Eye and Vision最新文献

{"title":"STING deficiency alleviates scar formation after glaucoma filtration surgery by suppressing p38 MAPK-induced inflammation in mice.","authors":"Huifang Ye, Xinlei Lu, Hongjin Chen, Xi Yang, Han Xu, Lei Huang, Qinxiang Zheng, Rongrong Le, Yuanbo Liang","doi":"10.1186/s40662-026-00475-3","DOIUrl":"10.1186/s40662-026-00475-3","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma filtration surgery (GFS) often fails because of excessive scar formation driven by inflammation and fibroblast activation. Although the stimulator of interferon genes (STING) pathway is involved in inflammatory responses, its role in post-surgical fibrosis remains unclear.</p><p><strong>Methods: </strong>A mouse GFS model was established in wild-type (WT) and STING-knockout (STING-KO) animals. A parallel cohort of WT mice received a single intraoperative subconjunctival injection of the STING inhibitor H151. Bleb survival, intraocular pressure, histopathology, collagen deposition, and inflammatory/fibrotic markers were evaluated for 28 days. RNA sequencing, Western blotting, and ELISA were employed to profile the p38/MAPK axis. Primary human Tenon's capsule fibroblasts were treated with angiotensin II in the presence or absence of STING silencing or H151 to corroborate mechanisms in vitro.</p><p><strong>Results: </strong>STING expression was markedly up-regulated in fibroblasts within human and mice post-GFS tissues. STING-KO mice exhibited prolonged bleb survival together with reduced collagen deposition and fibroblast activation. RNA-sequencing revealed that STING deletion significantly altered the p38 mitogen-activated protein kinase (MAPK) pathway. Mechanistically, STING deficiency suppressed p38 MAPK phosphorylation, leading to decreased levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α, IL-18, and IL-1β, as well as the fibrogenic factors α-SMA, collagen I, fibronectin, connective tissue growth factor, and collagen type III alpha 1 at the surgical sites. Consistently, the selective STING inhibitor H151 recapitulated these effects by suppressing p38 MAPK signaling and markedly reducing fibrotic scarring.</p><p><strong>Conclusions: </strong>STING deficiency alleviates scar formation after GFS by suppressing p38 MAPK pathway. Targeting STING/p38 axis may improve surgical outcomes by modulating the balance between inflammation and tissue repair.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"7"},"PeriodicalIF":4.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRG1 orchestrates diabetic corneal neuropathy via PI3K/AKT-mediated glycolytic reprogramming.","authors":"Yuyang Deng, Wenqu Chen, Danling Liao, Jianzhang Hu","doi":"10.1186/s40662-026-00474-4","DOIUrl":"10.1186/s40662-026-00474-4","url":null,"abstract":"<p><strong>Background: </strong>Mounting evidence indicates metabolic dysregulation in diabetic corneal neuropathy (DCN). This study elucidates how the chromatin remodeler Brahma-related gene 1 (BRG1) orchestrates glycolytic reprogramming to drive neurodegeneration and epithelial repair defects in DCN.</p><p><strong>Methods: </strong>Type 1 diabetic mice were established via streptozotocin (STZ) injection. Glycolysis was inhibited using 2-deoxy-D-glucose (2-DG) to assess its role in DCN pathogenesis. BRG1 expression was modulated by subconjunctival plasmid delivery (overexpression/knockdown). Pathway screening identified BRG1 downstream effectors, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) inhibition (LY294002) confirmed regulatory hierarchy. Glycolytic flux was evaluated via Western blotting and immunofluorescence; corneal nerve integrity and epithelial healing were assessed by βIII-tubulin staining and sodium fluorescein assay.</p><p><strong>Results: </strong>Hyperglycemia upregulated BRG1 and glycolytic enzymes in diabetic corneal nerves. BRG1 overexpression exacerbated epithelial repair delay and neurodegeneration, while knockdown partially reversed damage. BRG1 overexpression activated PI3K/AKT transcription, and PI3K/AKT inhibition did not alter BRG1 levels but rescued BRG1-induced pathologies.