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To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre.Design: Randomised, double-masked, parallel-group, phase III equivalence study.Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ.Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

Purpose: To compare differences between the original criteria for diagnosis of ocular sarcoidosis (OS) (first International Workshop for OS [IWOS] 2009) and the revised criteria (sixth IWOS 2017), and their clinical usefulness when assessing OS in Korean patients. Methods: We analyzed patients with suspected OS who visited our tertiary referral ophthalmological and pulmonary clinic from 2007 to 2018. We diagnosed patients using both sets of criteria. Blood test and biopsy data (collected by physicians) and slit-lamp, fundus, and fluorescein angiography data (collected by ophthalmologists) were reviewed. Results: Thirty-four patients were diagnosed using both criteria. Of 32 patients who underwent biopsies, 31 had OS (96.87%). Using either set of criteria, 31 patients were diagnosed with definite OS and two with presumed OS. One patient diagnosed with possible OS using the previous criteria was diagnosed with presumed OS using the revised criteria. The new criteria add the lysozyme level, the CD4/CD8 ratio, and positron emission tomography imaging data to the old criteria and add the descriptors “presumed OS” and “probable OS”. There is no need to use the revised criteria in Korea; the biopsy and imaging data are adequately diagnostic. Conclusions: IWOS revised the OS diagnostic criteria by adding new parameters. However, this was unnecessary for Korea, where the biopsy and imaging data are adequately diagnostic.

The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome.Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography.A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P0.001 and P0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity.X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.

Purpose To investigate the long-term progression of pericentral hydroxychloroquine retinopathy. Design Multicenter, retrospective cohort study. Participants Eighty eyes (60 with pericentral pattern) of 41 Korean patients with hydroxychloroquine retinopathy followed up for 2 years or more after drug cessation. Methods Patients were screened for hydroxychloroquine retinopathy using spectral-domain or swept-source OCT, fundus autofluorescence (FAF), and Humphrey visual field (VF) tests. Follow-up was divided into short-term (≤2 years) and subsequent periods, and progression was evaluated in each period and severity group. Retinopathy progression on OCT was defined as increased length of the ellipsoid zone defect, decreased distance from the fovea to the photoreceptor defects, or newly developed or enlarged retinal pigment epithelium defects. On FAF, progression was defined as an increase in the area of hyperautofluorescence or hypoautofluorescence. Functional progression was defined as a regression coefficient of less than 0 dB/year for mean deviation and more than 0 dB/year for pattern standard deviation, based on linear regression analysis of 3 or more VF tests. Structural and functional progression rates were calculated using the slopes of retinal thicknesses on the Early Treatment Diabetic Retinopathy Study grid and perimetric parameters over time, respectively. Main Outcome Measures Structural and functional progression of retinopathy. Results Approximately one third of eyes with early pericentral retinopathy showed limited progression during the short-term period after drug cessation, but they subsequently showed stable or improved photoreceptors. Most eyes with moderate pericentral retinopathy showed continuous progression, particularly when converted to the severe stage. Severe eyes showed progressive damage throughout the follow-up period. In all severity groups, the rates of retinal thinning decreased over time. In eyes with pericentral retinopathy showing progression, circumferential enlargement of retinal damage was prominent in earlier stages, whereas centripetal enlargement of the ring-shaped lesion was noted in advanced stages. Functional progression, noted in 58.7% of the pericentral eyes, corresponded with structural progression. Conclusions Pericentral hydroxychloroquine retinopathy showed severity-dependent progression. Moderate pericentral retinopathy usually progressed, but centripetal progression threatening the fovea was remarkable mostly in severe retinopathy. Our results suggest that early detection of retinopathy may minimize the risk of progression to foveal involvement in pericentral retinopathy.

