Retinal Vein Occlusion Eyes Research Articles

The prevalence of vitreomacular adhesion in eyes with macular oedema secondary to retinal vein occlusion selected for intravitreal injections.

To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with macular oedema (ME) secondary to retinal vein occlusion (RVO) and to longitudinally evaluate the incidence of vitreomacular interface changes over time and the influence on response to treatment. Retrospective cross-sectional analysis and longitudinal cohort study conducted at two Italian tertiary referral centres. A total of 295 eyes, treated with intravitreal ranibizumab and/or dexamethasone for ME secondary to RVO between June 2008 and May 2018, were enrolled in the study. 280 fellow eyes met the inclusion criteria and were included as control group. The vitreomacular interface status was evaluated by spectral domain optical coherence tomography (OCT) and graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study (IVTS) group. At baseline, VMA was present in 130 (44.07%) RVO eyes and 142 (50.7%) control eyes (no statistically significant difference was found; p=0.455). Mean follow-up (FU) was 35.98months (min 6 - max 112). Throughout the FU, the incidence of spontaneous release of VMA (RVMA) in RVO eyes was significantly higher in comparison with that of the control group [59 (41.84%) RVO eyes versus 18 (12.33%) control eyes; p<0.0001]. The number of injections in VMA+ eyes was significantly higher when compared with VMA- eyes. No significant difference was found between VMA+ and VMA- eyes regarding their mean best-corrected visual acuity (BCVA) at baseline and at each annual time point (p=0.2). Differences in central macular thickness (CMT) were significant only at the baseline evaluation (p=0.0303). Vitreomacular adhesion (VMA) was not found to be more prevalent in eyes with RVO compared to healthy fellow eyes, and RVO, in turn, did not result in a higher persistence of VMA over time. This suggests that VMA and RVO might be two independent retinal phenomena, with no mutual pathogenetic influence. Vitreomacular adhesion (VMA) might have an impact on the response to treatment, since it was found to result in a more intensive treatment regimen; however, it did not affect visual and anatomic outcomes. These results do not support vitrectomy or PVD induction in the prevention, nor the treatment, of RVO.

PSS22 Intravitreal Therapies Pattern of Use in Italy: A Real-World Evidence Study on Maculopathies

To investigate drug utilization and prescribing practices regarding intravitreal therapies for neovascular age-related macular degeneration (wAMD), retinal vein occlusions (RVO), diabetic macular edema (DME) and choroidal neovascularization (CNV) treatment, providing real-world evidence regarding their patterns of use, in the Italian clinical context. A study, based on data from pharmacy databases, was conducted in 6 Italian hospitals. Treatment-naïve wAMD, RVO, DME, and CNV patients’ eyes, who received an intravitreal injection from 01/01/2016 to 06/31/2017, were eligible for inclusion, and a 24-month follow-up was assumed. Information about the number of injections received and administered drugs were considered, for whom frequencies and descriptive statistics were assessed. 5,527 eyes were diagnosed for a maculopathy requiring intravitreal therapy. 33% received treatment up to 24 months. Focusing on wAMD, considering a single-year treatment (N=3,260;64%), eyes received on average 3.39±0.04(range:1-12), 3.54±0.06(range:1-8) and 3 injections with ranibizumab, aflibercept and pegaptanib respectively. Considering a two-year treatment (N=1,798;36%), wAMD eyes received on average 8.00±0.10(range:2-18) and 8.11±0.10(range:2-14) ranibizumab or aflibercept injections. Out of 1,210 DME eyes, 71% received a single-year treatment, with 3.02±0.02(range:1-8), 3.60±0.13(range:1-8), 1.43±0.05(range:1-5) ranibizumab, aflibercept and dexamethasone respectively. Within a 24-month timeframe (N=348; 29%), 8.05±0.23(range:1-17) ranibizumab, 8.12±0.24(range:3-14) aflibercept and 4.59±0.17(range:2-11) dexamethasone injections were administered. 560 RVO eyes received treatment within a 12-month period, with 3.31±0.11(range: 1-10), 3.24±0.15(range:1-9), 1.47±0.06(range:1-7) or 1.67±0.33(range:1-2) ranibizumab, aflibercept, dexamethasone or triamcinolone injections. Considering a two-year treatment (N=197), 8.67±0.29(range:3-15) ranibizumab, 8.51±0.27(range:2-15) aflibercept or 3.92±0.21(range:2-6) injections were performed. CNV eyes (N=300) were treated with ranibizumab and aflibercept drugs receiving 2.08±0.08(range:1-8) and 1.83±0.40(range:1-3) injections respectively considering a single-year treatment (N=244 eyes). 56 eyes treated for a 24-month time horizon, were administered with 5.52±0.36(range:1-6) ranibizumab injections. The study highlights differences between clinical practice and prescribing information, in terms of intravitreal injections frequency, suggesting the need to further analyze and describe reasons and related organizational factors and potential problems.

