Age‐related macular degeneration (AMD), especially wet AMD with choroidal neovascularization (CNV), commonly causes blindness in older patients and disruption of the choroid followed by second‐wave injuries, including chronic inflammation, oxidative stress, and excessive matrix metalloproteinase 9 (MMP9) expression. Increased macrophage infiltrate in parallel with microglial activation and MMP9 overexpression on CNV lesions is shown to contribute to the inflammatory process and then enhance pathological ocular angiogenesis. Graphene oxide quantum dots (GOQDs), as natural antioxidants, exert anti‐inflammatory effects and minocycline is a specific macrophage/microglial inhibitor that can suppress both macrophage/microglial activation and MMP9 activity. Herein, an MMP9‐responsive GOQD‐based minocycline‐loaded nano‐in‐micro drug delivery system (C18PGM) is developed by chemically bonding GOQDs to an octadecyl‐modified peptide sequence (C18‐GVFHQTVS, C18P) that can be specifically cleaved by MMP9. Using a laser‐induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti‐inflammatory action followed by antiangiogenic effects. Moreover, C18PGM combined with antivascular endothelial growth factor antibody bevacizumab markedly increases the antiangiogenesis effect by interfering with the “inflammation‐MMP9‐angiogenesis” cascade. The prepared C18PGM shows a good safety profile and no obvious ophthalmic or systemic side effects. The results taken together suggest that C18PGM is an effective and novel strategy for combinatorial therapy of CNV.

Rationale: Angle-closure glaucoma secondary to iridocorneal endothelial syndrome (ICE) is challenging to treat, especially in patients who have already undergone multiple surgical procedures. Long-term success is difficult to achieve with traditional filtration surgery again. This case report describes a novel nonbleb-dependent surgery for managing such a young patient. Patient concerns: A 30-year-old male with glaucoma secondary to ICE was referred to West China Hospital, Sichuan University for uncontrolled intraocular pressure following multiple failed filtering surgeries under maximum topical antiglaucoma medications in his right eye. Diagnoses: The patient was diagnosed with angle-closure glaucoma secondary to ICE in the right eye based on a series of ophthalmic examinations. Interventions: Penetrating canaloplasty was performed to manage glaucoma secondary to ICE in the right eye. Outcomes: The patient’s visual acuity improved, the intraocular pressure was reduced to 11 to 15 mm Hg through 30 months of follow-up, and no antiglaucoma medication or additional surgical procedures were needed. Lessons: Penetrating canaloplasty could be considered as an option for the treatment of refractory angle-closure glaucoma secondary to ICE with extensive angle adhesion.

The Wuerzburg bleb classification system (WBCS) is an established tool for evaluating filtering blebs, while anterior segment optical coherence tomography (ASOCT) provides detailed information on inner bleb structure. The present study aimed to investigate the clinical value of ASOCT-assisted WBCS following trabeculectomy (TRAB). The present prospective, observational study included eyes that underwent TRAB. Bleb assessments using the WBCS were based on the image acquired by ASOCT. The WBCS scores were assessed at postoperative week 2 and postoperative month (POM) 1, 2, 3, 6 and 12. The surgical outcomes at 1 year were determined as success or failure. Spearman's analysis explored the correlation of WBCS scores with intraocular pressure (IOP) and surgical outcome. A total of 32 eyes from 32 patients were included in the present study. The WBCS total score significantly correlated with IOP at POM 1, 2, 3, 6 and 12 (P<0.05). For single parameters, microcysts demonstrated a good correlation with IOP at POM 1, 2, 3, 6 and 12 (P<0.05). The WBCS total score correlated well with surgical outcome at POM 2, 3, 6 and 12 (P≤0.005). Microcysts, vascularity and encapsulation significantly correlated with surgical outcomes (P<0.05). The results of the present study suggest that ASOCT-assisted WBCS is a simple and effective measurement system for blebs after TRAB in clinical practice, which correlates well with IOP and surgical outcomes. Blebs with a higher WBCS total score and microcysts score in the early postoperative period, such as at POM 2 and 3, are less likely to have surgical failure in the long term.

Glaucoma is the leading cause of irreversible blindness globally and is associated with retinal ganglion cell (RGC) death. Brain-derived neurotrophic factor (BDNF) is a potent neurotrophin that promotes neuronal survival via its receptor, tropomyosin receptor kinase B (TrkB) encoded by NTRK2. Our current understanding of the mechanism of action and therapeutic potential of the BDNF pathway is limited by the lack of knowledge of its interaction with TrkB at atomic resolution. We developed an artificial intelligence (AI) model to predict the three-dimensional protein structures of BDNF and TrkB, as well as their interaction. The AI model was further applied to compare smallmolecule drugs that mimic BDNF-TrkB interaction, leading to the identification of 7,8-dihydroxyflavone (DHF) as an agonist of TrkB. We verified the neuroprotective effects of DHF in an in vivo acute glaucoma model in which RGC apoptosis caused by acute elevation of intraocular pressure was prevented by the intraocular application of DHF and to a lesser extent by BDNF. Our results provide AI-enabled prediction of ligand-receptor interactions between BDNF and TrkB at the atomic level and demonstrate the great potential for AI-enabled drug discovery.