Management of acute proliferative diabetic retinopathy related complications during the first COVID-19 wave.

BACKGROUND: Routine hospital eye services (HES) across the National health service (NHS), and diabetic eye screening (DES) in Scotland were paused during the COVID-19 lockdown in March 2020. Alternate pathways for managing acute ophthalmic pathology were devised in NHS Grampian covering the North-East of Scotland. Emergency eye treatment centres (EETC) manned by community optometrists were set up to treat and triage referrals to HES. METHODS: Retrospective study analysing consecutive patients referred to a tertiary eye centre (Aberdeen Royal Infirmary) with proliferative diabetic retinopathy (PDR) related complications between March and August 2020. General demographical data, diabetic history, visual acuity, ocular complication, type of management, time to follow-up, and any appointment cancellations were extracted for analysis. RESULTS: Fifty two eyes of 46 patients with PDR related complications were identified. HES appointment had been delayed or cancelled in 22 patients (48%) due to COVID-19. Mean age was 54.5 years (±15.1), 21 (46%) were female, 21 (46%) had type 1 diabetes; mean HbA1c was 78 mmol/l (±18.7). Vision ranged from 6/6 to perception of light. 36 (78%) patients had unilateral vitreous haemorrhage (VH), 6 (13%) bilateral, 2 (4%) tractional retinal detachments and 3 (6.5%) had neovascular glaucoma. Of 48 acute PDR presentations, 18 (38%) were given anti-VEGF within 72 h and two (4%) had PRP the same day. 16 (33%) were rebooked into the laser clinic, 13 (27%) referred for urgent surgical review, and 17 (35%) advised observation and review in clinic. After a median follow-up of 6 months, 12 eyes (23%) of 11 patients progressed to have vitrectomy. CONCLUSION: Despite lockdown, hospital appointment cancellations and recommended footfall reduction limiting capacity due to COVID-19, patients reaching out with PDR complications were promptly referred to HES and appropriate treatments carried out with COVID-19 precautions as recommended.

Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study.

BACKGROUND/AIMS: Prospective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity. METHODS: SAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed. RESULTS: One hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of -30.75 µm (95% CI -59.50,-20.50; p<0.0001) to day 90. Improvements were also observed in other quantitative and qualitative optical coherence tomography parameters. In Early Treatment Diabetic Retinopathy Study letters assessed by category, 55% and 59% of patients gained 0-≥15 letters versus baseline at day 90 and day 180, respectively. However, mean improvements in BCVA (CfB) to each time point were small (≤2 letters). No new safety signals were identified. CONCLUSION: Switching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.

Translating evidence into practice: recommendations by a UK expert panel on the use of aflibercept in diabetic macular oedema.

OBJECTIVES: This paper describes recommendations from a panel of UK retina experts on aflibercept in diabetic macular oedema (DMO). METHODS: A roundtable meeting was held in London, UK in March 2018. The meeting was sponsored by Bayer. RESULTS: Recommendations are based on clinical experience and level 1 evidence. Clinical experience supports the evidence base, reinforcing that aflibercept should be initiated with intensive proactive dosing at 2 mg every 4 weeks. Most panel members use six initial 4-weekly doses as in Protocol T, rather than five initial monthly doses as recommended in the Summary of product characteristics (SmPC). After intensive proactive dosing, patients with a good response (meet Protocol T 'improvement' criteria ≥5-letter improvement in visual acuity [VA] and/or ≥10% improvement in central subfield thickness [CST] from baseline) but who are not yet stable should continue with 4-weekly aflibercept until stability is reached. Patients with a good response and stability should initiate monitor-and-extend (not in line with SmPC). Those with a sub-optimal response (meet 'improvement' criteria but with additional concerns e.g. fluid worsening on macular volume map) should continue with 4-weekly aflibercept but additional treatments should be considered (aflibercept is not licensed for combination treatment). For patients with no response (no change, or meeting Protocol T 'worsening' criteria [≥5-letter decrease in VA and/or ≥ 10% increase in CST] from baseline), switching to a non-anti-vascular endothelial growth factor treatment should be considered. CONCLUSIONS: Clinical experience reinforces that, when using aflibercept in DMO, the licensed posology or Protocol T regimens achieve the best outcomes.

New features in MEK retinopathy.

