Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.

BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg. METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing. FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]). INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD. FUNDING: Bayer AG and Regeneron Pharmaceuticals.

TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparisons of choroidal thickness and volume in eyes with central serous chorioretinopathy to that of control eyes determined by ultra-widefield optical coherence tomography.

PURPOSE: To compare choroidal thickness and volume in eyes with central serous chorioretinopathy (CSC) and healthy control eyes over a wide area of the fundus using ultra-widefield optical coherence tomography (UWF-OCT). METHODS: Thirty-three eyes of 29 patients with CSC and 36 eyes of 21 healthy controls were examined retrospectively. Choroidal images were obtained with a prototype UWF-OCT device with a field of view of 105° or approximately 31.5-mm wide by 10.9-mm deep. Choroidal thickness and volume were measured in the images of 12 radial scans (every 15°) from the horizontal scan. The "new index" of the extent of focal choroidal protrusion was defined as the maximum steepness of choroidal thickness (MSCT). RESULTS: Choroidal volume in CSC eyes was significantly larger than in control eyes within the central 50° (P < 0.001). However, there was no significant difference in choroidal volume in the peripheral 50 to 105° (P = 0.071). The MSCTs were significantly steeper in CSC eyes than in control eyes at scan lines 1, 6, 7, 8, and 10 (P < 0.01, P < 0.001, P < 0.05, P < 0.01, P < 0.05). CONCLUSIONS: The choroid in CSC eyes was thickened only at the posterior pole, and its protrusion was significant mainly in the vertical direction. Focal choroidal thickening at the posterior pole, which we speculate includes congenital scleral changes, may affect the pathophysiology of CSC.

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

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

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

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

Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile. CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.

Morphological differences of choroid in central serous chorioretinopathy determined by ultra-widefield optical coherence tomography.

PURPOSE: The purpose of this study was to compare the morphology of the central and peripheral choroid of eyes with central serous chorioretinopathy (CSC) to that of normal eyes using ultra-widefield optical coherence tomography (UWF-OCT). METHODS: We reviewed the medical records of 29 eyes of 25 patients (23 men, 2 women; average age 44.4 years) with CSC and 34 eyes of 22 healthy subjects (19 men, 3 women; average age, 49.5 years) with normal eyes. The images obtained by a prototype swept source UWF-OCT (Topcon, Tokyo, Japan) of about 31.5-mm wide and a depth of 10.9 mm were analyzed. The choroidal thickness was measured for each sector of the eye using the conventional automated layer analysis method. The local morphological differences were quantified by the maximum steepness (µm/deg) which was obtained by differentiating the changes in the choroidal thickness from the periphery to the fovea. Only the vertical scans were evaluated to avoid the influence of the optic disc. RESULTS: The choroid was thicker in the macular area than the peripheral area in both normal and CSC eyes. The choroid at the subfovea was significantly thicker in the CSC eyes than that of the normal eyes (P < 0.0001); however, the difference at the periphery was not significant. The mean of the maximum steepness of the choroidal thickness was 20.8 ± 3.8 µm/deg in the CSC eyes which was significantly steeper than the 16.0 ± 4.6 µm/deg in healthy eyes (P < 0.0001). CONCLUSION: The choroid in CSC eyes has a steeper slope around the posterior pole. UWF-OCT can be used to evaluate the abnormalities of the choroidal structures from the posterior pole to the periphery in eyes with CSC.

