Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

A Modified Suturing Technique to Produce Temporary Scleral Buckling Effect for Noncomplex Rhegmatogenous Retinal Detachment.

PURPOSE: To introduce a surgical technique for temporary scleral buckling of noncomplex rhegmatogenous retinal detachment using a combination of nonabsorbable and absorbable sutures that would induce minimal permanent refractive changes. METHODS: Twenty consecutive patients (20 eyes) with noncomplex rhegmatogenous retinal detachment were prospectively included. Scleral buckling was performed in all eligible subjects, and encircling buckling was added when necessary. The silicone elements were fixed on the sclera with 5-0 nonabsorbable sutures and tightened to form a ridge with 6-0 absorbable sutures. Best-corrected visual acuity, scleral ridge status, axial length, spherical diopter, and cylinder diopter were collected. RESULTS: All patients achieved primary retinal reattachment with significant improvement of best-corrected visual acuity after surgery. Scleral ridge was obvious and in situ at the 1-month follow-up but diminished at the 3-month follow-up. At the 1-month follow-up, axial length increased from 24.78 mm ± 2.14 mm preoperatively to 25.22 mm ± 2.11 mm, and cylinder diopter increased from -1.99 ± 1.03 to -2.95 ± 1.55 (both P < 0.001). At the 3-month follow-up, axial length, spherical diopter, and cylinder diopter decreased significantly compared with the values at the 1-month follow-up (all P < 0.05). No obvious complications were observed during the whole follow-up. Patients who underwent additional encircling buckling exhibited greater changes in axial length and cylinder diopter at the 1-month follow-up (both P < 0.001). CONCLUSION: The modified technique of scleral buckling with/without encircling buckling using both nonabsorbable and absorbable sutures offers a safe and effective option to repair noncomplex rhegmatogenous retinal detachment, which would offer an adequate temporary scleral buckling effect and induce minimal permanent refractive changes.

Scleral remodeling in early adulthood: the role of FGF-2.

Emmetropization, a natural process of ocular elongation, is closely associated with scleral remodeling. The Fibroblast growth factor-2 (FGF-2) was reported involved in scleral remodeling in myopia models. Herein, we aimed to investigate the role of scleral fibroblast-to-myofibroblast differentiation and FGF-2 in scleral remodeling during maturation. Our findings revealed that the posterior scleral fibroblasts (SFs) from mature guinea pigs exhibit increased stiffness compared to those from young guinea pigs. Moreover, mature SFs displayed decreased cell proliferation but increased levels of α-SMA, matrix metalloproteinase 2 (MMP2), and collagen 1, when compared to young SFs. Additionally, the mRNA expression of scleral Fgf-2, Fgf receptor 1 (Fgfr1), Fgfr2, Fgfr3, and Fgfr4 was increased in mature SFs. Notably, exogenous FGF-2 showed increased cell proliferation and led to decreased expression of α-SMA, MMP2, and collagen 1 in mature SFs. Overall, our findings highlight the influence of maturation on SFs from posterior scleral shells, resulting in increased stiffness and the manifestation of fibroblast-to-myofibroblast differentiation during development. Exogenous FGF-2 increased cell proliferation and reversed the age-related fibroblast-to-myofibroblast differentiation, suggesting a potential role of FGF-2 in regulating scleral remodeling.

27­Gauge vitrectomy vs. 25­gauge vitrectomy in the management of proliferative diabetic retinopathy with preoperative intravitreal injection of conbercept.

