Primary rhegmatogenous retinal detachment (RRD) is one of the most
common ophthalmic emergencies. RRD is caused by a full thickness break in
the retina which initiates separation of the neurosensory retina from the
underlying retinal pigment epithelium. The subsequent accumulation of fluid
within this potential space extends the area of detachment and causes visual
loss.
Previous assessments of RRD incidence have demonstrated large differences
in case definition and methodology, with incidence estimates varying 3-fold
geographically and in different time periods. To date there have been no
systematic or prospective incidence estimates of primary RRD in the U.K. In
this thesis I present the findings of a 2-year epidemiology study that
prospectively aimed to recruit all incident cases of primary RRD diagnosed in
Scotland. Case recruitment from consenting participants comprised a
detailed questionnaire and a blood sample. In this thesis, I present the
findings of the Scottish retinal detachment study that examined the
incidence, demographic features, temporal incidence trends, as well as
clinical and socio-economic associations of primary RRD in Scotland. From
the clinical and genetic resource I assembled, I calculated the first
population based estimate of the sibling recurrence risk ratio for RRD and
designed and assisted in the analysis of the first case-control genome wide
association study of this condition.
Results from this study have estimated the annual incidence of primary RRD
in Scotland to be 12.05 per 100,000 population. Based on this estimate,
there are approximately 7,300 new cases annually in the United Kingdom.
RRD incidence increases with age, is more common in men and right eyes,
and is strongly associated with socio-economic affluence. In addition, using
hospital episode data, the overall age-standardised incidence of RRD in
Scotland was shown to be steadily increasing since 1987 with an average
annual increase of 1.9%.
Analysis of the clinical findings highlighted that the majority of RRD cases
are caused by more than one retinal break; an important consideration for
appropriate surgical management. Ocular trauma, previous cataract surgery,
family history, and retinal degeneration are important predisposing features.
In addition, over a 2 year period approximately 7% of individuals will suffer
a RRD in the fellow eye representing an important risk of bilateral visual
loss.
Furthermore, I demonstrate that the risk of having an affected sibling with
RRD is increased 2-fold given that one sibling has had the condition,
substantiating a genetic component to the pathogenesis of this condition. In
the final aspect of this thesis I will present the design and analysis of a two
stage case-control genome-wide association study examining the role of
common genetic variants and selected candidate genes in predisposing to
RRD development