visual field sensitivity in BRVO. Non-invasive m-NPA evaluation was possible using OCT angiography and HFA 10-2.

Background: To evaluate the quadrantal effect of branch retinal vein occlusion (BRVO) on retinal microvasculature and ganglion cell-internal plexiform layer thickness (GC-IPL)Materials and Methods: This retrospective study included 62 eyes of 31 patients diagnosed with unilateral BRVO. Participants had optical coherence tomography (OCT) and OCT angiography (OCTA) analyses after complete regression of the macular edema. The macular central subfield thickness (CST), GC-IPL thickness, vessel and perfusion density (VD and PD), and foveal avascular zone (FAZ) area of the superficial capillary plexus (SCP) were evaluated in both groups. We also compared the affected and opposite unaffected quadrant measurements in BRVO eyes with the corresponding quadrant to BRVO (BRVO-corresponding) in the fellow eye.Results: The mean FAZ area, VD, and PD of SCP demonstrated no significant difference between BRVO and fellow eyes of BRVO (p&amp;gt;0.05 all). The mean GC-IPL thickness, the mean VD of the parafoveal and perifoveal ring, and mean PD of the perifoveal ring were significantly decreased in the affected quadrant of BRVO eyes (p&amp;lt;0.05 all). In the post hoc tests, the VD of the parafoveal and perifoveal ring was significantly lower in the affected quadrant than the unaffected and BRVO-corresponding quadrant (p&amp;lt;0.05 all). A post hoc analysis revealed that the PD was significantly lower in the affected quadrant than the unaffected and BRVO-corresponding quadrant (p=0.017, p=0.025). Conclusions: The microvascular changes in the macular superficial capillary plexus accompany significant ganglion cell loss in BRVO. The microvascular and microstructural alterations were mainly localized to the distribution area of the occluded vein.Key Words: Retinal blood vessels, Retinal vein occlusion, Macular edema

The retinal and choroidal parameters were analyzed to understand the impairment of microcirculation of both retina and choroid in patients with diabetic retinopathy (DR). Fifty-five treatment-naive non-proliferative diabetic retinopathy (NPDR) patients (75 eyes) with type 2 diabetes mellitus (T2DM), including 28 patients (36 eyes) with diabetic macular edema (DME) and 27 patients (39 eyes) without DME, and 25 healthy subjects (47 eyes) were enrolled in this study. The following parameters of DR patients with and without DME were evaluated: the foveal avascular zone area (FAZ-a), FAZ perimeter (FAZ-p), FAZ circularity index (FAZ-CI), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow area percentage, superficial capillary plexus (SCP), and deep capillary plexus (DCP). SCP, DCP, and the percentage of choriocapillaris flow area were significantly different between DR patients with and without DME. The DR patients presented lower LA, CVI, and FAZ-CI compared to those of healthy controls (all p < 0.05). The percentage of choriocapillaris flow area in DR patients with and without DME was significantly lower than that in healthy controls (p < 0.05). SCP and DCP were significantly correlated with FAZ-a and FAZ-p but presented insignificant associations with FAZ-CI. Optical coherence tomography (OCT) and OCT angiography (OCTA) parameters, such as LA, CVI, FAZ-CI, and the percentage of choriocapillaris flow area, were reduced compared to those in controls, indicating that the microcirculations of the retina and choroid in the macular area were impaired in DR patients with DME and without DME.

Understanding the natural history of visual outcome in branch retinal vein occlusion (BRVO) is fundamental to its management. To investigate the natural history of visual outcome in major and macular BRVO. Observational cohort study at a university-based referral practice from 1973 until 1999. The study comprised 216 consecutive eyes with BRVO (144 eyes with major and 72 eyes with macular BRVO) seen within 3 months of onset. At first visit, all patients had a detailed ophthalmic and medical history and comprehensive ophthalmic evaluation. Ophthalmic evaluation at initial and follow-up visits included recording best-corrected visual acuity (VA) using the Snellen VA chart and visual fields with a Goldmann perimeter. Best-corrected VA and visual field outcome on follow-up. The median time to macular edema resolution was 21 months in those with major BRVO and 18 months in those with macular BRVO. Overall, for eyes with initial VA of 20/60 or better, VA improved or remained stable in 75% (95% CI, 63%-86%) for major BRVO and 86% (95% CI, 73%-95%) for macular BRVO. In those with initial VA of 20/70 or worse, VA improved in 69% (95% CI, 56%-80%) for major BRVO and in 53% (95% CI, 27%-79%) for macular BRVO, with median final VA of 20/60 for both BRVO types. Major and macular BRVOs are 2 distinct clinical entities, and initial visual status and final visual outcome in the 2 types are quite different. Overall, on resolution of macular edema, our study suggests that in both major and macular BRVO, VA and visual fields improved to a variable degree in the majority of eyes without any treatment.

