Brolucizumab in patients with neovascular age-related macular degeneration: Real-life outcomes from a tertiary care eye hospital.

PURPOSE: To report real-world clinical evidence of brolucizumab in treating neovascular age-related macular degeneration (nAMD). METHODS: This study included 37 eyes with nAMD treated with intravitreal injections of brolucizumab. The main outcomes were best corrected visual acuity (BCVA) changes, central retinal thickness (CRT), and serious ocular adverse events. Intraretinal fluid (IRF) and subretinal fluid (SRF), subretinal hyperreflective material (SHRM), pigment epithelial detachments (PEDs), hyperreflective foci, macular atrophy, and retinal pigment epithelial tears were evaluated. RESULTS: The mean BCVA of all patients showed a post-treatment value of 0.47 ± 0.33 log of minimum angle of resolution (LogMAR), compared to a baseline measure of 0.50 ± 0.28 LogMAR ( P = 0.372). For treatment-naïve patients, a non-statistically significant improvement in BCVA was observed ( P = 0.116). Both treatment-naive patients and the entire patient cohort exhibited a statistically significant improvement in the mean CRT after injections. Majority of patients exhibited improvements in optical coherence tomography findings, specifically in the resolution of IRF, SRF, SHRM, and PEDs. Four eyes experienced ocular adverse events in the form of intraocular inflammation. CONCLUSION: Brolucizumab did not yield a substantial improvement in BCVA, but it exhibited efficacy in reducing CRT in the entire study population and treatment-naive patients with nAMD. Our study identified intraocular inflammation as a significant adverse event with brolucizumab. Thus, precise patient selection, education, and vigilant inflammation monitoring are crucial for patients undergoing this treatment.

Subthreshold laser compared to oral spironolactone for the treatment of chronic central serous chorioretinopathy: a retrospective study.

PURPOSE: To compare functional and morphological outcomes of Subthreshold Laser (STL) and Oral Spironolactone (SPR) in treating chronic central serous chorioretinopathy (CSCR). METHODS: This is a retrospective observational study. Treatment-naïve patients with chronic CSCR treated with STL or SPR were included, and data was reviewed at baseline, 1, 3, 6 and 12-month follow-up. Main outcome measures were changes in Central Macular Thickness (CMT) and Subretinal Fluid (SRF) height, and complete resolutions of SRF. Sub-analysis based on retinal pigmented epithelium (RPE) status at baseline was performed. RESULTS: 47 and 47 patients received STL and SPR, respectively. At all timepoints, both treatments significantly improved CMT and SRF (p < 0.05). No significant changes in best corrected visual acuity (BCVA) were recorded and no significant differences between treatment groups were present at each corresponding follow-up. Complete resolution of SRF was achieved in 29% and 36% of patients treated with STL or SPR, respectively, at 12-months follow up. Eyes treated with STL and intact RPE showed significant SRF decrease at 6 months and significantly better BCVA at 1, 3 and 6 months compared to eyes with disrupted RPE layer (p < 0.05). In both treatment groups, intact RPE was associated with a higher rate of complete SRF resolutions, with 43% vs 13% in the STL group and 50% vs 26% in the SPR group. CONCLUSION: STL and SPR are effective treatments for chronic CSCR. Greater resolution of subretinal fluid was observed in eyes with intact RPE, hence both treatments should be initiated in the earlier stages of the disease.

Uveitis Following Intravitreal Injections of Faricimab: A Case Report.

PURPOSE: Faricimab, a novel pharmaceutical agent targeting both angiopoietin-2 and vascular endothelial growth factor-A pathways, has gained approval for treating neovascular age-related macular degeneration and diabetic macular oedema. While clinical trials have demonstrated its favorable safety profile, this research presents two cases of hypertensive uveitis following intravitreal Faricimab injections. METHODS: Medical history, clinical findings and multimodal images were retrospectively collected. RESULTS: The patients experienced elevated intraocular pressure, mutton-fat keratic precipitates, anterior and posterior segment inflammation shortly after faricimab administration. CONCLUSIONS: These cases prompt further investigation into the potential risk of uveitis associated with faricimab and underscore the importance of continued monitoring and research to elucidate its real-world safety profile.

Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration: Case Series.

