Association between time to treatment and outcome in branch retinal vein occlusion.

PURPOSE: To investigate the association between the time from onset to initial treatment and changes in visual acuity or the number of treatments in patients with branch retinal vein occlusion (BVO). DESIGN: Retrospective. METHODS: Thirty-nine eyes of 39 consecutive patients with untreated acute-phase BVO who visited the University of Tokyo Hospital and were followed up for at least one year were included. The patients were initially treated with anti-vascular endothelial growth factor (VEGF) therapy and additional pro re nata therapy within six months of onset. The patients were classified according to the time from disease onset to the first treatment (group A: 28 days or less, group B: over 28 days). RESULTS: The mean (SD) age was 73 ± 8 years, and 19 patients were male. The mean (SD) time to the first treatment was 31.6 ± 17.9 days. The mean (SD) logMAR visual acuity at first treatment was 0.37 ± 0.30. After 12 months of treatment, the mean (SD) logMAR change was - 0.15 ± 0.23, and the mean number (SD) of treatments was 3.1 ± 1.7. No significant association was observed between the timing of treatment initiation and changes in logMAR visual acuity. Patients in group A and central macular thickness at the initial visit were independently associated with the greater number of treatments at one year (p = 0.03 and p = 0.01, respectively). CONCLUSIONS: At one year, the time between onset and the start of anti-VEGF therapy for BVO was not associated with subsequent visual acuity changes. Meanwhile, it may have significant association with the number of treatments.

Time to initiate anti-vascular endothelial growth factor therapy and visual outcome in central retinal vein occlusion.

This retrospective study aimed to investigate the progression of central retinal vein occlusion (CVO) prior to treatment initiation and its impact on prognosis. Of the 54 studied eyes with acute CVO, the average logMAR visual acuity (VA) at the initial visit was 0.65 ± 0.49 with an average time to treatment of 14.9 ± 14.5 days. VA at the initial treatment was identified as a stronger predictor of VA at the final visit compared to VA at the first visit or other factors. Patients who received treatment more than 28 days after the initial visit experienced a significant decline in VA compared to those treated within 28 days (0.21 ± 0.35 vs. 0.04 ± 0.13, p = 0.006). Additionally, patients who were treated between 15 and 28 days showed a greater decrease in VA compared to those treated within 14 days (0.12 ± 0.46 vs. 0.018 ± 0.02, p = 0.026). These findings from the current retrospective analysis suggesting that there is a possibility of VA decline at the initial treatment associating with worse prognosis even when treatment is administered within a month should be further investigated in the prospective study. Also, it may be crucial to consider frequent monitoring of acute CVO patients for initiating treatment at the optimal timing.

Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy.

BACKGROUND: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear. METHODS: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCTR from baseline. RESULTS: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 µm to 263 µm) and remained unchanged up to 3 years (255 µm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60). CONCLUSIONS: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years.

Trousseau's Syndrome With Severe Visual Loss As the Initial Symptom.

There are limited reports on patients with Trousseau syndrome, a condition characterized by hypercoagulability associated with malignant tumors, initially manifesting with reduced visual function. We present a case of a patient who experienced bilateral vision loss and was subsequently diagnosed with Trousseau's syndrome following examination and investigations. A 70-year-old man, undergoing chemotherapy for advanced pancreatic cancer, reported decreased visual acuity in both eyes. A dilated fundus examination revealed retinal pigment epithelial atrophy in the posterior pole and cotton-wool spots. Optical coherence tomography exhibited partial disruption of the ellipsoid zone in the parafoveal region, and full-field electroretinogram results were subnormal, although the macular retinal structure was preserved. Brain magnetic resonance imaging (MRI) detected occipital lobe infarction. Elevated coagulability markers, including D-dimer (5.5µg/mL), led to the diagnosis of Trousseau's syndrome. In cases where patients with malignant tumors present with profound visual loss, considering the possibility of Trousseau's syndrome and conducting assessments of brain function and coagulability is crucial for accurate diagnosis and appropriate management.

Nonsurgical closure of full thickness macular hole under topical therapy in two eyes with pathologic myopia.

