Sex differences in choroidal vessels using novel wide-field choroidal en-face images from optical coherence tomography.

This study aims to develop a method to quantify choroidal vessels in normal eyes using wide-field optical coherence tomography (OCT) en-face images. The study included participants with normal eyes in whom wide-angle OCT images were acquired to generate planarized choroidal en-face and thickness map images. The images were segmented into central, midperipheral, and peripheral areas, and the midperipheral and peripheral areas were further segmented into supratemporal, infratemporal, supranasal, and infranasal sectors. The mean planarized choroidal-vessel density (p-CVD), planarized choroidal-vessel size (p-CVS), and choroidal thickness (CT) were calculated in each sector. Sex differences were analyzed using the Mann-Whitney U test. The study included 162 participants comprising 84 female (mean age, 43.5 years; axial length, 24.0 mm) and 78 male (mean age, 44.4 years; axial length, 24.2 mm) participants with no significant differences in demographics (P ≥ 0.107). Men had a higher mean p-CVD in all regions (P < 0.001). The mean p-CVS was greater in men in all regions except for the supratemporal sector (P < 0.001). No significant differences in sex in the mean CT were observed in all regions (P ≥ 0.106). The p-CVD and p-CVS in normal eyes differ between sexes. This finding may contribute to the understanding of the pathophysiology of choroidal diseases.

Longitudinal changes of funduscopic optic disc size, color and cup-to-disc ratio in school children.

BACKGROUND: To investigate the relationship between changes in the optic disc size and color, cup-to-disc (C/D) ratio, and axial elongation in schoolchildren. METHODS: A prospective cohort study was performed in 75 right eyes of elementary school students for six years (from 8.5 to 14.5 years old). In the first and last year, all participants underwent optical axial length measurement and color fundus photography. The optic disc color was calculated by dividing the intensity of red by the sum of the intensity of red, green, and blue. The optic disc area was calculated by modifying the number of pixels according to Bennett's formula. The C/D ratio was calculated by dividing the vertical cup diameter by vertical optic disc diameter. Wilcoxon signed rank test was used to compare these optic disc parameters and axial length in the first and last year. RESULTS: Mean axial length in the last year (24.82 mm) was significantly longer than that in the first year (23.34 mm). Likewise, the mean optic disc size was significantly smaller in the last year (41,946 pixels) than that in the first year (46,144 pixels). The mean optic disc color in the last year (0.49) was significantly more reddish than that in the first year (0.46), while the mean C/D ratio in last year (0.50) was significantly smaller than that in first year (0.52). CONCLUSIONS: During the period from 8.5 years to 14.5 years of age, both the optic disc size and C/D ratio became smaller, while the color became more red.

Familial Exudative Vitreoretinopathy With and Without Pathogenic Variants of Norrin/ß-Catenin Signaling Genes.

Purpose: To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/ß-catenin genes. Design: This was a multicenter, cross-sectional, observational, and genetic study. Subjects: Two-hundred eighty-one probands with FEVR were studied. Methods: Whole-exome sequence and/or Sanger sequence was performed for the Norrin/ß-catenin genes, the FZD4, LRP5, TSPAN12, and NDP genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/ß-catenin genes. Main Outcome Measures: The phenotype associated with or without pathogenic variants of the Norrin/ß-catenin genes. Results: One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the FZD4, 42 with the LRP5, 10 with the TSPAN12, and 12 with the NDP gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, P < 0.0001), progression during infancy (75.0% vs. 53.8%, P = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, P = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, P = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, P < 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, P = 0.0346). Nine probands with NDP variants had features different from probands with typical Norrin/ß-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease. Conclusions: The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/ß-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy.

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 µm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2;P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Stratified choroidal vascular structure in treatment-naïve diabetic retinopathy.

