Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy.

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 µm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2;P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population.

PURPOSE: To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population. DESIGN: Retrospective, multicenter, observational study. PARTICIPANTS: A total of 173 eyes from 173 patients from 6 university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years and had definite GA associated with AMD in at least 1 eye. METHODS: The GA area was measured semiautomatically using fundus autofluorescence (FAF) images. In the follow-up group followed for > 6 months with FAF images, the GA progression rate was calculated by 2 methods: mm2 per year and mm per year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate. MAIN OUTCOME MEASURES: Clinical characteristics of GA and the GA progression rate. RESULTS: The mean age was 76.8 ± 8.8 years, and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm2 (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 (42.2%) eyes, respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 µm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm2 per year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, the baseline GA area (SQRT; P = 0.002) and the presence of reticular pseudodrusen (P < 0.001) were significantly associated with a greater GA progression rate (SQRT). CONCLUSIONS: Certain clinical characteristics of GA in Asian populations may differ from those in White populations. Asian patients with GA showed male dominance and relatively thicker choroid than White patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in White populations. Large GA and reticular pseudodrusen were associated with a greater GA progression rate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hyperreflective material in patients with non-neovascular pachychoroid disease.

BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. CONCLUSION: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Intravitreal anti-vascular endothelial growth factor monotherapy in age-related macular degeneration with submacular hemorrhage.

The purpose of this study was to evaluate the 1-year visual outcomes of patients treated with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD). We retrospectively studied 62 treatment-naïve eyes with SMHs exceeding one disc area (DA) secondary to AMD treated with IVA or IVBr. All patients received three monthly intravitreal injections in the loading phase followed by as-needed injections or fixed dosing. If a vitreous hemorrhage (VH) developed during the follow-up period, injections were discontinued and vitrectomy was performed. We evaluated the changes in the best-corrected visual acuity (BCVA) and factors that affected the BCVA improvement and VH development. A VH during treatment developed in five eyes (8.1%) (VH + group), and the mean BCVA worsened from 0.45 to 0.92. The BCVA improved significantly (P = 0.040) in the remaining 57 eyes (VH - group) from 0.42 to 0.36. The development of VHs was associated with significantly (P < 0.001) less VA improvement. Furthermore, large DAs and younger age at baseline were associated significantly (P = 0.010 and 0.046, respectively) with the development of VHs. Both IVA and IVBr appeared to improve functional outcomes in patients with SMH secondary to AMD when VHs did not develop. However, a VH developed in 8.1% of eyes after treatment. Although anti-vascular endothelial growth factor treatments were well-tolerated, for cases with large SMH at baseline, it should be considered that VH may occur during the monotherapy treatment process using IVA or IVBr, and that achieving good visual outcomes may be difficult in some cases.

Short-term outcomes of switching to brolucizumab in japanese patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the outcomes of a 6-month follow-up after switching to brolucizumab from aflibercept to treat neovascular age-related macular degeneration (AMD) in Japanese patients. STUDY DESIGN: Retrospective observational study. METHODS: We studied 45 consecutive eyes of 42 patients diagnosed with neovascular AMD, who were switched to intravitreal brolucizumab injection (IVBr) after receiving intravitreal aflibercept injection (IVA) using a treat-and-extend (TAE) regimen. Patients who had brolucizumab-associated intraocular inflammation (IOI) were excluded from the study. The mean changes in the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness (CCT), and treatment intervals were evaluated at 6 months after the switch to IVBr. RESULTS: One eye of 1 patient was excluded because of IOI after the switch; 44 eyes of 41 patients were enrolled in this study. The mean logMAR BCVA was maintained throughout the follow-up period when compared with the baseline value (P > .05 at 6 months). However, the mean CFT and CCT at 6 months had decreased significantly (P < .05 and P < .001, respectively). The mean treatment interval was extended from 5.75 to 8.12 weeks. CONCLUSION: Switching to brolucizumab from aflibercept using a TAE regimen might be effective for maintaining functional outcomes and extending intervals in Japanese patients with AMD.

One-year outcomes of intravitreal brolucizumab injections in patients with polypoidal choroidal vasculopathy.

