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Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a systematic review to evaluate efficacy and safety outcomes of intravitreal therapies for macular edema in CRVO and BRVO. MEDLINE, Embase, and the Cochrane Library were systematically searched for RCTs with no limitations of language and year of publication. 11 RCTs investigating anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) and steroids (triamcinolone, dexamethasone implant) with a minimum follow-up of 1 year were evaluated. Greatest gain in visual acuity after 12 months was observed both under aflibercept 2 mg: +16.2 letters (8.5 injections), and under bevacizumab 1.25 mg: +16.1 letters (8 injections). Ranibizumab 0.5 mg improved vision by +13.9 letters (8.8 injections). Triamcinolone 1 mg and 4 mg stabilized visual acuity at a lower injection frequency (-1.2 letters, 2 injections). Ranibizumab 0.5 mg resulted in a visual acuity gain of +18.3 letters (8.4 injections). The effect of dexamethasone implant was transient after 1.9 implants in both indications. Serious ocular adverse events were rare, e.g., endophthalmitis occurred in 0.0-0.9%. Major differences were found in an indirect comparison between steroids and anti-VEGF agents for cataract progression (19.8-35.0% vs. 0.9-7.0%) and in required treatment of increased intraocular pressure (7.0-41.0% vs. none). No major differences were identified in systemic adverse events. Anti-VEGF agents result in a promising gain of visual acuity, but require a high injection frequency. Dexamethasone implant might be an alternative, but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen. The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids. Because comparative data from head-to-head trials are missing currently, clinicians and patients should carefully weigh the benefit-harm ratio.

Patients suffering from type 2 diabetes are at an increased risk of developing classical microvascular complications such as retinopathy, neuropathy, and nephropathy, which represent a significant health burden. Tight control of blood glucose, blood pressure, and serum cholesterol reduce the risk of microvascular complications but effective pharmacologically targeted treatment options for the treatment and prevention of diabetic microangiopathy are still lacking. Pharmacological inhibition of sodium glucose cotransporter 2 (SGLT2) might have the potential to directly protect against microvascular complications and could represent a potential treatment option. Randomized controlled clinical proof of concept trials are needed to investigate a potential central role of SGLT2 inhibitors in the prevention of diabetic microangiopathy and its classical clinical complications of retinopathy, neuropathy, and nephropathy.

Central retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO. Vitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray. Expression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE). Proteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach.

PurposeCentral serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy.Material and methodsThis is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 μs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®).ResultsMean CRT at BSL was 387.69 ± 110.4 μm. CRT significantly decreased by 106.31 μm in wk4 (95%-KI: 21.42–191.2; p = 0.01), by 133.63 μm in wk12 (95%-KI: 50.22–217.03; p = 0.001) and by 133.81 μm (95%-KI: 48.88–218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures.ConclusionSingle or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.

Purpose. To evaluate the anatomical and functional outcome of intravitreal dexamethasone implant for macular edema secondary to central (C) or branch (B) retinal vein occlusion (RVO) in patients with persistent macular edema (ME) refractory to intravitreal antivascular endothelial growth factor (VEGF) treatment compared to treatment naïve patients and to dexamethasone-refractory eyes switched to anti-VEGF. Methods. Retrospective, observational study including 30 eyes previously treated with anti-VEGF (8 CRVO, 22 BRVO, mean age 69 ± 10 yrs), compared to 11 treatment naïve eyes (6 CRVO, 5 BRVO, 73 ± 11 yrs) and compared to dexamethasone nonresponders (2 CRVO, 4 BRVO, 69 ± 12). Outcome parameters were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by spectral-domain optical coherence tomography. Results. Mean BCVA improvement after switch to dexamethasone implant was 4 letters (p=0.08), and treatment naïve eyes gained 10 letters (p=0.66), while we noted no change in eyes after switch to anti-VEGF (p=0.74). Median CFT decrease was most pronounced in treatment naïve patients (−437 μm, p=0.002) compared to anti-VEGF refractory eyes (−170 μm, p=0.003) and dexamethasone-refractory eyes (−157, p=0.31). Conclusions. Dexamethasone significantly reduced ME secondary to RVO refractory to anti-VEGF. Functional gain was limited compared to treatment naïve eyes, probably due to worse BCVA and CFT at baseline in treatment naïve eyes.