OBJECTIVE: To analyze the anatomical choroidal vascular layers in topical treatment-naïve diabetic retinopathy (DR) eyes. DESIGN: A retrospective, clinical case-control study. METHODS: A total of 328 eyes from 228 patients with treatment-naive DR and 192 eyes matched for axial length from 174 healthy controls were enrolled in the study. Choroidal structure was quantitatively analyzed using enhanced depth imaging optical coherence tomography (EDI-OCT). Each choroidal vascular layer was divided into the choriocapillaris, Sattler's layer, and Haller's layer, and then the choroidal area (CA), luminal area (LA), stromal area (SA), and central choroidal thickness (CCT) were calculated using binarization techniques. The ratio of LA to CA was defined as the L/C ratio. RESULTS: In the choriocapillaris, CA was significantly lower in the mild/moderate non-proliferative DR (mNPDR) group than in the control group, and SA was significantly higher in all DR groups (each P < 0.01). The L/C ratio was significantly lower in all DR groups than controls (P < 0.01). In Sattler's layer, CA, LA, and SA were significantly higher in the severe NPDR (sNPDR) and PDR groups than in the control group (P < 0.01). In Haller's layer, the L/C ratio was significantly high among the PDR groups (P < 0.05). CONCLUSIONS: The choroidal parameters of DR patients by the binarization method were associated with the stage of DR, in which the choriocapillaris lumen decreased in all the DR stages. The expansion of CA seen in more advanced DR eyes mainly resulted from changes in the Sattler's and Haller's layers.

Age prediction using fundus parameters of normal eyes from the Kumejima population study.

PURPOSE: Artificial intelligence can predict the age of an individual using color fundus photographs (CFPs). This study aimed to investigate the accuracy of age prediction in the Kumejima study using fundus parameters and to clarify age-related changes in the fundus. METHODS: We used nonmydriatic CFPs obtained from the Kumejima population study, including 1,646 right eyes of healthy participants with reliable fundus parameter measurements. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. Least absolute shrinkage and selection operator regression with leave-one-out cross-validation was used to predict age. The relationship between the actual and predicted ages was investigated using Pearson's correlation coefficient. RESULTS: The mean age of included participants (834 males and 812 females) was 53.4 ± 10.1 years. The mean predicted age based on fundus parameters was 53.4 ± 8.9 years, with a mean absolute error of 3.64 years, and the correlation coefficient between actual and predicted age was 0.88 (p < 0.001). Older patients had greater red and green intensities and weaker blue intensities in the peripapillary area (p < 0.001). CONCLUSIONS: Age could be predicted using the CFP parameters, and there were notable age-related changes in the peripapillary color intensity. The age-related changes in the fundus may aid the understanding of the mechanism of fundus diseases such as age-related macular degeneration.

Evaluating photodynamic therapy versus brolucizumab as a second-line treatment for polypoidal choroidal vasculopathy.

BACKGROUND: To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy. METHODS: This case-control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders. RESULTS: Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: - 36.3 ± 99.4 µm vs. - 114.7 ± 181.4 µm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42-2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44. CONCLUSIONS: Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.

Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial.

BACKGROUND: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. METHODS: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). FINDINGS: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). INTERPRETATION: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. FUNDING: Regeneron Pharmaceuticals and Bayer.

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

Efficacy and Safety of Faricimab for Macular Edema due to Retinal Vein Occlusion: 24-Week Results from the BALATON and COMINO Trials.

PURPOSE: To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion. DESIGN: Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192). PARTICIPANTS: Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO. METHODS: Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24 weeks. MAIN OUTCOME MEASURES: Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug. RESULTS: Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change, +16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs. +17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs. +17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 µm [95.03% CI, -316.4 to -306.4 µm] and -304.4 µm [95.03% CI, -309.3 to -299.4 µm]) and COMINO (-461.6 µm [95.03% CI, -471.4 to -451.9 µm] and -448.8 µm [95.03% CI, -458.6 to -439.0 µm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P = 0.0023) and COMINO (44.4% vs. 30.0%; nominal P = 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n = 45] and 23.0% [n = 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n = 56] and 27.7% [n = 100], respectively). CONCLUSIONS: These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of age and axial length on choroidal stratified structure in normal eyes.

To quantify the choroidal structures of normal eyes by optical coherence tomography (OCT)-based binarization and evaluate the relationships among age, refractive power, and ocular axial length. This was a retrospective observational study. One hundred and eighty nine eyes of 189 subjects without ocular diseases were examined by enhanced depth imaging (EDI)-OCT. A choroidal OCT horizontal image with a width of 1500 µm centered on the fovea was binarized. The lumen, stroma, and total choroidal area in the choriocapillaris (CC), Sattler's layer (SL), and Haller's layer (HL) were measured, and the ratio of the luminal area to total choroidal area (L/C ratio) was calculated. Multiple regression analysis was performed for choroidal parameters in each choroidal layer and for age, refractive power, and ocular axial length. Multiple regression analysis showed that an older age was significantly correlated with a lower choroidal area and the L/C ratio in all choroidal layers (each P < 0.05). A Long axial length was significantly associated with lower SL and HL (P < 0.05), but not with refractive power. In the choroid of normal eyes, age-related decreases in the choroidal area and L/C ratio were associated with all choroidal layers, and elongation of the axial length was associated with thinning of SL and HL.

