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To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated.Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases.IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

PURPOSE To elucidate clinical factors related to the presence of loculation of fluid (LOF) in the posterior choroid in central serous chorioretinopathy (CSC). DESIGN Retrospective, cross-sectional study. METHODS This single-center study included 158 eyes from 158 patients with CSC who were classified into LOF and non-LOF groups. The groups were compared for age, sex, spherical equivalent, axial length, subfoveal choroidal thickness (SCT), and scleral thickness. Using swept-source optical coherence tomography (OCT), we determined the presence of LOF based on B-scan and en face images. Scleral thickness was measured 6 mm posterior to the scleral spur in four directions using anterior segment OCT. RESULTS The 158 eyes were classified into 98 eyes in the LOF group and 60 eyes in the non-LOF group. In univariable analyses, the LOF group was younger (P = .01) and had a higher male ratio (P = .03) and greater SCT (P < .001) than the non-LOF group. All scleral thicknesses at the superior, temporal, inferior, and nasal points were greater in the LOF group than in the non-LOF group (426.2 μm vs. 395.1 μm, 445.7 μm vs. 414.9 μm, 459.2 μm vs. 428.8 μm, 445.4 μm vs. 414.3 μm, all P < .05). Multivariable analyses found that SCT (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.02, P < .001) and mean scleral thickness (OR: 1.02, 95% CI: 1.02-1.03, P = .002) were significantly associated with the presence of LOF. CONCLUSION A thick choroid and thick sclera appeared to be related to the presence of LOF in CSC.

PURPOSE Asymmetric dilated vortex vein (ADVV) observed in eyes with pachychoroid spectrum diseases is thought to be due to congestion of choroidal blood flow. The purpose of this study was to quantitatively investigate the blood flow velocity of ADVV using laser speckle flowgraphy (LSFG). STUDY DESIGN Retrospective case series. METHODS This was a retrospective case series with 23 eyes of 18 patients with ADVV on en-face OCT. A pair of choroidal veins from ADVV side (defined as ADVV vein) and non-ADVV side (defined as non-ADVV vein) was selected in each eye under the following criteria: (i) equivalent proximity to the deviated watershed, (ii) does not overlap with retinal blood vessels in the en-face OCT image, (iii) has approximately the same blood vessel diameter. Rubber bands were placed on the selected choroidal veins on the LSFG color map. Mean blur rate (MBR) values of ADVV and non-ADVV veins were statistically compared. RESULTS The average MBR was 10.11 ± 1.9 in the ADVV veins and 13.49 ± 6.2 in the non-ADVV veins, showing significantly lower values in the ADVV veins (P = 0.03). The blood vessel diameter of the ADVV was 10.26 ± 3.0 and in the non-ADVV veins, 10.63 ± 2.9 pixels; not significantly different (P = 0.66). The distance from the deviated watershed to the ADVV was 53.3 ± 24.8 and to the non-ADVV veins, 46.80 ± 20.3 pixels; not significantly different (P = 0.41). CONCLUSION In eyes with ADVV, the blood flow velocity in the ADVV veins was lower than in the non-ADVV veins, suggesting anatomical congestion of ADVV.

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Purpose To investigate the efficacy of aflibercept for the treatment of diabetic macular edema via a treat-and-extend regimen. Methods This prospective, single-center, open-label, interventional study involved 30 patients with a best-corrected visual acuity (BCVA) ≤0.6 and a central retinal thickness (CRT) ≥300 μm. The enrolled eyes each received a monthly intravitreal aflibercept injection until the CRT decreased below 300 μm, upon which the administration interval was extended for 1 month until the CRT once again increased to ≥300 μm. Main outcome measures were median BCVA and CRT at 6 and 12 months after initiation of treatment via last observation carried forward analysis, the median number of injections over the 12 months, and the effects on the diabetic retinopathy severity scale (DRSS) score of the patients who completed the 12-month follow-up period. Results Of the 30 enrolled patients, 29 and 25 respectively completed the 6- and 12-month follow-up examinations. From baseline to 6 and 12 months after treatment initiation, the median BCVA (logarithm of the minimum angle of resolution) significantly improved from 0.52 to 0.30 and 0.35, respectively, and the median CRT significantly decreased from 439.5 to 268.5 and 249.0 μm, respectively. The median number of injections over the 12-month follow-up period was 6.0. Compared to baseline, the DRSS score at 12 months was improved by 2 steps in 16% of patients; in no cases did the DRSS score worsen or improve by three steps or more. Conclusions When administered in a treat-and-extend regimen, aflibercept is an effective treatment option for diabetic macular edema.

Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria. We retrospectively investigated the clinical features, including choroidal layer thickness and luminal area to stromal area ratio, in a case series of preeclampsia with serous retinal detachment (SRD). The subjects were pregnant women with SRD during hospitalization for preeclampsia from October 2014 to June 2021. Based on medical records, affected eyes, time of onset, fundus examination findings, and subfoveal choroidal thickness (SCT), the choroidal layer thickness and choroidal vascular index (CVI) in each patient was examined. Thirteen eyes from seven patients (mean age 30.7 ± 4.7 years) were included in the study. In all cases, SRD improved without topical ocular treatment. The mean SCT at the initial visit was 424.4 ± 70.5 μm, and all patients had choroidal thickening, which significantly decreased to 286.0 ± 57.9 μm (p < 0.01) at the last visit. The mean choroidal inner layer was 162.7 ± 69.4 μm at the initial visit and 122.3 ± 35.5 μm at the final follow-up visit (p = 0.06), showing no significant difference; however, the mean choroidal outer layer was 261.7 ± 47.6 μm at the initial visit and 163.7 ± 37.1 μm at the final follow-up visit (p < 0.01), thus showing a significant decrease. The mean CVI was 67.2 ± 1.3% at the initial visit, yet it had significantly decreased to 65.4 ± 1.1% (p < 0.01) at the final follow-up visit. The findings of this study show that SRD with preeclampsia is associated with increased thickening of the choroidal outer layer, especially in the choroidal luminal area.

To investigate the prevalence of ciliochoroidal effusion (CE) in central serous chorioretinopathy (CSC) using anterior-segment optical coherence tomography and its association with the clinical features of CSC.Overall, 164 eyes of 164 patients with CSC and 51 eyes of 51 age- and sex-matched normal control participants were retrospectively examined. Anterior-segment optical coherence tomography was used to assess patients with CSC and control subjects for CE and scleral thickness. Central serous chorioretinopathy eyes were divided into two groups: eyes with CE (CE group) and eyes without CE (non-CE group). Scleral thickness was measured at the point that was 6 mm posterior to the scleral spur in four directions.Among the 164 eyes with CSC, 32 eyes (19.5%) displayed CE, and this proportion was significantly higher than that in control subjects (2.0%) (P = 0.001). Scleral thickness was significantly greater in the CE group compared with the non-CE group at all four directions (P0.05 for all). Multivariable analysis revealed that the mean scleral thickness (odds ratio: 1.01; 95% confidence interval: 1.00-1.02; P = 0.007) was significantly associated with the incidence of CE.Central serous chorioretinopathy may accompany fluid accumulation in the anterior segment more frequently than previously expected in association with thick sclera.

Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD.This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography.The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 μm at baseline to 216.9 ± 110.2 μm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group.Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.

