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PurposeTo demonstrate superiority of intravitreal ranibizumab 0.5 mg compared to focal and peripheral laser treatment in patients with radiation retinopathy for choroidal melanoma.MethodsInclusion criteria were as follows: patients with radiation retinopathy and visual acuity impairment due to radiation maculopathy accessible for laser therapy, age ≥ 18 years, and BCVA less than 20/32. The main objective was to study the change in best-corrected visual acuity (BCVA) over 6 months from ranibizumab 0.5 mg (experimental) compared to focal laser of the macula and panretinal laser treatment of the ischemic retina (control) in patients with radiation retinopathy in choroidal melanoma. The secondary objectives of the radiation retinopathy study were to compare functional and anatomical results between ranibizumab and laser group over 12 months and to measure the frequency of vitreous hemorrhage and rubeosis iridis.ResultsThe intention-to-treat analysis included 31 patients assigned to ranibizumab (n = 15) or laser treatment (n = 16). In terms of BCVA at month 6, ranibizumab was superior to laser treatment, with an advantage of 0.14 logMAR, 95% CI 0.01 to 0.25, p = 0.030. The positive effect of ranibizumab disappeared after treatment was discontinued. Similar results without statistically significant difference were found with respect to macular thickness. In both groups, no change was observed at month 6 in the size of ischemia in the macula or periphery compared to baseline. There was 1 case of vitreous hemorrhage in the laser group and no case of rubeosis iridis over time.ConclusionsThis study showed a statistically significant improvement in visual acuity and clear superiority of ranibizumab compared to laser treatment up to 26 weeks, but this effect disappeared at week 52 after completion of intravitreal treatment. Ranibizumab and PRP are considered equivalent in terms of the non-appearance of proliferative radiation retinopathy during the study.Trial registrationEudraCT Number: 2011-004463-69

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.

The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases. Degradable polymeric porous microcapsules loaded with exosomes from mesenchymal stem cells or regulatory T cells led to the restoration of retinal thickness in mice with retinal ischaemia-reperfusion injury and to reductions in inflammatory cells in monkeys with mycobacterial uveitis.

This study aims to report a case of unilateral Purtscher-like retinopathy (PLR) secondary to systemic lupus erythematosus (SLE) and explore its clinical features, diagnosis, and therapeutic outcomes. A retrospective analysis was performed on the clinical data of a 23-year-old female SLE patient, including medical history, ophthalmic examinations, visual acuity, fundus assessment, optical coherence tomography (OCT), fundus fluorescein angiography (FFA), laboratory tests, and treatment follow-up results. The patient was admitted with acute left eye vision loss for over 2 days and had an 8-year history of SLE. Clinical manifestations included left eye Purtscher flecken and retinal microcirculatory abnormalities. The initial left eye visual acuity was 0.05 (no improvement with correction). The fundus examination revealed Purtscher flecken along vascular tracts, OCT showed hyperreflectivity in the inner macular retina, and FFA confirmed PLR. The laboratory tests indicated elevated erythrocyte sedimentation rate (109.00 mm/h), increased immunoglobulin G (34.88 g/L), and a SLE Disease Activity Index score of 4 (low disease activity). The treatment included prednisone acetate combined with cyclophosphamide for primary disease control, Guhong Injection for circulatory improvement, peribulbar injection of compound anisodine combined with methylcobalamin for neuroprotection, and laser photocoagulation for macular non-perfusion areas. After 11 days of treatment, the left eye visual acuity improved to 0.25 with symptom relief; the 1-month follow-up showed reduced Purtscher flecken, improved macular hyperreflectivity, and stable vision. PLR is a rare ocular complication of SLE that can occur even during low disease activity. Early diagnosis combined with primary disease control, microcirculatory improvement, and laser therapy can effectively improve visual prognosis, highlighting the importance of regular fundus screening for SLE patients.

Appropriate nutrients are essential for cellular function. Dietary components can alter the risk of systemic metabolic diseases, including cardiovascular diseases, cancer, diabetes, and obesity, and can also affect retinal diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. Dietary nutrients have been assessed for the prevention or treatment of retinal ischemic diseases and the diseases of aging. In this article, we review clinical and experimental evidence concerning the potential of some nutritional supplements to prevent or treat retinal ischemic diseases and provide further insights into the therapeutic effects of nutritional supplementation on retinopathies. We will review the roles of nutrients in preventing or protecting against retinal ischemic diseases.