Small-gauge vitrectomy has become popular due to its notable advantages, including less trauma, shortened convalescence and improved manoeuvrability. The aim of the present study was to compare the surgical outcomes of 27-gauge (27-G) vitrectomy with those of 25-gauge (25-G) vitrectomy in the management of proliferative diabetic retinopathy (PDR) with preoperative intravitreal injection of conbercept. The data of 48 consecutive patients with PDR (48 eyes) were retrospectively collected. The patients underwent conbercept intravitreal injection and pars plana vitrectomy with a 27-G group (23 eyes) or 25-G group (25 eyes) vitrectomy system. The operating time, suturing rate, endodiathermy rate, postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP) and complications were recorded. The mean postoperative BCVA at final follow-up was significantly improved compared with that at the baseline in both groups (P<0.001 for both). The differences in the mean BCVA changes between the two groups were not significant (P>0.99), and no differences were observed in the final central foveal thickness (P=0.51) between the two groups. The final IOP remained stable compared with that at the baseline in the 27-G group (P=0.36) and the 25-G group (P=0.05). The suturing rate was significantly decreased in the 27-G group compared with the 25-G group (P=0.04). There were no significant differences between the two groups in terms of the operating time (P=0.18), rate of endodiathermy use (P>0.99), iatrogenic retinal breaks (P=0.42) or postoperative recurrent vitreous haemorrhage (P>0.99). In addition, no case of ocular hypotony was observed in either group. In conclusion, 27-G vitrectomy was as efficient and safe as 25-G vitrectomy in the management of PDR in terms of operating time and complications. With reference to the literature, preoperative conbercept injection appears to assist in decreasing the incidence of intraoperative and postoperative complications.

ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN MILD FAMILIAL EXUDATIVE VITREORETINOPATHY.

PURPOSE: To investigate ultra-widefield optical coherence tomography angiography (UWF-OCTA) to detect and evaluate mild familial exudative vitreoretinopathy and compare the detective ratio of UWF-OCTA with ultra-widefield scanning laser ophthalmoscopy and ultra-widefield fluorescein angiography. METHODS: The patients with familial exudative vitreoretinopathy were included in this study. UWF-OCTA, using a 24- × 20-mm montage, was performed for all patients. All images were independently tested for the presence of familial exudative vitreoretinopathy-associated lesions. Statistical analysis was performed with SPSS V.24.0. RESULTS: Forty-six eyes of 26 participants were included in the study. Ultra-widefield optical coherence tomography angiography was found to be greatly superior to ultra-widefield scanning laser ophthalmoscopy in detecting peripheral retinal vascular abnormality ( P < 0.001) and peripheral retinal avascular zone ( P < 0.001). The detection rates of peripheral retinal vascular abnormality, peripheral retinal avascular zone, retinal neovascularization, macular ectopia, and temporal midperipheral vitreoretinal interface abnormality were comparable with ultra-widefield fluorescein angiography images ( P > 0.05). Furthermore, vitreoretinal traction (17/46, 37%) and small foveal avascular zone (17/46, 37%) were detected effectively on UWF-OCTA. CONCLUSION: Ultra-widefield optical coherence tomography angiography is a reliable noninvasive tool to detect familial exudative vitreoretinopathy lesions, especially in mild patients or asymptomatic family members. The unique manifestation of UWF-OCTA offers an alternative to ultra-widefield fluorescein angiography for the screening and diagnosis of FEVR.

NDP-related retinopathies: clinical phenotype of female carriers.

BACKGROUND/AIMS: Norrin cysteine knot growth factor (NDP) located on the X chromosome, was previously reported to cause Norrie disease and familial exudative vitreoretinopathy (FEVR), which are blindness-causing ocular disorders, in males. In this study, we aimed to explore the clinical characteristics of female carriers with NDP mutations. METHODS: Twelve female carriers from 11 unrelated families with pathogenic NDP mutations were recruited. Clinical data were collected from the NDP carriers. Comprehensive ocular examinations, including best corrected visual acuity, slit lamp examination, fundus photography and fundus fluorescein angiography (FFA) were evaluated. Targeted gene or whole exome sequencing was performed in the probands, and Sanger sequencing was performed to confirm NDP mutations in female carriers. RESULTS: Of the 12 females, 1 (1/12, 8.3%) presented with decreased visual acuity and 11 (11/12, 91.7%) were asymptomatic. Based on the FFA, peripheral vascular changes were noted in 66.7% (16/24) of the eyes of 75.0% (9/12) of the carriers. A total of 33.3% (8/24) had typical FEVR phenotype, 33.3% (8/24) had mild vascular abnormalities and 33.3% (8/24) was unremarkable. In addition, predominant changes such as telangiectatic endings (66.7%), anomalous circumferential vessel (37.5%), supernumerary vascular branching (33.3%), fluorescein leakage (29.2%), avascular area (8.3%), retina fold (8.3%) and peripheral straightening of retinal vessels (33.3%) were noted. CONCLUSION: Although NDP-related retinopathy is an X-linked recessive disorder, most of the female carriers of NDP exhibited clinical features of FEVR. Thus, timely examinations and lifelong monitoring should be conducted in the NDP female carriers.

