Congenital cataract (CC) is one of the most common causes of pediatric visual impairment. As our understanding of CC's etiology, clinical manifestations, and pathogenic genes deepens,various CC categorization systems based on diferent classifcation criteria have been proposed. Regrettably, the application of the CC category in clinical practice and scientifc research is limited. It is challenging to obtain preciseinformation that could guide the timely treatment decision-making for pediatric cataract patients or predict their prognosis from a specific CC classification. This review aims to discuss the statusquo of CC categorization systems and the potential directions for future research in this field, focusingon categorization principles and scientific application in clinical practice. Additionally, it aims to propose the potential directions for future research in this domain.

Congenital cataract is one of the leading causes of treatable childhood blindness. The existing classification systems of congenital cataracts are mainly used for clinical and molecular diagnosis of the disease. Limited information was provided by the current classification systems, which was needed for the evaluation, formulation, and optimization of treatment plans. Moreover, research on the classification of congenital cataracts still needs exploration to provide further evidence supporting molecular diagnosis and syndromic disease diagnosis. The relevant studies on the classification of congenital cataracts were reviewed, and the prospects of research on the classification of congenital cataracts were discussed.

Purpose: To identify plasma proteins that are causally related to primary open-angle glaucoma (POAG) for potential therapeutic targeting. Methods: Summary statistics of plasma protein quantitative trait loci (pQTL) were derived from two extensive genome-wide analysis study (GWAS) datasets and one systematic review, with over 100 thousand participants covering thousands of plasma proteins. POAG data were sourced from the largest FinnGen study, comprising 8,530 DR cases and 391,275 European controls. A two-sample MR analysis, supplemented by bidirectional MR, Bayesian co-localization analysis, and phenotype scanning, was conducted to examine the causal relationships between plasma proteins and POAG. The analysis was validated by identifying associations between plasma proteins and POAG-related traits, including intraocular pressure (IOP), retinal nerve fibre layer (RNFL), and ganglion cell and inner plexiform layer (GCIPL). By searching druggable gene lists, the ChEMBL database, and the ClinicalTrials.gov database, the druggability and clinical development activity of the identified proteins were systematically evaluated. Results: Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments. The ORs per standard deviation increase in protein levels ranged from 0.39 (95% CI: 0.24–0.62; P = 7.70×10-5) for phospholipase C gamma 1 (PLCG1) to 1.29 (95% CI: 1.16–1.44; P = 6.72×10-6) for nidogen-1 (NID1). Bidirectional MR indicated that reverse causality did not interfere with the results of the main MR analyses. Five proteins exhibited strong co-localization evidence (PH4 ≥ 0.8): protein sel-1 homolog 1 (SEL1L), tyrosine-protein kinase receptor UFO (AXL), nidogen-1 (NID1) and FAD-linked sulfhydryl oxidase ALR (GFER) were negatively associated with POAG risk, while roundabout homolog 1 (ROBO1) showed a positive association. The phenotype scanning did not reveal any confounding factors between pQTLs and POAG. Further, validation analyses identified nine proteins causally related to POAG traits, with five proteins including interleukin-18 receptor 1 (IL18R1), interleukin-1 receptor type 1 (IL1R1), phospholipase C gamma 1 (PLCG1), ribonuclease pancreatic (RNASE1), serine protease inhibitor Kazal-type 6 (SPINK6) revealing consistent directional associations. In addition, 18 causal proteins were highlighted for their druggability, of which 5 proteins are either already approved drugs or in clinical trials and 13 proteins are novel drug targets. Conclusions: This study identifies 18 plasma proteins as potential therapeutic targets for POAG, particularly emphasizing the role of genomic and proteomic integration in drug discovery. Future experimental and clinical studies should be conducted to validate the efficacy of these proteins and to conduct more comprehensive proteomic explorations, thus taking a significant leap toward innovative POAG treatments.

Congenital cataract is a common treatable blinding eye disease in children. The existing classification system of congenital cataract is mainly used for clinical and molecular diagnosis of the disease. Still, it does not focus on whether there are differences in visual prognosis after treatment in children with different categories. It provides limited reference information for the evaluation, formulation, and optimization of treatment plans. Research on the classification of congenital cataract still needs further exploration. The relevant research on the classification of congenital cataracts was reviewed, and the direction of research on the classification of congenital cataracts was discussed.

Purpose: To identify plasma proteins that are causally related to primary open-angle glaucoma (POAG) for potential therapeutic targeting. Methods: A two-sample MR analysis, supplemented by bidirectional MR, Bayesian co-localization analysis, and phenotype scanning, was conducted to examine the causal relationships between plasma proteins and POAG. The analysis was validated by identifying associations between plasma proteins and POAG-related traits, followed by a systematic evaluation of protein druggability. Results: Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments. The ORs per standard deviation increase in protein levels ranged from 0.39 (95% CI: 0.24–0.62; P = 7.70 × 10-5) for Phospholipase C gamma 1 (PLCG1) to 1.29 (95% CI: 1.16–1.44; P = 6.72 × 10-6) for Nidogen-1 (NID1). Five proteins (SEL1L, ROBO1, AXL, NID1, GFER) demonstrated strong genetic linkage to POAG. Further, validation analyses identified nine proteins causally related to POAG traits, with five (IL18R1, IL1R1, PLCG1, RNASE1, SPINK6) revealing consistent directional associations. In addition, 18 causal proteins were highlighted for their druggability, 5 of which are either approved drugs or under clinical trial. Conclusions: This study identifies 18 plasma proteins as potential therapeutic targets for POAG, particularly emphasizing the role of genomic and proteomic integration in drug discovery.

