Associations with baseline visual acuity in 12,414 eyes starting treatment for neovascular AMD.

AIMS: To determine baseline visual acuity before the start of treatment for neovascular age-related macular degeneration (AMD), compare median and visual acuity states between treatment sites and investigate the association of socio-demographic and clinical characteristics with baseline acuity. METHODS: Anonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation. Associations with baseline acuity were investigated using multivariate linear regression. RESULTS: Analysis included 12,414 eyes of 9116 patients at 13 NHS Trusts. Median baseline acuity was LogMAR 0.46 (interquartile range = 0.26-0.80) and 34.5% of eyes had good acuity, defined as LogMAR ≤0.3. Baseline acuity was positively associated with second-treated eye status, younger age, lower socio-economic deprivation, independent living, and female sex. There was little evidence of association between baseline acuity and distance to the nearest treatment centre, systemic or ocular co-morbidity. Despite case-mix adjustments, there was evidence of significant variation of baseline visual acuity between sites. CONCLUSIONS: Despite access to publicly funded treatment within the NHS, variation in visual acuity at the start of neovascular AMD treatment persists. Identifying the characteristics associated with poor baseline acuity, targeted health awareness campaigns, professional education, and pathway re-design may help to improve baseline acuity, the first eye gap, and visual acuity outcomes.

CNGB3 mutations cause severe rod dysfunction.

PURPOSE: Congenital achromatopsia or rod monochromatism is a rare autosomal recessive condition defined by a severe loss of cone photoreceptor function in which rods purportedly retain normal or near-to-normal function. This report describes the results of electroretinography in two siblings with CNGB3-associated achromatopsia. METHODS: Full field light- and dark-adapted electroretinograms (ERGs) were recorded using standard protocols detailed by the International Society for Clinical Electrophysiology of Vision (ISCEV). We also examined rod-mediated ERGs using series of stimuli that varied over a 6 log unit range of retinal illuminances (-1.9-3.5 log scotopic trolands). RESULTS: Dark-adapted ERGs in achromatopsia patients exhibited severely reduced b-wave amplitudes with abnormal b:a ratios (1.3 and 0.6). In comparison, the reduction in a-wave amplitude was less marked. The rod-mediated ERG took on an electronegative appearance at high-stimulus illuminances. CONCLUSION: Although the defect that causes achromatopsia is primarily in the cone photoreceptors, our results reveal an accompanying disruption of rod function that is more severe than has previously been reported. The differential effects on the b-wave relative to the a-wave points to an inner-retinal locus for the disruption of rod function in these patients.

Appropriateness of quality standards for meaningful intercentre comparisons of aflibercept service provision for neovascular age-related macular degeneration.

PurposeReal-world data give different information on health-care delivery compared with randomised controlled trials. We aimed to evaluate the appropriateness of possible quality standards for intersite comparisons of outcomes of providing Aflibercept for neovascular age-related macular degeneration (nAMD) in clinical practice.Patients and methodsRetrospective data analysis from an electronic medical record. A consecutive series of treatment-naive patients initiated on aflibercept for nAMD, in the UK from March 2013 to October 2015. Age, visual acuity (VA) at baseline and 1 year, and injection episodes were remotely extracted in an anonymised format.ResultsThe mean baseline VA was 54.3 letters, ranging from 51.3 to 58.1 between different centres, in 5620 eyes taken from 12 centres. Out of these, 3360 were initiated on treatment more than a year before. The percentage with <35 letters at baseline was 19.9-3% and that with >70 letters was 24.8-10.7%. Eyes with ≥70 letters at 1 year ranged from 20.2 to 42.9% and those with <35 ranged from 4.5 to 21.6% across different sites. Injection rates in 1 year varied from 5.5 to 8.6, and data available at 1 year also varied from 82.3 to 46.4%.ConclusionsSignificant variation was found between sites attempting to provide the same therapeutic regime. For fair comparisons between sites, we recommend that both VA measures and process measures, such as injection numbers, retention rates, and discharge policies, are used. More work is required to explain the differences. Such real-world data are not generated in the same way as a randomised clinical trial, and maybe best used to help improve service provision.

The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care.

PurposeInternational variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intra-country inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and inter-centre regional variations in outcomes for treatment of nAMD.Patients and methodsProspective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.ResultsMean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.ConclusionThere are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.

Aflibercept in wet AMD beyond the first year of treatment: recommendations by an expert roundtable panel.

This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.

Intravitreal bevacizumab injection in unrecognised early pregnancy.

