RETINAL VEIN OCCLUSIONS BEFORE AND DURING THE COVID-19 PANDEMIC: Visual Outcomes and Treatment Patterns in a Country with no Mandatory Lockdown.

PURPOSE: To investigate the incidence, treatment patterns, and visual outcomes in patients with branch retinal vein occlusion (RVO) and central RVO before and during the COVID-19 pandemic in a country with no mandatory lockdown. METHODS: This retrospective study included 788 patients presenting with a RVO during the years 2019 to 2022 at St. Erik Eye Hospital. The control group and study groups consisted of patients presenting before and during the pandemic, respectively. RESULTS: The incidence of diagnosed RVO cases decreased from 281 patients before the pandemic to 236 patients during the first year of the pandemic ( P < 0.05). In patients with branch RVO at the end of follow-up, the best-corrected visual acuity improved 10.3 letters (95% confidence intervals [CI] 7.6-12.9) in the control group compared with 14.3 letters (95% CI 12.6-16.0) in the study groups ( P < 0.05). In patients with central RVO, the best-corrected visual acuity improved 6.3 letters (95% CI 2.7-10.0) in the control group compared with 8.6 letters (95% CI 5.7-11.4) in the study groups (p = NS). Overall, the number of intravitreal anti-vascular endothelial growth factor injections increased from 7.0 (95% CI 6.6-7.3) in the control group to 7.6 (95% CI 7.4-7.8) in the study groups ( P < 0.05). CONCLUSION: Good visual and anatomical outcomes were sustained, and the number of intravitreal anti-vascular endothelial growth factor injections increased significantly in patients with RVO during the COVID-19 pandemic.

RELATIONSHIP BETWEEN RETINAL HEMORRHAGE ON GREEN AND RED CHANNELS OF ULTRA-WIDEFIELD FUNDUS IMAGES AND RETINAL PERFUSION IN ACUTE BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To explore the relationship between retinal hemorrhage in the green and red channels on ultra-widefield fundus images and the nonperfusion area (NPA) on ultra-widefield fundus fluorescein angiography in patients with acute branch retinal vein occlusion (BRVO). METHODS: This was a retrospective cross-sectional study with 96 patients, including 46 with ischemic BRVO and 50 with nonischemic BRVO. Correlation analysis between green channel hemorrhage (GCH), red channel hemorrhage (RCH), and NPA was performed. Panretina was divided into posterior and peripheral areas. RESULTS: Ischemic BRVO showed significantly higher GCH% and RCH% than nonischemic BRVO in the peripheral regions (both P < 0.001), whereas no significant differences were observed in the panretinal and posterior areas (all P > 0.05). Significant correlations were found between NPA% in the panretinal and peripheral areas and the corresponding GCH% and RCH% (all P < 0.01). However, no significant correlation was observed between posterior NPA% and posterior GCH% or RCH% (both P > 0.05). In addition, peripheral GCH% and RCH% were related to panretinal NPA% (r = 0.506, P < 0.001; r = 0.558, P < 0.001). CONCLUSION: Retinal hemorrhage on ultra-widefield fundus image was significantly associated with NPA, providing insights for assessing retinal perfusion status in acute BRVO patients.

Disorganization of the inner retinal layers in diabetic macular edema: systematic review / Desorganização das camadas internas da retina sem edema macular diabético: uma revisão sistemática