Contrast Sensitivity Testing in Retinal Vein Occlusion Using a Novel Stimulus.

PurposeThis study evaluated a novel tool known as the motion diamond stimulus (MDS), which utilizes contrast-generated illusory motion in dynamic test regions to determine contrast sensitivity (CS).MethodsPatients with treated unilateral retinal vein occlusions (RVOs) underwent three assessments: the MDS, the Pelli-Robson (PR), and the National Eye Institute's Visual Function Questionnaire (VFQ-25). The MDS assessment produced two data end points, α and β. The α value represents the overall contrast threshold level and the β value serves to quantify the adaptability of the visual contrast system. The CS parameters from the MDS and log CS PR output values were used to compare RVO eyes (n = 20) to control eyes (n = 20).ResultsThe study participants had a mean composite VFQ-25 score of 89.5 ± 10.4 on the VFQ-25. A significant difference was observed between the RVO eyes and the control eyes in PR log CS scores (P value = 0.0001) and in MDS α value (P value = 0.01). No difference in MDS β value was found between the study groups (P value = 0.39).ConclusionsThe results for the MDS assessment's α parameter corroborated the PR scores, suggesting contrast sensitivity threshold impairment in patients with RVO. No significant difference in β value was observed, suggesting that adaptability of the visual system is maintained in treated RVO eyes.Translational RelevanceCurrently, visual complaints cannot be entirely identified by Snellen visual acuity alone. The MDS offers potentially a more complete look at visual function, by including contrast sensitivity and may be able to quantify changes otherwise overlooked in retinal disease progression.

Hyperreflectivity of Inner Retinal Layers as a Quantitative Parameter of Ischemic Damage in Acute Retinal Vein Occlusion (RVO): An Optical Coherence Tomography Study.

PurposeTo investigate the reflectivity changes of inner retinal layers in acute retinal vein occlusion (RVO) on spectral-domain optical coherence tomography (SD-OCT) and to correlate these values with other known parameters of acute ischemic damage.Patients and MethodsIn this retrospective and observational case series, 230 eyes from 115 patients with acute RVO (central or branch) were categorized as ischemic or non-ischemic depending on fluorescein angiography (FA) images at baseline. Thickness and reflectivity of selected retinal layers were measured from SD-OCT images at baseline. Reflectivity values were correlated with other parameters of acute ischemic damage (best-corrected visual acuity (BCVA), retinal thickness, extent of macular edema, ischemic area on fluorescein angiography). The data were compared with contralateral eyes (controls). Prominent middle limiting membrane sign (p-MLM) was also registered.ResultsRVO reflectivity values differed significantly in all retinal layers compared to controls (P<0.001). Ischemic RVO eyes had higher optical intensity values for the innermost retinal layer (IMRL; P=0.008) and inner retinal layer (P=0.019) compared to non-ischemic cases. For all RVO eyes as well as central RVO, severity parameters like BCVA, central and total retinal thickness showed a strong correlation with the IMRL reflectivity. In branch RVO, BCVA remained significantly correlated with the IMRL reflectivity, while the thickness values showed significant correlation only for central foveal thickness in non-ischemic branch RVO type. The p-MLM was seen on OCT in 94% of the ischemic and in 66% of the non-ischemic RVO cases.ConclusionAcute RVO leads to increased reflectivity of inner retinal layers with significantly higher values in the ischemic vs non-ischemic type. Increased inner retinal layers’ reflectivity correlated significantly with BCVA, retinal thickness of separate retinal layers, as well as ischemic area on FA. Quantitative non-invasive measurement of inner retinal layers’ reflectivity might be used to determine the extent of acute ischemic retinal damage in RVO.

Measuring Contrast Sensitivity Function With Active Learning in Retinal Vein Occlusion: A New Endpoint of Visual Function.

