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As the most common primary intraocular malignancy of childhood, retinoblastoma (RB) has had a complex journey in its management, following a course from enucleation as the first life-saving treatment to numerous globe-salvaging therapies during the last century. Currently, this potentially lethal disease has achieved high survival rates owing to multidisciplinary management and the introduction of neoadjuvant and multimodal chemotherapy. Therefore, the goal of treatment is shifting toward conserving the globe and vision as much as possible. Up until recently, many advanced cases of RB were enucleated primarily; however, targeted chemotherapy via the ophthalmic artery and management of intraocular seeding by local administration of chemotherapeutic agents have revolutionized the globe-conserving therapies. The added benefit of avoiding systemic complications of cytotoxic drugs resulted in these methods gaining popularity, and they are becoming a main part of care in many referral centers. Initially, there were some safety concerns regarding these approaches; however, increasing experience has shown that these modalities are relatively safe procedures and many complications can be averted by changing the choice of the drug and using some prophylactic measures. It is hoped that, in the near future, with advances in early diagnosis and patient-targeted molecular therapies, as well as gene-editing techniques, the patient's vision can be saved even in advanced RB.

Von Hippel-Lindau (VHL) syndrome is an autosomal dominant inherited multisystem neoplasia disorder caused by the VHL tumor suppressor gene, coding for VHL protein (pVHL), variants. Various types of VHLvariants present different clinical phenotypes that later lead to events resulting in benign or malignant lesions including Retinal Capillary Hemangioblastoma (RCH). In this case series study, 3 families (5 RCH patients) with novel mutations were included. VHL mutational analysis was performed by Sanger sequencing. We reported on 3 novel mutation sites, including c.511A>C, c.514C>T, and c.511A>T in exon 3 of the VHL gene. According to the ACMG classifications, c.514C>T and c.511A>T variations are likely pathogenic, and c.511A>C is a variant of uncertain significance (VUS) and in accordance with autosomal dominant inheritance. The location and impact of the incidence mutations on pVHL were computed using in silico analysis. The obtained structural information and computational analysis showed that the studied mutations induce conformational changes that limit the flexibility of the pVHL interaction interface with elonginB/C, elongin C/B, and cullin2, which is necessary for HIF1 alpha binding. The recently added gene variants and their related clinical phenotypes will improve the VHL diagnosis accuracy and the patients’ population carrying VHLgene mutations. These pioneering results could be a model for future functional studies.

Von Hippel-Lindau (VHL) syndrome is an autosomal dominant inherited multisystem neoplasia disorder caused by theVHLtumor suppressor gene, coding for VHL protein (pVHL), variants. Various types ofVHLvariants present different clinical phenotypes that later lead to events resulting in benign or malignant lesions including Retinal Capillary Hemangioblastoma (RCH). We reported on 3 novel mutation sites observed in 3 families (5 RCH patients), including c.511A>C, c.514C>T, and c.511A>T in exon 3 of theVHLgene. According to the ACMG classifications, c.514C>T and c.511A>T variations are likely pathogenic, and c.511A>C is a variant of uncertain significance (VUS) and in accordance with autosomal dominant inheritance. The location and impact of the incidence mutations on pVHL were computed using in silico analysis. The obtained structural information and computational analysis showed that the studied mutations induce conformational changes that limit the flexibility of the pVHL interaction interface with elonginB/C, elongin C/B, and cullin2, which is necessary for HIF1 alpha binding. The recently added gene variants and their related clinical phenotypes will improve the VHL diagnosis accuracy and the patients’ population carryingVHLgene mutations. These pioneering results could be a model for future functional studies.

