Severe Corneal Melt Post Trans-Scleral Cyclodiode in a Case of Neovascular Glaucoma Secondary to Coats Disease: A Case Report.

A novel case of neurotrophic keratitis and severe corneal melt requiring surgical management is presented 1 month following trans-scleral cyclodiode for Coats disease and neovascular glaucoma. Risk factors contributing to the complication include previous extracapsular cataract surgery, perioperative use of topical non-steroidal anti-inflammatories and dexamethasone/neomycin, as well as other topical drops containing preservatives such as benzalkonium chloride. Meticulous consideration of preoptimization of the ocular surface and rationalization of perioperative eye drop regimes is discussed.

Evaluating multidisciplinary glaucoma care: visual field progression and loss of sight year analysis in the community vs hospital setting.

BACKGROUND: A variety of shared care models have been developed, which aim to stratify glaucoma patients according to risk of disease progression. However, there is limited published data on the rate of glaucoma progression in the hospital vs community setting. Here we aimed to compare rates of glaucomatous visual field progression in the Cambridge Community Optometrist Glaucoma Scheme (COGS) and Addenbrooke's Hospital Glaucoma Clinic (AGC). METHODS: A retrospective comparative cohort review was performed. Patients with five or more visual field tests were included. Zeiss Forum software was used to calculate the MD progression rate (dB/year). Loss of sight years (LSY) were also calculated for both COGS and AGC. RESULTS: Overall, 8465 visual field tests from 854 patients were reviewed. In all, 362 eyes from the AGC group and 210 eyes from COGS were included. The MD deterioration rate was significantly lower in the COGS patients compared with the AGC group (-0.1 vs -0.3 dB/year; p < 0.0001). No patients in the COGS group were predicted to become blind within their lifetime by LSY analysis. Fifteen patients were at risk in the AGC group. CONCLUSION: This service evaluation shows that COGS is an effective scheme to stratify lower risk glaucoma patients, increasing the capacity within hospital eye services. COGS patients have a lower rate of visual field deterioration compared to AGC patients. Effective communication between community and tertiary schemes is essential to facilitate transfer of patients requiring further hospital management reliably and efficiently, with the potential for low-risk patients to be followed safely in the community.

Distribution and extent of electronic medical record utilisation in eye units across the United Kingdom: a cross-sectional study of the current landscape.

OBJECTIVES: Ophthalmology units across the UK vary widely in their adoption of electronic medical records (EMR). There is a lack of evidence to show the extent and progress of EMR adoption. The aim of this study was to capture a snapshot of the current landscape of EMR use, as a baseline for comparison in future studies. SETTING: An electronic survey questionnaire was sent to all NHS ophthalmology Units in the UK. PARTICIPANTS: A total of 104 National Health Service (NHS) ophthalmology units participated in the survey, which was carried out over 6 months from December 2013 to June 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Respondents were asked about technology usage pertaining to specific processes in the clinic workflow. This allowed us to determine the extent of EMR usage and details about current use or planned implementation by each unit. RESULTS: 77.6% (n=104) of NHS ophthalmology units responded. 45.3% (n=48) of units were currently using an EMR and a further 26.4% (n=28) of units plan to implement EMR within 2 years. 70.8% of units with a current EMR system use Medisoft. EMR is used by all clinicians in 37.5% and by all subspecialties offered at the unit in 27.0%. In 56.3%, new clinical notes are entered into EMR only by clinicians. All imaging devices are networked to EMR in 28.3%. In 46.7%, EMR is accessible by other specialties within the same hospital. 71.1% would recommend EMR to a colleague. CONCLUSIONS: EMR has the potential to address current limitations of patient information transfer and sharing in ophthalmology. It is pleasing to see a significant proportion of units already engaging with EMR or having plans to do so in the near future. However, differing EMR systems and lack of remote access mean further optimisation of these record systems are needed to allow data transfer between units.

Analysis of copy number variation at DMBT1 and age-related macular degeneration.

BACKGROUND: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. METHODS: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. RESULTS: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. CONCLUSIONS: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD.

Pre-operative intraocular pressure does not influence outcome of trabeculectomy surgery: a retrospective cohort study.