To characterize contrast sensitivity function (CSF) in patients with retinal vein occlusion (RVO) compared to age-matched controls using novel computerized contrast sensitivity (CS) testing with active learning algorithms. CSF was prospectively measured in RVO patients with visual acuity (VA) greater than 20/200 and age-matched controls using the novel Manifold Contrast Vision Meter implementing quantitative CSF testing. Outcomes included area under the Log CSF (AULCSF), contrast acuity (CA), and CS thresholds at 1, 1.5, 3, 12, and 18 cycles per degree (cpd). A sub-analysis was performed on RVO eyes with good acuity (VA ≥ 20/30). Twenty-two eyes with RVO and 63 control eyes were included. Mean AULCSF (± standard deviation) in RVO eyes was 0.817 (0.28) compared to 1.217 (0.28) in controls (P < .0001). Mean contrast acuity in the RVO group was 1.054 (0.19) versus 1.286 ± 0.16 in controls (P < .0001). For individual spatial frequencies, CS loss at 6.0 cpd was most prominent in the RVO group. In 10 RVO eyes with VA of 20/30 or greater, mean AULCSF was 0.978 versus 1.217 in control eyes. (P = .008). CSF in eyes with RVO was found to be significantly reduced compared to age-matched controls. CSF seems to be a promising visual function endpoint with potential applications in clinical practice and future clinical trials. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:392-400.].

CORRELATION OF EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AVERAGING VERSUS SINGLE-IMAGE QUANTITATIVE MEASUREMENTS WITH RETINAL VEIN OCCLUSION VISUAL OUTCOMES

To demonstrate the effect of averaging multiple en face optical coherence tomography angiography images on the correlation between retinal microvasculature quantitative metrics and best-corrected visual acuity (BCVA) in eyes with retinal vein occlusion. A cross-sectional cohort with unilateral retinal vein occlusion was imaged in both eyes. Five 3 mm × 3-mm spectral domain optical coherence tomography angiography images were averaged, and quantitative parameters from averaged versus single images were correlated with logMAR BCVA. Regression analyses were performed to correlate quantitative metrics with BCVA. Ten patients (5 male, average age 64.3 years) were included. Among retinal vein occlusion eyes, vessel length density was significantly less in averaged versus a single image for both the superficial retinal layer (15.5 ± 2.5 vs. 17.8 ± 2.4/mm, P = 0.05) and deep retinal layer (16.2 ± 1.4 vs. 18.5 ± 1.6/mm, P = 0.003). Multivariate linear regression showed an increased R value with averaging (0.93 to 0.95, for single and averaged groups, respectively). Foveal avascular zone circularity was associated with BCVA on single images (coefficient = -0.96, P = 0.002), but not with averaged images (P = 0.063). Scan averaging of en face optical coherence tomography angiography images improves the clarity of vessels and may allow for more accurate quantification of vessel metrics. Quantitative metrics are significantly associated with BCVA, and averaging does not further improve this association compared with single-scan analysis.

Macular profile of eyes developing macular holes in cases of central retinal vein occlusion treated with Bevacizumab

Background: Anti-vascular endothelial growth factors are commonly used for treatment for central retinal vein occlusion. There have been numerous reports regarding both the benefits and disadvantages of its use. Recently, a rather surprising complication- development of macular holes have started emerging.&#x0D; Objectives: The purpose of this study was to evaluate if the patient's profile, baseline optical coherence tomography parameters, status of the vitreous and subsequent response pose a risk for macular hole formation in cases of central retinal vein occlusion central retinal vein occlusion following treatment with bevacizumab. &#x0D; Methodology: This prospective exploratory analytical study was conducted at a tertiary eye care center of Nepal and evaluated 97 eyes with central retinal vein occlusion undergoing treatment with bevacizumab.&#x0D; Results: Full Thickness Macular Hole developed in eight (8.24%) of the central retinal vein occlusion eyes treated with bevacizumab. Elderly age and eyes with cystoid edema at baseline were found to have greater risk of developing macular hole following treatment (OR: 8.97 , p&lt;0.05). Twelve eyes (12.3%) of the eyes treated developed vitreoretinal interface anomalies and were the result of dramatic decrease in central macular thickness . All of them had cystoid macular edema at baseline. Five of them (42%) developed full thickness macular hole.&#x0D; Conclusion: Anti-vascular endothelial growth factor agents have been widely accepted as the first line of choice for treatment of macular edema secondary to central retinal vein occlusion. Cystoid macular edema, eyes of the elderly and those showing dramatic decrease in central macular thickness with the development of anomalous vitreoretinal interface are potential risk factors for full thickness macular hole.

NOVEL OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY BIOMARKER IN BRANCH RETINAL VEIN OCCLUSION MACULAR EDEMA.

