Tiarnan D. L. Keenan

Time trends and geographical variation in cataract surgery rates in England: study of surgical workload.

Background: Phacoemulsification, day case surgery and Action on Cataracts have increased the national capacity for cataract surgery in England. Aims: To examine time trends and geographical variation in rates of cataract surgery, and to determine whether there is evidence of overcapacity in current levels of surgical provision. Methods: Hospital episode statistics (HES), the hospital inpatient enquiry (HIPE) and the Oxford record linkage study (ORLS) were analysed for cataract admissions between the 1960s and 2003. Results: Annual rates of admission for cataract surgery in England rose 10-fold from 1968 to 2003: from 62 episodes per 100 000 population in 1968, through 173 in 1989, to 637 in 2004. The overall increase in cataract surgery was reflected by increases in every age group for both men and women. Geographical analysis showed that there was wide variation across local authority areas in annual rates of cataract surgery, from 172 to 548 people per 100 000 population in 1998–2003. The rate of surgery by local authority was positively correlated with the index of multiple deprivation (r2 = 0.24). Conclusion: The huge increase in cataract surgery over time and the wide geographical variation in rates, raise the question of whether there is now overcapacity for cataract surgery. High levels of social deprivation are associated with high rates of cataract surgery; this may be due to an increased prevalence of cataract or differences in referral patterns.

Trends in the Indications for Corneal Graft Surgery in the United Kingdom: 1999 Through 2009

OBJECTIVE To examine trends in the indications for corneal graft surgery in the United Kingdom. METHODS National Health Service Blood and Transplant data were analyzed for keratoplasty operations performed in the United Kingdom between April 1, 1999, and March 31, 2009, distinguishing the type of graft and the surgical indication. RESULTS The total number of annual keratoplasty operations increased from 2090 in 1999-2000 to 2511 in 2008-2009. Among these, the annual number of grafts performed for endothelial failure increased from 743 (35.6%) in 1999-2000 to 939 (37.4%) in 2008-2009. The performance of penetrating keratoplasty (PK) for endothelial failure decreased from 98.3% of all grafts in 1999-2000 to 46.6% of all grafts in 2008-2009, while the performance of endothelial keratoplasty increased from 0.3% of all grafts in 1999-2000 to 51.2% of all grafts in 2008-2009. The annual number of grafts performed for keratoconus increased from 514 (24.6%) in 1999 to 564 (22.5%) in 2008-2009. The performance of PK for keratoconus decreased from 88.4% of all grafts in 1999-2000 to 57.1% of all grafts in 2008-2009, while the performance of deep anterior lamellar keratoplasty increased from 8.8% of all grafts in 1999-2000 to 40.1% of all grafts in 2008-2009. The number of annual regraft operations increased from 249 (11.9%) in 1999-2000 to 401 (16.0%) in 2008-2009, most commonly for endothelial failure. In 2008-2009, PK regrafts (78.1%) far outnumbered endothelial keratoplasty regrafts (17.0%). CONCLUSIONS Endothelial failure is the most common indication for keratoplasty in the United Kingdom, and endothelial keratoplasty is performed more commonly than PK for this indication. The number of grafts performed for pseudophakic bullous keratopathy has remained stable, while the number of grafts performed for Fuchs endothelial dystrophy is likely to continue increasing. Keratoconus is the second most common indication for keratoplasty, and deep anterior lamellar keratoplasty numbers are approaching those for PK. Regraft surgery is the third most common indication for keratoplasty, required in most cases because of endothelial failure.