</p><p><strong>Conclusions: </strong>Glycolytic reprogramming is a critical driver of DCN progression. BRG1 activates PI3K/AKT signaling to enhance glycolytic flux, thereby regulating DCN pathogenesis. Targeting this axis may offer novel therapeutic strategies.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"5"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global burden and cross-country inequalities of age-related eye diseases from 1990 to 2021: a comprehensive analysis of temporal trends and socioeconomic disparities.","authors":"Kuan Li, Jing Tang, Zicheng Zhang, Xuyan Li, Yongxiang Zheng, Dan Jiang, Jie Sun","doi":"10.1186/s40662-026-00473-5","DOIUrl":"10.1186/s40662-026-00473-5","url":null,"abstract":"<p><strong>Background: </strong>Age-related eye diseases (AREDs) are leading causes of visual impairment worldwide. With global population aging, understanding their epidemiological trends and socioeconomic disparities is crucial for public health planning and equitable resource allocation.</p><p><strong>Methods: </strong>We conducted a secondary epidemiological analysis of AREDs using data from the Global Burden of Disease (GBD) Study 2021. We evaluated years lived with disability (YLDs) and age-standardized YLD rates (ASYR) and conducted trend analysis using Joinpoint regression. Cross-country inequalities were assessed using the slope index of inequality (SII) and concentration index, with correlation and regression analyses examining associations with the socio-demographic index (SDI).</p><p><strong>Results: </strong>Global YLDs for AREDs increased from 78.503 to 100.006, while ASYR decreased from 112.815 to 92.803 per 100,000 populations between 1990 and 2021. Despite a global increase in the relative burden of glaucoma, both absolute and relative inequalities for age-related macular degeneration (AMD) and cataracts decreased. Low-SDI countries showed slight improvements in reducing these inequalities. The SII for AREDs improved in lower-SDI countries between 1990 and 2021, with reductions in AMD (from - 9.250 to - 6.033), cataract (from - 258.131 to - 173.762), and glaucoma (from - 21.090 to - 20.064). The concentration index for AMD and cataract decreased from - 0.167 and - 0.335 in 1990 to - 0.129 and - 0.272 in 2021, respectively, while the concentration index for glaucoma increased from - 0.208 to - 0.263, Regional disparities in the AREDs burden were evident, with most regions showing improved inequality in lower-SDI countries as reflected in both the SII and concentration index.</p><p><strong>Conclusions: </strong>Despite global improvements in the relative burden of AREDs, significant socioeconomic and geographical inequalities persist, particularly in low-SDI regions. Targeted public health strategies and strengthened eye care systems are urgently needed to address these disparities and achieve equitable eye health outcomes worldwide.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"4"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Light and myopia: a focus on the expanding role of non-visual opsins.","authors":"Kate Gettinger, Kazuo Tsubota, Kazuno Negishi, Toshihide Kurihara","doi":"10.1186/s40662-025-00472-y","DOIUrl":"10.1186/s40662-025-00472-y","url":null,"abstract":"<p><p>Myopia, or near-sightedness, is a growing global concern as its incidence rate continues to dramatically rise. It has been linked to significant ocular morbidity and reduced quality of life. Despite this, much is still largely unknown about the development of and the mechanisms driving the pathogenesis of myopia. As such, myopia prevention and myopia mitigation treatment strategies are occasionally ineffective, can be difficult to adhere to, and have diminishing returns over time. Recently, non-visual opsins (OPN3, OPN4, and OPN5) have emerged as potentially impacting myopia regulation. This narrative review aims to summarize the current understanding of the non-visual opsins and how they might influence myopia. In addition, this review explores how utilizing this knowledge can help develop promising future treatment strategies to reduce the incidence and severity of myopia.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"6"},"PeriodicalIF":4.