91 Circulating inflammatory proteins and the risk of age-related macular degeneration: A bidirectional Mendelian randomization study.

Previous observational studies have indicated a correlation between circulating inflammatory proteins and age-related macular degeneration (AMD), yet the causal nature of this relationship remains uncertain. This study aims to investigate the causal link between circulating inflammatory proteins and AMD utilizing a bidirectional two-sample Mendelian randomization approach. The findings indicated that elevated levels of four circulating inflammatory proteins, including C-C Motif Chemokine Ligand 11 (CCL11), Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1), TNF Superfamily Member 11 (TRANCE) and Vascular Endothelial Growth Factor A (VEGF-A) lead to the increased risk of AMD, while increased levels of two circulating inflammatory proteins, including Fibroblast Growth Factor 19 (FGF-19) and Interleukin 10 Receptor Subunit Alpha (IL-10RA), resulted in the decreased risk of AMD. Conversely, the results from reverse Mendelian randomization suggested that the presence of AMD lead to the reduction in levels of 15 circulating inflammatory proteins. The findings of this study support the association between elevated levels of circulating inflammatory proteins and the risk of AMD, as well as the potential impact of AMD on reducing circulating inflammatory protein levels. CCL11, SLAMF1, TRANCE and VEGF-A are identified as potential molecular markers in the progression of AMD. These results offer a novel molecular therapeutic target for the prevention and treatment of AMD.

Epigenetic mechanism of SET7/9-mediated histone methylation modification in high glucose-induced ferroptosis in retinal pigment epithelial cells.

Ferroptosis of the retinal pigment epithelial (RPE) cells leads to retinal neuron injury and even visual loss. Our study aims to investigate the role of the SET domain with lysine methyltransferase 7/9 (SET7/9) in regulating high glucose (HG)-induced ferroptosis in RPE cells. The cell model was established by HG treatment. The levels of SET7/9 and Sirtuin 6 (SIRT6) were inhibited and Runt-related transcription factor 1 (RUNX1) was overexpressed through cell transfection, and then their levels in ARPE-19 cells were detected. Cell viability and apoptosis was detected. The levels of reactive oxygen species, malondialdehyde, glutathione, ferrous ion, glutathione peroxidase 4, and acyl-CoA synthetase long-chain family member 4 were detected. SET7/9 and trimethylation of histone H3 at lysine 4 (H3K4me3) levels in the RUNX1 promoter region and RUNX1 level in the SIRT6 promoter region were measured. The relationship between RUNX1 and SIRT6 was verified. SET7/9 and RUNX1 were highly expressed while SIRT6 was poorly expressed in HG-induced ARPE-19 cells. SET7/9 inhibition increased cell viability and inhibited cell apoptosis and ferroptosis. Mechanistically, SET7/9 increased H3K4me3 on the RUNX1 promoter to promote RUNX1, and RUNX1 repressed SIRT6 expression. Overexpression of RUNX1 or silencing SIRT6 partially reversed the inhibitory effect of SET7/9 silencing on HG-induced ferroptosis. In conclusion, SET7/9 promoted ferroptosis of RPE cells through the SIRT6/RUNX1 pathway.

Integrating Single-cell and Bulk RNA-seq to Construct a Metastasis-related Model for Evaluating Immunotherapy and Chemotherapy in Uveal Melanoma.

BACKGROUND: Metastasis is a major cause of death in UM, highlighting the need to use highly specific and sensitive prognostic markers to identify patients with a risk of developing metastasis. AIMS: The aim of this study was to improve the current precision treatment for patients with metastatic uveal melanoma (UM). OBJECTIVE: The objective of this work was to investigate the heterogeneity between primary human UM and metastatic UM at the single-cell level and to discover potential molecules regulating UM metastasis. METHODS: Seurat R toolkit was employed to analyze single-cell sequencing data of UM and to identify differentially expressed genes (DEGs) between primary and metastatic UM. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed on the DEGs from the bulk RNA-seq cohort to develop a prognostic model. Based on the model, patients were divided into high and low groups. The correlations among the risk score, immune indicators, immune checkpoint blockade (ICB) therapy, and anti-tumor drug therapy were analyzed. RESULTS: Cell types in primary UM and metastatic UM tumors include B/plasma cells, endothelial cells, melanocytes, monocytes/macrophages, photoreceptor cells, and T cells. Among 157 DEGs between the two tumor types, S100A4, PDE4B, CHCHD10, NSG1, and C4orf48 were selected to construct a prognostic model. The model could accurately and independently predict response to ICB treatment and sensitivity to antineoplastic drugs for UM patients as well as their immune infiltration levels, risk of death, and metastasis possibility. CONCLUSIONS: This study analyzed the tumor ecosystem of primary and metastatic UM, providing a metastasis-related model that could be used to evaluate the prognosis, risk of metastasis, immunotherapy, and efficacy of antineoplastic drug treatment of UM.