ABSTRACT The objective of this article was to review the disorganization of inner retinal layers as a biomarker in diabetic macular edema. A systematic search was conducted in PubMed®/MEDLINE®, Cochrane and Embase until August 2021. The keywords used were: "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" and "biomarkers". No restrictions were imposed on the types of study to be included. The studies selected for eligibility were those that included the diagnosis of diabetic macular edema (center involved, resolved), that were well documented with spectral domain optical coherence tomography, that included disorganization of inner retinal layers as one of the reported alterations, with a follow-up of at least 3 months, and those in which the best corrected visual acuity was evaluated pre and post. There were no limitations regarding the type of treatment established. References of identified studies were searched for additional relevant articles. Articles not published in peer review journals were excluded. All studies were evaluated by two investigators independently. When one of them was in doubt, it was assessed by a third evaluator. A total of seven studies were included. Four were retrospective, longitudinal cohort study and three cross-sectional observational. Regarding the population studied, 61.5% were men and 38.4% were women, most of them had diabetes mellitus type 2 (85.8%). Regarding the stage of diabetes, the percentage of patients with mild nonproliferative diabetic retinopathy was 28.2%, with moderate nonproliferative diabetic retinopathy was 28.5%, with severe nonproliferative diabetic retinopathy was 15.9% and with nonproliferative diabetic retinopathy was 27.4%. In 100% of the studies, the diagnosis of diabetic macular edema in the center involved was included by spectral domain optical coherence tomography (Heidelberg). In all the studies, the presence of disorganization of inner retinal layers was recorded and its association with best corrected visual acuity was evaluated. The measurement was carried out using the LogMAR scale. In all the studies, the presence or absence of disorganization of inner retinal layers was associated with the best corrected worse/better final visual acuity using p <0.05 as a statical significance. The disorganization of inner retinal layers as a biomarker and their presence have shown to be important predictors of visual acuity in the future in patients with diabetic macular edema. Histopathological studies are required to understand its mechanism of action.

RESUMO O objetivo deste artigo foi revisar sobre a desorganização das camadas internas da retina como biomarcador no edema macular diabético. Uma busca sistemática foi realizada no PubMed®/MEDLINE®, Cochrane e Embase até agosto de 2021. As palavras-chave utilizadas foram "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" e "biomarkers". Não foram impostas restrições quanto aos tipos de estudo a serem incluídos. Os estudos selecionados para elegibilidade foram aqueles que incluíram o diagnóstico de edema macular diabético (centro envolvido, resolvido), que foram bem documentados com tomografia de coerência óptica de domínio espectral, que incluíram a desorganização das camadas internas da retina como uma das alterações relatadas, com acompanhamento de pelo menos 3 meses, e aqueles em que a melhor acuidade visual corrigida foi avaliada pré e pós. Não houve limitações quanto ao tipo de tratamento estabelecido. Referências de estudos identificados foram pesquisadas para artigos relevantes adicionais. Foram excluídos os artigos não publicados em revistas de revisão por pares. Todos os estudos foram avaliados por dois investigadores de forma independente. Quando havia dúvida com algum deles, a mesma era avaliada por um terceiro avaliador. Um total de sete estudos foram incluídos. Quatro eram estudos de coorte retrospectivos longitudinais e três eram observacionais transversais. Em relação à população estudada, a proporção de homens foi de 61,5% e de mulheres, 38,4%, a maioria com diabetes mellitus tipo 2 (85,8%). Em relação ao estágio do diabetes, o percentual de pacientes com retinopatia diabética não proliferativa leve foi de 28,2%, retinopatia diabética não proliferativa moderada foi de 28,5%, de retinopatia diabética não proliferativa grave foi de 15,9% e de retinopatia diabética não proliferativa foi de 27,4%. Em 100% dos estudos, o diagnóstico de edema macular diabético no centro envolvido foi incluído pela tomografia de coerência óptica de domínio espectral (Heidelberg). Em todos os estudos, foi registrada a presença de desorganização das camadas internas da retina e avaliada sua associação com a melhor acuidade visual corrigida. A medição foi realizada usando a escala LogMAR. Em todos os estudos, a presença ou ausência de desorganização das camadas internas da retina foi associada a pior/melhor acuidade visual final melhor corrigida usando p<0,05 como significância estática. A desorganização das camadas internas da retina como biomarcador e sua presença têm se mostrado importantes como preditor da acuidade visual no futuro em pacientes com edema macular diabético. Estudos histopatológicos são necessários para entender seu mecanismo de ação.

Collateral Vessel Development in Central and Branch Retinal Vein Occlusions Are Associated With Worse Visual and Anatomic Outcomes.