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postural changes in retinal vascular parameters and risk of diabetic retinopathy progression in type 2 diabetes mellitus: a pilot study.","authors":"Truong X Nguyen, Yu Meng Wang, Anni Ling, Chunwen Zheng, Kenny H W Lai, Ziqi Tang, John H K Liu, Carol Y Cheung","doi":"10.1186/s40662-025-00471-z","DOIUrl":"10.1186/s40662-025-00471-z","url":null,"abstract":"<p><strong>Background: </strong>To investigate whether postural changes in retinal vascular parameters, measured using smartphone-based imaging, differ between healthy individuals and patients with diabetes mellitus (DM), and whether these changes independently predict diabetic retinopathy (DR) progression over a 5-year period.</p><p><strong>Methods: </strong>Retinal images were captured using a smartphone with a clip-on adapter lens in sitting and supine positions. Vascular parameters (caliber, fractal dimension, tortuosity, branching) were quantified using the Singapore I Vessel Assessment software. Cross-sectional analyses compared postural-induced vascular responses between 38 healthy controls and 49 DM participants. DM participants were followed for 5 years, with DR progression defined as ≥ 2-step increase in severity on the Early Treatment Diabetic Retinopathy Study scale. Cox proportional hazards models evaluated associations between baseline postural changes and DR progression.</p><p><strong>Results: </strong>Healthy controls exhibited significant arteriolar and venular constriction upon moving from sitting to supine (P < 0.05). In contrast, participants with DM showed diminished or paradoxical responses that did not reach statistical significance. Significant linear trends were observed for arteriolar caliber, fractal dimension, and simple tortuosity across healthy controls, DM with and without DR (all P-trend < 0.05). Greater arteriolar tortuosity was associated with a 2.41-fold higher risk of DR progression (HR = 2.41, 95% CI: 1.37-4.23; P = 0.002), while wider venular branching angles correlated with a 45% lower risk (HR = 0.55, 95% CI: 0.35-0.87; P = 0.011). Adding these parameters improved predictive discrimination beyond established factors (arteriolar tortuosity: C-statistic 0.630-0.740; venular branching angle: 0.630-0.683; P < 0.05).</p><p><strong>Conclusions: </strong>Smartphone-based imaging of retinal vascular responses to postural changes provides additional prognostic value for DR progression, potentially enhancing early risk stratification and proactive management.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"3"},"PeriodicalIF":4.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12772113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-visual opsins and their role in circadian photoentrainment.","authors":"Ethan D Buhr, Russell N Van Gelder","doi":"10.1186/s40662-025-00470-0","DOIUrl":"10.1186/s40662-025-00470-0","url":null,"abstract":"<p><p>Photoreception is common in animals without a visual system. In animals with visual systems, it is sometimes presumed that the same photoreceptors and pathways will accommodate both visual and non-visual light detection. However, mounting evidence reveals that most animals exhibit broad extra-visual photoreceptive functions that are wholly independent of the visual system. One of these functions is the synchronization of the circadian clock to light-dark signals, or photoentrainment. In mammals, behavioral photoentrainment is achieved exclusively through visual and non-visual opsin proteins within the retina, and molecular photoentrainment of individual cells occurs using non-visual opsins in some peripheral tissues. This is in contrast to insects and fish where nearly all peripheral organs are directly photoentrainable. This review will summarize the family of opsins in mammals and focus on the role of non-visual opsins in circadian photoreception. Particular emphasis will be given to photoentrainment in other vertebrates in order to compare and contrast the use of the wide range of non-visual opsins in circadian photoentrainment throughout the animal kingdom.