A sutureless technique for securing leaking sclerotomies with viscoelastic substances in 23-gauge microincision vitrectomy surgery.

AIM: To introduce and evaluate the clinical efficacy of a new technique, the use of viscoelastic substances (VS) to close leaking sclerotomy in 23G microincision vitrectomy, and to observe its effect on the visual acuity and intraocular pressure (IOP) of patients. METHODS: Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique (June 2019 to September 2020) and after the use of VS technique (October 2020 to December 2021) were selected as the subjects of this study. The above cases underwent operation by the same surgeon and were retrospectively analyzed. VS technique was used as the alternative to suturing, in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure. RESULTS: A total of 174 eyes were covered in the study, including 84 eyes in the control group (before the use of VS technique) and 90 eyes in the VS technique group. The number of eyes that needed to be sutured decreased considerably from 42.9% in the control group to 3.3% in the VS technique group, and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7% in the control group to 2.2% in the VS technique group. No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group. No major complications associated with VS technique were identified during the study. CONCLUSION: In 23G microincision vitrectomy, VS technique is a safe, simple, and effective method to close leaking sclerotomy.

miR-204 suppresses uveal melanoma cell migration and invasion through negative regulation of RAB22A.

Uveal melanoma (UM), a frequently seen adulthood primary ocular malignancy, shows high aggressiveness. Accumulating studies have revealed the crucial effects of microRNAs (miRNAs) on tumorigenesis and development in various human tumors. miR-204, the cancer-associated miRNA, shows dysregulation and is related to several human malignancies, but its effect on UM remains unknown. The present work focused on exploring miR-204's effect on UM and elucidating its possible molecular mechanisms. According to our results, miR-204 expression markedly increased within both UM tissues and cell lines. As revealed by functional analysis, miR-204 suppressed UM cell invasion and migration. Besides, RAB22A expression decreased through directly binding miR-204 into the corresponding 3' untranslated region (3'UTR) in UM cells. Furthermore, the RAB22A mRNA level increased, which was negatively related to the miR-204 level within UM samples. As revealed by mechanical research, miR-204 exerted its inhibition on the invasion and migration of UM cells via RAB22A. Taken together, this study suggested the tumor-suppressing effect of miR-204 on UM through down-regulating RAB22A. Thus, miR-204 may serve as the new anti-UM therapeutic target.

The protective effect of URP20 on ocular Staphylococcus aureus and Escherichia coli infection in rats.

BACKGROUND: Infectious keratitis, a medical emergency with acute and rapid disease progression may lead to severe visual impairment and even blindness. Herein, an antimicrobial polypeptide from Crassostrea hongkongensis, named URP20, was evaluated for its therapeutic efficacy against keratitis caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infection in rats, respectively. METHODS: A needle was used to scratch the surface of the eyeballs of rats and infect them with S. aureus and E.coli to construct a keratitis model. The two models were treated by giving 100 µL 100 µM URP20 drops. Positive drugs for S. aureus and E. coli infection were cefazolin eye drops and tobramycin eye drops, respectively. For the curative effect, the formation of blood vessels in the fundus was observed by a slit lamp (the third day). At the end of the experiment, the condition of the injured eye was photographed by cobalt blue light using 5 µL of 1% sodium fluorescein. The pathological damage to corneal tissues was assessed using hematoxylin-eosin staining, and the expression level of vascular endothelial growth factor (VEGF) was detected by immunohistochemistry. RESULTS: URP20 alleviated the symptoms of corneal neovascularization as observed by slit lamp and cobalt blue lamp. The activity of S. aureus and E.coli is inhibited by URP20 to protect corneal epithelial cells and reduce corneal stromal bacterial invasion. It also prevented corneal thickening and inhibited neovascularization by reducing VEGF expression at the cornea. CONCLUSION: URP20 can effectively inhibit keratitis caused by E.coli as well as S. aureus in rats, as reflected by the inhibition of corneal neovascularization and the reduction in bacterial damage to the cornea.