The aim of this review is to identify the common characteristics and prognoses of different subtypes of neovascular age-related macular degeneration (nAMD). We also propose recommendations on how to tailor treatments to the subtype of neovessels to optimise patient outcomes. The authors, selected members of the Vision Academy, met to discuss treatment outcomes in nAMD according to macular neovascularisation (MNV) subtypes, using evidence from a literature search conducted on the PubMed database (cut-off date: March 2019). This review article summarises the recommendations of the Vision Academy on how the characterisation of MNV subtypes can optimise treatment outcomes in nAMD. The identification of MNV subtypes has been facilitated by the advent of multimodal imaging. Findings from fluorescein angiography, indocyanine green angiography and spectral-domain optical coherence tomography collectively help refine and standardise the determination of the MNV subtype. To date, three subtypes have been described in the literature and have specific characteristics, as identified by imaging. Type 1 MNV is associated with better long-term outcomes but usually requires more intense anti-vascular endothelial growth factor dosing. Type 2 MNV typically responds quickly to treatment but is more prone to the development of fibrotic scars, which may be associated with poorer outcomes. Type 3 MNV tends to be highly sensitive to anti-vascular endothelial growth factor treatment but may be associated with a higher incidence of outer retinal atrophy, compared with other subtypes. Accurately assessing the MNV subtype provides information on prognosis and helps to optimise the management of patients with nAMD.摘要: 本综述的目的是确定新生血管性年龄相关性黄斑变性 (nAMD) 不同亚型的特征和预后.并建议如何根据新生血管的亚型调整治疗方案, 以优化患者的预后.作者为视觉学会的选定成员, 根据黄斑区新生血管 (MNV) 的不同亚型, 利用PubMed数据库中检索的文献 (截止日期: 2019年3月),讨论了nAMD的治疗效果.这篇综述文章总结了视觉学会关于不同MNV亚型如何优化nAMD治疗结果的建议.多模式成像促进了MNV亚型的识别.荧光素血管造影术、吲哚菁绿血管造影术和谱域光学相干断层扫描的结果共同完善并标准化了MNV亚型的确定.迄今为止,文献中已经描述了三种亚型,并通过成像确定了它们的具体特征.1型MNV具有更好的长期预后,但通常需要更高剂量的抗血管内皮生长因子.2型MNV通常对治疗反应迅速,但更容易形成纤维化瘢痕,这可能与较差的预后相关.3型MNV往往对抗血管内皮生长因子治疗高度敏感,但与其他亚型相比,可能与更高的视网膜外萎缩发生率相关.准确评估MNV的亚型可提供预后的信息,并有助于优化nAMD患者的管理.

Purpose: To report the anatomical and functional outcomes of Argus II retinal prosthesis implantation in Korean patients. Methods: We included 5 consecutive patients with end-stage retinitis pigmentosa (RP) who underwent Argus II retinal prosthesis implantation and were followed for at least 12 months. The transcorneal electrical evoked response was utilized for patient selection. We used intraoperative optical coherence tomography (OCT) for optimal placement of the array and provided specialized vision rehabilitation training. A morphological evaluation using SD-OCT and a functional evaluation using computer-based visual function tests, a letter-reading ability test, and the Functional Low-Vision Observer Rated Assessment (FLORA) were conducted. Results: Postoperatively, the array was completely apposed to the retinal surface in all eyes, except for one eye which had a preexisting macular concavity. Fibrosis-like tissues of ≥50-μm thickness developed at the interface in 2 eyes. All of the patients showed improvement in computer-based visual function tests and could read ETDRS letters at a distance of 50 cm. Three patients could read Korean words. FLORA was improved in all patients, mainly in tasks of visual mobility, daily activities, and social interactions. Conclusions: Along with good anatomical outcomes and specialized rehabilitation practices, recipients of the Argus II implant showed profound improvements in functional vision and mobility.

