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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.

BackgroundA consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed.MethodsThe panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions.ResultsThe panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle’s fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness.ConclusionsThe use of the proposed definitions may provide uniform language for clinicians and future research.

Background/aimsTo study peripapillary retinal nerve fibre layer (RNFL) and macular thickness in amblyopia using high-definition spectral-domain optical coherence tomography (SD-OCT) and to compare the results with available literature using the time-domain modality.MethodsThis was a prospective institutional study of patients ≥6 years of age with unilateral amblyopia (strabismic or anisometropic) and non-amblyopic anisometropia. RNFL and macular thicknesses were measured using SD-OCT and compared between fellow eyes.ResultsThe mean age was 20 (±12) years; 45 patients had amblyopia: 14 strabismic and 31 anisometropic. 20 patients had non-amblyopic anisometropia. The mean macular thickness was significantly increased in the amblyopic (273.8 μm) vs fellow eyes (257.9 μm), p=0.001. This difference remained significant in the anisometropic group (p=0.002) but not the strabismic group. The mean RNFL thickness was similar in amblyopic (95.4 μm) and fellow eyes (94.0 μm). Similar results were obtained regardless of the level of visual acuity, age or refractive error. In the control group of non-amblyopic anisometropia, the interocular difference did not reach statistical significance.ConclusionsCentral macular thickness was significantly increased in anisometropic amblyopia using SD-OCT. Anisometropia alone did not produce such a difference, which points to a possible correlation between amblyopia and the development of the retinal layers.

Background/aimsTo examine longitudinal optical coherence tomography angiography (OCTA) changes in macula and optic nerve head (ONH) in healthy, glaucoma suspect (GS) and primary open-angle glaucoma (POAG) eyes.MethodsHealthy, GS and POAG eyes from Diagnostic Innovations in Glaucoma Study with ≥2 years follow-up and four visits of macular/ONH OCTA imaging were included. Rates of macular wiVD (whole-image vessel density) and ONH wiCD (whole-image capillary density) changes were calculated for each diagnosis group using join mixed-effect modelling. Differences in wiVD/wiCD change rates across diagnoses were examined through pairwise comparison. Relationships of baseline 24-2 visual field (VF) mean deviation (MD) with wiVD/wiCD change rates were evaluated for POAG eyes.ResultsThere were 36, 57 and 79 eyes (25, 38 and 50 subjects) in healthy, GS and POAG groups, respectively. Rates of wiVD (range:−0.72 to −0.92 %/year) and wiCD (range:−0.28 to −0.66 %/year) loss were different from zero in all groups (p<0.05). The rates of wiCD loss differed across all diagnosis groups (p<0.001), while wiVD change rates did not increase when comparing healthy to GS eyes (p=0.167). Baseline VF MD showed a significant but modest correlation with the rates of both wiVD and wiCD loss (p<0.05), and the correlation with wiCD change rate was slightly stronger (R2=0.27 vs 0.16).ConclusionsIn glaucoma, there is earlier microvasculature loss in the ONH than in the macula. Moreover, ONH VD loss shows a slightly stronger association with baseline VF than macular VD. Observing ONH VD loss with OCTA may help to monitor early glaucoma, which should be confirmed by future larger studies.

AimsTo explore the correlation of local macular ganglion cell/inner plexiform layer (GC/IPL) thickness measurements with sensitivity at individual test locations on the central 10-2 visual fields (VFs) in patients with glaucoma.MethodsOne hundred thirty-seven eyes of 125 patients with spectral domain optical coherence tomography (OCT) and 10-2 VFs were included. The exported thickness matrices (200×200) of GC/IPL measurements were centred on the fovea. Total deviation values at each test location were correlated with the 20 000 GC/IPL thickness measurements in the corresponding inferior or superior hemiretina, and areas of highest correlation were plotted. Macular structure–function relationships were also examined between six wedge-shaped GC/IPL sectors and the corresponding VF clusters. A multivariate model was built to identify the 10-2 VF test locations associated with each GC/IPL sector thickness.ResultsAverage mean deviation on 10-2 VFs was −9.2±6.1 dB. The 10-2 VF test points demonstrated correlations with GC/IPL thickness in localised arcuate patterns mostly limited within the central 4.8×4.0 mm measurement ellipse (ρ=0.43–0.74, p<0.05 for all). Twenty-one test points of the 10-2 VF were the best predictors of sectoral GC/IPL thickness. Sectoral VF-OCT correlations were high (ρ=0.53–0.66, p<0.001) and did not significantly change after adjusting for retinal GC displacement (p>0.05).ConclusionsMacular OCT/VF relationships have localised arcuate characteristics in the central region of the macula. Given the overlapping nature of structure–function relationships, a smaller number of VF test locations may be used to summarise macular functional damage.Trial registration numberNCT01742819.

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1–G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, p<0.001). If CIRD was limited to three outer ETDRS quadrants (G4), mean BCVA was better compared to CIRD involving all four ETDRS quadrants (G5) (0.254 logMAR vs. 0.522 logMAR, p<0.001). Reading ability (BCVA ≤ 0.4 logMAR) was restored in 97.6% of eyes with G1–G3 compared to 86.9% of eyes with G4 (p=0.072) and 52.4% of eyes with G5 (p<0.001). In multivariable regression analysis of eyes with CIRD, a lower grade of detachment (G4 vs. G5: p<0.05) and lower extent of cystoid edema (focal/none vs. wide: p<0.001) were both associated with better postoperative function. The functional outcome after MIRD may be worse in the presence of foveal involvement (CIRD), but a lower grade of detachment and the absence of intraretinal edema can predict a good recovery in spite of CIRD.