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"1"},"PeriodicalIF":4.0,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory and dry eye benefits of accelerated epi-off corneal cross-linking in pediatric keratoconus with allergic ocular surface disease and elevated MMP-9.","authors":"Cosimo Mazzotta, Caterina Gagliano, Fabiana D'Esposito, Francesco Cappellani, Carlos Rocha De Lossada, Davide Borroni, Alessandro Meduri, Marco Ferrise","doi":"10.1186/s40662-025-00469-7","DOIUrl":"10.1186/s40662-025-00469-7","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the functional and ocular surface anti-inflammatory outcomes of epithelium-off accelerated corneal cross-linking (ACXL) in adolescents with progressive keratoconus associated with allergic ocular surface disease and dry eye disease (DED) characterized by elevated tear matrix metalloproteinase-9 (MMP-9) concentrations.</p><p><strong>Methods: </strong>Prospective interventional case series of 30 eyes from 15 patients (mean age 16.41 ± 2.36 years; Krumeich stage II) undergoing epi-off ACXL. Outcomes at baseline and 1, 3, 6, and 12 months included corrected distance visual acuity (CDVA), maximum keratometry (Kmax), minimum corneal thickness (MCT), computerized non-invasive tear break-up time (cBUT), Ocular Surface Disease Index (OSDI), and tear MMP-9 (point-of-care test). In vivo qualitative confocal microscopy (IVCM) investigation provided supportive imaging. Paired t-tests were used and results reported with 95% confidence intervals (CI).</p><p><strong>Results: </strong>CDVA improved to 0.09 logMAR at 12 months (≈ 0.81 decimal; 95% CI: 0.10-0.08 logMAR; P < 0.001). Kmax decreased from 55.00 to 53.75 D (95% CI: 53.55-53.95 D; Δ =  - 1.25 D; P < 0.001), indicating ectasia stabilization. cBUT increased from 10.11 to 14.41 s (95% CI: 14.11-14.71; P < 0.01). OSDI decreased to 12.15 (95% CI: 11.65-12.65). Tear MMP-9 levels diminished from 64.79 to 16.15 ng/mL (P < 0.0001) and the proportion < 38.6 ng/mL reached 86.7% of the study cohort at 12 months. IVCM documented disappearance of inflammatory infiltrates. No postoperative persistent adverse events occurred.</p><p><strong>Conclusions: </strong>Epi-off ACXL stabilized ectasia, improving visual and ocular surface outcomes, markedly lowering tear MMP-9 levels. Although exploratory, these findings are consistent with a potential ocular surface anti-inflammatory and neuromodulatory role of ACXL, meriting validation in studies involving inflammatory DED beyond keratoconus.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"13 1","pages":"2"},"PeriodicalIF":4.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12763881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Recent advances and current challenges in suture and sutureless scleral fixation techniques for intraocular lens: a comprehensive review.","authors":"Han Sun, Caixia Wang, Hong Wu","doi":"10.1186/s40662-025-00468-8","DOIUrl":"10.1186/s40662-025-00468-8","url":null,"abstract":"","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"12 1","pages":"51"},"PeriodicalIF":4.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12742187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The physiological functions of OPN5m.","authors":"Jiali Ma, Sheikh Mizanur Rahaman, Yu Ohmura, Akihiro Yamanaka","doi":"10.1186/s40662-025-00467-9","DOIUrl":"10.1186/s40662-025-00467-9","url":null,"abstract":"<p><p>Opsin 5 (OPN5), also known as neuropsin, is a violet/ultraviolet (UV) light-sensitive G protein-coupled receptor (GPCR) conserved across vertebrates. Most mammals possess a single OPN5 gene (OPN5m), whereas non-mammalian species also express OPN5L1 and OPN5L2 with distinct molecular properties. Mammalian OPN5 (OPN5m) functions as a non-visual photopigment, expressed in diverse extra-retinal tissues including the skin, testis, and brain. Recent studies reveal species-specific signaling: human OPN5m preferentially activates Gq-mediated Ca²⁺ signaling, mouse OPN5m couples with Gi to reduce cyclic adenosine monophosphate (cAMP), avian OPN5m engages either Gi or Gq depending on species and tissue, and amphibian/fish OPN5m homologs primarily signal through Gq pathways. These diverse signaling