Real-World Data on Faricimab Switching in Treatment-Refractory Neovascular Age-Related Macular Degeneration.

Faricimab is a newly approved bispecific antibody for neovascular age-related macular degeneration (nAMD). Our study aims to evaluate clinical outcomes of faricimab switching in patients with treatment-refractory nAMD; determine parameters that predict these outcomes; and obtain patient subjective experience on this new injection. This is a retrospective case review with clinical and imaging data from a tertiary referral unit (Birmingham and Midland Eye Centre, UK), involving patients who were switched to faricimab between 1 January and 1 December 2023. In all, 63 eyes (54 patients) with a mean age of 79.2 ± 7.8 and mean of 41.5 ± 22.4 previous anti-VEGF injections were analysed. With a mean of 4.81 ± 1.16 faricimab injections over 6.98 ± 1.75 months, post-treatment visual acuity was logMAR 0.49 ± 0.36 and central macular thickness (CMT) was 320.3 ± 97.9 µm. After first dose, 39.1% achieved complete dryness and 89.1% had anatomical improvement. Presence of subretinal fluid was a predictor of better functional outcomes (p = 0.001, ß = -0.182), while initial CMT predicted better anatomical outcomes (p = 0.001, ß = 0.688). Compared to their experiences of previous anti-VEGF injections, 89% of patients reported no more discomfort and 87.0% experienced no more floaters, photopsia, or bubbles post-injection. Faricimab switching has anatomical efficacy but limited functional improvement in treatment-refractory AMD. Patient experiences of faricimab compared to previous injections were overall positive.

Diabetic retinopathy progression in patients under monitoring for treatment or vision loss: external validation and update of a multivariable prediction model.

INTRODUCTION: The number of people with diabetes mellitus is increasing globally and consequently so too is diabetic retinopathy (DR). Most patients with diabetes are monitored through the diabetic eye screening programme (DESP) until they have signs of retinopathy and these changes progress, requiring referral into hospital eye services (HES). Here, they continue to be monitored until they require treatment. Due to current pressures on HES, delays can occur, leading to harm. There is a need to triage patients based on their individual risk. At present, patients are stratified according to retinopathy stage alone, yet other risk factors like glycated haemoglobin (HbA1c) may be useful. Therefore, a prediction model that combines multiple prognostic factors to predict progression will be useful for triage in this setting to improve care.We previously developed a Diabetic Retinopathy Progression model to Treatment or Vision Loss (DRPTVL-UK) using a large primary care database. The aim of the present study is to externally validate the DRPTVL-UK model in a secondary care setting, specifically in a population under care by HES. This study will also provide an opportunity to update the model by considering additional predictors not previously available. METHODS AND ANALYSIS: We will use a retrospective cohort of 2400 patients with diabetes aged 12 years and over, referred from DESP to the NHS hospital trusts with referable DR between 2013 and 2016, with follow-up information recorded until December 2021.We will evaluate the external validity of the DRPTVL-UK model using measures of discrimination, calibration and net benefit. In addition, consensus meetings will be held to agree on acceptable risk thresholds for triage within the HES system. ETHICS AND DISSEMINATION: This study was approved by REC (ref 22/SC/0425, 05/12/2022, Hampshire A Research Ethics Committee). The results of the study will be published in a peer-reviewed journal, presented at clinical conferences. TRIAL REGISTRATION NUMBER: ISRCTN 10956293.

Clinical efficacy and safety of intravitreal fluocinolone acetonide implant for the treatment of chronic diabetic macular oedema: five-year real-world results.

