Background/Objectives: This study aimed to evaluate the clinical characteristics and identify the prognostic factors affecting visual outcomes, retinal detachment, and recurrence in cytomegalovirus retinitis (CMVR) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of 54 CMVR patients (84 eyes) who underwent allo-HSCT between 2015 and 2024 was conducted. Ophthalmologic and systemic evaluations were performed. The visual outcomes were classified as improvement, stabilization, and deterioration. Logistic regression and LASSO regression models were used to identify the prognostic factors. Results: Improved or stabilized visual outcomes were found in 22 eyes, while 62 eyes suffered from deterioration. Larger lesion areas were independently associated with poorer visual outcomes (OR 0.989, p = 0.002). Eight (9.5%) eyes had rhegmatogenous retinal detachment and thirteen (15.5%) eyes suffered from recurrence. Retinal detachment was significantly predicted by higher baseline aqueous CMV DNA load (OR 5.087, p = 0.026). Macula involvement (OR 5.322, p = 0.032) and more intravitreal injections (IVs) (OR 1.263, p = 0.008) were independent risk factors for recurrence. No systemic factors were found to be associated with the clinical outcome of eyes with CMVR. Conclusions: Ocular characteristics, rather than systemic factors, were more useful to predict the clinical outcome of eyes with CMVR. Routine ophthalmic screening and early intervention are essential to improving outcomes in this vulnerable population.

Vaccine-associated uveitis (VAU) usually refers to a rare adverse reaction that occurs after vaccination. The clinical manifestations of VAU are most often anterior with mild symptoms and responded promptly to topical corticosteroids. However, more severe forms of posterior and panuveitis may also occur, such as multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada syndrome, and acute posterior multifocal placoid pigment epitheliopathy. The pathogenesis of VAU is still unclear. Currently, it mainly includes vaccine Shoenfeld syndrome, type Ⅲ hypersensitivity reaction caused by immune complex deposition, direct infection with live attenuated vaccine, and molecular mimicry theory. VAU is self-limiting, and most patients heal without treatment. In the future, it is recommended to ask all patients with uveitis about their recent vaccination history in the clinic. For patients with inactivated vaccine or recombinant/subunit vaccination history, the possibility of developing Shoenfeld syndrome should be considered, and the history, signs and symptoms related to autoimmune diseases should be carefully looked for.

Objective:To observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment.Methods:A retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration.Results:At the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [ R2=0.385, P<0.000 1, B=-0.237 log 10 copies/(ml·time)], and the duration of treatment [ R2=0.394, P <0.000 1, B=-0.301 log 10 copies/(ml·week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity ( t=-1.223), intraocular pressure ( t=1.538), aqueous humor CMV-DNA load ( t=-0.109), retinitis lesion area ( Z=-0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved ( Z=-0.024) and whether the macula was involved ( Z=-1.826), combined with anterior segment inflammation ( Z =-0.499), combined with high intraocular pressure ( Z=-1.342), terminal visual acuity ( t =-0.845), intraocular pressure ( t=-0.068), total IVG times ( Z=0.907), age ( Z=-0.832), gender composition ( Z=-1.074), etc. The difference was not statistically significant ( P>0.05). Conclusion:The CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.

Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients.Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models.Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways.Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

Cytomegalovirus (CMV) retinitis (CMVR) is a common opportunistic infection of the eye after allogeneic hematopoietic stem cell transplantation in patients with hematological diseases. It often occurs within 3 months after the operation, with CMV activation and high blood CMV peaks. It often occurs on patients with long-term CMV viremia, human leukocyte antigen incompatible transplantation, unrelated donor transplantation, haploid transplantation, childhood hematopoietic stem cell transplantation, delayed lymphocyte engraftment, acute and chronic graft-versus-host disease after surgery. The visual prognosis of patients is related to the area of CMVR lesions on the retina, the number of quadrants involved, whether the macula is involved, and the CMV load of the vitreous body is involved, and it is not related to whether the Epstein-Barr virus infection is combined with blood and vitreous humor. The incidence of CMVR is increasing year by year. It is helpful that paying attention to systemic risk factors and epidemiology can provide more effective guidance for ophthalmologists during diagnosis and treatment, help patients improve the prognosis of vision, and reduce or even avoid the occurrence of blindness caused by CMVR.

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure. Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study. Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline. Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P > 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335–35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen (P = 0.162), were predictors of the treatment duration. Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background.