To evaluate the association between deep-superficial flow ratio (DSFR) and the treatment response of macular edema in branch retinal vein occlusion. Thirty eyes from 30 patients with branch retinal vein occlusion who had received optical coherence tomography angiography examination were included. Seventeen normal fellow eyes acted as the control group. Patients were classified into the "good response group" and the "refractory group" by absence or presence of macular edema after 6 months of treatment. The DSFRs were calculated by dividing deep capillary plexus vessel density by superficial capillary plexus vessel density on optical coherence tomography angiography. The DSFR was 1.00 (SD ± 0.05) over parafoveal area in the control group. Among branch retinal vein occlusion eyes, parafoveal DSFR remained stable in the good response group (P = 0.822) and significantly decreased in the refractory group (P = 0.002). The DSFRs in the most severe nonperfusion area were significantly lower in the refractory group than in the good response group (0.85 ± 0.13 vs. 1.01 ± 0.15, P = 0.004). The DSFR in the most severe nonperfusion area was associates with treatment response in multivariate logistic regression (P = 0.015). Deep-superficial flow ratio can represent the relative damage of deep capillary plexus to superficial capillary plexus. Decreased DSFR was found in branch retinal vein occlusion eyes with refractory macular edema.

A Novel Automatic Method to Estimate Visual Acuity and Analyze the Retinal Vasculature in Retinal Vein Occlusion Using Swept Source Optical Coherence Tomography Angiography.

The assessment of vascular biomarkers and their correlation with visual acuity is one of the most important issues in the diagnosis and follow-up of retinal vein occlusions (RVOs). The high workloads of clinical practice make it necessary to have a fast, objective, and automatic method to analyze image features and correlate them with visual function. The aim of this study is to propose a fully automatic system which is capable of estimating visual acuity (VA) in RVO eyes, based only on information obtained from macular optical coherence tomography angiography (OCTA) images. We also propose an automatic methodology to rapidly measure the foveal avascular zone (FAZ) area and the vascular density (VD) in the superficial and deep capillary plexuses in swept-source OCTA images centered on the fovea. The proposed methodology is validated using a representative sample of 133 visits of 50 RVO patients. Our methodology estimates VA with very high precision and is even more accurate when we integrate depth information, providing a high correlation index of 0.869 with the real VA, which outperforms the correlation index of 0.855 obtained when estimating VA from the data obtained by the semiautomatic existing method. In conclusion, the proposed method is the first computational system able to estimate VA in RVO, with the additional benefits of being automatic, less time-consuming, objective and more accurate. Furthermore, the proposed method is able to integrate depth information, a feature which is lacking in the existing method.

Comparison of subfoveal choroidal thickness in eyes with CRVO and BRVO

BackgroundTo evaluate the subfoveal choroidal thickness (SFCT) in eyes with macular edema (ME) secondary to retinal vein occlusion(RVO), and to investigate the short term response after a single intravitreal ranibizumab (IVR) injection. What is more, to compare SFCT and SFCT change between central RVO (CRVO) and branch RVO (BRVO).MethodsIn the retrospective study, we had collected 36-six treatment-naïve patients with unilateral ME secondary to RVO (including 19 CRVO and 17 BRVO). All patients had received IVR injection after newly diagnosed. The SFCT was measured at the onset and after 2 weeks of IVR injection. Paired t test was performed to compare the SFCT of RVO eyes and fellow eyes, as well as the SFCT of pre-injection and post-injection. In further, independent t test was used to compare SFCT and SFCT change between CRVO eyes and BRVO eyes.ResultsThe mean SFCT at the onset was 326.03 ± 30.86 μm in CRVO eyes, which was significantly thicker than that in contralateral fellow eyes (p < 0.01, paired t test), and reduced to 294.15 ± 30.83 μm rapidly after 2 weeks of IVR injection (p < 0.01, paired t test). Similarly, the SFCT in BRVO eyes was significantly thicker than that in contralateral eyes at the onset, and decreased significantly after IVR injection. However, our findings showed that there was no statistically significant difference in SFCT and SFCT reduction after IVR injection between CRVO eyes and BRVO eyes.ConclusionsThe SFCT in eyes with ME secondary to CRVO and BRVO was significantly thicker than that in fellow eyes, and decreased significantly within a short time in response to a single IVR injection. In further, the study showed that SFCT and SFCT change had no correlation with RVO subtypes.

Impact of Intravitreal Dexamethasone Implant on Vessel Diameters in Patients with Retinal Vein Occlusion.