BACKGROUND/AIM: To report 5-year real-world efficacy and safety data following the treatment of chronic diabetic macular oedema (DMO) with the intravitreal 0.19 mg fluocinolone acetonide implant(ILUVIEN). METHODS: Retrospective cohort study of 31 eyes treated with ILUVIEN for chronic DMO at a tertiary centre in Birmingham (UK). Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline, and then at 1-,2-,3-, and 5-years. Safety was assessed based on intraocular pressure (IOP) -lowering medication, surgery, and other complications. RESULTS: BCVA significantly improved 1-year post-ILUVIEN (+4.2 letters, p < 0.05) and gradually reverted to baseline levels over the 5-year period of follow-up (+0.2 letters at year-5). A significant and sustained CRT reduction was observed throughout the 5-years. The proportion of eyes on IOP-lowering medication increased from 16% at baseline, to 70% at 5-years (p < 0.001) with eyes on a mean of 1.3 medications. Laser trabeculoplasty (n = 2), cyclodiode laser (n = 1), and trabeculoplasty and trabeculotomy (n = 1, in the same eye; 3.2%) were required for uncontrolled IOP. Other complications included endophthalmitis (n = 1) and vitreous haemorrhage (n = 1). 58% of eyes required additional intravitreal injections, with a mean 29.2 months to first injection. We observed a 69% reduction in treatment burden following treatment with ILUVIEN implant. CONCLUSIONS: Our real-world results confirm the efficacy of the ILUVIEN implant over 5 years, with two-thirds of eyes having improved or stable visual acuity 5 years after ILUVIEN, and an overall sustained improvement in anatomical outcome. Although the rate of IOP-lowering medications use was higher than previously reported, the rate of incisional IOP-lowering surgery and other complications remained low and in keeping with rates reported in larger studies.

ACUTE MACULAR NEURORETINOPATHY AFTER COVID-19 VACCINATION.

PURPOSE: To report a case of acute macular neuroretinopathy after the vaccination for coronavirus disease 2019. METHODS: A 22-year-old White woman presented with symptoms of paracentral scotomas within a week of receiving coronavirus disease 2019 vaccination. Complete evaluation was performing using multimodal imaging techniques. RESULTS: Spectral domain optical coherence tomography and near-infrared imaging showed characteristic features of acute macular neuroretinopathy. CONCLUSION/DISCUSSION: To the best of our knowledge this is the first reported case of acute macular neuroretinopathy after coronavirus disease 2019 vaccination. Optical coherence tomography angiography did not reveal any signal attenuation, and multifocal electroretinogram and central visual fields were normal indicating that near-infrared imaging and spectral domain optical coherence tomography remain the gold standard in diagnosing this condition especially in smaller lesions.

Comparing Effectiveness of Three Different Anti-VEGF Treatment Regimens for Neovascular Age-Related Macular Degeneration: Two Years' Real-World Clinical Outcomes.

PURPOSE: To compare and report the 2-year treatment outcomes from 3 different anti-VEGF treatment regimens in treating neovascular aged-related macular degeneration (nAMD): Ranibizumab pro re nata (Ranibizumab-PRN); Ranibizumab treat and extend (Ranibizumab-T&E); Aflibercept fixed first year dosing (7 injections) with treat and extend in subsequent year (Aflibercept-Fixed). METHODS: All treatment-naïve nAMD patients who completed 24 months of monitoring from a single treatment center were included. Patients received the initial loading dose of three injections (4-weekly interval), followed by one of the 3 treatment regimens. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcome was number of injections required in each year. Data analysis included last observation carried forward (LOCF) for patients with incomplete year-2 follow-up. RESULTS: A total of 249 eyes (230 patients) were studied: 121 Ranibizumab-PRN; 65 Ranibizumab-T&E, and 63 Aflibercept-Fixed. Baseline median VA (ETDRS letters) for Ranibizumab-PRN, Ranibizumab-T&E, and Aflibercept-Fixed was 53.9, 61.1, and 54.9 letters, achieving final VA of 54.9, 65.1, and 65.1 letters, respectively. Hence, the number of letters increased at the end of 24 months for each group was +1.0 (Ranibizumab-PRN), +4.0 (Ranibizumab-T&E), highest +10.2 in Aflibercept-Fixed group. Median number of injections over 2 years (year-1/year-2) was 5/1 for Ranibizumab-PRN, 9/6 for Ranibizumab-T&E, and 7/5 for Aflibercept-Fixed. Both Ranibizumab-T&E and Aflibercept-Fixed also shared the same reduction of median CRT (115 µm), higher than Ranibizumab-PRN (83 µm). CONCLUSION: We report VA improvement from all three different treatment regimens with both Aflibercept-Fixed and Ranibizumab-T&E regimens achieving the same higher final VA. Aflibercept-Fixed dosing may have more favorable efficacy with the highest VA gain and comparatively lower dosing frequency whereas Ranibizumab-T&E may be more efficient than Ranibizumab-PRN regimen, according to our study.