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

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

PERIPHERAL CHOROIDAL THICKNESS DETERMINED BY WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY IN EYES WITH CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To determine the central and peripheral choroidal thickness in eyes with central serous chorioretinopathy (CSC) and to compare these thicknesses values with those of control normal eyes. METHODS: Wide-field optical coherence tomographic images of 24 eyes of 19 patients with CSC and 14 normal eyes of 7 individuals were recorded. A 20-mm vertical scan through the fovea was obtained with the Xephilio optical coherence tomographic S1 (Canon, Japan), a wide-field optical coherence tomographic device. The subfoveal choroidal thickness and the thickness at 5 mm superior (S5) and inferior (I5), 7 mm superior (S7) and inferior (I7), 8.5 mm superior (S8) and inferior (I8), and 10 mm superior (S10) and inferior (I10) from the fovea in the CSC eyes and normal eyes were compared. RESULTS: There was no significant difference in the age ( P = 0.8) or the refractive error ( P = 0.7) between the CSC and normal eyes. The choroidal thickness was significantly thicker in the eyes with CSC than that in the normal eyes at subfoveal choroidal thickness ( P < 0.01), S5 ( P = 0.01), and S7 ( P = 0.02). However, there was no significant difference in the choroidal thickness at the more peripheral points (all P > 0.1). CONCLUSION: The thickened choroid in CSC was observed at the fovea and the area just superior to the fovea. The pathogenesis of CSC may be associated with the choroidal thickening confined to the fovea and superior foveal area.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS OF CLASSIC CHOROIDAL NEOVASCULARIZATION IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate the flow signals in subretinal hyperreflective material (SHRM) that represents classic choroidal neovascularization (CNV) on fluorescein angiography in eyes with polypoidal choroidal vasculopathy. METHODS: We retrospectively reviewed 20 eyes with polypoidal choroidal vasculopathy that appeared to have classic CNV on fluorescein angiography, accompanied by SHRM on optical coherence tomography (OCT) at the same location. Using OCT angiography (OCTA), we analyzed intrinsic flow signals in the SHRM (cross-sectional B-scans and en face). The possible association between pretreatment OCT angiography findings and fibrotic scar formation after antivascular endothelial growth factor (VEGF) treatment was evaluated. RESULTS: Six of 20 eyes (30%) showed vascular SHRM; the remaining 14 eyes (70%) showed avascular SHRM at the classic CNV site at baseline. The SHRM corresponded with polypoidal lesions seen on indocyanine green angiography in 5 of 6 eyes with vascular SHRM and in all 14 eyes with avascular SHRM. After anti-VEGF treatment, all 6 eyes with vascular SHRM left a fibrotic scar, whereas all 14 eyes with avascular SHRM showed no scar formation (P < 0.001). CONCLUSION: Using OCT angiography, we evaluated the flow signals in SHRM that represented classic CNV in eyes with polypoidal choroidal vasculopathy and successfully differentiated true Type 2 macular neovascularization from pseudo classic CNV.

A CONSENSUS ON RISK MITIGATION FOR BROLUCIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Patient Selection, Evaluation, and Treatment.

PURPOSE: Brolucizumab has high efficacy in retinal fluid resolution and provides the possibility for longer dosing intervals in the treatment of neovascular age-related macular degeneration. However, brolucizumab has been associated with events of retinal vasculitis and retinal vascular occlusion typically in the presence of other signs of intraocular inflammation (IOI). The purpose of this report is to provide guidance on the use of brolucizumab for neovascular age-related macular degeneration to a global audience. METHODS: A literature review was conducted on adverse events related to IOI after administration of brolucizumab in eyes with neovascular age-related macular degeneration. RESULTS: Possible risk factors for IOI and retinal vascular occlusion after brolucizumab should be considered before administering brolucizumab. Patients who receive brolucizumab should be educated on the symptoms, signs, and time course of IOI after brolucizumab. Before each injection of brolucizumab, physicians should assess the eye for any signs of inflammation and not treat with brolucizumab if inflammation is detected. Treatment of IOI should be prompt and provided with particular attention to the posterior segment. CONCLUSION: Careful patient selection, patient education, assessment for inflammation, and intensive treatment of possible inflammation are important when using brolucizumab in patients with neovascular age-related macular degeneration.

Characteristics of treatment-naïve quiescent choroidal neovascularization detected by optical coherence tomography angiography in patients with age-related macular degeneration.

