Danny Mitry

The epidemiology of rhegmatogenous retinal detachment: geographical variation and clinical associations.

Aims/Background Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition. Obtaining an accurate estimate of RRD incidence in the population is essential in understanding the healthcare burden related to this disorder. Methods A systematic review of all population-based epidemiology studies of RRD published between January 1970 and January 2009 from Medline database searches was performed. Results RRD incidence demonstrates significant geographical variation and its incidence has been reported to be between 6.3 and 17.9 per 100 000 population. For studies with a sample size >300 the median annual incidence per 100 000 population was 10.5 (IQR 8.1–13.2) and the mean proportion of bilateral RRD was 7.26%. Overall, the mean prevalence of lattice degeneration was 45.7±20.3% and myopia was 47.28±12.59%. Conclusions Estimates of RRD incidence have varied threefold, but inclusion criteria and other design features have differed across studies making direct comparisons difficult. The overall incidence of RRD is not yet well established: more incidence studies of adequate methodology are needed to explore temporal changes in incidence. RRD incidence varies with ethnicity and is strongly associated with increasing age, myopia and certain vitreo-retinal degenerations. Due to changes in cataract surgery trends, the proportion of pseudophakic RRD presenting to specialised centres appears to be increasing.

The epidemiology and socioeconomic associations of retinal detachment in Scotland: a two-year prospective population-based study.

PURPOSE Rhegmatogenous retinal detachment (RRD) is a common ophthalmic emergency. Population-based data on primary RRD incidence has been variable, with large differences reported. This study is the first large-scale prospective examination of the incidence of primary RRD in the United Kingdom. METHODS The authors established a two-year prospective, population-based observational study recruiting all cases of primary RRD in Scotland. The annual incidence was calculated and analyzed in relation to age, sex, refractive error, and lens status. A national, population-based tool, the Scottish Index of Multiple Deprivation (SIMD), was used to examine the socioeconomic distribution of all incident cases. RESULTS A total of 1244 cases were identified during the study period from a population of 5,168,500 yielding an annual incidence of 12.05 per 100,000 population (95% confidence interval, 11.35-12.70). The age-specific incidence increased to a peak in both sexes in the 60- to 69-year age group. RRD was significantly more frequent in males than in females (14.70 vs. 8.75 per 100,000; P < 0.001). Of the cases without previous intraocular surgery, 53.2% were myopic, with a spherical equivalent refractive error > -1 D, 23.4% had undergone cataract surgery, and 10.4% had sustained traumatic injury. A strong association was found between RRD incidence and affluence, with a significant rising trend across quintiles of deprivation. CONCLUSIONS The estimated annual incidence of primary RRD in Scotland is 12.05 per 100,000. Based on this estimate, there are approximately 7300 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 affluence.

The Predisposing Pathology and Clinical Characteristics in the Scottish Retinal Detachment Study

PURPOSE To describe the predisposing pathology and clinical features of all incident cases of rhegmatogenous retinal detachment (RRD) recruited in Scotland during a 2-year period. DESIGN Prospective surveillance study of incident cases of RRD. PARTICIPANTS All incident cases of RRD recruited as part of the Scottish Retinal Detachment Study. METHODS During a 2-year period, we coordinated a comprehensive system in which every case of primary RRD presenting to 1 of 6 vitreoretinal surgical sites in Scotland was examined and approached for study inclusion. MAIN OUTCOME MEASURES Rhegmatogenous retinal detachment incidence, predisposing features, and clinical characteristics. RESULTS A total of 1202 cases were recruited. Detailed clinical information was available on 1130 (94%) of cases. By causative break, the proportions of RRD were horseshoe tear (HST) associated with posterior vitreous detachment (PVD) in 86.2%, giant retinal tear (GRT) and PVD in 1.3%, non-PVD round hole (RH) in 4.9%, retinal dialysis in 5.9%, and retinoschisis RRD in 1.6%. One in 10 cases reported significant ocular trauma. One in 5 cases were pseudophakic. Round hole RRD more frequently presented with multiple retinal breaks compared with HST RRD (67.8% vs. 48.7%; P = 0.003). In PVD-associated RRD, 56.1% (95% confidence interval [CI], 53.8-58.3) of breaks were identified in the superotemporal retina. In non-PVD RRD, 54.6% (95% CI, 47.9-61.1) of breaks were inferotemporal, followed by superotemporal in 34.9% (95% CI, 28.7-41.5). Lattice degeneration was present in 18.7% of affected eyes and more common in RH RRD (35.7%) than in HST RRD (19.3%) (P = 0.003). Seven percent reported an affected first-degree relative, and these cases were significantly more myopic than nonfamilial cases. CONCLUSIONS More than 85% of RRD cases are associated with PVD and related tractional tears. Non-PVD RH RRD occurred in younger and more myopic individuals. The majority of cases are caused by more than 1 retinal break, and the macula is affected in more than 50% at presentation. Ocular trauma, previous cataract surgery, family history, and lattice degeneration are important predisposing features.

