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Laser photocoagulation is the current gold standard treatment for proliferative retinopathy of prematurity (ROP). However, it permanently reduces the visual field and might induce myopia. Vascular endothelial growth factor (VEGF) inhibitors for the treatment of ROP may enable continuing vascularization of the retina, potentially allowing the preservation of the visual field. However, for their use in infants concern remains. This meta-analysis explores the safety of VEGF inhibitors. The Ovid Interface was used to perform a systematic review of the literature in the databases PubMed, EMBASE and the Cochrane Library. This meta-analysis included 24 original reports (including 1.457 eyes) on VEGF inhibitor treatment for ROP. The trials were solely observational except for one randomized and two case-control studies. We estimated a 6-month risk of retreatment per eye of 2.8%, and a 6-month risk of ocular complication without the need of retreatment of 1.6% per eye. Systemic complications were only reported as isolated incidents. VEGF inhibitors seem to be associated with low recurrence rates and ocular complication rates. They may have the benefit of potentially allowing the preservation of visual field and lower rates of myopia. Due to the lack of data, the risk of systemic side effects cannot be assessed.

Purpose To evaluate the relevance of external limiting membrane (ELM) on the visual and morphological results in eyes with diabetic macular edema (DME) that underwent pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling. Methods Medical records of patients with DME who underwent PPV at our unit between January 2017 and December 2019 were reviewed. We assessed preoperative and postoperative best-corrected visual acuity (BCVA), central macular thickness (CMT) using spectral domain OCT (optical coherence tomography). Exclusion criteria were previous PPV; incomplete data; concomitant diseases including retinal vein occlusion, age-related macular degeneration, uveitis; and a follow-up of less than 12 months. The surgeries were performed using 23- or 27-gauge vitrectomy. The ELM was graded depending on its configuration (grade 0 = intact, grade 1 to 3: disruption of varying extent). Results Ninety-nine eyes were enrolled. The postoperative follow up averaged 23.7 months. The preoperative and final BCVA averaged 0.71 ± 0.28 and 0.52 ± 0.3 logMAR, respectively ( p  = 0.002). The CMT averaged 515.2 ± 209.1 μm preoperatively and 327 ± 66.1 μm postoperatively ( p  = 0.001). Eyes with intact ELM ( n  = 8) had a significantly better BCVA compared to those with ELM disruption (0.28 ± 0.14 vs. 0.7 ± 0.25 logMAR, p  = 0.01). The final CMT was similar among the groups (intact ELM: 317 ± 54.6 μm; ELM disruption: 334 ± 75.2, p  = 0.31). Conclusions PPV with ERM and ILM peeling is an effective treatment of DME. Eyes with intact ELM preoperatively had a significantly better final visual outcome. To maximize the benefit for patients with DME we recommend early PPV as long as ELM is intact.

An amendment to this paper has been published and can be accessed via the original article.

High-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients. Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants. In our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01). The investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis.

To identify preoperative markers on spectral domain optical coherence tomography (SD-OCT) for residual inner limiting membrane (ILM) in epiretinal membrane (ERM) peeling. In this retrospective case series the preoperative SD-OCTs from 119 eyes of 119 consecutive patients who underwent surgery for idiopathic ERM by a single surgeon were evaluated for markers predisposing for ILM persistence after ERM removal. ILM persistence was determined via intraoperative indocyanine green staining. The main outcome measures were correlation of central foveal thickness (CFT), ERM thickness, extent of elevated ERM and retinal folding, intraretinal cysts, and discontinuation of the ERM, with ILM persistence after ERM peeling. The persistence of the ILM was found in 50.4% (n = 60). After Bonferroni correction for multiple testing, a greater extent of elevated ERM and thicker ERMs were associated with persistence of the ILM (p<0.005). The other parameters showed no statistically significant correlations with the persistence of the ILM (p≥0.005). Residual ILM can be found in nearly half of the eyes after ERM peeling. A loose connection between the ERM and the retinal surface predisposes for ILM persistence. Preoperative SD-OCT is helpful in identifying risk markers for the persistence of the ILM in ERM surgery.

[This corrects the article DOI: 10.1371/journal.pone.0154397.].