BACKGROUND: The use of molecularly targeted therapy is becoming widespread in oncology. These agents cause tumour-specific genetic alterations in signal transduction pathways, hence less generalised toxicity. Dabrafenib, a BRAF inhibitor and Trametinib, a MEK inhibitor are two molecularly targeted agents recently approved for treatment of advanced, unresectable melanomas. MEK retinopathy is a recently introduced term describing retinal toxicity secondary to MEK inhibitors. CASE PRESENTATION: A 71-year-old man presented with 'circular, green patches' in his central vision for 2 weeks. He had multiple relapsed stage IV BRAF gene mutant malignant melanoma. He was on treatment with Dabrafenib (Tafinlar) for 7 months and Trametinib (Mekinist) for 4 months respectively. The fundus looked normal. The OCT scan showed bilateral symmetrical cystoid macular edema, intraretinal and subretinal fluid, thickening of elliposoid zone and subretinal granular deposits. The symptoms resolved with temporary cessation of chemotherapy but OCT signs persisted. CONCLUSION: This case report identifies two new remarkable features of MEK retinopathy as thickening of ellipsoid zone and 'starry sky' pattern of distribution of subretinal granular deposits. These changes signify photoreceptors/ RPE toxicity and dysfunction. The subretinal granular deposits showed increased autofluorescence suggested abnormal lipofuscin clearance due to RPE dysfunction. The molecularly targeted therapy has revolutionized the cancer treatment and increased the survival rate. These agents are relatively new and recently approved for clinical use and most of them are associated with ocular toxicities. Awareness of ocular symptoms, side-effect profile of drugs, monitoring regime and liaison between oncologist and eye care professional with ocular imaging is key to early diagnosis and management of ocular adverse events.

Clinical response of pigment epithelial detachment associated with neovascular age-related macular degeneration in switching treatment from Ranibizumab to Aflibercept.

BACKGROUND: To study the clinical outcomes of pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (nAMD) in patients switched from Ranibizumab to Aflibercept. METHODS: Retrospective non-comparative case series. 50 eyes with active nAMD and fovea involving PED of ≥100 µm measured manually using the caliper on the OCT, initially treated with intravitreal Ranibizumab (0.5 mg/0.05 ml) and later switched to Aflibercept (2.0 mg/0.05 ml). The outcome measures of best corrected visual acuity (BCVA), PED height, PED width and number of injections were measured at baseline and at time point of switch, 4 months, 1 year and at last follow up visit post-switch. Three paired t-tests and Pearson's correlations were calculated to analyze variables at switch and change in variables at 1 year. RESULTS: After switch to Aflibercept, the improvement of BCVA was 1.84 (p = 0.11), 1.74 (p = 0.21) and 1.16 (p = 0.45) letters, the change in PED height was - 65.6µm (p < 0.001), - 50.64µm (p = 0.007) and - 68.48µm (p < 0.001) and the change in PED width was - 36.6µm (p = 0.514), + 29.7µm (p = 0.922) and + 118.4µm (p = 0.210) at 4 months, 1 year and the last visit respectively. There was a moderate negative correlation between reduction in PED height at 1 year after switch and PED height at the time of switch to Aflibercept (r = - 0.474, p < 0.05). CONCLUSION: The improvement in BCVA and change in PED width was not statistically significant however the reduction in PED height was significant after switching treatment to Aflibercept. The change in BCVA at 1 year after switch was not correlated with any of the analyzed anatomical characteristics of PED.

Improving the cost-effectiveness of photographic screening for diabetic macular oedema: a prospective, multi-centre, UK study.

BACKGROUND/AIMS: Retinal screening programmes in England and Scotland have similar photographic grading schemes for background (non-proliferative) and proliferative diabetic retinopathy, but diverge over maculopathy. We looked for the most cost-effective method of identifying diabetic macular oedema from retinal photographs including the role of automated grading and optical coherence tomography, a technology that directly visualises oedema. METHODS: Patients from seven UK centres were recruited. The following features in at least one eye were required for enrolment: microaneurysms/dot haemorrhages or blot haemorrhages within one disc diameter, or exudates within one or two disc diameters of the centre of the macula. Subjects had optical coherence tomography and digital photography. Manual and automated grading schemes were evaluated. Costs and QALYs were modelled using microsimulation techniques. RESULTS: 3540 patients were recruited, 3170 were analysed. For diabetic macular oedema, England's scheme had a sensitivity of 72.6% and specificity of 66.8%; Scotland's had a sensitivity of 59.5% and specificity of 79.0%. When applying a ceiling ratio of £30,000 per quality adjusted life years (QALY) gained, Scotland's scheme was preferred. Assuming automated grading could be implemented without increasing grading costs, automation produced a greater number of QALYS for a lower cost than England's scheme, but was not cost effective, at the study's operating point, compared with Scotland's. The addition of optical coherence tomography, to each scheme, resulted in cost savings without reducing health benefits. CONCLUSIONS: Retinal screening programmes in the UK should reconsider the screening pathway to make best use of existing and new technologies.

Bilateral 'vitelliform-like' macular lesions in a patient with multiple myeloma.

A 73-year-old woman was referred to the eye clinic in February 2005 with reduced vision in both eyes. On examination, her visual acuity was 20/40, N6 right eye and 20/64, N6 left eye. Bilateral unusual 'vitelliform-like' lesions at the macula (accumulation of yellow material in the subretinal space), which demonstrated blocked fluorescence on fluorescein angiography and a lack of increased autofluorescence signal on fundus autofluorescence imaging, were detected. The patient was followed-up until April 2007 when retinal haemorrhages were detected and blood work-up was undertaken; during this follow-up period the material present at the macula progressively disappeared. As a result of the blood work-up, the diagnosis of multiple myeloma was established; the macular lesions were thought to relate to the latter disease and represent subretinal deposition of immunoglobulin.