PURPOSE: To determine the characteristics of eyes with treatment-naïve quiescent choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA). METHODS: Thirty-eight eyes of 37 treatment-naïve consecutive patients (30 men, 7 women, average 69.8 years) were studied. Quiescent CNVs were detected by OCTA (RTVue XR Avanti, Optovue, Fremont, CA) in all eyes. Swept-source OCT (SS-OCT; DRI-OCT, Topcon, Japan) confirmed the absence of exudation. The symptoms, visual acuity, CNV size, and status of the fellow eye were evaluated. Patients were followed longitudinally and the length of follow-up period and development of exudation were recorded for each patient. We also investigated patients' medical records from their referral hospitals in search of prior exudation. RESULTS: All eyes with quiescent CNV were diagnosed at the initial visit with sub-retinal pigment epithelium CNVs, i.e., type 1 CNV, from the OCT and OCTA images. Prior exudation was confirmed in 15 eyes (39.5%) from their medical records of the referral hospitals. Symptoms were present in 18 eyes (47.3%). An exudative CNV was present in 12 of the fellow eyes. Exudation developed in 12 eyes (31.6%) during an average follow-up period of 25.1 months. One-half of the eyes had a prior exudation. The CNV at the baseline in eyes that developed exudation during the follow-up period was larger than eyes without exudation; however, the difference was not significant (0.59±0.47 vs 0.48±0.32 mm2, P = 0.50). CONCLUSION: Quiescent CNVs will develop exudation in approximately 30% of the eyes during a mean 2-year follow-up period. These findings must be remembered when investigating quiescent CNVs that could not be distinguished from eyes with former active CNV and naturally deactivate CNV.

MISALIGNMENT BETWEEN CENTER OF FOVEAL AVASCULAR ZONE AND CENTER OF FOVEAL PHOTORECEPTORS IN EYES WITH IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: To determine the degree of misalignment between the center of foveal avascular zone and the center of foveal photoreceptors in eyes with an idiopathic epiretinal membrane (ERM). METHODS: We reviewed the medical records of 61 eyes with an idiopathic ERM. A 3 × 3 mm area centered on the fovea was scanned with optical coherence tomography angiography before and at 6 months after surgery. The center of foveal avascular zone and the center of foveal photoreceptors were detected by en-face optical coherence tomography angiography images and sequential optical coherence tomography B-sections in the macular region. The presence or absence of ectopic inner foveal layers was also evaluated. RESULTS: The mean distance from the center of foveal photoreceptors to the center of foveal avascular zone was 111.7 ± 106.8 µm in eyes with preoperative ERM. This distance was significantly correlated with the preoperative central foveal thickness (r = 0.33, P = 0.0104). Preoperatively, the ectopic inner foveal layers were present in 27 (44.3%) of 61 eyes. The foveal misalignment was greater in eyes with ectopic inner foveal layers than in those without ectopic inner foveal layers (158.6 ± 140.0 vs. 74.4 ± 45.4 µm, P < 0.0003). At 6 months after ERM surgery, the foveal misalignment was significantly reduced to 73.7 ± 48.0 µm (P = 0.0018). CONCLUSION: Determining the degree of misalignment between the center of foveal avascular zone and the center of foveal photoreceptors might be a useful way to evaluate the degree of ERM traction.

CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3,418 individuals followed by TaqMan assays in 2,692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10-10 and 6.75 × 10-8, respectively). Case-control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10-5 and 5.14 × 10-5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology.