PURPOSE: The use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age. PATIENTS AND METHODS: We present our experiences following intravitreal injection of bevacizumab during the first trimester of unrecognised pregnancies in four women. RESULTS: All our patients were inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place. There were three cases of pregnancy without complication and one case of complicated pregnancy in which there was a significant past obstetric history. CONCLUSION: This case series provides further insights into intravitreal injection of bevacizumab in early pregnancy. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections. Should a woman become pregnant, counselling is needed to explain the potential risks and benefits, and the limited available data relating to the use of these agents in early pregnancy.

Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective.

BACKGROUND/AIMS: The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. METHODS: Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. RESULTS: Questionnaires were completed with 200 participants. Responses indicated that participants' perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p<0.02). Participants reported a range of perceived benefits (eg, family planning, access to treatment) and risks (eg, impact upon family relationships, emotional consequences). CONCLUSIONS: Adults with inherited retinal disease strongly support the provision of publicly funded genetic testing. Support was stronger for diagnostic and predictive testing than for testing as part of reproductive planning.

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study.

AIMS: To evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis. METHODS: Phase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24-78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least -6 dioptres. Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months. RESULTS: At 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 µm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified. CONCLUSIONS: Results from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.

Adverse ophthalmic reaction in poppers users: case series of 'poppers maculopathy'.

BACKGROUND: Poppers are a recreational substance of abuse belonging to the alkyl nitrite family of compounds. In the United Kingdom, where they are legal to purchase but illegal to sell for human consumption, 10% of the general population have tried them. They are considered low risk to physical and mental health. Two recent case series from France demonstrated foveal pathology in individuals associated with poppers use. METHOD: A case series of seven patients presenting to four hospitals in the United Kingdom with visual impairment and maculopathy associated with inhalation of poppers. RESULTS: All patients experienced visual symptoms associated with poppers use. The majority had impaired visual acuity, central scotomata, distortion, or phosphenes. Clinical signs on fundoscopy ranged from normal foveal appearance to yellow, dome-shaped lesions at the foveola. Spectral domain optical coherence tomography (SD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction. DISCUSSION: Although poppers have been in use for several decades, in 2007, following legislative changes, there was a change in the most commonly used compound from isobutyl nitrite to isopropyl nitrite. There were no reports of 'poppers maculopathy' before this. Poppers maculopathy may be missed if patients are not directly questioned about their use. The disruption or loss of the presumed IS/OS junction on SD-OCT are a characteristic feature. Further study of maculopathy in poppers users is now needed. Raising public awareness of the ocular risks associated with their use may be necessary.

Visual impairment certification secondary to ARMD in Leeds, 2005-2010: is the incidence falling?

AIM: The aim of this study was to evaluate trends in visual impairment certification due to age-related macular degeneration (ARMD) in the Leeds metropolitan area between 2005 and 2010. METHODS: In this retrospective study, the primary causes of visual impairment certification in the Leeds metropolitan area between 2005 and 2010 were reviewed. ARMD was considered to be the cause of certification when recorded as the primary factor contributing to visual impairment in one or both eyes. The incidence of visual impairment certification due to ARMD was calculated using population estimates from the Office of National Statistics. RESULTS: ARMD was the primary cause of visual impairment certification in all study years, accounting for 58.7 and 50.8% of certifications in 2005 and 2010, respectively. For the same period, the incidence of certification due to ARMD fell from 364 to 248 per million population per year. This was largely the result of a fall in the incidence of visual impairment certification due to neovascular ARMD from 225 to 137 per million population per year, beginning in 2008 after the introduction of a local commissioning policy on the use of intra-vitreal ranibizumab. CONCLUSION: The incidence of visual impairment certification due to ARMD in the Leeds metropolitan area appears to be falling. This is largely the result of a decrease in certification secondary to neovascular ARMD. This represents a change in the previously described trend for ARMD visual impairment certification.

Trends in the incidence of visual impairment certification secondary to diabetic retinopathy in the Leeds metropolitan area, 2005-2010.