Quantification of peripapillary nerve fibre elevation and its association with axial length, optic disc tilt, and parapapillary atrophy area in young, healthy eyes.

BACKGROUND: Eyes with peripapillary nerve fibre elevation (pNFE) may have a gap between the optic nerve papillary margin on colour fundus photography and Bruch's membrane opening on cross-sectional optical coherence tomography (OCT). This study was conducted to evaluate the quantification of the height of pNFE in young healthy eyes and examine the relationship between pNFE height and axial length. METHODS: A prospective, observational, cross-sectional study was performed involving 117 right eyes. All participants (mean age 25.8 years) underwent comprehensive ophthalmologic examination involving axial length, fundus photography, and peripapillary and optic disc OCT. pNFE height was defined as the distance between the retinal surface plane and the upper edge of the pNFE in optic disc cross-sectional OCT images. Optic disc tilt was evaluated using a sine curve on retinal nerve fibre layer B-scan images. Parapapillary atrophy (PPA) area in colour fundus images was calculated using ImageJ and corrected using Bennett's formula. We evaluated relationships between pNFE height, axial length, optic disc papillary tilt, and PPA area using Spearman's correlation analysis. RESULTS: Sixty-five eyes had pNFE, with a mean pNFE height of 84.7 µm. pNFE height was significantly positively correlated with axial length (r = 0.32, p < 0.001), optic disc tilt (r = 0.25, p = 0.008), and PPA area (r = 0.27, p = 0.004). CONCLUSIONS: pNFE is not rare in young healthy eyes. Eyes with higher pNFE had a longer axial length and larger optic disc tilt and PPA area.

Colour tone of retinal arterioles imaged with a colour scanning laser ophthalmoscope can be an indicator of systemic arterial stiffness.

OBJECTIVE: Colour scanning laser ophthalmoscope (cSLO) offers several advantages, including improved image quality and better visualisation of the retinal structures compared with colour fundus photograph (CFP). This study aimed to identify whether cSLO could be used to predict systemic arterial stiffness. METHODS AND ANALYSIS: We retrospectively analysed the data of 54 patients with 103 eyes. In addition to blood pressure and blood data, all patients had cardio-ankle vascular index (CAVI) measurements, as well as images of the fundus acquired using cSLO and CFP. We determined the retinal artery sclerosis (RAS) index from the colour of the retinal artery in cSLO images, the ratio of arterial to venous diameter (A/V ratio), and Scheie's classification in CFP images. The correlation between each parameter and CAVI was examined using Spearman's rank correlation coefficient, and the correlation between Scheie's classification and CAVI was examined using Steel-Dowass tests. RESULTS: CAVI showed a significant positive correlation with the RAS index (r=0.679, p<0.001) but not with the A/V ratio or Scheie's classification. Multiple regression analysis showed that the RAS index was significantly and independently correlated with CAVI. CONCLUSION: cSLO is a non-invasive imaging modality that has the potential to accurately and instantaneously detect early systemic arterial stiffness.

Broadband design of silica-PLC mode-dependent-loss equalizer for 2LP-mode transmission systems.

A new configuration of mode-dependent-loss (MDL) equalizer for two linearly-polarized mode transmission systems using the silica planar lightwave circuit platform is proposed. This device acts as an LP01-mode attenuator (precisely, LP01/LP21 mode converter) to adjust the MDL keeping a high transmission of the LP11 modes. Almost all components constructing the device are based on the adiabatic mode conversion, which brings broadband operation. Especially, a newly proposed E12/E22 mode converter plays a key role in broadband MDL equalization. It is numerically revealed that the flattened spectra with designated transmission can be obtained for the wavelength from 1200 nm to 1650 nm.

Three-year changes in sex judgment using color fundus parameters in elementary school students.