QUANTIFICATION OF CHOROIDAL VASCULATURE BY HIGH-QUALITY STRUCTURE EN FACE SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY IMAGES IN EYES WITH CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To determine the density of the choroidal vasculature by high-quality structure en face optical coherence tomography (OCT) scanned at the same time as OCT angiography in eyes with central serous chorioretinopathy (CSC). METHODS: Thirty-five eyes of 30 patients with CSC (20 men and 10 women; average age, 48.4 years) were studied. Volume scans (12 × 12 mm-square) were obtained at the same time as OCT angiographic scans (Plex Elite 9000; Swept-Source OCT, Zeiss). High-quality structure en face images were flattened at Bruch membrane and binarized to identify and quantify the choroidal vascular density by the Bernsen method of the segmentation slab of one-half of the choroidal thickness. Similarly, high-quality structure en face choroidal images of 35 healthy eyes of 29 patients (18 men and 11 women; average age, 51.7 years) were binarized and analyzed as controls. The en face images were cropped to exclude the optic disk. RESULTS: The mean cropped image size was 9.57 mm × 9.57 mm in the eyes with CSC and 9.48 mm × 9.48 mm in the healthy eyes (P = 0.41). In the eyes with CSC, the choroidal vascular density was 61.6 ± 7.5% of the choroid, which was significantly greater than that in the healthy eyes at 49.4 ± 7.5% (P < 0.01). CONCLUSION: High-quality structure en face OCT can be used to assess the density of the choroidal vessels quantitatively and noninvasively in eyes with CSC.

Choroidal neovascularization imaging using multiple en face optical coherence tomography angiography image averaging.

PURPOSE: To determine the effects of averaging five en face optical coherence tomography angiographic (OCTA) images on the quality of the images in eyes with a choroidal neovascularization (CNV). METHODS: Twenty-seven eyes of 25 patients (18 men, 7 women; average age 71.0 years) with a CNV were examined by OCTA (OCT HS-100, Canon. Japan). A 3 × 3-mm image including the CNV was recorded and automatically segmented between the retinal outer layers. Analyses were performed on a single image (S-image) and the average of five single images of the same area (A-images). The region of the CNV was selected by ImageJ, and the peak signal-to-noise ratio (PSNR), the vascular density (VD), fractal dimension (FD), and the noise component using band pass filter (BPF) processing of the S- and A-images of each case were compared. RESULTS: The average PSNR for the A-images was 14.0 which was significantly higher than the 12.2 for the S-images (P < 0.01). However, the average VD was 33.6% for the S-images and 34.8% for the A-images (P > 0.1). The average FD was 1.67 for the S-images and 1.54 for the A-images (P < 0.01). The mean luminance difference obtained by subtracting the luminance of the A-image from the S-image after BPF processing was 10.41 ± 14.66 db which was positive for all eyes. CONCLUSIONS: The better quality of the A-images of a CNV and absence of a significant difference in the vascular density indicates that the improvement was due to the removal of the same signal levels of the noise component and blood vessels.

EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT AND RANIBIZUMAB IN ASIAN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Subgroup Analyses From the VIEW Trials.

PURPOSE: To assess the treatment effect of intravitreal aflibercept and ranibizumab in Asian patients with neovascular age-related macular degeneration. METHODS: We evaluated data from VIEW 1 and VIEW 2, comparing functional and morphologic outcomes at Week 96 between intravitreal aflibercept 2 mg monthly (2q4) or 2 mg bimonthly after 3 initial monthly doses (2q8) versus ranibizumab 0.5 mg monthly among Asian patients (n = 269) and between Asian and white patients (n = 2044). RESULTS: In Asian patients, there were no significant differences between intravitreal aflibercept 2q4 and 2q8 compared with ranibizumab in mean gain in best-corrected visual acuity (10.23 and 8.35 vs. 8.51 letters). Reduction in central retinal thickness was greater for intravitreal aflibercept 2q4 (150.43 µm, P = 0.0075) and 2q8 (148.15 µm, P = 0.0126) than ranibizumab (119.46 µm). The proportion of dry retinas was greater for intravitreal aflibercept 2q4 (65.7%, P < 0.01) than ranibizumab (41.7%). There were no differences in outcomes between Asian and white patients. Serious treatment-emergent ocular adverse events occurred in <8% of treated eyes, evenly distributed across subgroups. CONCLUSION: In Asian patients with neovascular age-related macular degeneration, functional and morphologic outcomes were largely similar between intravitreal aflibercept and ranibizumab groups, and to results seen in white patients.