PURPOSE: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK. METHODS: The approaches of this research include clinical examinations and multimodal imaging-based description of cases of nAMD with BALAD. RESULTS: We report multimodal imaging findings of bacillary layer detachment (BALAD) in patients with nAMD. CONCLUSIONS: A bacillary layer detachment was detected in patients with neovascular age-related macular degeneration. This multimodal imaging finding is not commonly described in the literature for this disease.

Long-term outcomes of anti-VEGF treatment of macular oedema due to retinal vein occlusions.

PURPOSE: retinal vein occlusion (RVO) is classified as either branch (BRVO) or central (CRVO) RVO. The gold standard treatment for macular oedema (MO) secondary to RVO is intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Our study aimed to compare ranibizumab and aflibercept outcomes over a maximum follow-up of five years. METHODS: this retrospective study assessed treatment-naïve RVO patients. Active disease was treated with three loading injections followed by a pro-re-nata (PRN) regimen of an anti-VEGF agent. Visual outcomes and injection frequency were analyzed, with patients stratified according to RVO subtype, anti-VEGF agent used, baseline vision, and age. RESULTS: 316 CRVO-affected eyes and 467 BRVO-affected eyes were analysed. Visual benefits between different treatments did not significantly differ, except in year 1 in ranibizumab-treated BRVO eyes. However, aflibercept-treated CRVO and BRVO eyes required significantly fewer injections during the follow up period. Furthermore, our results confirm that younger patients achieve better visual outcomes with fewer intravitreal injections. Overall, half of our patients did not require further injections after 1 year from diagnosis. CONCLUSION: the results demonstrate that anti-VEGF treatment of RVO benefits vision for up to 5 years. Our findings are the first to suggest that compared to ranibizumab, fewer aflibercept injections may be required over five years follow up. Prospective randomised trials are needed to confirm this, alongside further attention to OCT scan features and the effect of patient demographics on treatment outcomes.

Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic.

DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has been developed within the last 2 decades from basic laboratory science to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to identify stressed and apoptotic cells in the living eye. During its development, DARC has undergone biochemistry optimisation, scale-up and GMP manufacture and extensive preclinical evaluation. Initially tested in preclinical glaucoma and optic neuropathy models, it has also been investigated in AMD, Alzheimer's, Parkinson's and Diabetic models, and used to assess efficacy of therapies. Progression to clinical trials has not been speedy. Intravenous ANX776 has to date been found to be safe and well-tolerated in 129 patients, including 16 from Phase 1 and 113 from Phase 2. Results on glaucoma and AMD patients have been recently published, and suggest DARC with an AI-aided algorithm can be used to predict disease activity. New analyses of DARC in GA (Geographic Atrophy) prediction are reported here. Although further studies are needed to validate these findings, it appears there is potential for the technology to be used as a biomarker. Much larger clinical studies will be needed before it can be considered as a diagnostic, although the relatively non-invasive nature of the nasal as opposed to intravenous administration would widen its acceptability in the future as a screening tool. This review describes DARC development and its progression into Phase 2 clinical trials from lab-based research. It discusses hypotheses, potential challenges, and regulatory hurdles in translating technology.

Long-term outcomes of intravitreal anti-VEGF therapies in patients affected by neovascular age-related macular degeneration: a real-life study.

PURPOSE: To describe real-life data from wet age-related macular degeneration (AMD) patients treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials. METHODS: This retrospective monocentric cohort study analyzed 865 eyes of 780 wet-AMD patients treated with an anti-VEGF treat-and-extend regimen over a long-term follow-up period. Aflibercept and Ranibizumab were considered first-line agents whereas Bevacizumab was reserved for use on a compassionate basis in patients not meeting treatment criteria. All patients underwent a best corrected visual acuity (BCVA) assessment at each follow-up visit. RESULTS: One-year follow-up figures were available for 82.5% of patients, whilst follow-up data was recorded for 55.6%, 37.6%, 25.1%, and 15.0% of the cohort at years 2, 3, 4, and 5 respectively. Patients treated with Bevacizumab received fewer yearly injections than those treated with Ranibizumab. However, no significant difference in the number of injections per year was detected in other comparisons between groups. Whilst our data showed no significant difference in mean BCVA between the three groups, there was a gradual deterioration of visual function over time for the patient cohort as a whole. CONCLUSION: No significant differences between the 3 anti-VEGF molecules were recorded in wet-AMD patients in real-life conditions. Despite the long-term therapy, we found a slight reduction in visual function especially after the third year of treatment.

