Marie Tsaloumas

UK AMD EMR USERS GROUP REPORT V: benefits of initiating ranibizumab therapy for neovascular AMD in eyes with vision better than 6/12.

Background/aims To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy. Methods Multicentre national nAMD database study on patients treated 3–5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections. Results The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12–6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001–0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12. Conclusions All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients’ funding.

Social deprivation as a risk factor for late presentation of proliferative diabetic retinopathy

Purpose The aim of this study was to determine whether social deprivation is a risk factor for late presentation of patients with proliferative diabetic retinopathy and whether it affects their access to urgent laser treatment. Methods Using a 2:1 case: control design, 102 patients referred to a UK teaching hospital as part of the UK Diabetic Retinopathy National Screening Programme were identified for the period between 1 June 2010 to 1 June 2013. Social deprivation was scored using the Index of Multiple Deprivation 2010. Additional variables considered included age, duration of disease, ethnicity, and HbA1c at time of referral. Results The cases comprised 34 patients referred with proliferative (grade R3) retinopathy with a control group of 68 patients with lower retinopathy grades; two control patients were excluded due to incomplete data. On univariate analysis, R3 retinopathy was associated with higher social deprivation (P<0.001, Mann–Whitney U-test), and with higher HbA1c (11.5% vs 8.4%; P<0.001, Mann–Whitney U-test). Forward stepwise multivariable analysis showed that the association of R3 retinopathy with deprivation was significant even after adjusting for HbA1c (P=0.016). On univariate analysis South Asian ethnicity was also identified as being a risk factor for presentation with R3 retinopathy, but this was no longer significant when HbA1c was adjusted for in a forward stepwise logistic regression analysis. Conclusion In our cohort social deprivation appears to be associated with late presentation of proliferative diabetic retinopathy. Our study supports the need to target these groups to reduce preventable blindness and to identify strategies which overcome barriers to care.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group, Report 1: baseline characteristics and visual acuity outcomes in eyes treated with intravitreal injections of ranibizumab for diabetic macular oedema

Aims To describe baseline characteristics and visual outcome for eyes treated with ranibizumab for diabetic macular oedema (DMO) from a multicentre database. Methods Structured clinical data were anonymised and extracted from an electronic medical record from 19 participating UK centres: age at first injection, ETDRS visual acuity (VA), number of injections, ETDRS diabetic retinopathy (DR) and maculopathy grade at baseline and visits. The main outcomes were change in mean VA from baseline, number of injections and clinic visits and characteristics affecting VA change and DR grade. Results Data from 12 989 clinic visits was collated from baseline and follow-up for 3103 eyes. Mean age at first treatment was 66 years. Mean VA (letters) for eyes followed at least 2 years was 51.1 (SD=19.3) at baseline, 54.2 (SD: 18.6) and 52.5 (SD: 19.4) at 1 and 2 years, respectively. Mean visual gain was five letters. The proportion of eyes with VA of 72 letters or better was 25% (baseline) and 33% (1 year) for treatment naïve eyes. Eyes followed for at least 6 months received a mean of 3.3 injections over a mean of 6.9 outpatient visits in 1 year. Conclusions In a large cohort of eyes with DMO treated with ranibizumab injections in the UK, 33% of patients achieved better than or equal to 6/12 in the treated eye at 12 months compared with 25% at baseline. The mean visual gain was five letters. Eyes with excellent VA at baseline maintain good vision at 18 months.

The role of social deprivation in severe neovascular age-related macular degeneration

Background/aims Advances in therapy have improved outcomes for patients with neovascular age-related macular degeneration (nAMD). Prompt access to treatment is a priority and may be used as a key performance indicator. In this study, we investigate how social deprivation may impact on access to services, treatment and visual impairment registration. Methods Patients were identified retrospectively through the Certificate of Visual Impairment system for the University Hospitals Birmingham Medical Retina service. The Index of Multiple Deprivation (IMD) 2007 score was calculated for each patient. The impact of deprivation, age, gender and ethnicity on key stages in the care pathway was assessed. Results 120 patients were identified. Patients with greater social deprivation were under-represented, had worse visual acuity at first presentation (correlation of the better-seeing eye with IMD 0.225 (p=0.013)) and had sight-impairment registration earlier (correlation −0.246; p=0.007). Deprivation did not affect time to first appointment, and was not associated with a higher rate of non-attendance. Conclusions The late presentation and under-representation of patients with greater social deprivation is a serious concern. Our study strongly suggests that this vulnerable group is encountering barriers in accessing treatment in nAMD, and that these occur prior to entry into the Hospital Eye Service.

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.

Evaluation of visual function and needs in adult patients with bardet-biedl syndrome.