Combination Therapy for Macular Oedema in Retinal Vein Occlusions: 3-Year Results from a Real-World Clinical Practice.

PURPOSE: To report long-term efficacy and treatment outcomes of the combination therapy for treating macular oedema (MO) in retinal vein occlusions (RVOs) from a real-world UK practice. METHODS: The initial reported 66 RVO patients with MO treated with combination therapy (initial Ranibizumab, later optional addition of Ozurdex and laser) were followed up to Year 3: visual acuity (VA) and central retinal thickness (CRT) were analysed against baseline and previous Year 1 results. Safety and adverse events were also recorded. RESULTS: Baseline LogMAR VA of 0.71 (Snellen 6/30) improved to 0.48 (Snellen 6/18) at Year 3 (p=0.006); 63% experienced VA improvement (40% improved ≥3 lines), 27% had worse vision. Stability of mean VA (6/18) was already achieved at first post-loading phase review and was maintained in each subsequent year. Statistically significant CRT improvement was noted in each year (Year 3 median CRT=264µm) compared to baseline (median CRT=531µm). There was a reduction in the mean number of total injections to 2.5 in Year 3 (vs 5.5 in Year 1). Comparing Year 3 against Year 1, mean Ranibizumab injection frequency was 2.1 vs 4.3; mean Ozurdex injection frequency was 0.2 vs 1.1. In Year 3, 39.6% of patients did not require any form of injections, laser frequency was also reduced to 22.9% (vs 81.8% in Year 1). There was no endophthalmitis in the cohort, one progressed to neovascular glaucoma in Year 2 and mortality rate was recorded as 6%. CONCLUSION: Our real-world clinical practice for RVO patients using a combined therapy is associated with good long-term VA and anatomical outcomes with less intravitreal re-treatment rates.

Real-World Visual And Clinical Outcomes For Patients With Neovascular Age-Related Macular Degeneration Treated With Intravitreal Ranibizumab: An 8-Year Observational Cohort (AMD8).

PURPOSE: To report the long-term clinical outcomes for patients with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy as part of a standardised treatment protocol in a real-world setting. PATIENTS AND METHODS: This is a retrospective audit of all treatment-naïve patients with nAMD who commenced a pro re nata (PRN) treatment regimen of intravitreal Ranibizumab from January to December 2009 and completed 8 years of follow-up in one single-treatment centre. Electronic medical notes were reviewed to evaluate the outcome measures. Outcome measures included progression of visual acuity (VA), central retinal thickness (CRT) and treatment frequency. RESULTS: 95 eyes from 86 patients had complete data for 8 years of follow-up. Baseline median CRT was 295µm [IQR 254-349] and improved to 209µm [IQR 182-254] in year 8 (p<0.001); baseline median VA was 61 ETDRS letters which increased to 70 letters post-loading however was reduced to 55 letters by year 8 (mean VA change from baseline was -9.1 letters); 47.4% had stable or improved vision, 10.5% gained ≥15 letters and 33.7% had lost ≥15 letters. The highest visual gain was achieved after the initial loading-phase, with a subsequent steady decline, 26.3% (compared to baseline 33.4%) achieved driving vision standard. Median injection frequency was 6 (range 3-10) in year 1 and 3 injections (range 0-10) in year 8. 51.6% of eyes required at least one injection each year and only 34.7% required no injections in year 8. CONCLUSION: Our real-world nAMD treatment cohort using Ranibizumab PRN regimen achieved an encouraging almost 50% stable or improved VA at year 8 and total injections of 31.6 injections per patient over an 8-year period.