BACKGROUND: To investigate whether pre-operative intraocular pressure (IOP) predicts outcome of trabeculectomy surgery in patients with primary open angle glaucoma over a 3-year period of follow-up. METHODS: Retrospective cohort study, of a total of 61 patients (80 procedures) who had undergone trabeculectomy surgery after failed medical management at a single centre between 2000 and 2011. Patients were identified through surgical logbooks. A subsequent case note-review identified 61 patients (80 procedures) with primary open angle glaucoma (POAG). The primary outcome was success of trabeculectomy surgery, with failure defined as intraocular pressure (IOP) > 21 mmHg, ≤ 5 mmHg or not reduced by 20% at two consecutive follow-up visits 3-months post-operatively. Qualified success was defined as surgical success with the use of supplemental medical therapy. Secondary outcomes included visual acuity, Humphrey visual field MD, surgical complications and post-operative interventions. RESULTS: At 3 years, the odds ratio of failure was 0.93 per mmHg pre-operative IOP (95% C.I. 0.83-1.03, p = 0.15 Wald Χ (2) test), and the odds ratio of failure or qualified success was 0.96 (95% C.I. 0.89-1.04, p = 0.35). The incidence of surgical complications showed an odds ratio of 1.02 per mmHg pre-operative IOP (95% C.I. 0.95-1.10, p = 0.55 Wald Χ (2) test). The incidence of post-operative interventions showed an odds ratio of 1.01 per mmHg pre-operative IOP (95% C.I. 0.94-1.09, p = 0.80 Wald Χ (2) test). CONCLUSIONS: Pre-operative IOP does not predict success of trabeculectomy surgery in POAG patients during the first 3 years of follow-up. The incidence of surgical complications and post-operative interventions shows no association with pre-operative IOP.

Cambridge community Optometry Glaucoma Scheme.

BACKGROUND: With a higher life expectancy, there is an increased demand for hospital glaucoma services in the United Kingdom. DESIGN: The Cambridge community Optometry Glaucoma Scheme (COGS) was initiated in 2010, where new referrals for suspected glaucoma are evaluated by community optometrists with a special interest in glaucoma, with virtual electronic review and validation by a consultant ophthalmologist with special interest in glaucoma. PARTICIPANTS: 1733 patients were evaluated by this scheme between 2010 and 2013. METHODS: Clinical assessment is performed by the optometrist at a remote site. Goldmann applanation tonometry, pachymetry, monoscopic colour optic disc photographs and automated Humphrey visual field testing are performed. A clinical decision is made as to whether a patient has glaucoma or is a suspect, and referred on or discharged as a false positive referral. The clinical findings, optic disc photographs and visual field test results are transmitted electronically for virtual review by a consultant ophthalmologist. MAIN OUTCOME MEASURES: The number of false positive referrals from initial referral into the scheme. RESULTS: Of the patients, 46.6% were discharged at assessment and a further 5.7% were discharged following virtual review. Of the patients initially discharged, 2.8% were recalled following virtual review. Following assessment at the hospital, a further 10.5% were discharged after a single visit. CONCLUSIONS: The COGS community-based glaucoma screening programme is a safe and effective way of evaluating glaucoma referrals in the community and reducing false-positive referrals for glaucoma into the hospital system.

Identification of a rare coding variant in complement 3 associated with age-related macular degeneration.

Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: previously described p.Arg1210Cys encoded in the CFH gene (case frequency (fcase) = 0.51%; control frequency (fcontrol) = 0.02%; odds ratio (OR) = 23.11) and newly identified p.Lys155Gln encoded in the C3 gene (fcase = 1.06%; fcontrol = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by complement factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology.

A retrospective analysis of long-term outcomes following a single episode of transscleral cyclodiode laser treatment in patients with glaucoma.

OBJECTIVES: To investigate the efficacy of a single cyclodiode laser photocoagulation treatment for refractory glaucoma and its effect on visual outcome in patients with good visual potential as well as to evaluate possible predictive factors in establishing optimal treatment parameters. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PARTICIPANTS: The notes of 87 patients with refractory glaucoma who underwent cyclodiode photocoagulation as a first surgical intervention over a 7-year period. MAIN OUTCOME MEASURES: Maintenance of intraocular pressure (IOP) reduction, number of medications and visual acuity outcomes post-treatment. RESULTS: The mean IOP after a single treatment decreased from 39.5±1.3 to 17.8±1.5 mm Hg after a 6-week follow-up period (p<0.0001). This reduction in IOP was maintained over a 3-year period. Here, 61.5% of patients were able to reduce the number of medications used, with mean reduction from 2.6 to 1.5 medications (p<0.05). The mean initial visual field loss prior to treatment was 8.74 dB and at 6 months post-treatment was measured at 9.06 dB (p>0.05), suggesting no significant overall change. Visual acuity remained unchanged or improved for 83.6% of patients (p>0.05) with relatively good visual potential (average vision preoperatively was 0.57 logMAR). Hypotony occurred in 5.3% of patients. No patients required enucleation or evisceration. CONCLUSIONS: A single session of cyclodiode laser therapy was associated with significant IOP reduction in a majority of patients with refractory glaucoma. The majority were able to maintain the IOP reduction over a 3-year period without the need for a further surgical intervention. Additionally, over 80% of the patients in our study were able to maintain their baseline visual acuity. These results support the view that a single cyclodiode treatment can be sufficient in achieving long-term IOP control and may be considered in eyes with relatively good visual potential.

Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration.

It is a longstanding puzzle why non-coding variants in the complement factor H (CFH) gene are more strongly associated with age-related macular degeneration (AMD) than functional coding variants that directly influence the alternative complement pathway. The situation is complicated by tight genetic associations across the region, including the adjacent CFH-related genes CFHR3 and CFHR1, which may themselves influence the alternative complement pathway and are contained within a common deletion (CNP147) which is associated with protection against AMD. It is unclear whether this association is mediated through a protective effect of low plasma CFHR1 concentrations, high plasma CFH or both. We examined the triangular relationships of CFH/CFHR3/CFHR1 genotype, plasma CFH or CFHR1 concentrations and AMD susceptibility in combined case-control (1256 cases, 1020 controls) and cross-sectional population (n = 1004) studies and carried out genome-wide association studies of plasma CFH and CFHR1 concentrations. A non-coding CFH SNP (rs6677604) and the CNP147 deletion were strongly correlated both with each other and with plasma CFH and CFHR1 concentrations. The plasma CFH-raising rs6677604 allele and raised plasma CFH concentration were each associated with AMD protection. In contrast, the protective association of the CNP147 deletion with AMD was not mediated by low plasma CFHR1, since AMD-free controls showed increased plasma CFHR1 compared with cases, but it may be mediated by the association of CNP147 with raised plasma CFH concentration. The results are most consistent with a regulatory locus within a 32 kb region of the CFH gene, with a major effect on plasma CFH concentration and AMD susceptibility.

Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.

Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)-HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10(-72)), CFH (complement factor H) (P =2.3 × 10(-47)), C2 (complement component 2)-CFB (complement factor B) (P =5.2 × 10(-9)), C3 (complement component 3) (P =2.2 × 10(-3)) and CFI (P =3.6 × 10(-3)) and with more recently reported risk loci at VEGFA (P =1.2 × 10(-3)) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)-FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(-7), replication P =3.0 × 10(-4), combined P =1.3 × 10(-9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3-1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(-8), replication P =3.8 × 10(-5), combined P =2.0 × 10(-11), OR = 1.3, 95% CI = 1.2-1.4). These associations remained significant in conditional analyses which included the adjacent C2-CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD.

Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype.

BACKGROUND: Variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case-control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking. METHODS: To precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, 'Y402H') with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26,494 individuals, including 14,174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene-smoking interaction; and 16 published studies from non-European ancestry. RESULTS: In individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10-2.45; P = 1.1 x 10(-161)]. There was no evidence of effect modification by smoking (P = 0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies. CONCLUSION: The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association.

Age-related macular degeneration: the importance of family history as a risk factor.

BACKGROUND: Family history is considered a risk factor for age-related macular degeneration (AMD). With the advent of effective therapy for the disease, the importance of family history merits further investigation. This study quantifies the risk associated with family history, first, by a case-control study of reported family history and, second, by examining the siblings of AMD cases. METHODS: The authors recruited cases with advanced AMD, spouses and siblings. All subjects were carefully phenotyped. Clinical findings in the siblings were compared with spouses. Information about family history was collected. The ORs for reported family history of AMD were calculated. Analyses were adjusted for age, smoking and genotype. RESULTS: 495 AMD cases, 259 spouses and 171 siblings were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001) with a history of an affected sibling. ORs adjusted for age and smoking were higher. Examination of siblings confirmed their increased risk with 23% affected by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the OR to 16.1 (6.2 to 41.8). CONCLUSION: The risk of AMD is greatly increased by having an affected first-degree relative. Those at risk need to be made aware of this and AMD patients should advise siblings and children to seek prompt ophthalmological advice if they develop visual symptoms of distortion or reduced vision.

Genetic variation in complement regulators and susceptibility to age-related macular degeneration.

OBJECTIVES: Age-related macular degeneration (AMD) is the commonest cause of blindness in Western populations. Risk is influenced by age, genetic and environmental factors. Complement activation appears to be important in the pathogenesis and associations have been found between AMD and genetic variations in complement regulators such as complement factor H. We therefore investigated other complement regulators for association with AMD. METHODS: We carried out a case-control study to test for association between AMD and single nucleotide polymorphisms (SNPs) spanning the genes encoding complement factor P (CFP, properdin), CD46 (membrane cofactor protein, MCP), CD55 (decay accelerating factor, DAF) and CD59 (protectin). All cases and controls were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. RESULTS: 20 SNPs were genotyped in 446 cases and 262 controls. For two SNPs with p-values approaching significance additional subjects were genotyped to increase the numbers to 622 cases and 359 controls. There was no evidence of association between AMD and any of the SNPs typed in CFP, CD46, CD55 or CD59. CONCLUSIONS: In a case-control sample that has shown the well established associations between AMD and variants in CFH, CFB and C3 there was absence of association with SNPs in CFP, CD46, CD55 and CD59. This suggests that these are not important susceptibility genes for AMD.

