Neurodegeneration and neuroprotection in retinal detachment.

Retinal detachment (RD) occurs when the neurosensory retina separates from the retinal pigment epithelium (RPE). The most frequent type, rhegmatogenous retinal detachment (RRD), is caused by full-thickness retinal breaks that typically arise from vitreoretinal traction during posterior vitreous detachment. These breaks permit fluid to enter the subretinal space, leading to acute and often severe visual loss. Key risk factors include aging, myopia, pseudophakia, and the occurrence of posterior vitreous detachment. RRD constitutes a surgical emergency. Modern vitreoretinal procedures achieve high rates of anatomic reattachment; however, functional recovery remains highly variable. A major reason is that photoreceptor loss begins rapidly after detachment, driven by apoptosis, necroptosis, and inflammatory pathways, leading to irreversible damage even after successful surgical repair. This has stimulated interest in adjunctive neuroprotective strategies. Experimental and early clinical data suggest that repurposed agents such as tauroursodeoxycholic acid (TUDCA), ursodeoxycholic acid (UDCA), and iron chelators may preserve photoreceptor integrity. A multicenter randomized controlled trial (NCT06294847) is currently investigating oral UDCA in patients with macula-off RRD. Given that photoreceptor degeneration is a major determinant of limited visual recovery, combining surgery with neuroprotective therapies targeting cell-survival pathways may represent an important advance in improving postoperative visual outcomes.