Ocular diseases affect over 2.2 billion people globally, imposing a significant socioeconomic burden, with annual productivity losses estimated at US$411 billion. Conventional drug delivery methods—topical, local injection, and systemic administration—face challenges such as low bioavailability (< 5%), rapid clearance, and physiological barriers like the cornea and blood-retinal barrier (BRB). Nanomedicine offers promising solutions by enhancing drug bioavailability, prolonging release, and enabling targeted delivery. This review explores nanomedicine-based ophthalmic drug delivery systems, including organic nanomaterials (eg, liposomes, polymer micelles, dendrimers), inorganic nanomaterials (eg, metal nanoparticles, quantum dots), and biological components (eg, exosomes). These systems improve drug penetration, reduce administration frequency, and minimize toxicity, addressing conditions like dry eye disease, keratitis, glaucoma, uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vascular occlusion (RVO). For instance, Ocular Therapeutix (OTX)-TP, a sustained-release intracanalicular implant combining poly (ethylene glycol)-based hydrogel with travoprost-loaded poly (lactic acid) microspheres, has shown therapeutic efficacy lasting up to three months in the management of glaucoma and ocular hypertension in Phase III clinical trial. Additionally, a liposomal formulation of verteporfin, approved for the treatment of neovascular AMD, administered intravenously and activated by laser photodynamic therapy, demonstrates a durable response, with a marked reduction in treatment frequency from an average of 3.5 sessions in the first year to only 0.1 by the fifth year post-diagnosis. Despite these advantages, challenges such as manufacturing costs, potential toxicity, and limited clinical translation persist. Future advancements in nanomedicine hold potential for personalized, non-invasive ocular therapies, revolutionizing ophthalmology.

Age-related macular degeneration (AMD) is the leading cause of blindness; however, its underlying pathogenesis remains unclear. This study investigated the role of the neuropeptide VF (NPVF) in AMD. Transcriptome profiling in retinal-choroid tissues was analyzed using a public dataset. There was an increase in NPVF expression in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD. Serological validation was conducted to verify the expression of NPVF in 30 wet AMD patients and 30 controls, and a statistically significant increase in serum NPVF concentration was observed in wet AMD patients. The role of NPVF in AMD was then investigated through in vitro experiments involving the overexpression of NPVF in a human retinal pigment epithelium (RPE) cell line. Overexpression of NPVF resulted in a marked upregulation of hypoxia-inducible factor-1α (HIF-1α), a key regulator implicated in the pathogenesis of AMD and associated neovascularization, and further promotes the secretion of vascular endothelial growth factor and enhances endothelial tube formation. By integrating transcriptomic and metabolomic data, it was found that aldehyde dehydrogenase 2 (ALDH2) was upregulated, whereas its substrate, D-glycerate, was downregulated in NPVF-overexpressing RPE cells. Further experimental validation confirmed that NPVF regulates HIF-1α expression through the ALDH2/D-glycerate axis. In summary, the present findings suggest that NPVF contributes to AMD pathogenesis via the ALDH2/D-glycerate/HIF-1α pathway.

Background: To determine the clinical characteristics and molecular genetic background responsible for USH2A mutations associated with nonsyndromic retinitis pigmentosa (RP) in five Chinese families, a retrospective cross‐sectional study was performed.Methods: Data on detailed history and comprehensive ophthalmological examinations were extracted from medical charts. Genomic DNA was sequenced by whole‐exome sequencing. The pathogenicity predictions were evaluated by in silico analysis. The structural modeling of the wide‐type and mutant USH2A proteins was displayed based on the I‐Tasser software.Results: The ultra‐wide‐field fundus imaging showed a distinctive pattern of hyperautofluorescence in the parafoveal ring with macular sparing. Ten USH2A variants were detected, including seven missense mutations, two splicing mutations, and one insertion mutation. Six of these variants have already been reported, and the remaining four were novel. Of the de novo mutations, the p.C931Y and p.G4489S mutations were predicted to be deleterious or probably damaging; the p.M4853V mutation was predicted to be neutral or benign; and the IVS22+3A>G mutation was a splicing mutation that could influence mRNA splicing and affect the formation of the hairpin structure of the USH2A protein.Conclusions: Our data further confirm that USH2A protein plays a pivotal role in the maintenance of photoreceptors and expand the spectrum of USH2A mutations that are associated with nonsyndromic RP in Chinese patients.

Macular neovascular diseases can cause severe vision loss. A newly approved anti—VEGF drug Conbercept has shown good efficacy and safety in rigorous random controlled trials (RCT), however, it cannot fully reflect the clinical application of Conbercept in real world clinical practice. Moreover, anti-VEGF drugs are expensive and often require multiple treatments, and some patients have poor or even no response to the drugs,this resulted enormous waste of medical resources. Therefore, how to find out those patients who have good response, and how to develop individualized therapeutic regimen in real world need to be urgently investigated in the aspect of pharmacogenomics and pharmacometabolomics. This study is a multicenter, prospective, observational study of Conbecept treating macular neovascular diseases in China. Patients suffered from age-related macular degeneration, polypoidal choroidal vasculopathy, and pathological myopia who already planned to receive Conbercept treatment will be recruited. We aimed to enroll more than 5000 patients from 43 ophthalmic centers in China. Patients’ clinical data and blood samples will be collected during the one-year follow-up period. Finally, the safety and efficacy of Conbercept, and the potential predictors of patients’ response to Conbercept will be investigated by pharmacogenomics and pharmacometabolomics analysis. This study will provide important data of Conbercept in treating macular neovascular diseases in real world. Besides, finding the predictor of patients’ response will help doctor make more precise individualized therapeutic regimens. ClinicalTrials.gov, NCT03128463 . Registered on 9 March 2017.