Management of retinal detachment in retinoblastoma with globe conserving treatment.

PURPOSE: To investigate the features and outcomes of retinoblastoma (Rb) patients complicated by development of retinal detachment (RD) following systemic chemotherapy with or without local focal consolidation treatment and without external beam radiotherapy (EBRT). METHODS: A retrospective study of all Rb patients between April 2002 and April 2012 at a tertiary hospital center (Birmingham Children's Hospital and Birmingham Midlands Eye Centre, United Kingdom). All eyes that had developed RD during or after systemic treatment with or without local focal consolidation treatment were included in the study. The time interval between the type of treatment of Rb, development of RD and relevant surgical intervention were analyzed. Patients with exudative RD were treated conservatively through observation and patients with rhegmatogenous RD were treated with scleral buckling. Final anatomical retinal reattachment rate and visual acuity outcomes were analyzed. RESULTS: A total of 258 patients were treated for Rb over the 10-year period. One hundred sixty-nine patients were managed with globe conserving treatment. Ten (5.92%) eyes of 10 patients were complicated with RD. Five eyes were exudative or presumed exudative type of RD while the other five eyes were rhegmatogenous or presumed rhegmatogenous RD. In the exudative group, two patients achieved visual acuity (VA) of 0.2 Single Kays (20/32 Snellen), and the other two patients achieved 0.85 and 0.86 Crowded Kays (20/142 and 20/145 Snellen), respectively, after the RD had resolved. The last patient in the group had to be enucleated due to tumor recurrences. The median time for the exudative RD to resolve is 15 weeks (range, 4-36 weeks). In the rhegmatogenous group, 3 of the 4 operated patients achieved retinal reattachment. The final postoperative VA ranged between 0.05 Crowded Kays to 1.84 Crowded Kays (20/22 to 20/1384 Snellen). The other patient was treated conservatively as no retinal breaks were found with previous cryotherapy and thermotherapy. The final VA in this patient was hand movement, and the RD did not reattach. The median time for the rhegmatogenous RD to reattach is 6 weeks (range, 4-8 weeks). There were no intra- and postoperative complications. CONCLUSIONS: With long-term conservative management through observation, exudative Rb after systemic treatment of Rb will tend to resolve by itself. However, supplementary local treatment with cryoretinopexy or laser photocoagulation during the systemic treatment of Rb can lead to an increased risk of rhegmatogenous RD. In these cases, most rhegmatogenous RD are successfully repaired with non-drainage scleral buckling and cryoretinopexy.

United Kingdom Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group: report 4, real-world data on the impact of deprivation on the presentation of diabetic eye disease at hospital services.