Pathogenesis of rhegmatogenous retinal detachment: predisposing anatomy and cell biology

Background: The pathogenesis of rhegmatogenous retinal detachment is complex, and our knowledge of the exact mechanism of vitreoretinal attachment and detachment remains incomplete. Methods: We performed a Medline, Ovid, and EMBASE search using search words rhegmatogenous, retinal detachment, vitreous, and retinal adhesion. All appropriate articles were reviewed, and the evidence was compiled. Results: Cortical vitreous contains fibrillar collagens type II, V/XI, and IX. The inner limiting membrane of the retina contains collagens type I, IV, VI, and XVIII as well as numerous other glycoproteins and potential adhesion molecules. The distribution and age-related changes in the structure of these molecules play an important role in the formation of a retinal break, which may compromise and disrupt the normal mechanisms of neurosensory retinal adhesion. Conclusion: Rhegmatogenous retinal detachment development is intimately related to changes in the fibrillar structure of the aging vitreous culminating in posterior vitreous detachment with regions of persistent and tangential vitreoretinal traction predisposing to retinal tear formation. A complex interplay of factors such as weakening of vitreoretinal adhesion, posterior migration of the vitreous base, and molecular changes at the vitreoretinal interface are important in predisposing to focal areas of vitreoretinal traction precipitating rhegmatogenous retinal detachment. Once formed, the passage of liquefied vitreous through a retinal break may overwhelm normal neurosensory-retinal pigment epithelium adhesion perpetuating and extending detachment and causing visual loss. To understand the molecular events underlying rhegmatogenous retinal detachment so that new therapies can be developed, it is important to appreciate the structural organization of the vitreous, the biology underlying vitreous liquefaction and posterior vitreous detachment, and the mechanisms of vitreoretinal attachment and detachment.

Surgical outcome and risk stratification for primary retinal detachment repair: results from the Scottish Retinal Detachment study

Objectives To report the early surgical outcome, risk of failure and predictive value of rhegmatogenous retinal detachment (RRD) classification based on all participants in the Scottish Retinal Detachment study. Methods Over 2 years, all incident cases of RRD in Scotland were approached for recruitment. Early postoperative success was defined as an attached retina following one procedure with a minimum follow-up of 6–8 weeks. Using a regression model, the influence of clinical factors on the failure risk was estimated and the sensitivity and specificity of the Royal College of Ophthalmologists (RCOphth) grading for RRD and the vitrectomy in retinal detachment stratification risk formula (VR-SRF) in predicting operative failure were assessed. Results Primary outcome data were available for 86.2% (975/1130) of patients. The overall primary success rate was 80.8% (95% CI 78.1 to 83.3%). The presence of preoperative proliferative vitreoretinopathy of any degree and each additional clock hour of detachment increased the risk of failure by an OR of 2.4 and 1.13 respectively (p<0.05). A specificity of >95% in predicting early surgical failure was noted for highly complex RRDs according to the VR-SRF formula and the RCOphth classification. Conclusions Consistent with previous series, the overall early success rate of RRD repair was 80% after one operation. The type of surgical repair did not influence overall success rates. Significant predictors of failure are the presence of preoperative proliferative vitreoretinopathy of any grade and the extent of detachment. The analytical value of current classification systems in predicting failure is most useful in complex RRDs.