Skills assessment after a grape-based microsurgical course for ophthalmology residents: randomised controlled trial.

AIMS: To introduce and assess a course using grapes as training models for ophthalmology residents to acquire basic microsurgical skills. METHODS: Ophthalmology residents who were novices at microsurgery were included. Participants were randomised into a 1:1 ratio to a 4-hour training programme based on fruit models (group A) or virtual reality (VR) modulator and silicone suture pads (group B), respectively. Before and after training, questionnaires were designed to measure their self-confidence with ophthalmic operations and with their coming role as surgical assistants. After training, each participant provided their interest in further studying microsurgery and was assessed for their general competence of ophthalmic microsurgery on porcine eyes. RESULTS: Eighty-three participants were included, with 42 ones in group A and 41 ones in group B. After training, participants in group A performed better in the uniformities of the suture span (p<0.05), suture thickness (p<0.05) and tissue protection (p<0.05) during the corneal suturing assessment. The overall scores of corneal suturing and circular capsulorhexis in the porcine eye in group A were comparable to those in group B (p=0.26 and 0.87, respectively). Group A showed a more positive attitude to withstand the training for more than 4 hours (p<0.001), as well as a higher willingness to receive more times of the training in the future (p<0.001). CONCLUSIONS: Training models based on grapes are equal to VR simulators and silicon suture pads to provide solid training tasks for ophthalmology residents to master basic microsurgical skills, and might have advantages in lower economic cost, and easy availability. TRIAL REGISTRATION NUMBER: ChiCTR2000040439.

Ocular findings and genetic test in Alström syndrome in childhood.

This study aimed to investigate the mutation spectrums and ocular features of Alström syndrome (AS) patients. Six AS patients from five unrelated families were included. Ocular and systemic examinations were performed in all subjects. Whole-exome sequencing (WES) was performed in the probands, and Sanger sequencing was performed for mutation validation and segregation analysis. Among the six patients, the first symptoms included nystagmus, poor fixation, and photophobia. Five patients had high hyperopia, four of whom (80%) were initially diagnosed with amblyopia before referral with prescribed corrective lenses and amblyopia treatment, but no improvement was obtained. Optical coherence tomography (OCT) revealed progressive damage to the photoreceptor layer, including blurred ellipsoid zone (EZ) and lack of interdigitation zone (IZ) within the macula, and thorough loss of photoreceptor layer in the peripheral retina. Electroretinograms (ERG) demonstrated severely diminished cone and rod responses. WES identified biallelic variants of ALMS1 in all the six patients, including two novels, c.3892C > T (p.Gln1298*) and c.2888_2897del (p.Ser963Thrfs*15) and five knowns, c.10819C > T (p.Arg3607Trp), c.2090C > A (p.Ser697*), c.4891C > T (p.Gln1631*), c.10825C > T (p.Arg3069*) and c.6430C > T (Arg2146*). In conclusion, this study expanded the ocular features and genotypic spectrum of AS. High hyperopia is a significant and common feature of AS. OCT and ERG are essential accessory techniques for the diagnosis of AS. If a patient had high hyperopia with a noneffective response to amblyopic treatment, the diagnosis of AS should be suspected, and detailed ocular examination, systemic evaluation, and genetic testing recommended.

CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt/cadherin axis.

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder that can cause vision loss. CTNND1 encodes a cellular adhesion protein p120-catenin (p120), which is essential for vascularization with unclear function in postnatal physiological angiogenesis. Here, we applied whole-exome sequencing to 140 probands of FEVR families and identified 3 candidate variants in the human CTNND1 gene. We performed inducible deletion of Ctnnd1 in the postnatal mouse endothelial cells (ECs) and observed typical phenotypes of FEVR with reactive gliosis. Using unbiased proteomics analysis combined with experimental approaches, we conclude that p120 is critical for the integrity of adherens junctions (AJs) and that p120 activates Wnt signaling activity by protecting ß-catenin from glycogen synthase kinase 3 beta-ubiqutin-guided (Gsk3ß-ubiquitin-guided) degradation. Treatment of CTNND1-depleted human retinal microvascular ECs with Gsk3ß inhibitors LiCl or CHIR-99021 enhanced cell proliferation. Moreover, LiCl treatment increased vessel density in Ctnnd1-deficient mouse retinas. Variants in CTNND1 caused FEVR by compromising the expression of AJs and Wnt signaling activity. Genetic interactions between p120 and ß-catenin or α-catenin revealed by double-heterozygous deletion in mice showed that p120 regulates vascular development through the Wnt/cadherin axis. In conclusion, variants in CTNND1 can cause FEVR through the Wnt/cadherin axis.

Update on the Phenotypic and Genotypic Spectrum of KIF11-Related Retinopathy.

Background: This study aimed to report the frequency of KIF11-mutations in a large familial exudative vitreoretinopathy (FEVR) population, extend the clinical spectrum of KIF11-associated retinopathy and compare KIF11-associated retinopathy to FEVR with mutations in other genes. Methods: Genetic data collected from 696 FEVR families were reviewed. The ocular phenotypes in patients with KIF11 mutations were analyzed and compared with those of FEVR patients with mutations in other genes (FZD4, TSPAN12, LRP5, NDP and JAG1). Results: In a cohort of 696 FEVR families, disease-causing KIF11 mutations were identified in 3.6% of families (25/696). Among 25 KIF11 mutations, 80% (20/25) carried variants of loss of function and 48% (12/25) of variants were de novo. The phenotypes were variable. Compared with FEVR with disease-causing mutations in other genes, chorioretinal dysplasia was observed in 44.2% (31/70) of eyes with KIF11-associated retinopathy and in only 1.3% (1/70) of eyes with FEVR with mutations in other genes (p < 0.01). Increase and straightening of peripheral vessels (ISPV) was observed in 17.1% (12/70) of eyes with KIF11-associated retinopathy, and in 50% (39/78) of eyes with FEVR with mutations in other genes (p < 0.01). Conclusions: The frequency of the KIF11 mutation in FEVR was 3.6% in our database. The manifestation of KIF11-associated retinopathy was variable and different from the phenotype in FEVR caused by other genes. Chorioretinal dysplasia, instead of retinal folds, was the dominant phenotype in KIF11-associated retinopathy. ISPV was rare in KIF11-associated retinopathy. Moreover, our study revealed that most pathogenic KIF11 mutations were de novo.

FZD4 in a Large Chinese Population With Familial Exudative Vitreoretinopathy: Molecular Characteristics and Clinical Manifestations.

