Faruque Ghanchi

Background: Long-term real-world data on the efficacy of Faricimab in nAMD remains scarce. Functional and structural outcomes for both treatment naïve (TN) and previous treatment exposed (TE) patients up to 104 weeks are reported. Methods: 107 eyes (37 TN and 70 TE) from 92 patients treated at Bradford Macula Centre were included in this retrospective cohort study. TE patients were grouped according to their pre-switch injection interval; the short interval (4–5 weeks) “SITE” group and the long interval ( ≥ 6 weeks) “LITE” group. Data was extracted on visual acuity (VA), central macular thickness (CMT), presence and type of retinal fluid and injection interval at the following timepoints: baseline, 12weeks, 26 weeks, 52 weeks, 78 weeks and 104 weeks. Results: TN patients gained a mean of +5.4 letters by 52 weeks reducing to +4.5 by 104 weeks. This coincided with a reduction in CMT and decrease in all types of retinal fluid. TE eyes showed attrition of VA despite a reduction in CMT, and by 104 weeks the “LITE” group had lost significantly more letters than the “SITE” group ( p = 0.003). By 104 weeks the macula was dry in 48.5% of TN eyes, 42.4% of “LITE” eyes and 31.0% of “SITE” eyes. The proportion of patients achieving a ≥12week interval by 104 weeks was 54.5% TN, 32.4% “LITE” and 17.2% “SITE” respectively. Conclusion: Faricimab is an effective treatment for naïve eyes with nAMD, where retinal structural and functional improvement can be maintained for 2 years in real-world practice. Treatment experienced eyes show modest improvement in structure and no improvement in vision with Faricimab, and some TE eyes continue to lose vision over 2 years. Longer treatment intervals can be possible, but vigilance for undertreatment is needed. Further studies will help evaluate the long-term impact.

Background/objectives: Therapies with robust visual outcomes and reduced patient and healthcare system treatment burden are needed amidst the rising incidence of neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg is an additional treatment option with demonstrated potential for extended dosing intervals of up to 24 weeks. The objective of this publication is to introduce a clinical care pathway, developed by expert consensus of experienced UK clinicians, to support best practice with aflibercept 8 mg in nAMD. Methods: A structured, face-to-face roundtable meeting of 13 UK retina specialists was held on 8 October 2024, organised and funded by Bayer. The expert panel reached consensus following review of key clinical trial data and consideration of current NHS clinical practice to provide guidance on the use of intravitreal aflibercept 8 mg in nAMD. Results: The panel provided recommendations for an aflibercept 8 mg treat-and-extend pathway for both treatment-naïve and previously treated patients with nAMD. Criteria were developed to guide dosing interval extension, reduction or maintenance based on visual acuity and optical coherence tomography imaging. More detailed guidance includes considerations for switching treatments to or from aflibercept 8 mg, monitoring, and discontinuing treatment. Conclusions: Aflibercept 8 mg may offer opportunities for longer treatment intervals and reduced patient and clinic burden compared with first-generation agents. The proposed treatment pathway is practical and accounts for variability in healthcare structures and capacity pressures, providing clinicians with flexibility in implementing these recommendations while addressing patient needs.

Purpose To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect. Methods Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations. In addition, VA outcomes based on different combinations of eligibility criteria were assessed. Results A total of 1999 eyes of 1862 patients were analysed. The mean age was 79.3 (SD 7.8) years. The mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. A statistical difference in VA was found after first injection (visit 2, 61.6, SD 14.3 ETDRS letter score) and after three monthly injections (visit 4, 62.7, SD 14.9 ETDRS letter score) (P < 0.001). Lower baseline VA and OCT features suggestive of structural changes in the fovea are associated with lower VA after both first and post- initiating doses. Eyes with baseline VA > / = 54 letters alone had similar VA outcomes to eyes with both VA > / = 54 letters and central subfield thickness (CST) of <500 microns. Conclusion Mean VA outcomes after three monthly anti-VEGF injections are significantly better than after the first initiating dose. However, baseline OCT characteristics associated with VA in these two timepoints are not clinically different.

Purpose To identify demographic and baseline OCT characteristics that are predictive of VA outcomes after the first and post-loading injections in patients treated with 2 mg aflibercept. Methods This study evaluated VA outcomes in 1999 eyes of 1862 patients with nAMD initiated on aflibercept therapy. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA outcome defined as VA ≥ 68 ETDRS letters (Snellen ≥ 6/12) and poor VA outcome of <54 ETDRS letters (Snellen < 6/18) or a loss of ≥5 ETDRS letters after first and post-loading injections were analysed using logistic regression via generalised estimating equations. Results The mean age was 79.3 (SD 7.8) years, 1126 (60.5%) were females, and predominantly white ethnic background (1772 [95.2%]). The mean presenting VA was 58.0 (SD 14.5) ETDRS letters. After the loading phase, 930/1994 (46.6%) eyes achieved VA ≥ 68 ETDRS letters, and 457 (22.9%) attained VA < 54 ETDRS letters. Increasing age, non-white ethnicity, and baseline VA < 54 letter score is associated with VA < 54 letters. The OCT parameters associated with reduced odds of VA ≥ 68 ETDRS letters and increased odds of VA < 54 ETDRS letters after first and post-loading phase included fovea-involving intraretinal fluid, all types of macular neovascularisation (MNV) versus type 1 MNV, fovea-involving MNV (vs. non-foveal MNV), subfoveal MNV complex, increased central subfield thickness, foveal presence of subretinal hyper-reflective material, atrophy, fibrosis, ungradable or ellipsoid zone and/or external limiting membrane loss. Conclusion This study could provide individual-level visual prognosis about their post-loading VA based on demography, VA and OCT characteristics at presentation.