PURPOSE: Non-surgical closure of a full-thickness macular hole (FTMH) with eye drops has recently been reported, but there are few similar reports in cases with pathologic myopia. CASE PRESENTATION: (Case 1) The right eye of a 75-year-old female with an axial length of 28.83 mm had undergone anti-vascular endothelial growth factor (VEGF) treatment for choroidal neovascularization presented with FTMH. Topical betamethasone, bromfenac, and blinzolamide treatments were started, and the FTMH was closed with visual improvement (20/32 to 20/20) after 5 weeks. (Case 2) In the right eye of a 55-year-old male with an axial length of 30.81 mm and lacquer cracks, subretinal hyperreflective material and FTMH developed. The above three drugs were started after anti-VEGF drug injection. Sixteen weeks later, the FTMH was closed with visual improvement (20/63 to 20/20). CONCLUSION: Nonoperative closure of FTMH has already been reported, but few in eyes with pathologic myopia. Our results suggest that nonoperative closure of FTMH associated with pathologic myopia under eye drops may be possible in some cases.

Mound-like Epiretinal Material: Its Short-term Changes and Association with Posterior Vitreous Detachment.

PURPOSE: To describe clinical characteristics of a retinal finding termed mound-like epiretinal material (MOLEM), and distinguish it from epiretinal proliferation, a similar epiretinal finding previously described in various pathologies. METHODS: Five eyes from five patients were retrospectively identified from medical records. Clinical findings and images, including fundus photographs and optical coherence tomography (OCT), were reviewed. RESULTS: All eyes displayed mound-like material with uniform and low-to-moderate reflectivity on an otherwise intact retinal surface detected on OCT. No eyes presented with concurrent pathology typically observed in cases of epiretinal proliferation, such as lamellar/full-thickness macular hole, epiretinal membrane, vitreomacular traction, or uveitis. Two eyes exhibited central serous chorioretinopathy, but there was no association of MOLEM with serous retinal detachment. In three out of five eyes, MOLEM appeared simultaneously with posterior vitreous detachment (PVD). Some lesions underwent irregular transformations over months and occasionally disappeared. While all cases were monitored without intervention, no visual decline or complications attributed to MOLEM were detected. CONCLUSION: MOLEM represents a novel clinical finding, characterized by transient morphological changes without symptoms and potential association with PVD. It may occur in eyes lacking macular diseases linked with epiretinal proliferation, a similar yet distinct lesion. The incidence, etiology, and clinical significance of MOLEM warrant further investigation by accumulating comparable cases, although the lesion appears benign and self-limiting.

Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study.

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy.

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

Retinal sensitivity and fundus autofluorescence in adult-onset foveomacular vitelliform dystrophy.

The present study aimed to compare retinal sensitivity (RS) at each stage and to evaluate the relationship between RS and fundus autofluorescence (FAF) pattern in adult-onset foveomacular vitelliform dystrophy (AOFVD). We retrospectively reviewed 17 eyes of 13 patients with AOFVD. In addition to best-corrected visual acuity (VA), RS within the affected lesion and optical coherence tomography (OCT) measurements were carried out in each participant. All the examined eyes were classified into 4 stages and 3 FAF patterns. RS was superimposed on OCT fundus image and RS within the affected lesion was calculated in each eye. The relationships between visual functions (VA and RS within the affected lesion) and stages and also FAF patterns were analyzed using the linear mixed model. As a result, RS within the affected lesion was significantly associated with FAF pattern, but not with stage. In contrast, VA was correlated with neither stages nor FAF patterns. Our current result suggested that RS within the affected lesion was related to FAF patterns but this was not the case with VA in eyes with AOFVD, demonstrating the usefulness of measuring RS, not only VA, to comprehend the disease status in AOFVD.

Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy.

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

Clinically Diagnosed Occult Macular Dystrophy Habouring an m.14502T>C Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy: Case Report and Literature Review.

