Yoichi Sakurada

Purpose: This study aimed to evaluate how the temporal dynamics of polyp regression influence 24-month outcomes in eyes with polypoidal choroidal vasculopathy (PCV) treated with as-needed vascular endothelial growth factor (VEGF) inhibitors. Methods: Sixty-three eyes of 63 patients were included. All patients initially received three monthly intravitreal injections of either aflibercept (2 mg) or brolucizumab, followed by as-needed treatment for 24 months. The selection of a VEGF inhibitor depends on time. Indocyanine green angiography (ICGA) was performed at baseline, 3 months, and 12 months in all patients. Results: Among the 63 eyes, complete regression was observed in 39 eyes (61.9%) at 3 months. Of these 39 eyes, 29 eyes (46.0%) maintained complete regression at 12 months. Among the 24 eyes that did not show complete regression at 3 months, 5 eyes (20.8%) achieved complete regression at 12 months. Visual acuity improved over 24 months regardless of the timing of regression. Early regression at 3 months was associated with fewer additional injections during the first year. In contrast, regression at 12 months—rather than at 3 months—was more strongly associated with fewer additional injections during the second year. Conclusions: The most recent status of the polypoidal lesion was associated with the number of additional injections during the corresponding 12-month period, suggesting that ICGA-based assessment may be important for predicting treatment responsiveness.

Purpose To investigate the association between genetic variants susceptible to exudative age-related macular degeneration (AMD) and the treatment response to as-needed intravitreal brolucizumab (IVBr) therapy. Study design Interventional study Methods This retrospective study included 103 treatment-naïve eyes with exudative AMD. All eyes received three monthly IVBr injections (6.0 mg/0.05 mL) followed by a pro re nata regimen for 12 months. Seven major AMD-associated single nucleotide polymorphisms—ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH rs1329428, C2-CFB-SKIV2L rs429608, C3 rs2241394, CETP rs3764261, and ADAMTS9 rs6795735—were genotyped using TaqMan assays. The requirement for retreatment, the number of additional injections, and visual outcomes were compared across genotypes. Results Of the 103 patients, 68 (66.0%) required additional injections. The T allele of ARMS2 A69S was significantly more frequent in the retreatment group than in the retreatment-free group (65.0% vs. 42.9%, p = 1.9 × 10⁻³) and remained independently associated with retreatment after adjustment for age, sex, and baseline visual acuity (p = 3.0 × 10⁻³). Eyes with the TT genotype required significantly more additional injections than those with the TG or GG genotypes (2.4 ± 1.7 vs. 1.3 ± 1.6 and 1.3 ± 1.5, respectively; p = 5.0 × 10⁻³). Kaplan–Meier analysis demonstrated a significant difference in retreatment-free survival among ARMS2 genotypes (p = 4.1 × 10⁻⁴). Visual outcomes did not differ across any genotypes. Conclusions ARMS2 A69S may serve as a predictor of recurrence and number of additional injections in as-needed brolucizumab therapy for exudative AMD.

Endophthalmitis continues to represent a vision-threatening complication of intravitreal injection. Herein, we present a rare case of endophthalmitis caused by α-streptococcal following intravitreal ranibizumab biosimilar administration using a prefilled syringe. A 72-year-old woman was referred to our clinic and diagnosed with acute endophthalmitis in the left eye, following intravitreal administration of a ranibizumab biosimilar delivered via a prefilled syringe. A hypopyon was noted at a height of 3 mm, and the fundus examination of the left eye was obscured by corneal edema. The best-corrected visual acuity (BCVA) in the left eye was limited to hand motion. Urgent vitrectomy was performed with intraoperative irrigation using ceftazidime sodium (20 mg/500 mL) and vancomycin (10 mg) in the left eye. α-Streptococcal was isolated from both the aqueous humor and vitreous culture specimens. At 19 days postoperatively, the fundus was clearly visible, and the BCVA had recovered to 0.4 in the left eye, which corresponded to the pretreatment level. Urgent vitrectomy with irrigation using ceftazidime sodium and vancomycin may facilitate visual recovery in the affected eye.