PURPOSE: In a previous cross-sectional study, we reported that the sexes can be distinguished using known factors obtained from color fundus photography (CFP). However, it is not clear how sex differences in fundus parameters appear across the human lifespan. Therefore, we conducted a cohort study to investigate sex determination based on fundus parameters in elementary school students. METHODS: This prospective observational longitudinal study investigated 109 right eyes of elementary school students over 4 years (age, 8.5 to 11.5 years). From each CFP, the tessellation fundus index was calculated as red/red + green + blue (R/[R+G+B]) using the mean value of red-green-blue intensity in eight locations around the optic disc and macular region. Optic disc area, ovality ratio, papillomacular angle, and retinal vessel angles and distances were quantified according to the data in our previous report. Using 54 fundus parameters, sex was predicted by L2 regularized binomial logistic regression for each grade. RESULTS: The right eyes of 53 boys and 56 girls were analyzed. The discrimination accuracy rate significantly increased with age: 56.3% at 8.5 years, 46.1% at 9.5 years, 65.5% at 10.5 years and 73.1% at 11.5 years. CONCLUSIONS: The accuracy of sex discrimination by fundus photography improved during a 3-year cohort study of elementary school students.

Efficacy, Durability, and Safety of Faricimab in Patients From Asian Countries With Diabetic Macular Edema: 1-Year Subgroup Analysis of the Phase III YOSEMITE and RHINE Trials.

PURPOSE: To assess the 1-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema from Asian and non-Asian countries. DESIGN: Global, multicenter, randomized, double-masked, active comparator-controlled, phase III trials. METHODS: Subgroup analysis of patients from Asian (N=144) and non-Asian (N=1747) countries randomized to faricimab 6.0 mg every 8 weeks (Q8W), faricimab per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W in the YOSEMITE/RHINE (NCT03622580/NCT03622593) trials. Primary endpoint: best-corrected visual acuity (BCVA) changes from baseline at 1 year, averaged over weeks 48, 52, and 56. RESULTS: Mean BCVA change from baseline at 1 year in the Asian country subgroup was similar between arms: faricimab Q8W (n=50), +10.9 (95% CI: 8.6-13.2); faricimab PTI (n=48) +10.0 (7.7-12.4) letters; aflibercept Q8W (n=46) +9.0 (6.6-11.4) letters. BCVA gains in the non-Asian country subgroup (n=582, 584, 581) were +11.3 (10.5-12.1), +11.2 (10.5-12.0), and +10.7 (9.9-11.5) letters, respectively. At 1 year, 49% of Asian country patients in the faricimab PTI arm achieved Q16W dosing (vs. 52% non-Asian) and 78% achieved ≥Q12W dosing (vs. 72% non-Asian). Anatomic improvementswere generally greater with faricimab versus aflibercept and similar between the Asian and non-Asian country subgroups. Faricimab was well tolerated, with no new safety signals. CONCLUSIONS: Vision, durability, anatomic, and safety outcomes were generally similar between the Asian and non-Asian country subgroups, suggesting that global YOSEMITE/RHINE results may be generalized to the Asian population. These data support the benefit-risk profile of faricimab for treating Asian patients with diabetic macular edema.

Effect of the macular shape on hole findings in idiopathic macular hole differs depending on the stage of the macular hole.

This study aimed to investigate the relationship between macular shape and idiopathic macular hole (MH) findings using an objective method. We present retrospective observational case series on patients with MH. The shape of the macular area was quantified using quadratic equations, and the ocular shape (OS) index was calculated. The correlation between the OS index and macular hole findings for each stage was evaluated. Pearson's correlation coefficient showed a significant correlation between the OS index and horizontal hole diameter (p = 0.044), bottom diameter (p = 0.006), and vertical bottom diameter (p = 0.024) in stage 2. For stage 4, there was a negative and significant correlation between the OS index and age (p = 0.037), and horizontal (p = 0.021) and vertical (p = 0.027) bottom diameter. Multiple regression analysis showed that the horizontal (p = 0.0070) and vertical (p = 0.031) bottom diameter and OS index were independently and positively correlated in stage 2. In stage 4, the OS index was independently and negatively correlated with the horizontal (p = 0.037) and vertical (p = 0.048) bottom diameter. The ocular shape of the macula affects MH findings, and its impact depends on its stage.