Vision serves as the cornerstone of rountine human life activities, wherein approximately 80% of information is perceived visually. Eye diseases, however, frequently culminate in vision impairment or blindness, severely affecting the quality of life. Due to the obscurity of the underlying molecular mechanisms, therapeutic outcomes for various blinding eye diseases remain suboptimal. Over the past decade, the development of single-cell genomics technology has made it possible to obtain multi-dimensional insights into genomes, epigenomes, transcriptomes, and proteomes of tissues and organs at the single-cell level, providing a potent tool for elucidating the molecular mechanisms of eye diseases and advancing precision diagnosis. Meanwhile, single-cell genomics technology has also been harnessed in drug discovery and screening, promising to transform traditional drug development paradigm that is often characterized by high cost ^[1], time-consuming ^[2], and substantial failure rate. This review aims to describe the cutting-edge advances in single-cell omics technology  and its applications in precision diagnosis of eye diseases as well as drug discovery and screening.

Vision serves as the cornerstone of rountine human life activities, wherein approximately 80% of information is perceived visually. Eye diseases, however, frequently culminate in vision impairment or blindness, severely affecting the quality of life. Due to the obscurity of the underlying molecular mechanisms, therapeutic outcomes for various blinding eye diseases remain suboptimal. Over the past decade, the development of single-cell genomics technology has made it possible to obtain multi-dimensional insights into genomes, epigenomes, transcriptomes, and proteomes of tissues and organs at the single-cell level, providing a potent tool for elucidating the molecular mechanisms of eye diseases and advancing precision diagnosis. Meanwhile, single-cell genomics technology has also been harnessed in drug discovery and screening, promising to transform traditional drug development paradigm that is often characterized by high cost ^[1]，time-consuming ^[2], and substantial failure rate. This review aims to describe the cutting-edge advances in single-cell omics technology  and its applications in precision diagnosis of eye diseases as well as drug discovery and screening.

Autoimmune uveitis is one of the most common inflammatory eye diseases leading to blindness globally. Its etiology is primarily associated with autoimmune responses. Patients with this condition often exhibit complex and chronic disease courses, with a high propensity for recurrence. Current treatments mainly involve corticosteroids and immunosuppressive agents, which, despite their effectiveness, entail significant side effects that severely impact patients' vision and quality of life. There are still unresolved questions regarding the etiology and immunopathogenesis of autoimmune uveitis, and traditional high-throughput sequencing techniques fall short of adequately elucidatingits pathogenic mechanisms at the cellular level. With the continuous advancement of single-cell sequencing technology, an increasing number of studies are leveraging this approach to deeply investigate the pathogenesis of autoimmune uveitis, thereby offering new insights for identifying novel diagnostic and therapeutic targets. This paper reviews the latest applications of single-cell sequencing technology in exploring the pathogenesis of autoimmune uveitis. Through the utilization of this technology, researchers can gain a more comprehensive understanding of cellular-level changes in patients, providing robust support for the search for new therapeutic avenues. These studies offer new directions for the diagnosis and treatment of autoimmune uveitis and provide valuable information for the development of future therapeutic strategies and approaches.

Autoimmune uveitis is one of the most common inflammatory eye diseases leading to blindness globally. Its etiology is primarily associated with autoimmune responses. Patients with this condition often exhibit complex and chronic disease courses, with a high propensity for recurrence. Current treatments mainly involve corticosteroids and immunosuppressive agents, which, despite their effectiveness, entail significant side effects that severely impact patients' vision and quality of life. There are still unresolved questions regarding the etiology and immunopathogenesis of autoimmune uveitis, and traditional high-throughput sequencing techniques fall short of adequately elucidatingits pathogenic mechanisms at the cellular level. With the continuous advancement of single-cell sequencing technology, an increasing number of studies are leveraging this approach to deeply investigate the pathogenesis of autoimmune uveitis, thereby offering new insights for identifying novel diagnostic and therapeutic targets. This paper reviews the latest applications of single-cell sequencing technology in exploring the pathogenesis of autoimmune uveitis. Through the utilization of this technology, researchers can gain a more comprehensive understanding of cellular-level changes in patients, providing robust support for the search for new therapeutic avenues. These studies offer new directions for the diagnosis and treatment of autoimmune uveitis and provide valuable information for the development of future therapeutic strategies and approaches.