To investigate the factors associated with visual improvement in response to oral carbonic anhydrase inhibitors (CAIs) and the occurrence of microvascular changes in patients with retinitis pigmentosa-associated cystoid macular edema (RP-CME).This retrospective cohort study included 59 eyes from 39 patients with RP-CME who underwent at least 3 months of oral CAI treatment. The eyes were divided into responding and nonresponding groups based on optical coherence tomography (OCT) criteria (resolution of cyst and reduction of foveal or parafoveal volume). All eyes were assessed before and after treatment using OCT and OCT angiography.Thirty-three eyes (55.9%) demonstrated a positive response to treatment, and 26 eyes (44.1%) did not. Compared with nonresponding eyes, responding eyes had a significantly higher frequency of multilayer CME than CME limited to the inner nuclear layer ( P = 0.016). Subgroup analysis within the responding group revealed that improvements in visual acuity were more likely in eyes with fovea-involving CME and a higher baseline external limiting membrane and ellipsoid zone width. Microvascular parameters showed no significant changes after treatment.Eyes with CME extending to the outer nuclear layer or central fovea, and higher initial photoreceptor integrity may be prognostic factors associated with structural and functional improvements after carbonic anhydrase inhibitors treatment. Early treatment of multilayer CME with foveal involvement seems to be crucial in preventing irreversible photoreceptor damage.

Tamoxifen-induced retinopathy (TR) and macular telangiectasia type 2 (MacTel) share a highly similar retinal phenotype. In this study, we aimed to evaluate differences and similarities that may point toward underlying mechanisms linking both disease entities.Retrospective, cross sectional study.Patients diagnosed with MacTel or TR.Patients underwent multimodal retinal imaging, including color fundus photography, spectral-domain OCT, fundus autofluorescence, fluorescein angiography, and OCT angiography (if available). Age, age of onset, best-corrected visual acuity, and bilaterality of changes were evaluated. Patients' eyes were graded for different morphologic characteristics by 4 experienced graders.Phenotypical characterization and comparison of frequencies of retinal characteristics of TR and MacTel on multimodal imaging.Twenty-eight eyes of 14 patients with TR and 118 eyes of 59 patients with MacTel were included. Age, age of onset, and best-corrected visual acuity were similar in both cohorts. All but 1 patient showed bilateral changes. In patients with MacTel, neurodegenerative changes and vascular alterations were equally present, whereas in patients with TR, neurodegenerative changes usually prevailed. Predilection sites within the central retina differed between the 2 diseases: most findings in patients with TR were limited to the foveal center, whereas changes in patients with MacTel were present throughout a slightly larger region ("MacTel area"), with an epicenter temporal to the foveal center. Distinct morphologic features included the distribution of retinal crystals, the size and position of ellipsoid zone breaks, and the presence of hyperreflective changes on OCT images. Focal hyperpigmentation and neovascular membranes were only present in eyes with MacTel.Macular telangiectasia and TR share a highly similar retinal phenotype, especially in early disease stages. Subtle differences on multimodal retinal images may help distinguish between these 2 disease entities. Our findings indicate the involvement of Müller cells in both diseases, which may explain the observed phenotypic characteristics and similarities.

Due to the genotype–phenotype heterogeneity in retinitis pigmentosa (RP), molecular diagnoses and prediction of disease progression is difficult. This study aimed to report ocular and genetic data from Korean patients with PDE6B-associated RP (PDE6B-RP), and establish genotype–phenotype correlations to predict the clinical course. We retrospectively reviewed targeted next-generation sequencing or whole exome sequencing data for 305 patients with RP, and identified PDE6B-RP in 15 patients (median age, 40.0 years). Amongst these patients, ten previously reported PDE6B variants (c.1280G > A, c.1488del, c.1547T > C, c.1604T > A, c.1669C > T, c.1712C > T, c.2395C > T, c.2492C > T, c.592G > A, and c.815G > A) and one novel variant (c.712del) were identified. Thirteen patients (86.7%) experienced night blindness as the first symptom at a median age of 10.0 years. Median age at diagnosis was 21.0 years and median visual acuity (VA) was 0.20 LogMAR at the time of genetic analysis. Nonlinear mixed models were developed and analysis revealed that VA exponentially decreased over time, while optical coherence tomography parameters linearly decreased, and this was related with visual field constriction. A high proportion of patients with the c.1669C > T variant (7/9, 77.8%) had cystoid macular edema; despite this, patients with this variant did not show a higher rate of functional or structural progression. This study will help clinicians predict functional and structural progression in patients with PDE6B-RP.