Purpose To investigate the vasomotor responses and diameter of retinal vessels in patients with macular edema secondary to retinal vein occlusion (RVO) who were treated with intravitreal dexamethasone implant. Methods We enrolled 17 eyes of 17 patients with macular edema secondary to RVO. All patients were evaluated through optical coherence tomography and dynamic and static retinal vessel analysis, using the Dynamic Vessel Analyzer (Imedos, Jena, Germany) before administration (baseline) and 1 week, 1 month, and 2 months after administration of intravitreal dexamethasone. Measurements of patients were compared to those of 17 eyes of age- and sex-matched control subjects. Results In static analysis, arteriovenous ratio (AVR) in control subjects was 0.86 (0.80–0.88). In RVO patients, baseline AVR was 0.71 (0.54–0.84) and significantly lower than that in control subjects (p=0.016). Baseline AVR in the RVO group was significantly lower than AVR at month 1 and month 2 (p=0.001 and p < 0.001, respectively). CRVE in healthy control subjects was 183.59 ± 21.79 measurement units (MU) which was significantly different from CRVE of RVO eyes at baseline (207.00 ± 26.35 MU) (p=0.008). Static analysis showed a significant decrease of central retinal vein equivalent (CRVE) from baseline to 1 week, 1 month, and 2 months (p < 0.001, p < 0.001, and p < 0.001, respectively). CRAE in the control group was 176.24 ± 22.45 MU. CRAE in the RVO group was significantly lower at baseline, week 1, month 1, and month 2 compared to that in the control group (p=0.008, p=0.003, p=0.013, and p=0.011, respectively). Dynamic analysis showed that maximum venous and arterial dilations did not statistically differ from baseline to 1 week, 1 month, or 2 months. Conclusion Using the Dynamic Vessel Analyzer, we found that retinal veins in patients with RVO were significantly larger compared to those in the control group, and intravitreal dexamethasone treatment reduced the diameters of these veins.

Microvascular Retinal and Choroidal Changes in Retinal Vein Occlusion Analyzed by Two Different Optical Coherence Tomography Angiography Devices

Purpose: To investigate retinal and choroidal microvascular changes and structural choroidal involvement in retinal vein occlusion (RVO). Methods: Retrospective analysis of treatment-naïve macular edema secondary to RVO, studied by optical coherence tomography (OCT) and OCT angiography (OCTA), before and after the loading phase of intravitreal injections of ranibizumab (IVR-LP). OCTA was performed using two different devices: AngioVue RTVue XR Avanti (spectral-domain OCTA) and Zeiss PLEX® Elite 9000 (swept-source OCTA). Results: 30 eyes of 30 consecutive patients (17 branch and 13 central RVO) were included. Central macular thickness and subfoveal choroidal thickness (SCT) were significantly reduced after IVR-LP (p < 0.001 and p = 0.046, respectively). 23 eyes were eligible for OCTA analysis. Baseline vessel density (VD) in deep capillary plexus (DCP) was significantly reduced in RVO eyes compared with fellow eyes (p = 0.03 and p = 0.002 for PLEX® Elite and AngioVue, respectively). After IVR-LP, no significant VD changes in any vascular layer was found. PLEX® Elite VD analysis showed significant differences in DCP between ischemic versus non-is­chemic eyes (p = 0.011). Conclusion: OCTA suggests a retinal vascular impairment of DCP but no involvement of choroid in RVO eyes. A greater baseline SCT could be due to a choroidal exudation. OCTA imaged with PLEX® Elite allowed to differentiate ischemic and non-ischemic patients at baseline.

The effect of macular edema on quantitative analysis of foveal avascular zone in branch retinal vein occlusion eyes