AIM: This study reports the incidence of visual impairment certification due to diabetic retinopathy in Leeds between 2008 and 2010 and makes a comparison with data from 2005, immediately before the introduction of a comprehensive screening service. METHODS: The primary causes of visual impairment certification between 2008 and 2010 were collected and reviewed. Mid-year population estimates and a diabetes prevalence model were used to determine the incidence of certification secondary to diabetic retinopathy. RESULTS: Diabetic retinopathy was the primary cause of visual impairment certification in 33 of 446 (7.4%) certificates in 2008, 34 of 410 (8.3%) certificates in 2009 and 24 of 392 (6.1%) in 2010. For the total population in 2008, 2009 and 2010, the combined incidence of either sight impairment or severe sight impairment due to diabetic retinopathy was 42.3, 43.2 and 30 per million per year, respectively. For the population with diagnosed diabetes mellitus, the combined incidence of either sight impairment or severe sight impairment secondary to diabetic retinopathy was 1227, 1192 and 796 per million per year, respectively. For each year, the incidence of visual impairment was lower than the corresponding figure for 2005. CONCLUSION: Following the introduction of a comprehensive retinal screening service, the incidence of visual impairment certification secondary to diabetic retinopathy in the Leeds Metropolitan area appears to be decreasing. However, a multifaceted approach, addressing all the avoidable risk factors, may be required to maintain this trend in view of the increasing prevalence of Type 2 diabetes.

One-year outcome after intravitreal ranibizumab for large, serous pigment epithelial detachment secondary to age-related macular degeneration.

AIM: To report the effects of intravitreal ranibizumab therapy for large, serous pigment epithelial detachment (PED), secondary to age-related macular degeneration, and occupying more than 50% of the total lesion area. MATERIALS AND METHODS: In a retrospective case series, visual acuity, ocular coherence tomography (OCT), and safety data were collected for 19 eyes of 19 patients, with serous PED and evidence of disease progression. Intravitreal ranibizumab of 0.5 mg was given with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to visual acuity and OCT findings. The change in visual acuity and maximum PED height from baseline to month 12 was determined. RESULTS: Moderate visual loss was avoided in 18/19 eyes (95%) at the 12-month examination. In all, 12 eyes (63%) had an increase in ETDRS letter score from baseline, and five eyes (26%) had a gain of 15 or more letters. Although there was a trend for the PED height to reduce with treatment, in none of the cases was the PED seen to resolve completely. There was no difference in functional or anatomical outcome between the avascular and vascularised serous PED. A single eye developed a retinal pigment epithelium rip, complicated by extensive sub-retinal haemorrhage, during the study period. CONCLUSIONS: Visual acuity outcomes of intravitreal ranibizumab for large serous PED are comparable to those seen in multicentre, phase 3 trials of other lesion types, and were obtained without the need for either monthly, fixed treatment, or for continued treatment until the PED resolves.

Ranibizumab monotherapy for sub-foveal haemorrhage secondary to choroidal neovascularisation in age-related macular degeneration.

PURPOSE: In a retrospective review, the functional effects of intra-vitreal ranibizumab monotherapy in patients with sub-foveal haemorrhage secondary to choroidal neovascularisation (CNV) in age-related macular degeneration (ARMD) are reported. PATIENTS AND METHODS: Twelve eyes of 12 patients were treated with intra-vitreal ranibizumab (0.5 mg in 0.05 ml) in accordance with current practice. Follow-up was arranged at monthly intervals. Eleven patients completed 6 months and seven completed 12 months of follow-up. Duration of haemorrhage, lesion size, ETDRS letter score at baseline, and follow-up were analysed. RESULTS: The mean time for complete clearance of sub-retinal haemorrhage was 4.7 months (range 3-7 months). After 6 months, visual acuity was stable or improved in 7 of 11 eyes and the mean change in ETDRS letter score was +7.6 letters (P>0.05). After 12 months, visual acuity was stable or improved in five of seven eyes and the mean change in ETDRS letter score was +7.3 letters (P>0.05). For the seven cases with 12 months of follow-up, a mean of six injections were given. Two patients had a decrease in acuity of >15 ETDRS letters during follow-up. No other local or systemic side-effects were reported. CONCLUSIONS: Intra-vitreal ranibizumab monotherapy may be an effective treatment for sub-foveal haemorrhage secondary to CNV in ARMD.

Colour vision testing for diabetic retinopathy: a systematic review of diagnostic accuracy and economic evaluation.