Purpose To compare the efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) versus ranibizumab every 4 weeks in treatment-naive patients with neovascular age-related macular degeneration (AMD). Design Two randomized, multicenter, double-masked, parallel-group, active-controlled, phase 3 clinical trials (CEDAR, SEQUOIA) with identical protocols were conducted. Data from both trials were pooled for analysis. Participants Patients with active choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) of 24–73 Early Treatment Diabetic Retinopathy Study letters in the study eye were enrolled. Methods Patients (n = 1888) were randomized in a 1:1:1 ratio to study eye treatment with abicipar 2 mg every 8 weeks after 3 initial doses at baseline and weeks 4 and 8 (Q8), abicipar 2 mg every 12 weeks after 3 initial doses at baseline and weeks 4 and 12 (Q12), or ranibizumab 0.5 mg every 4 weeks (Q4). Main Outcome Measures The primary efficacy end point was proportion of patients with stable vision (defined as Results The proportion of patients with stable vision at week 52 was 93.2%, 91.3%, and 95.8% in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively, with both abicipar Q8 and Q12 noninferior to ranibizumab Q4. Week 52 mean change from baseline in BCVA was 7.5, 6.4, and 8.4 letters and in CRT was −144, −145, and −144 μm in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3%, respectively. The IOI AEs were typically mild or moderate in severity and treated with topical corticosteroids; 62 of 192 patients (32.3%) received oral and/or injectable corticosteroids. Conclusions Abicipar Q8 and Q12 were both noninferior to ranibizumab Q4 in the primary end point of stable vision at week 52. Intraocular inflammation was more frequent with abicipar. Quarterly and Q8 abicipar reduce nAMD disease and treatment burden compared with monthly treatment.

We investigated the microvascular changes in eyes with lamellar macular holes (LMHs) using optical coherence tomography angiography (OCTA), compare them between two subtypes of LMH. Tractional and degenerative LMH were differentiated based on the morphological characteristics of OCT. In OCTA images, foveal and parafoveal vessel density (VD) in the superficial and deep capillary plexus (SCP, DCP) and foveal avascular zone (FAZ) area were measured. Eyes that underwent vitrectomy for LMH were included in subgroup analysis. We analysed 63 LMH (42 tractional and 21 degenerative) eyes and 63 control eyes. Compared with degenerative LMH, tractional LMH had better BCVA (p = 0.010), smaller FAZ area (p = 0.001), and higher foveal VD in the SCP (p = 0.130) and DCP (p = 0.002). In degenerative LMH, better BCVA was associated with greater foveal VD in the SCP (p = 0.040) and DCP (p = 0.005), and parafoveal VD in the SCP (p = 0.006). In subgroup analysis, only the tractional LMH group showed significant increases in foveal and parafoveal VDs in the SCP after vitrectomy (p = 0.001 and p = 0.026, respectively). Significant differences in microvascular changes were noted between tractional and degenerative LMH, suggesting that two subtypes are distinct pathogenetic entities.

Purpose The prevalence of diabetes and diabetes-related complications, including diabetic macular edema (DME), is increasing in Asia and worldwide. Methods VIVID-East was a 12-month, double-masked, randomized, active-controlled, Phase 3 trial (NCT01783886) enrolling adult patients (aged ≥18 years) with DME at 25 centers across China, Hong Kong, Republic of Korea, and Russia. Eyes were randomized 1:1:1 to 2 mg intravitreal aflibercept (IVT-AFL) every 4 weeks (2q4; N=127), 2 mg IVT-AFL every 8 weeks (after 5 initial monthly doses from baseline to week 16) with sham injections on nontreatment visits (2q8; N=127), or macular laser photocoagulation at baseline and sham injections at every visit (laser control group; N=124). The primary efficacy endpoint was mean change in best corrected visual acuity (BCVA) from baseline to week 52. Results Compared with baseline, at week 52 the mean (SE) BCVA in the 2q4 and 2q8 groups gained +13.6 (0.9) and +13.1 (1.0) letters, respectively, versus -0.5 (1.4) letters in the laser group (P