PURPOSE: To examine baseline OCT characteristics of patients initiated on aflibercept 2mg that achieved good and suboptimal VA after the first injection and post-loading. METHODS: Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA>=68 ETDRS letter score, Snellen >= 6/12) and poor VA (VA < 54 letter score, Snellen < 6/18) or lost >= 5 ETDRS letters after first injection (V2) and after the loading phase (V4) were analysed using logistic regression via generalised estimating equations. RESULTS: A total of 1,999 eyes of 1,862 patients were analysed. The mean age was 79.3 (SD 7.8) years, 1,126 (60.5%) were female, predominantly white ethnic background (1,772 [95.2%]) and the mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. After V4, 930 (46.6%) of 1,994 eyes achieved VA>=68 ETDRS letter score and 457 (22.9%) achieved VA=68 ETDRS letter score and increased odds of VA < 54 ETDRS letter score included foveal-involving IRF, PCV (vs. Type 1), RAP (vs. Type 1), Type 2 eyes (vs. Type 1), foveal-involving CNV (vs. non-foveal CNV), any component of CNV complex, increased CST, foveal-involving SRHM, foveal-involving atrophy, foveal-involving fibrosis, foveal-involving EZ loss, foveal-involving ELM loss, ungradable EZ loss, ungradable ELM loss and foveal-involving EZ/ELM loss. CONCLUSION: This study could help inform patients about their post-loading VA based on OCT characteristics at presentation.

Objectives: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)’s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. Methods: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. Results: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). Conclusions: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.

Objective To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD). Methods Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated. Results A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST) are considered, 90% will be eligible for interval extension. Conclusion Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.

The development of many tools and technologies for people with visual impairment has become a major priority in the field of assistive technology research. However, many of these technology advancements have limitations in terms of the human aspects of the user experience (e.g., usability, learnability, and time to user adaptation) as well as difficulties in translating research prototypes into production. Also, there was no clear distinction between the assistive aids of adults and children, as well as between “partial impairment” and “total blindness”. As a result of these limitations, the produced aids have not gained much popularity and the intended users are still hesitant to utilise them. This paper presents a comprehensive review of substitutive interventions that aid in adapting to vision loss, centred on laboratory research studies to assess user-system interaction and system validation. Depending on the primary cueing feedback signal offered to the user, these technology aids are categorized as visual, haptics, or auditory-based aids. The context of use, cueing feedback signals, and participation of visually impaired people in the evaluation are all considered while discussing these aids. Based on the findings, a set of recommendations is suggested to assist the scientific community in addressing persisting challenges and restrictions faced by both the totally blind and partially sighted people.

Purpose: To compare the baseline characteristics in patients with and without early residual fluid (ERF) after aflibercept loading phase (LP) in patients with treatment naïve neovascular age related macular degeneration (nAMD). Methods: Patients with nAMD initiated on LP of three intravitreal aflibercept doses were recruited from December 2019 to August 2021. Baseline demographic and OCT features associated with any ERF were analysed using Generalised Estimating Equations to account for inter-eye correlation. Receiver operating characteristic (ROC) curve was performed for selection of CST threshold. Results: Of 2128 patients enrolled, 1999 eyes of 1862 patients with complete data were included. After LP, ERF was present in 1000 (50.0%), eSRF in 746(37.3%) and eIRF in 428 (21.4%) eyes. In multivariable analysis of baseline features, eyes with increased central subfield thickness (CST) (OR 1.31 per 100 microns increase [95% CI 1.22 to 1.41]; P < 0.001), eyes with IRF and SRF at baseline (1.62 [95% CI 1.17 to 2.22]; P = 0.003), and those with SRF only (OR 2.26 [95% CI 1.59 to 3.20]; P < 0.001) relative to IRF only were determinants of ERF. CST ≥ 418 microns had 57% sensitivity and 58% specificity to distinguish ERF from no ERF at visit 4. Conclusion: On average, 50% of eyes have ERF after aflibercept LP. Clinically relevant baseline determinants of ERF include CST ≥ 418 µ and presence of only SRF. These eyes may require further monthly treatment before extending treatment intervals.

Purpose To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD). Methods Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA ≥ 68 ETDRS letters, Snellen ≥ 6/12) and poor VA (VA < 54 letters, Snellen < 6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation. Results Of 2274 eyes of 2128 patients enrolled, 2039 eyes of 1901 patients with complete data were analysed. Mean age was 79.4 (SD 7.8) years, female:male 3:2 and mean VA 58.0 (SD 14.5) letters. On multivariable analysis VA < 54 letters was associated with increased central subfield thickness (CST) (OR 1.40 per 100 µm; P < 0.001), foveal intraretinal fluid (OR 2.14; P < 0.001), polypoidal vasculopathy (PCV) relative to Type 1 macular neovascularisation (MNV) (OR 1.66; P = 0.049), presence of foveal subretinal hyperreflective material (SHRM) (OR 1.73; P = 0.002), foveal fibrosis (OR 3.85; P < 0.001), foveal atrophy (OR 5.54; P < 0.001), loss of integrity of the foveal ellipsoid zone (EZ) or external limiting membrane (ELM) relative to their preservation (OR 3.83; P < 0.001) and absence of subretinal drusenoid deposits (SDD) (presence vs absence; OR 0.75; P = 0.04). These features were associated with reduced odds of VA ≥ 68 letters except MNV subtypes and SDD. Conclusion Presence of baseline fovea-involving atrophy, fibrosis, intraretinal fluid, SHRM, PCV EZ/ELM loss and increased CST determine poor presenting VA. This highlights the need for early detection and treatment prior to structural changes that worsen baseline VA.