A multi-omics deep learning model for hypoxia phenotype to predict tumor aggressiveness and prognosis in uveal melanoma for rationalized hypoxia-targeted therapy.

Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults and is characterized by aggressive behaviors and a lack of targeted therapies. Hypoxia-targeted therapy has become a promising new therapeutic strategy in tumors. Therefore, a better understanding of the tumor hypoxia microenvironment is critical to improve the treatment efficacy of UM. In this study, we conducted an extensive multi-omics analysis to explore the heterogeneity and prognostic significance of the hypoxia microenvironment. We found that UM revealed the most significant degree of intertumoral heterogeneity in hypoxia by quantifying tumor hypoxia compared with other solid tumor types. Then we systematically correlated the hypoxia phenotypes with clinicopathological features and found that hypoxic UM tumors were associated with an increased risk of metastasis, more aggressive phenotypes, and unfavorable clinical outcomes. Integrative multi-omics analyses identified multidimensional molecular alterations related to hypoxia phenotypes, including elevated genome instability, co-occurring of 8q arm gains and loss of chromosome 3, and BAP1 mutations. Furthermore, hypoxic UM tumors could be characterized by increased CD8+ T cell infiltration and decreased naïve B cell and dysregulated metabolic pathways. Finally, we introduced DNN2HM, an interpretable deep neural network model to decode hypoxia phenotypes from multi-omics data. We showed that the DNN2HM improves hypoxia phenotype prediction and robustly predicts tumor aggressiveness and prognosis in different multi-center datasets. In conclusion, our study provides novel insight into UM tumor microenvironment, which may have clinical implications for future rationalized hypoxia-targeted therapy.

Single-string, closed-loop fixation modification to reposit a dislocated triple-looped haptic intraocular lens.

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed.

iUMRG: multi-layered network-guided propagation modeling for the inference of susceptibility genes and potential drugs against uveal melanoma.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor. The use of precision medicine for UM to enable personalized diagnosis, prognosis, and treatment require the development of computer-aided strategies and predictive tools that can identify novel high-confidence susceptibility genes (HSGs) and potential therapeutic drugs. In the present study, a computational framework via propagation modeling on integrated multi-layered molecular networks (abbreviated as iUMRG) was proposed for the systematic inference of HSGs in UM. Under the leave-one-out cross-validation experiments, the iUMRG achieved superior predictive performance and yielded a higher area under the receiver operating characteristic curve value (0.8825) for experimentally verified SGs. In addition, using the experimentally verified SGs as seeds, genome-wide screening was performed to detect candidate HSGs using the iUMRG. Multi-perspective validation analysis indicated that most of the top 50 candidate HSGs were indeed markedly associated with UM carcinogenesis, progression, and outcome. Finally, drug repositioning experiments performed on the HSGs revealed 17 potential targets and 10 potential drugs, of which six have been approved for UM treatment. In conclusion, the proposed iUMRG is an effective supplementary tool in UM precision medicine, which may assist the development of new medical therapies and discover new SGs.

Application Research of Artificial Intelligence Screening System for Diabetic Retinopathy.

According to the latest data from the Bureau of Disease Control and Prevention of the National Health and Family Planning Commission, China currently has 199.6 million diabetic patients and has become the world's largest country with diabetes. The prevalence rate is as high as 14.3%, which is much higher than the world average of 5.8%. The primary-level ophthalmic screening service is one of the important tasks to improve primary-level medical services, and the corresponding ophthalmic imaging diagnosis technology is an important support for primary-level medical and health services. Therefore, it is very necessary for us to study the application of artificial intelligence image recognition technology for diabetic retinopathy under the medical consortium mode and to study the precise initial diagnosis, precise referral, and precise follow-up of diabetic retina under the medical conjoined mode, so as to better promote the transformation of the ophthalmology primary service model. Based on this background, in this article, we have proposed and carried out the following solution: (1) diabetes data collation. Based on medical artificial intelligence technology, this paper collected 2,265 electronic medical records from an eye hospital in Ningbo and selected 2,000 qualified medical records for data integration and preprocessing. The contents of electronic medical records mainly include age, gender, and examination records. (2) Establish diabetic retinopathy diagnosis model based on neural network algorithm. This article first uses the classic algorithm of BP neural network for modeling, chooses the Levenberg-Marquardt method as the training function, and selects 10 hidden layer units through comparison experiments. After that, ophthalmologists assessed 80 sets of test results and determined the right diagnosis rate. Finally, this article compares and analyzes the accuracy of the two routes in 80 tests.