To compare the efficacy of intraoperative intravitreal dexamethasone implant for macular edema secondary to diabetic retinopathy (DME), retinal vein occlusion (RVO), and noninfectious posterior uveitis.A retrospective review of 62 patients (29 men and 33 women; mean age 51.19 ± 14.41 years; 65 eyes) was performed. Best-corrected visual acuity (in logarithm of the minimal angle of resolution), central foveal thickness, intraocular pressure, and postoperative edema-free period were postoperatively assessed up to 1 year. The preoperative and postoperative numbers of other intravitreal injections needed were compared.Best-corrected visual acuity gradually improved in the DME group (from 0.87 to 0.51) but failed to improve from Month 3 onward in the RVO and uveitis groups. Central foveal thickness decreased in all groups, especially in the DME group (from 550.93 to 338.10 μm). Edema-free period was longest in the DME group (19.34 ± 15.12 months), followed by the uveitis (12.91 ± 7.85 months) and RVO (8.50 ± 8.76 months) groups. Subjects in the uveitis group used more intraocular pressure-lowering agents (1.00 ± 1.27) than those in the DME (0.13 ± 0.49) and RVO (0.36 ± 0.79) groups. Increased intraocular pressure events were most frequent in postoperative Week 1, especially in the uveitis group.Vitrectomy combined with intravitreal dexamethasone implant for DME, RVO, and noninfectious posterior uveitis had a favorable clinical outcome.

To evaluate plasma antiretinal autoantibody (ARA) profiling and diagnostic efficacy for autoimmune retinopathy (AIR).A multicenter, diagnostic evaluation study.Forty-nine patients with a clinical diagnosis of AIR, disease controls including 20 patients with retinitis pigmentosa (RP), and 30 normal controls were included. Plasma samples from patients were analyzed for the presence of 6 ARAs, including recoverin, α-enolase, carbonic anhydrase II, heat shock protein 60, aldolase C, and cone-rod homeobox/cone-rod retinal dystrophy 2 using western blotting.Autoantibody detection rates against cone-rod homeobox/cone-rod retinal dystrophy 2, heat shock protein 60, and aldolase C in AIR were 67.3%, 40.8%, and 42.9%, respectively, which were higher than those in RP and normal controls (P.001, P.001, and P = .007, respectively), but recoverin, α-enolase, and carbonic anhydrase II were not different from other control groups (P = .117, P = .774, and P = .467, respectively). Among ARAs, antirecoverin antibody was the most specific, as it was found in 3 (6.1%) patients with AIR and none of the control groups. As the number of detected ARAs increased, the probability of AIR increased (odds ratio: 1.913; P.001; 95% confidence interval: 1.456-2.785). The positive number of ARAs was significantly higher when photoreceptor disruption was observed on optical coherence tomography, or severe dysfunction was observed in electroretinography (P = .022 and P = .029, respectively).The profiles of ARAs in the AIR group were different from those in the RP and normal controls. The higher number of positive ARAs suggests a higher possibility of AIR diagnosis. ARAs should be used as adjunct tools for the clinical diagnosis of AIR.

Purpose: To describe the design and rationale of the phase 3 TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) trials that aimed to assess efficacy, safety, and durability of faricimab, the first bispecific antibody for intraocular use, which independently binds and neutralizes both angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A) versus aflibercept in patients with neovascular age-related macular degeneration (nAMD). Design: Identical, global, double-masked, randomized, controlled, phase 3 clinical trials. Participants: Adults with treatment-naïve nAMD. Methods: These trials were designed to evaluate patients randomized to receive faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses. The initial doses in the faricimab arm were followed by individualized fixed treatment intervals up to week 60, based on disease activity assessment at weeks 20 and 24, guided by central subfield thickness, best-corrected visual acuity (BCVA), and investigator assessment. The primary efficacy end point was BCVA change from baseline averaged over weeks 40, 44, and 48. Secondary end points included the proportion of patients receiving every-8-week, every-12-week, and every-16-week faricimab and anatomic outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. From week 60, faricimab-treated patients followed a personalized treatment interval (PTI), a novel protocol-driven treat-and-extend regimen with interval adjustment from every 8 weeks to every 16 weeks based on individualized treatment response measured by anatomic criteria, functional criteria, and investigator assessment of patients’ disease activity. Main Outcome Measures: Rationale for trial design and PTI approach. Results: The TENAYA and LUCERNE trials were the first registrational trials in nAMD to test fixed dosing regimens up to every 16 weeks based on patients' disease activity in year 1 and incorporate a PTI paradigm during year 2. The PTI approach was designed to tailor treatment intervals to individual patient needs, to reflect clinical practice treatment practice, and to reduce treatment burden. Conclusions: The innovative trial design rationale for the TENAYA and LUCERNE trials included maximizing the benefits of angiopoietin-2 blockade through dosing up to every 16 weeks and PTI regimens based on patients' disease activity while fulfilling health authority requirements for potential registrational efforts.

