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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 To quantify the pericyte density in the macular capillaries, define the distribution of the transition zones, and characterize inter-pericyte tunneling nanotubules (IP-TNTs) in postmortem donor eyes. Methods Six healthy postmortem donor retinas were immunostained with NG2 (neural/glial antigen 2; pericytes), αSMA (alpha-smooth muscle actin; vascular smooth muscle cells), and CD31 (cluster of differentiation 31, endothelial cells), along with DAPI nuclear staining. Pericytes were identified by their NG2 staining and their density quantified in the superficial, middle, and deep capillary plexuses (SCP, MCP, DCP). The transition zone was identified by pericytes double-labeled with αSMA/NG2 along downstream branches of the major arterioles. IP-TNTs were identified as tubular structures, marked by NG2 staining and devoid of CD31 staining, that connect pericytes on separate capillary systems. Results Pericyte density as well as the ratio of pericytes per junction were significantly higher in the transition zones than within the capillary plexuses (51.6 ± 14.7 versus 22.7 ± 5.9 pericytes per 1000 μm, P  < 0.001; 1.22 ± 0.35 vs. 0.73 ± 0.3, P  < 0.001, respectively). A lower density of pericytes was observed in the DCP (20.1, 17–23) compared to the SCP (22.9, 18–29) and MCP (23.6, 19–27, P  = 0.002). While they were more abundant in the SCP, transition zone vessels were identified in all the capillary plexuses, and IP-TNTs were more abundant within the MCP. Conclusion Our results suggest that the macular capillary layers have unique structural attributes, with transition zones likely contributing to independent functional regulation of each layer. The significantly higher pericyte density and junctional coverage in the transition zones and their extension into the different plexuses underscores their important regulatory role in the human macula. The lower pericyte density in the DCP, and prevalence of IP-TNTs in the MCP suggest these layers have unique functional adaptations.

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.

Objective This study examined the relationship between visual field performance measured with the Humphrey Field Analyzer and macular thickness measured using optical coherence tomography across three groups: individuals without diabetes, individuals with diabetes but no diabetic retinopathy, and individuals with diabetic retinopathy. The aim was to determine whether structural and functional measures show meaningful associations within and across disease stages in a Trinidad and Tobago population. Results In unadjusted comparisons, macular and visual-field measures differed across groups (all p  < 0.001). After age adjustment, most between-group differences were no longer significant, and age independently predicted VFI, confirming age as a major confounder. Within-group, age-adjusted associations persisted in DR (OD): lower VFI correlated with greater superior (partial r  = − 0.519, p  = 0.027) and temporal ETDRS thickness (partial r  = − 0.585, p  = 0.011), and higher PSD correlated with greater superior (partial r = + 0.603, p  = 0.013) and temporal thickness (partial r = + 0.592, p  = 0.016); all four remained significant after FDR correction. Macular total volume showed limited functional relevance. In DM_no_DR (exploratory), small-sample regressions suggested similar direction, but estimates were imprecise. MD was not analyzed via ANCOVA due to incomplete data.

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.