Improving Patient Outcomes after Ocular Trauma (IPOOT): Eye injuries are a major cause of visual loss and often cause disfigurement, major lifestyle changes and loss of career. Eye injuries can be divided into closed and open globe injuries, of which that latter is more severe. After open globe eye injuries, visual outcomes are poor due to retinal cell death, scarring and a failure of neuronal regeneration. Little is known about the extent of retinal cell death after retinal injury, its mechanisms and potential strategies to reduce it.
Almost all open globe injuries require vitreo-retinal surgery. The main cause of poor outcomes after vitreo-retinal surgery for trauma or any other indication is proliferative vitreoretinopathy (PVR), a progressive intra-ocular scarring process, which occurs in 8.3% of eyes operated on for retinal detachment and 17% of eyes operated on after open globe injury.
PVR is characterised by the development of membranes that place traction on the retina and cause retinal detachment. There are currently no effective treatments to prevent the development of PVR and the only treatment is further surgery to remove the scar tissue and reattach the retina. There is thus a strong need for research in this area to improve our understanding of the pathogenesis of PVR and find new treatments. A number of recent studies have examined vitreous and sub-retinal fluid samples taken at the time of surgical repair for retinal detachments (excluding trauma patients) using multiplex beads, ELISA and RT-PCR and have found a series of alterations in cytokine levels which predict subsequent development of PVR including increased expression of interleukin-6, pigment epithelium-derived factor, macrophage migration inhibitory factor and a number of chemokines.
We are investigating PVR and cell death in patients with trauma and other more defined retinal pathologies such as retinal detachment, diabetic retinopathy, uveitis, macular holes and floaters (ERM). We plan to develop a biomarker screen to predict visual outcomes, complications and the potential for therapeutic interventions after vitreo-retinal surgery; evaluate the extent and mechanisms of cell death after ocular injury; and identify candidate molecules as therapeutic targets to treat or prevent PVR. Investigate the aetiology of PVR.
We are recruiting patients due to undergo vitreo-retinal surgery for a variety of conditions including rhegmatogenous retinal detachment, macular hole, trauma, uveitis, diabetic retinopathy and established PVR. Patients have baseline clinical examination, as part of routine clinical care and are followed up, also as part of standard care, at six months. We are collecting samples of ocular fluid (vitreous and aqueous) at the time of surgery that would otherwise be disposed of, along with blood and urine, and looking for metabolomics and cytokine changes that predict the development of PVR.
This study is ongoing but so far we have identified key biomarkers (Decorin and TGF-β) in the vitreous after retinal detachment, established PVR and developed PVR; some encouraging findings from cytokine measurements although more samples need to be analysed to increase the power of the study. We have had some reviews published and several papers being written up for publication which will inform future grant applications.