The proportion of fatal nontraffic injuries that involve high levels of alcohol use or alcohol intoxication was assessed by cause of injury to generate alcohol-attributable fractions. Updated alcohol-attributable fractions can contribute to improved estimates of the public health impact of excessive alcohol use.Peer-reviewed and gray literature for 1995-2019 on 15 causes of fatal nontraffic injuries in the U.S., Canada, or Mexico were systematically reviewed, and state data systems were queried for available estimates of fatalities with recorded blood alcohol concentration levels and proportions of decedents with blood alcohol concentrations ≥0.10 g/dL by cause of injury. For each injury cause, alcohol-attributable fractions across studies were synthesized by meta-analysis of single proportions using generalized linear mixed models.In total, 60 published studies and 40 additional population-level data points from 6 state data systems were included. The meta-analyzed alcohol-attributable fractions by cause of injury are as follows: air-space transport (0.03), aspiration (0.24), child maltreatment (0.09), drowning (0.31), fall injuries (0.37), fire injuries (0.34), firearm injuries (0.24), homicide (0.29), hypothermia (0.29), motor vehicle nontraffic crashes (0.42), occupational and machine injuries (0.08), other road vehicle crashes (railroad trespasser injuries) (0.63), poisoning (not alcohol) (0.20), suicide (0.21), and water transport (0.27), yielding an overall median alcohol-attributable fraction of 0.27.Excessive alcohol use is associated with substantial proportions of violent and nonviolent injury deaths. These findings can improve the data used for estimating alcohol-attributable injury deaths and inform the planning and implementation of evidence-based strategies (e.g., increasing alcohol taxes, regulating alcohol outlet density) to prevent them.

To describe the design and rationale of the phase 3 TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) trials that aimed to assess efficacy, safety, and durability of faricimab, the first bispecific antibody for intraocular use, which independently binds and neutralizes both angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A) versus aflibercept in patients with neovascular age-related macular degeneration (nAMD).Identical, global, double-masked, randomized, controlled, phase 3 clinical trials.Adults with treatment-naïve nAMD.These trials were designed to evaluate patients randomized to receive faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses. The initial doses in the faricimab arm were followed by individualized fixed treatment intervals up to week 60, based on disease activity assessment at weeks 20 and 24, guided by central subfield thickness, best-corrected visual acuity (BCVA), and investigator assessment. The primary efficacy end point was BCVA change from baseline averaged over weeks 40, 44, and 48. Secondary end points included the proportion of patients receiving every-8-week, every-12-week, and every-16-week faricimab and anatomic outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. From week 60, faricimab-treated patients followed a personalized treatment interval (PTI), a novel protocol-driven treat-and-extend regimen with interval adjustment from every 8 weeks to every 16 weeks based on individualized treatment response measured by anatomic criteria, functional criteria, and investigator assessment of patients' disease activity.Rationale for trial design and PTI approach.The TENAYA and LUCERNE trials were the first registrational trials in nAMD to test fixed dosing regimens up to every 16 weeks based on patients' disease activity in year 1 and incorporate a PTI paradigm during year 2. The PTI approach was designed to tailor treatment intervals to individual patient needs, to reflect clinical practice treatment practice, and to reduce treatment burden.The innovative trial design rationale for the TENAYA and LUCERNE trials included maximizing the benefits of angiopoietin-2 blockade through dosing up to every 16 weeks and PTI regimens based on patients' disease activity while fulfilling health authority requirements for potential registrational efforts.