Mapping the differential distribution of glycosaminoglycans in the adult human retina, choroid and sclera

PURPOSE. To map the distribution of different classes of glycosaminoglycans (GAGs) in the healthy human retina, choroid, and sclera. METHODS. Frozen tissue sections were made from adult human donor eyes. The GAG chains of proteoglycans (PGs) were detected with antibodies directed against various GAG structures (either directly or after pretreatment with GAG-degrading enzymes); hyaluronan (HA) was detected using biotinylated recombinant G1-domain of human versican. The primary detection reagents were identified with FITC-labeled probes and analyzed by fluorescence microscopy. RESULTS. Heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), and HA were present throughout the retina and choroid, but keratan sulfate (KS) was detected only in the sclera. HS labeling was particularly strong in basement membrane-containing structures, the nerve fiber layer (NFL), and retinal pigment epithelium (RPE)-for example, intense staining was seen with an antibody that binds strongly to sequences containing 3-O-sulfation in the internal limiting membrane (ILM) and in the basement membrane of blood vessels. Unsulfated CS was seen throughout the retina, particularly in the ILM and interphotoreceptor matrix (IPM) with 6-O-sulfated CS also prominent in the IPM. There was labeling for DS throughout the retina and choroid, especially in the NFL, ganglion cell layer, and blood vessels. CONCLUSIONS. The detection of GAG chains with specific probes and fluorescence microscopy provides for the first time a detailed analysis of their compartmentalization in the human retina, by both GAG chain type and sulfation pattern. This reference map provides a basis for understanding the functional regulation of GAG-binding proteins in health and disease processes.

Trends in corneal graft surgery in the UK

Aims The aims of this study were to examine trends over time and regional variation in rates of corneal graft surgery in the UK. Methods The hospital in-patient enquiry (HIPE) and hospital episode statistics (HES) were analysed for keratoplasty admissions in England from 1971 to 2006. NHS Blood and Transplant (NHSBT) data were analysed for keratoplasty operations in the UK from 1999 to 2009. Results Annual rates of penetrating keratoplasty (PK) under HIPE and HES increased from 0.7 per 100 000 population (1971) to 3.9 (1992), then decreased to 3.1 (2006). Rates of lamellar keratoplasty (LK) increased from 0.1 (1971) to 0.9 (2006). Annual PK operations under NHSBT decreased from 1901 (1999/00) to 1473 (2008/9). Over the same period, deep anterior lamellar keratoplasty operations increased from 91 to 327 per year, while endothelial keratoplasty operations increased from 2 to 569 per year. Geographical analysis showed a wide variation across local authority areas in rates of keratoplasty around 1998–2004, especially for LK. Conclusion The total number of corneal graft operations performed in the UK has increased slowly over the past decade. The proportion of lamellar versus penetrating keratoplasty has increased, with LK performed at the highest rates in specialist centres distributed across the UK.

Mapping the Differential Distribution of Proteoglycan Core Proteins in the Adult Human Retina, Choroid, and Sclera

PURPOSE To examine the presence and distribution of proteoglycan (PG) core proteins in the adult human retina, choroid, and sclera. METHODS Postmortem human eye tissue was dissected into Bruchs membrane/choroid complex, isolated Bruchs membrane, or neurosensory retina. PGs were extracted and partially purified by anion exchange chromatography. Trypsinized peptides were analyzed by tandem mass spectrometry and PG core proteins identified by database search. The distribution of PGs was examined by immunofluorescence microscopy on human macular tissue sections. RESULTS The basement membrane PGs perlecan, agrin, and collagen-XVIII were identified in the human retina, and were present in the internal limiting membrane, blood vessel walls, and Bruchs membrane. The hyalectans versican and aggrecan were also detected. Versican was identified in Bruchs membrane, while aggrecan was distributed throughout the retina, choroid, and sclera. The cartilage link protein HAPLN1 was abundant in the interphotoreceptor matrix and sclera, while HAPLN4 (brain link protein 2) was found throughout the retina and choroid. The small leucine-rich repeat PG (SLRP) family members biglycan, decorin, fibromodulin, lumican, mimecan, opticin, and prolargin were present, with different patterns of distribution in the retina, choroid, and sclera. CONCLUSIONS A combination of proteomics and immunohistochemistry approaches has provided for the first time a comprehensive analysis of the presence and distribution of PG core proteins throughout the human retina, choroid, and sclera. This complements our knowledge of glycosaminoglycan chain distribution in the human eye, and has important implications for understanding the structure and functional regulation of the eye in health and disease.