Backgrounds: Retinal capillary hemangioblastoma (RCH) although may also be observed sporadically, is the most frequent and earliest manifestation of the Von Hippel-Lindau disease (VHL). This is the first report of different types of variants spectrum and genotype-phenotype correlations in the Iranian families with RCH. Methods: In this Prospective Observational Case Series study, 17 families with RCH were included. PCR was performed to amplify 3 exons of the VHL gene. Afterwards, Sanger sequencing was performed on all the PCR products. For the detection of VHL copy number variations, MLPA was used. Results: Our study identified 10 different types of predominantly pathogenic VHL variants. Missense mutations were the most common variants located on the α domain of the VHL protein (pVHL) in exon 3. Also, the pathogenic variants in RCH patients with CNS hemangioblastoma (CHB) mostly (72.7%) were located on the α domain. In a family, Proband’s sister had a different mutation with more severe clinical manifestations and a poor prognosis.Conclusion: α domain of VHL may play a potential role in the pathogenesis of RCH. Our findings suggest that the genotype-phenotype characteristics in those variants in α- domain may predispose patients to RCH with CHB.

Background: To investigate the effect of various factors on ocular motility disturbance after episcleral plaque brachytherapy with Ruthenium 106 (106Ru).Methods: Twenty consecutive patients who und...

The purpose of this study was to introduce a new deep learning (DL) model for segmentation of the fovea avascular zone (FAZ) in en face optical coherence tomography angiography (OCTA) and compare the results with those of the device’s built-in software and manual measurements in healthy subjects and diabetic patients. In this retrospective study, FAZ borders were delineated in the inner retinal slab of 3 × 3 enface OCTA images of 131 eyes of 88 diabetic patients and 32 eyes of 18 healthy subjects. To train a deep convolutional neural network (CNN) model, 126 enface OCTA images (104 eyes with diabetic retinopathy and 22 normal eyes) were used as training/validation dataset. Then, the accuracy of the model was evaluated using a dataset consisting of OCTA images of 10 normal eyes and 27 eyes with diabetic retinopathy. The CNN model was based on Detectron2, an open-source modular object detection library. In addition, automated FAZ measurements were conducted using the device’s built-in commercial software, and manual FAZ delineation was performed using ImageJ software. Bland–Altman analysis was used to show 95% limit of agreement (95% LoA) between different methods. The mean dice similarity coefficient of the DL model was 0.94 ± 0.04 in the testing dataset. There was excellent agreement between automated, DL model and manual measurements of FAZ in healthy subjects (95% LoA of − 0.005 to 0.026 mm2 between automated and manual measurement and 0.000 to 0.009 mm2 between DL and manual FAZ area). In diabetic eyes, the agreement between DL and manual measurements was excellent (95% LoA of − 0.063 to 0.095), however, there was a poor agreement between the automated and manual method (95% LoA of − 0.186 to 0.331). The presence of diabetic macular edema and intraretinal cysts at the fovea were associated with erroneous FAZ measurements by the device’s built-in software. In conclusion, the DL model showed an excellent accuracy in detection of FAZ border in enfaces OCTA images of both diabetic patients and healthy subjects. The DL and manual measurements outperformed the automated measurements of the built-in software.

Cystoid macular oedema (CMO), which is defined as a macular thickening and cystic changes due to accumulation of fluid, could be asymptomatic and only diagnosed using paraclinical techniques. Fluorescein angiography (FA) and optical coherence tomography (OCT) are useful in detecting CMO in clinical practice. Non-leaking CMO, also known as angiographically silent CMO, is referred to as cases of CMO without leakage in fluorescein angiography. This type of CMO has been reported in some retinal dystrophies, in cases of maculopathy as a side effect of certain drugs, and also in some systemic disorders. The exact mechanism and treatment options for this type of CMO are still not clear. This literature review aims to discuss different causes of non-leaking CMO, proposed mechanisms, and management options. Three sections including drugs, retinal dystrophies, and systemic disorders are discussed in this review.摘要: 黄斑囊样水肿 (CMO) 定义为液体蓄积造成的黄斑区增厚和囊样改变, 可能无症状, 并且只能由临床辅助检查所诊断。荧光血管造影 (FA) 和光学相干断层扫描 (OCT) 是临床上检测CMO的有效手段。无渗漏的CMO, 在造影中以“安静的CMO”著称, 特指那些在荧光素血管造影中没有荧光渗漏的CMO。在某些视网膜营养不良、药物副作用及全身性疾病中可见这种类型的CMO。该类型CMO的发病机制和治疗方法仍不明确。本综述旨在讨论造成无渗漏CMO的不同病因、潜在机制和管理方法。本综述讨论了药物、视网膜营养不良及系统性疾病三个部分。.

