Patient acceptability of intravitreal complement inhibitors in geographic atrophy (GA): protocol for a UK-based cross-sectional study.

INTRODUCTION: Geographic atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD). Previously untreatable, complement inhibitors delivered by regular intravitreal injections have recently been demonstrated to slow down the progression of GA lesions in phase 3 trials. One such treatment, Syfovre (pegcetacoplan), was approved by the US Food and Drug Administration in February 2023. These therapies slow down, but do not stop or reverse, the progression of GA; they may also increase the risk of developing the neovascular ('wet') type of AMD. In light of these developments, this study aims to quantify the acceptability of these new intravitreal injection treatments to patients with GA in the UK and explore factors that may influence the acceptability of these treatments. METHODS AND ANALYSIS: In this cross-sectional, non-interventional study, the primary objective is to determine the proportion of patients with GA that find regular intravitreal therapy acceptable for slowing the progression of GA. We will use a validated acceptability questionnaire in order to quantify the acceptability of new treatments among patients with GA. The correlation between acceptability and functional and structural biomarkers of GA will be established. We will also explore demographic, general health and ocular factors that may influence acceptability. 180 individuals with a diagnosis of GA will be recruited from 7 to 8 participating National Health Service trusts across the UK. Multiple regression analysis will be conducted to determine the simultaneous effects of multiple factors on patient acceptability. ETHICS AND DISSEMINATION: The study received ethical approval from the Health Research Authority on 14 March 2023 (IRAS Project ID: 324854). Findings will be disseminated through peer-reviewed publications and conference presentations to the medical retina community, as well as through dialogue with patients and macular disease charities.

Piloting a forced-choice task to elicit treatment preferences in geographic atrophy.

OBJECTIVE: Geographic Atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD) and responsible for one-quarter of legal blindness in the UK. New therapies delivered by intravitreal injection are in late-stage development, and two such therapies (pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay)) have now been approved for clinical use by the US Food and Drug Administration. These therapies slow down, but do not stop or reverse, progression of GA and they may also increase the risk of developing the neovascular ('wet') type of AMD. Within a larger study exploring the acceptability of these new treatments to people living with GA, we developed a forced-choice exercise to evaluate how participants weigh up benefits and drawbacks of different treatment regimens. This research note reports quantitative and qualitative findings from this exercise. RESULTS: Twenty-eight participants took part in this exercise. The exercise demonstrated that participants were generally, although not unanimously, in favour of less frequent treatment for GA that was slightly less efficacious in terms of preserving visual function but presented a lower risk of developing wet AMD. Even among a small sample, the exercise demonstrated the highly personal and idiosyncratic decision-making processes influencing participants' choices of preferred hypothetical GA treatment.

Exploring patient acceptability of emerging intravitreal therapies for geographic atrophy: A mixed-methods study.

BACKGROUND/OBJECTIVES: The acceptability of emerging intravitreal therapies for patients with Geographic Atrophy (GA) is currently unknown. This study therefore aimed to investigate the extent to which regular intravitreal injections may be acceptable to GA patients. SUBJECTS/METHODS: Thirty UK-based individuals with GA secondary to age-related macular degeneration (AMD), recruited from two London-based hospitals, were interviewed in April-October 2021 regarding acceptability of new GA treatments. Participants responded to a structured questionnaire, as well as open-ended questions in a semi-structured interview. The Theoretical Framework of Acceptability (TFA) informed framework analysis of the qualitative data. RESULTS: Twenty participants (67%) were female, and median (interquartile range (IQR)) age was 83 (78, 87) years. 37% of participants had foveal centre-involving GA, and better eye median (IQR) logMAR visual acuity was 0.30 (0.17, 0.58). Data suggested that 18 participants (60% (95% CI: 41-79%)) would accept the treatment, despite awareness of potential drawbacks. Eight participants (27% (95% CI: 10-43%) were ambivalent or undecided about treatment, and four (13%) (95% CI: 0-26%) would be unlikely to accept treatment. Reducing the frequency of injections from monthly to every other month increased the proportion of participants who considered the treatments acceptable. Conversely, factors limiting acceptability clustered around: the limited magnitude of treatment efficacy; concerns about side effects or the increased risk of neovascular AMD; and the logistical burden of regular clinic visits for intravitreal injections. Misunderstandings of potential benefits indicate the need for appropriately-designed patient education tools to support decision-making. CONCLUSIONS: Our study suggests a majority of participants would be positive about intravitreal treatment for GA, in spite of potential burdens.

