Response to photodynamic therapy combined with intravitreal aflibercept for polypoidal choroidal vasculopathy depending on fellow-eye condition:2-year results.

We investigated whether response to photodynamic therapy (PDT) with intravitreal aflibercept injection (IAI) for polypoidal choroidal vasculopathy (PCV) differs depending on fellow eye condition. A retrospective review was conducted for consecutive 60 eyes with PCV treated with PDT combined with IAI as well as 2-years of follow-up data. Fellow eyes were divided into 4 groups; Group 0: no drusen, Group 1; pachydrusen, Group 2; soft drusen, Group 3: PCV/fibrovascular scarring. Best-corrected visual acuity improved at 24-months irrespective of groups and there were no significant differences in visual improvement among treated eyes among the 4 groups. Within 2-years, 35 (58.3%) required the retreatment. The need for retreatment including additional injection and the combination therapy was significantly less in Group 1(12.5%) compared to the others (P = 0.0038) and mean number of additional IAI was also less in Group 1 compared to the others (P = 0.017). The retreatment-free period from the initial combination therapy was longest in Group 1 (23.6±1.1 months) (P = 0.0055, Group 0: 19.1±6.9, Group 2: 12.8±7.9, Group 3: 11.5±9.9). The need for retreatment was significantly different according to fellow-eye condition. Among PCV patients, pachydrusen in fellow eyes appear to be a predictive characteristic for a decreased treatment burden at 2 years

Contribution of corneal neovascularization to dendritic cell migration into the central area during human corneal infection.

Compared with the peripheral corneal limbus, the human central cornea lacks blood vessels, which is responsible for its immunologically privileged status and high transparency. Dendritic cells (DCs) are present in the central avascular area of inflamed corneas, but the mechanisms of their migration to this location are poorly understood. Here, we investigated the contribution of vessel formation to DC migration into the central cornea, and analyzed the DC chemotactic factors produced by human corneal epithelial (HCE) cells. Using human eyes obtained from surgical procedures, we then assessed vessel formation, DC distribution, and activin A expression immunohistochemically. The results demonstrated increased numbers of vessels and DCs in the central area of inflamed corneas, and a positive correlation between the number of vessels and DCs. Activin A was expressed in the subepithelial space and the endothelium of newly formed blood vessels in the inflamed cornea. In infected corneas, DCs were present in the central area but no vascularization was observed, suggesting the presence of chemotactic factors that induced DC migration from the limbal vessels. To test this hypothesis, we assessed the migration of monocyte-derived DCs toward HCE cell supernatants with or without lipopolysaccharide (LPS) stimulation of HCE cells and inflammatory cytokines (released by HCE cells). DCs migrated toward tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and activin A, as well as LPS-stimulated HCE cell supernatants. The supernatant contained elevated TNF-α, IL-6, and activin A levels, suggesting that they were produced by HCE cells after LPS stimulation. Therefore, vessels in the central cornea might constitute a DC migration route, and activin A expressed in the endothelium of newly formed vessels might contribute to corneal vascularization. Activin A also functions as a chemotactic factor, similar to HCE-produced TNF-α and IL-6. These findings enhance our understanding of the pathophysiology of corneal inflammation during infection

A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4–8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1–2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10−7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10−3 and 1.0 × 10−3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept

Five-Year Outcome of Aflibercept Monotherapy for Exudative Age-Related Macular Degeneration with Good Baseline Visual Acuity

We investigated the long-term visual and anatomical outcomes of aflibercept monotherapy for exudative age-related macular degeneration (AMD) with good baseline best-corrected visual acuity (BCVA). A medical chart review was performed for 40 consecutive patients with baseline decimal BCVA ≥ 0.6 secondary to exudative AMD. Three monthly injections were administrated, and thereafter additional injection was performed if needed over 5 years. In total, 13 eyes with neovascular AMD (nAMD) and 27 eyes with polypoidal choroidal vasculopathy (PCV) were enrolled. In both groups, the mean BCVA significantly improved at the 12-month visit (p < 0.05). However, the significant improvement in BCVA disappeared at the 24-month visit, and the final mean BCVA was equivalent to that at baseline (p = 0.17 in the nAMD group and p = 0.15 in the PCV group). The median number of injections required after the loading dose was 15.0 during the 5-year follow-up (nAMD:15.0 vs. PCV:15). During the study period, 37 (92.5%) eyes required retreatment(s). Cox regression analysis demonstrated that the protective allele of ARMS2 A69S was associated with a retreatment-free period from the initial injection (p = 0.041, repeated forward selection method). As-needed aflibercept monotherapy is a preferable treatment option for exudative AMD with good initial visual acuity regardless of nAMD or PCV during the 5-year study period

Repeated Measurements Are Necessary for Evaluating Accurate Diurnal Rhythm Using a Self-Intraocular Pressure Measurement Device