Glaucoma, a leading cause of blindness, is often driven by elevated intraocular pressure (IOP), which damages the optic nerve. Transscleral filtration surgery reduces IOP but is frequently complicated by excessive wound healing from Tenon fibroblasts (TFs), impeding aqueous humor absorption. Mitomycin C (MMC), used for over 30 years in ophthalmic surgeries, inhibits TF proliferation but carries significant side effects, including hypotony, blebitis, and endophthalmitis, due to its non-selective cytotoxicity. MMC's inability to entirely prevent fibrosis increases surgical failure risk, often necessitating further interventions like bleb needling. This study investigates whether ascorbic acid (AA) and hydrogen peroxide (H2O2) can selectively target TFs without damaging scleral fibroblasts (SFs) in vitro, using MMC as a benchmark. Primary human TFs and SFs were cultured from patient trabeculectomy tissues. Cells were treated with various concentrations of MMC, AA, or H2O2. Cytotoxic effects were analyzed via live-cell imaging. Immunocytochemistry and Western Blot assessed catalase expression in both cell types and recombinant catalase was used to validate its protective effect against AA- and H2O2-induced cell death. Short-term exposure (5 min) to 0.02%-0.04% MMC or long-term exposure to 0.00025%-0.001% MMC caused cytotoxicity in TFs and SFs, with SFs dying significantly earlier. In contrast, AA (6-8 mM) selectively induced cell death in TFs without harming SFs. H2O2 also showed selective cytotoxicity towards TFs. Lower catalase expression in TFs compared to SFs was determined via Western blot and immunocytochemistry, highlighting a mechanism for this selective effect. Recombinant catalase neutralized the cytotoxic effects of AA and H2O2 on TFs. Unlike MMC, Ascorbic acid and hydrogen peroxide exhibit selective cytotoxicity towards Tenon fibroblasts, which may provide a safer, more targeted approach for preventing fibrosis in glaucoma surgery. Additional in vivo studies are needed to explore the clinical applicability of these findings.

To evaluate the relationship between macular pigment optical density (MPOD) and glaucoma. Forty-three patients with an established glaucoma diagnosis (25 females, 18 males, mean age 70 (range 34-84)) and 43 healthy controls (28 females, 15 males, mean age 62 (range 30-87)) were included in this prospective diagnostic case-control study. All subjects underwent detailed eye examination including ophthalmoscopy, best-corrected visual acuity, biomicroscopy, measurement of the axial length of the eye, objective refraction, lens status, central foveal thickness on spectral-domain optical coherence tomography (SD-OCT). In all glaucoma patients, a visual field assessment and a measurement of the retinal nerve fibre layer (RNFL) on SD-OCT were done. MPOD was determined using the macula pigment module of the Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) at 0.51°, 1.02° and 1.99° retinal eccentricity using two-wavelength autofluorescence imaging. In the glaucoma group, the median of the visual field mean defect was 5.1 db (quartiles 3.0 and 13.5) and the mean RNFL-thickness global was 65.9 µm (SD ± 16.1). Median MPOD measured at 0.51°, 1.02° and 1.99° retinal eccentricity in the glaucoma group was 0.42 DU, 0.34 DU and 0.13 DU, in the control group 0.40 DU, 0.35 DU and 0.12 DU respectively. There was no statistically significant difference of median MPOD between glaucomatous and control eyes (p=0.510, 0.735, 0.481). No significant relation between MPOD at 1.02 retinal eccentricity and the presence of glare symptoms was found (p=0.948). However, age seems to correlate with median MPOD measured at 1.02 retinal eccentricity (p=0.017). There was no evidence for lower MPOD levels in our glaucoma patients; lower MPOD was not related to the presence of glare symptoms. However there seems to be a positive correlation between age and MPOD at 1.02° retinal eccentricity. To further investigate the relation between glare reported by glaucoma patients and glare disability linked to lower MPOD levels, additional studies are necessary that include both detailed inquiry of the quality of glare and a glare quantification and precise analysis of MPOD levels in glaucoma patients.