Aim: The objective of this study was to investigate the prognosis of massive vitreous hemorrhage(VH) secondary to polypoidal choroidal vasculopathy(PCV) after vitrectomy.

Methods: Forty-nineeyes in 48 patients with PCV and breakthrough VH who underwent 23-gauge pars plana vitrectomy between January 2015 and December 2020 were enrolled. The main outcome parameters were best-corrected visual acuity, postoperative adverse events, and reoperation.

Results:The average follow-up time was 20.0±15.82 months. The average preoperative best-corrected visual acuity (BCVA) was 2.12±0.65 logarithm of the minimum angle of resolution (logMAR), the BCVA at six monthswas 1.65±0.64 logMAR, and the six-month follow-up BCVA was 1.67±0.76 logMAR. Compared to the average preoperative BCVA, the six-months and last follow-up BCVA after vitrectomy improved (P<0.05). The BCVAat the fnal follow-up was better than 1.3logMAR only in 14 eyes (28.6%). Postoperative complications were observed in 10 eyes (20.4%), including recurrent retinal detachment, recurrent vitreous hemorrhage, macular hole, hyphema and lens dislocation. Fourteen eyes(28.6%) underwent cataract surgery procedure an average of 10.16±5.14 months after vitrectomy. BCVAone week and three monthsafter cataract surgery improved compared toBCVAbefore cataract surgery (P<0.05). Hypertension was associated with BCVAsix months after vitrectomy (P=0.017). The BCVA at baseline and three months after PPV were worse in patients who underwent vitrectomy combined with silicone oil filling (P<0.05). Eyes with postoperative complications had worse BCVA at six months, 12 months, and at the final follow-up after PPV (P<0.05).The duration of VH is related to the BCVA12 months after PPV visual acuity after surgery. Patients who underwent vitrectomy within one month of the onset of vitreous hemorrhage had better BCVA 12 months after vitrectomy than those who underwent vitrectomy surgery one month later (P=0.015). 

Conclusions: Although the prognosis of vitrectomy varies greatly, cataract surgery could be considered to improve BCVAif polypoidal lesions are inactive six months after vitrectomy.

Background: Diabetic retinopathy (DR) urgently needs novel and effective therapeutic targets. Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel targets for diseases, but no systematic screening for DR has been performed.

Methods: Summary statistics of plasma protein quantitative trait loci (pQTL) were derived from two extensive genome-wide analysis study (GWAS) datasets and one systematic review, with over 100 thousand participants covering thousands of plasma proteins. DR data were sourced from the largest FinnGen study, comprising 10,413 DR cases and 308,633 European controls. Genetic instrumental variables were identified using multiple filters. In the two-sample MR analysis, Wald ratio and inverse variance-weighted (IVW) MR were utilized to investigate the

causality of plasma proteins with DR. Bidirectional MR, Bayesian Co-localization, and phenotype scanning were employed to test for potential reverse causality and confounding factors in the main MR analyses. By systemically searching druggable gene lists, the ChEMBL database, DrugBank, and Gene Ontology database, the druggability and relevant functional pathways of the identified proteins were systematically evaluated.

Results: Genetically predicted levels of 24 proteins were significantly associated with DR risk at a false discovery rate <0.05 including 11 with positive associations and 13 with negative associations. For each standard deviation increase in plasm protein levels, the odds ratios (ORs) for DR varied from 0.51 (95% CI: 0.36-0.73; P=2.22×10-5) for tubulin polymerization-promoting protein family member 3 (TPPP3) to 2.02 (95% CI: 1.44-2.83; P=5.01×10-5) for olfactomedin like 3 (OLFML3). Bidirectional MR indicated there was no reverse causality that interfered with the results of the main MR analyses. Four proteins exhibited strong co-localization evidence (PH4 ≥0.8): cytoplasmic tRNA synthetase (WARS), acrosin binding protein(ACRBP), and intercellular adhesion molecule 1 (ICAM1) were negatively associated with DR risk, while neurogenic locus notch homolog protein 2 (NOTCH2) showed a positive association. No confounding factors were detected between pQTLs and DR according to the phenotypic scan. Drugability assessments highlighted 6 proteins already in drug development endeavor and 18 novel drug targets, with metalloproteinase inhibitor 3 (TIMP) currently in phase I clinical trials for DR. GO analysis identified 18 of 24 plasma proteins enriching 22 pathways related to cell differentiation and proliferation regulation.