Objective To observe the effect of different macular edema on the area of foveal avascular zone (FAZ) and its correlation in eyes with branch retinal vein occlusion (BRVO). Methods A total of 72 patients (75 eyes) diagnosed with BRVO were included in the study. There were 40 patients males (42 eyes) and 32 females (33 eyes), with the mean age of (56.00±9.96) years. All the eyes were examined by BCVA, intraocular pressure, slit lamp microscope combined with preset lens, fundus color photography and optical coherence tomography angiography (OCTA). BRVO patients were divided into two groups according to the degree of macular edema: group M300 that was CRT ≥300 μm (38 patients, 39 eyes) and group L300 that was CRT<300 μm (34 patients, 36 eyes). The macular angiography scan protocol covered a 3 mm×3 mm area. The parameters of macular were measured by the built-in measurement software of the system: (1) area of FAZ, perimeter of FAZ (PERIM), avascular index of FAZ (AI), vascular density within a width of 300 μm around the FAZ region (FD-300); (2) central retinal thickness (CRT); (3) vascular density (VD): the superficial central fovea vascular density (SFVD), the deep central fovea vascular density (DFVD), the superficial hemi-macular vascular density (SHVD), the deep hemi-macular vascular density (DHVD). Spearman test was used to test the correlation between FAZ area and other parameters in each group. Results The FAZ area in group M300 and L300 were 0.388±0.166 mm2 and 0.596±0.512 mm2, respectively. The results of Spearman test showed that the FAZ area of group M300 was positively correlated with PERIM and AI (r=0.932, 0.591; P=0.000, 0.000), negatively correlated with SFVD, DFVD and SHVD (r=−0.490, −0.429, −0.339; P=0.002, 0.006, 0.035). But there was no significant negative correlation between FAZ area and FD-300, CRT, DHVD in group M300 (r=−0.129, −0.053, −0.400; P=0.435, 0.749, 0.395). The FAZ area in group L300 was positively correlated with PERIM and AI (r=0.887, 0.633; P=0.000, 0.000), negatively correlated with SFVD, DFVD, SHVD and DHVD (r=−0.413, −0.643, −0.630, −0.370, −0.411; P=0.012, 0.000, 0.000, 0.026, 0.013). But there was no significant positive correlation between FAZ area and FD-300 in group L300 (r=0.093, P=0.590). Conclusion FAZ area varies with the degree of macular edema. The degree of macular edema is higher, the FAZ area is smaller. FAZ area is positively correlated with PERIM and AI significantly, and negatively correlated with SFVD, DFVD and SHVD. Key words: Retinal vein occlusion; Macular edema; Foveal avascular zone; Tomography, optical coherence

The alterations of microvascular structure in branch retinal vein occlusion eyes before and after anti-vascular endothelial growth factor drug therapy

Objective To observe the alterations of microvascular structure in patients with macular edema (ME) associated with branch retinal vein occlusion (BRVO) before and after anti-VEGF drug therapy. Methods A retrospective case study. Thirty-two eyes of 32 patients with unilateral BRVO-ME at Department of Ophthalmology in Beijing Hospital during November 2016 to June 2018 were enrolled in this study. There were 14 males (14 eyes) and 18 females (18 eyes), with the mean age of 57.81±10.58 years, and the mean course of the disease of 12.13±7.13 d. The affected eyes was defined as the eyes with BRVO-ME. All the affected eyes received intravitreal anti-VEGF drug injections (3+PRN). BCVA and OCT angiography (OCTA) were performed on the BRVO and fellow eyes before and after intravitreal anti-VEGF drug injections. The scanning region in the macular area was 3 mm×3 mm. Macular blood flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), macular hemodynamics parameters [foveal avascular area (FAZ) area, perimeter (PERIM), acircularity index (AI) and vessel density within a 300um width ring surrounding the FAZ (FD-300)] and central retinal thickness (CRT) were measured in all eyes. Paired samples t-test and Univariate Linear Regression were used in this study. Results Comparing with fellow eyes, the mean macular blood flow density measured in the entire scan was lower in BRVO-ME eyes in the SCP (t=6.589, P=0.000) and DCP (t=9.753, P=0.000), PERIM (t=4.054, P=0.000) ), AI enlarged in BRVO-ME eyes (t=4.988, P=0.000), FD- 300 was lower in BRVO-ME eyes (t=2.963, P=0.006), FAZ area enlarged in BRVO-ME eyes (t=0.928, P=0.361). The blood flow density in the DCP was the parameter most significantly correlated with BCVA and FAZ area (r=0.462, −0.387; P 0.05). The blood flow density in the SCP decreased (t=2.814, P<0.05), but the blood flow density in the DCP was not changed significantly (t=0.661, P=0.514). Contrarily, comparing with after 1 anti- VEGF drug injection, the blood flow density in the DCP increased after 2 anti-VEGF drug injections (t=3.132, P<0.05). FAZ area enlarged in BRVO-ME eyes (t=5.340, P<0.001). Comparing with last anti-VEGF drug injection, FAZ area enlarged after every anti-VEGF drug injection (t=2.907, 3.742, 2.203; P<0.05). Conclusions In BRVO-ME eyes, the blood flow density in the SCP and DCP are decreased. The blood flow density in the DCP is positively correlated with BCVA and negatively correlated with FAZ area. After anti- VEGF drug therapy, the blood flow density is decreased in the SCP and increased in the DCP, FAZ area enlarged gradually, PERIM and AI are not changed significantly. Key words: Retinal vein occlusion/therapy; Macular edema/therapy; Angiogenesis inhibitors/therapeutic use; Tomography, optical coherence; Regional blood flow

RETINAL MICROVASCULATURE AND VISUAL ACUITY AFTER INTRAVITREAL AFLIBERCEPT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study.

