Real-world service costs for neovascular-AMD clinics in the United Kingdom: structured literature review and scenario analysis.

OBJECTIVE: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity). METHODS: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice. These items underwent meta-synthesis and were then determined in a consensus exercise. RESULTS: Of 237 cost items identified, 217 (91.6%) met the consensus threshold of >0.51 and were included in the nAMD Service Non-Drug Cost Instrument (nAS). Sensitivity of cost items taken from UK Health Technology Assessment (HTA) using the nAS as the reference standard was low (HTAmin: 1.84%, 95% CI 0.50-4.65%; HTAmax: 70.51%, 95% CI 63.96-76.49%). False negative rates showed variable likelihood of misclassifying a service by cost burden depending on prevalence. Scenario analysis using cost magnitudes estimated annual per-patient clinic cost at £845 (within capacity) to £13,960 (under strain) compared to an HTAmin estimate of £210. Accounting for cost of strain under an assumed 50% increase in health resource utilization influenced cost-effectiveness in a hypothetical genericisation scenario. CONCLUSION: Findings suggested that HTA underestimates UK NHS nAMD clinic cost burden with cost of strain contributing substantial additional unmeasured expense with impact on CEA. Given potential undertreatment due to strain, durability is suggested as one of the relevant factors in CEA of nAMD anti-VEGF treatments due to robustness under limited capacity conditions affecting UK ophthalmology services.

When considering how well treatments work versus how much they cost, the focus is usually only on the price of the medicine itself. However, other real-world costs exist. In the UK, when treating certain eye problems such as neovascular age-related macular degeneration (nAMD), there are additional expenses related to running clinics and managing treatments that often go unnoticed. To get a better understanding of these hidden costs, the study examined factors like clinic workload and the extra expenses that come with it. Ten eye doctors in the UK were consulted for their expert opinions and numerous research papers were reviewed to identify these additional costs. The study grouped different costs in a tool called the nAMD Service Non-Drug Cost Instrument (nAS). When the findings of the nAS tool were compared to the usual methods of calculating costs, it was found that the conventional approach overlooked many of the actual expenses. Busy clinics face unique challenges, such as higher operational costs associated with staffing for extended hours, emergency appointments, extended waiting times and the potential to miss optimal treatment windows. This can lead to disease progression and the onset of comorbidities, which require more complex and costly treatments. Recognizing these real costs is crucial when making decisions about treatments, especially when treatments require more frequent visits to eye clinics. This study emphasizes the importance of considering all expenses, not just the obvious ones like medication and doctor visits when determining the most effective way to manage eye conditions like nAMD in the UK.

Diagnostic and therapeutic considerations in patients with bilateral diffuse uveal melanocytic proliferation.

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of bilateral diffuse uveal melanocytic proliferation (BDUMP). METHODS: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Our search strategy utilized the following keywords: "bilateral diffuse uveal melanocytic proliferation", "BDUMP", and "Paraneoplastic Syndrome". Articles were considered based on their relevance, with the search spanning publications up to 2023. Studies were excluded if they did not contribute pertinent information or lacked methodological rigor. A critical appraisal of included studies was conducted, assessing study design, sample size, methodology, and potential bias, ensuring a thorough and transparent review process. RESULTS: BDUMP is a rare and potentially sight-threatening condition characterized by the bilateral proliferation of melanocytes within the uvea. BDUMP is typically observed in middle-aged or elderly individuals and is often associated with an underlying malignancy, most commonly of gastrointestinal origin. BDUMP is frequently misdiagnosed as a benign nevus or choroidal metastasis, leading to delayed diagnosis and treatment. The ophthalmic symptoms and signs typically precede the diagnosis of a systemic malignancy, emphasizing the crucial role of ophthalmologists in the recognition of BDUMP. Several diagnostic modalities can aid in the diagnosis of BDUMP, including ophthalmic examination, imaging studies such as optical coherence tomography, fluorescein angiography, and indocyanine green angiography, and biopsy of the uveal tissue. Treatment of BDUMP is directed towards the underlying malignancy and may include chemotherapy, radiotherapy, or surgical resection. Additionally, strict monitoring with regular follow-ups may contribute to the detection of new lesions and the reduction in the size of existing ones. CONCLUSIONS: BDUMP can be considered a potential biomarker in the management of malignancies, especially when the primary underlying tumor has not been detected. Further research is needed to better understand the pathogenesis of BDUMP and its association with malignancy.