A 29-year-old female with no family history presented with bilateral progressive blurred vision. Her symptoms appeared at 12-years-old and her visual acuity had since deteriorated from 0.6 to 0.2 bilaterally with decreased critical flicker frequency and bilateral central scotomas. She did not have a relative afferent pupillary defect. Fundoscopy revealed no distinct disc hyperaemia, atrophy, or peripapillary telangiectatic vessels. The retinal nerve fibre layer appeared normal on optical coherence tomography in each eye; however, loss of the interdigitation zone and the disruption of the ellipsoid zone at the fovea were observed in both eyes. Multifocal electroretinography revealed decreased amplitudes at both macula regions. Mitochondrial deoxyribonucleic acid analysis identified an m.14502T>C mutation, one of the primary mutations causing Leber's hereditary optic neuropathy (LHON). Despite the presence of a marked LHON mutation, however, she was clinically diagnosed as having an occult macular dystrophy. There have only been five previous case reports, all of which were sporadic, which detail the clinical characteristics of the m.14502T>C mutation. The m.14502T>C phenotype is somewhat consistent with that of the other major mutations, including young onset, bilateral progressive visual impairment, and a typical LHON fundus. Nevertheless, m.14502T>C alone has an extremely low penetrance and its phenotype may be minimal or subclinical, as seen in our case. Since little is known about the clinical course of the m.14502T>C mutation it may be possible that the LHON phenotype may appear in later stages of life. Moreover, m.14502T>C may function as a modifier gene, which alters the phenotype of other coexisting major LHON mutations, including penetrance and the severity of the disease, through synergistic effects.

Longitudinal anatomical and visual outcome of macular telangiectasia type 2 in Asian patients.

Limited information regarding the anatomical and visual prognosis of macular telangiectasia (MacTel) type 2 in the Asian population is currently available. Herein, we conducted a retrospective longitudinal analysis of Japanese patients diagnosed with MacTel type 2. Disease progression was evaluated using the Simple MacTel Classification developed by Chew EY et al. in 2023, and its association with visual changes was analyzed. Sixteen eyes of eight Japanese patients were included in the study, with an average follow-up period of 8.2 ± 3.9 years (range, 2.2-14.0). At the initial visit, 7 (44%) and 5 (31%) eyes were classified as Grade 2 (central ellipsoid zone break) and Grade 3 (noncentral pigment), respectively. The proportion of eyes that progressed by 1 or 2-steps in grade after 1, 3, 5, 8, and 12 years was 0%, 14%, 43%, 70%, and 100%, or 0%, 7%, 7%, 30%, and 75%, respectively. The visual acuity significantly deteriorated during the follow-up period, particularly in the two eyes with full-thickness macular holes (FTMH). Three out of 7 patients exhibited low serum serine concentrations, although no apparent correlation with anatomical or visual outcomes was observed. Overall, this cohort demonstrated chronic disease progression, both anatomically and functionally, in eyes with MacTel type 2, with FTMH potentially associated with greater visual loss.

Investigating the clinical validity of the guided progression analysis definition with 10-2 visual field in retinitis pigmentosa.

PURPOSE: To investigate the clinical validity of the Guided Progression Analysis definition (GPAD) and cluster-based definition (CBD) with the Humphrey Field Analyzer (HFA) 10-2 test in retinitis pigmentosa (RP). METHODS: Ten non-progressive RP visual fields (VFs) (HFA 10-2 test) were simulated for each of 10 VFs of 111 eyes (10 simulations × 10 VF sequencies × 111 eyes = 111,000 VFs; Dataset 1). Using these simulated VFs, the specificity of GPAD for the detection of progression was determined. Using this dataset, similar analyses were conducted for the CBD, in which the HFA 10-2 test was divided into four quadrants. Subsequently, the Hybrid Definition was designed by combining the GPAD and CBD; various conditions of the GPAD and CBD were altered to approach a specificity of 95.0%. Subsequently, actual HFA 10-2 tests of 116 RP eyes (10 VFs each) were collected (Dataset 2), and true positive rate, true negative rate, false positive rate, and the time required to detect VF progression were evaluated and compared across the GPAD, CBD, and Hybrid Definition. RESULTS: Specificity values were 95.4% and 98.5% for GPAD and CBD, respectively. There were no significant differences in true positive rate, true negative rate, and false positive rate between the GPAD, CBD, and Hybrid Definition. The GPAD and Hybrid Definition detected progression significantly earlier than the CBD (at 4.5, 5.0, and 4.5 years, respectively). CONCLUSIONS: The GPAD and the optimized Hybrid Definition exhibited similar ability for the detection of progression, with the specificity reaching 95.4%.

Effects of Progesterone and Other Gonadal Hormones on Glutamatergic Circuits in the Retina.

