Systematic Review of Neovascular Age-Related Macular Degeneration Disease Activity Criteria Use to Shorten, Maintain or Extend Treatment Intervals with Anti-VEGF in Clinical Trials: Implications for Clinical Practice

Introduction: Clinical trials in neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor (ant-VEGF) injections use disease activity (DA) criteria to shorten, maintain or increase the interval between injections. Differences in these DA criteria may contribute to differences in the proportions of patients with macular fluid at key time points or achieving extended dosing intervals in these trials. We identified, collated and evaluated DA criteria from pivotal anti-VEGF nAMD trials to understand how differences impact on these studies and real-world visual acuity and extending dosing outcomes. Methods: This was a systematic review of literature on Pubmed for randomised clinical trials in nAMD using a proactive treatment regimen. We excluded case reports, review articles and studies on fewer than 50 participants. Results: Twelve clinical trials (LUCAS, VIEW, TREX-AMD, FLUID, TREND, RIVAL, ALTAIR, CANTREAT, ARIES, TREX-Conbercept, HAWK & HARRIER, TENAYA & LUCERNE) investigating anti-VEGF treatment of nAMD were identified according to our search strategy. Different studies utilised a different combination of DA criteria. Specifically, six trials included visual acuity change; four included macular thickness change; one included visual acuity change if associated with macular thickness change; one with qualitative optical coherence tomography (OCT) features; four with qualitative OCT features if also associated with visual acuity change; 10 with macular haemorrhage and five with other fluorescein angiographic features. Conclusion: Different clinical trials use different DA criteria when altering the interval between anti-VEGF injections. This makes it difficult to draw meaningful conclusions about secondary outcomes such as proportion of patients treated at extended dosing intervals or proportions of eyes with persistent subretinal or intraretinal fluid. Standardising DA criteria in clinical trials and preferentially using those easily applied in a real-world setting would lead to results more achievable in real-world settings and for a meaningful comparison of treatment durability

Management of Neovascular Age-Related Macular Degeneration in Clinical Practice: Initiation, Maintenance, and Discontinuation of Therapy

Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in elderly populations. In recent years, pharmacological inhibition of vascular endothelial growth factor (VEGF), via intravitreal injection of ranibizumab (Lucentis) or bevacizumab (Avastin), has offered the first opportunity to improve visual outcomes in patients diagnosed with this disorder. In this paper, we provide recommendations on how bevacizumab and ranibizumab may be best applied in current clinical practice, with an emphasis on their underlying pharmacology and efficacy. In addition, we review current guidelines for the initiation, maintenance, and discontinuation of anti-VEGF therapies, as well as emerging treatment strategies and future directions in the field

Initial clinical experience of ranibizumab therapy for neovascular age-related macular degeneration

PURPOSE: To describe the visual acuity and safety outcomes for the first 50 patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab at Moorfields Eye Hospital. METHODS: A retrospective analysis of case notes from the first 50 consecutive patients with Primary Care Trust funding for ranibizumab therapy for nAMD. Visual acuity outcomes and adverse events were noted, as were service delivery-related indicators. RESULTS: The mean (±standard deviation) age of the 50 patients was 81 ± 17 years. The mean follow-up of patients was 13.6 ± 2 (range 7.7-18) months. The mean change in visual acuity ± standard error was +4.6 ± 2.2 letters at the end of follow-up, with 26% gaining 15 letters or more. The mean (median) number of injections was 4.7 (4.5) per 12-month period. The mean (median) delay in Primary Care Trust funding approval was 35 days (32 days) prior to the final appraisal document from the National Institute of Health and Clinical Excellence. CONCLUSIONS: The real-world outcomes of ranibizumab therapy in this initial cohort of patients with nAMD are comparable with those reported in the pivotal, randomized, controlled trials using fewer injections and a prn strategy of retreatment to achieve the gain in visual acuity

Drug utilization pattern in acute coronary syndrome at tertiary care hospital: a prospective cross-sectional observational study