Effects of Anti-Vascular Endothelial Growth Factor Drugs Before and After Pars Plana Vitrectomy in Patients with Polypoidal Choroidal Vasculopathy and Vitreous Hemorrhage.

Purpose: To compare the clinical effects of postoperative versus perioperative injection of anti-vascular endothelial growth factor (VEGF) drugs before and after pars plana vitrectomy (PPV) in patients with vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Methods: This was a retrospective study of patients who underwent PPV due to vitreous hemorrhage between October 2013 and June 2019 at Ningbo Eye Hospital. The patients who underwent PPV surgery due to PCV-secondary vitreous hemorrhage were included. The primary outcome was the changes in best-corrected visual acuity. The secondary outcome was the central macular thickness. Results: Compared with the postoperative group (n = 20), the perioperative group (n = 18) showed a smaller number of postoperative anti-VEGF injections (5.1 ± 0.8 vs. 8.0 ± 1.5, P < 0.05) and lower frequencies of early hyphema (5.6% vs. 30.0%, P < 0.05), and recurrent vitreous hemorrhage (11.1% vs. 30.0%, P < 0.05). The logarithm of minimal angle resolution (LogMAR) was smaller in the perioperative group compared with the postoperative group at 1 week, 1 month, and 3 months after PPV (P < 0.05), but there were no differences thereafter. Compared with the postoperative group, the perioperative group had thinner fovea at 1 week, 1 month, and 3 months (P < 0.05), but the differences disappeared after 3 months. Conclusion: In patients with PCV and vitreous hemorrhage, compared with postoperative anti-VEGF, perioperative anti-VEGF could reduce the difficulty of surgery and reduce the occurrence of postoperative complications, but there were no differences in long-term vision and macular thickness after surgery.

The P300/XBP1s/Herpud1 axis promotes macrophage M2 polarization and the development of choroidal neovascularization.

Neovascular age-related macular degeneration (AMD), which is characterized by choroidal neovascularization (CNV), leads to vision loss. M2 macrophages produce vascular endothelial growth factor (VEGF), which aggravates CNV formation. The histone acetyltransferase p300 enhances the stability of spliced X-box binding protein 1 (XBP1s) and promotes the transcriptional activity of the XBP1s target gene homocysteine inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (Herpud1). Herpud1 promotes the M2 polarization of macrophages. This study aimed to explore the roles of the p300/XBP1s/Herpud1 axis in the polarization of macrophages and the pathogenesis of CNV. Hypoxia-induced p300 interacted with XBP1s to acetylate XBP1s in RAW264.7 cells. Additionally, hypoxia-induced p300 enhanced the XBP-1s-mediated unfolded protein response (UPR), alleviated the proteasome-dependent degradation of XBP1s and enhanced the transcriptional activity of XBP1s for Herpud1. The hypoxia-induced p300/XBP1s/Herpud1 axis facilitated RAW264.7 cell M2 polarization. Knockdown of the p300/XBP1s/Herpud1 axis in RAW264.7 cells inhibited the proliferation, migration and tube formation of mouse choroidal endothelial cells (MCECs). The p300/XBP1s/Herpud1 axis increased in infiltrating M2-type macrophages in mouse laser-induced CNV lesions. Blockade of the p300/XBP1s/Herpud1 axis inhibited macrophage M2 polarization and alleviated CNV lesions. Our study demonstrated that the p300/XBP1s/Herpud1 axis in infiltrating macrophages increased the M2 polarization of macrophages and the development of CNV.

Scleral Buckling with Viscoelastics or Gas Injection for Bulging Retinal Detachments: A Retrospective Cohort Study.

