Short-Term Outcomes of 3 Monthly intravitreal Faricimab On Different Subtypes of Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes. Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA. Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10-4) and central retinal thickness (CRT) (P = 1.3 × 10-5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4. Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes.

Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma.

Dendritic cells (DCs) vaccine is a potential tool for oncoimmunotherapy. However, it is known that this therapeutic strategy has failed in solid tumors, making the development of immunoadjuvants highly relevant. Recently, we demonstrated that Phoneutria nigriventer spider venom (PnV) components are cytotoxic to glioblastoma (GB) and activate macrophages for an antitumor profile. However, the effects of these molecules on the adaptive immune response have not yet been evaluated. This work aimed to test PnV and its purified fractions in DCs in vitro. For this purpose, bone marrow precursors were collected from male C57BL6 mice, differentiated into DCs and treated with venom or PnV-isolated fractions (F1-molecules < 3 kDa, F2-3 to 10 kDa and F3->10 kDa), with or without costimulation with human GB lysate. The results showed that mainly F1 was able to activate DCs, increasing the activation-dependent surface marker (CD86) and cytokine release (IL-1ß, TNF-α), in addition to inducing a typical morphology of mature DCs. From the F1 purification, a molecule named LW9 was the most effective, and mass spectrometry showed it to be a peptide. The present findings suggest that this molecule could be an immunoadjuvant with possible application in DC vaccines for the treatment of GB.

Natural Course of Pachychoroid Pigment Epitheliopathy.

Purpose: To investigate the natural course of pachychoroid pigment epitheliopathy (PPE). Design: A retrospective cohort study. Subjects: From the Kyoto central serous chorioretinopathy (CSC) cohort consisting of 548 patients with CSC as of September 2020, we included consecutive unilateral patients with acute or chronic CSC between January 2013 and December 2016. Methods: All patients underwent complete ophthalmic examination, including multimodal imaging such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. The fellow eyes of eyes diagnosed with CSC were screened for PPE, and their natural course was evaluated. We also evaluated the association of ARMS2 rs10490924, CFH rs800292, TNFRSF10A rs13278062, and GATA5 rs6061548 genotypes with the natural course. Main Outcome Measures: Incidence of CSC, pachychoroid neovasculopathy, and pachychoroid geographic atrophy (GA). Results: In total, 165 patients with unilateral CSC (mean age, 55.7 ± 12.6 years; female, 22.4%) were included from the Kyoto CSC cohort. Among them, 148 (89.7%) were diagnosed as having PPE in their non-CSC eye. Survival analysis revealed that 16.8% of PPE eyes developed CSC during the 6-year follow up, whereas non-PPE eyes did not. Although genetic factors did not have significant association with CSC development (P > 0.05, log-rank test), choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SFCT) were significantly associated with CSC incidence (P = 0.001, log-rank test). Survival analysis showed that eyes without CVH and eyes with SFCT < 300 µm did not develop CSC during the 6-year follow-up. Pachychoroid neovasculopathy developed in only 1 eye with PPE during a follow-up of 46.4 months. Pachychoroid GA did not develop in any of the studied eyes. Conclusions: This study revealed a natural history of PPE in a relatively large Japanese cohort. Choroidal vascular hyperpermeability and SFCT were significant risk factors for the development of CSC in PPE eyes. Although the current results cannot be generalized for all eyes with PPE, these findings present an important clinical implication.

Age-Related Maculopathy Susceptibility 2 and Complement Factor H Polymorphism and Intraocular Complement Activation in Neovascular Age-Related Macular Degeneration.

Purpose: To investigate the association of risk alleles in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) with complement activation products in the aqueous humor in eyes with neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and pachychoroid neovasculopathy (PNV). Design: Prospective, comparative, observational study. Participants: Treatment-naïve patients with nAMD and cataract patients as controls. Methods: The study included 236 eyes of 236 patients with nAMD and 49 control eyes of 49 patients. Aqueous humor samples were collected from 67 eyes with drusen-associated nAMD, 72 eyes with PCV, 26 eyes with RAP, and 71 eyes with PNV before intravitreal anti-VEGF injection and cataract surgery in the 49 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, and C5a using a bead-based immunoassay. Genotyping of the ARMS2 A69S (rs10490924), CFH I62V (rs800292), and CFH Y402H (rs1061170) was performed using TaqMan genotyping. Main Outcome Measures: The levels of complement activation products (C3a, C4a, and C5a) in the aqueous humor in each genotype of ARMS2 and CFH. Results: The C3a level in the aqueous humor was significantly elevated (P = 0.006) in patients with nAMD and the ARMS2 A69S risk allele, whereas the levels of the complement activation products were not associated with CFH I62V and Y402H genotypes. Among the control eyes, no significant differences were seen in any complement activation products for all genetic polymorphisms. The levels of the complement activation products in the aqueous humor of eyes with the nAMD subtypes for each genetic polymorphism did not show significant differences. Conclusions: The C3a concentration in the aqueous humor was significantly higher in Japanese nAMD patients with the ARMS2 A69S risk allele, whereas it was not elevated in the patients with CFH I62V. Age-related maculopathy susceptibility 2 A69S polymorphism is strongly associated with local complement activation in nAMD patients.