Purpose: The purpose of this study was to investigate the effects of the extension of collateral vessels on the outcomes of eyes affected by central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Methods: The study was designed as a cross-sectional case series. Patients affected by CRVO and BRVO were progressively recruited, along with an age- and sex-matched control group of healthy subjects. Structural optical coherence tomography (OCT) and OCT angiography (OCTA; 4.5 × 4.5 mm and 9.0 × 9.0 mm acquisitions) were performed on all participants in order to assess the relationship between the presence of collateral vessels and final anatomical outcomes - central macular thickness (CMT), foveal avascular zone - and functional outcomes - best corrected visual acuity (BCVA). Results: Fifty-six eyes affected by CRVO and 47 eyes affected by BRVO were included. Baseline LogMAR BCVA was 0.41 ± 0.33 LogMAR in CRVO, and 0.39 ± 0.25 LogMAR in BRVO (P < 0.01), improving to 0.20 ± 0.26 LogMAR in CRVO (P < 0.01), and 0.19 ± 0.22 LogMAR in BRVO (P < 0.01). Baseline CMT was 511 ± 214 µm in CRVO and 482 ± 178 µm in BRVO (P > 0.05), decreasing to 328 ± 105 µm (P < 0.01) and 321 ± 78 µm in CRVO and BRVO, respectively (P < 0.01). Collateral vessels were detected in 16 of 56 eyes (29%) in CRVO and in 47 of 47 eyes (100%) in BRVO. Their extension was correlated with worse anatomic and visual outcomes. Remarkably, no correlation was found with peripheral capillary nonperfusion and vessel density impairment. Conclusions: The present study demonstrates that collateral vessel extension is associated with worse anatomic and functional outcomes in patients affected by CRVO and BRVO.

Elevated retinal artery vascular resistance determined by novel visualized technique of laser speckle flowgraphy in branch retinal vein occlusion.

We aimed to investigate the increase in resistivity of the retinal artery in the branch retinal vein occlusion (BRVO)-affected area, and to visualize it. Thirty-two eyes of 32 patients with BRVO were measured by laser speckle flowgraphy (LSFG). The retinal artery and vein running to the BRVO-affected area and vertically symmetrical vessels in the unaffected area were examined. We applied the LSFG parameter beat strength over mean blur rate (BOM), calculated using a similar method to the pulsatility index used in Doppler flowmetry to evaluate resistivity of the vessels. Our results showed that the BOM map could clearly visualize the increase of resistivity in the retinal artery as a two-dimensional map. The BOM of the arteries in the affected area was significantly higher than that of the unaffected area (P = 0.001). Multiple regression analysis showed that the ratio of BOM in retinal arteries of the affected area to the unaffected was significantly associated with the extent of retinal hemorrhage (ß = 0.447, P = 0.009). In conclusion, the index of resistivity of the retinal artery in the BRVO-affected area was higher and could be visualized in a two-dimensional map. These findings and techniques would contribute to elucidate the pathophysiology of BRVO.

OUTCOMES IN PATIENTS RESUMING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOLLOWING TREATMENT DELAY DURING THE CORONAVIRUS-19 PANDEMIC.

PURPOSE: To evaluate the outcomes of delay in care secondary to the coronavirus pandemic in patients requiring intravitreal anti-vascular endothelial growth factor therapy. METHODS: A retrospective review was performed, and subjects were divided into two groups: 1) a study group of patients who experienced a treatment delay of ≥6 weeks from the intended follow-up during the coronavirus pandemic and resumed treatment with ≥2 anti-vascular endothelial growth factor injections over 6 months following treatment delay, and 2) a control group of patients who received regular care throughout the coronavirus pandemic. RESULTS: Totally, 234 subjects were analyzed. The mean treatment delay from the intended follow-up in the study group was 11.8 (±4.0) weeks. Visual acuity and central macular thickness worsened from baseline to 6 months after resuming anti-vascular endothelial growth factor therapy in the study group (P < 0.0001 and P = 0.001, respectively). Visual acuity and central macular thickness were better in the control group compared with the study group at the end of the 6-month study period (P < 0.0001 for both). CONCLUSION: Treatment delay in subjects undergoing anti-vascular endothelial growth factor therapy for retina disease during the coronavirus pandemic had worse visual and anatomical outcomes despite reinitiating treatment over 6 months compared with a control group, suggesting irreversibility and permanence of outcomes.