OBJECTIVE: To determine the diagnostic performance and cost-effectiveness of colour vision testing (CVT) to identify and monitor the progression of diabetic retinopathy (DR). DATA SOURCES: Major electronic databases including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Database of Systematic Reviews were searched from inception to September 2008. REVIEW METHODS: A systematic review of the evidence was carried out according to standard methods. An online survey of National Screening Programme for Diabetic Retinopathy (NSPDR) clinical leads and programme managers assessed the diagnostic tools used routinely by local centres and their views on future research priorities. A decision tree and Markov model was developed to estimate the incremental costs and effects of adding CVT to the current NSPDR. RESULTS: In total, 25 studies on CVT met the inclusion criteria for the review, including 18 presenting 2 x 2 diagnostic accuracy data. The quality of studies and reporting was generally poor. Automated or computerised CVTs reported variable sensitivities (63-97%) and specificities (71-95%). One study reported good diagnostic accuracy estimates for computerised CVT plus retinal photography for detection of sight-threatening DR, but it included few cases of retinopathy in total. Results for pseudoisochromatic plates, anomaloscopes and colour arrangement tests were largely inadequate for DR screening, with Youden indices (sensitivity + specificity - 100%) close to zero. No studies were located that addressed patient preferences relating to CVT for DR. Retinal photography is universally employed as the primary method for retinal screening by centres responding to the online survey; none used CVT. The review of the economic evaluation literature found no previous studies describing the cost and effects of any type of CVT. Our economic evaluation suggested that adding CVT to the current national screening programme could be cost-effective if it adequately increases sensitivity and is relatively inexpensive. The deterministic base-case analysis indicated that the cost per quality-adjusted life-year gained may be 6364 pounds and 12,432 pounds for type 1 and type 2 diabetes respectively. However, probabilistic sensitivity analysis highlighted the substantial probability that CVT is not diagnostically accurate enough to be either an effective or a cost-effective addition to current screening methods. The results of the economic model should be treated with caution as the model is based on only one small study. CONCLUSIONS: There is insufficient evidence to support the use of CVT alone, or in combination with retinal photography, as a method for screening for retinopathy in patients with diabetes. Better quality diagnostic accuracy studies directly comparing the incremental value of CVT in addition to retinal photography are needed before drawing conclusions on cost-effectiveness. The most frequently cited preference for future research was the use of optical coherence tomography for the detection of clinically significant macular oedema.

Phenotypic progression in X-linked retinitis pigmentosa secondary to a novel mutation in the RPGR gene.

PURPOSE: To report phenotypic progression for a novel mutation in the RPGRgene causing X-linked retinitis pigmentosa (RP), and describe the phenotype in affected males and females. METHODS: Bidirectional fluorescent sequencing analysis was used to screen for mutations in RPGR. Five affected males and eight affected females from two English families underwent refraction, ETDRS visual acuity, OCT imaging, and Goldmann visual field testing. RESULTS: DNA analysis identified a novel c.350G>A sequence change in exon 5 of RPGR. The change segregated with disease in both families. For affected males there was a significant correlation between age and visual acuity (r=-0.91, P=0.034), and a non-significant correlation between age and visual field area (r=-0.56, P=0.4). For affected females, there was a significant correlation between age and visual acuity (r=-0.8, P=0.018), and between age and visual field area (r=-0.94, P=0.005). All affected females were highly myopic. No correlation between retinal thickness, and either age or sex was noted. CONCLUSION: This novel mutation in RPGRcauses X-Linked RP with complete penetrance in males and females. Affected females are highly myopic but retain better visual function than affected males. The phenotypic data can be used to provide a mutation-specific visual prognosis, and may also help recognition of the genotype.

Benchmark standards for refractive outcomes after NHS cataract surgery.

PURPOSE: To establish benchmark standards for refractive outcome after cataract surgery in the National Health Service when implementing the 2004 biometry guidelines of the Royal College of Ophthalmologists and customising A constants. METHODS: Three cycles of prospective data were collected throughout the cataract care pathway on all patients using an electronic medical record system (Medisoft Ophthalmology), between January 2003 and February 2006. The electronic medical record automatically recommends the formula to be used according to the College guidelines and allows A constants to be customised separately for either ultrasound or partial coherence interferometry methods of axial length measurement and for different intraocular lens models. Consultants and trainees performed routine phacoemulsification cataract surgery and new intraocular lens models were introduced during the cycles. Uncomplicated cases with 'in-the-bag fixation', achieving 6/12 Snellen acuity or better were included. Community ophthalmic opticians performed refraction at 4 weeks. RESULTS: The postoperative subjective refraction was within 1 D of the predicted value in 79.7% of the 952 cases in cycle 1, 83.4% of 2406 cases in cycle 2, and 87.0% of 1448 cases in cycle 3. CONCLUSIONS: On the basis of our data, using College formula, optimising A constants and partial coherence interferometry, a benchmark standard of 85% of patients achieving a final spherical equivalent within 1 D of the predicted figure and 55% of patients within 0.5 D should be adopted.