PURPOSE:To report the incidence and clinical features of neovascular complications from cytomegalovirus (CMV) necrotizing retinopathy in patients after haploidentical hematopoietic stem cell transplantation.METHODS:Thirty-nine patients (58 eyes) of CMV necrotizing retinopathy after haploidentical hematopoietic stem cell transplantation in our institute between January 2018 and June 2020 were retrospectively reviewed, and cases that developed neovascular complications during follow-up were identified and described.RESULTS:Two (2 eyes) cases that developed neovascular glaucoma from CMV necrotizing retinopathy were identified. Both of them manifested as granular peripheral retinitis, panretinal occlusive vasculitis, and some degree of intraocular inflammation, which were consistent with chronic retinal necrosis. Insidious progression of isolated immune-mediated occlusive vasculitis that could only be observed on fundus fluorescein angiography without active retinitis or intraocular inflammation was recognized to be the cause in one of two cases.CONCLUSION:Neovascular glaucoma developed in 5.1%/cases and 3.4%/eyes complicated by CMV chronic retinal necrosis and vasculitis in patients after haploidentical hematopoietic stem cell transplantation, which warrants the needs for long-term follow-up. Immune-mediated CMV vasculitis could be an isolated manifestation in patients with a minimal immune deviation and may only be found on fundus fluorescein angiography, which emphasizes the importance of fundus fluorescein angiography on a regular basis during follow-up.

Chinese ophthalmology residency training is continuously evolving with an emphasis on standardization. In this article, we assess the current status of ophthalmology residency training in China compared with that in the United States through analysis of literature review and onsite data collection. We comprehensively review various aspects of the residency training structure in China, including accreditation, resident selection, clinical and surgical curricula, research requirements, and evaluation. Our report demonstrates significant regional differences among training programs due to the lack of a national standard, resulting in varying competencies of graduating Chinese ophthalmology residents. The Chinese ophthalmology community is determined to improve the standardization process and quality of training for their ophthalmologists, an important goal that will facilitate international fellowship studies, exchange scholars, and research collaboration.

Yaping Li, Dong Chen, Luguo Sun, Yannan Wu, Ying Zou, Chen Liang, Yongli Bao, Jingwen Yi, Yu Zhang, Jing Hou, Zhen Li, Fengyun Yu, Yanxin Huang, Chunlei Yu, Lei Liu, Zaoxia Liu, Yi Zhang, and Yuxin Li National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China Department of Ophthalmology, Second Hospital, Jilin University, Changchun, China Center for Genome Analysis, ABLife, Inc., Wuhan, People’s Republic of China Laboratory for Genome Regulation and Human Health, ABLife, Inc., Wuhan, People’s Republic of China

Cytomegalovirus (CMV) retinitis is the most frequent ocular opportunistic infection after hematopoietic stem cell transplantation (HSCT) (Ochs et al. 1995). For now, the diagnosis of cytomegalovirus retinitis (CMVR) after HSCT is mainly based on clinical history and ophthalmic examination (Port et al. 2017). The traditional treating end-point is also depended on clinical findings, usually described as 'complete quiescence' of lesion on the retina in literature (Choopong et al. 2016). But in clinical practice, signs acquired by fundus examination are not always in accordance with actual state of the disease. Here, we conducted an assessment of an antiviral strategy for CMVR after HSCT, using aqueous CMV-DNA load and interleukin-8 (IL-8) level as quantitative variables. Prospective consecutive series of nine patients (15 eyes) who diagnosed as CMVR base on clinical history and fundus examination were given systemic and intravitreous injection of antiviral drugs. Intravitreous injection of ganciclovir (IVG) 3 mg was given to every patient, twice per week for four times (induction phase). Aqueous and serum sample was collected 1 day before the first injection (baseline), during the fourth time of injection, and then every time since the fifth injection. Serum CMV-DNA load, aqueous CMV-DNA load and aqueous IL-8 level were determined by real-time PCR and cytometric beads array, respectively. Compared with baseline, if aqueous CMV-DNA load decreased by two magnitudes or IL-8 level decreased by one magnitude acquired during the fourth injection, IVG 3 mg would continue to be given weekly (maintenance phase), otherwise, therapy would be adjusted to IVG 3 mg combined with foscarnet sodium 2.4 mg once per week (maintenance phase). Local treating end-point was defined as negative aqueous CMV-DNA load (<1.0 × 103 copies/ml) or IL-8 level (<30 pg/ml). Then patients were requested to come back every other week and followed up for 3 months at least. Systemic treating end-point was defined as negative serum CMV-DNA after local treating end-point had been reached. Best corrected visual acuity (BCVA, in form of Logarithm of the minimum angle of resolution, LogMAR), intraocular pressure (IOP; Goldmann applanation tonometry), ophthalmic examination using slit-lamp microscope were performed during each time of visit. Patients were evaluated and followed up for a median of 5 months (3–7 months). Best corrected visual acuity (BCVA) and IOP at base line and last time of visit were (0.679 ± 0.552; LogMAR) and (0.641 ± 0.609; LogMAR), (17.2 ± 5.9) mmHg and (15.9 ± 5.9) mmHg, respectively. No significant difference was found between baseline and last time of visit (p = 0.554 and p = 0.864, respectively). The median times of intravitreous injection were six times (4–11 times). At local treating end-point, systemic antiviral drugs were stopped for all patients, but vessel infiltration, exudation and haemorrhage still could be found in 13 of 15 eyes during fundus examination. Negative aqueous CMV-DNA was found in six eyes (40%), but CMV-DNA could still be detected in nine eyes (60%), while aqueous IL-8 was negative. Median follow-up period was 5 months (3–7 months). At last time of visit, all CMVR lesions became quiescent completely, without any signs of recurrence. Our data indicated that, none of the nine patients experienced recurrence at the last visit, even if CMV-DNA still could be detected in nine eyes at local treating end-point. Furthermore, lesion on the retina continued healing until complete quiescent was achieved even after both systemic and local antiviral therapies were stopped, which proved the efficacy and safety of this strategy. If local treating end-point was set as 'negative aqueous CMV-DNA' or 'complete quiescent lesions on retina', which is described in literature, the treatment duration must be much longer than actual needs. In summary, aqueous CMV-DNA and IL-8 are excellent quantitative variables that could be used to adjust local antiviral treatment and provide local treating end-point effectively, safely and efficiently.

The aim of the present study was to analyze proteins in the aqueous humor (AH) of patients' retinoblastoma (RB), and investigate their potential role in RB using the comparative proteomic technique of isobaric tags for relative and absolute quantitation (iTRAQ) coupled with offline two-dimensional liquid chromatography-tandem mass spectrometry. A total of 0.1 ml AH was collected from 10 children with RB (mean age, 3.8 years; range, 2-5 years) and patients with senile cataracts (mean age, 70.4 years; range, 65-79 years), which was used as the control. iTRAQ was used to analyze proteins in the AH of patients and controls. Proteins with a fold change of >1.20 or <0.83 were considered to be significantly differentially expressed (with corrected P<0.05). The identified proteins were subjected to subsequent gene ontology (GO) analysis using the DAVID database. A total of 83 proteins that were expressed differently between the controls and patients' AH samples were identified using iTRAQ analysis. Of these proteins, 44 were upregulated and 39 were downregulated. On the basis of biological processes in GO, the identified proteins were primarily involved in glycoprotein, amyloid acute-inflammatory and defensive responses. Among these proteins, pigment epithelium-derived factor serves a potential role in the treatment of RB, and stimulated by retinoic acid 6 may serve as a potential protein involved in RB development. To the best of our knowledge, the present study is the first to identify 83 proteins associated with RB using iTRAQ technology. The results of the present study will aid in furthering the understanding of RB and developing novel therapy targets in the future.

Objective: To explore clinical and laboratory factors that influencing treating procedure of cytomegalovirus retinitis (CMVR) after allogeneic bone marrow hematopoietic stem cell transplantation (HSCT). Methods: This is a retrospective case series study. A total of 9 CMVR patients (15 eyes) between January 2016 and March 2017 were included in this study. All patients received intravenous or oral ganciclovir, together with intravitreous injection of ganciclovir alone or combined with foscanet sodium. One day before the first injection, aqueous humor samples from the affected eyes were collected, and CMV-DNA and interleukin-8 (IL-8) level were examined. Blood samples were acquired and CMV-DNA was examined too. Best corrected visual acuity, intraocular pressure (Goldmann), slit-lamp and fundus examination, ultra-wide fundus photography were performed before the first injection and every visit since then. Fifty eyes were divided into stop treating group (Group A) and continue-to-treat group (Group B) according to whether local treatment could be seized after loading phase. Image-Pro plus 6.0 was exploited to determine the area of CMVR in the retina, together with number of quadrants involved and whether macular was involved.Then the clinical and laboratory data were compared between two groups. ROC curve was used to calculate the cutoff values for quantitative factors that showed significant differences between two groups. Results: The interval time between HSCT and diagnosis of CMVR, visual acuity and CMV-DNA in the blood at baseline, area of CMVR and number of quadrants involved and whether macular was involved didn't show any difference between two groups. But the intraocular pressure (Z=-2.488, P=0.017), CMV-DNA (Z=-2.239, P=0.013) and IL-8 level (Z=-2.475, P=0.012) in aqueous humor at baseline, proportion of eyes with active inflammation in anterior (P=0.003) and proportion of eyes with ocular hypertension (P=0.021) in group B were significantly higher than those in group A. The cutoff values of intraocular pressure, CMV-DNA and IL-8 level in aqueous humor at baseline were 14.5 mmHg (P=0.013), 2.99×10(5) copy/ml (P=0.025) and 447.8 pg/ml (P=0.013), respectively. Conclusion: Higher intraocular pressure, CMV-DNA and IL-8 in aqueous humor at baseline, especially combined with active inflammation in anterior segment and ocular hypertension suggest longer treating period and more times of intravitreous injections. (Chin J Ophthalmol, 2017, 53: 740-745).

PURPOSE:We determined the receiver operating characteristic (ROC) curves for Peristat online perimetry at detecting varying degrees of glaucoma and the correlation between Peristat online perimetry and Humphrey visual field. METHODS:A prospective, comparative study of Peristat online perimetry (an achromatic static computer threshold testing program) and Humphrey visual field (HVF) 24-2 SITA standard testing was performed by 63 glaucoma patients and 30 healthy controls in random order. The number of total adjacent abnormal test points were identified for each test, and compared with Spearman correlation. Receive operating characteristic curves were generated for Peristat online perimetry detection of mild and moderate-severe glaucoma patients using contrast sensitivity thresholds of -16.7, -21.7, and -26.7 dB. RESULTS:The area under the ROC curve for glaucoma detection ranged from 0.77 to 0.81 for mild disease (mean deviation [MD], >-6 dB on HVF) and 0.85 to 0.87 for moderate to severe disease (MD, <-6 dB on HVF) depending on contrast threshold. Peristat online perimetry and Humphrey visual field abnormal points were highly correlated with Spearman rank correlations ranging from 0.55 to 0.77 (all P < 0.001). CONCLUSIONS:Peristat online perimetry exhibits a reasonable ROC curve without specialized equipment and exhibited significant correlation with the conventional 24° Humphrey visual field test. TRANSLATIONAL RELEVANCE:Low cost widely available internet-based visual fields may complement traditional office-based visual field testing.

The etiology of corneal decompensation after aqueous shunt implantation remains poorly understood. With the use of anterior segment optical coherence tomography and specular microscopy, the relationship of these implants to the surrounding tissues can be investigated over time. This article will review the current knowledge pertaining to endothelial cell loss related to glaucoma and surgery and highlight possible causes that have been proposed for endothelial cell loss after aqueous shunt implantation.

PURPOSE:The aim of this study was to assess the effect of various tube parameters on corneal endothelial cell density (ECD) after insertion of Ahmed valves.METHODS:Thirty-nine eyes of 33 patients with previous superotemporal (ST) Ahmed valve implantation and 20 eyes of 13 participants with previous uncomplicated phacoemulsification and intraocular lens implantation but no history of glaucoma surgery were evaluated. Various tube parameters were measured with anterior segment optical coherence tomography. ST, central, and inferonasal (IN) ECD and pachymetry were measured. Endothelial cell loss and corneal thickness in the ST cornea was compared with those in the IN cornea.RESULTS:The mean age of the operated patients was 58 ± 22 years, and the mean time since glaucoma surgery was 2.5 ± 2.6 years. Thirty-two of the 39 study eyes were pseudophakic. The ECD was significantly lower in the ST endothelium than in the IN endothelium in eyes with glaucoma tube surgery (P < 0.001), although this relative reduction in ST ECD was not greater than that seen in pseudophakic control eyes (P = 0.16). In univariate analysis, tube angle relative to the cornea and distance from the tip of the tube to the cornea were significant risk factors for decreased ST endothelial cell loss when assessed relative to the IN ECD (P = 0.01 and P = 0.02, respectively). In multivariate analysis, only the distance of the tube tip to the cornea remained significantly associated with ST endothelial cell loss.CONCLUSIONS:Although this was a retrospective study with inherent limitations, tubes that are closer to the cornea seem to lead to increased loss of adjacent endothelial cells.