Towards a Therapy for Geographic Atrophy: A Patient's Experience.

Purpose: Geographic atrophy (GA) is the advanced form of the non-neovascular (dry) type of age-related macular degeneration. Presently, GA cannot be treated. However, new therapies administered by intravitreal injection are in late-stage development. These can slow down, but do not stop or reverse, GA progression. The acceptability of these emerging therapies to people with GA is currently unknown. The present case study explores the perspectives of a person living with GA who took part in the terminated Phase 3 clinical trial of Lampalizumab, a candidate intravitreal treatment for GA. We explored this patient's perspective on the retrospective acceptability of regular Lampalizumab injections, and the prospective acceptability of future intravitreal therapies for GA. Patients and Methods: A 78-year-old woman living in the UK was recruited as part of a mixed-methods pilot study and interviewed by telephone, regarding: her experience of the Lampalizumab trial injections; and her thoughts regarding emerging intravitreal therapies for GA. The Framework Method was used for initial inductive analysis of the interview transcript. Subsequently, deductive analysis was undertaken, informed by the Theoretical Framework of Acceptability (TFA). Results: For this participant, intravitreal injections in the Lampalizumab trial were acceptable, although streamlining processes within the clinic would have improved the patient experience. Regarding prospective acceptability of new intravitreal therapies, the participant considered a delay in progression of GA a valuable goal. Potential discomfort, anxiety and inconvenience associated with regular intravitreal injections would be acceptable in the context of preserving her vision for as long as possible. Conclusion: Analysis of one participant's experience demonstrates the value of exploring GA patients' unique views on the acceptability of new intravitreal treatments. Larger prospective studies will provide more insight that help to optimise treatment design and delivery, thereby maximising likelihood of adherence and persistence when these therapies eventually arrive in clinic.

Correction: Aflibercept for treatment-naïve diabetic macula oedema in a multi-ethnic population: Real-world outcomes from North West London.

[This corrects the article DOI: 10.1371/journal.pone.0246626.].

Factors Influencing Response to Aflibercept in Diabetic Macular Oedema Patients in a Diverse North West London Population: A Real-World Study.

BACKGROUND: Diabetic macular oedema (DMO) is the leading cause of sight impairment in working age populations in developed countries. Current first line treatment for centre-involving DMO involves intravitreal anti-VEGF but treatment response can be variable. In this retrospective, real world, multi-centre cohort study, we aim to identify ocular and systemic characteristics that correlate with anatomical and functional outcomes for treatment-naive DMO patients treated with intravitreal aflibercept. METHODS: Retrospective multicentre cohort study of treatment-naive DMO patients initiated on aflibercept at three North West London hospitals between 2016 and 2018. Baseline systemic and ocular factors, best corrected visual acuity (BCVA) and central macular thickness (CMT) at 12 months were determined and statistically analysed. RESULTS: A total of 270 eyes of 221 DMO patients met inclusion criteria. Mean age was 62.8 ± 12.1, mean baseline HbA1c was 67 ± 20 mmol/mol, and mean eGFR was 72 mL/min/1.7m2. Mean number of aflibercept injections at 12 months was 6.2. Better baseline BCVA, lower baseline CMT, and absence of epiretinal membrane (ERM) were associated with better BCVA at 12 months whilst lower baseline CMT and proliferative retinopathy status were associated with lower CMT at 12 months. CONCLUSION: Our study is the largest real-world dataset examining factors influencing functional and anatomical response to aflibercept in DMO in the UK. Older age, lower baseline BCVA, higher baseline CMT and more severe diabetic retinopathy were associated with poorer visual acuity at 12 months and prioritisation of these patients within a pressured healthcare setting is recommended.