BACKGROUND: Gonadal hormones function in the retina; however, their targets have not yet been identified. Therefore, the present study examined the effects of progesterone and other gonadal hormones on glutamatergic circuits in the retina. METHODS: Extracellular glutamate concentrations, which correspond to the amount of glutamate released, were examined using an enzyme-linked fluorescent assay system. The activity of glutamatergic synapses between bipolar cells and ganglion cells was investigated using a patch clamp technique. Changes in retinal thickness during pregnancy were assessed using optical coherence tomography (OCT) images. RESULTS: Progesterone and pregnenolone sulfate increased extracellular glutamate concentrations, whereas estrogen and testosterone did not. Progesterone increased the activity of glutamatergic synapses between bipolar cells and ganglion cells. A temporal decrease in the thickness of the peripheral retina was observed in the 1st trimester. CONCLUSIONS: Progesterone, but not estrogen or testosterone, activated glutamate release in the mouse retina. Increases in the concentration of progesterone during pregnancy did not induce any detectable change in retinal thickness.

Investigating the factors affecting myopia in retinopathy of prematurity after laser treatment.

BACKGROUND: We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes. METHODS: A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared. RESULTS: Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p < 0.001). SE was associated with AL, corneal refraction (CR), and crystalline lens power (CLP) in the ROP group. Of these three factors (AL, CR, and CLP), CLP and the number of laser shots applied were significantly correlated (p = 0.003); however, no correlations were observed between the number of laser shots and AL or CR (p = 0.15 and 0.10, respectively). Very similar tendency was observed in the analysis of the difference between right and left eyes in each child. CONCLUSIONS: In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration.

PURPOSE: To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration. METHODS: Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI +) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI -) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay. RESULTS: C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI + than in IVBrIOI - and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI - compared to that in IVBrIOI + and IVA. In the IVBrIOI + group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI - group. CONCLUSION: The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Recent trends in anti-vascular endothelial growth factor intravitreal injections: a large claims database study in Japan.

PURPOSE: To clarify recent trends in the use of intravitreal injections of anti-vascular endothelial growth factor (VEGF) in Japan. STUDY DESIGN: Retrospective cohort study. METHODS: We used the DeSC database, a large-scale claims database for Japan, for entries between April 2014 and March 2021. We counted the number of anti-VEGF drug injections (aflibercept, ranibizumab, brolucizumab, and pegaptanib) administered every year, calculated the sex- and age-adjusted injection rates, and stratified these rates according to sex, age categories, anti-VEGF drugs, and diagnoses. We also calculated the number of injections administered within one year after the first injection according to the diagnoses. RESULTS: In total, 164,451 cases of anti-VEGF injections were identified. The sex- and age-adjusted rates of anti-VEGF injections per 1000 person-years increased from 7.9 in 2014 to 16.1 in 2020. Men were approximately twice as likely to receive anti-VEGF injections than women. The 70-79, 80-89, and ≥90 age categories had the highest rates, accounting for approximately 80%. Neovascular age-related macular degeneration had the highest rate, accounting for 60-70% over the study period. Aflibercept was the most commonly used drug, accounting for approximately 80% over the study period. The average number of injections within one year after the first injection was 4.4 for neovascular age-related macular degeneration, 2.7 for branch retinal vein occlusion, 3.1 for central retinal vein occlusion, and 3.5 for diabetic macular edema in 2020. CONCLUSION: These findings can be used as a benchmark for the clinical practice of anti-VEGF therapy.

Relationship between visual acuity and visual field and its reproducibility in patients with retinitis pigmentosa.

BACKGROUND/OBJECTIVES: To investigate the association between visual acuity (VA) and visual field (VF) and its reproducibility in patients with retinitis pigmentosa (RP). SUBJECTS/METHODS: The study cohort comprised 227 eyes of 227 patients with RP. The reproducibility of two Humphrey VF tests (10-2 Swedish Interactive Threshold Algorithm [SITA] tests) performed within a period of 3 months was calculated using the root mean squared error (RMSE) of each VF test point's sensitivity. The association between the logarithm of the minimum angle of resolution (logMAR) VA and VF sensitivity was investigated. Additionally, the relationship between RMSE and age, fixation loss, false positives, false negatives, and logMAR VA was determined. RESULTS: The association between visual sensitivity and VA was most tight at the fovea, and it became weak toward the peripheral region in an eccentric manner. VF reproducibility appreciably increased as VA decreased. In particular, reproducibility was significantly decreased when logMAR VA was >0.5 compared with logMAR VA ≤ 0. CONCLUSION: Reproducibility of VF tests decreases with a decrease in VA. Careful consideration is necessary when a patient's logMAR VA is >0.5.