AIM: To assess the impact of deprivation on diabetic retinopathy presentation and related treatment interventions, as observed within the UK hospital eye service. METHODS: This is a multicentre, national diabetic retinopathy database study with anonymised data extraction across 22 centres from an electronic medical record system. The following were the inclusion criteria: all patients with diabetes and a recorded, structured diabetic retinopathy grade. The minimum data set included, for baseline, age and Index of Multiple Deprivation, based on residential postcode; and for all time points, visual acuity, ETDRS grading of retinopathy and maculopathy, and interventions (laser, intravitreal therapies and surgery). The main  outcome measures were (1) visual acuity and binocular visual state, and (2) presence of sight-threatening complications and need for early treatment. RESULTS: 79 775 patients met the inclusion criteria. Deprivation was associated with later presentation in patients with diabetic eye disease: the OR of being sight-impaired at entry into the hospital eye service (defined as 6/18 to better than 3/60 in the better seeing eye) was 1.29 (95% CI 1.20 to 1.39) for the most deprived decile vs 0.77 (95% CI 0.70 to 0.86) for the least deprived decile; the OR for being severely sight-impaired (3/60 or worse in the better seeing eye) was 1.17 (95% CI 0.90 to 1.55) for the most deprived decile vs 0.88 (95% CI 0.61 to 1.27) for the least deprived decile (reference=fifth decile in all cases). There is also variation in sight-threatening complications at presentation and treatment undertaken: the least deprived deciles had lower chance of having a tractional retinal detachment (OR=0.48 and 0.58 for deciles 9 and 10, 95% CI 0.24 to 0.90 and 0.29 to 1.09, respectively); in terms of accessing treatment, the rate of having a vitrectomy was lowest in the most deprived cohort (OR=0.34, 95% CI 0.19 to 0.58). CONCLUSIONS: This large real-world study suggests that first presentation at a hospital eye clinic with visual loss or sight-threatening diabetic eye disease is associated with deprivation. These initial hospital visits represent the first opportunities to receive treatment and to formally engage with support services. Such patients are more likely to be sight-impaired or severely sight-impaired at presentation, and may need additional resources to engage with the hospital eye services over complex treatment schedules.

Retinal embolic events: frequency and impact following transcatheter aortic valve implantation (TAVI) for aortic stenosis.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe symptomatic aortic stenosis. It has a cerebrovascular accident rate of about 5% but the effect on retinal embolic events has not been previously reported. This study investigated the occurrence of retinal emboli following TAVI. METHODS AND ANALYSIS: In this prospective observational study, 20 patients underwent full ophthalmic examination to assess retinal embolic events prior to TAVI and at 48 hours and 1 month post-TAVI. RESULTS: At 48 hours post-TAVI, one patient had a new cotton wool spot in the right eye. At 1 month, another two patients had new retinal emboli events in at least one eye and a fourth patient developed retinal splinter haemorrhages in the right eye. CONCLUSION: Retinal embolic events and new retinal abnormalities following TAVI occurred in 15% and 20% of our cohort, respectively, without any associated retinal damage or significant visual problems. Retinal evaluation may be a useful surrogate test for cerebral embolisation in future studies assessing the utility of new valve prostheses and embolic protection devices.

Bilateral visual outcomes and service utilization of patients treated for 3 years with ranibizumab for neovascular age-related macular degeneration.

BACKGROUND: The aim of this study was to describe bilateral visual outcomes and the effect of incomplete follow-up after 3 years of ranibizumab therapy for neovascular age-related macular degeneration. Secondarily, the demands on service provision over a 3-year period were described. METHODS: Data on visual acuity, hospital visits, and injections were collected over 36 months on consecutive patients commencing treatment over a 9-month period. Visual outcome was determined for 1) all patients, using last observation carried forward for missed visits due to early discontinuation and 2) only those patients completing full 36-month follow-up. RESULTS: Over 3 years, 120 patients cumulatively attended hospital for 1,823 noninjection visits and 1,365 injection visits. A visual acuity loss of <15 letters (L) was experienced by 78.2% of patients. For all patients (n=120), there was a mean loss of 1.68 L using last observation carried forward for missing values. Excluding five patients who died and 30 who discontinued follow-up, mean gain was 1.47 L. In bilateral cases, final acuity was on average 9 L better in second eyes compared to first eyes. Also, 91% of better-seeing eyes continued to be the better-seeing eye. CONCLUSION: We have demonstrated our approach to describing the long-term service provision and visual outcomes of ranibizumab therapy for neovascular age-related macular degeneration in a consecutive cohort of patients. Although there was a heavy burden with very frequent injections and clinic visits, patients can expect a good level of visual stability and a very high chance of maintaining their better-seeing eye for up to 3 years.

A Case of Candida albicans Endophthalmitis with No Predisposing Risk Factors and a Distant Source of Infection.