Age-related macular degeneration (AMD) is a leading cause of irreversible central blindness among the elderly worldwide. We use exome sequencing to analyse nonsynonymous single-nucleotide variants (SNVs) across the whole genome of 216 neovascular AMD cases and 1,553 controls. As a follow-up validation, we evaluate 3,772 neovascular AMD cases and 6,942 controls from five independent cohorts in the East Asian population. Here we show strong evidence of an association at a novel, missense SNV, rs7739323, which is located in the ubiquitin protein ligase E3D (UBE3D) gene (Pmeta=1.46 × 10−9, odds ratio (OR)=0.74, 95% confidence interval (CI): 0.63–0.88). Furthermore, ablation of the UBE3D protein lead to an abnormal amount of pigment granules deposited in retinal pigment epithelium microvilli area and an abnormal response on electroretinography (ERG) in UBE3D+/− heterozygous mice. Our findings indicate that the ubiquitin-proteasome system may play a role in the pathogenesis of neovascular AMD. Age-related macular degeneration is a prominent cause of irreversible blindness among the elderly. Here Huang et al.identify a novel missense variant in UBE3D that sheds new light on the pathogenesis of the disease.

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PURPOSE To evaluate the relationship between aqueous inflammation cytokines and cytomegalovirus (CMV) particles in patients with cytomegalovirus retinitis (CMVR), and evaluate the changes in aqueous inflammation cytokines during multiple intravitreal injections of antiviral drugs for CMVR. METHODS There were 10 patients (12 eyes; 16 courses of treatment per eye) who underwent continued intravitreal ganciclovir or foscarnet for treatment of CMVR. Before each intravitreal injection, 50-100 μL of aqueous humor was removed and sent to the laboratory to examine the concentration of the CMV DNA load by using polymerase chain reaction and to examine the concentration of interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and IL-12p70 using a cytometric bead array. RESULTS A Kendall correlation test showed that the concentration of the CMV DNA load in the aqueous humor was significantly associated with the aqueous level of IL-6 (P<0.001, r=0.327) and IL-8 (P<0.001, r=0.381), but not significantly associated with IL-1β, IL-10, IL-12p70, and TNF-α. The boxplots showed that the concentration of the aqueous CMV DNA load, IL-8 and IL-10 continuously declined after multiple intravitreal injections of antiviral drugs, and the decline trend of IL-8 was most remarkable. IL-1β, IL-10, TNF-α, and IL-12p70 were negative in some of the aqueous levels of CMVR patients throughout the course of treatment (25.0%-62.5%). CONCLUSIONS Our study showed that IL-8 was significantly associated with the aqueous level of CMV copies and continuously declined during a course of treatment that involved multiple intravitreal injections of antiviral drugs. IL-8 may be considered a good quantitative laboratory indicator of the recovery of CMVR.

Purpose: To determine whether long-term, slow-release exposure to corticosteroids with Retisert promotes better surgical outcomes after Ahmed valve implantation. Patients: This comparative retrospective cohort study included 17 study eyes (10 patients) with uncontrolled uveitis requiring Retisert and Ahmed implantation, and 55 control eyes (51 patients) with other types of medically uncontrolled glaucoma that only received Ahmed. Materials and Methods: Main outcome measures were intraocular pressure (IOP), glaucoma eye drops per day, best-corrected visual acuity, early complications, and late complications at 1, 3, 6, and 12 months. Linear mixed effects models were used to model IOP, glaucoma drops per day, and visual acuity at 1 year after surgery. Results: At 1 year, the study eyes had a mean IOP of 12.24, which was lower than that for control eyes at 15.17 ( P =0.04). At 1 year, the average number of glaucoma eye drops used per day for study eyes was 1.4, which was lower than that for control eyes at 2.3 ( P =0.03). At 1 year, there were no statistically significant differences in change in visual acuity, early complications, and late complications between study and control eyes. Conclusions: Patients who received a Retisert implantation had lower IOP and used fewer glaucoma eye drops compared with control eyes at 1-year post-Ahmed valve surgery. This study suggests that long-term, slow-release corticosteroid medication from Retisert (fluocinolone acetonide) may improve the surgical outcome for patients with an Ahmed valve implantation and/or Retisert helps control uveitis in patients with uveitic glaucoma receiving Ahmed valves.