Changes in peripapillary and subfoveal choroidal thickness in patients with central retinal vein occlusion.

PURPOSE: We sought to evaluate changes of mean peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) over 12 months in patients with unilateral central retinal vein occlusion (CRVO). METHODS: Our retrospective, observational study included 19 patients with treatment-naïve, unilateral CRVO who completed at least 12 months of follow-up period. Mean PCT and mean SFCT in CRVO-affected eyes and unaffected contralateral eyes were measured at each follow-up visit, and then compared. Differences between baseline and 12 months (ΔSFCT and ΔPCT) and percentage changes (ΔSFCT or ΔPCT/baseline×100%) were determined. We also investigated the predictive factors for visual outcome in the CRVO-affected eyes. RESULTS: In the CRVO-affected eyes, mean PCT was 146.7±41.9 µm at baseline, and 106.5±24.2 µm at 12 months (P < 0.001). Mean PCT of the contralateral eyes was 129.8±42.6 µm at baseline and 124.6±39.7 µm at 12 months (P = 0.089). Mean SFCT of CRVO-affected eyes was 225.8±77.9 µm at baseline, and 199.4±66.6 µm at 12 months (P = 0.009). Mean SFCT of the contralateral eyes was 218.4±83.0 µm at baseline, and 208.4±78.1 µm at 12 months (P = 0.089). Δ PCT was -41.6±25.3 µm in the CRVO-affected eyes, and -5.2±5.8 µm in the contralateral eyes (P<0.001). % PCT was -24.9±14.0% in the CRVO-affected eyes, and -4.0±0.4% in the contralateral eyes (P = 0.001). Δ SFCT was -26.4±24.6 µm in the CRVO-affected eyes, and -9.5±16.7µm in the contralateral eyes (P = 0.016). % SFCT was -10.4±9.8% in the CRVO-affected eyes, and -3.4±6.4% in the contralateral eyes (P = 0.015). Among the various factors, BCVA at baseline (ß = 0.797, P = 0.001) and % SFCT (ß = 0.712, P = 0.001) were significantly associated with visual outcome at 12 months in the CRVO-affected eyes. CONCLUSION: Both peripapillary and subfoveal choroidal thickness reduced significantly over 12 months in the CRVO-affected eyes, but not in the contralateral eyes. In addition, the absolute reduction amount and reduction ratio of PCT and SFCT were significantly greater in the CRVO-affected eyes than the contralateral eyes.

Short-Term Efficacy Of Intravitreal Bevacizumab In Treatment Naive Patients- Real World Evidence In Pakistan.

BACKGROUND: Anti-VEGF agents have been proven to be effective in treating macular oedema secondary to a multitude of pathological conditions. However, in large clinical trial settings, the results may be overstated. This study aimed to evaluate the short-term efficacy of intraocular Bevacizumab in consecutive patients with macular oedema being treated in a 'real-world' setting in Pakistan. METHODS: A prospective study was conducted at Amanat Eye Hospital, Rawalpindi from August 2018 to November 2019. Thirty-five eyes of 29 patients with macular oedema were treated with monthly intravitreal Bevacizumab injections for three consecutive months. Best-corrected visual acuity (BCVA), and OCT parameters including central retinal thickness (CRT) and macular volume were assessed prior to the injections and then 4 weeks post the final injection and compared. RESULTS: BCVA improved from 1.00±0.44 at baseline to 0.83±0.48 four weeks after the third intravitreal injection. CRT decreased significantly from 492.77±192.31 at baseline to 362.91±126.11 (p<0.05), and macular volume decreased significantly from 11.61±2.39 at baseline to 9.87±1.68 (p<0.05) four weeks after the third intravitreal injection. No systemic or ocular complications were observed during the course of the study. CONCLUSIONS: Treatment with intravitreal Bevacizumab injections was found safe and resulted in clinically and statistically significant improvement in SD-OCT parameters and visual acuity in patients with macular oedema secondary to various retinal pathologies. However, the improvement in a real-world setting was sub-optimal in comparison to larger clinical trials for specific diseases in the developed world.