To evaluate the relationship between the extent of branch retinal vein occlusion (BRVO) and the incidence of serous retinal detachment (SRD) in the macular area. One hundred nine eyes of 109 consecutive patients with BRVO comprised the study population. These eyes were characterized as having either macular BRVO or major BRVO. We compared the tomographic macular findings between the two groups. Thirty-nine eyes had macular BRVO, and 70 eyes had major BRVO. The incidence of SRD was higher in the group with major BRVO (63%) than in the group with macular BRVO (21%) (P < 0.001). The incidence of cystoid macular edema was similar in both groups (macular BRVO, 97%; and major BRVO, 90%). Foveal thickness of major BRVO (610 +/- 190 micro m) was significantly greater than that of macular BRVO (500 +/- 140 micro m) (P < 0.01). There was no significant difference in thickness of the neurosensory retina between the group with macular BRVO (450 +/- 120 micro m) and the group with major BRVO (480 +/- 140 micro m). Serous macular detachment occurs more frequently in major BRVO than in macular BRVO. Vascular leakage from congested retinal veins outside the macular area appears to be a major source of subretinal fluid at the fovea.

The retinal microvascular density changes have been identified in thyroid-associated ophthalmopathy (TAO) patients. Whereas a lack of research has been done on the diagnostic ability of optical coherence tomography (OCT) combined with optical coherence tomography angiography (OCTA) parameters. This study aims to evaluate the retina perfusion variations in eyes with active and stable TAO and its diagnostic abilities using OCT and OCTA. This is cohort longitudinal retrospective study. A total of 51 patients with TAO and 39 healthy controls (HCs) were recruited. The TAO eyes were divided into active and stable stage groups. The foveal avascular zone (FAZ), macular perfusion density (mPD), and peripapillary PD were measured by OCTA. The peripapillary retinal nerve fiber layer (RNFL), central retinal thickness (CRT), and whole macular volume (wMV) were measured by OCT. Visual evoked potential (VEP) and visual field (VF) were also assessed. The mPD of the superficial retinal capillary plexus (SRCP) was significantly different in all subfields among active, stable, and HC groups (p < 0.05) except for the temporal inner (p = 0.137), and the active group achieved the lowest PD. The FAZ size increased significantly in the active and stable groups compared with the HC group (p < 0.001). Significant difference was observed in mPD of deep retinal capillary plexus (DRCP) in all quadrants among three groups (p < 0.05). Moreover, PD parameters of optic nerve head (ONH) and radial peripapillary capillary plexus (RPCP) showed a different trend among three groups (p < 0.05). The r-value of visual field-mean deviation (VF-MD) of TAO with DRCP-whole PD (wPD) and RPCP-wPD was 0.421 and 0.299, respectively (p < 0.05). The DRCP-wPD in OCTA and RNFL in OCT were significantly higher in area under the receiver operating characteristic curve (AUC) than that of HC eyes. OCT and OCTA can noninvasively detect the peripapillary and macular changes in various stages of TAO patients, and it might be a high diagnostic value tool to monitor the TAO progression.

Combining Optical Coherence Tomography and Optical Coherence Tomography Angiography Longitudinal Data for the Detection of Visual Field Progression in Glaucoma

Purpose: To provide clinical evidence of the associations between retinal neuronal degeneration and microvasculopathy in diabetic retinopathy (DR).Methods: This case-control study included 76 patients (76 eyes) with type 2 diabetes mellitus (DM), and refraction error between −3.0 and +3.0 D. The eyes were assigned into DM (without DR), non-proliferative DR (NPDR), and proliferative DR (PDR) groups. Age-, sex-, and refractive error-matched normal subjects were enrolled as controls. The mean retinal thickness (mRT), the relative mean thickness of the retinal nerve fiber layer (rmtRNFL, mtRNFL/mRT), ganglion cell layer (rmtGCL), ganglion cell complex (rmtGCC) layer, foveal avascular zone area (FAZa), FAZ perimeter (FAZp), FAZ circularity index (FAZ-CI), and vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Group comparison and Spearman's partial correlation coefficient analysis were applied to evaluate the correlation between these morphological parameters.Results: rmtRNFL, FAZa, and FAZp in SCP and DCP increased with the DR severity (prmtRNFL < 0.001; pFAZa, SCP = 0.001; pFAZa, DCP = 0.005; pFAZp, SCP < 0.001; pFAZp, DCP < 0.001). The rmtGCL, FAZ-CI in SCP and DCP, and VD in DCP decreased with the DR severity (prmtGCL = 0.002, pFAZ−CI, SCP = 0.002; pFAZ−CI, DCP < 0.001, pVD, DCP < 0.001). After controlling age, sex, duration of diabetes, and hypertension, the rmtRNFL, FAZa in SCP and DCP, and FAZp in SCP and DCP were correlated with the severity of DR (p < 0.05), while VD in SCP and DCP, FAZ-CI, and rmtGCL were negatively correlated with the severity of DR (p < 0.05). The rmtGCL was negatively correlated with the FAZa in SCP (r = −0.34, p = 0.002) and DCP (r = −0.23, p = 0.033), and FAZp in SCP (r = −0.37, p = 0.001) and DCP (r = −0.32, p = 0.003), but positively correlated with VD in SCP (r = 0.26, p = 0.016), VD in DCP (r = 0.28, p = 0.012), and FAZ-CI in DCP (r = 0.31, p = 0.006).Conclusions: rmtRNFL, FAZ-CI in SCP and DCP, and FAZp in SCP are strong predictors of the severity of DR. The ganglion cell body loss is highly correlated with increased FAZp and FAZa, decreased FAZ-CI, and reduced VD with the severity of DR.

