Japanese Journal of Ophthalmology最新文献

{"title":"Binocular visual function in middle-aged patients with unilateral cataract: multifocal versus enhanced monofocal intraocular lens.","authors":"Ken Hayashi, Motoaki Yoshida, Shin-Ichi Manabe, Koichi Yoshimura","doi":"10.1007/s10384-025-01190-7","DOIUrl":"10.1007/s10384-025-01190-7","url":null,"abstract":"<p><strong>Purpose: </strong>To compare binocular visual function of middle-aged patients in the process of presbyopia progression with unilateral cataract who received a trifocal intraocular lens (IOL; Alcon PanOptix^®) with those who received an enhanced monofocal (EM) IOL (Johnson & Johnson Eyehance^®).</p><p><strong>Study design: </strong>Nonrandomized comparative study.</p><p><strong>Methods: </strong>This study enrolled patients in their 40s and 50s with unilateral cataract whose fellow eyes were myopic and the operated eyes were implanted with either a trifocal IOL (n=28, targeting emmetropia) or an EM IOL (n=28, targeting myopia), and patients whose fellow eyes were emmetropic and the operated eyes were implanted with a trifocal IOL (n=25, targeting emmetropia) or an EM IOL (n=23; targeting emmetropia). At 3 months postoperatively, binocular uncorrected and corrected all-distance VA and contrast VA were compared between patients receiving the trifocal and EM IOLs.</p><p><strong>Results: </strong>In the myopia category, mean binocular uncorrected VA from ∞ to 1.0 m was significantly better (P<0.001) and at near distance was significantly worse (P<0.001) in the trifocal group than in the EM group. In the emmetropia category, binocular uncorrected VA from ∞ to 2.0 m and binocular contrast VA at most contrasts were significantly better in the EM group than in the trifocal group (P≤0.043).</p><p><strong>Conclusion: </strong>Trifocal IOLs provide significantly better binocular uncorrected far to intermediate VAs and worse near VA than EM IOLs in patients whose fellow eye is myopic, while EM IOLs provide significantly better far VA and contrast sensitivity in patients whose fellow eye is emmetropic.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"558-567"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japanese clinical guidelines for neovascular age-related macular degeneration.","authors":"Tomohiro Iida, Fumi Gomi, Tsutomu Yasukawa, Kenji Yamashiro, Shigeru Honda, Ichiro Maruko, Keiko Kataoka","doi":"10.1007/s10384-025-01240-0","DOIUrl":"10.1007/s10384-025-01240-0","url":null,"abstract":"<p><p>Recent advances in imaging technology and increased options of pharmaceutical therapy require that guidelines on the diagnostic criteria and treatment of neovascular age-related macular degeneration (AMD) be updated at regular intervals. These guidelines aim to standardize the management of neovascular AMD based on the latest understanding of its pathophysiology, advancements in diagnostic imaging modalities, and treatment options. The key updates include: (1) a revision of terminology and stage classification, adopting the AMD classifications of atrophic and neovascular, and adding end-stage AMD to the existing early, intermediate, and late stages; (2) the inclusion of pachychoroid in addition to drusen in the initial pathophysiology and pathogenic background; (3) diagnostic criteria defined by the presence of macular neovascularization based on multimodal imaging, including optical coherence tomography (OCT) and OCT angiography; (4) assessment of disease activity based on OCT; and (5) treatment guidance, including prophylaxis and low vision care as well as loading and maintenance phases by use of anti-vascular endothelial growth factor therapy and adjunctive therapies. We hope that these guidelines will be useful for those working in clinical practice in Japan, in other Asian countries, and in countries outside Asia.