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.

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.

Aims: Divided nevus of the eyelid is a congenital pigmented nevus that impacts eyelid function and aesthetics. While surgical excision and laser ablation are current treatment options, they have limitations when dealing with large lesions. This study aims to investigate the efficacy and safety of carbon dioxide (CO₂) laser excision treatment for divided nevus of the eyelid. Methods: This retrospective study included 10 patients (5 males, 5 females) with a mean age of 23.7 years (9-54 years). All underwent CO₂ laser excision and were followed up for 12 months. Treatment outcomes were assessed through clearance and recurrence rates, evaluated using digital photography. Postoperative complications were closely monitored throughout the 12-month follow-up period. Patient satisfaction was assessed using a comprehensive questionnaire. Results:All patients presented with unilateral divided nevus of the eyelid, with lesion diameters ranging from 25 to 50 mm and heights ranging from 0.3 to 6 mm (mean: 3.93 mm). Patients received between 1 and 5 laser treatment sessions. At the 12-month follow-up, a 100% clearance rate was achieved, with no recurrence observed in any patient. All patients maintained a continuous eyelid margin with acceptable irregularity. Complications were minimal, with partial eyelash loss in 8 patients, hyperpigmentation in 2 patients, and mild upper eyelid trichiasis in 1 patient. No severe complications, such as ectropion, eyelid margin notching, corneal erosion, or significant scar hypertrophy, were reported. All patients expressed being "very satisfied" with the functional and cosmetic outcomes in a questionnaire. Conclusions: CO₂ laser excision offers a simple, precise, and effective treatment approach for divided nevus of the eyelid. This innovative technique simplifies the treatment process, achieves excellent cosmetic outcomes, and eliminates the need for skin grafting, making it a promising option for the management of large divided nevus.

Aims: Divided nevus of the eyelid is a congenital pigmented nevus that impacts eyelid function and aesthetics. While surgical excision and laser ablation are current treatment options, they have limitations when dealing with large lesions. This study aims to investigate the efficacy and safety of carbon dioxide (CO₂) laser excision treatment for divided nevus of the eyelid. Methods: This retrospective study included 10 patients (5 males, 5 females) with a mean age of 23.7 years (9-54 years). All underwent CO₂ laser excision and were followed up for 12 months. Treatment outcomes were assessed through clearance and recurrence rates, evaluated using digital photography. Postoperative complications were closely monitored throughout the 12-month follow-up period. Patient satisfaction was assessed using a comprehensive questionnaire. Results: All patients presented with unilateral divided nevus of the eyelid, with lesion diameters ranging from 25 to 50 mm and heights ranging from 0.3 to 6 mm (mean: 3.93 mm). Patients received between 1 and 5 laser treatment sessions. At the 12-month follow-up, a 100% clearance rate was achieved, with no recurrence observed in any patient. All patients maintained a continuous eyelid margin with acceptable irregularity. Complications were minimal, with partial eyelash loss in 8 patients, hyperpigmentation in 2 patients, and mild upper eyelid trichiasis in 1 patient. No severe complications, such as ectropion, eyelid margin notching, corneal erosion, or significant scar hypertrophy, were reported. All patients expressed being "very satisfied" with the functional and cosmetic outcomes in a questionnaire. Conclusions: CO₂ laser excision offers a simple, precise, and effective treatment approach for divided nevus of the eyelid. This innovative technique simplifies the treatment process, achieves excellent cosmetic outcomes, and eliminates the need for skin grafting, making it a promising option for the management of large divided nevus.