To analyze microvascular and structural changes in radiation maculopathy and their influence on visual acuity (VA), using optical coherence tomography (OCT) and OCT angiography (OCTA). This was a retrospective analysis of consecutive patients with radiation maculopathy, 12 months or more after proton-beam irradiation for uveal melanoma, imaged with fluorescein angiography, OCT, and OCTA. Clinical parameters potentially affecting VA were recorded, including OCTA-derived metrics: foveal avascular zone (FAZ) area, vascular density, and local fractal dimension of the superficial (SCP) and deep capillary plexuses (DCP). Nonirradiated fellow eyes served as controls. Ninety-three patients were included. FAZ was larger, while SCP/DCP capillary density and local fractal dimension were lower in the 35 irradiated than in the 35 fellow eyes (P < 0.0001). Microvascular alterations graded on fluorescein angiography (minimally damaged/disrupted/disorganized) were correlated to FAZ area and SCP/DCP density on OCTA (P < 0.01). By univariate analysis, worse VA was associated to macular detachment at presentation (P = 0.024), total macular irradiation (P = 0.0008), higher central macular thickness (CMT) (P = 0.019), higher absolute CMT variation (P < 0.0001), cystoid edema (P = 0.030), ellipsoid zone disruption (P = 0.002), larger FAZ (P < 0.0001), lower SCP (P = 0.001) and DCP capillary density (P < 0.0001), and lower SCP (P = 0.009) and DCP local fractal dimension (P < 0.0001). Two multivariate models with either capillary density or fractal dimension as covariate showed that younger age (P = 0.014/0.017), ellipsoid zone disruption (P = 0.034/0.019), larger FAZ (P = 0.0006/0.002), and lower DCP density (P = 0.008) or DCP fractal dimension (P = 0.012), respectively, were associated with worse VA. VA of eyes with radiation maculopathy is influenced by structural and microvascular factors identified with OCTA, including FAZ area and DCP integrity.

Background/aimsTo evaluate the respective roles of systemic vascular vulnerability and local vascular anatomy in the onset of branch retinal vein occlusion (BRVO) by analysing the retinal age gap and arteriovenous crossing patterns.MethodsThis observational study enrolled 202 patients with unilateral BRVO and 100 age-matched, sex-matched and axial length-matched healthy controls. A deep learning model was applied to colour fundus images to estimate the retinal age; the retinal age gap (predicted retinal age minus chronological age) in the fellow eye was used as a surrogate residual marker of systemic vascular vulnerability. At the occlusion site, arteriovenous crossing was classified (arterial vs venous overcrossing) using optical coherence tomography angiography (OCTA).ResultsThe mean retinal age gap was 1.8±6.5 years and 0.2±6.0 years in the BRVO and control groups, respectively. Retinal age gap was significantly larger in BRVO eyes than in control eyes (p=0.046). A larger retinal age gap in the fellow eye correlated with younger age at BRVO onset (ρ= –0.350, p<0.001). Among 156 BRVO eyes with OCTA data, venous overcrossing at the occlusion site was more frequent in younger-onset major BRVO (p=0.031), whereas in macular BRVO, onset age did not differ by crossing pattern (p=0.734).ConclusionBoth systemic vascular vulnerability, reflected by a larger retinal age gap and local anatomical configuration, represented by venous overcrossing, may jointly contribute to BRVO susceptibility, particularly in younger patients. These findings should be interpreted with caution because the retinal age gap is a prediction, using a deep learning model, rather than a direct biological measure.