Phase II/III Clinical Trial of Sub-Tenon Injection of Triamcinolone Acetonide (WP-0508ST) for Diabetic Macular Edema.

PURPOSE: To assess the efficacy and safety of sub-Tenon injection of triamcinolone acetonide (WP-0508ST) for the patients with diabetic macular edema (DME). METHODS: This multicenter, randomized, double-masked, comparative, controlled study was performed in 95 patients with DME. The patients were randomly divided into 20 mg WP-0508ST, 40 mg WP-0508ST, and control groups. RESULTS: A significant improvement in central macular thickness (CMT) was observed (p < 0.001) at 12 weeks after a single sub-Tenon injection of 20 mg WP-0508ST. The 40 mg group also demonstrated improvement in CMT, but the difference was not significant. In addition, the best-corrected visual acuity was improved in both the 20 mg and 40 mg groups at 12 weeks. The major side effects were increased intraocular pressure (9.4% in the 20 mg group and 13.3% in the 40 mg group) and lenticular opacity (6.3% in the 20 mg group and 10.0% in the 40 mg group). However, none of the patients with increased intraocular pressure required surgery. CONCLUSION: The efficacy and tolerability of WP-0508ST in the treatment of DME were confirmed, and 20 mg was determined to be the optimal dose.

CLINICAL FINDINGS OF EYES WITH MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION REFRACTORY TO RANIBIZUMAB.

PURPOSE: To determine the relationship between the clinical findings and the response to ranibizumab therapy in eyes with macular edema associated with branch retinal vein occlusion. METHODS: We reviewed the medical records of 68 patients with macular edema associated with a branch retinal vein occlusion. The patients were placed in the refractory group if the central foveal thickness remained more than 250 µm throughout the 6-month study period despite the ranibizumab therapy; otherwise, they were placed in the responsive group. RESULTS: Sixty (88.2%) of 68 eyes were placed in the responsive group and the other 8 eyes (11.8%) were placed in the refractory group. At the pretreatment examination, fluorescein angiography showed extensive leakage from occluded vessels in 52 (86.7%) of the 60 eyes in the responsive group and focal leakages from microaneurysms or dilated capillaries in the other 8 eyes (13.3%). In the refractory group, 7 (87.5%) of 8 eyes had only focal leakage and 1 eye (12.5%) had extensive leakage (P < 0.0001). The mean initial subfoveal choroidal thickness in the eyes with branch retinal vein occlusion in the responsive group was significantly thicker than that in the fellow eyes (278.0 ± 90.5 µm, 249.9 ± 94.4 µm; P < 0.0001). On the other hand, the mean initial subfoveal choroidal thickness in the refractory group was not significantly different from that of the fellow eyes (P = 0.4002). CONCLUSION: The dye leakage pattern in the fluorescein angiography images and choroidal thickness may be associated with response to ranibizumab therapy.

Sneaker Male Squid Produce Long-lived Spermatozoa by Modulating Their Energy Metabolism.

Spermatozoa released by males should remain viable until fertilization. Hence, sperm longevity is governed by intrinsic and environmental factors in accordance with the male mating strategy. However, whether intraspecific variation of insemination modes can impact sperm longevity remains to be elucidated. In the squid Heterololigo bleekeri, male dimorphism (consort and sneaker) is linked to two discontinuous insemination modes that differ in place and time. Notably, only sneaker male spermatozoa inseminated long before egg spawning can be stored in the seminal receptacle. We found that sneaker spermatozoa exhibited greater persistence in fertilization competence and flagellar motility than consort ones because of a larger amount of flagellar glycogen. Sneaker spermatozoa also showed higher capacities in glucose uptake and lactate efflux. Lactic acidosis was considered to stabilize CO2-triggered self-clustering of sneaker spermatozoa, thus establishing hypoxia-induced metabolic changes and sperm survival. These results, together with comparative omics analyses, suggest that postcopulatory reproductive contexts define sperm longevity by modulating the inherent energy levels and metabolic pathways.