Sunderland Eye Infirmary

Idiopathic epiretinal membrane (iERM) can affect vision in complex ways, requiring assessment beyond visual acuity. We developed a core outcome set (COS) for patients undergoing surgery for macular pucker secondary to iERMs for use in both clinical practice and clinical trials. An online modified Delphi technique was used, incorporating literature review, stakeholder workshops and two-round Delphi survey, each followed by a hybrid consensus meeting. Stakeholders, including health professionals and patients rated the importance of each outcome on a 9-point Likert scale (1-3, not important; 4-6, important; 7-9, very important). Outcomes scored as 'very important' by ≥80% of stakeholders were included in the COS. Sixty-two outcomes were initially included. Only one outcome reached consensus after the first vote, a further 10 after the second vote and five in the final vote. After discussion and considering clinical relevance and patient importance, the initial list of 17 outcomes was reduced to 13 core outcomes, grouped into six overarching domains: measured visual function, symptoms, adverse events, functional ability, quality of life and other, including objective measurements of anatomical findings. A minimum COS for iERMS comprising 13 outcomes covering six domains was generated by the modified Delphi process. The COS is not yet ready for use as the methods of assessment and the time points remain to be determined before it can be used in practice. Future research will test the implementation of the COS in clinical practice and its' potential incorporation into future trials.

We report a rare case of a 59-year-old male with bilateral chronic multifocal central serous chorioretinopathy (CSCR) who developed retinal neovascularization (RNV). This patient had been under review for CSCR for several years before developing a new frond of RNV in his right eye. Comprehensive investigations, including fundus fluorescein angiography, were performed to exclude alternative causes such as diabetic retinopathy, vascular occlusion, or retinal vasculitis. He was treated with three intravitreal injections of bevacizumab and received sectoral panretinal photocoagulation laser with good response and regression of the vessel appearance.

To identify risk factors affecting the change in visual acuity in successfully re-attached macula-off rhegmatogenous retinal detachment (RD) surgery. A cohort study, using an online database, of visual outcomes for 2770 macula-off retinal detachments that were successfully re-attached by vitrectomy and internal tamponade. The database included detailed retinal diagrams of each detachment. The change in LogMAR visual acuity from pre-operatively to post-operatively. Male patients accounted for 64.6% of the sample and the median age was 63 years old. The median pre-operative VA was counting fingers (LogMAR 1.98); this improved to 0.30 LogMAR post-operatively. An improvement in VA of ≥0.30 LogMAR was achieved by 88.0% eyes. The change in VA model identified the preoperative VA, patient age, duration of central vision loss, lens status at follow up, extent of detachment, and the number of breaks in the detached retina, as factors influencing the change in VA. The model had an adjusted R2 of 0.749, and for 75.5% of eyes, the model prediction was within ±0.30 LogMAR of the recorded VA change. Greater post-operative visual acuity improvement was more likely in eyes that were pseudophakic at follow up, and had shorter durations of central vision loss. Non modifiable factors associated with greater vision improvement included worse presenting vision, younger age, less extensive detachment and less than three breaks in the detached retina. These results confirm that prompt surgery improves functional outcomes in successfully treated macula off retinal detachments irrespective of presenting visual acuity.

Abstract 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<54 ETDRS letter score. The OCT parameters found to be associated with reduced odds of 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.

TopicTo assess the anatomical and visual effects of facedown positioning (FDP) advice in patients undergoing vitrectomy with gas tamponade for idiopathic full-thickness macular holes (FTMHs), and to explore differential treatment effects by macular hole size and FDP duration. Clinical relevanceThe necessity and duration of FDP for FTMH closure remain contentious, with no consensus guidelines. MethodsProspectively registered systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials comparing FDP to no FDP (nFDP) across the MEDLINE, Embase, and Cochrane Library databases and clinical trial registries from January 2000 to March 2023 (CRD42023395152). All adults with idiopathic FTMHs undergoing vitrectomy with gas tamponade were included. The main outcomes were primary macular hole closure and post-operative visual acuity at 6 months or nearest time point. ResultsOf 8 eligible trials, 5 contributed IPD for 379 eyes and were included in our analysis. The adjusted odds ratio (OR) for primary closure with FDP versus nFDP was 2.41 (95% CI 0.98 to 5.93, P = 0.06) [GRADE: Low], translating to a relative risk (RR) of 1.08 (1.00 to 1.11) and a number needed to treat (NNT) of 15. The FDP group exhibited a mean improvement in post-operative visual acuity of -0.08 logMAR (-0.13 to -0.02, P = 0.006) [GRADE: Low] compared to the nFDP group. Benefits were more certain in participants with larger holes of minimum linear diameter ≥ 400 μm: adjusted OR for closure ranged from 1.13 to 10.12 (P = 0.030) (NNT 12), with a mean visual acuity improvement of -0.18 to -0.01 logMAR (P = 0.022). Each additional day of FDP was associated with improved odds of anatomical success (adjusted OR 1.02 to 1.41, RR 1.00 to 1.02, P = 0.026) and visual acuity improvement (-0.02 logMAR, -0.03 to -0.01, P = 0.002), possibly plateauing at 3 days. ConclusionThis study provides low certainty evidence that FDP improves the anatomical and visual outcomes of macular hole surgery modestly and indicate that the effect may be more substantial for macular holes exceeding 400 μm. The findings support recommending FDP for patients with macular holes exceeding 400 μm pending further investigation.