Anaphylactic response to topical fluorescein 2% eye drops: a case report.

INTRODUCTION: The intravenous use of fluorescein 10% during retinal angiography can cause severe systemic reactions including, on rare occasions, anaphylaxis. Fluorescein 2% eye drops are used extensively for clinical examination and diagnosis, but to the best of our knowledge, they have only been reported as being responsible for a systemic anaphylactic response on two previous occasions. CASE PRESENTATION: We report the case of a 51-year-old woman who developed an anaphylactic reaction when she was administered fluorescein sodium 2% eye drops after cataract surgery. This was the second time she had been exposed to fluorescein. She had brittle asthma and a history of anaphylaxis following exposure to a variety of drug and food allergens. She was successfully resuscitated and recovered completely over a period of two days. CONCLUSIONS: Fluorescein 2% drops are universally used in general practice, ophthalmology, optometry, and casualty departments. Our case report reveals the potential for this benign eye drop to cause a life-threatening systemic reaction and emphasises the importance of considering this consequence when administering topical fluorescein 2% to a patient with a history of anaphylaxis to other allergens.

Use of 5-Fluorouracil injections to reduce the risk of trabeculectomy bleb failure after cataract surgery.

PURPOSE: To determine whether the use of postoperative subconjunctival 5-fluorouracil (5-FU) reduces the risk of trabeculectomy bleb failure after uncomplicated small incisional cataract surgery. METHODS: Twenty-five consecutive patients with primary open-angle glaucoma and a functioning trabeculectomy bleb and who underwent uncomplicated phacoemulsification surgery were given subconjunctival injections of 5 mg 5-FU at 2, 4, and 12 weeks after cataract surgery (5-FU group). The mean postoperative intraocular pressure (IOP) over a 2-year period and the trabeculectomy survival rate, as determined by Kaplan-Meier survival analysis, was compared with a historical series of patients who had undergone cataract surgery in the presence of a filtering trabeculectomy bleb, but who had not received 5-FU (control group). RESULTS: After a 2-year follow-up period, there was no significant difference in the mean IOP between the 5-FU (15.1 mm Hg SD 3.1) and control (15.3 mm Hg SD 3.3) groups (P = 0.67). An IOP > 21 mm Hg at any time point after the first postoperative month after cataract surgery was found in 4.0% cases in the 5-FU group and 16.7% cases in the control group (P = 0.78). Using Kaplan-Meier survival analysis, the difference in the cumulative probability of survival between the 5-FU and control groups was not significant (P = 0.30). CONCLUSION: Cataract surgery is a significant risk factor for trabeculectomy bleb failure. The use of subconjunctival 5-FU injections at 2, 4, and 12 weeks after cataract surgery in elderly white patients with primary open-angle glaucoma does not reduce the risk of trabeculectomy failure.

Charles Bonnet syndrome in age-related macular degeneration: the nature and frequency of images in subjects with end-stage disease.

INTRODUCTION: The term Charles Bonnet syndrome (CBS) is used to describe visual hallucinations resulting from ocular pathology. As part of a larger case-control study we assessed factors which may predispose to this phenomenon in Age-related macular degeneration (AMD). METHODS: Three-hundred and sixty cases of late AMD underwent a detailed questionnaire about visual symptoms experienced. Potential ocular and environmental risk factors were compared in two groups; those experiencing symptoms of CBS (n = 97) and those not experiencing CBS symptoms (n = 263). RESULTS: Twenty-seven percent experienced CBS. Poor visual acuity was the only factor associated with the development of these images in AMD with an odds ratio of 3.50 (95% CI 1.64-7.48, p = 0.001) for those with best binocular visual acuity worse than 6/36. In those who experienced CBS, the images tended to be straight ahead (84.5%), colored (72.2%), have moving parts (62.9%), and occur on average once per day (34%). The most common visual image was of people (19.6%) followed by geometric patterns (15.8%). The majority (71.1%) felt the experience to be neither pleasant nor unpleasant. In 41% images were present throughout the course of their disease. There was no association between visual acuity and complexity of images. CONCLUSION: The prevalence of CBS in late AMD is high, the main risk factor being poor better eye visual acuity. The most commonly experienced hallucinations were of people. Although most patients were unperturbed by the images, reassurance of their benign nature was welcomed. Practitioners should be aware that resolution of symptoms over time does not always occur.

Complement C3 variant and the risk of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis. METHODS: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls. RESULTS: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9x10(-5)) and the Scottish group (244 cases and 351 controls, P=5.0x10(-5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%. CONCLUSIONS: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease.