Purpose: Anti-vascular endothelial growth factor (VEGF) therapy is the most prevalent intervention for exudative lesions secondary to neovascular age-related macular degeneration (nAMD) and other macular neovascularization (MNV). However, in some cases refractory to the latest anti-VEGF agents is associated with epiretinal membrane (ERM) or vitreomacular traction. We applied a vitrectomy to remove those pathologies which may be effective for reducing the exudation. Observations: In this case report, we present 2 cases with sustained subretinal fluid and macular neovascularization secondary to nAMD or dome-shaped macula that poorly responded to anti-VEGF therapy. In both cases, removing thin ERM or vitreomacular traction with an inner limiting membrane peeling promptly resolved the subretinal fluid and no recurrence was observed thereafter. Conclusions and importance: Vitrectomy could be an effective modality for anti-VEGF drug-resistant MNV cases with vitreomacular traction or ERM even in the anti-VEGF era.
PURPOSE: To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. METHODS: After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. RESULTS: EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. CONCLUSIONS: It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.
Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation in the phenotype of AMD. For example, several reports demonstrated that the incidence of drusen in AMD patients is less in Asians compared to Caucasians though the reason has not been clarified yet. In the last decades, several genome association studies have disclosed many susceptible genes of AMD and revealed that the association strength of some genes was different among races and AMD phenotypes. In this review article, the essential findings of the clinical studies and genome association studies for the most significant genes CFH and ARMS2/HTRA1 in AMD of different races are summarized, and theoretical hypotheses about the molecular mechanisms underlying the ethnic variation in the AMD manifestation mainly focused on those genes between Caucasians and Asians are discussed.
PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD). METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329). RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2. CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.
Purpose: To examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma. Methods: Observational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images. Results: GS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value <0.25). The GS with the greatest difference in expression was the GS of epithelial-mesenchymal transition (EMT). Based on this GS change, immunohistochemical staining was added using E-cadherin as an epithelial marker and vimentin as a mesenchymal marker for EMT. There was significant staining of vimentin in orbital lymphoma (P<0.01, N=129) and of E-cadherin in conjunctival lesions (P=0.023, N=129). Vimentin staining correlated with Ann Arbor staging (1 versus >1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P<0.01). Conclusion: GS changes including EMT and stromal area in tumor were used to demonstrate the molecular biological differences between conjunctival MALT lymphoma and orbital MALT lymphoma in ocular adnexa lymphomas.
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.
PURPOSE: To investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis. METHODS: This retrospective study examined vitreous inflammatory cells (hyperreflective particles) of posterior uveitis on widefield optical coherence tomography (WOCT). We examined the number of hyperreflective particles (possibility of vitreous inflammatory cells) observed on WOCT and the correlations with interleukin-6 (IL-6) levels. The relationship between vitreous IL-6 levels and image findings from WOCT from 37 eyes (34 patients) with posterior uveitis were analyzed. Mean patient age was 63.4±15.7 years. (Mean± standard deviation) IL-6 concentration in vitreous humor was 79.9±7380.9 pg/mL Uveitis was infectious in 9 cases and non-infectious in 28 cases with multiplex polymerase chain reaction system. We measured the number and size of vitreous cells in the posterior vitreous, defined as the space between the upper vitreous and the internal limiting membrane on WOCT at the macular, upper, and lower regions. Image analysis software was also used for cell counting. RESULTS: A strong correlation was seen between human and software counts. Pearson's correlation coefficient (PCC) was performed to compare categorial variables (on macular +0.866; upper cavity +0.713; lower cavity +0.568; total vitreous cavity +0.834; P<0.001 each). IL-6 levels correlated with both vitreous cell counts and cell counts observed on macular WOCT (human-counted group +0.339, P = 0.04; software-counted group +0.349, P = 0.03). Infectious uveitis showed higher IL-6 levels (P = 0.016) and high cell counts compared with non-infectious uveitis (P = 0.04). CONCLUSIONS: Vitreous number of hyperreflective particles (cells) findings on WOCTcorrelated well with human and software cell counts. Vitreous cells findings on WOCT also correlated with IL-6 concentrations on macular.
Uveitis, Posterior , Uveitis , Humans , Middle Aged , Aged , Interleukin-6 , Retrospective Studies , Tomography, Optical Coherence/methods , Uveitis/diagnostic imaging , Retina
Introduction: Ocular metastases from breast cancer, particularly involving the optic nerve, are rare and pose a diagnostic challenge. Typically, optic nerve metastases are believed to originate from nearby choroidal metastases or hematogenous spread through the posterior ciliary arteries. However, there have been some reports of metastases through leptomeningeal dissemination. The aim of this report was to describe a case of multiple brain metastases from breast cancer without subjective symptoms other than central scotoma, which was diagnosed with repeated magnetic resonance imaging (MRI). Case Presentation: A 62-year-old woman who had previously undergone a mastectomy for left breast cancer complained of left ocular pain during eye movement and left visual loss. Initial contrast-enhanced MRI showed no significant abnormalities, and idiopathic optic neuritis was suspected. Despite steroid pulse therapy, her visual function did not improve. After four and a half months, her visual acuity worsened, and repeat contrast-enhanced MRI showed brain metastases involving the optic nerve sheath. Conclusion: Despite the multiple brain metastases, ultimately the patient's only symptom was unilateral visual loss. These findings highlight the usefulness of repeated contrast-enhanced MRI for detecting brain metastases, especially in cases without other apparent neurological symptoms or initial imaging abnormalities.
PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.
Antibodies, Monoclonal, Humanized , Macular Degeneration , Retinal Vasculitis , Uveitis , Female , Humans , Angiogenesis Inhibitors , Incidence , Inflammation , Intravitreal Injections , Japan , Retina , Risk Factors , Vision Disorders , Male
To investigate whether aldosterone (ALD) and hydrocortisone (HC) change the gene expression of SLC7A5, which encodes the large neutral amino acid transporter small subunit 1 (LAT1), and the transport activity of LAT1 in the retinal pigment epithelium (RPE) in vitro. ARPE-19 cells were grown to confluence. After withdrawing the serum, ALD or HC was added with several doses and incubated, and SLC7A5 gene expression was measured. The influx and efflux transport of sodium fluorescein (Na-F) were evaluated using the Transwell culture system. SLC7A5 gene expression was upregulated by ALD and downregulated by HC in a dose-dependent manner. Both ALD and HC significantly increased the influx and efflux Na-F transport of RPE cells at a dose that did not change the expression of SLC7A5. JPH203, a specific inhibitor of LAT1, significantly reduced accelerated Na-F transport. Both ALD and HC increased the gene expression of zonula occludin-1 (ZO-1) although they did not change the immunoreactivity of ZO-1 in RPE cells. LAT1 may play an important role in increasing Na-F transport associated with ALD and HC administration. A specific LAT1 inhibitor may effectively regulate the increased material transport of RPE induced by ALD and HC.
Epithelial Cells , Large Neutral Amino Acid-Transporter 1 , Large Neutral Amino Acid-Transporter 1/metabolism , Fluorescein , Biological Transport , Epithelial Cells/metabolism , Adrenal Cortex Hormones , Retinal Pigments/metabolism
PURPOSE: The purpose of this study was to develop artificial intelligence algorithms that can distinguish between orbital and conjunctival mucosa-associated lymphoid tissue (MALT) lymphomas in pathological images. METHODS: Tissue blocks with residual MALT lymphoma and data from histological and flow cytometric studies and molecular genetic analyses such as gene rearrangement were procured for 129 patients treated between April 2008 and April 2020. We collected pathological hematoxylin and eosin-stained (HE) images of lymphoma from these patients and cropped 10 different image patches at a resolution of 2048 × 2048 from pathological images from each patient. A total of 990 images from 99 patients were used to create and evaluate machine-learning models. Each image patch of three different magnification rates at ×4, ×20, and ×40 underwent texture analysis to extract features, and then seven different machine-learning algorithms were applied to the results to create models. Cross-validation on a patient-by-patient basis was used to create and evaluate models, and then 300 images from the remaining 30 cases were used to evaluate the average accuracy rate. RESULTS: Ten-fold cross-validation using the support vector machine with linear kernel algorithm was identified as the best algorithm for discriminating between conjunctival mucosa-associated lymphoid tissue and orbital MALT lymphomas, with an average accuracy rate under cross-validation of 85%. There were ×20 magnification HE images that were more accurate in distinguishing orbital and conjunctival MALT lymphomas among ×4, ×20, and ×40. CONCLUSION: Artificial intelligence algorithms can successfully distinguish HE images between orbital and conjunctival MALT lymphomas.
Conjunctival Neoplasms , Eye Neoplasms , Lymphoma, B-Cell, Marginal Zone , Humans , Lymphoma, B-Cell, Marginal Zone/genetics , Artificial Intelligence , Conjunctival Neoplasms/diagnosis , Conjunctival Neoplasms/pathology , Machine Learning
PURPOSE: To evaluate the 1-year efficacy, durability, and safety of faricimab versus aflibercept in patients with neovascular age-related macular degeneration (nAMD) enrolled in the Japan subgroup of the TENAYA trial. STUDY DESIGN: TENAYA (NCT03823287) was a global, phase 3, multicenter, randomized, active comparator-controlled, double-masked, noninferiority, parallel-group, 112-week trial. After completion of global enrollment, additional patients were enrolled in the Japan extension of TENAYA. METHODS: Treatment-naïve patients aged ≥ 50 years with nAMD were randomized (1:1) to intravitreal faricimab 6 mg up to every 16 weeks (Q16W) after 4 initial Q4W doses based on disease activity at weeks 20 and 24 or aflibercept 2 mg Q8W after 3 initial Q4W doses. Primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. Anatomical/durability outcomes were assessed. RESULTS: Overall, 133 patients were included in the TENAYA Japan subgroup analysis (faricimab, n = 66; aflibercept, n = 67). The adjusted mean (95% confidence interval) BCVA changes were + 7.1 (4.6â9.7) and + 7.7 (5.2â10.1) letters in the faricimab and aflibercept treatment groups, respectively. At week 48, 66.1%, 22.6%, and 11.3% of patients in the faricimab group were on Q16W, Q12W, Q8W and dosing intervals, respectively. Ocular adverse event rates were similar between treatment groups (faricimab, n = 14 [21.2%] versus aflibercept, n = 17 [25.4%]). CONCLUSION: The TENAYA Japan subgroup analysis showed that faricimab up to Q16W had sustained efficacy with an acceptable safety profile. These findings are consistent with the global TENAYA and LUCERNE findings.
Macular Degeneration , Wet Macular Degeneration , Humans , Angiogenesis Inhibitors , Japan/epidemiology , Visual Acuity , Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Macular Degeneration/drug therapy , Recombinant Fusion Proteins , Treatment Outcome , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/drug therapy
PURPOSE: Persistent central serous chorioretinopathy (pCSC) may be treated by laser photocoagulation (PC), selective retina therapy (SRT), or photodynamic therapy (PDT). We conducted retrospective analyses regarding the choice of therapy for pCSC in the best clinical practice and the outcomes of these modalities. STUDY DESIGN: A retrospective interventional study. METHODS: The records of 71 eyes of 68 treatment naïve pCSC cases who underwent PC, SRT, or PDT were reviewed. First, the baseline clinical parameters were evaluated to find significant factors associated with the choice of treatment option. Second, the 3 months' visual and anatomical outcomes of each modality were assessed. RESULTS: The PC, SRT, and PDT groups included 7, 22, and 42 eyes, respectively. The leakage pattern in fluorescein angiography (FA) was significantly associated with the choice of treatment (p<0.005). The dry macula ratio at 3 months post-treatment was 29%, 59%, and 81% in the PC, SRT, and PDT groups, respectively, which significantly differed among the groups (p<0.01). The best-corrected visual acuities tended to be improved after the treatments in all groups. Central choroidal thickness (CCT) was significantly decreased in all groups (p<0.05, p<0.01, and p<0.00001, in PC, SRT, and PDT groups, respectively). Logistic regression analysis for dry macula revealed that SRT (p<0.05), PDT (p<0.05), and the changes in CCT (p<0.01)were the significant association factors. CONCLUSION: The leakage pattern in FA was associated with the choice of treatment option for pCSC. PDT achieved a significantly higher dry macula ratio than PC, 3 months after the treatment.
Central Serous Chorioretinopathy , Photochemotherapy , Porphyrins , Humans , Central Serous Chorioretinopathy/therapy , Central Serous Chorioretinopathy/drug therapy , Photosensitizing Agents/therapeutic use , Retrospective Studies , Visual Acuity , Fluorescein Angiography , Tomography, Optical Coherence , Chronic Disease
PURPOSE: The present study assesses the utility of en-face widefield optical coherence tomography angiography (OCTA) imaging for evaluating the retinal vascular network during the course of treatment in acute retinal necrosis(ARN). OBSERVATIONS: OCTA images of two cases of acute retinal necrosis were analyzed. Case 1 was a 15-year-old male with visual crowding in his right eye who had best-corrected visual acuity of 16/20 and intraocular pressure of 25 mmHg in his right eye on initial evaluation. Case 2 was a 57-year-old male with visual crowding in his left eye who had best-corrected visual acuity of 20/20 in his left eye on initial examination and intraocular pressure of 19.3 mmHg. In both patients, dynamic changes could be tracked by en-face ultra-widefield OCTA imaging before and up to 1 year after surgical treatment. The images showed arteriovenous anastomosis and the nonperfused area on the surface of the retina. CONCLUSIONS AND IMPORTANCE: En-face widefield OCTA is useful for monitoring the structure of retinal vessels over time in acute retinal necrosis. Wide-angle OCTA is used to non-invasively examine retinal vascular dynamic changes in ARN. OCTA artifacts due to intraocular inflammation appeared, making interpretation difficult. These will remain as issues in the future. It seems difficult for a while to completely replace FA due to the problem of image clarity.
The purpose of this study was to compare the safety and efficacy of selective retina therapy (SRT) combined with the intravitreal injection of ranibizumab (IVR) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). This trial was a 12-month single-center, randomized, single-masked prospective study. Eligible patients were randomized (1:1) to IVR and SRT (IVR + SRT group), or IVR and sham SRT (IVR + sham group). After the initial IVR, all participants received ME resolution criteria-driven pro re nata treatment. SRT or sham SRT was always applied one day after IVR. The primary outcome measure of this study was the mean change in central macular thickness (CMT) from baseline, and the secondary outcome measures were the mean change in visual acuity from baseline and the number of IVR treatments at a 52-week follow-up. Thirteen patients were in the IVR + SRT group, and 11 were in the IVR + sham group. Compared to the baseline, mean CMT and BCVA improved significantly after 52 weeks in both groups, with no significant difference between the two groups. The mean number of IVR was 2.85 ± 1.52 in the IVR + SRT group and 4.73 ± 2.33 in the IVR + sham group at the 52-week follow-up, with a significant difference between the two groups (p < 0.05). IVR combined with SRT may significantly decrease the number of IVR treatments while maintaining the visual and anatomical improvement effect of IVR monotherapy.
This study retrospectively determined the relationship between vitreous IL-6 levels and clinical and laboratory data collected from uveitis patients. We examined an unknown cause of posterior uveitis, collecting vitreous fluid to investigate vitreous IL-6 levels. The samples were analyzed in consideration of clinical and laboratory factors, such as the male/female ratio. The present study included 82 eyes from 77 patients with a mean age of 66.20 ± 15.41 years. The IL-6 concentrations of the vitreous specimens were 6255.0 ± 14,108.3 pg/mL in males and 277.6 ± 746.3 pg/mL in females, which was found to be a statistically significant difference (p = 0.048) (n = 82). There was also a statistically significant correlation between vitreous IL-6 concentrations, serum C-reactive protein (CRP) value and white blood cell counts (WBCs) (n = 82). In multivariate analysis, vitreous IL-6 levels were significantly correlated with gender and CRP in all cases (p = 0.048 and p < 0.01, respectively) and were also significantly correlated with CRP in non-infectious uveitis (p < 0.01). In infectious uveitis, there were no significant differences between IL-6 level and several variables. Vitreous IL-6 concentrations were higher in males than in females in all cases. In non-infectious uveitis, vitreous IL-6 levels were correlated with serum CRP. These results might suggest that intraocular IL-6 levels depend on gender differences in posterior uveitis, and intraocular IL-6 levels in non-infectious uveitis may reflect systemic inflammations, including increased serum CRP.
PURPOSE: To confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis. METHOD: We retrospectively studied patients who had been diagnosed with uveitis and had undergone W-OCT. All patients had visited at Osaka Metropolitan University between January 2019 and January 2022. On W-OCT, vitreous opacity ("W-OCT VO") and the presence of vitreous cells ("W-OCT Cells") were identified by three specialists. We compared findings from ophthalmoscopy ("Ophthalmoscopic findings") and fluorescein angiography ("FAG findings") with those from W-OCT. RESULTS: This study investigated 132 eyes from 68 patients (34 males, 34 females; mean age, 53.97±22.71 years). Vitreous cells in posterior uveitis and panuveitis differed significantly between "W-OCT Cells" and "Ophthalmoscopic findings" for all cases (P = 0.00014). Vitreous opacities in posterior uveitis and panuveitis did not differ significantly between "W-OCT VO" and "Ophthalmoscopic findings" (P = 0.144) for all cases. Compared to "Ophthalmoscopic findings", "W-OCT Cells" offered 51.1% sensitivity and 66.7% specificity for all cases (p<0.01). Compared to "Ophthalmoscopic findings", "W-OCT VO" offered 78.6% sensitivity and 30% specificity for all cases (p = 0.19). In addition, "W-OCT Cells" did not differ significantly from "FAG findings" for all cases (P = 0.424). CONCLUSION: W-OCT was shown to offer significantly greater sensitivity than ophthalmoscopy for detecting vitreous cells. The results of this study may add an option for the evaluation of uveitis.
Panuveitis , Uveitis, Posterior , Uveitis , Male , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Tomography, Optical Coherence/methods , Uveitis, Posterior/diagnostic imaging , Panuveitis/diagnostic imaging , Uveitis/diagnostic imaging , Inflammation , Ophthalmoscopy , Fluorescein Angiography/methods , Vitreous Body/diagnostic imaging
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.
Central Serous Chorioretinopathy , Macular Degeneration , Humans , Genome-Wide Association Study , Genetic Predisposition to Disease , Central Serous Chorioretinopathy/diagnosis , Central Serous Chorioretinopathy/genetics , Macular Degeneration/genetics , Genotype , Polymorphism, Single Nucleotide , Genetic Loci