To evaluate the 1-year visual outcomes and anatomic responses of Japanese patients who received intravitreal brolucizumab (IVBr) injections for polypoidal choroidal vasculopathy (PCV). This was a retrospective study of 17 treatment-naïve eyes with PCV that were treated with IVBr. We evaluated the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT) and number of injections for 1 year. The eradication of polypoidal lesions was also evaluated using by indocyanine green angiography during the 1-year follow-up. Non-infectious intraocular inflammation developed in two (11.8%) eyes; 15 eyes were assessed at the 1-year follow-up examination. The mean BCVA improved significantly from 0.28 at baseline to 0.13 (P < 0.05) at 1 year. The CMT and CCT decreased significantly after 1 year. The mean number of injections was 6.4 ± 0.13. The rate of complete resolution of polypoidal lesions at 1 year was 93.3%. A dry macula was achieved in 13 eyes (86.6%) after the loading phase and in 11 eyes (73.3%) at 1 year. The IVBr injections appeared to be effective for improving both functional and anatomic outcomes in Japanese patients with PCV, with a high regression rate of polypoidal lesions.

Incidence of elevated intraocular pressure after intravitreal injection in Japanese patients with age-related macular degeneration.

The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.

Sensitivity and specificity of high-resolution wide field fundus imaging for detecting neovascular age-related macular degeneration.

PURPOSE: Early detection and treatment are important management strategies for neovascular age-related macular degeneration (AMD). The purpose of this study was to determine the sensitivity and specificity in detecting neovascular AMD using two wide-field imaging systems: ClarusTM (CLARUS 500™, Carl Zeiss Meditec AG, Jena, Germany) and Optos®(Optos California®, Optos PLC, Dunfermline, United Kingdom), compared to conventional digital fundus photographs. METHODS: We retrospectively analyzed 109 eyes of 73 consecutive patients with neovascular AMD, who underwent standard examination and multimodal imaging, including fundus photography, and optical coherence tomography (OCT). Unmasked graders utilized slit-lamp biomicroscopy and OCT to diagnose neovascular AMD. Masked graders evaluated ClarusTM, Optos®, and digital fundus photograph methods to determine the presence of choroidal neovascularization associated with AMD. Sensitivity and specificity analyses were performed using combined fundoscopy and OCT as the reference standard. RESULTS: Ninety eyes were diagnosed with neovascular AMD and the remaining 19 eyes were normal based on the reference standard. Of these, neovascular AMD was detected using ClarusTM in 94.4% (85/90). The sensitivities of Optos® and digital fundus photographs were 81.1% (73/90) and 87.8% (79/90), respectively. The specificities using ClarusTM, Optos®, and digital fundus photographs were 89.5% (17/19), 94.7% (18/19), and 89.5% (17/19), respectively. CONCLUSION: ClarusTM, with its ability to image high-resolution wide field fundus, was considered superior for diagnosing neovascular AMD with high sensitivity and specificity. It may be a useful screening tool for early detection of neovascular AMD, facilitating prompt referral and treatment.

Comparison of one-year results of photodynamic therapy combined with ranibizumab or aflibercept for treating polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.

One-year outcome of combination therapy with intravitreal anti-vascular endothelial growth factor and photodynamic therapy in patients with pachychoroid neovasculopathy.

PURPOSE: To identify the functional outcome and evaluate the morphologic changes of patients with pachychoroid neovasculopathy (PNV) undergoing intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) at the 1-year follow-up. METHODS: We retrospectively studied all the treatment-naïve PNV patients who were scheduled to undergo combination therapy between September 2017 and November 2018. All the patients received three consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as loading doses. Full-dose PDT was performed within 1 week of the first injection. Retreatment was allowed if evidence of clinical deterioration or the presence of fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The best-corrected visual acuity (BCVA) was compared before treatment and at 3, 6, and 12 months after the initial treatment. Changes in the central foveal thickness (CFT), central choroidal thickness (CCT), and retreatment rate during the maintenance phase were also evaluated. RESULTS: Eleven eyes were enrolled in this study. Significantly, better BCVA was observed at 12 months than at baseline (P = 0.010). The mean CFT significantly decreased from 331 ± 93 to 237 ± 72 µm at 12 months (P < 0.001). The mean CCT also significantly decreased from 361 ± 74 to 310 ± 83 µm at 12 months (P < 0.001). The mean number of injections per eye was 3.9 ± 1.3 during the follow-up period. A total of 45.5% (5 /11) of the patients required retreatment during the maintenance phase. CONCLUSION: Anti-VEGF combined with full-dose PDT was well tolerated and appeared to be effective treatment for patients with treatment-naïve PNV. Combination therapy might also reduce the treatment burden with fewer injections in patients with PNV.