Clinical significance of subclinical atherosclerosis in retinal vein occlusion.

Retinal vein occlusion (RVO) is associated with atherosclerotic cardiovascular risk factors; however, its association with the specific markers of subclinical atherosclerosis has not yet been established. To investigate this association, we compared 70 patients with RVO to 70 age- and sex-matched patients without RVO. Low-density lipoprotein cholesterol (LDL-C) levels and brachial-ankle pulse wave velocity (baPWV) were significantly higher in the RVO group than in the control group. Carotid plaques (54.3% vs. 28.6%, p = 0.004) were more frequent in the RVO group. Multivariate logistic regression analysis showed that the presence of carotid plaques (odds ratio [OR]: 3.15, 95% confidence interval [CI] 1.38-7.16, p = 0.006), as well as smoking, LDL-C level, and baPWV were associated with RVO. Additionally, a multinomial logistic regression model showed that the presence of carotid plaques (OR: 3.94, 95% CI 1.65-9.41, p = 0.002) and LDL-C level were associated with branch RVO, whereas smoking and baPWV were associated with central RVO. In conclusion, RVO was associated with subclinical atherosclerosis markers, including carotid plaques and baPWV. These results support the hypothesis that atherosclerosis contributes to the etiology of RVO and suggest the evaluation of subclinical atherosclerosis in patients with RVO.

Anatomic-Functional Correlates in Lesions of Retinal Vein Occlusion.

Purpose: To evaluate anatomic-functional associations at sites of retinal lesions in retinal vein occlusion (RVO). Methods: This pilot, prospective, observational study was conducted at the Northern Ireland Clinical Research Facility (NICRF) of Queen's University and the Belfast Health and Social Care Trust, Northern Ireland, between August 1, 2018, and September 30, 2019. The study included 10 treatment-naïve patients with RVO (10 RVO eyes and 10 fellow eyes). There were 81 points/sites assessed for each eye at baseline; six patients were re-assessed 6 months after anti-vascular endothelial growth factor therapy at the same locations. We investigated associations between retinal sensitivity and presence of structural RVO lesions, including retinal ischemia, hemorrhages, intraretinal fluid (IRF) and subretinal fluid outside the foveal/parafoveal regions. Comparisons were made between RVO eyes and fellow eyes at baseline, and between RVO eyes at baseline and at 6 months after treatment. Regression models were used to investigate anatomic-functional associations. Results: At baseline, strong associations were found between reduced retinal sensitivity and presence of ischemia (estimate = -2.08 dB; P < 0.001), intraretinal fluid (estimate = -7.82 dB; P < 0.001), and subretinal fluid (estimate = -8.66 dB; P < 0.001). Resolution of subretinal fluid but not intraretinal fluid was associated with improved function (estimate = 2.40 dB [P = 0.022]; estimate = 1.16 dB [P = 0.228], respectively). However, reperfusion of ischemic retina, observed in 31 of 486 points (6%) 6 months after anti-vascular endothelial growth factor therapy, was associated with a further decrease in retinal sensitivity (estimate = -2.34 dB; P = 0.035). Conclusions: Retinal sensitivity was decreased at sites of RVO lesions. Decreased function at sites of retinal ischemia did not recover after treatment, even when reperfusion occurred.

Non-dipping pattern of nocturnal blood pressure as a risk factor for macular ischemia in branch retinal vein occlusion.

