Local therapy plays a pivotal role in the management of noninfectious uveitis, providing targeted drug delivery with reduced systemic adverse effects. Advances in corticosteroid formulations and delivery routes have significantly improved therapeutic outcomes. Topical corticosteroids remain first-line for anterior uveitis, while periocular and intravitreal injections such as triamcinolone acetonide and dexamethasone implants (Ozurdex®) are effective for intermediate and posterior disease. Long-acting fluocinolone acetonide implants (Retisert®, Yutiq®) offer sustained control for chronic or recurrent cases, though ocular hypertension and cataract formation are common. The introduction of suprachoroidal corticosteroid delivery (Xipere®) allows precise posterior segment targeting with fewer anterior complications. Nonsteroidal intravitreal agents, including methotrexate and sirolimus, serve as steroid-sparing options, and topical immunomodulators such as cyclosporine and tacrolimus can be rarely used in chronic anterior uveitis. Emerging modalities like intravitreal biologics, nanocarrier systems, and gene-based delivery hold promise for long-term disease modulation. A tailored, evidence-based approach to local therapy can optimize inflammation control and visual outcomes in uveitis management.

Pyroptosis represents an important pathway to initiate immunogenic cell death (ICD) mediated by N-terminal fragment of gasdermin E (GSDME-N). Although chemodynamic therapy (CDT) has the potential to elicit pyroptosis, epigenetic silencing of gasdermin E (GSDME) in tumor cells commonly shifts cell fate toward immunologically silent apoptosis. Herein, we develop a mitochondria-targeted CDT agent (Mito-CA/TA NPs) that incorporates tetrachloro-p-benzoquinone (chloranil, CA) with transcriptional regulator triamcinolone acetonide (TA) for enhanced pyroptosis immunotherapy. The encapsulated CA facilitates chemodynamic conversion of intramitochondrial hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) under physiological pH, surmounting the acidic constraint of classical Fenton chemistry-based CDT. Simultaneously, H2O2-induced hydrophilic transformation of CA ensures TA release to rescue GSDME downregulation in cancer cells, reversing epigenetic silencing of GSDME. Intramitochondrial •OH generation by Mito-CA/TA NPs in situ disrupts mitochondrial integrity, leading to cytochrome c release and subsequent caspase-3 activation, which causes the proteolytic cleavage of transcriptionally upregulated GSDME into GSDME-N. Additionally, integrating •OH-responsive chemiluminescent functionality into Mito-CA/TA NPs enables real-time monitoring of •OH formation and chemodynamic immunotherapeutic processes. The coordinated action of GSDME restoration and in situ mitochondrial •OH generation potently triggers pyroptosis to stimulate systemic antitumor immune responses, offering a universal strategy for improving pyroptosis-based cancer immunotherapy.