Background: To study the pattern of utilization of drug in the patients of Acute Coronary Syndrome at tertiary care hospital.Methods: Prospective cross-sectional observational drug utilization study was conducted in patients of acute coronary syndrome admitted in ICCU, for the period of two months. Data was collected in preformed Case record form. Analysis was done by using drug use indicators, demographic pattern, morbidity pattern of disease, pattern of drug use. Data analysed using Microsoft Excel SPSS software - version 21.l. Total 71 cases were analysed.Results: In our study we analysed 71 patients out of that 50 were male and 21 were female patients. The mean age of patient was 57.61±11.09 yr; most belonging to age group of 51-60 years (36.62%). Number of patients undergoing thrombolysis were 28(39.43%) and 43(60.57%) underwent percutaneous coronary intervention (PCI). Total 44 different drugs were used and 565 drugs were prescribed in 71 patients. Most frequently prescribed drugs were Clopidogrel and aspirin in 100% encounters, followed by atorvastatin (85%).Average number of drugs per encounter was 7.96. Percentage of drugs prescribed by generic name was 16.28%.Conclusions: The present study provides valuable insight about the overall pattern of drug used in Acute Coronary syndrome. Physician should be encouraged to prescribe drugs with generic name

Biomarkers of macular neovascularisation activity using optical coherence tomography angiography in treated stable neovascular age related macular degeneration

BACKGROUND: The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA). METHODS: Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval. RESULTS: All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm2 ± 4.6mm2 and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe. CONCLUSIONS: MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe

Cohort profile:rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

Purpose: the retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.Participants: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to date: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plans: the collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia

An Analysis of the Effect of ABCA4 p.Asn1868Ile Genotypes on Retinal Structure in 26,558 Participants in the UK Biobank

PURPOSE: To determine whether the ABCA4 retinopathy-associated variant p.Asn1868Ile (c.5603A>T) is associated with retinal structure or subclinical disease among the general population. METHODS: UK Biobank participants of European ancestry with available spectral-domain optical coherence tomography (OCT) passing quality control metrics and exome sequencing data were included. Regression analyses using both linear and recessive models tested for the association between the p.Asn1868Ile variant and total retinal thickness, clinically relevant segmented layer thicknesses, and visual acuity. Further regression analyses were performed with automated quality control metrics to determine if the p.Asn1868Ile variant is associated with poor quality or abnormal scans. RESULTS: Retinal layer segmentation and sequencing data for the p.Asn1868Ile variant were available for 26,558 participants, following exclusions. We identified no significant association between the p.Asn1868Ile variant and retinal thickness, any of the segmented layers, or visual acuity. There was also no significant difference for homozygous p.Asn1868Ile when tested under the assumption of a recessive model. No association was identified for any of the quality control metrics, and a χ2 test showed that participants with the p.Asn1868Ile variant were not more likely to be excluded during quality control due to poor quality scans (P = 0.56). CONCLUSIONS: The p.Asn1868Ile variant does not appear to affect the retinal structure or have pathogenic or subclinical effects on its own within the general population. The variant is likely to require other specific cis- or trans-acting modifying factors to cause ABCA4 retinopathy

Confidence of UK Ophthalmology Registrars in Managing Posterior Capsular Rupture: Results from a National Trainee Survey

Introduction: To establish the level of confidence amongst UK ophthalmology specialist registrars (residents) in managing posterior capsule rupture (PCR) during cataract surgery. / Methods: An online nine-item questionnaire was distributed to all registrars, recruited nationwide via regional representatives. Data collected included stage of training, number of completed cataract operations, cumulative PCR rate, number of PCRs independently managed, understanding of vitrectomy settings and fluidic parameters and access to simulation. Respondents self-evaluated their confidence in managing PCR with vitreous loss. / Results: Complete responses were obtained from 248 registrars (35% response rate). Mean number of phacoemulsification procedures performed was 386. For senior registrars (OST 6–7), 35 out of 70 (50%) felt confident to manage PCR independently and 55 out of 70 (78.6%) were either quite confident or very confident at deciding when to implant an intraocular lens during PCR management. Lower confidence levels were noted for junior trainees (OST 1–2). Over 65% of survey respondents had access to relevant simulation. / Conclusions: Our results represent the largest UK survey analysing the confidence of PCR management amongst registrars. Confidence improves with duration of training and increased exposure to management of PCR. However, 50% of senior registrars still lacked confidence to independently manage PCR and vitreous loss. A specific competency-based framework, potentially using a simulator or simulating a PCR event, incorporated into the curriculum may be desirable