Descemet Stripping Automated Endothelial Keratoplasty After Failed Penetrating Keratoplasty: Survival, Rejection Risk, and Visual Outcome

IMPORTANCE Descemet stripping automated endothelial keratoplasty (DSAEK) for isolated endothelial dysfunction has become the preferred surgical option for many corneal surgeons. However, there are limited large-scale reports on DSAEK survival and clinical variables affecting the risk of rejection and failure after failed penetrating keratoplasty (PK). OBJECTIVE To report the survival, risk factors for graft rejection and failure, and visual outcome of DSAEK after failed PK. DESIGN, SETTING, AND PARTICIPANTS A multicenter retrospective interventional case series included patients recruited from 6 tertiary referral surgical centers: 3 in the United States, 2 in Europe, and 1 in Asia. A total of 246 consecutive eyes (246 patients) that underwent DSAEK after failed PK, with a minimum follow-up period of 1 month, was included. Data comprising demographic details, preoperative and postoperative risk factors, time to rejection, time to failure, and corrected distance visual acuity were collected. MAIN OUTCOMES AND MEASURES Cumulative probability of graft survival, hazard ratio estimates for survival, and corrected distance visual acuity were determined. RESULTS The mean (SD) recipient age was 63.2 (16.6) years and the median follow-up period was 17 months (interquartile range, 6-30 months). One-third of the grafts (n = 82) had follow-up data for more than 2 years; 18.3% had more than 1 failed PK before DSAEK. In total, 19.1% (47 of 246) of DSAEK grafts failed. The cumulative probability of DSAEK survival after a failed PK was 0.89 (95% CI, 0.84-0.92), 0.74 (95% CI, 0.64-0.81), and 0.47 (95% CI, 0.29-0.61) at 1 year, 3 years, and 5 years, respectively. Based on multivariate analysis, significant preoperative risk factors for failure were young recipient age (hazard ratio [HR], 5.18 [95% CI, 1.57-17.18]), previous tube filtration surgery (HR, 5.23 [95% CI, 1.47-7.33]), and rejection episodes before PK failure (HR, 3.28 [95% CI, 1.47-7.33]); single-surgeon centers had a protective effect. Any rejection episode prior to PK failure was a significant predictor of post-DSAEK rejection, which in turn was a significant predictor of DSAEK failure. After a median follow-up of 17 months, 33.3% of the grafts achieved 0.3 or greater logMAR (20/40) corrected distance visual acuity. CONCLUSIONS AND RELEVANCE Descemet stripping automated endothelial keratoplasty after failed PK combines greater wound stability and reduced suture-related complications, with visual outcomes and graft survival rates comparable to those of a second PK.

Temporal trends in retinal detachment incidence in Scotland between 1987 and 2006

Aim Rhegmatogenous retinal detachment (RRD) is a common and sight-threatening condition. The reported incidence of RRD has varied considerably in published literature and few studies have examined the temporal trends in incidence rate over a long time period. Our aim is to examine the time trends of primary RRD in Scotland. Methods We obtained linked hospital episode statistics data for all patients admitted with a primary diagnostic code of RRD in Scotland between 1987 and 2006. Using this database as an estimate of RRD incidence, we calculated the annual age- and sex-specific incidence rates of RRD in Scotland. Log-linear Poisson regression analysis was used to explore age, period and cohort trends. Results The overall age-standardised incidence of RRD in Scotland has steadily increased from 9.36 per 100 000 (95% CI 8.19 to 10.53) in 1987 to 13.61 per 100 000 (95% CI 12.25 to 14.97) in 2006 with an average annual increase of 1.9% (p<0.001) during the 20-year period. Men have been affected more frequently than women in all age groups with a significant temporal trend towards earlier age of onset. The peak incidence of RRD in men and women is in the sixth decade of life. No significant period or recent birth cohort trend effects were found. Conclusions The estimated incidence of RRD is within the range reported from previous population-based studies worldwide. The rise in RRD incidence between 1987 and 2006 is attributed in part to the changing demographic in Scotland. There is an increasing sex imbalance in incidence, with men being affected more frequently and at a younger age.