PURPOSE: To report a case of Candida albicans endophthalmitis with no identifiable predisposing risk factors. CASE REPORT: A 57-year-old male presented with a 3-day history of worsening floaters and reduced visual acuity. Fundoscopy and optical coherence tomography showed presence of fluffy white preretinal and intraretinal infiltrates. With no past medical history or evidence of immunosuppression but having travelled abroad and suffered from diarrhoea, fungal aetiology was thought to be unlikely and as a result, treatment was commenced for toxoplasma. Despite treatment, his vision did not improve. Initial investigations including inflammatory markers, serology for toxoplasmosis, blood culture, chest radiograph and aqueous sampling could not identify a source of infection. However, polymerase chain reaction results from vitreous sampling revealed C. albicans. As a result, the patient was treated with intravenous voriconazole and intravitreal amphotericin B. As initial clinical improvement was limited, a vitrectomy was performed with further intravitreal amphotericin B. Clinical improvement was rapid following vitrectomy. After repeated Gram staining and culture of infected toenails, Gram-positive yeast cells were isolated. CONCLUSION: Although C. albicans is a frequent cause of endogenous endophthalmitis, patients often have one or more predisposing systemic condition assisting the diagnosis. The present case illustrates that (1) even in the absence of any predisposing risk factors, C. albicans should be considered as a possible differential diagnosis in recalcitrant uveitis, and (2) endogenous candida endophthalmitis can be a result of fungal infections from distant sites such as the toenails.

The effect of the first application of verteporfin photodynamic therapy on lesion growth in choroidal neovascularisation and its potential impact on combination therapy.

PURPOSE: To evaluate the impact of lesion size on the observed growth of the choroidal neovascularisation (CNV) following the first application of photodynamic therapy (PDT). METHODS: A retrospective study of consecutive patients with subfoveal classic CNV or predominantly classic CNV undergoing first verteporfin photodynamic therapy (VPDT) according to treatment of age-related macular degeneration with photodynamic therapy (TAP) protocol between June 2005 and September 2005. Patients were classified into two groups according to baseline greatest linear dimension (GLD) at the time of VPDT monotherapy. Group 1 comprised patients with lesion GLD less then 2000 microm and Group 2, patients with lesion GLD 2000 microm or larger. Difference between the mean GLD at baseline and at three months post-treatment were investigated for clinical significance using the paired t-test. RESULTS: Group 1 (n = 16) showed a mean change in GLD from 1380.25 microm to 2031.25 microm, while Group 2 (n = 26) showed a mean change of 2909.26 microm to 3023.07 microm. Data of mean percentage change in GLD for Group 1 showed a 51.97 per cent increase in the lesion size [95% CI, 22.93 - 81.01%] in comparison to Group 2, which showed only 5.8 per cent increase in the lesion [95% CI, -9.65 - 21.61%]. Comparison of the mean percentage change in GLD between the two groups showed a statistically significant difference (p = 0.003). CONCLUSIONS: Our study demonstrates that following the first application of VPDT, smaller lesions enlarge disproportionately more than larger lesions. As we have entered into the era of using angiostatic agents in combination with VPDT, it may be important to evaluate this effect with regards to the timing of VPDT commencement.

Occult giant cell arteritis and steroid therapy: how urgent is urgent?

We report two cases of sudden loss of vision in the second eye, within few hours of loss of vision in the first, in association with occult giant cell arteritis. Both cases presented with bilateral disc edema. The importance of starting steroid therapy to prevent sight or life threatening complications, as soon as a diagnosis is suspected is emphasized.

Occult giant cell arteritis and steroid therapy: how urgent is urgent?

We report two cases of sudden loss of vision in the second eye, within a few hours of loss of vision in the first, in association with occult giant cell arteritis. Both cases presented with bilateral disc edema. The importance of starting steroid therapy to prevent sight- or life-threatening complications, as soon as a diagnosis is suspected is emphasized.