Abstract ObjectiveComplement biomarker analysis in ocular fluid samples from subjects with geographic atrophy (GA) in a Phase I/II clinical trial of subretinal AAV2 complement factor I (CFI; FI) gene therapy, PPY988 (formerly GT005), to understand target pharmacokinetics/pharmacodynamics. Clinical findings were subsequently utilized to investigate the therapeutic dose in anin vitrocomplement activation assay.Design, setting and participantsBiomarker data were evaluated from 28 subjects in FOCUS, a Phase I/II clinical trial evaluating the safety and efficacy of three ascending doses of PPY988.Main outcomes and measuresVitreous humor (VH), and aqueous humor (AH) from subjects before surgery and at serial timepoints (week 5 or 12, 36, 96) were evaluated for changes in levels of intact complement factors I, B and H (FI, FB, FH) components C3, C4, and C1q and breakdown products (Ba, C3a, C3b/iC3b, C4b) using validated assays and OLINK®proteomics.A modifiedin vitroassay of complement activation modelling VH complement concentrations was used to compare PPY988 potency to the approved intravitreal C3 inhibitor pegcetacoplan (Apellis) and complement Factor H (FH).ResultsAn average 2-fold increase in VH FI was observed post-treatment at week 36 and week 96. This correlated with a marked post-treatment reduction in VH concentration of the FB breakdown product Ba and Ba:FB ratio, but minimal changes in C3a and C3b/iC3b levels. Variable concordance in complement biomarker levels in VH versus AH suggest AH is not a reliable proxy for VH for complement activation. During the experimental comparison of doses, a 2-fold increase of FI achieved in the vitreous had only a minor effect on the complement amplification loopin vitro, indicating limited impact [IC50: 1229nM]. Pegcetacoplan completely blocks C3a generation at concentrations much lower than the estimated trough level for monthly intravitreal injections [IC50: 2nM]. Supplementation with FH in the assay revealed similar potency to pegcetacoplan [IC50: 6nM].Conclusions and relevancePPY988 subretinal gene therapy may not have provided sufficient FI protein to meaningfully modulate complement activation to slow GA growth. Reviewing VH biomarkers is important for understanding target expression, pathway engagement, and determining optimal dose, thereby informing future clinical development.

Despite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal therapies. Further research is likely to have an important impact on our confidence in the estimates of adverse effects and may change these. The optimal dosing regimens, treatment duration, and cost-effectiveness of such therapies are yet to be established.

PurposeOptical coherence tomography (OCT) has recently emerged as a source for powerful biomarkers in neurodegenerative diseases such as multiple sclerosis (MS) and neuromyelitis optica (NMO). The application of machine learning techniques to the analysis of OCT data has enabled automatic extraction of information with potential to aid the timely diagnosis of neurodegenerative diseases. These algorithms require large amounts of labeled data, but few such OCT data sets are available now.MethodsTo address this challenge, here we propose a synthetic data generation method yielding a tailored augmentation of three-dimensional (3D) OCT data and preserving differences between control and disease data. A 3D active shape model is used to produce synthetic retinal layer boundaries, simulating data from healthy controls (HCs) as well as from patients with MS or NMO.ResultsTo evaluate the generated data, retinal thickness maps are extracted and evaluated under a broad range of quality metrics. The results show that the proposed model can generate realistic-appearing synthetic maps. Quantitatively, the image histograms of the synthetic thickness maps agree with the real thickness maps, and the cross-correlations between synthetic and real maps are also high. Finally, we use the generated data as an augmentation technique to train stronger diagnostic models than those using only the real data.ConclusionsThis approach provides valuable data augmentation, which can help overcome key bottlenecks of limited data.Translational RelevanceBy addressing the challenge posed by limited data, the proposed method helps apply machine learning methods to diagnose neurodegenerative diseases from retinal imaging.