Background There is strong and consistent evidence that oxidative stress is crucially involved in the development of atherosclerotic vascular disease. Overproduction of reactive oxygen species (ROS) in mitochondria is an unifying mechanism that underlies micro- and macrovascular atherosclerotic disease. Given the central role of mitochondria in energy and ROS production, mitochondrial DNA (mtDNA) is an obvious candidate for genetic susceptibility studies on atherosclerotic processes. We therefore examined the association between mtDNA haplogroups and coronary artery disease (CAD) as well as diabetic retinopathy. Methods This study of Middle European Caucasians included patients with angiographically documented CAD (n = 487), subjects with type 2 diabetes mellitus with (n = 149) or without (n = 78) diabetic retinopathy and control subjects without clinical manifestations of atherosclerotic disease (n = 1527). MtDNA haplotyping was performed using multiplex PCR and subsequent multiplex primer extension analysis for determination of the major European haplogroups. Haplogroup frequencies of patients were compared to those of control subjects without clinical manifestations of atherosclerotic disease. Results Haplogroup T was significantly more prevalent among patients with CAD than among control subjects (14.8% vs 8.3%; p = 0.002). In patients with type 2 diabetes, the presence of diabetic retinopathy was also significantly associated with a higher prevalence of haplogroup T (12.1% vs 5.1%; p = 0.046). Conclusion Our data indicate that the mtDNA haplogroup T is associated with CAD and diabetic retinopathy in Middle European Caucasian populations.

PurposeTo report outcomes of re-vitrectomy using light silicone oil (SO) tamponade for persistent macular holes (MHs).MethodsWe reviewed cases of patients with full-thickness MHs that underwent pars plana vitrectomy (PPV) with air/gas and were re-vitrectomized using light SO tamponade after primary non-closure (persistent MHs). Outcome measures included anatomic closure rates and patterns confirmed by optical coherence tomography (OCT) and changes in best-corrected visual acuity (BCVA).ResultsA total of 42 eyes of 41 patients with unsuccessful primary PPV with air/gas were included. After re-vitrectomy with light SO (1000-centistoke), 29 (69%) eyes demonstrated type 1 closure without neurosensory defects in OCT scans, whereas 9 eyes (21%) showed type 2 closure with persisting neurosensory defects. Available data (n = 21) showed a significant mean improvement of BCVA from 0.99 logMAR (SD 0.25, range 0.7–1.3) preoperatively to 0.74 logMAR (SD 0.42, range 0.2–1.5) postoperatively (p = 0.035).ConclusionThe treatment of persistent MHs with PPV and light SO tamponade resulted in high closure rates.

Aim The current accepted standard treatment for neovascular age-related macular degeneration (AMD) consists of antivascular endothelial growth factor agents including ranibizumab and bevacizumab. The aim of the study was to examine whether bevacizumab is inferior to ranibizumab with respect to maintaining/improving visual acuity. Methods In this prospective randomised parallel group multicentre trial patients aged more than 50 years with treatment naive nAMD were included at 10 Austrian centres. Patients were randomised to treatment either with 0.5 mg ranibizumab or 1.25 mg bevacizumab. Both groups received three initial monthly injections and thereafter monthly evaluation of visual acuity and the activity of the lesion. Re-treatment was scheduled as needed. Outcome measures were early treatment of diabetic retinopathy visual acuity, retinal thickness, lesion size and safety evaluation. Results A total of 321 patients were recruited of which four had to be excluded due to different reasons. Of the 317 remaining patients 154 were randomised into the bevacizumab group and 163 into the ranibizumab group. At month 12, there was a mean increase of early treatment of diabetic retinopathy visual acuity of 4.9 letters in the bevacizumab and 4.1 letters in the ranibizumab group (p=0.78). Furthermore, there were no significant differences in the decrease of retinal thickness, change of lesion size and number of adverse events between the groups. Conclusions Bevacizumab was equivalent to ranibizumab for visual acuity at all time points over 1 year. There was no significant difference of decrease of retinal thickness or number of adverse events.

PurposeNumerous studies suggest that reactive oxygen species play a crucial role in the development of glaucoma. Since glaucoma patients exhibit posterior vitreous detachment earlier than controls, it has been suggested that reactive oxygen species—increased in glaucoma—also affect the vitreous. In the present study we evaluated the influence of open-angle glaucoma oxidative stress on the redox state of vitreous albumin. MethodsAlbumin redox states of the vitreous and plasma were evaluated in 22 subjects—11 open-angle glaucoma patients and 11 controls—matched for age, gender, and vitreous state. According to the redox state of cysteine-34, albumin can be separated into: human mercaptalbumin (the thiol form), human nonmercaptalbumin1 (a reversible modification due to mild oxidation), and human nonmercaptalbumin2 (an irreversible modification due to severe oxidation). ResultsAlbumin of both, the open-angle glaucoma group and the control group, was more oxidized in the vitreous compared to plasma. Furthermore, significantly higher human nonmercaptalbumin1 fractions were found in the vitreous of open-angle glaucoma patients compared to controls. No significant differences were found in the plasma albumin fractions between the groups.ConclusionOur results support the hypothesis that oxidative stress plays a crucial role in open-angle glaucoma and that reactive oxygen species in glaucomatous eyes may also affect the vitreous.