Hiroyuki Kamao

Purpose: To evaluate the performance and usability of a commercially available non-woven fabric electrode as a cost-effective and user-friendly alternative to standard corneal contact lens electrodes for recording murine electroretinograms. Methods: Using a paired design, full-field electroretinograms were recorded in the same mice using the commercially available non-woven fabric electrode and a conventional contact lens electrode. Key parameters evaluated included (1) stability of baseline noise, (2) dark-adapted intensity–response curves (0.01–100 cd·s·m⁻²), (3) light-adapted intensity–response curves (3–100 cd·s·m⁻²), (4) 20-Hz and 30-Hz flicker responses, (5) extended recordings targeting slow c-wave kinetics under dark-adapted conditions, and (6) inter-eye consistency via bilateral simultaneous recordings. Results: Eliminating the need for viscous lubricants, the non-woven fabric electrode simplified placement on the cornea, alignment, and re-application. It yielded a-wave and b-wave amplitudes and peak times comparable or superior to those obtained with standard contact lens electrodes. Notably, during prolonged recordings, the non-woven fabric electrode yielded significantly larger c-wave amplitudes while maintaining equivalent baseline noise stability. Bilateral simultaneous recordings demonstrated high inter-eye correlation and low variability of measurements between contralateral eyes. Conclusions: The non-woven fabric electrode provides high-quality, reproducible electroretinographic recordings comparable to (and for c-waves superior to) those obtained using standard corneal contact lens electrodes. This method facilitates standardized data acquisition and improves inter-laboratory reproducibility of murine electroretinography. Translational Relevance: By reducing financial and technical barriers, this non-woven fabric electrode offers an alternative to specialized recording setups, improving experimental throughput and efficiency in ophthalmic research.

Background/Objectives: Punctate hyperfluorescence (PH) on indocyanine green angiography (ICGA) is frequently observed in pachychoroid disease. However, the spatial relationship between PH lesions and vortex vein abnormalities remains unclear. This study quantified PH distribution in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) and examined its association with vortex vein asymmetry and watershed-zone status. Methods: This retrospective observational study included 58 fellow eyes with PH from patients with unilateral nAMD. PH lesions were quantified on late-phase ICGA images using ImageJ software. Vortex vein distribution was classified as symmetric, superior-dominant, or inferior-dominant. Eyes were also classified by the presence of a horizontal watershed zone. PH distribution was compared by vortex vein morphology. Results: A watershed zone was absent in 14 eyes (24.1%). Vortex vein distribution was asymmetric in 27 eyes (46.6%), including 17 (29.3%) superior-dominant and 10 (17.2%) inferior-dominant. Overall, 3401 PH lesions were detected. Eyes without a watershed zone had significantly more PH lesions than those with a watershed zone (p = 0.002). The proportion of superior-region PH lesions differed significantly by vertical vortex vein predominance, with preferential distribution on the dominant side (p < 0.001). Although PH distribution did not differ significantly among the four quadrants overall, 30 eyes (51.7%) had >50% of PH lesions clustered in a single quadrant. Conclusions: PH lesions were preferentially distributed on the dominant side of vortex vein asymmetry, and eyes without a watershed zone had more PH lesions. These findings indicate that PH distribution and lesion burden are associated with vortex vein morphology and watershed-zone status and may reflect underlying alterations in choroidal venous drainage.

Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA–hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen.

Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen−/PH−, Drusen+/PH−, Drusen−/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan–Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH− group had a higher retreatment rate and required more injections than the Drusen−/PH+ and Drusen+/PH+ groups. The Drusen+/PH− group was older than the Drusen−/PH+ and Drusen−/PH− groups. The Drusen−/PH+ group had a thicker choroid than the Drusen+/PH− group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH− group and the thicker choroid of the Drusen−/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies.

Background/Objectives: To compare the treatment outcomes of intravitreal faricimab (IVF) and intravitreal aflibercept (IVA) in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), stratified by the presence or absence of punctate hyperfluorescence (PH). Methods: This retrospective study included 301 treatment-naïve patients with nAMD who underwent either IVF or IVA. After 1:1 propensity score matching based on baseline best-corrected visual acuity (BCVA), age, and PH status, 56 eyes (28 per group) were analyzed within each PH subgroup. Outcome measures included BCVA, central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and no retinal fluid rate during the loading dose regimen, and the retreatment rate after the loading dose regimen. The prespecified primary endpoint was the 1-year retreatment rate after completion of the loading dose regimen, analyzed by Kaplan–Meier curves with log-rank tests. Comparisons were performed separately between the PH and non-PH groups. Results: In the PH group, no significant differences were observed between IVF and IVA groups in terms of BCVA, CRT, SFCT, no retinal fluid rate, or retreatment rate at any time point. In the non-PH group, IVF and IVA groups showed no significant differences in BCVA, CRT, or SFCT at any time point; however, the IVF group achieved a significantly higher no retinal fluid rate (100.0% vs. 64.3%, p < 0.001) and a lower retreatment rate at 1 year (71.4% vs. 92.9%, p = 0.004) than the IVA group. Conclusions: IVF and IVA showed comparable efficacy in nAMD with PH. In contrast, IVF demonstrated superior anatomical outcomes in nAMD without PH. These retrospective findings suggest distinct pathophysiological mechanisms between PH and non-PH subtypes.