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"639-660"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in robotic surgery for vitreoretinal diseases: current trends and the future.","authors":"Shintaro Nakao, Kotaro Tadano, Koh-Hei Sonoda","doi":"10.1007/s10384-025-01231-1","DOIUrl":"10.1007/s10384-025-01231-1","url":null,"abstract":"<p><p>Medical robotics, such as the da Vinci Surgical System, Hinotori, and Saroa, has been rapidly expanding in the field of general surgery in recent years. Because of the need for high precision in vitreoretinal surgery, general surgery robots are not applicable; therefore, a variety of robots specifically designed for vitreoretinal surgery have been developed around the world. These robotic systems can be broadly categorized into operation systems, operation assistance systems, and observation systems. The purpose of the operation robots is mainly internal limiting membrane peeling and retinal vascular cannulation. The PRECEYES Surgical System was already approved in the European Union in 2019 on the basis of positive clinical results. The aim of operation assistance robots, such as iARMs, is to suppress tremors. Meanwhile, we have developed an observation robot, an intraocular endoscope-holding robot (OQrimo), which was approved as a medical device in Japan in 2023. This robot allows surgeons to perform intraocular manipulations using both hands during vitreoretinal surgery for proliferative diabetic retinopathy and other intractable retinal diseases and may also make it easier to manipulate the anterior tissues around the ciliary body. In the future, by being combined with artificial intelligence in vitreoretinal clinics, robotic surgery will be applied to preoperative, intraoperative, and postoperative surgical procedure decisions, programs, and education.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"483-494"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased macular atrophy area with photodynamic therapy over intravitreal aflibercept at 2-year follow-up of pachychoroid neovasculopathy.","authors":"Hirokazu Kojima, Chieko Shiragami, Ayana Yamashita, Yukiko Miyoshi, Rie Osaka, Aoi Ono, Kiyoshi Suzuma","doi":"10.1007/s10384-025-01232-0","DOIUrl":"10.1007/s10384-025-01232-0","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the therapeutic outcomes of intravitreal aflibercept injection (IVA) and reduced-fluence photodynamic therapy (rfPDT) for pachychoroid neovasculopathy (PNV) over 2 years.</p><p><strong>Study design: </strong>Observational, retrospective case series. Single-center study.</p><p><strong>Methods: </strong>This study involved 36 eyes of 36 patients with PNV. The IVA group comprised 18 eyes treated with IVA monotherapy (injection every 3 months followed by a pro re nata regimen), whereas the rfPDT group consisted of 18 eyes treated with rfPDT monotherapy. Post-treatment changes in best-corrected visual acuity (BCVA), macular atrophy (MA) area, central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) were compared between the 2 groups.</p><p><strong>Results: </strong>The IVA group received 8.94 ± 4.77 injections, whereas the rfPDT group received rfPDT 1.06 ± 0.24 times. The logMAR BCVA improved in both groups but did not differ between the 2 groups. The MA area increased from 0.163 ± 0.418 mm² to 0.227 ± 0.480 mm² (P = .024) and from 0.139 ± 0.402 mm² to 0.597 ± 0.939 mm² (P < .001) in the IVA and rfPDT groups, respectively, with the rfPDT group showing a greater increase than the IVA group (P = .013). The CRT was reduced in both groups but did not differ between the 2 groups. The SFCT was reduced in both groups, but the reduction was higher in the rfPDT group than in the IVA group (P = .027). The factors affecting change in the MA area were the treatment method and patient age.</p><p><strong>Conclusions: </strong>The increase in the MA area and the decrease in the SFCT were greater in the rfPDT group than in the IVA group for PNV, suggesting that IVA may be preferred over rfPDT for PNV treatment.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"529-535"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic outcomes of ranibizumab for zone ii stage 2 retinopathy of prematurity with plus disease.","authors":"Yoshihiro Nakagawa, Yoshifumi Murayama, Yasuyuki Suzuki, Atsushi Uchiyama, Takahiro Suzuki","doi":"10.1007/s10384-025-01199-y","DOIUrl":"10.1007/s10384-025-01199-y","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the efficacy of intravitreal injections of ranibizumab (IVR) in treating zone II stage 2 retinopathy of prematurity with plus disease (ROP II2+) in preterm infants, focusing on two primary outcomes: reactivation and persistent avascular retina (PAR).</p><p><strong>Study design: </strong>Retrospective and consecutive case series.</p><p><strong>Methods: </strong>This retrospective study reviewed the medical records of preterm infants treated with IVR at Tokai University hospital between December 2019 and September 2023. Data on reactivation, PAR, and other clinical outcomes were analyzed using generalized estimating equations to account for correlations between eyes.</p><p><strong>Results: </strong>Thirty eyes from 16 infants received IVR treatment. Following initial IVR all eyes achieved remission for over one year with IVR alone. Forty percent of these eyes required subsequent treatment due to reactivation, with a median reactivation time of 70 days. One year after initial IVR, PAR was observed in 11 out of the 30 eyes. Lower birth weight was associated with a tendency toward reactivation, and it also showed a significant correlation with the development of PAR.</p><p><strong>Conclusions: </strong>This research supports the effectiveness of IVR for ROP II2+ over a one-year period. The links between lower birth weight and both reactivation and PAR might guide refinements in therapeutic strategies.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"543-548"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes and the association between early detection of retinal pigment epithelial atrophy and remission after loading dose in eyes with retinal angiomatous proliferation.","authors":"Wataru Kikushima, Yoichi Sakurada, Daphne Viel Tsuru, Kenji Kashiwagi","doi":"10.1007/s10384-025-01189-0","DOIUrl":"10.1007/s10384-025-01189-0","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the association between early detection of retinal pigment epithelial (RPE) atrophy after anti-vascular endothelial growth factor (VEGF) treatment and the long-term treatment outcomes in eyes with retinal angiomatous proliferation (RAP).</p><p><strong>Study design: </strong>A retrospective observational study METHODS: All patients with treatment-naive RAP initially received three monthly anti-VEGF administration with or without photodynamic therapy (PDT), followed by as-needed anti-VEGF administration. At 12 months post-injection, they were divided into two groups depending on the presence or absence of RPE atrophy. The visual and anatomic outcomes, and the incidence of 12-month remission were investigated within a 48-month follow-up.</p><p><strong>Results: </strong>Thirty-seven eyes of 37 patients were included. The mean age was 80.4 ± 7.0 years, 54% were women. In the atrophy (+) group, 58.3% of patients achieved 12-month remission, significantly higher than the atrophy (-) group (p = 0.04). During the study period, best corrected visual acuity in the atrophy (+) group deteriorated from 0.50 ± 0.43 logMAR to 0.66 ± 0.47 logMAR (p = 0.14), while in the atrophy (-) group, it deteriorated significantly from 0.48 ± 0.27 logMAR to 0.76 ± 0.42 logMAR (p = 6.7×10^-3). The mean additional injections in the atrophy (+) group were significantly smaller compared with the atrophy (-) group at 3.5 ± 4.7 versus 15.3 ± 4.3, respectively (p = 9.0×10^-6).</p><p><strong>Conclusion: </strong>Early detection of RPE atrophy was associated with the incidence of 12-month remission and reduced number of additional injections. The formation of RPE atrophy might suggest a decrease in the disease activity of RAP.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"504-511"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between aldosterone-induced retinal ganglion cell loss, blood pressure, and intraocular pressure.","authors":"Ayaka Edo, Kazuyuki Hirooka, Hiromitsu Onoe, Yoshiaki Kiuchi","doi":"10.1007/s10384-025-01201-7","DOIUrl":"10.1007/s10384-025-01201-7","url":null,"abstract":"<p><strong>Purpose: </strong>To elucidate whether systemic blood pressure affects retinal ganglion cell (RGC) survival in rats administered systemic aldosterone STUDY DESIGN: Experimental study design METHODS: Rats were continuously administered aldosterone or vehicle via a subcutaneous osmotic mini-pump. Hypertension was induced by the provision of saline as their drinking water. Systolic and diastolic blood pressures and intraocular pressure (IOP) were measured at the baseline and at 1-6 weeks after administration of aldosterone-water, aldosterone-saline, vehicle-water, or vehicle-saline. The number of retrogradely labelled RGCs in retinal flat mounts were counted after 6 weeks of treatment. Aldosterone-treated rats also received eplerenone (a mineralocorticoid receptor antagonist) or hydralazine (a vasodilator), and changes in systolic and diastolic blood pressures, IOP, and the number of RGCs were examined.</p><p><strong>Results: </strong>The number of RGCs was significantly reduced in rats treated with aldosterone, regardless of whether they drank water or saline (aldosterone/saline group vs vehicle/saline group: 1464.8 ± 29.7 vs 1763.3 ± 106.5, respectively, P = 0.01; aldosterone/water group vs vehicle/water group: 1433.3 ± 30.2 vs 1815.0 ± 193.9, respectively, P <0.01). No change in IOP with aldosterone or saline administration was observed (P >0.05). Although eplerenone or hydralazine treatment in animals receiving aldosterone and saline reduced the systolic and diastolic blood pressures as compared with in the controls, the number of RGCs was only preserved in the eplerenone-treated group (eplerenone group vs control group: 1868.5 ± 177.7 vs 1464.8 ± 29.7, respectively, P <0.01; hydralazine group vs control group 1554.5 ± 34.9 vs 1464.8 ± 29.7, respectively, P = 0.48). No change in IOP after eplerenone or hydralazine treatment was observed (P >0.05).</p><p><strong>Conclusion: </strong>Aldosterone-induced RGC loss is not affected by systemic blood pressure or IOP.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"624-632"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ab interno removal of malpositioned ex-press glaucoma device combined with bleb needling.","authors":"Daigo Kobayashi, Tadamichi Akagi, Tetsuya Togano, Ryu Iikawa, Takeo Fukuchi","doi":"10.1007/s10384-025-01203-5","DOIUrl":"10.1007/s10384-025-01203-5","url":null,"abstract":"<p><strong>Purpose: </strong>We present an ab interno removal technique combined with a needling procedure for a malpositioned Ex-PRESS glaucoma shunt.</p><p><strong>Study design: </strong>Retrospective case series.</p><p><strong>Methods: </strong>This study examined four cases of malpositioned Ex-PRESS shunts. Needle bleb revision was performed to expand the space under the scleral flap and bleb area. Clinical data, including corneal endothelial cell density (ECD), intraocular pressure (IOP), and anterior segment optical coherence tomography images (AS-OCT), were retrieved from clinical records.</p><p><strong>Results: </strong>All four cases underwent ab interno shunt removal combined with needle bleb revision without any serious complications. In three cases of anterior shunt malposition, a reduction in ECD was apparent before surgery but remained relatively stable after surgery. In one patient with posterior shunt malposition, shunt occlusion was suspected before surgery, but bleb formation and IOP improved after surgery. IOP was 8 mmHg to 21 mmHg (median, 10.5 mmHg) before surgery and 5 mmHg to 17 mmHg (median, 10 mmHg) 12 months after surgery. No additional glaucoma surgery was required within the first 12 months; however, after 12 months, two patients required additional glaucoma surgery.</p><p><strong>Conclusion: </strong>Ab interno Ex-PRESS device removal combined with bleb needling is an important procedure in patients with malpositioned Ex-PRESS devices.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":"577-582"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short‑term outcomes of switching to faricimab for macular edema secondary to retinal vein occlusion.","authors":"Taiichi Hikichi, Haruka Kurabe, Amane Notoya, Yuuna Oguro, Misaki Hirano, Yumeka Doi","doi":"10.1007/s10384-025-01237-9","DOIUrl":"https://doi.org/10.1007/s10384-025-01237-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated the anatomical and functional outcomes in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who were switched from conventional anti-vascular endothelial growth factor (VEGF) agents to faricimab.</p><p><strong>Study design: </strong>Retrospective observational study.</p><p><strong>Methods: </strong>This study included 42 eyes from 42 patients treated at Hikichi Eye Clinic between April and August 2024. All patients had relapsed ME despite prior treatment with aflibercept and were switched to intravitreal faricimab (6.0 mg). The primary endpoints included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intravitreal injection intervals over six months.</p><p><strong>Results: </strong>The mean (± standard error) CFT significantly decreased from 356 ± 23 μm to 214 ± 3 μm at one month (p < 0.01) and remained stable at the final visit (205 ± 4 μm). Logarithm of the minimum angle of resolution (logMAR) BCVA improved from 0.16 ± 0.03 to 0.04 ± 0.03 at one month (p < 0.01) and remained at 0.02 ± 0.02 at the final visit. The mean injection interval was significantly extended from 12.3 ± 0.4 weeks to 16.2 ± 0.5 weeks (p < 0.01).</p><p><strong>Conclusion: </strong>Faricimab improved anatomical and functional outcomes while extending treatment intervals in ME secondary to RVO. Further large-scale, prospective, and long-term follow-up studies are needed to confirm these findings.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of SIX6 gene in juvenile open-angle glaucoma: a subtle contributor to the mutational landscape.","authors":"Manoj Yadav, Sumit Sachdeva, Anshu Yadav, Aarti Bhardwaj, Vishal Panghal, Ankit Kumari, Ritu Yadav, Rakesh Kumar, Mayank Singh, Sapna Sharma, Mukesh Tanwar","doi":"10.1007/s10384-025-01233-z","DOIUrl":"https://doi.org/10.1007/s10384-025-01233-z","url":null,"abstract":"<p><strong>Purpose: </strong>Juvenile onset open-angle glaucoma (JOAG) typically affects individuals under 40 years of age, causing a rise in intraocular pressure that results in considerable damage to the optic nerve. To expand the spectrum of mutations linked to JOAG and explore their structural consequences, we examined the genetic alterations within the SIX6 gene.</p><p><strong>Study design: </strong>We focused on assessing the whole coding region of the SIX6 gene and the clinical significance of the common SIX6 gene single nucleotide polymorphisms (SNP) rs10483727 and rs33912345, specifically analyzing its association with key clinical factors, including intraocular pressure (IOP), visual acuity, and the vertical cup-to-disc ratio (VCDR).</p><p><strong>Method: </strong>The study included 111 unrelated patients with confirmed JOAG and 100 healthy adult controls without any ocular or systemic conditions. The patients initially underwent genetic screening for pathogenic variants in the CYP1B1, MYOC, and OPTN genes. Individuals who tested negative for pathogenic variants in these three genes (n=81) were subsequently screened for variants in the SIX6 gene while all 111 patients and 100 control samples were screened for SNPs to strengthen the statistical correlation. Identified sequence variations were searched in the ClinVar databases, HGMD, and dbSNP. Six different online available algorithms including REVEL, SIFT, CADD, Mutation Taster, IMutant2.0, and MetaLR were used for the pathogenicity prediction of missense variations. The Structural consequences of detected possible pathogenic variations were predicted by using PyMol, Chimera and molecular dynamics (MD) simulation of these changes. Statistical analyses assessed the association of rs33912345 with disease phenotypes.</p><p><strong>Results: </strong>Sanger sequencing identified seven nucleotide variants in the SIX6 gene, including five missense and two synonymous variants. Two missense variants, p.(A99G) and p.(S156R), were predicted to be pathogenic. The novel variant p.(A99G) was absent in controls and demonstrated significant structural disruption, with altered intramolecular interactions and steric clashes. Homology analysis revealed high evolutionary conservation at the mutated positions, highlighting their functional significance. MD simulations confirmed altered stability in the mutant proteins. Logistic regression linked rs33912345 to JOAG, with significant associations observed for IOP (p = 0.01538), and VCDR (p = 0.019).</p><p><strong>Conclusion: </strong>This study identified novel and known pathogenic variants in the SIX6 gene that may contribute to JOAG pathogenesis. Structural and functional analyses suggest that these mutations disrupt protein function. The findings enhance our understanding of JOAG genetics and may aid in early diagnosis and therapeutic targeting.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}