To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity. Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined. After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm in the SCP and 3.25 ± 0.91 mm in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm in the SCP and 1.78 ± 1.73 mm in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P < 0.001) and with smaller SCP and DCP foveal avascular zone areas (both P < 0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P < 0.05) and ischemia (determined via pretreatment fluorescein angiography, P < 0.05), and positively correlated with photoreceptor integrity (P < 0.001). Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.

OCT angiography fractal analysis-based quantification of macular vascular density in branch retinal vein occlusion eyes

ObjectiveTo compare the macular vascular density in branch retinal vein occlusion (BRVO) versus normals on optical coherence tomography angiography (OCTA) using fractal analysis and to describe the factors bearing on final visual outcomes. ParticipantsThis study is a retrospective observational comparative case series. Diagnosed cases of unilateral BRVO that underwent treatment and resolved were included. The other eye served as control. MethodsOCTA images of the cases and control eyes were analyzed using fractal dimension on the MATLAB platform. Vascular density fraction was calculated for each eye for both the retinal vascular layers. Images were cleaned of artifacts before processing. Total vascular density in normals was compared with those with branch retinal vein occlusion. Results116 eyes were normal and 98 had BRVO. The mean age of the normals was 56.63 ± 12.5 years and 58.41 ± 10.7 years of the BRVO group (p = 0.6). Superficial vascular density fraction was noted as 0.29 ± 0.08 (95% CI 0.27–0.31) and 0.25 ± 0.1 (95% CI 0.23–0.27) respectively (p = 0.003). Deep vascular density was noted as 0.39 ± 0.11 (95% CI 0.32–0.41) and 0.14 ± 0.09 (95% CI 0.12–0.19) (p < 0.0001). Pearson's correlation coefficient was -0.4 (p = 0.04) for the effect of age on vascularity, -0.53 (p = 0.001) for the effect of vascularity on final vision, and 0.35 (p = 0.09) for the effect of duration of symptoms on final vision. ConclusionsIn BRVO vascular density decreases significantly in the deeper retinal layer. Vision deficit correlates to increased age, duration of symptoms, and greater vascularity loss.

Optical coherence tomography angiography in retinal vein occlusions.

To examine the vascular density in different retinal layers and in the choriocapillaris in eyes with retinal vein occlusions (RVO). Applying optical coherence tomography angiography (OCTA), we examined patients with unilateral RVOs and normal individuals of a control group. The study group included 48 patients with unilateral RVO and the control group 17 normal individuals. Eyes affected by RVO as compared to the contralateral unaffected eyes (all P < 0.001), and the contralateral unaffected eyes as compared to the eyes of the control group (P < 0.05), showed a lower vessel density in the superficial and deep retinal layers in all regions except for the foveal region. Choriocapillaris density was lower (P < 0.001), foveal retinal thickness and subfoveal choroidal thickness (P < 0.001) were thicker, and the foveal avascular zone was larger (P = 0.003) in the RVO eyes than in the contralateral eyes. For 29 eyes undergoing OCTA and fluorescein angiography, two examiners independently rated the retinas to be ischemic in fluorescein angiography in 14 eyes and in OCTA in 9 of these 14 eyes. Upon OCTA, unaffected eyes of patients with unilateral RVOs showed vascular abnormalities in the superficial and deep retinal layers when compared to those of healthy individuals.

One year clinical observation of dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema secondary to retinal vein occlusion