Conclusions:Twenty-four promising drug targets for DR were identified, including four plasma proteins with particular co-localization evidence. These findings offer new insights into DR's etiology and therapeutic targeting, exemplifying the value of genomic and proteomic data in drug target discovery.

Abstract Aim: The objective of this study was to investigate the prognosis of massive vitreous hemorrhage (VH) secondary to polypoidal choroidal vasculopathy (PCV) after vitrectomy. Methods: Forty-nine eyes in 48 patients with PCV and breakthrough VH who underwent 23-gauge pars plana vitrectomy between January 2015 and December 2020 were enrolled. The main outcome parameters were best-corrected visual acuity, postoperative adverse events, and reoperation. Results: The average follow-up time was 20.0±15.82 months. The average preoperative best-corrected visual acuity (BCVA) was 2.12±0.65 logarithm of the minimum angle of resolution (logMAR), the BCVA at six months was 1.65±0.64 logMAR, and the six-month follow-up BCVA was 1.67±0.76 logMAR. Compared to the average preoperative BCVA, the six-months and last follow-up BCVA after vitrectomy improved (P<0.05). Postoperative complications were observed in 10 eyes (20.4%), including recurrent retinal detachment, recurrent vitreous hemorrhage, macular hole, hyphema and lens dislocation. Fourteen eyes (28.6%) underwent cataract surgery procedure an average of 10.16±5.14 months after vitrectomy. BCVA one week and three months after cataract surgery improved compared to BCVA before cataract surgery (P<0.05). Conclusions: Although the prognosis of vitrectomy varies greatly, cataract surgery could be considered to improve BCVA if polypoidal lesions are inactive six months after vitrectomy. Keywords: polypoidal choroidal vasculopathy; vitreous hemorrhage; vitrectomy; visual acuity

Aims: To identify plasma proteins with causal links to diabetic retinopathy (DR) for potential therapeutic targets. Materials and methods: Summary statistics of plasma protein quantitative trait loci (pQTL) were derived from two extensive GWAS datasets and one systematic review, with over 100 thousand participants covering thousands of plasma proteins. DR data were sourced from the largest FinnGen study, comprising 10,413 DR cases and 30,863 European controls. Two-sample MR approach was utilized to investigate the causality of plasma proteins with DR, followed by bidirectional MR, Bayesian Co-localization analysis, and phenotype scanning to ensure robustness of the MR results. Druggability of the identified proteins were systematically evaluated. Results: Genetically predicted levels of 24 proteins were significantly associated with DR risk after multiple testing correction. For each standard deviation increase in plasm protein levels, the odds ratio (OR) for DR varied from 0.51 (95% CI: 0.36-0.73; P=2.22×10-5) for Tubulin Polymerization-Promoting Protein Family Member 3 (TPPP3) to 2.02 (95% CI: 1.44-2.83; P=5.01×10-5) for Olfactomedin like 3 (OLFML3). Four proteins exhibited strong co-localization evidence (PH4 ≥0.8): WARS, ACRBP, and ICAM1 were negatively associated with DR risk, while NOTCH2 showed a positive association. Drugability assessments highlighted these 24 proteins as potential DR targets, with two of them currently in phase I clinical trials. Conclusions: Twenty-four promising drug targets for DR were identified, including four plasma proteins with particularly promise. These findings offer new insights into DR's etiology and therapeutic targeting, exemplifying the value of genomic and proteomic data in drug target discovery.

Aims: To identify plasma proteins with causal links to diabetic retinopathy (DR) for potential therapeutic targets. Materials and methods: Summary statistics of plasma protein quantitative trait loci (pQTL) were derived from two extensive GWAS datasets and one systematic review, with over 100 thousand participants covering thousands of plasma proteins. DR data were sourced from the largest FinnGen study, comprising 10,413 DR cases and 30,863 European controls. Two-sample MR approach was utilized to investigate the causality of plasma proteins with DR, followed by bidirectional MR, Bayesian Co-localization analysis, and phenotype scanning to ensure robustness of the MR results. Druggability of the identified proteins were systematically evaluated. Results: Genetically predicted levels of 24 proteins were significantly associated with DR risk after multiple testing correction. For each standard deviation increase in plasm protein levels, the odds ratio (OR) for DR varied from 0.51 (95% CI: 0.36-0.73; P=2.22×10-5) for Tubulin Polymerization-Promoting Protein Family Member 3 (TPPP3) to 2.02 (95% CI: 1.44-2.83; P=5.01×10-5) for Olfactomedin like 3 (OLFML3). Four proteins exhibited strong co-localization evidence (PH4 ≥0.8): WARS, ACRBP, and ICAM1 were negatively associated with DR risk, while NOTCH2 showed a positive association. Drugability assessments highlighted these 24 proteins as potential DR targets, with two of them currently in phase I clinical trials. Conclusions: Twenty-four promising drug targets for DR were identified, including four plasma proteins with particularly promise. These findings offer new insights into DR's etiology and therapeutic targeting, exemplifying the value of genomic and proteomic data in drug target discovery.