Long-term visual acuity and the duration of macular detachment: findings from a prospective population-based study

Aim To report the long-term visual outcome of a multicentre prospectively recruited cohort of macula-off rhegmatogenous retinal detachments (RRD) Methods The Scottish retinal detachment study was a prospectively recruited study that recruited all incident cases of primary RRD in Scotland over a 2-year period (2007–2009). All patients with a macula-off RRD from four participating sites were invited for clinical examination at 6 weeks, 3 months, 6 months and 1 year after the initial surgery. Using a joinpoint model we estimated the effect of duration of macular detachment on final visual outcome. Results In total, there were 291 patients with macula-off RRD without pre-existing retinal disease who had successful repair after one operation. 65.9% achieved a final visual acuity (VA) of 0.48 logMAR(6/18). Our model identified two time points (day 8 (95% CI 3 to 15 days) and (day 21 (95% CI 6 to 26 days)) after which there was a statistically significant worsening in final VA. Conclusions Our study suggests that the majority of patients with macula-off RRD successfully repaired with one operation will achieve a VA of 6/18 or better at final follow-up. After 8 days of macular detachment, the final visual outcome may be adversely affected and, thus, operative repair within this period is desirable. Duration of macular detachment of ≤8 days demonstrated a continuing improvement in VA for up to 1 year, a finding which was not found in macula detachments of longer duration.

Genome-wide association study identifies genetic risk underlying primary rhegmatogenous retinal detachment

Rhegmatogenous retinal detachment (RRD) is an important cause of vision loss and can potentially lead to blindness. The underlying pathogenesis is complex and incompletely understood. We applied a two-stage genetic association discovery phase followed by a replication phase in a combined total of 2833 RRD cases and 7871 controls. The discovery phase involved a genome-wide association scan of 867 affected individuals and 1953 controls from Scotland, followed by genotyping and testing 4347 highest ranking or candidate single nucleotide polymorphisms (SNPs) in independent sets of cases (1000) and controls (2912) of Dutch and British origin. None of the SNPs selected reached a Bonferroni-corrected threshold for significance (P < 1.27 × 10(-7)). The strongest association, for rs12960119 (P = 1.58 × 10(-7)) located within an intron of the SS18 gene. Further testing was carried out in independent case-control series from London (846 cases) and Croatia (120 cases). The combined meta-analysis identified one association reaching genome-wide significance for rs267738 (OR = 1.29, P = 2.11 × 10(-8)), a missense coding SNP and eQTL for CERS2 encoding the protein ceramide synthase 2. Several of the top signals showing suggestive significance in the combined meta-analysis encompassed genes with a documented role in cell adhesion or migration, including SS18, TIAM1, TSTA3 and LDB2, which warrant further investigation. This first genetic association study of RRD supports a polygenic component underlying RRD risk since 27.4% of the underlying RRD liability could be explained by the collective additive effects of the genotyped SNP from the discovery genome-wide scan.

Causes of certifications for severe sight impairment (blind) and sight impairment (partial sight) in children in England and Wales

Aim To explore and describe trends in the principal disorders/conditions (‘cause’) for severe sight impairment (SSI) (blind) and sight impairment (SI) (partial sight) certification in children in England and Wales since 1999. Methods We obtained certification data for SI and SSI from a national database for all individuals aged 16 years or less at the time of certification in England and Wales for the years 1999/2000 and for the years 2007/2008–2009/2010. Results In total, there were 861 certifications in the year 1999/2000, rising to 1040 certifications in 2009/2010. The commonest single causes of SSI certification in 1999/2000 were cerebral visual impairment (23.2%) and optic nerve disorders (23.2%). The commonest single causes of SI certification in the same year comprised nystagmus (16.7%) and optic nerve disorders (15.5%). Cerebral visual impairment was the commonest single cause of SSI in children in England and Wales annually between 2007/2008 and 2009/2010 accounting for 21%–31% of certifications. The commonest causes of SI certification in 2009/2010 were congenital globe anomalies (18.4%) and retinal dystrophy (16.6%). The proportion of SI and SSI due to optic nerve disorders has decreased since 1999/2000. Conclusions Our findings suggest that in England and Wales, cerebral visual impairment is now the commonest cause of paediatric SSI certification and hereditary retinal dystrophy and congenital globe anomalies are the commonest causes of SI certification.