Purpose: The purpose of this study was to establish a genotype-phenotype correlation of familial exudative vitreoretinopathy (FEVR) caused by FZD4 gene mutations. Methods: Six hundred fifty-one probands and their family members were recruited based on a clinical diagnosis of FEVR between 2015 and 2021 at Zhongshan Ophthalmic Center. Ocular examinations were performed in all participants. Targeted gene panel sequencing and whole-exome sequencing were performed in the probands, and Sanger sequencing was used to verify the mutations and segregation analysis was performed in the family members. Results: Fifty-one FZD4 mutations (24 novels and 27 known) were detected in 84 families. Of these 168 eyes with FEVR, the eyes at stages 1, 2, 3, 4, and 5 were 29 (17.3%), 15 (8.9%), 19 (11.3%), 55 (32.7%), and 12 (7.1%), respectively. Exact stage of 38 (22.6%) eyes could not be determined. The FEVR phenotypes were more severe in the probands than the phenotypes in the family members (P < 0.001). The families were divided into two groups, probands that inherited the variant from the mother, and probands that inherited the variant from the father. In addition, the FEVR stage differences between these two groups were different (P < 0.05). Despite the mutations being located in different domains of FZD4, no significant differences were identified among the domains in terms of FEVR staging, retinal folds, retinal detachment, temporal midperipheral vitreoretinal interface abnormality, and foveal hypoplasia. Conclusions: The FZD4 probands had severer phenotype than the family members, and the FEVR stage difference was greater between the probands and mothers than that between the probands and fathers.

Intraocular Lens Fixation Technique Without Corneal Incision in Minimally Invasive Vitrectomized Eyes.

INTRODUCTION: To introduce a modified technique for primary/secondary intraocular lens (IOL) fixation without corneal incision in vitrectomized eyes. METHODS: Consecutive case series who had undergone previous or concomitant pars plana vitrectomy (PPV) to have primary/secondary IOL fixation were prospectively included. A self-sealing scleral incision was made underneath the superior scleral flap, through which the IOL was inserted into the anterior chamber. The suture tied with the IOL passed through the sclera to fix the IOL in the ciliary sulcus. Patients were followed up for at least 3 months. Main outcomes were best corrected visual acuity (BCVA), intraocular pressure (IOP), surgically induced astigmatism (SIA), and intraoperative and postoperative complications. RESULTS: A total of 31 patients were included in the study. The mean follow-up time was 5.35 ± 4.14 months. The BCVA (log MAR unit) improved from 0.97 ± 0.58 preoperative to 0.42 ± 0.36 postoperative (P < 0.001). Mean IOP remained unchanged (preoperative IOP 14.03 ± 2.90 mmHg, postoperative IOP 13.26 ± 3.46 mmHg, P = 0.130). The mean SIA was 0.91 ± 0.76 diopters. No obvious intraoperative and postoperative complications were observed. CONCLUSION: This method has favorable postoperative visual recovery and IOP control. This modified method could be taken into account as an option by surgeons in vitreoretinal surgery.

Intraoperative choroidal detachment during small-gauge vitrectomy: analysis of causes, anatomic, and visual outcomes.

INTRODUCTION: To investigate the incidence and causes of intraoperative choroidal detachment (CD) during small-gauge vitrectomy, as well as the anatomic and visual outcomes. METHODS: We retrospectively reviewed the medical records of 1026 consecutive patients who underwent small-gauge vitrectomy from June 2017 to December 2018 at Zhongshan Ophthalmic Centre, Guangzhou, China. Data on the presence, location, and extent of intraoperative CD and its relationship to the infusion cannula were collected. Patient demographic characteristics and postoperative anatomic and visual outcomes were also assessed. RESULTS: A total of six cases were found to have intraoperative CD, including two with serous CD, three with limited haemorrhagic CD, and one with CD caused by inadvertent perfusion of gas during air/fluid exchange. Retraction of the infusion cannula and acute ocular hypotony were found to be the main causes of intraoperative CD in five out of the six cases. The best-corrected visual acuity of all cases significantly improved after the surgery. CONCLUSION: The incidence of intraoperative CD during small-gauge vitrectomy is low; the predominant causes are retraction of the infusion cannula and acute ocular hypotony. Immediate awareness and timely closure of the incision may contribute to a better surgical prognosis.