Branch retinal vein occlusion (BRVO) is ocular vascular disease affecting approximately 14 million people worldwide, and is closely associated with high blood pressure (BP). Although macular ischemia is a critical factor in the visual prognosis of BRVO, the relationship between macular ischemia and different patterns of nocturnal BP is unknown. Here, we investigated whether a dipping pattern of nocturnal BP is associated with the development of macular ischemia in patients with BRVO. A total of 273 patients were reviewed; of these, 86 (86 eyes) patients were included. All recruited patients had a macular thickness map by optical coherence tomography and underwent 24-h ambulatory BP monitoring. According to their dipping patterns, the participants were divided into dipper and non-dipper groups. The non-dipper group had worse visual outcomes at the initial and 6-month visits (P = 0.014 and P = 0.003, respectively). Five of 32 eyes (15.6%) in the dipper group and 32 of 54 (59.3%) in the non-dipper group had macular ischemia. In a multivariate analysis, the night-to-day systolic BP ratio was associated with the degree of macular ischemia (ß = - 0.313, P = 0.004). Thus, a non-dipping pattern may be a risk factor for macular ischemia in patients with BRVO.

Diabetic and Retinal Vascular Eye Disease.

The retinal vasculature is the only neurovascular system directly visible to the human eye, easily evaluated by fundoscopy and many imaging modalities. This window allows physicians to diagnose and treat retinal pathologies and detect systemic diseases including diabetes, hypertension, hypercoagulable/hyperviscosity syndromes, and vasculitis. Diabetic retinopathy is the most common retinal vascular disease, followed by retinal vein and artery occlusion. Patients with these conditions require medical optimization to prevent further damage to the eyes and to the other organs. Both the internists and medical subspecialists play a crucial role in the prevention, detection, evaluation, and management of vision-threatening retinal vascular diseases.

Real-Life Management of Central and Branch Retinal Vein Occlusion: A Seven-Year Follow-Up Study.

Retinal vein occlusion is the second most common retinal vascular pathology after diabetic retinopathy and a major cause of vision impairment. Nowadays, both central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) can be well-managed by intravitreal treatments. However, considering the long-life expectance of the patients, few data are present in the literature about the very long-term outcome of CRVO and BRVO. The present study was an interventional, retrospective analysis of the morphological and functional long-term outcome of CRVO and BRVO patients, followed in an Italian referral center. We collected data from 313 eyes (178 CRVO eyes and 135 BRVO eyes). Mean follow-up was 45 ± 25 months (range 12-84 months). Both CRVO and BRVO eyes experience a significant visual acuity improvement secondary to anti-vascular endothelial growth factor/dexamethasone treatments (from 0.57 ± 0.25 to 0.41 ± 0.24 LogMAR in CRVO and from 0.53 ± 0.42 to 0.30 ± 0.41 LogMAR in BRVO, respectively) (p < 0.01). Also, central macular thickness (CMT) resulted significant recovery at the end of the follow-up (from 585.54 ± 131.43 to 447.88 ± 245.07 µm in CRVO and from 585.54 ± 131.43 to 447.88 ± 245.07 µm in BRVO, respectively) (p < 0.01). CRVO eyes received a mean of 10.70 ± 4.76 intravitreal treatments, whereas BRVO underwent 9.80 ± 5.39 injections over the entire 7-year follow-up. Our analyses highlighted different time points indicating the best obtainable improvement. This was the first year for CRVO (12-month follow-up) and the second year for BRVO (24-month follow-up). After these two time points, both visual acuity and CMT resulted stable up to the end of the follow-up. Ischemia was associated with significantly worse outcome.

Optical coherence tomography angiography and Humphrey field analyser for macular capillary non-perfusion evaluation in branch retinal vein occlusion.

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.

Retinal oximetry does not predict 12-month visual outcome after anti-VEGF treatment for central retinal vein occlusion: A multicentre study.