OBJECTIVE: To examine the use of a viscoelastic agent instead of air in the vitreous cavity during surgery for scleral buckling. METHODS: This was a retrospective cohort study of patients who underwent scleral buckling surgery for bulging rhegmatogenous retinal detachment (RRD) at Ningbo Eye Hospital from 07/2016 to 12/2019. The patients were grouped into drainage, air injection, cryotherapy and explant (DACE) and drainage, viscoelastic injection, cryotherapy, and explant (DVCE) groups, which were comparatively assessed. RESULTS: There were 25 and 22 patients in the DVCE and DACE groups, respectively. The surgery was significantly shorter with DVCE than DACE (P < 0.05), with less intraoperative external pressure adjustment (P < 0.05). BCVA was lower in the DVCE group at 1 week compared with the DACE group (P < 0.05). Successful retinal reattachment was observed in 92.0% and 81.8% of the DVCE and DACE groups, respectively (P < 0.05). Cases requiring laser replenishing after the operation were less in the DVCE group compared with the DACE group (P < 0.05). There were no differences in complications and intraocular pressure between the two groups (all P < 0.05). CONCLUSION: DVCE has better operative characteristics and faster vision recovery than DACE, with similar outcomes.

Implication of inflammatory cytokines in the aqueous humour for management of macular diseases.

PURPOSE: To characterize profile of cytokines in aqueous humour of common macular diseases during intravitreal anti-VEGF therapy. METHODS: Aqueous humour from eyes with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), diabetic macular oedema (DME), neovascular age-related macular degeneration (nAMD) or pathologic myopia associated choroidal neovascularization (pmCNV) was sampled prior to 1st (n = 144) and 2nd (n = 48) intravitreal anti-VEGF therapy. Cytokines including vascular endothelium growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1) and interleukin 6 (IL-6) were quantitated and analysed along with retinal thickness data by optical coherence tomography (OCT) across two intravitreal injections and five macular disease types. RESULTS: ICAM-1, IL-6 and VEGF are positively associated in the aqueous humour of naive eyes (r = 0.39-0.77, p = 0.018 to <0.0001). ICAM-1, VEGF and IL-6 were significantly higher in CRVO and DME while lowest in pmCNV (p < 0.0001). Reduction of central retinal thickness (CRT) as a favourable response to anti-VEGF therapy was in the order of CRVO, BRVO, DME and nAMD/pmCNV (p < 0.0001). The strongest predictor for favourable CRT reduction was baseline CRT (p < 0.0001) followed by baseline ICAM-1 (p = 0.04). After the 1st intravitreal anti-VEGF therapy, VEGF in aqueous humour lowered significantly but ICAM-1 and IL-6 levels remained unchanged. ICAM-1 was not predictive for CRT reduction following 2nd anti-VEGF therapy. CONCLUSION: Rate of cytokine production is disease-dependent and higher in CRVO and DME. Anatomical response to intravitreal anti-VEGF therapy is disease-specific and best in RVO patients. A combination therapy using both anti-VEGF and anti-inflammatory therapeutics may be superior to single anti-VEGF therapy, at least for RVO and DME.

Cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope: A modified technique of ciliary body photocoagulation.

PURPOSE: This study aimed to investigate the efficacy of cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope in treating refractory glaucoma. METHODS: Eleven patients (11 eyes) with refractory neovascular glaucoma were treated with ciliary body photocoagulation. Preoperative and postoperative corrected visual acuity, intraocular pressure (IOP), ophthalmofundoscopy, B-ultrasound and ultrasound biomicroscopy, optical coherence tomography, and fundus fluorescein angiography were performed. RESULTS: Preoperative IOP ranged from 45 to 58 mmHg (mean 51.9 mmHg). At postoperative 1, 3, and 6 months, the IOPs ranged between 16 and 33 mmHg (mean 27.1 mmHg), 14-28 mmHg (mean 20.6 mmHg), and 14-28 mmHg (mean 18.5 mmHg), respectively. IOP at the last follow-up (range 7-12 months) was 15-24 mmHg (mean 18.8 mmHg). An average of 63.8% decrease in postoperative IOP was found in these patients with no associated complications. The postoperative fibrotic exudate, anterior chamber hyphema, and exudative choroidal detachment were all well-managed and resolved. No patients experienced intraocular lens deviation or dislocation, hypotonia oculi, atrophy of eyeball, retinal detachment, endophthalmitis, or sympathetic ophthalmia. CONCLUSION: Cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope is a safe and effective technique for the treatment of neovascular glaucoma.

Managing dislocated hard lens nuclei: 23-gauge vitrectomy and lens extraction via a corneoscleral limbal incision versus 23-gauge vitrectomy and phacofragmentation.