Objective To evaluate the efficacy and safety of dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO). Methods Thirty-nine patients (39 eyes) with ME secondary to RVO were enrolles in this study. Of the patients, 27 were male and 12 were female. The mean age was (41.9±16.3) years. The mean course of disease was (5.0±5.3) months. The best corrected visual acuity (BCVA), intraocular pressure and optical coherence tomography (OCT) were performed. BCVA was measured by Early Treatment Diabetic Retinopathy Study charts. Central macular thickness (CMT) was measured by OCT. The mean BCVA was (13.4±15.3) letters. The mean intraocular pressure (IOP) was (14.1±2.8) mmHg (1 mmHg=0.133 kPa). The mean CMT was (876.1±437.9) μm. Of the 39 eyes, 33 were central RVO, 6 were branch RVO. Patients were categorized into ischemic (18 eyes)/nonischemic (21 eyes) groups and previous treatment (22 eyes)/treatment naive (17 eyes) groups. All eyes underwent intravitreal 0.7 mg Ozurdex injections. BCVA, IOP and CMT were assessed at 1, 2, 3, 6, 9, 12 months after injection. Three months after injection, intravitreal injections of Ozurdex, triamcinolone acetonide or ranibizumab could be considered for patients with ME recurrence or poor treatment effects. Change of BCVA, IOP and CMT were evaluated with paired t test. The presence of ocular and systemic adverse events were assessed. Results BCVA, IOP significantly increased and CMT significantly decreased at 1 month after injection compared to baseline in all groups (t=3.70, 3.69, 4.32, 3.08, 4.25, 6.09, 6.25, 4.02, 5.49, 8.18, 6.54, 5.73; P 0.05); BCVA of non-ischemic RVO group and treatment naive group significantly increased compared to baseline (t=2.27, 2.30; P<0.05); IOP significantly increased and CMT significantly decreased in all groups (t=0.30, 0.13, 4.60, 3.26, 0.64, 1.53, 3.00, 4.87; P<0.05). Twenty-seven eyes (69.2%) experiences ME recurrence (4.5±1.5) months after injection. Most common side-effect was secondary glaucoma. 41.0% eyes had IOP more than 25 mmHg, most of which were lowered to normal range with use of topical IOP lowering drugs. Four eyes (10.3%) presented with significant cataract progression and needed surgical treatment, all were central RVO eyes. No serious ocular or systemic adverse events such as vitreous hemorrhage, retinal detachment or endophthalmitis were noted. Conclusions Intravitreal injection of Ozurdex for patients with ME secondary to RVO is effective in increasing BCVA and lowering CMT in the first few months. Significant treatment effect could be seen at 1 month after injection and was most significant at 2 months after injection. The long-term vision of eyes in non-ischemic RVO group and treatment naive group are better. 69.2% eyes experience ME recurrence at 4 months after injection. Short term adverse events were mostly secondary glaucoma and long term adverse events are mostly cataract progression. Key words: Dexamethasone/therapeutic use; Retinal vein occlusion/drug therapy; Macular edema/drug therapy

Gene expression profiling in a mouse model of retinal vein occlusion induced by laser treatment reveals a predominant inflammatory and tissue damage response.

PurposeRetinal vein occlusion (RVO) has been investigated in several laser-induced animal models using pigs, rabbits and rats. However, laser-induced RVO has been rarely reported in mice, despite the impressive number of available mutants, ease of handling and cost effectiveness. The aim of this study was to further assess the feasibility of a RVO mouse model for gene expression analysis and its possible use to investigate effects of hypoxia.MethodsC57Bl/6J mice were injected with eosin Y for photo-sensitization. Subsequently, large retinal veins were laser-treated in one eye to induce vascular occlusion. Contralateral control eyes received non-occlusive retinal laser treatment sparing large vessels. The animals were followed for up to eight days and assessed by funduscopy, angiography, hypoxyprobe staining, histopathology and gene expression analysis by qPCR and RNA sequencing (RNAseq). Another group of mice was left untreated and studied at a single time point to determine baseline characteristics.ResultsLaser-induced RVO persisted in half of the treated veins for three days, and in a third of the veins for the whole observation period of 8 days. Funduscopy revealed large areas of retinal swelling in all laser-treated eyes, irrespective of vascular targeting or occlusion status. Damage of the outer retina, retinal pigment epithelium (RPE), and even choroid and sclera at the laser site was observed in histological sections. Genes associated with inflammation or cell damage were highly up-regulated in all laser-treated eyes as detected by RNAseq and qPCR. Retinal hypoxia was observed by hypoxyprobe staining in all RVO eyes for up to 5 days with a maximal extension at days 2 and 3, but no significant RVO-dependent changes in gene expression were detected for angiogenesis- or hypoxia-related genes.ConclusionThe laser-induced RVO mouse model is characterized by a predominant general inflammatory and tissue damage response, which may obscure distinct hypoxia- and angiogenesis-related effects. A non-occlusive laser treatment control is essential to allow for proper data interpretation and should be mandatory in animal studies of laser-induced RVO to dissect laser-induced tissue damage from vascular occlusion effects.

Neuroretinal atrophy following resolution of macular oedema in retinal vein occlusion

Background/aimsTo characterise neuroretinal atrophy in retinal vein occlusion (RVO).MethodsWe included patients with central/branch RVO (CRVO=196, BRVO=107) who received ranibizumab according to a standardised protocol for 6 months. Retinal atrophy was...