The prevention and pathogenesis of retinal detachment

Retinal detachment contributes to nearly 500 new blind registrations in the United Kingdom each year. In contrast to other retinal blinding disorders, blindness from retinal detachment is potentially avoidable with a better understanding of the mechanisms defining sub-groups at risk of the event. The majority of retinal detachments are rhegmatogenous, resulting from retinal tears that occur during the process of posterior vitreous detachment. Posterior vitreous detachment is generally considered to be a common, age-related synchitic and syneretic degeneration of the vitreous gel. However, this current understanding fails to explain the significant number of elderly individuals who never undergo posterior vitreous detachment, or the number of young patients with co-existing intraocular pathology who do. Furthermore, the factors distinguishing the majority of patients who undergo ‘physiological’ posterior vitreous detachment (with no associated retinal tears or detachment) from the minority of patients who suffer ‘pathological’ posterior vitreous detachment (associated with retinal tears and/or detachment), remain poorly understood. The objectives of this research project were two-fold: Firstly, to investigate the hypothesis that appropriate prophylactic intervention could reduce blindness from retinal detachment if a high-risk sub-group of individuals were defined. This clinical study retrospectively evaluated a group of molecularly confirmed type 1 Stickler syndrome patients, a homogenous cohort who have been identified to carry the greatest risk of inherited retinal detachment at the time of their posterior vitreous detachment. Multiple analyses comparing patients and eyes that received prophylactic intervention with appropriate controls, consistently demonstrated that the Cambridge Prophylactic Cryotherapy protocol is safe and markedly reduces the risk of retinal detachment in type 1 Stickler syndrome. Secondly, to investigate the anatomical and cellular mechanisms of posterior vitreous detachment in the wider population. This laboratory study sought to isolate and immunohistochemically phenotype posterior hyaloid membranes and associated laminocytes from donor human globes that had undergone ‘physiological’ posterior vitreous detachment. The isolated posterior hyaloid membranes were demonsatrated to be distinct basement membranes composed of type IV collagen and laminin, and morphologically correlated with posterior hyaloid membranes observed clinically in patietns presenting with posterior vitrous detachment. Furthermore, the laminocyte cell population adherent to the vitreal aspect of the posterior hyaloid membrane, was identified to express macrophage cell markers.