HODD: A Manually Curated Database of Human Ophthalmic Diseases with Symptom Characteristics and Genetic Variants Towards Facilitating Quick and Definite Diagnosis.

Ophthalmic diseases are disorders that affect the eyes. Hundreds of causal genes and biological pathways have been reported to be closely correlated with ophthalmic diseases. However, these information are scattered across various resources, which has hindered a thorough and deep understanding of ophthalmic diseases. In the present work, we proposed the Human Ophthalmic Diseases Database (HODD), which currently deposits 730 ophthalmic diseases and 653 related genes and is available at http://bio-bigdata.cn/HODD/ . The disease-related information and genes related to ophthalmic diseases were collected from the several well-known databases. To comprehensively understand the ophthalmic diseases, the basic information was provided for each disease, including disease description, related genes, gene location, ocular and extraocular effect of the disease, protein-protein interaction and disease-associated pathways. All these data were reorganized and made accessible through multiple entrances. We hope that HODD will facilitate studies on ophthalmic diseases. The workflow for the construction of the HODD (Human Ophthalmic Diseases Database, http://bio-bigdata.cn/HODD/ ) database.

Pars plana subcapsulotomy to remove condense subcapsular opacification in combined surgery of silicone oil removal and phacoemulsification.

PURPOSE: Because of the direct contact of intravitreal silicone oil (SO) with the subcapsular membrane, cataract is one of the main SO-related complications. In a group of patients, condense subcapsular opacification occurs, which adds difficulty and risk when having sequential treatment of it. The aim of the current study is to assess the long-term outcomes of pars plana subcapsulotomy to remove condense subcapsular opacification in combined surgery of SO removal and phacoemulsification. METHODS: Retrospective cohort study. Consecutive patients who were scheduled to have combined surgery of SO removal and phacoemulsification, and with condense subcapsular opacification were included. After phacoemulsification and SO removal, circular subcapsulotomy (diameter = 3-5 mm) was performed with a 23-/25-gauge vitrectomy probe on each subject during the combined surgery. Main outcomes were pre- and postoperative best-corrected visual acuity (BCVA), intra- and postoperative complications. RESULTS: One hundred and twenty patients (120 eyes) were included. Postoperative logMAR BCVA at day 1, week 1, month 1, and final follow-up examinations was 1.0 ± 0.5, 0.7 ± 0.4, 0.6 ± 0.4, and 0.6 ± 0.3, respectively. Statistically significant median differences of logMAR BCVA occurred between the preoperative examination and each postoperative follow-up examination (all p < 0.001). The sharpest median increase in logMAR BCVA occurred between the day 1 and week 1 postoperative examinations (p < 0.001). CONCLUSIONS: For condense subcapsular opacification caused by SO tamponade, pars plana subcapsulotomy with a 23-/25-gauge vitrectomy probe during combined surgery of SO removal and phacoemulsification is effective and safe to have surgical management of it. The systemic approach enables patients to experience rapid and long-lasting vision rehabilitation in a single procedure.

Choroidal Neovascularization in Pediatric Patients: Analysis of Etiologic Factors, Clinical Characteristics and Treatment Outcomes.