Acceptability of intravitreal injections in geographic atrophy: protocol for a mixed-methods pilot study.

INTRODUCTION: Age-related macular degeneration (AMD) is a common cause of visual impairment, affecting central vision. Geographic atrophy (GA) is an advanced form of the non-neovascular (dry) type of AMD. Late-stage clinical trials suggest that intravitreal injections of novel therapeutics may slow down the rate of GA progression by up to 30% in 1 year, thus allowing people with GA to preserve central vision for a longer period. While intravitreal injections have become an established treatment modality for neovascular (wet) AMD, it is unknown whether patients with (more gradually progressing) GA would accept regular injections that slow down, but do not stop or reverse, vision loss. Therefore, this mixed-methods pilot study will aim to explore whether regular intravitreal injections will be acceptable as treatment for patients with GA, and the factors that may affect treatment acceptability. METHODS AND ANALYSIS: A mixed-methods survey has been designed in collaboration with a GA patient advisory group. The survey comprises of structured questionnaires, semi-structured interview questions regarding patients' perceptions of intravitreal injections and the burden of treatment, and a task eliciting preferences between different potential treatments. Due to COVID-19 restrictions, this study will be conducted remotely by telephone. Thirty individuals will be recruited from NHS Medical Retina clinics at Central Middlesex Hospital, London. Half of the participants will be naïve to intravitreal injections, while half will have previous experience of intravitreal injections for neovascular (wet) AMD. Qualitative data analysis will be conducted using the Framework Method of analysis to identify key themes from participants' accounts. ETHICS AND DISSEMINATION: The study received Health Research Authority approval on 23 March 2021 (IRAS Project ID: 287824). Findings will be disseminated through peer-reviewed publications and conference presentations to the medical retina community, as well as through dialogue with patients and macular disease charities.

Aflibercept for treatment-naïve diabetic macula oedema in a multi-ethnic population: Real-world outcomes from North West London.

PURPOSE: To evaluate the clinical outcomes of patients with treatment-naïve diabetic macula oedema (DMO) treated with Aflibercept in routine clinic settings in ethnically diverse North West London (NWL) and compare to outcomes reported in the VIVID and VISTA clinical trials. METHODS: This was a retrospective multicentre interventional case series. Two hundred and seventy eyes of 221 treatment-naïve patients at three NWL hospitals initiated on Aflibercept and who had at least 12 months follow-up were included in the study. Visual acuity, central subfield thickness and macula volume were recorded at baseline, month 3, 6 and 12. RESULTS: There were significant differences between the NWL cohort and participants in the VIVID and VISTA trials at baseline including higher HbA1c and a higher proportion of eyes with proliferative diabetic retinopathy in the NWL cohort. The mean VA, mean CSFT and mean MV at baseline was 66.4 (± 14.6) letters, 417 (± 94) µm and 10.3 (± 1.9) mm3. The mean VA gain at 12 months was 4.0 (± 11.8) letters (p < 0.001); a total of 26% of eyes gained ≥ 10 letters, 15% of eyes gained ≥ 15 letters and 6% lost ≥15 letters. At 12-months, the mean reduction in CSFT was 108 (± 96) µm (p<0.001) and the mean reduction in MV was 1.05 (± 1.21) mm3 (p<0.001). An average of 6.2 (± 2.3) injections was given over 12 months. There was a significant association between functional and anatomical response category at 3 months and response category at 12 months (p<0.001). CONCLUSION: The effectiveness of treatment with Aflibercept for patients in NWL was meaningfully lower than was reported in the VIVID and VISTA clinical trials. A high proportion of patients with good visual acuity at baseline, poorer glycaemic control, worse diabetic retinopathy and under-treatment likely contributed to lower functional and anatomical outcomes.