Objective: The present study was designed to evaluate the effects of Atorvastatin (ATO) plus Melatonin (MEL) on streptozocin-induced Diabetic Retinopathy (DR) in rats. Methods: Diabetes was induced in Wistar rats with an intraperitoneal injection of streptozocin (50 mg/kg). Animals were randomly assigned to one of the following groups (8 rats/group): Control group, Diabetic group, Diabetic + MEL group (20 mg/kg/day), Diabetic + ATO group (10 mg/kg/day), Diabetic + MEL + ATO group (as above). Treatments were started one week after induction of diabetes and continued for 7 weeks. At the end of the experiment, angiography was performed and the rats were killed and retinas were harvested for pathological and molecular examinations. Results: Administration of MEL reduced the fluorescein leakage, MDA and ROS levels compared to diabetic group. Treatment with ATO only reduced ROS levels compared to diabetic group. In addition, administration of ATO plus MEL decreased these indices compared to the diabetic and ATO groups. Histologically, retinal vascular congestion was not observed in the combined ATO and MEL group as compared to the diabetic, ATO, and MEL groups. Conclusion: These data provide evidence for the therapeutic value of MEL in combination with ATO in clinical practice for prevention of DR.

Purpose: To report the clinical outcome of rhuthenium-106 plaque radiotherapy in acquired retinal pigment epithelial (RPE) tumors. Methods: In this interventional case series, two eyes of two patients with clinically diagnosed ocular-acquired RPE tumors including adenoma and adenocarcinoma underwent plaque radiotherapy with rhuthenium-106. The clinical findings and visual outcome of the patients were evaluated. Results: The first patient was a 44-year-old male, and the second was a 32-year-old female. The follow-up times were 24 and 32 months. The tumor was unilateral and hyperpigmented in both cases, located at juxtapapillary in one patient and on peripheral part of the retina in the other. Vitreous hemorrhage and peripheral exudation were obvious in one patient. Macular edema, epiretinal membrane, and retinal feeder vessels were also detected in the examination. The patients underwent plaque radiotherapy with rhuthenium-106 as the first step of management. The tumor has been stable until the last follow-up in both patients with globe preservation and acceptable visual acuity (5/10 for the first case and 4/10 for the second case). Conclusion: Rhuthenium-106 plaque radiotherapy might be a conservative therapy in the management of acquired RPE tumors and prevent early enucleation.

Optical coherence tomography angiography (OCTA) is a revolutionary method in the visualization of the vascular system in different retinal and choroidal layers. During the last 4 years since the commercial availability of different OCTA devices, attempts have been made to utilize this technology in various aspects of ocular oncology from the differentiation of benign and malignant lesions to assisting in evaluation of post-treatment complications, such as radiation retinopathy. However, current OCTA technology is restricted by various artefacts and inherent limitations, some of which are more pronounced in the presence of elevated tumoural lesions. Imminent advancements in OCTA systems and image acquisition processes promise a great potential for application of OCTA in ocular oncology.摘要: 光学相干断层扫描血管成像技术 (Optical Coherence Tomography Angiography, OCTA) 是针对视网膜以及脉络膜各层血管可视化的一种革命性的方法。在过去四年中, 由于各种OCTA设备商业化的可能, OCTA已经应用于眼科肿瘤诊疗的各个方面——从良性恶性肿瘤的的鉴别诊断到辅助性针对治疗后各种并发症如放射性视网膜病变的评估。然而, 目前OCTA技术仍受到各种人工以及固有的局限性的限制, 特别是在肿瘤增高病变进展的情况下这种局限性就更为明显。OCTA系统和图像采集技术的迅速发展将使得OCTA在眼科肿瘤领域的应用具有更大的潜力。.

Retinal pigment epithelium (RPE) degeneration is the hallmark of age-related macular degeneration (AMD). AMD, as one of the most common causes of irreversible visual impairment worldwide, remains in need of an appropriate approach to restore retinal function. Wet AMD, which is characterized by neovascular formation, can be stabilized by currently available therapies, including laser photocoagulation, photodynamic therapy, and intraocular injections of anti-VEFG (anti-vascular endothelial growth factor) therapy or a combination of these modalities. Unlike wet AMD, there is no effective therapy for progressive dry (non-neovascular) AMD. However, stem cell-based therapies, a part of regenerative medicine, have shown promising results for retinal degenerative diseases such as AMD. The goal of RPE cell therapy is to return the normal structure and function of the retina by re-establishing its interaction with photoreceptors, which is essential to vision. Considering the limited source of naturally occurring RPE cells, recent progress in stem cell research has allowed the generation of RPE cells from human pluripotent cells, both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC). Since iPSCs face neither ethical arguments nor significant immunological considerations when compared to ESCs, they open a new horizon for cell therapy of AMD. The current study aims to discuss AMD, review the protocols for making human iPSCs-derived RPEs, and summarize recent developments in the field of iPSC-derived RPEs cell therapy.

The purpose of this study was to introduce a new machine learning approach for differentiation of a pachychoroid from a healthy choroid based on enhanced depth-optical coherence tomography (EDI-OCT) imaging. This study included EDI-OCT images of 103 eyes from 82 patients with central serous chorioretinopathy or pachychoroid pigment epitheliopathy, and 103 eyes from 103 age- and sex-matched healthy subjects. Choroidal features including choroidal thickness (CT), choroidal area (CA), Haller layer thickness (HT), Sattler-choriocapillaris thickness (SCT), and the choroidal vascular index (CVI) were extracted. The Haller ratio (HR) was obtained by dividing HT by CT. Multivariate TwoStep cluster analysis was performed with a preset number of two clusters based on a combination of different choroidal features. Clinical criteria were developed based on the results of the cluster analysis, and two independent skilled retina specialists graded a separate testing dataset based on the new clinical criteria. TwoStep cluster analysis achieved a sensitivity of 1.000 (95-CI: 0.938–1.000) and a specificity of 0.986 (95-CI: 0.919–1.000) in the differentiation of pachy- and healthy choroid. The best result for identification of pachychoroid was obtained for a combination of CT, HR, and CVI, with a correct classification rate of 0.993 (95-CI: 0.980–1.000). Based on the relative variable importance (RVI), the cluster analysis prioritized the choroidal features as follows: HR (RVI: 1.0), CVI (RVI: 0.87), CT (RVI: 0.70), CA (RVI: 0.59), and SCT (RVI: 0.27). After performing a receiver operating characteristic curve analysis on the cluster membership variable, a cutoff point of 389 µm and 0.79 was determined for CT and HR, respectively. Based on these clinical criteria, a sensitivity of 0.793 (95-CI: 0.611–0.904) and a specificity of 0.786 (95-CI: 0.600–0.900) and 0.821 (95-CI: 0.638–0.924) were achieved for each grader. Cohen's kappa of inter-rater reliability was 0.895. Based on an unsupervised machine learning approach, a combination of the Haller ratio and choroidal thickness is the most valuable factor in the differentiation of pachy- and healthy choroids in a clinical setting.

