Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.

PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified. CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Long-term changes of choroidal blood flow velocity in Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate changes in choroidal blood flow in patients with Vogt-Koyanagi-Harada (VKH) disease after initiation of corticosteroid treatment. METHODS: Fourteen patients (10 men and 4 women) with acute VKH disease followed for 2 years were retrospectively reviewed; only right eyes were included in the analysis. Mean blur rate (MBR) in the macula was measured by laser speckle flowgraphy (LSFG) and central choroidal thickness (CCT) was measured by optical coherence tomography (OCT), both prior to treatment and over 2 years after initiation of corticosteroid treatment. RESULTS: Of 14 patients included in this study, 13 received initial treatment consisting of intravenous corticosteroid pulse therapy and one patient was treated using bilateral sub-Tenon injections of triamcinolone acetonide. Mean percentage change in MBR was significantly increased after initiation of treatment compared to pretreatment values (P < 0.001). Mean CCTs were significantly decreased after initiation of treatment, compared to pretreatment thicknesses (P < 0.001). There was no significant change in either MBR change or CCT at 1 month after initiation of treatment through 2 years of follow-up. The mean MBR percentage change was significantly higher in eyes with sunset glow fundus (SGF) compared to eyes without SGF at 1 year. CONCLUSION: With initiation of corticosteroid treatment in VKH disease patients, choroidal blood flow improved and was maintained for 2 years. However, the presence of SGF should be taken into consideration when interpreting MBR results in VKH disease patients.

Clinical features and visual outcomes of ocular sarcoidosis at a tertiary referral center in Tokyo.

BACKGROUND: To analyze clinical features, treatment, complications, and visual outcomes of ocular sarcoidosis at a tertiary center in Tokyo. METHODS: Clinical records of 53 patients with ocular sarcoidosis ("definite" or "presumed") presenting between 2013 and 2018 to the Kyorin Eye Center were retrospectively reviewed. Diagnosis was based on the revised criteria of the International Workshop on Ocular Sarcoidosis. RESULTS: Definite (biopsy-proven) disease was present in 87% of patients and presumed disease in 13%. The mean age at presentation was 58 years (13-81 years) and 68% were women. The mean follow-up was 34 months (6-70 months). Forty-five patients (85%) had panuveitis, and the most common ocular clinical sign suggestive of ocular sarcoidosis was bilaterality (92%). Ocular complications were observed in 93 eyes (85%), most commonly cataract (73%), epiretinal membrane (24%), macular edema (24%) and glaucoma (19%). Thirty-one eyes (30%) underwent cataract surgery and 12 eyes (12%) underwent pars plana vitrectomy. Ten patients (19%) received systemic corticosteroid therapy and 33 eyes (32%) received periocular corticosteroid injections. The best-corrected visual acuity was 1.0 or better in 51% of eyes at presentation, 57% at 6 months, 50% at 12 months, and 58% at 36 months. CONCLUSIONS: The majority of ocular sarcoidosis patients were women, had bilateral disease and panuveitis involvement. Most eyes maintained good visual acuity, although surgical interventions for cataract and epiretinal membrane were common.

Subfoveal choroidal thickness after brolucizumab therapy for neovascular age-related macular degeneration: a short-term multicenter study.

BACKGROUND/PURPOSE: Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD. METHODS: This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography. RESULTS: The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P < 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 µm at baseline to 216.9 ± 110.2 µm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group. CONCLUSION: Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.

Comparative Analysis of Serum microRNA in Diagnosed Ocular Sarcoidosis versus Idiopathic Uveitis with Ocular Manifestations of Sarcoidosis.

"Idiopathic" is the most common category of uveitis, representing cases in which a specific diagnosis has not been established despite work-up. Sarcoidosis is a systemic granulomatous disorder affecting multiple organs including the lungs, skin, kidneys, and eyes. We used microRNA (miRNA) microarrays to investigate serum miRNA profiles of patients with ocular sarcoidosis as diagnosed by specific criteria (diagnosed ocular sarcoidosis), and patients with idiopathic uveitis characterized by ocular manifestations of sarcoidosis (suspected ocular sarcoidosis). Principal component analysis (PCA) and hierarchical clustering showed that serum miRNA profiles of diagnosed ocular sarcoidosis and suspected ocular sarcoidosis were both clearly distinguishable from healthy controls. Furthermore, comparative analysis of the miRNA profiles showed highly similar patterns between diagnosed ocular sarcoidosis and suspected ocular sarcoidosis. Pathway analysis revealed common pathways were involved in the two groups, including those of WNT signaling and TGF-beta signaling. Our study demonstrated a high overlap of differentially expressed serum miRNAs in patients with diagnosed ocular sarcoidosis and suspected ocular sarcoidosis, suggesting that these groups share a similar underlying pathology and may represent possible variants of the disease. Characterization of serum miRNA profiles may provide an opportunity for earlier diagnosis and treatment, and may inform more accurate clinical prognosis in patients with an ocular sarcoidosis phenotype.

Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study.

PURPOSE: To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study. METHODS: Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study. RESULTS: The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF. CONCLUSION: IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02305238.

Pachychoroid: current concepts on clinical features and pathogenesis.

PURPOSE: The term "pachychoroid" refers to a newly described phenotype in which functional and structural choroidal changes are thought to play a key pathogenic role in a spectrum of related retinal disorders. A more detailed understanding of how the choroid is involved within this spectrum and a better knowledge of the most relevant clinical signs of the pachychoroid phenotype are important to differentiate these disorders from other retinal conditions. Our objectives are to provide a literature review of pachychoroid and the commonalities that may be present across pathologies included in the spectrum, and to provide details on the examination, monitoring, and management of these disorders. METHODS: We searched the PubMed web platform to identify relevant studies using the following keywords: pachychoroid, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome, vasculopathy pachysclera, pachychoroid geographic atrophy, and pachydrusen. We selected 157 publications and identified the most important features related to pachychoroid. RESULTS: The presence of hypertrophic or congested vessels in the choroid, not thickened choroid per se, under an area of reduced or absent choriocapillaris in the posterior pole seems to be the most salient feature of pachychoroid. However, other qualitative/quantitative features are needed to differentiate the uncomplicated pachychoroid from the pathological pachychoroid clinical spectrum, which may be associated with exudation, neovascularization, and/or retinal pigment epithelium and photoreceptor atrophy. CONCLUSIONS: The most salient feature of pachychoroid appears to be the presence of large vessels under an area of reduced or absent choriocapillaris. Knowledge of the features and pathogenesis of the different disorders in the pachychoroid spectrum may assist in the management of patients.

Anti-VEGF intravitreal injections in the era of COVID-19: responding to different levels of epidemic pressure.

PURPOSE: Following the first wave of the COVID-19 pandemic in early 2020, the easing of strict measures to reduce its spread has led to a resurgence of cases in many countries at both the national and local level. This article addresses how guidance for ophthalmologists on managing patients with retinal disease receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) during the pandemic should be adapted to the local epidemic pressure, with more or less stringent measures implemented according to the ebb and flow of the pandemic. METHODS: The Vision Academy's membership of international retinal disease experts analyzed guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic and graded the recommendations according to three levels of increasing epidemic pressure. The revised recommendations were discussed, refined, and voted on by the 14-member Vision Academy Steering Committee for consensus. RESULTS: Protocols to minimize the exposure of patients and healthcare staff to COVID-19, including use of personal protective equipment, physical distancing, and hygiene measures, should be routinely implemented and intensified according to local infection rates and pressure on the hospital/clinic or healthcare system. In areas with many COVID-19-positive clusters, additional measures including pre-screening of patients, postponement of non-urgent appointments, and simplification of complex intravitreal anti-VEGF regimens should be considered. Treatment prioritization for those at greatest risk of irreversible vision loss should be implemented in areas where COVID-19 cases are increasing exponentially and healthcare resources are strained. CONCLUSION: Consistency in monitoring of local infection rates and adjustment of clinical practice accordingly will be required as we move forward through the COVID-19 era. Ophthalmologists must continue to carefully weigh the risk-benefits to minimize the exposure of patients and healthcare staff to COVID-19, ensure that patients receive sight-saving treatment, and avoid the potential long-term impact of prolonged treatment postponement.

MANAGEMENT OF RETINAL PIGMENT EPITHELIUM TEAR DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019). RESULTS: Three key recommendations were made based on existing literature and clinical experience: 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed. 3) After RPE tear develops, anti-VEGF treatment should be continued in patients with active disease (as indicated by presence of intraretinal or subretinal fluid), although cessation of therapy should be considered in eyes with multilobular tears. CONCLUSION: Although evidence to support the assumption that anti-VEGF treatment contributes to development of RPE tear is not definitive, some data suggest this link.

Elevated fecal calprotectin and lactoferrin associated with small intestinal lesions in patients with Behçet disease.

BACKGROUND AND AIMS: Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. METHODS: This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. RESULTS: Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 µg/g) and FL (cutoff value = 17 µg/g) were biomarkers for small intestinal lesions in patients with BD. CONCLUSION: The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic.

PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy's Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.

SUSPENDING TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN CASES OF FUTILITY.

PURPOSE: To provide guidance on the management of patients with neovascular age-related macular degeneration and its subtypes who respond poorly to anti-vascular endothelial growth factor (anti-VEGF) therapy, and to identify cases where suspending anti-VEGF treatment may be warranted. METHODS: Through a literature review and the combined knowledge and clinical experience of retinal experts, the Steering Committee of the Bayer-sponsored Vision Academy developed an algorithm for determining when to suspend anti-VEGF treatment of neovascular age-related macular degeneration in cases of futility. RESULTS: Consideration of factors that may cause suboptimal response to anti-VEGF therapy, such as undertreatment or misdiagnosis of the underlying condition, and factors that may preclude continued treatment, such as injection- or drug-induced complications, is necessary for adjusting treatment protocols in patients who respond poorly to anti-VEGF. If poor response to treatment persists after switching to an alternative anti-VEGF agent and no change in response is observed after withholding treatment for a predetermined period of time ("treatment pause"), anti-VEGF treatment may be considered futile and should be suspended. CONCLUSION: This publication introduces an algorithm to guide the management of neovascular age-related macular degeneration in patients showing poor response to anti-VEGF treatment and provides expert guidance for suspending anti-VEGF treatment in cases of futility.

One-Year Outcomes of a Treat-and-Extend Regimen of Aflibercept for Exudative Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to investigate the 1-year outcomes of treat-and-extend aflibercept for exudative age-related macular degeneration (AMD) in Japan. PROCEDURES: Clinical records of 67 patients (67 eyes) were reviewed. Monthly aflibercept was administered until resolution of exudation and maximal reduction of pigment epithelial detachment. Injection intervals were extended by 2-week units up to 12 weeks if no exudation was observed and shortened for recurrence. RESULTS: Mean best-corrected visual acuity (logarithm of the minimum angle of resolution) improved from 0.29 to 0.14 at 12 months (p < 0.0001). Mean central retinal thickness decreased from 430 µm to 236 µm at 12 months (p < 0.0001). Fifty-nine eyes (88.0%) achieved a dry macula with a mean of 8.3 injections by study end. The injection interval was extended to 10 weeks in 44.8% and to 12 weeks in 17.9% of eyes. CONCLUSIONS: At 1 year, good outcomes were obtained using treat-and-extend aflibercept for exudative AMD in Japan.

Subfoveal Choroidal Thickness during Aflibercept Therapy for Neovascular Age-Related Macular Degeneration: Twelve-Month Results.

PURPOSE: To investigate changes in subfoveal choroidal thickness after intravitreal aflibercept injections (IAIs) for neovascular age-related macular degeneration (AMD) at 12 months. DESIGN: Retrospective, consecutive, interventional case series. PARTICIPANTS: One hundred forty-four patients with treatment-naïve neovascular AMD examined at 3 university hospitals. METHODS: After a loading phase of 3 monthly 2.0-mg IAIs, the patients were injected bimonthly with additional rescue injections performed for worsening. Subfoveal choroidal thickness in IAI-treated eyes was evaluated using enhanced depth imaging optical coherence tomography (OCT) or swept-source OCT. MAIN OUTCOME MEASURES: Changes in subfoveal choroidal thickness over a 12-month period. RESULTS: Of the 144 treated eyes, 58 (40.3%) had typical neovascular AMD and 86 (59.7%) had polypoidal choroidal vasculopathy (PCV). The mean subfoveal choroidal thickness of treated eyes decreased from 268.1±101.3 µm at baseline to 233.0±99.7 µm at 3 months and remained unchanged at 232.4±99.6 µm at 12 months (percentage decrease, 13.3% at 12 months compared with baseline; P < 0.0001), although there was some fluctuation in between treatments. This decrease in subfoveal choroidal thickness was associated significantly with gain in visual acuity for PCV eyes (P = 0.0087; R = 0.28), but not for eyes with typical neovascular AMD (P = 0.17; R = 0.18). Eyes without persistent or recurrent retinal fluid after the loading phase showed greater decrease in subfoveal choroidal thickness compared with those with persistent or recurrent retinal fluid, in both typical neovascular AMD (P = 0.042) and PCV (P = 0.038) eyes. CONCLUSIONS: Subfoveal choroidal thickness decreased over 12 months with IAI therapy in eyes with neovascular AMD. Changes in subfoveal choroidal thickness after IAIs seem to be related to visual and anatomic outcomes.