Background and Objectives: Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy, but very limited published data have reported in pediatric patients. This study aimed to investigate the etiologic factors, clinical features, and treatment outcomes of choroidal neovascularization (CNV) in children. Methods: In this study, 33 eyes in 30 patients aged 18 years or younger with CNV were included. Comprehensive ophthalmic examination was performed in all the patients. The demographic profiles, laterality, visual acuity, optical coherence tomographic findings, fundus fluorescein angiographic findings, and the underlying pathology were analyzed. The types, locations, treatment outcomes, and recurrences of CNV were noted. Results: The average age was 11.2 ± 4.6 (range, 1-18) years. Most CNVs affecting children were classic and type 2. The most common etiologic factors of CNV in pediatric patients were congenital/developing abnormalities (9/30, 30.0%) and inflammatory retinochoroidopathy (9/30, 30.0%), followed by idiopathic CNV (8/30, 26.7%). Subtype analysis showed that the etiologic factor was inflammatory retinochoroidopathy in children 12 years or older, whereas congenital/developing abnormalities were present in children younger than 12 years. Eyes with active CNVs required a mean of 1.40 ± 0.58 injections. No recurrence was observed during follow-up. Conclusions: The etiologic factors of CNV in young Chinese patients were diverse, with congenital/developing abnormalities, inflammatory retinochoroidopathy and idiopathic CNV being the 3 most common ones. Eyes with active CNVs had good responses to antivascular endothelial growth factor treatment with low recurrence.

Generation of induced pluripotent stem cell (iPSC) line ZOCi003-A derived from peripheral blood mononuclear cells of X-linked juvenile retinoschisis harboring a hemizygous mutation in RS1 gene.

X-linked juvenile retinoschisis (XLRS) is an inherited disease characterized by splitting within inner retinal layers and impaired vision, which begins in childhood and occurs mostly in males. Peripheral blood mononuclear cells (PBMCs) were isolated from a seven-year-old boy carrying a hemizygous mutation in RS1 gene, and were reprogrammed into human induced pluripotent stem cells (iPSCs) using non-integrative episomal vectors. The cell line, ZOCi003-A, had normal karyotype, expressed pluripotency markers, and could differentiate into three germ layers in vivo. This IPSC line may be used for studying the molecular basis of XLRS and selecting potential therapeutic targets and drugs.

Knobloch Syndrome Associated with Novel COL18A1 Variants in Chinese Population.

Knobloch syndrome is an inherited disorder characterized by high myopia, retinal detachment, and occipital defects. Disease-causing mutations have been identified in the COL18A1 gene. This study aimed to investigate novel variants of COL18A1 in Knobloch syndrome and describe the associated phenotypes in Chinese patients. We reported six patients with Knobloch syndrome from four unrelated families in whom we identified five novel COL18A1 mutations. Clinical examination showed that all probands presented with high myopia, chorioretinal atrophy, and macular defects; one exhibited rhegmatogenous retinal detachment in one eye. Occipital defects were detected in one patient.

Beyond the Visual Acuity: Assessing the Visual Function in mCNV Patients After Anti-VEGF Treatment.

Purpose: To investigate visual function and vision-related quality of life (VR-QoL) changes in patients with myopic choroidal neovascularization (mCNV) after ranibizumab treatment. Methods: Quantitatively evaluate the objective tests of visual function (visual acuity, microperimetry, and metamorphopsia by m-Charts) before and after 3+prn (pro re neta) ranibizumab treatment for 1 year. The National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) was performed to evaluate the VR-QoL. Results: A total of 57 eyes of 57 patients were included in this study. The median average metamorphopsia score was 0.65 before treatment and improved to 0.45 after treatment (p = 0.0003). There was also a significant difference in the average threshold, macular integrity, and proportion of patients with stable fixation by the microperimetry (p < 0.000, p < 0.0001, and p = 0.03, respectively). After treatment, the VR-QoL composite, general vision subscale, and vision-related mental health subscale score were increased with borderline or statistical significance (p = 0.088, p = 0.0038, and p = 0.012, respectively). Subgroup analysis demonstrated parallel improvement of the VR-QoL score, metamorphopsia, average macular threshold, and fixation stability in patients with or without visual acuity increase. By multiple linear regression analysis, the VFQ-25 score after anti-VEGF treatment was only associated with the baseline VFQ-25 score and macular integrity. Improvements in the VFQ-25 score were only associated with changes in the metamorphopsia score. Conclusions: Integral lifting in several aspects of visual function was observed in mCNV after ranibizumab treatment. Macular integrity and metamorphopsia, but not visual acuity, were associated with VR-QoL.