Brolucizumab is a second-generation vascular endothelial growth factor (VEGF) inhibitor. To date, there have been no reports comparing treatment outcomes between exudative age-related macular degeneration with or without the pachychoroid phenotype using a second-generation VEGF inhibitor. The present study compared two-year as-needed brolucizumab treatment outcomes in patients with and without pachychoroid phenotypes. Sixty-six eyes completed two years of follow-up, and 14 and 52 eyes were classified into the pachychoroid and non-pachychoroid phenotypes, respectively. At 24 months, best-corrected visual acuity (BCVA) significantly improved in both groups, from 0.30 ± 0.29 to 0.12 ± 0.21 in the pachychoroid phenotype and 0.43 ± 0.36 to 0.31 ± 0.37 in the non-pachychoroid phenotype (p = 0.014 and 0.0013, respectively). At the 24-month follow-up, there were significantly fewer eyes requiring retreatment in the pachychoroid phenotype than in the non-pachychoroid phenotype (50% vs. 83%, p = 0.03). Although the number of additional injections was comparable between the two groups in the first 12 months (1.2 ± 1.4 vs. 1.7 ± 1.6, p = 0.29), the number of additional injections was significantly lower in the pachychoroid phenotype than in the non-pachychoroid phenotype (1.5 ± 2.4 vs. 3.2 ± 2.6, p = 0.0098) in the second 12 months. In the 24-month as-needed brolucizumab treatment group, the response to the pachychoroid phenotype was favorable, with significant BCVA improvement and fewer additional injections, particularly in the second 12 months.

We compared 12-month treatment outcomes of intravitreal injections of brolucizumab (IVBr) with aflibercept (IVA) for treatment-naïve exudative age-related macular degeneration (AMD). Patients were given three monthly IVBr or IVA injections and were followed up monthly for 12 months. Additional injections were given if exudation or hemorrhage recurred. The study included 339 eyes in 339 patients divided into the IVBr or IVA groups. In both groups, central retinal thickness (CRT) and subfoveal choroidal thickness significantly decreased, and best-corrected visual acuity (BCVA) significantly improved at the 12-month visit. BCVA improvement was similar in both groups (P = 0.27). Age, baseline BCVA, and thickness of the central retina and subfoveal choroid were associated with the 12-month BCVA. The proportion of patients who did not require additional injections was 33% in the IVBr and 30% in the IVA group (P = 0.58). The number of additional injections showed a trend favoring IVBr over IVA but the difference was insignificant (P = 0.055). Age, risk alleles of ARMS2 A69S, and baseline CRT were associated with shorter retreatment-free period. In conclusion, IVBr achieved similar visual and anatomic treatment outcomes to IVA with a trend toward requiring fewer additional injections during 12-month follow-up of as-needed regimen for exudative AMD.

Purpose: The aim was to compare the short-term outcomes of aflibercept 8 mg and brolucizumab for the treatment of polypoidal choroidal vasculopathy (PCV). Methods: This study included 48 eyes of 48 patients with PCV. Drug selection was based on the treatment period. Sixteen eyes received aflibercept 8 mg and thirty-two eyes received brolucizumab. All eyes underwent three consecutive monthly injections: aflibercept (114.3 mg/mL; 0.07 mL) or brolucizumab (120 mg/mL; 0.05 mL). Indocyanine green angiography was performed at baseline and at the 3-month visit to confirm the presence of polypoidal lesions. Results: In the aflibercept 8 mg group, best-corrected visual acuity (BCVA) significantly improved from 0.28 ± 0.26 at baseline to 0.18 ± 0.25 at the 3-month visit (p < 0.001). In the brolucizumab 6 mg group, BCVA improved from 0.35 ± 0.26 to 0.29 ± 0.27, although the change was not statistically significant (p = 0.08). Multivariate regression analysis showed that better BCVA at 3 months was associated with better baseline BCVA and lower central retinal thickness (CRT), independent of the drug used. CRT decreased from 382 ± 157 to 198 ± 98 in the brolucizumab 6 mg group and from 358 ± 152 to 192 ± 76 in the aflibercept 8 mg group at 3 months. Subfoveal choroidal thickness (SCT) decreased from 201 ± 78 to 167 ± 60 in the brolucizumab 6 mg group and from 186 ± 76 to 153 ± 67 in the aflibercept 8 mg group. The dry macula rate at 3 months was the same for aflibercept 8 mg and brolucizumab 6 mg at 93.8%. Complete regression of polypoidal lesions was observed in 62.5% and 75.0% of patients in the aflibercept and brolucizumab groups, respectively (p = 0.57). Conclusions: During the induction phase, aflibercept 8 mg demonstrated comparable outcomes to brolucizumab 6 mg in reducing CRT and SCT, achieving a dry macula, improving BCVA, and regressing polypoidal lesions in eyes with PCV.