The efficacy of dexamethasone implants following anti-VEGF failure for macular oedema in retinal vein occlusion.

PURPOSE: To investigate the efficacy of intravitreal dexamethasone implants (DEX) after anti-VEGF failure in retinal vein occlusion macular oedema. METHODS: Retrospective cohort study of DEX implant (0.7 mg) given after anti-VEGF 'failure'. Switch to DEX occurred if a ⩽ +5 ETDRS letter gain and ⩽20% reduction in central subfield thickness was present following ⩾6 consecutive anti-VEGF injections. The primary endpoint was VA change 30 days after DEX. Secondary outcomes were peak VA change, VA change at monthly timepoints, percentage achieving 15-letter gain, central subfield thickness (CST) and intraocular pressure (IOP). RESULTS: Sixty-two injections in 62 patients associated with 26% central retinal vein occlusion (CRVO) and 74% branch retinal vein occlusion (BRVO) were eligible. There was a modest, significant improvement in mean VA change at 30 days compared to baseline (+6 letters, 95% CI +2.2 to +9.1 letters, p < 0.01). DEX implant significantly improved mean peak VA change compared to preceding anti-VEGF by +18.1 letters in CRVO (p = 0.002) and +13.2 letters in BRVO (p < 0.0001). IOP peaked between 30 and 60 days following injection, with 31% of CRVO and 11% of BRVO patients experiencing an IOP ⩾ 25 mmHg. CONCLUSION: DEX implant provides useful rescue therapy in cases of anti-VEGF 'failure' for macular oedema following retinal vein occlusion, resulting in improved functional outcomes at 30 days.

Predicting wet age-related macular degeneration (AMD) using DARC (detecting apoptosing retinal cells) AI (artificial intelligence) technology.

OBJECTIVES: To assess a recently described CNN (convolutional neural network) DARC (Detection of Apoptosing Retinal Cells) algorithm in predicting new Subretinal Fluid (SRF) formation in Age-related-Macular-Degeneration (AMD). METHODS: Anonymized DARC, baseline and serial OCT images (n = 427) from 29 AMD eyes of Phase 2 clinical trial (ISRCTN10751859) were assessed with CNN algorithms, enabling the location of each DARC spot on corresponding OCT slices (n = 20,629). Assessment of DARC in a rabbit model of angiogenesis was performed in parallel. RESULTS: A CNN DARC count >5 at baseline was significantly (p = 0.0156) related to development of new SRF throughout 36 months. Prediction rate of eyes using unique DARC spots overlying new SRF had positive predictive values, sensitivities and specificities >70%, with DARC count significantly (p < 0.005) related to the magnitude of SRF accumulation at all time points. DARC identified earliest stages of angiogenesis in-vivo. CONCLUSIONS: DARC was able to predict new wet-AMD activity. Using only an OCT-CNN definition of new SRF, we demonstrate that DARC can identify early endothelial neovascular activity, as confirmed by rabbit studies. Although larger validation studies are required, this shows the potential of DARC as a biomarker of wet AMD, and potentially saving vision-loss.

Three-year real-world outcomes of intravitreal anti-VEGF therapies in patients affected by myopic choroidal neovascularization.

PURPOSE: To describe real world data in patients affected by myopic choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials. METHODS: This retrospective monocentric cohort study analyzed 96 eyes of 96 myopic-CNV patients treated with an anti-VEGF pro-re-nata regimen over a 3-year-long follow up period. Aflibercept and Ranibizumab were considered as first-line agents whereas Bevacizumab was reserved on a compassionate basis in patients outside the criteria for treatment. All patients underwent a best-corrected visual acuity (BCVA) recording at each follow up visit. RESULTS: Our data showed that all three molecules produced significant improvements in BCVA at year 1, with no significant differences between the three drugs. Moreover, during the second year of treatment, Ranibizumab and Bevacizumab showed a significant improvement in the visual function. However, at year 3 of treatment, the data available indicated the BCVA improvement was not significant with Ranibizumab and Bevacizumab. In addition, no significant difference in the average number of injections between the three groups was detected over the follow up period. No serious adverse events were recorded, but five minor adverse events documented. CONCLUSION: Our study correlates with previous studies showing significant BCVA gains with the use of these molecules. Similarly, all three molecules seem to provide a similar duration of effects as previous studies have shown, with a low ocular adverse event rate.

Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients.

The ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2's) to cause multi-organ ischemia and coronavirus-induced posterior segment eye diseases in mammals gave concern about potential sight-threatening ischemia in post coronavirus disease 2019 patients. The radial peripapillary capillary plexus (RPCP) is a sensitive target due to the important role in the vascular supply of the peripapillary retinal nerve fiber layer (RNFL). Eighty patients one month after SARS-CoV-2 infection and 30 healthy patients were selected to undergo structural OCT (optical coherence tomography) and OCTA (optical coherence tomography angiography) exams. Primary outcome was a difference in RPCP perfusion density (RPCP-PD) and RPCP flow index (RPCP-FI). No significant difference was observed in age, sex, intraocular pressure (IOP) and prevalence of myopia. RPCP-PD was lower in post SARS-CoV-2 patients compared to controls. Within the post-COVID-19 group, patients with systemic arterial hypertension had lower RPCP-FI and age was inversely correlated to both RPCP-FI and RPCP-PD. Patients treated with lopinavir + ritonavir or antiplatelet therapy during admission had lower RPCP-FI and RPCP-PD. RNFL average thickness was linearly correlated to RPCP-FI and RPCP-PD within post-COVID-19 group. Future studies will be needed to address the hypothesis of a microvascular retinal impairment in individuals who recovered from SARS-CoV-2 infection.

BLIND-SIDED BY COSMETIC VEIN SCLEROTHERAPY: A CASE OF OPHTHALMIC ARTERIAL OCCLUSION.

PURPOSE: Cosmetic vein sclerotherapy is increasingly used to treat varicose veins because of its effectiveness and adherence with British Pharmacopoeia specifications. We present the first documented case of ophthalmic artery occlusion resulting in panocular ischemia secondary to intravascular injection of sodium tetradecyl sulfate sclerosant in a young healthy women seeking treatment for prominent facial veins in her forehead. METHODS: The patient presented with unilateral sudden loss of vision. Funduscopy demonstrated a pale retina, cherry-red spot, and sclerosant visualized directly at the macula. She underwent emergency treatment for central retinal artery occlusion followed by fundal photographs, fluorescein angiography, and optical coherence tomography. RESULTS: Despite intervention, the vision remained no perception to light. Magnetic resonance imaging, echocardiography, and Doppler ultrasound were unremarkable. The patient later developed neovascular sequelae requiring laser pan-retinal photocoagulation. CONCLUSION: Widely regarded as safe, and approved by the U.S. Food and Drug Administration, the only published ocular side effects of foam sclerotherapy are transient visual disturbances or temporary scotomas. This case demonstrates irreversible loss of vision as a previously unreported complication. While undoubtedly rare, we believe physicians and surgeons using sclerosant in the orbital adnexa, face, nose, and sinuses should be aware of this sight-threatening complication of injection and counsel potential patients accordingly.

Initiation and maintenance of a Treat-and-Extend regimen for ranibizumab therapy in wet age-related macular degeneration: recommendations from the UK Retinal Outcomes Group.

The treatment of neovascular (wet) age-related macular degeneration (AMD) with ranibizumab is now very well established in terms of efficacy and safety. Recent clinical trials and real-world studies have demonstrated the advantages of a Treat-and-Extend (T&E) regimen, and many hospital departments are now in the process of adopting this new regimen in favor of the pro re nata regimen for initiating and continuing ranibizumab therapy for patients with wet AMD. The comprehensive spectrum of issues related to implementation of the regimen is covered qualitatively in ten didactic topics provided by a group of clinicians with direct experience of this regimen in their department. The topics include definition, new and previously treated eyes, management of high-frequency injections, maximum extensions, discontinuing T&E, bilateral cases, clerical, audit, and patient counseling. This article aims to provide a useful resource for the implementation of the T&E regimen. A quantitative summary of the visual outcomes in key publications is also provided in this article. This article should be a valuable resource for staff training.

RITONAVIR-ASSOCIATED TOXICITY MIMICKING RETINITIS PIGMENTOSA IN AN HIV-INFECTED PATIENT ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY.