Retinoblastoma (Rb) is a rare childhood intraocular malignancy with an incidence rate of approximately 9000 children per year worldwide. The management of Rb is inherently complex and depends on several factors. The orders of priorities in the treatment of Rb are saving life, globe salvage and vision salvage. Rarity and the young age at diagnosis impede conducting randomized clinical trials (RCTs) for new therapeutic options, and therefore pre-RCTs studies are needed. This review provides an overview of advances in Rb treatment options, focusing on the emergence of new small molecules to treat Rb. Articles related to the management and treatments of Rb were searched in different databases. Several studies and animal models discussing recent advances in the treatment of Rb were included to have a better grasp of the biological mechanisms of Rb. Over the years, the principles of management and treatment of Rb have changed significantly. Innovations in targeted therapies and molecular biology have led to improved patient and ocular survival. However, there is still a need for further evaluation of the long-term effects of these new treatments.

Background and Aims: Retinoblastoma tumors are the most common intraocular malignancy in childhood, leading to death after two years. The Human Adenovirus (HAdV) infection could be critical in the retinoblastoma pathogenesis due to the virus and retinoblastoma 1 interactions. The objective of the current study was to investigate the possible presence of the HAdV genome in the retinoblastoma patient's tumors. Materials and Methods: In this study, we evaluated the HAdV infection in 96 pathological confirmed retinoblastoma samples. The DNA was extracted from formalin-fixed paraffin-embedded blocks, and the virus infection was assessed using polymerase chain reaction. SPSS version 22 was used for statistical analysis. Results: The mean age ± SD of the retinoblastoma patients was 28.89 ± 17 months. In addition, the demographic evaluation indicated that 43 (46.7%) of patients were female. The retinoblastoma laterality assessment indicates 87 (90.4%) unilateral and 9 (9.4%) bilateral tumors. Growth pattern analysis indicates endophytic 58 (77.3%), exophytic 8 (10.7%), and 9 (12%) of tumors with mix endophytic and exophytic patterns. The polymerase chain reaction results could not found any evidence of HAdV infection in all 96 formalin-fixed paraffin-embedded samples. Conclusions: The study results suggest that there is not any association between HAdV infection and retinoblastoma tumors in studied samples. The HAdV infection may not a concern in retinoblastoma pathogenesis. Further investigations are recommended in this field of study.

Retinoblastoma tumor (RB) is one of the most prevalent ocular cancers among children. RB may be caused by inherited mutations in RB1 gene as well as some environmental risk factors. Human papillomaviruses (HPV) are suspected as a risk factor of RB due to their pRb inactivating protein. This study evaluated the molecular prevalence of HPV among the RB tumor specimens in Iran. The RB tumor samples were tested for detection of HPV-L1 gene using a nested-PCR approach, and then followed by sequencing and phylogenetic analysis to reveal HPV types. Overall, there were 61 RB tumor samples; 54/61 (88.5%) had unilateral and 7/61 (11.5%) bilateral RB; 55/61 cases (90.2%) had sporadic non-familial RB tumor. HPV-DNA was detected in 6/61 (9.8%) of patients’ tumors; the HPV positive RB cases all had unilateral and unfamiliar sporadic RB tumor. HPV type 16 was the most prevalent type identified across the RB tumor samples (3/61, 4.9%). The rate of detected HPV among the RB specimens seems to be considerable. Further investigations are required to elucidate the exact association between HPV and progression to RB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-019-00540-7) contains supplementary material, which is available to authorized users.

Purpose: To evaluate the role of intrasilicone oil injection of methotrexate (MTX) at the end of vitrectomy surgery for rhegmatogenous retinal detachment (RRD) associated with proliferative vitreor...