Purpose: To investigate how many tests need to be performed to adequately assess intraocular pressure (IOP) diurnal change using a self-measuring rebound tonometer among glaucoma patients. Subjects and Methods: Adult patients with primary open-angle glaucoma were included. IOP was measured in the morning (6 AM to 9 AM), afternoon (12 PM to 3 PM), and at night (6 PM to 9 PM) for seven consecutive days. Twenty-four (7 males and 17 females, mean age 59.5 ± 11.0 years) patients who successfully measured IOP at least three times per day during the correct time periods for four days were subjected to analysis. Results: The IOP rhythm was significantly greater on the first day of measurement (6.6 ± 3.6 mmHg) than that averaged during subsequent days (4.4 ± 2.2 mmHg). The time of the highest and lowest IOP measurements on the first day of IOP measurement and during the entire measurement period coincided in 72.9% and 64.6% of cases, respectively. The concordance rate of the highest IOP time between the whole measurement period and each measurement day was less than 60%. Conclusion: The diurnal IOP rhythm measured by the patients themselves was not consistent, and multiple days of measurements may be necessary to correctly assess diurnal IOP rhythm

Expression of activin A.

<p>Activin A expression was determined using anti-activin A antibodies (goat polyclonal; 1∶50; R&D Systems; Minneapolis, MN, USA). <b>A.</b> Case 17; infected endophthalmitis. Activin A was expressed in the corneal epithelial and the subepithelial space with inflammatory cells. <b>B.</b> Case 19; bacterial endophthalmitis. Activin A was expressed in the endothelium of newly formed blood vessels, which suggests the presence of vessel formation in the central cornea.</p

Distribution of dendritic cells (DCs).

<p>DCs were observed under a light microscope. Primary antibodies against CD1a (MTB1; mouse IgG1, κ; 1∶30 dilution; Novocastra; Newcastle-upon-Tyne, UK), DC-SIGN (CD209; H-200; rabbit polyclonal; 1∶400; Santa Cruz Biotechnology; Santa Cruz, CA, USA), langerin (CD207; 12D6; mouse IgG2b; 1∶100; Ylem S.R.L.; Rome, Italy), and CD83 (1H4b; mouse IgG1, κ; 1∶40; Novocastra) were used to observe DCs. <b>A.</b> Case 17; infected endophthalmitis. CD1a⁺ DCs were observed mainly in the epithelium and the subepithelial space of an inflamed cornea. <b>B.</b> Case 17; infected endophthalmitis. Langerin⁺ DCs were observed in the epithelium. <b>C.</b> Case 18; infected keratitis. DC-SIGN⁺ DCs were observed in the stroma. <b>D.</b> Case 22; corneal perforation, post PKP. CD83⁺ DCs were observed in the subepithelial space together with lymphocytic infiltration.</p

Increasing levels of cytokines in the supernatant of human corneal epithelial (HCE) cells.

<p><b>A.</b> Levels of activin A in the supernatants from group A (HCE cells), B (HCE cells stimulated with 5 µg/mL LPS), C (HCE cells co-cultured with 10⁵/well, and D (HCE cells co-cultured with imDCs and stimulated with LPS for 1 hour, 3 hours, and 6 hours). The levels of activin A increased in a time-dependent manner in supernatants from group B. After 6 hours, they were higher in groups B and D than in group C (<i>p</i><0.01, Uni-ANOVA with a Bonferroni correction). <b>B.</b> Levels of IL-6 in the supernatants of the groups described in <b>A.</b> The levels of IL-6 increased in a time-dependent manner in groups B, C, and D. The levels of IL-6 increased after 6 hours in supernatants from groups B, C, and D, but were undetectable in those from group A. There were no significant differences in the levels of IL-6 among the supernatants from groups B, C, and D after 6 hours. <b>C.</b> Levels of TNF-α in supernatants from the groups described in <b>A.</b> TNF-α was not detectable in those from group A. TNF-α levels increased significantly only in group D, and the increase was time-dependent (<i>p</i><0.01, Uni-ANOVA with a Bonferroni correction).</p

Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy

Purpose: We compared 12-month outcomes of eyes with polypoidal choroidal vasculopathy (PCV) with or without complete regression of polyps observed one month after three monthly intravitreal administrations (loading phase) of aflibercept (2.0 mg/0.05 mL) or brolucizumab (6.0 mg/0.05 mL). Methods: All patients underwent indocyanine green angiography at both baseline and 3 months after initial injection and were followed up monthly with an as-needed regimen for up to 12 months. A total of 62 patients with PCV were included: 30 eyes were treated with brolucizumab, and 32 were treated with aflibercept. Eyes with complete regression of polyps (regression group) had significantly smaller maximum polyp diameter and were more frequently treated with brolucizumab than those without complete regression (non-regression) group. Results: Best corrected visual acuity was comparable between the two groups at 12 months. Although the 12-month retreatment-free proportion was comparable between the two groups (33.0% versus 27.0%, p = 0.59), a retreatment-free period was significantly longer in the regression group than in the non-regression group (8.3 ± 3.3 versus 6.5 ± 3.6 months, p = 0.022), and the number of additional injections was significantly fewer in the regression group than in the non-regression group (1.2 ± 1.2 versus 3.0 ± 2.6, p = 0.007). Conclusions: Complete regression of polyps observed after the initial phase possibly prolongs the retreatment-free period and reduces the number of additional injections irrespective of aflibercept or brolucizumab