Purpose To investigate the clinical and morphological factors related to asymmetric dilated vortex veins in central serous chorioretinopathy (CSC). Design Retrospective, comparative study. Participants One hundred fifty-eight eyes of 158 patients with CSC. Methods All CSC patients underwent ophthalmic examination and multimodal imaging, including measurements of axial length (AL), fluorescein angiography, indocyanine green angiography, swept-source optical coherence tomography (OCT), and anterior-segment OCT. Using en face OCT images at the level of the outer choroid, the eyes were divided into two groups: eyes with symmetric vortex veins (symmetry group) and those with asymmetric vortex veins (asymmetry group). Main Outcome Measures Clinical and morphological factors related to asymmetric vortex veins in CSC. Results Of the 158 eyes, 120 (75.9%) were classified into the asymmetry group and 38 (24.1%) into the symmetry group. The asymmetry group significantly showed greater spherical equivalent (-0.32 ± 1.78 diopters vs. -1.35 ± 2.64 diopters; P = 0.033), shorter AL (23.52 ± 0.86 mm vs. 24.10 ± 1.06 mm; P = 0.005), and greater subfoveal choroidal thickness (414.6 ± 105.3 μm vs. 360.4 ± 91.8 μm; P = 0.005) than the symmetry group. No significant differences existed between the two groups regarding the age, sex, and all scleral thicknesses at the superior, temporal, inferior, and nasal points. In the multivariable analyses, shorter AL (odds ratio, 0.56; 95% confidence interval, 0.36–0.88; P = 0.011) was found to be significantly associated with the presence of asymmetric vortex veins. Conclusions The asymmetric dilated vortex vein is a common finding in patients with CSC. Our results suggest that certain biometric factors, such as short AL, may be associated with developing asymmetric dilated vortex veins in CSC.

To evaluate scleral thickness in central serous chorioretinopathy (CSC) using anterior segment (AS) OCT.Retrospective, comparative study.Forty-seven eyes of 40 patients with CSC and 53 eyes of 47 age- and gender-matched normal control participants.Spherical equivalent, axial length, subfoveal choroidal thickness, and scleral thickness were compared between the CSC and control groups. Scleral thickness was measured by AS OCT 6 mm posterior to the scleral spur in 4 directions.Scleral thickness in CSC eyes.No differences were found between the 2 groups in age, gender, spherical equivalent, or axial length. Subfoveal choroidal thickness was significantly greater in CSC eyes than in normal control eyes (424.0 ± 101.4 μm vs. 324.3 ± 91.8 μm; P0.001). Scleral thickness was significantly greater in CSC eyes than in normal control eyes at the superior (429.4 ± 50.3 μm vs. 395.2 ± 55.4 μm; P = 0.005), temporal (447.7 ± 45.7 μm vs. 396.5 ± 64.1 μm; P0.001), inferior (455.7 ± 81.2 μm vs. 437.8 ± 46.9 μm; P = 0.022), and nasal (454.9 ± 44.7 μm vs. 416.6 ± 51.2 μm; P = 0.001) points.Scleral thickness measured by AS OCT was significantly greater in CSC eyes than in normal control eyes, although no differences were found in spherical equivalent or axial length. Thick sclera may have a role in the pathogenesis of CSC.

This study investigated the pathophysiological features of pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) by analysing and comparing cytokine profiles in aqueous humour (AH) collected from 18 PNV, 18 nAMD and 11 control patients. Responses to intravitreal injection of aflibercept were also analysed in the PNV and nAMD groups. In the PNV group, vascular endothelial growth factor (VEGF)-A was significantly lower than in the nAMD group (p = 0.03) but was almost identical to that in the control group (p = 0.86). The nAMD group showed positive correlations between interleukin (IL)-6 and IL-8 (r = 0.78, p r = 0.68, p = 0.002) and IL-8 and MCP-1 (r = 0.68, p = 0.002). In the nAMD group, eyes with dry maculae one month after the first aflibercept injection showed significantly lower VEGF-A and placental growth factor (PlGF) at baseline than those with wet maculae (p = 0.02 for both). However, there was no significant difference between dry and wet maculae in the PNV group. The results suggest that angiogenic factors and proinflammatory cytokines may play the distinct roles in the pathogenesis of PNV and nAMD.

Purpose: Large-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls.Methods: Aqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). The severity of macular edema was measured as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Proteins were filtered by requiring quantification in at least 50% of the samples in each group without imputation of missing values. Significantly changed proteins were identified with a permutation-based calculation with a false discovery rate at 0.05.Results: In BRVO, 52 proteins were differentially expressed. Regulated proteins were involved in cell adhesion, coagulation, and acute-phase response. Apolipoprotein C-III, complement C3, complement C5, complement factor H, fibronectin, and fibrinogen chains were increased in BRVO and correlated with CRT. Fibronectin also correlated with best corrected visual acuity (BCVA) and vascular endothelial growth factor (VEGF). Monocyte differentiation antigen CD14 (CD14) and lipopolysaccharide-binding protein (LBP) were upregulated in BRVO. Contactin-1 and alpha-enolase were downregulated in BRVO and correlated negatively with CRT.Conclusions: Multiple proteins, including complement factors, fibrinogen chains, and apolipoprotein C-III, correlated with CRT, indicating a multifactorial response. Fibronectin correlated with BCVA, CRT, and VEGF. Fibronectin may reflect the severity of BRVO. The proinflammatory proteins CD14 and LBP were upregulated in BRVO.