Purpose: We aimed to investigate whether genetic variants susceptible to age-related macular degeneration (AMD) are associated with intraocular inflammation after brolucizumab administration in eyes that have exudative AMD. Methods: A total of 206 eyes from 206 patients (156 men/50 women, 74.0 ± 8.4 years; treatment-naïve, 128 [62.1%]; switching, 78 [37.9%]) were included in this study. All patients were treated with intravitreal brolucizumab at least once. The genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH (rs1329428), SKIV2L (rs429608), C3 (rs2241394), cholesteryl ester transfer protein (CETP) (rs3764261), and ADAMTS9 (rs6795375) was performed using TaqMan technology. Results: Out of the 206 patients who were included, 21 eyes from 21 patients (10.2%) exhibited intraocular inflammation (IOI). Four (19.0%) exhibited severe IOI, including retinal vasculitis and/or retinal vascular occlusion, and 17 (81.0%) showed mild IOI. The frequency of the T allele of the CETP gene was significantly lower in patients who developed IOI compared to patients who did not develop IOI (T allele frequency: 9.5% vs. 23.5%, p = 0.036). After adjusting for confounding factors, the T allele remained significantly associated with protection against IOI (p = 0.028, 95% confidence interval: 0.098–0.88). Conclusions: The T allele of the CETP gene, a risk allele for AMD and the protective allele for atherosclerosis, may be associated with protection against IOI after brolucizumab administration in eyes that have exudative AMD.

Purpose To investigate the association between early detection of retinal pigment epithelial (RPE) atrophy after anti-vascular endothelial growth factor (VEGF) treatment and the long-term treatment outcomes in eyes with retinal angiomatous proliferation (RAP). Study Design A retrospective observational study Methods All patients with treatment-naive RAP initially received three monthly anti-VEGF administration with or without photodynamic therapy (PDT), followed by as-needed anti-VEGF administration. At 12 months post-injection, they were divided into two groups depending on the presence or absence of RPE atrophy. The visual and anatomic outcomes, and the incidence of 12-month remission were investigated within a 48-month follow-up. Results Thirty-seven eyes of 37 patients were included. The mean age was 80.4 ± 7.0 years, 54% were women. In the atrophy (+) group, 58.3% of patients achieved 12-month remission, significantly higher than the atrophy (-) group (p = 0.04). During the study period, best corrected visual acuity in the atrophy (+) group deteriorated from 0.50 ± 0.43 logMAR to 0.66 ± 0.47 logMAR (p = 0.14), while in the atrophy (-) group, it deteriorated significantly from 0.48 ± 0.27 logMAR to 0.76 ± 0.42 logMAR (p = 6.7×10^-3). The mean additional injections in the atrophy (+) group were significantly smaller compared with the atrophy (-) group at 3.5 ± 4.7 versus 15.3 ± 4.3, respectively (p = 9.0×10^-6). Conclusion Early detection of RPE atrophy was associated with the incidence of 12-month remission and reduced number of additional injections. The formation of RPE atrophy might suggest a decrease in the disease activity of RAP.

Background/Objectives: The aim was to investigate the short-term outcomes of three consecutive monthly aflibercept 8 mg administrations for treatment-naïve eyes with exudative age-related macular degeneration (AMD). Methods: Twenty-one eyes with exudative AMD were included (type 1 macular neovascularization: eleven eyes; type 2 macular neovascularization, four eyes; and polypoidal choroidal vasculopathy (PCV), six eyes). All eyes received three consecutive monthly administrations of aflibercept 8 mg (114.3 mg/mL) at an injection volume of 0.07 mL. Indocyanine green angiography (ICGA) was performed on eyes with PCV at baseline and at the 3-month visit. Results: The best-corrected visual acuity significantly (BCVA) improved from 0.31 ± 0.38 (baseline) to 0.25 ± 0.38 at the 3-month visits (p = 0.035). Dry macula achieved 62% and 100% at the 1-month and 3-month visits, respectively. Central retinal thickness and subfoveal choroidal thickness significantly decreased by 55.7% and 19.8%, from 341 ± 112 (baseline) to 190 ± 64 (3-month visits) and from 192 ± 50 (baseline) to 154 ± 51 (3-month visits), respectively (both p < 0.001). Complete regression of polypoidal lesions was seen in five (83.3%) eyes out of six on ICGA at the 3-month visit. No systemic adverse events were noted, and one eye developed a retinal pigment epithelial tear one month after the first injection. Conclusions: Three consecutive monthly administrations of aflibercept (8 mg) were safe and effective for resolving exudation and polyp regression, with significant BCVA improvement in treatment-naïve eyes with exudative AMD.