M McKibbin

Benchmark standards for refractive outcomes after NHS cataract surgery

PurposeTo 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 Aconstants.MethodsThree 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 Aconstants 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.ResultsThe postoperative subjective refraction was within 1u2009D 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.ConclusionsOn the basis of our data, using College formula, optimising Aconstants and partial coherence interferometry, a benchmark standard of 85% of patients achieving a final spherical equivalent within 1u2009D of the predicted figure and 55% of patients within 0.5u2009D should be adopted.

Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial

BACKGROUNDnProliferative diabetic retinopathy is the most common cause of severe sight impairment in people with diabetes. Proliferative diabetic retinopathy has been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We report the 1 year safety and efficacy of intravitreal aflibercept.nnnMETHODSnIn this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged ≥18 years) with type 1 or 2 diabetes and previously untreated or post-laser treated active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic centres. Patients were randomly assigned (1:1) to repeated intravitreal aflibercept (2 mg/0·05 mL at baseline, 4 weeks, and 8 weeks, and from week 12 patients were reviewed every 4 weeks and aflibercept injections were given as needed) or PRP standard care (single spot or mutlispot laser at baseline, fractionated fortnightly thereafter, and from week 12 patients were assessed every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by minimisation with a web-based computer generated system. Primary outcome assessors were masked optometrists. The treating ophthalmologists and participants were not masked. The primary outcome was defined as a change in best-corrected visual acuity at 52 weeks with a linear mixed-effect model that estimated adjusted treatment effects at both 12 weeks and 52 weeks, having excluded fluctuations in best corrected visual acuity owing to vitreous haemorrhage. This modified intention-to-treat analysis was reapplied to the per protocol participants. The non-inferiority margin was prespecified as -5 Early Treatment Diabetic Retinopathy Study letters. Safety was assessed in all participants. This trial is registered with ISRCTN registry, number 32207582.nnnFINDINGSnWe recruited 232 participants (116 per group) between Aug 22, 2014 and Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group) contributed to the modified intention-to-treat model, and 210 participants (104 in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was non-inferior and superior to PRP in both the modified intention-to-treat population (mean best corrected visual acuity difference 3·9 letters [95% CI 2·3-5·6], p<0·0001) and the per-protocol population (4·0 letters [2·4-5·7], p<0·0001). There were no safety concerns. The 95% CI adjusted difference between groups was more than the prespecified acceptable margin of -5 letters at both 12 weeks and 52 weeks.nnnINTERPRETATIONnPatients with proliferative diabetic retinopathy who were treated with intravitreal aflibercept had an improved outcome at 1 year compared with those treated with PRP standard care.nnnFUNDINGnThe Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

First-Year Visual Acuity Outcomes of Providing Aflibercept According to the VIEW Study Protocol for Age-Related Macular Degeneration

PURPOSEnAflibercept has the potential advantage of reducing capacity problems by allowing 2 monthly visits for patients with neovascular macular degeneration (nAMD) compared with monthly pro re nata regimens that are the most commonly used in the United Kingdom. This study aimed to report the visual outcomes achieved in routine clinical practice using the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) protocol at 1 year and compare with trials data and other real-world reports.nnnDESIGNnRetrospective data analysis from an electronic medical record.nnnPARTICIPANTSnConsecutive series of treatment-naïve patients initiated on aflibercept for nAMD at least 1 year before data extraction.nnnMETHODSnData were anonymized and remotely extracted from 16 centers in the United Kingdom that use the same electronic medical record (EMR) system (Medisoft Ophthalmology; Medisoft Limited, Leeds, UK).nnnMAIN OUTCOME MEASURESnThe minimum data set defined before first data entry and mandated by the EMR included age, gender, visual acuity, injection episodes, and complications.nnnRESULTSnThe mean age was 80.0 years (median, 81.0 years) and 63.7% were women. During the first year of treatment with aflibercept, 1840 treatment-naïve eyes of 1682 patients received a median of 8 (mean, 7.0) injections at a median of 8 (mean, 7.3) visits. The mean baseline visual acuity was 53.7 letters, improving to 58.8 letters (+5.1-letter gain) at 1 year. In first-treated eyes, the respective figures were 52.7 letters at baseline and 58.2 letters at 1 year, a gain ofxa0+5.5 letters. The proportion achieving 70 letters or more increased from 16.4% at baseline to 33.7% at 1 year, and 92% avoided moderate visual loss at 1 year.nnnCONCLUSIONSnThe visual acuity outcomes are comparable to randomized trials and better than many previous real-world data collections, with a meanxa0+5.1-letter gain at 1 year compared withxa0+8.4 letters in the integrated analysis of the VIEW 1 and VIEW 2 studies. Early visual gains were maintained through the year. Collection of outcomes beyond clinical trials can have limitations but better reflect the full pool of patients actually treated and are important to determine whether a particular treatment is performing as expected. Such data also have the potential to improve services by setting up a mechanism to compare sites.

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

AimsTo 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.MethodsPhase 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 −6u2009dioptres.Patients received 0.5u2009mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months.ResultsAt 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 108u2009μm 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.ConclusionsResults 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.

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 3–5u2005years 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 12u2005951 treatment-naive eyes of 11u2005135 patients receiving 92u2005976 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 2u2005years. 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.

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

This supplement has been sponsored by Bayer HealthCare. Please see acknowledgements for full disclaimer. Prescribing Information can be found in the appendices. L.GB.COM.05.2015.11280. Date of preparation: June 2015 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.