Intravitreal injection of chemotherapy drugs for intraocular retinoblastoma, for the prevalent pediatric malignancy treatment with the side effects of severe infection. This study tried to synthesize the novel approach to deliver Melphalan to the vitreous cavity through the cornea to increase drug efficacy with non-invasive effects. For this purpose, lauric acid-grafted chitosan-alginate and chitosan-alginate loaded by Melphalan nanoparticles were fabricated. Fourier-transform infrared spectroscopy (FTIR) and x-ray diffraction (XRD) were the basic characterizations of chitosan modification. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) are the other assessments of synthesized nanoparticles. Drug encapsulation and in vitro release were studied using UV-spectroscopy, also ex vivo and in vivo corneal permeation was studied using Franz diffusion cell, fluorescence microscopy, and in vivo animal imaging. FTIR and XRD confirm the successful grafting of lauric acid and spherical shape with the average size of 50 nm and 80 nm observed for modified and chitosan-alginate nanoparticles respectively. In the release study, encapsulation efficiency of 98% with sustained drug release of 80% for 100 h with the Fickian drug diffusion mechanism was reported. Ex vivo corneal permeation exhibited an improved drug penetration rate in the sample of lauric acid-grafted-chitosan-alginate nanoparticles with the results of 5.8 times higher than chitosan-alginate nano-carriers and 15.5-fold compared to drug solution. Also, in vivo study shows that the designed nanoparticles containing Melphalan reached the vitreous cavity with high efficacy. Current investigations illustrate the novel Melphalan delivery with sustained behavior through the cornea with the high potential of corneal layer penetration for retinoblastoma management.

Background/objectives Early diagnosis, care and treatment of retinoblastoma is a challengeable issue for Iranian health system. This study was designed and conducted in a referral multidisciplinary centre in the capital city of Iran to evaluate management, care, prognosis and survival rates of paediatric patients with retinoblastoma. Methods In this retrospective study, a total number of 309 patients younger than 15 years, diagnosed with retinoblastoma, who referred for diagnosis and treatment to MAHAK's Pediatric Cancer Treatment and Research Center (MPCTRC) from 2007 to 2017 were evaluated. All data were analyzed via SPSS version 22 software in regard of parametric and non-parametric data. Survival rates were analyzed using the Kaplan-Meyer method. Results The mean age of patients was 20 months and the majority of patients (77%) had leukocoria as a common clinical symptom at the time of diagnosis. Primary treatment methods were systemic chemotherapy (94%), laser (35%) and primary enucleation (28%). Relapses occurred in nearly 42% of cases, and the median time from diagnosis to the first relapse was 9 months. At the time analyzing the data, 11% of patients died. Patients' 5-year OS and RFS rates were 79.6% and 41.5%, respectively. Conclusion Comparing results with other conducted studies identifies that the recurrence rate was high in our considered patients. Also, OS and RFS rates in our study were not as considerable as other reports. Screening methods, updating protocols and follow-up of patients may lead to improvements in survival rates of patients with retinoblastoma.

This study evaluates the outcomes of ruthenium-106 (Ru-106) plaque brachytherapy for vasoproliferative tumors (VPTs) of the ocular fundus in a single referral ocular oncology center. The clinical charts of all patients diagnosed with VPT who underwent plaque radiotherapy from 2002 to 2017 were reviewed. Clinical features, types of treatment, outcomes and complications were evaluated. Of 46 patients with VPT diagnosis in our ocular oncology clinic, 25 (54.34%) cases were treated with Ru-106 plaque brachytherapy. Eleven patients (44%) were male, and the mean age at the time of diagnosis was 40.92 ± 13.11 years. The mean follow-up time was 47.56 ± 36.87 months. Inferotemporal quadrant was the most common site of the tumor (64.00%). The mean delivered apex and scleral dose was 101.56 ± 6.51 and 412.26 ± 113.66 Gray (Gy), respectively. Initial tumor length, width and thickness were 10.26 ± 3.42, 8.05 ± 2.83 and 4.27 ± 1.10 mm, respectively. The mean tumor thickness decreased to 2.60 ± 0.63 mm, postoperatively. Complete resolution of subretinal fluid around the tumor was achieved in 81.80% of cases. Visual acuity was more than 20/400 in 64% of patients before treatment and 60% of patients at last follow-up. Our study showed that Ru-106 plaque radiotherapy is an effective and safe method of treatment in VPTs.