Background/aimsTo describe the clinical impact of external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption and subretinal fluid (SRF) seen on optical coherence tomography (OCT) in eyes with vitreomacular traction (VMT) without macular hole (MH) in the Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole study.MethodsPhase 3b randomised double-blind sham-controlled multicentre study including 144 eyes with VMT without MH. Eyes were randomised to receive a single intravitreal injection of ocriplasmin or sham injection and were followed for 24 months. Eyes were analysed for presence, course and clinical impact of ELM disruption, EZ disruption and SRF on OCT.ResultsELM disruption, EZ disruption and SRF were present in 32.6%, 52.2% and 45.8% of ocriplasmin-treated eyes and 39.6%, 42.6% and 37.5% of sham-treated eyes at baseline. VMT resolution was associated with resolution of ELM and EZ disruption and SRF. A small number of eyes had persistent ELM disruption, EZ disruption and/or SRF at the seventh visit or later (17 months or later) following medical or surgical VMT resolution. Resolution of ELM disruption, EZ disruption and/or SRF was associated with an improvement of visual acuity from baseline. Following VMT resolution, ELM recovery usually preceded EZ recovery and SRF resolution.ConclusionsELM disruption, EZ disruption and/or SRF are present in a significant percentage of eyes with VMT without MH. Release of VMT is usually associated with outer retinal recovery and an associated improvement in visual acuity. ELM recovery typically precedes EZ recovery and SRF resolution following VMT release.

N6-Methyladenosine (m6A) modification, the most abundant internal chemical modification in eukaryotic messenger RNA, plays a central role in gene expression by dynamically regulating RNA metabolism. The present review systematically summarizes the regulatory mechanisms and pathological significance of m6A modification in major retinal diseases, including diabetic retinopathy, age-related macular degeneration, retinoblastoma, uveitis and retinitis pigmentosa. Studies indicate that m6A methyltransferases (METTL3), demethylases (FTO and ALKBH5) and reader proteins (the YTH domain-containing family of proteins) participate in pathological processes such as angiogenesis, inflammatory responses, pyroptosis and photoreceptor degeneration by modulating the stability, translation efficiency and degradation of key gene mRNAs. Furthermore, this review explores the therapeutic potential of targeting m6A-modifying enzymes (for example, small-molecule inhibitors STM2457 and FB23-2) and highlights challenges in tissue specificity, delivery systems and clinical translation. Future research should integrate multi-omics technologies and precision intervention strategies to advance the application of m6A modification in the diagnosis and treatment of retinal diseases.

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.Erratum to “Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management”dx.doi.org/10.1155/2013/861251

Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt's disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber's congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber's congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.

Background/Objective Adolescents with type 1 diabetes have early macrovascular changes (increased intima‐media thickness [IMT]) and early retinal changes that predict clinical disease in adulthood. We hypothesized that early changes in the macrovascular and retinal microvascular beds develop in parallel before retinopathy develops. We therefore aimed to investigate the relationship between changes in atherosclerosis (carotid and aortic IMT) and retinal vascular geometry cross‐sectionally and longitudinally in adolescents with type 1 diabetes. Methods Ninety adolescents with type 1 diabetes (41 boys, aged 13.6 ± 3.5 years) who were enrolled in a randomized controlled trial had evaluations at baseline; 41 randomized to placebo were also investigated at 12 months for carotid and aortic IMT using ultrasound and retinal vascular geometry was measured from retinal photographs. Results There were significant associations between thicker mean/maximum carotid IMT and wider retinal arteriolar and venular calibers; for every 0.1 mm increase in mean carotid IMT, retinal arteriolar caliber increased by 7.90 μm (95% confidence interval [CI] 4.50, 11.30, P < 0.0001) and venular caliber by 9.61 μm (95% CI 4.16, 15.06, P = 0.0008). Increased mean aortic IMT was associated with increased arteriolar tortuosity (2.61, 95% CI 0.50, 4.71, P = 0.02). Conclusions The early changes of atherosclerosis are associated with retinal microvascular changes in adolescents with type 1 diabetes. This supports parallel adverse changes in the macro and microvascular circulations from early adolescence in type 1 diabetes, and highlights the importance of early intervention.