PURPOSE: To report ritonavir-associated retinal pigment epithelium toxicity in a patient infected with the HIV on highly active antiretroviral therapy including ritonavir. METHODS: Retrospective single case report. The authors describe a case of gradual onset of blurry vision in both eyes in an HIV-positive male. Visual acuity, clinical examination findings, and functional testing (electroretinogram and Goldmann perimetry) were reviewed. Diagnostic imaging, including fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fundus autofluorescence were assessed. RESULTS: 59-year-old HIV-infected male, treated with ritonavir for eight years, presented with a history of decreased night vision and peripheral field loss. Ophthalmologic examination confirmed the diagnosis of retinal toxicity. Goldmann perimetry showed areas of central and para-central scotomas. Electroretinograms demonstrated mild to moderate photoreceptor dysfunction. Fundus examination revealed a diffuse pattern of retinal pigment epithelium mottling in both eyes. Spectral domain optical coherence tomography confirmed the presence of choroidal thinning, whereas fundus autofluorescence showed mottled hypoautofluorescence. CONCLUSION: Although ritonavir-associated retinal toxicity is clinically uncommon, the clinical features of our findings support this diagnosis. Consideration of highly active antiretroviral therapy-associated retinal toxicity should be given to the differential diagnosis in HIV-positive patients with retinopathy of unclear etiology. This report also highlights the need for constant monitoring of patients using the ritonavir for early detection of possible retinal toxicity.

Macular morphology and response to ranibizumab treatment in patients with wet age-related macular degeneration.

PURPOSE: The purpose of this study was to assess whether specific characteristics of spectral domain optical coherence tomography (SD-OCT) affect structural and functional outcomes and number of injections needed in ranibizumab (0.05 mL of 10 mg/mL Lucentis solution)-treated wet age-related macular degeneration (AMD) patients. PATIENTS AND METHODS: This retrospective case series included 62 newly diagnosed wet AMD patients treated with three monthly intravitreal ranibizumab injections followed by monthly follow-up and pro re nata retreatment. The presence of dome-shaped pigment epithelial detachment (PED), disruption of the retinal pigment epithelium (RPE), and subretinal and intraretinal fluid was associated with changes in Early Treatment of Diabetic Retinopathy Study visual acuity, central macular thickness (CMT), and number of injections needed during the 6-month follow-up. RESULTS: The presence of PED was associated with lower values of CMT at presentation (399 µm [±132 µm] vs 310 µm [±51 µm], P=0.005). The presence of RPE disruption was associated with worse visual acuity in month 6 (0.36 [±0.22] vs 0.61 [0.45], P=0.027) and fewer injections (4.23 [±0.92] vs 3.55 [±0.60], P=0.007). The presence of intraretinal fluid at presentation was associated with worse visual acuity outcomes in month 4 (P=0.045) but not in month 6. CONCLUSION: The dome-shaped PED was associated with lower CMT at presentation, but it did not affect response to treatment. RPE disruption was associated with worse functional outcomes with fewer injections. Intraretinal fluid at presentation may suggest delayed response to treatment. Individualized SD-OCT analysis could lead to individualized approach to wet AMD patients. SD-OCT can offer imaging biomarkers to assess the prognosis of anti-VEGF treatment in AMD patients.

Topiramate-induced maculopathy in IgG4-related disease.

This report describes a case of reversible topiramate-induced maculopathy in a 32-year-old female patient with IgG4-related disease. The patient presented with decreased vision associated with anterior uveitis and cystoid macula edema, which was unresponsive to oral and topical steroids. Following topiramate cessation, both cystoid macula edema and vision improved. The ocular side effects of topiramate and putative pharmacological mechanisms for topiramate-induced maculopathy in the context of IgG4-related disease are discussed. This report highlights that neurologists and ophthalmologists should be aware that patients presenting with topiramate-associated maculopathy should be advised to discontinue topiramate promptly to prevent irreversible loss of vision.

Transient visual loss and delayed resolution of vitreomacular traction after intravitreal ocriplasmin.

Vitreomacular traction and vitreomacular traction with macular hole are conditions associated with visual disturbance and decreased visual acuity. Recent studies have demonstrated that ocriplasmin is effective and safe in specific patient groups with vitreomacular traction, and hence is recommended as a treatment option. We present here a case report of a patient treated with intravitreal ocriplasmin associated with severe loss of vision and delayed resolution of vitreomacular traction. This report highlights that it is important for patients to be made fully aware of the risks of intravitreal ocriplasmin and the prognosis for visual improvement.