Background/aimsTo evaluate the axial length (AL) and refractive status in central serous chorioretinopathy (CSC).MethodsThis retrospective observational case series involved 140 patients with CSC (180 eyes) and 78 age-matched and gender-matched control subjects. A detailed ophthalmic examination was performed, including an interferometer measurement of AL. Multimodal imaging comprised colour fundus photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence photography and spectral domain optical coherence tomography.ResultsEighty eyes of 40 patients were categorised into the bilateral-CSC (b-CSC) group and 100 eyes of 100 patients were categorised into the unilateral-CSC (u-CSC) group. AL of the b-CSC (23.19 mm) and u-CSC (23.75 mm) groups was significantly shorter than that of the control (24.85 mm) group (pConclusionAnatomical features, such as shorter AL and greater SE, may be associated with the pathogenesis of CSC.

Purpose To clarify the distinct molecular pathogenesis of central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV). Methods Aqueous humor (AH) was collected from 18 acute CSC, 20 chronic CSC, and 20 PNV patients. Concentrations of 30 cytokines in the AH were analyzed using a multiplex bead immunoassay, and the cytokine profiles were compared among these three groups of patients. The areas of choroidal vascular hyperpermeability (CVH) and choroidal thickness (CT), including measurement of the vascular layers, were investigated to analyze the features of choroidal abnormality in acute CSC, chronic CSC, and PNV. Additionally, associations between cytokine profiles and choroidal abnormalities were analyzed. Results Proinflammatory cytokines, IL-6 and IL-8 were significantly upregulated in the chronic CSC group compared with the acute CSC or PNV groups. Angiogenic cytokines and VEGF-A were upregulated at levels that almost reached significance along with disease progression from acute to chronic CSC, whereas the upregulation was not significant from chronic CSC to PNV. In the chronic CSC group, strong positive correlations were confirmed between VEGF-A and placental growth factor (PlGF) (r = 0.75, P < 0.001) and IL-6 and VEGF-A (r = 0.74, P < 0.001), and angiogenesis-related cytokines were positively correlated with the typical choroidal abnormalities, areas of CVH, mean CT, and mean large choroidal vessel layer thickness. However, there was no association between these choroidal abnormality parameters and AH cytokines in the PNV group. Conclusions The results suggest that choroidal abnormalities in chronic CSC may be associated with upregulated angiogenesis.

To investigate the clinical characteristics and surgical treatment in eyes with conjunctival epithelial inclusion cysts (CEIC).This study involved the retrospective, medical-record-based investigation of 37 eyes of 34 patients diagnosed with CEIC by slit-lamp biomicroscopy and anterior segment optical coherence tomography (AS-OCT).CEIC were found most commonly in the nasal area of the conjunctiva (64.9%). Thirteen eyes (35.1%) had more than 1 cyst, and 10 eyes (27.0%) had a past history of punctures. Adhesion (9 eyes) between cyst and surrounding connective tissues was found to be significantly more in eyes with a puncture history (5 eyes; p = 0.0234, Fisher's exact test). Complete excision of cysts through a small conjunctival incision could be performed significantly more often among the 28 eyes without adhesion than in the 9 eyes with adhesion (p = 0.002). Pathological examination of the cysts indicated that they involved goblet cells in 16 eyes and mild inflammation in 4 eyes, consistent with the findings in previous reports.CEIC are predominantly found in the nasal area of the conjunctiva. In eyes without puncture history, adhesion of cysts to the surrounding tissues was rarely observed and cysts were successfully excised "en bloc" via minimally invasive surgery.