modes underlie a wide range of physiological functions, such as circadian photoentrainment, thermoregulation, vascular development, myopia suppression, corneal wound healing, seasonal reproduction in birds, and light-dependent hormone release in fish pituitary. As modern artificial lighting and indoor lifestyles limit violet light exposure, insufficient OPN5m activation may contribute to emerging health issues, particularly the global rise in myopia. This review provides an updated overview of the molecular diversity, expression patterns, signaling mechanisms, and physiological roles of OPN5m across species, and discusses its potential clinical relevance in the context of changing light environments.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"12 1","pages":"48"},"PeriodicalIF":4.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic extranasal neurostimulation for dry eye disease: a 4-week stimulation and 6-week intermission regimen based on neural adaptation dynamics.","authors":"Xirenayi Zhuoruo, Yike Li, Yiting Sun, Chongyang Mu, Hongjing Sun, Tao Jiang, Chunyang Wang, Ning Wang, Xiuming Jin","doi":"10.1186/s40662-025-00466-w","DOIUrl":"10.1186/s40662-025-00466-w","url":null,"abstract":"<p><strong>Background: </strong>Extranasal neurostimulation is a promising therapy for aqueous-deficient dry eye (ADDE), but neural adaptation and optimal treatment duration remain poorly characterized. This study investigated duration-dependent neural sensitivity dynamics to formulate an optimized cyclic treatment regimen.</p><p><strong>Methods: </strong>In this prospective, randomized, open-label trial, 50 ADDE patients (Schirmer test: 2-5 mm) were assigned to 2-week or 4-week bilateral extranasal neurostimulation (twice daily). Participants were followed for 6 weeks post-treatment. The primary outcomes were neural sensitivity changes (Δ Schirmer) and short-term recovery (6 weeks after stimulation cessation). Secondary endpoints included subjective symptoms and objective signs.</p><p><strong>Results: </strong>Distinct neural adaptation patterns were observed. The 4-week group exhibited reversible neural adaptation, with an attenuated stimulation response at treatment completion (Δ Schirmer: 1.18 ± 4.17 mm, P = 0.051, Cohen's d = 0.28) that fully recovered after the 6-week intermission (post-stimulation Schirmer: 10.90 ± 7.29 mm vs. initial 12.42 ± 6.67 mm, P = 0.90, η²p = 0.092). This reversible adaptation was associated with sustained improvements in tear film stability [fluorescent tear film break-up time (FBUT): 6.27 ± 2.49 s vs. baseline 3.18 ± 1.36 s, P < 0.001, η²p = 0.235] and tear volume [tear meniscus height (TMH): 0.25 ± 0.05 mm vs. 0.19 ± 0.02 mm, P < 0.001, η²p = 0.26]. Critically, this reversible adaptation pattern was exclusive to the 4-week protocol. The 2-week protocol showed preserved stimulation responses during treatment (Δ Schirmer: 3.22 ± 6.54 mm, P < 0.001, Cohen's d = 0.49) but developed persistent neural hyposensitivity (8.76 ± 5.95 mm vs. initial 14.88 ± 8.69 mm, P < 0.001, η²p = 0.24). Its clinical benefits, though significant for FBUT (5.20 ± 2.81 s vs. baseline 2.86 ± 1.01 s, P < 0.001, η²p = 0.109), were less pronounced than in the 4-week group, and TMH showed no sustained increase (0.21 ± 0.04 mm vs. baseline 0.19 ± 0.03 mm, P = 0.11, η²p = 0.112). Both protocols demonstrated excellent safety and high patient satisfaction.</p><p><strong>Conclusions: </strong>Based on neural adaptation and recovery characteristics, a cyclic regimen of 4-week extranasal neurostimulation followed by a 6-week intermission is proposed as a potentially effective and sustainable clinical strategy for managing ADDE. This approach synchronizes treatment with the nervous system's intrinsic recovery cycles, addressing limitations of continuous stimulation paradigms.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (ChiCTR2500100816). Registered on 15 April 2025 (retrospectively registered), https://www.chictr.org.cn/bin/project/edit?pid=265888 .</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"12 1","pages":"49"},"PeriodicalIF":4.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}