Choroidal neovascularization (CNV) may develop in association with a myriad of conditions including degenerative, inflammatory, traumatic, or congenital disorders. This chapter provides a brief review of conditions that may be infrequently encountered in routine clinical practice, but ophthalmologists must be familiar with the correct diagnosis, as prompt treatment is essential to preserve vision.

Purpose: To present a rare anaplastic form of retinal pleomorphic xanthoastrocytoma (PXA) unassociated with phakomatosis. Methods: A 9-year-old girl, presented with a rapidly growing unilateral intraocular white mass unresponsive to intra-arterial chemotherapy, underwent enucleation with the clinical suspicion of retinoblastoma versus malignant astrocytoma. Results: Histopathology revealed pleomorphic cells with rosenthal fibers, mitosis, and necrosis. Immunohistochemistry confirmed the diagnosis of anaplastic pleomorphic xanthoastrocytoma (aPXA). The patient had no signs of phakomatosis. Conclusion: Retinal PXA may occur in patients without phakomatosis and rarely progress toward malignant transformation. Keywords: Anaplasia, Pleomorphic xanthoastrocytoma, Retinal tumor

Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), remains as one of the major causes of vision loss worldwide. The release of pro-inflammatory cytokines and the adhesion of leukocytes to retinal capillaries are initial events in DR development. Inflammation, ER stress, oxidative stress and autophagy are major causative factors involved in the pathogenesis of DR. Diabetes associated hyperglycemia leads to mitochondrial electron transport chain dysfunction culminating in a rise in ROS generation. Since mitochondria are the major source of ROS production, oxidative stress induced by mitochondrial dysfunction also contributes to the development of diabetic retinopathy. Autophagy increases in the retina of diabetic patients and is regulated by ER stress, oxidative stress and inflammation-related pathways. Autophagy functions as a double-edged sword in DR. Under mild stress, autophagic activity can lead to cell survival while during severe stress, dysregulated autophagy results in massive cell death and may have a role in initiation and exacerbation of DR. Melatonin and its metabolites play protective roles against inflammation, ER stress and oxidative stress due to their direct free radical scavenger activities and indirect antioxidant activity via the stimulation antioxidant enzymes including glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. Melatonin also acts as a cell survival agent by modulating autophagy in various cell types and under different conditions through amelioration of oxidative stress, ER stress and inflammation. Herein, we review the possible effects of melatonin on diabetic retinopathy, focusing on its ability to regulate autophagy processes.

OBJECTIVE We assessed the effectiveness of educational interventions in increasing the perceived risk of fireworks and preventing fireworks-related injuries among male teenagers. METHODS In a field trial, using a cluster sampling approach, 3 high-, middle- and low-income municipality districts were selected. In each district, 5 male middle and high schools were randomly selected and assigned into one control and 4 intervention groups: (1) distribution of a multimedia disk regarding injury victims; (2) distribution of safety brochures; (3) mailing to parents from schools discussing the risk of fireworks and limiting the fireworks budget; and (4) peer-to-peer education by trained students about the risks of fireworks. Safety instructions were included in all interventions. RESULTS After analyzing 1584 students' responses, the use of firecracker inversely correlated with the economic level of families (p < .001). The risk factors for fireworks-related injury (N = 31, 2.0%) included use of hazardous fireworks, making bonfires, history of fireworks-related injury, fireworks budget, and "willingness to pay." Preventive interventions did not statistically change the use of fireworks, fireworks budget, making a bonfire, and fireworks-related injuries compared with the preceding year. The interest in hazardous fire crackers was less in intervention group; however, no statistically significant differences among the different interventions were observed. CONCLUSION The interventions failed to lessen risky behaviors and fireworks-related injuries among male teenagers.

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis.In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed.A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity.MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.