UK AMD/DR EMR REPORT IX: comparative effectiveness of predominantly as needed (PRN) ranibizumab versus continuous aflibercept in UK clinical practice

Aims To compare the effectiveness of continuous aflibercept versus pro re nata (PRN) ranibizumab therapy for neovascular age-related macular degeneration (nAMD). Methods Multicentre, national electronic medical record (EMR) study on treatment naive nAMD eyes undergoing PRN ranibizumab or continuous (fixed or treat and extend (F/TE)) aflibercept from 21 UK hospitals. Anonymised data were extracted, and eyes were matched on age, gender, starting visual acuity (VA) and year of starting treatment. Primary outcome was change in vision at 1u2009year. Results 1884 eyes (942 eyes in each group) were included. At year 1, patients on PRN ranibizumab gained 1.6 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (95%u2009CI 0.5 to 2.7, p=0.004), while patients on F/TE aflibercept gained 6.1 letters (95%u2009CI 5.1 to 7.1, p=2.2e-16). Change in vision at 1u2009year of the F/TE aflibercept group was 4.1 letters higher (95%u2009CI 2.5 to 5.8, p=1.3e-06) compared with the PRN ranibizumab group after adjusting for age, starting VA, gender and year of starting therapy. The F/TE aflibercept group had significantly more injections compared with the PRN ranibizumab group (7.0 vs 5.8, p<2.2e-16), but required less clinic visits than the PRN ranibizumab group (10.8 vs 9.0, p<2.2e-16). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 58u2009047.14 GBP/quality-adjusted life year for continuous aflibercept over PRN ranibizumab. Conclusion Aflibercept achieved greater VA gains at 1u2009year than ranibizumab. The observed VA differences are small and likely to be related to more frequent treatment with aflibercept, suggesting that ranibizumab should also be delivered by F/TE posology.

The UK Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group, Report 2: real-world data for the impact of cataract surgery on diabetic macular oedema

Aim To assess the rate of ‘treatment-requiring diabetic macular oedema (DMO)’ in eyes for the two u2009years before and after cataract surgery. Methods Multicentre national diabetic retinopathy (DR) database study with anonymised data extraction across 19 centres from an electronic medical record system. Inclusion criteria: eyes undergoing cataract surgery in patients with diabetes with no history of DMO prior to study start. The minimum dataset included: age, visual acuity (all time-points), injection episodes, timing of cataract surgery and ETDRS grading of retinopathy and maculopathy. Main outcome measure: rate of developing first episode of treatment-requiring DMO in relation to timing of cataract surgery in the same eye. Results 4850 eyes met the inclusion criteria. The rate of developing treatment-requiring DMO in this cohort was 2.9% in the year prior to surgery versus 5.3% in the year after surgery (p<0.01). The risk of ‘treatment-requiring DMO’ increased sharply after surgery, peaking in the 3–6 months period (annualised rates of 5.2%, 6.8%, 5.6% and 4.0% for the 0–3, 3–6, 6–9 and 9–12u2009months post-operative time periods respectively). Risk was associated with pre-operative grade of retinopathy: risk of DMO in the first year post-operatively being 1.0% (no DR pre-operatively), 5.4% (mild non-proliferative diabetic retinopathy; NPDR), 10.0% (moderate NPDR), 13.1% (severe NPDR) and 4.9% (PDR) (p<0.01). Conclusions This large real-world study demonstrates that the rate of developing treatment-requiring DMO increases sharply in the year after cataract surgery for all grades of retinopathy, peaking in the 3–6u2009months postoperative period. Patients with moderate and severe NPDR are at particularly high risk.

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 36u2009206 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.

UK Neovascular Age-Related Macular Degeneration Database. Report 6: time to retreatment after a pause in therapy. Outcomes from 92 976 intravitreal ranibizumab injections

Background/aims To study the time to retreatment in eyes with neovascular age-related macular degeneration (nAMD) that had been treatment-free for intervals of 3 months, 6 months, 9 months and 12u2005months during the maintenance phase of ranibizumab therapy within the UK National Health Service. Methods In this multicentre national nAMD database study, structured data were collected from 14 centres (involving 12u2005951 eyes receiving 92u2005976 ranibizumab injections). Patients were treated with three fixed, monthly injections in a loading phase of treatment, followed by a pro re nata retreatment regimen in a maintenance phase. Eyes with a treatment-free interval (TFI) of 3 months, 6 months, 9 months or 12u2005months in the maintenance phase were identified and the time to retreatment after these TFIs was determined. Results The time to retreatment for the 20th and 50th centiles was 0.58/2.54u2005months after a 3-month TFI, 2.07/9.62u2005months after a 6-month TFI, 3.69/15.84u2005months after a 9-month TFI and 5.90/22.49u2005months after a 12-month TFI. Following a TFI of 3 months, 6 months, 9 months and 12u2005months, 68%, 44%, 31% and 21% of eyes required retreatments after an additional 6u2005months of follow-up, respectively. Similarly, after 12u2005months of follow-up, 77%, 56%, 43% and 34% of these eyes required retreatment. Conclusions This study provides times to retreatment in eyes with nAMD that have been treatment-free for intervals of 3–12u2005months and demonstrates the likelihood of repeat therapy within the next year, even after a TFI of 12u2005months. These outcomes can help plan appropriate follow-up intervals for patients who have been treatment-free for intervals of up to 12u2005months.