Associations between age-related macular degeneration, Alzheimer disease, and dementia - record linkage study of hospital admissions

IMPORTANCE The potential association between age-related macular degeneration (AMD) and Alzheimer disease (AD) is uncertain and has implications for understanding disease pathogenesis, referral, and treatments. OBJECTIVES To determine whether individuals admitted to the hospital with AMD were significantly more or less likely to develop AD or dementia in the following years, as well as to assess whether people with AD or dementia were significantly more or less likely to be admitted to the hospital for AMD treatment in the years following diagnosis of dementia. DESIGN, SETTING, AND PARTICIPANTS An AMD cohort of 65,894 people was constructed from English National Health Service, linked hospital episode statistics from January 1, 1999, through February 28, 2011, by identifying computerized record abstracts for all people with an admission or day case care for AMD. A dementia cohort (168,092 people) and a reference cohort (>7.7 million people) were constructed in similar ways. MAIN OUTCOMES AND MEASURES Risk of AD or dementia following AMD and risk of AMD following AD or dementia. Rate ratios were calculated based on standardized rates of AD and dementia in the AMD cohort, as well as standardized rates of AMD in the AD and dementia cohort, relative to those in the reference cohort. RESULTS The risk of AD or dementia following AMD was not elevated. The rate ratio was 0.86 (95% CI, 0.67-1.08) for AD and 0.91 (0.79-1.04) for dementia. The likelihood of being admitted for AMD following AD or dementia was very low: the rate ratio was 0.04 (0.01-0.10) for people with AD and 0.07 (0.04-0.11) for those with dementia. CONCLUSIONS AND RELEVANCE These neurodegenerative conditions may share environmental risk factors and histopathologic features. However, considering AD and other dementia after AMD, their coexistence at the individual level is no different from that expected by chance. Our data also suggest that patients in England with dementia may be substantially less likely to receive AMD treatment. Further research is required to determine whether people with dementia receive appropriate investigation and treatment for AMD, as well as identify and address potential barriers.

Trends over time and geographical variation in rates of intravitreal injections in England

Aims The recent emergence of antivascular endothelial growth factor (anti-VEGF) drugs has led to increased numbers of patients undergoing intravitreal injection for age-related macular degeneration (AMD). The aims of this study were to report on trends over time and geographical variation in intravitreal injection rates in England, and consider the implications for publicly funded health services of introducing new and expensive treatments. Methods Hospital episode statistics were analysed for annual treatment rates of intravitreal injection between the NHS financial years of 1989/1990 and 2008/1999. Results Annual injection rates increased from 0.4 episodes (95% CI 0.37 to 0.49) per 100 000 population in 1989/1990 to 10.7 (10.4–11.0) in 2006/2007. Rates then rose exponentially to 59.5 (58.8–60.2) in 2008/2009, with increasing use of multiple injections per person. The largest growth in injection rates was found in older people, and for AMD. Numbers of treatment episodes increased from 203 (1989/1990) to 30 458 (2008/2009). Geographical analysis showed a very wide variation across local authority areas in injection rates, from 0.9 (0.2–2.2) to 42.2 (38.9–45.7) people per 100 000 population in 2005–2008. Conclusion Rates of intravitreal injection increased exponentially from 2006/2007. This followed the US Food and Drug Association licensing of ranibizumab for the treatment of neovascular AMD (2006), and its recommendation by National Institute for Health and Clinical Excellence (2008). This study demonstrates some of the major issues which arise with the emergence of expensive new treatments, including speed and cost of adoption, geographical variation in access, and implications for licensing, commissioning and health financing in an ageing society.

United Kingdom National Ophthalmology Database Study: Diabetic Retinopathy; Report 1: prevalence of centre-involving diabetic macular oedema and other grades of maculopathy and retinopathy in hospital eye services