PURPOSE: To compare 23-gauge vitrectomy and lens extraction via a corneoscleral limbal incision (CSLI) with 23-gauge vitrectomy and phacofragmentation to treat dislocation of hard lens nuclei. SETTING: Ningbo Eye Hospital, Zhejiang, China. DESIGN: Retrospective case series. METHODS: The study included consecutive patients with complete posterior dislocation of a hard nucleus (grade ≥ IV) into the vitreous cavity. All patients received 23-gauge 3-channel vitrectomy. Some patients also had phacofragmentation and others had lens extraction through a CSLI. RESULTS: The CSLI group comprised 21 eyes of 21 patients and the phacofragmentation group, 22 eyes of 22 patients. The median follow-up was 10.8 months (range 6 to 24 months) and 11.3 months (range 5 to 18 months), respectively. Demographic characteristics, reason for lens dislocation, preoperative corrected distance visual acuity (CDVA), preoperative intraocular pressure (IOP), lens nucleus grade, and comorbidities were similar between groups. The CSLI group had a shorter mean surgical time than the phacofragmentation group (42.5 ± 7.2 minutes versus 68.2 ± 16.5 minutes); less frequent use of perfluorocarbon liquid, octafluoropropane, or air tamponade; lower incidence of retinal tears (9.5% versus 31.8%); and better CDVA but worse astigmatism 1 day and 1 week postoperatively (P < .05). The postoperative IOP did not differ between groups. Corneal edema and recurrent retinal detachment were less common in the CSLI group than in the phacofragmentation group. CONCLUSION: The 23-gauge vitrectomy with lens extraction through a CSLI might have advantages over 23-gauge vitrectomy with phacofragmentation for management of dislocated hard lens nuclei.

Unilateral endogenous fungal endophthalmitis after esophageal cancer surgery: a case report.

BACKGROUND: This study reports a case of Unilateral Endogenous Fungal Endophthalmitis After Esophageal Cancer Surgery. CASE PRESENTATION: One patient presented with a month-long loss of vision in his left eye, he had surgery for esophageal cancer 2 months earlier. The patient underwent cataract surgery (by phacoemulsification) in the left eye combined with 25-gauge vitrectomy and silicone oil tamponade. The microbiological culture pointed to infection with Candida albicans. At 3-month follow-up, the unaided visual acuity of left eye was 0.02 and corrected visual acuity was 0.2. In addition, there was no recurrence of the endophthalmitis within 1 year of the surgery. CONCLUSION: The early diagnosis of endogenous fungal endophthalmitis is difficult, and the disease is very likely to be misdiagnosed as uveitis. It is therefore critical to improve awareness of this condition and to reduce the incidence of its misdiagnosis.

HSV­TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK.

Retinoblastoma is an severe ophthalmic disease and the most common type intraocular malignant tumor, particularly in infants. Currently, few drugs and therapies are available. Gene therapy has been considered to be a potential treatment to cure cancer effectively and Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV­TK/GCV) is one type of suicide gene therapy that has been extensively studied. Numerous in vitro and in vivo studied have shown that this system can kill tumor cells, including liver and lung cancer cells. GCV is used as an antiviral drug, and the thymidine kinase, HSV­TK can phosphorylate GCV to GCV­TP, a competitive inhibitor of DNA synthesis, instead of guanine­5'­triphosphate in the process of DNA synthesis. This process prevents DNA chain elongation causing cell death via apoptosis. However, the toxic effects of HSV­TK/GCV on retinoblastoma cells remain unknown, and the molecular mechanisms of its therapeutic effects have not been fully elucidated. Our results suggest that HSV­TK/GCV can significantly cause the death of retinoblastoma cell lines, HXO­RB44 and Y79. Further studies have reported that this cell death is induced by the inhibition of autophagy by activating the MAPK/ERK (mitogen­activated protein kinase/ERK) signaling pathway. The mTOR inhibitor Torin1 can partially block the toxic effects of HSV­TK/GCV on HXO­RB44 cells. The above results demonstrate that the mechanism undertaken by HSV­TK/GCV to exhibit therapeutic effects mechanism may inhibit autophagy by activating MAPK/ERK. The findings of the present study may provide novel insight for the exploration of HSV­TK/GCV in the treatment of retinoblastoma.