Suboptimal outcomes and treatment burden of anti-vascular endothelial growth factor treatment for diabetic macular oedema in phakic patients.

OBJECTIVES: In England and Wales, treatment options were limited for patients with diabetic macular oedema (DMO) with phakic eyes that failed anti-vascular endothelial growth factor (anti-VEGF) treatment pre-2022. This study aimed to quantify the response to, and treatment burden of, anti-VEGF treatment in phakic eyes. METHODS: Retrospective, cohort study using electronic patient record data from two UK centres between 2015 and 2020. Primary objective was proportion of phakic eyes with a suboptimal response after initial 6 months of anti-VEGF treatment. Data were available for 500 eyes from 399 patients. RESULTS: At 6 months significantly more eyes had a suboptimal response to anti-VEGF treatment: 65.8% (95% CI 61.5-70.0%) vs 34.2% (95% CI 30.0-38.5%), p < 0.0001. Baseline visual acuity (VA) predicted VA outcome, however, despite greater gains in eyes with poorer VA, such eyes did not achieve the same VA levels as those who started treatment with better VA. Only 53.6% of eyes had more than three injections in the first 6 months indicating difficulties in delivering high volume/high frequency treatment. Treatment and review burden were similar over the following years regardless of response to anti-VEGF treatment. CONCLUSIONS: Data confirm previous real world evidence around response to anti-VEGF treatment, importance of baseline VA and frequency of injections in predicting outcomes in a UK setting. Continuing treatment beyond 6 months in suboptimal responders imposes unnecessary treatment burden without significant change in VA. In suboptimal responders, consideration of early switch to longer acting steroid treatments may help to reduce treatment burden, whilst maintaining or improving vision.

An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma.

In the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.

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.

Beta radiation for glaucoma surgery.

BACKGROUND: The outcome of glaucoma surgery can be affected by the rate at which the surgical wound heals. Beta radiation has been proposed as a rapid and simple treatment to slow down the healing response. OBJECTIVES: To assess the effectiveness of beta radiation during glaucoma surgery (trabeculectomy). SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 3), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 March 2012. SELECTION CRITERIA: We included randomised controlled trials comparing trabeculectomy with beta radiation to trabeculectomy without beta radiation. DATA COLLECTION AND ANALYSIS: We collected data on surgical failure (intraocular pressure > 21 mmHg), intraocular pressure and adverse effects of glaucoma surgery. We pooled data using a fixed-effect model. MAIN RESULTS: We found four trials that randomised 551 people to trabeculectomy with beta irradiation versus trabeculectomy alone. Two trials were in Caucasian people (126 people), one trial in black African people (320 people) and one trial in Chinese people (105 people). People who had trabeculectomy with beta irradiation had a lower risk of surgical failure compared to people who had trabeculectomy alone (pooled risk ratio (RR) 0.23 (95% CI 0.14 to 0.40). Beta irradiation was associated with an increased risk of cataract (RR 2.89, 95% CI 1.39 to 6.0). AUTHORS' CONCLUSIONS: Trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone. A trial of beta irradiation versus anti-metabolite is warranted.