AimsTo report estimates of the prevalence of diabetic retinopathy (DR) and maculopathy grades for a large cohort of patients managed by the UK hospital eye service (HES).MethodsAnonymised data were extracted from 30 UK NHS hospital trusts using a single ophthalmic electronic medical record (EMR) for the period from April 2000 to November 2010 to create the National Ophthalmology Database (NOD). From 2007, the EMR facilitated capture of a nationally agreed-upon standardised data set (DR Structured Assessment) relating to the presence or absence of clinical signs of DR and maculopathy. An algorithm in the software automatically calculated the Early Treatment of Diabetic Retinopathy Study grades of retinopathy and maculopathy.ResultsBetween 2007 and 2010, 307 538 patients had data on the NOD, with 76 127 (24.8%) patients having been recorded as having diabetes. The proportion of patients with diabetes who had a structured assessment increased from 50.7% (2007) to 86.8% (2010). In each NHS year, 12.6–20.6% of eyes with structured assessments had no DR; 59.6–67.3% had non-proliferative DR; and 18.3–20.9% had active or regressed proliferative DR. Clinically significant macular oedema was present in 15.8–18.1% of eyes, and in 8.7–10.0% of eyes, this involved the central macula.ConclusionThis study provides contemporary estimates of the prevalence of retinopathy and maculopathy grades in a large cohort of patients with diabetes managed by the UK HES. Centre-involving diabetic macular oedema, potentially amenable to anti-VEGF therapy, is present in the eyes of almost 10% of these patients. This information is useful for clinicians, health-care economists, and commissioners involved in planning and delivering diabetic eye services.

Trends in rates of primary angle closure glaucoma and cataract surgery in England from 1968 to 2004.

AimEyes that are predisposed to primary angle closure usually have a shallow anterior chamber secondary to a relatively forward position of the lens and progressive lens thickening with ageing. The aim of this study was to examine trends over time in rates of primary angle closure glaucoma (PACG) in England, and to compare these rates with rates of cataract surgery. MethodsHospital episode statistics and the hospital inpatient inquiry were analyzed for PACG as the main diagnosis between the years 1968 and 2004, and for cataract surgery over the same period. Age-specific and sex-specific rates of PACG and cataract surgery were calculated over 3 representative time periods. ResultsAnnual rates of patients with PACG did not change significantly from the late 1960s to the mid-1980s and then increased until the early 1990s before reaching a plateau; from 1999 to 2004, rates of patients with PACG declined significantly. From the 1980s to 2004, annual rates of patients undergoing cataract surgery increased significantly and substantially. In the recent period of decline in PACG, the decline was greatest in older age groups, whereas rates of cataract surgery increased significantly in all age groups for both men and women throughout the whole time period. ConclusionsRates of patients with PACG have started to decline in recent years, after a long period of increases in rates of patients undergoing cataract surgery. Although other explanations are possible, this lends support to the hypothesis that cataract surgery may reduce the likelihood of acute angle closure.

Age-Dependent Changes In Heparan Sulfate In Human Bruch’s Membrane: Implications For Age-Related Macular Degeneration

PURPOSE Heparan sulfate (HS) has been implicated in age-related macular degeneration (AMD), since it is the major binding partner for complement factor H (CFH) in human Bruchs membrane (BrM), and CFH has a central role in inhibiting complement activation on extracellular matrices. The aim was to investigate potential aging changes in HS quantity and composition in human BrM. METHODS Postmortem human ocular tissue was obtained from donors without known retinal disease. The HS was purified from BrM and neurosensory retina, and after digestion to disaccharides, fluorescently labeled and analyzed by reverse-phase HPLC. The HS and heparanase-1 were detected by immunohistochemistry in macular tissue sections from young and old donors, and binding of exogenously applied recombinant CCP6-8 region of CFH (402Y and 402H variants) was compared. RESULTS Disaccharide analysis demonstrated that the mean quantity of HS in BrM was 50% lower (P = 0.006) in old versus young donors (average 82 vs. 32 years). In addition, there was a small, but significant decrease in HS sulfation in old BrM. Immunohistochemistry revealed approximately 50% (P = 0.02) less HS in macular BrM in old versus young donors, whereas heparanase-1 increased by 24% in old macular BrM (P = 0.56). In young donor tissue the AMD-associated 402H CCP6-8 bound relatively poorly to BrM, compared to the 402Y form. In BrM from old donors, this difference was significantly greater (P = 0.019). CONCLUSIONS The quantity of HS decreases substantially with age in human BrM, resulting in fewer binding sites for CFH and especially affecting the ability of the 402H variant of CFH to bind BrM.