We investigated changes in macular topography and their association with visual acuity and metamorphopsia in the idiopathic epiretinal membrane (iERM). Twenty-four eyes that underwent vitrectomy and ERM removal with internal limiting membrane peeling were included in this study. Best-corrected visual acuity (BCVA) and horizontal/vertical metamorphopsia scores (h and vM-scores in the M-chart) were assessed. The distances of fovea-disc (FD) and fovea-vascular arcade (FV), central subfield macular thickness (CSMT), and foveal location were measured using fundus photography, optical coherence tomography (OCT), and OCT angiography, respectively. The BCVA (logMAR) and vM-scores (P < 0.001, P = 0.014, respectively) improved after surgery. The distance of the FD decreased (P < 0.001) and FVs increased (P < 0.001, both). The fovea moved horizontally toward the disc (P < 0.001). The change in median total FVs (7.114 mm to 7.369 mm, P = 0.001) correlated with the change in BCVA (P = 0.049, Pearson's [r] = -0.404). No topographic parameters were associated with an improvement in the vM score. The macular topography significantly changed after iERM removal; the fovea moved nasally, and the distance between the superior and inferior vascular arcades increased. Such a change was relevant to the improvement in BCVA, but not metamorphopsia.

Sub-retinal fluid (SRF) has been discussed as a protective factor against macular atrophy in eyes with neovascular age-related macular degeneration (nAMD).To gauge the impact of SRF on macular atrophy, a database of 310 nAMD eyes was screened for eyes manifesting an SRF-only phenotype under treat & extend anti-VEGF treatment, defined as nAMD expressing CNV exudation beyond the three monthly anti-VEGF loading doses by SRF only without any signs of exudative intra-retinal fluid (IRF) for ≥3 years. Incidence of macular atrophy and treatment responses were evaluated on multimodal imaging, including optical coherence tomography (OCT), blue autofluorescence (BAF) and near-infrared (NIR) confocal scanning laser ophthalmoscopy and fluorescence and indocyanine green angiography (FAG/ICGA). In total, 27 eyes (8.7%) of 26 patients with a mean follow-up of 4.2 ± 0.9 (3–5) years met the inclusion criteria. Mean age was 72 ± 6 (range: 61–86) years. The SRF only phenotype was seen from baseline in 14 eyes (52%), and in 13 eyes (48%) after a mean 1.0 ± 1.3 (1–3) injections. In years 1 to 5, mean 7.5, 5.9, 6.1, 6.1 and 7.0 anti-VEGF injections were given (p = 0.33). Cumulative macular atrophy incidence was 11.5% at year 1, 15.4% throughout years 2 to 4, and 22.4% at year 5. In conclusion, eyes manifesting activity by SRF only in treat & extend anti-VEGF regimen for nAMD seem to exhibit rather low rates of macular atrophy during long-term follow-up. SRF might be an indicator of a more benign form of nAMD.

PurposeTo evaluate swept source optical coherence tomography angiography (SS-OCTA) in patients treated with hydroxychloroquine (HCQ) for more than 5 years and to compare results with the tests currently recommended for screening of HCQ retinopathy.MethodsIn this controlled pilot study, consecutive patients treated with HCQ for more than 5 years underwent SS-OCTA, SS-OCT B-scan and en-face C-scan, fundus autofluorescence (FAF), 10–2 automated visual field (AVF) testing and multifocal electroretinography (mfERG). On SS-OCTA, evaluation of the retinal superficial capillary plexus, middle capillary plexus, and deep capillary plexus (DCP) and the choriocapillaris (CC) was obtained.ResultsWe included 10 patients under HCQ treatment (20 eyes, mean age 38.91±11.73 years) and 18 healthy control patients (36 eyes, mean age 38.87±8.6 years). Mean duration of HCQ treatment was 10.0±3.25 (5–15) years and HCQ cumulative dose/body weight was 15.86±5.56 g/kg. The HCQ group showed a reduction of the vessel density in the 1 mm central, in the nasal and temporal subfields of DCP and in the 1 mm central subfield of CC, an increased foveal avascular zone in the three capillary plexuses, a greater frequency of CC flow voids and a reduced foveal choroidal thickness (p<0.05). Best-corrected visual acuity (BCVA), mfERG, SS-OCT B-scan and C-scan, AVF and FAF were normal in 20/20 eyes (100%).ConclusionsIn patients treated with HCQ for more than 5 years, choroidal thinning and flow abnormalities at SS-OCTA in the retinal capillary plexuses and CC may be observed even if BCVA, FAF, mfERG, AVF and SS-OCT are normal.

PurposeTo demonstrate the efficacy and safety of ranibizumab 0.5 mg pro re nata (PRN) versus laser photocoagulation for the treatment of Chinese patients with visual impairment due to diabetic macular edema (DME).MethodsREFINE was a phase III, 12-month, double-masked, multicenter, laser-controlled study in patients (aged ≥ 18 years) with DME. Patients were randomized 4:1 to receive either ranibizumab 0.5 mg or laser dosing regimen. Efficacy was evaluated as mean average change in best-corrected visual acuity (BCVA) from Months 1 to 12 versus baseline (primary endpoint), anatomical outcomes, treatment exposure, and safety were also assessed.ResultsRanibizumab was statistically superior (p < 0.001) to laser treatment, with a mean average BCVA gain of 6.8 letters (ranibizumab) over 12 months versus 1.1 letters (laser). At Month 12, mean BCVA gain was 7.8 letters (ranibizumab) and 2.5 letters (laser) from baseline. Patients in the ranibizumab arm received a mean number of 7.9 intravitreal injections, whereas those in the laser arm received a mean of 2.1 treatments. There were no new safety signals.ConclusionRanibizumab 0.5 mg PRN demonstrated a statistically significant and clinically meaningful treatment effect versus laser and was well tolerated in Chinese patients with visual impairment due to DME over 12 months.