Background/Objectives: To identify the predictive biomarkers of treatment response following a switch to brolucizumab in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 47 eyes of 44 patients with nAMD who were switched to brolucizumab; a two-year follow-up was completed for 37 eyes of 34 patients after the switch. The patients were classified into two groups based on the presence (fluid group) or absence (dry group) of retinal fluid at one and two years after switching, and their visual acuity, central retinal thickness, subfoveal choroidal thickness, injection interval, and dry macular rate were evaluated. Results: A dry macula was achieved for approximately 80% of patients at two years after the switch (p < 0.001), and the mean injection interval was significantly extended from 6.4 ± 1.8 weeks to 10.5 ± 2.6 weeks during the same period (p < 0.001). Both the mean central retinal thickness and subfoveal choroidal thickness showed a significant decrease at two years after the switch (p < 0.001 for both). A significantly higher proportion of patients in the Dry group exhibited punctate hyperfluorescence in the fellow eye (p < 0.001), and all patients in the dry group achieved a dry macula at two years. Conclusions: Switching to brolucizumab may be an effective treatment option for patients with aflibercept-refractory nAMD. Punctate hyperfluorescence may serve as a favorable prognostic factor following a switch to brolucizumab.

Objectives: To assess the association between clinical outcomes and the multimodal imaging-based classification of central serous chorioretinopathy (CSC). Methods: This retrospective study included 207 eyes from 155 treatment-naïve patients with CSC. The eyes were categorized into two groups, including the simple CSC group (n = 164) and the complex CSC group (n = 43), based on the presence of retinal pigment epithelial atrophy spanning two or more disc areas. All patients were initially observed without treatment for 3–6 months. For cases with persistent subretinal fluid after this observation period, treatment modalities, including continued observation, photocoagulation (PC), or photodynamic therapy (PDT), were selected. Results: Patients in the complex CSC group were more likely to be older (p = 0.01) and male (p = 0.01) than those in the simple group and to exhibit a higher prevalence of bilateral involvement (p < 0.001) and previous CSC episodes (p < 0.001) than those exhibited by patients in the simple group. Eyes with complex CSC exhibited a comparable incidence of spontaneous resolution within 6 months and a higher incidence of recurrence after spontaneous resolution within 6 months than eyes with simple CSC. In both the simple and complex CSC groups, the PDT subgroup exhibited a lower recurrence rate than that of the PC subgroup (simple CSC: p < 0.001, complex CSC: p = 0.03). Conclusions: Although CSC is typically a self-limiting disease often managed conservatively, patients with complex CSC, characterized by bilateral involvement or a history of previous episodes, are at a higher risk of subretinal fluid recurrence and may benefit from early interventions without a period of observation, such as PDT.

Objectives: To assess the clinical characteristics of patients with macular neovascularization (MNV) with no drusen in the fellow eye, we investigated the incidence of MNV in fellow eyes and the outcomes of intravitreal aflibercept (IVA) monotherapy in MNV eyes of patients with unilateral MNV with a punctate hyperfluorescence spot (PHS) in the fellow eye. Methods: We retrospectively studied 58 treatment-naïve patients with unilateral MNV with no drusen in the fellow eye. Patients were classified into a PHS group (n = 29) or no-PHS group (n = 29) based on the presence of PHS. We evaluated the incidence of MNV in the fellow eye, and the retreatment rate after initiation of three monthly aflibercept injections over one year. Results: Fellow eyes in the PHS group had a thicker choroid (p < 0.05) and higher prevalence of pachychoroid pigment epitheliopathy (PPE) (p < 0.001). MNV eyes in the PHS group had a thicker choroid (p = 0.09). The PHS group had a lower retreatment rate (p < 0.05) and required fewer injections (p < 0.05) than the no-PHS group. MNV developed in one eye in both the PHS and no-PHS groups, and both cases occurred in areas of hypofluorescence on indocyanine green angiography within the PPE area before the onset of MNV. Conclusions: The PHS group frequently exhibited pachychoroid disease characteristics and responded better to IVA monotherapy than the no-PHS group. These groups may represent distinct populations of patients with unilateral MNV with no drusen in the fellow eye.

Background/Objectives: To approach the clinical properties of pachydrusen that differ from conventional drusen, we investigated the incidence of macular neovascularization (MNV) in fellow eyes and the treatment outcomes of intravitreal aflibercept (IVA) in MNV eyes of unilateral MNV patients with pachydrusen in the fellow eye. Methods: We retrospectively studied 261 consecutive patients with treatment-naïve unilateral MNV. Patients were classified into four groups according to the type of drusen in the fellow eye: the pachydrusen group (n = 49), the soft drusen group (n = 63), the subretinal drusenoid deposit (SDD) group (n = 24), and the no drusen group (n = 125). The development of the MNV in the fellow eye was evaluated for five years, and the retreatment proportion after three monthly aflibercept injections was evaluated for one year. Results: The choroidal thickness in the fellow eyes and MNV eyes was the greatest in the pachydrusen group (all p < 0.001). The 5-year incidence of MNV in the pachydrusen group was similar to that in the soft drusen group and no drusen group. The pachydrusen group had a lower retreatment rate than the other groups did (pachydrusen group: 46.4%; soft drusen group: 78.1%; SDDs: 87.5%; no drusen group: 83.3%). Conclusions: Unilateral MNV patients with pachydrusen in the fellow eye had a lower retreatment rate (46.4%/1 year); therefore, aflibercept monotherapy using the PRN regimen is one of the preferred treatment methods for MNV patients with pachydrusen in the fellow eye.