PURPOSE: Central retinal vein occlusion (CRVO) entails retinal hypoxia that often causes visual impairment. It has been shown that oxygen saturation in larger retinal vessels correlates with the visual acuity at the time of diagnosis of CRVO but has no predictive value for the visual outcome in patients treated with anti-VEGF medication after 3 months. However, assessing the predictive value of retinal oxygen saturation after 12 months is essential because this is when the main restitution after CRVO occurs. METHODS: Retinal oximetry was performed in 117 patients referred with CRVO to three European centres. The correlation between oxygen saturation and visual acuity at baseline and the predictive value of oxygen saturation in larger retinal vessels for the 12-month visual outcome after treatment with anti-VEGF medication were studied. RESULTS: In the affected eye, the oxygen saturation was significantly higher in the arterioles, significantly lower in the venules, and the arterio-venous (A-V) significantly higher than in the unaffected eye (p < 0.001 for all comparisons). Correlations between best-corrected visual acuity (BCVA) and oxygen saturations were moderate and negative for arterioles (p < 0.001), positive for venules (p = 0.03) and negative for the A-V difference (p = 0.001). Best-corrected visual acuity (BCVA), but not oxygen saturation or the other explanatory variables at baseline, contributed significantly to predicting BCVA after 12 months. CONCLUSION: Retinal vessel oxygen saturation is affected in CRVO, and saturation correlates with BCVA. However, retinal oximetry cannot replace measures of visual function as a predictor of visual outcome after 12 months of anti-VEGF treatment for CRVO.

Oral administration of NSP-116, a free radical scavenger, suppresses the symptoms of retinal vein occlusion in the murine model.

Retinal vein occlusion (RVO) is an intractable eye disease that results in reduced visual acuity, associated with retinal ischemia, hemorrhage, and edema. RVO results in excessive ROS production in the retina, causing inflammation and retinal edema. A free radical scavenger, 4-(4-acetylpiperazin-1-yl)-2-(1H-imidazole-1-yl) aniline (NSP-116), has been reported to demonstrate antioxidative effects and prevent ROS production in the retina. Therefore, NSP-116 may represent a useful drug for treating the pathological symptoms of RVO, such as retinal edema and ischemic symptoms. This study aimed to investigate the effects of NSP-116 in a murine model of RVO. We evaluated the thickness of the retinal layer and the size of the non-perfused area following the oral administration of NSP-116. Moreover, we used western blot analysis to examine the expression levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, after NSP-116 administration, and examined the localization of 8-hydroxy-2'-deoxyguanosine (8-OHdG), by immunostaining. The findings indicate that NSP-116 suppressed retinal edema and expansion the non-perfused area by suppressing the increased expression of VEGF, TNF-α, and 8-OHdG in the murine RVO model. In conclusion, the oral administration of NSP-116 may serve as an effective pharmacological treatment for the pathological symptoms of RVO.

Macular Microvascular Changes and Their Correlation With Peripheral Nonperfusion in Branch Retinal Vein Occlusion.

PURPOSE: To investigate the correlation between macular microvascular alterations on optical coherence tomography angiography (OCTA) and retinal ischemia on ultra-widefield fluorescein angiography (UWF FA) in eyes with branch retinal vein occlusion (BRVO). DESIGN: Cross-sectional study. METHODS: This prospective study was performed from September 2019 to June 2020 at Yeungnam University Medical Center. We included 60 patients with treatment-naïve BRVO. Two independent, masked graders analyzed OCTA parameters, including vessel density, skeletal density, and fractal dimension (FD), and UWF FA parameters, including retinal nonperfusion area (NPA) and ischemic index (ISI), from various concentric regions (perimacular region, 0.5-3 mm radius; near-peripheral region, 3-10 mm; midperipheral region, 10-15 mm; far-peripheral region, >15 mm). A repeated-measures analysis of variance test and a paired t test were performed for inter-visit and inter-regional comparisons, and Pearson correlation coefficient and multivariate regression analyses were performed to examine the correlation between UWF FA and OCTA parameters. RESULTS: The OCTA parameters from both the superficial and deep capillary plexuses (DCP) were significantly correlated with NPA and ISI in all concentric regions. Even after adjusting for several covariates, all OCTA parameters revealed a significant association with ISI on UWF FA. Moreover, OCTA parameters from DCP were significantly correlated with concentrations of placental growth factor and vascular endothelial growth factor. Although all OCTA parameters achieved excellent results of area under the curve (AUC) > 0.9 for detecting severe retinal ischemia, defined as ISI >10%, FD reduction in DCP was the most reliable parameter (AUC = 0.948, P < .001), and 5.39% was the best cut-off point for predicting ISI > 10%. CONCLUSIONS: OCTA is a useful noninvasive tool not only for evaluation of macular microvasculature but for supposition of peripheral nonperfusion in eyes with BRVO.

Ranibizumab and aflibercept intravitreal injection for treatment naïve and refractory macular oedema in branch retinal vein occlusion.

BACKGROUND: Branch retinal vein occlusion complicated by macular oedema is a common disease treated with intravitreal injection of anti-vascular endothelial growth factor. Controversy exists surrounding anti-vascular endothelial growth factor selection for both treatment naïve and refractory cases. METHODS: A retrospective electronic medical record review at a single UK centre generated a cohort of 259 treatment naïve eyes from 258 patients receiving ranibizumab, aflibercept or a combination (n = 83, 97 and 79, respectively) from 2013 to 2018 with ⩾6 months follow-up. Number of intravitreal injections, visual acuity and macular oedema presence were noted at 3, 6, 12, 24, 36 and 48 months. A subgroup analysis examined refractory cases switched from ranibizumab to aflibercept (n = 77) or maintained on ranibizumab (n = 35). RESULTS: Eyes receiving ranibizumab or aflibercept had equivocal vision gain at 1 year, 8.0 (95% CI 5.0-11.0) and 9.6 (7.2-12.1) Early Treatment of Diabetic Retinopathy Study letters, respectively. About 35.6% had no macular oedema at 12 months with ranibizumab compared with 50.0% with aflibercept (p = 0.07) following 5.1 (4.7-5.6) and 6.0 (5.6-6.4) intravitreal injections, respectively. Visual prognosis declined significantly as treatment delay extended (p = 0.003) which was only apparent with ⩾3 months delay. Eyes with refractory macular oedema also had equivocal functional and anatomical outcomes whether they were maintained on ranibizumab or switched to aflibercept. CONCLUSION: These real world data demonstrate more modest clinical improvements from anti-vascular endothelial growth factor treatment than reported in clinical trials. The functional outcomes of ranibizumab and aflibercept in both treatment naïve and refractory cases were equivocal while the anatomical outcomes of aflibercept may be superior.

Higher Aqueous Levels of Resistin and Lipocalin-2 Indicated Worse Visual Improvement following anti-VEGF Therapy in Patients with Retinal Vein Occlusion.

PURPOSE: The aim of this study was to investigate the aqueous humor levels of elastase-2, lactoferrin, lipocalin-2 (LCN-2), resistin, and thrombospondin-1 (TSP-1) in patients with retinal vein occlusion (RVO) and their relationship with visual prognosis following intravitreal anti-vascular endothelial growth factor (VEGF) therapy. MATERIALS AND METHODS: 52 RVO patients (23 cases of central retinal vein occlusion (CRVO) and 29 cases of branch retinal vein occlusion (BRVO)) and 20 cases of senile cataract were enrolled in this study. All RVO patients underwent fundus examinations before and 6-8 months after intravitreal anti-VEGF treatment. Five milliliters of blood were collected from RVO patients before treatment for the measurement of lipids and coagulation factors. Sixty microliters of aqueous humor were collected during intravitreal injection of anti-VEGF or during cataract surgery. The levels of elastase-2, lactoferrin, LCN-2, resistin, and TSP-1 in aqueous humor were determined by Luminex xMAP multiple analysis. RESULTS: The aqueous levels of resistin and LCN-2 were significantly higher but the level of TSP-1 was significantly lower in RVO patients compared to controls. Further, sub-group analysis showed that CRVO patients had significantly higher levels of resistin and LCN-2 than controls. The aqueous levels of resistin and LCN-2 were negatively correlated with visual improvement following anti-VEGF therapy in CRVO but not in BRVO patients. Visual improvement in RVO patients was not associated with blood lipid levels or any of the coagulation factors. CONCLUSION: CRVO patients had significantly higher aqueous levels of resistin and LCN-2, which negatively impacted on visual improvement after anti-VEGF therapy.