Beta radiation for glaucoma surgery

BACKGROUND: The outcome of glaucoma surgery can be affected by the rate at which the surgical wound heals. Beta radiation has been proposed as a rapid and simple treatment to slow down the healing response. OBJECTIVE: To assess the effectiveness of beta radiation during glaucoma surgery (trabeculectomy). CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW: We searched the Cochrane Central Register of Controlled Trials (Central) in The Cochrane Library (which includes the Cochrane Eyes and Vision Group Trials Register) (Issue 4 2008), Medline (January 1966 to October 2008) and Embase (January 1980 to October 2008). The databases were last searched on 24 October 2008. SELECTION CRITERIA: We included randomized controlled trials comparing trabeculectomy with beta radiation to trabeculectomy without beta radiation. DATA COLLECTION AND ANALYSIS: We collected data on surgical failure (intraocular pressure > 21 mmHg), intraocular pressure and adverse effects of glaucoma surgery. We pooled data using a fixed-effect model. MAIN RESULTS: We found four trials that randomized 551 people to trabeculectomy with beta irradiation versus trabeculectomy alone. Two trials were in Caucasian people (126 people), one trial in black African people (320 people) and one trial in Chinese people (105 people). People who had trabeculectomy with beta irradiation had a lower risk of surgical failure compared to people who had trabeculectomy alone (pooled risk ratio (RR) 0.23 (95% CI 0.14 to 0.40). Beta irradiation was associated with an increased risk of cataract (RR 2.89, 95% CI 1.39 to 6.0). AUTHORS'CONCLUSIONS: Trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone. A trial of beta irradiation versus anti-metabolite is warranted.

Beta radiation for glaucoma surgery.

BACKGROUND: The outcome of glaucoma surgery can be affected by the rate at which the surgical wound heals. Beta radiation has been proposed as a rapid and simple treatment to slow down the healing response. OBJECTIVES: To assess the effectiveness of beta radiation during glaucoma surgery (trabeculectomy). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (which includes the Cochrane Eyes and Vision Group Trials Register) (Issue 4 2008), MEDLINE (January 1966 to October 2008) and EMBASE (January 1980 to October 2008). The databases were last searched on 24 October 2008. SELECTION CRITERIA: We included randomised controlled trials comparing trabeculectomy with beta radiation to trabeculectomy without beta radiation. DATA COLLECTION AND ANALYSIS: We collected data on surgical failure (intraocular pressure > 21 mmHg), intraocular pressure and adverse effects of glaucoma surgery. We pooled data using a fixed-effect model. MAIN RESULTS: We found four trials that randomised 551 people to trabeculectomy with beta irradiation versus trabeculectomy alone. Two trials were in Caucasian people (126 people), one trial in black African people (320 people) and one trial in Chinese people (105 people). People who had trabeculectomy with beta irradiation had a lower risk of surgical failure compared to people who had trabeculectomy alone (pooled risk ratio (RR) 0.23 (95% CI 0.14 to 0.40). Beta irradiation was associated with an increased risk of cataract (RR 2.89, 95% CI 1.39 to 6.0). AUTHORS' CONCLUSIONS: Trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone. A trial of beta irradiation versus anti-metabolite is warranted.

Age-related macular degeneration: what do patients find on the internet?

OBJECTIVE: To assess the quality of information and readability of the top internet sites for age-related macular degeneration (AMD). DESIGN: An examination of the technical information provision, quality and readability of websites found during an internet search for 'age-related macular degeneration'. Setting Six internet search engines were used to find 26 unique sites on AMD. MAIN OUTCOME MEASURES: Technical information and quality were assessed using a simple grading system. Readability was assessed using a Simple Measure Of Gobbledygook (SMOG) rating. RESULTS: Twelve organizational, seven academic and seven commercial sites were identified. The average technical scores were 82.3%, 67.9% and 65.2% for each type of site, respectively (P=0.097, one way ANOVA). The average quality scores were 62.2%, 62.6%, and 49.5% for each type of site, respectively (P=0.356, one-way ANOVA). The average SMOG ratings were 16.3, 16.1, and 16.2 for each type of site, respectively (P=0.983, one-way ANOVA). Fifteen of the sites provided details of new and emerging treatments, with seven providing a detailed discussion. CONCLUSIONS: Many websites are now meeting the challenge of providing comprehensive information about AMD and its new treatments. Quality scores were disappointing, with sites needing to provide more evidence of authorship and attribution of information. The majority of sites had SMOG scores above 10, making them difficult for the average person to understand. As physicians we need to help design and direct patients to sites that provide high quality, current information.