Purpose: To assess the visual needs of the adult population with Bardet–Biedl syndrome (BBS) and to ensure that this is addressed by a national Bardet–Biedl Service. Methods: A cross-sectional analysis of all adults under a national BBS Clinic (Birmingham, United Kingdom) was performed using the BBS Ophthalmic Assessment Tool, a novel tool designed to capture the key elements of visual function, impact on lifestyle, and clinical findings relevant to BBS. Results: Sixty-two adult patients were confirmed to have BBS. Bardet–Biedl syndrome mutations were identified in 51, most commonly BBS1 (n = 35), BBS2 (n = 6), and BBS10 (n = 5). In 11 patients (18%), BBS had not been diagnosed until adulthood. Median visual acuity was hand motion (range, 0.0 logMAR–no perception of light). More advanced retinopathy was associated with increasing age, worsening visual acuity, and the presence of nystagmus. Forty patients (65%) had undertaken mainstream education with 29 (47%) achieving higher education; 7 patients (11%) had moderate or severe learning difficulties. Most (90%) were registered sight-impaired or severely sight-impaired patients. Conclusion: The BBS Ophthalmic Assessment Tool provides a wide-ranging assessment of ophthalmic status and vision-related needs of the BBS population. This evaluation demonstrates the spectrum of visual disability in this population and its correlation with worsening retinopathy over time.

An unusual presentation of patent foramen ovale.

Lesson We report a case of retinal artery occlusion in a young adult in early pregnancy found to have a patent foramen ovale as the source of the embolism. This report suggests the importance of early cardiac investigation in such individuals.

Measurement bias between optical coherence tomography instruments can affect access to treatment: a new lottery

Dear editor It is with great interest that we read the publication entitled “Critical appraisal of ranibizumab in the treatment of diabetic macular edema” by Stewart.1 The author emphasized the importance of the vascular endothelial growth factor (VEGF) in the pathophysiology of diabetic macular edema (DME). As highlighted in that article, the anti-VEGF ranibizumab is a superior treatment compared to traditional argon photocoagulation, leading to better anatomical and functional results. In April 2013, the National Institute for Health and Care Excellence (NICE) of the UK approved the use of ranibizumab as a treatment option to treat diabetic macular edema of the eye if it has a central macular thickness (CMT) of 400 μm or more at the beginning of the treatment.2 The guidelines did not specify which optical coherence tomography (OCT) device(s) should be used for this assessment. This is important as, although good consistency has been shown in using the same instrument, there is a known divergence in CMT measurements between different instruments.3–6 For example, the Spectralis® OCT (Heidelberg Engineering; Carsbad, CA, USA) generally shows higher values of mean CMT in a normal eye compared to most other instruments, in part due to the retinal segmentation algorithm that it employs.4 We hypothesized that similar (or increased) differences might be observed in DME, and that for those countries (such as the UK) where a fixed CMT is used to define eligibility for treatment, the “lottery” of OCT instruments may influence eligibility. In light of this hypothesis, we conducted a preliminary analysis of 24 patients (48 eyes) with suspected DME who had OCT scans performed on the same day using both 3D OCT-1000 (Topcon; Itabashi, Tokyo, Japan) and Spectralis OCT. Matched macular-centered scans were obtained in 42 eyes; scans were not possible in 6 eyes due to media opacity or problems with patient fixation. The mean (standard deviation) CMT in this cohort was 282.0 (89.0) μm with a range of 191–689 μm using the Topcon OCT, and 312.4 (88.8) μm with a range of 224–719 μm using the Spectralis OCT (Figure 1A). Comparing the two instruments in our cohort using a Bland–Altman analysis, there was a bias of +10.73 μm to the Spectralis with a standard deviation of 10.32, and 95% limits of agreement of −9.497 to 30.96 μm (Figure 1B). Figure 1 Comparison of CMT measurements acquired on Topcon 3D OCT-1000 versus Spectralis® OCT for patients with DME. Direct comparison (A) and Bland– Altman plot (B). Recognizing this issue is important for all those involved in care of patients in countries or institutions where the entry to treatment is limited by a defined CMT level. In the specific example considered here, this finding has a direct clinical impact on patients who have DME with a central macular thickness of 390–410 μm. In our small cohort of matched scans from 42 eyes, there were three whose CMT was >400 μm on the Topcon and four whose CMT was >400 μm on the Spectralis: ie, even in this small study, a patient’s eligibility for treatment depended on which scan was used. “Real-world” studies of OCT will become increasingly important if defined CMT levels are to be used as the “gate-keeper” for treatment, and should include repeatability and inter-instrument variability in defined patient cohorts.