PurposeTo test if an encircling band improves outcomes in vitrectomy for pseudophakic retinal detachment (PRD) with inferior or with multiple (4 or more) breaks.MethodsSubgroup analysis of a prospective randomized controlled multicenter trial in patients with uncomplicated PRD assigned either to 20 G vitrectomy plus encircling band (group E1), or 20 G vitrectomy without any buckle (group C), or 23/25 G vitrectomy without any buckle (group E2). The primary endpoint was defined as no indication for any retina reattaching procedure during the review period of 6 months. One hundred out of 257 patients were identified with inferior breaks and 63 patients had 4 or more breaks.ResultsIn patients with retinal breaks between 5:00 and 7:00, treatment was successful in 77.4% (24/31, treatment arm E1) versus 57.1% (16/28, treatment arm C) (p = 0.301, odds ratio (OR) 1.83, 95% confidence interval (CI) 0.48 to 7.17). In patients with multiple breaks, success rates were 68.2% (15/22, E1) versus. 72.4% (21/29, C, p = 0.46, OR 0.52, CI 0.08–3.65).ConclusionCombining an encircling band with vitrectomy in patients with pseudophakic retinal detachment and inferior or multiple breaks does not significantly improve primary anatomical success in comparison to treatment with 20 G or 23/25 G vitrectomy alone.

Introduction The study analyses patients’ risk factors to determine prognostic and predictive factors in patients with acute central retinal artery occlusion (CRAO) treated in the randomized European Assessment Group for Lysis in the Eye (EAGLE) Study with local intra-arterial fibrinolysis (LIF) or conservative standard treatment (CST). These data could improve patient selection for either method. Methods Post hoc statistical analysis of effects of risk factors on overall best corrected visual acuity (BCVA [logarithm of the minimum angle of resolution (logMAR)]) at baseline and month 1 (prognostic effect) and on the difference between outcome of CST and LIF (predictive effect) was conducted. Results Seventy two of 84 EAGLE datasets were included. Prognostic effect: Patients with coronary heart disease (CHD) presented worse BCVA at baseline (0.39 logMAR, p  = 0.0097). Patients with time from occlusion to treatment <12 h showed a trend to better vision gain at month 1 (−0.23 logMAR, p  = 0.086), similarly smoking (−0.24 logMAR, p  = 0.077). Predictive effect: Age (<60 years favours LIF −0.54 logMAR; >70 years favours CST 0.28 logMAR; interaction p  = 0.070) and CHD (favours CST 0.44 logMAR; interaction p  = 0.073) might be predictors of therapeutic outcome. There were no strong effects in multivariate analysis. Conclusion CHD, time from occlusion to treatment and smoking influence BCVA at baseline and at month 1 (prognostic effect). Patients treated within 12 h are more likely to profit from treatment. In multivariate analysis, there is no clear trend to benefit from LIF even in patients with young age, no CHD and early treatment. Based on this preliminary report on a rather small sample size, we do not recommend LIF in CRAO patients.

Serious complications are disseminated intravascular coagulation (DIC), abruptio placentae, acute renal and hepatic failure, pulmonary oedema or cerebral haemorrhage. 7 Until recently, the maternal mortality from HELLP syndrome was 1%-25%, the rate of maternal complications was 12.5%-56% and perinatal infant mortality was 7.4%-34%. Choroidal vaso-occlusion and subsequent retinal pigment epithelium (RPE) damage with breakdown of the blood-retinal barrier due to hypertensive vasoconstriction or DIC triggered by placental thromboplastin have been suggested. 6 10 11 This is supported by the findings in fluorescein and indocyanine green angiography, where choroidal malperfusion was detected in preeclampsia. 12 Ophthalmoscopy shows choroidal involvement as yellow-white focal lesions on the RPE level and Elschnig's spots, that is, small areas of hyperpigmentation with surrounding yellow or red halos, which may indicate choriocapillary infarction.