Two-Thirds Dose Photodynamic Therapy for Pachychoroid Neovasculopathy.

Pachychoroid neovasculopathy (PNV) is treated with antivascular endothelial growth factor (VEGF) injection and photodynamic therapy (PDT), but no curative treatment has yet been established. We aimed to clarify the treatment results of a reduced dose of PDT for PNV. The subjects were 27 eyes of 27 patients (male:female = 20:7, mean age 58.9 years). PDT, at 2/3 of the conventional dose (2/3PDT), was administered once. The patients were then observed for one year. Eyes with polypoidal choroidal vasculopathy (PCV) were excluded. We investigated the associations among the central retinal thickness, choroidal thickness, and visual acuity changes before treatment and one, three, six and 12 months after PDT. When serous retinal detachment was increased or unchanged or new hemorrhages were observed, as compared with pretreatment findings, intravitreal injection of an anti-VEGF agent was performed. Visual acuity was significantly improved, as compared to before treatment, at three, six, and 12 months after 2/3PDT. Foveal retinal thickness was significantly decreased after versus before treatment in the 2/3PDT group (p < 0.001). Foveal choroidal thickness was also significantly reduced in the 2/3PDT group (p = 0.001). Additional intravitreal anti-VEGF agent injections were administered to three patients (11%), while 24 (89%) required no additional treatment during the one-year follow-up period. For PNV without polyps, 2/3PDT appears to be effective.

One-year outcomes of half-fluence photodynamic therapy combined with intravitreal injection of aflibercept for pachychoroid neovasculopathy without polypoidal lesions.

PURPOSE: To evaluate the 1-year efficacy of half-fluence photodynamic therapy (HFPDT) combined with intravitreal aflibercept injection on treatment-naïve pachychoroid neovasculopathy (PNV) without polypoidal lesions. STUDY DESIGN: Retrospective, interventional case series PATIENTS AND METHODS: We retrospectively studied 21 eyes with treatment-naïve PNV and assessed the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), pachyvessel vertical diameter, and choroidal neovascularization thickness (CNVT) at the fovea over a 12-month period. RESULTS: The median BCVA was 0.15 at baseline, 0.00 (P < .05) at 3 months, 0.05 at 6 months, and -0.08 (P < .05) at 12 months. The BCVA was significantly improved at 3 months and 12 months as compared with the baseline BCVA. The median CMT was 230 µm at baseline, 140 µm (P < .01) at 3 months, 150 µm (P < .01) at 6 months, and 150 µm (P < .01) at 12 months. The median CCT was 386 µm at baseline, 347 µm (P < .01) at 3 months, 331 µm (P < .01) at 6 months, and 352 µm (P < .01) at 12 months. The median pachyvessel vertical diameter was 309 µm at baseline, 246 µm (P < .01) at 3 months, 232 µm (P < .01) at 6 months, and 242 µm (P < .01) at 12 months. The median CNVT was 28 µm at baseline, 17 µm (P < .01) at 3 months, 19 µm (P < .05) at 6 months, and 21 µm (P < .05) at 12 months. The CMT, CCT, pachyvessel vertical diameter, and CNVT were significantly decreased at 3, 6, and 12 months as compared with those at baseline. Whilst 17 eyes (81.0%) showed no signs of CNV recurrence during the 12-month period, 4 eyes (19.0%) required additional combination therapy. CONCLUSIONS: HFPDT combined with intravitreal aflibercept injection may effectively improve BCVA and ameliorate exudative changes in eyes with PNV without polypoidal lesions for up to 1 year.

Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

PURPOSE: To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). METHODS: We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. RESULTS: The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). CONCLUSION: Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.