{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:06:42Z","timestamp":1789391202897,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Juvenile X-linked retinoschisis (XLRS; OMIM 300839) is an inherited retinal disorder characterized by foveal schisis and variable visual impairment. There is no approved disease-modifying treatment, and evidence for interventions targeting XLRS-associated macular changes remains limited. Objective: To assess the feasibility, short-term safety, and descriptive anatomical and functional outcomes of subthreshold micropulse laser (SMPL) delivered at two wavelengths in two brothers with molecularly confirmed XLRS. Methods: Two brothers aged 31 and 33 years, both hemizygous for the RS1 variant c.589C&gt;T (p.Arg197Cys), underwent bilateral SMPL in a single session. Each right eye received 520-nm green SMPL (300 mW), and each left eye received 577-nm yellow SMPL (350 mW). The remaining parameters were matched, as follows: 100 \u00b5m spot diameter, 200-ms exposure, 5% duty cycle, zero spot spacing, and 400 confluent applications across the macula. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were assessed at baseline and at months 4 and 8. Results: Descriptively, individual-eye measurements showed heterogeneous anatomical and visual changes over follow-up. In patient 1, right-eye CFT changed from 485 to 466 and 153 \u00b5m, while BCVA changed from 3\/10 to 4\/10 and 6\/10 at months 4 and 8, respectively. Left-eye CFT changed from 281 to 209 and 209 \u00b5m, while BCVA changed from 2\/10 to 3\/10 and 4\/10. In patient 2, right-eye CFT changed from 488 to 250 and 453 \u00b5m, with BCVA changing from 2\/10 to 4\/10 and 4\/10. Left-eye CFT changed from 398 to 249 and 498 \u00b5m, with BCVA changing from 2\/10 to 3\/10 and 3\/10. No treatment-related adverse events or visible changes on infrared reflectance or fundus autofluorescence imaging were observed through month 8. Conclusions: A single bilateral SMPL session was feasible and was followed by transient or sustained anatomical and visual changes in these two patients. Because this uncontrolled case series included only two related participants and assigned wavelength by eye laterality with different power settings, it cannot establish efficacy or comparative wavelength superiority. The findings are hypothesis-generating and warrant evaluation in a prospective controlled study.<\/jats:p>","DOI":"10.3390\/jcm15187093","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"7093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subthreshold Micropulse Laser at Two Wavelengths for Juvenile X-Linked Retinoschisis: A Two-Patient Feasibility Study with 8-Month Follow-Up"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-0823","authenticated-orcid":false,"given":"Pietro Emanuele","family":"Napoli","sequence":"first","affiliation":[{"name":"Studio Oculistico Dr. Pietro Emanuele Napoli, 09014 Carloforte, Sardinia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3645-6005","authenticated-orcid":false,"given":"Matteo","family":"Nioi","sequence":"additional","affiliation":[{"name":"Forensic Medicine Unit, Department of Medical Sciences and Public Health, University of Cagliari, 09040 Cagliari, Sardinia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"ref_1","first-page":"169","article-title":"Congenital X-Linked Retinoschisis: An Updated Clinical Review","volume":"7","author":"Rao","year":"2018","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_2","first-page":"8824995","article-title":"A Female Case of X-Linked Retinoschisis with Macular Hole Bilaterally","volume":"2020","author":"Altun","year":"2020","journal-title":"Case Rep. Ophthalmol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kirkby, J., Halford, S., Shanks, M., Moore, A., Gait, A., Jenkins, L., Clouston, P., Patel, C.K., and Downes, S.M. (2023). A Carrier Female Manifesting an Unusual X-Linked Retinoschisis Phenotype Associated with the Pathogenic Variant c.266delA, p.(Tyr89LeufsTer37) in RS1, and Skewed X-Inactivation. Genes, 14.","DOI":"10.3390\/genes14061193"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/bjo.2005.078048","article-title":"Molecular Pathology of X-Linked Retinoschisis: Mutations Interfere with Retinoschisin Secretion and Oligomerisation","volume":"90","author":"Wang","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1001\/archopht.120.7.979","article-title":"Hereditary X-Linked Juvenile Retinoschisis: A Review of the Role of M\u00fcller Cells","volume":"120","author":"Mooy","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.1523\/JNEUROSCI.23-14-06030.2003","article-title":"Retinoschisin, a Photoreceptor-Secreted Protein, and Its Interaction with Bipolar and M\u00fcller Cells","volume":"23","author":"Reid","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/eye.2017.281","article-title":"Swept-Source Optical Coherence Tomography and Optical Coherence Tomography Angiography in Patients with X-Linked Retinoschisis","volume":"32","author":"Arias","year":"2018","journal-title":"Eye"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.2147\/OPTH.S114568","article-title":"Rebound Macular Edema Following Oral Acetazolamide Therapy for Juvenile X-Linked Retinoschisis in an Italian Family","volume":"10","author":"Galantuomo","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1167\/iovs.16-20078","article-title":"Carbonic Anhydrase Inhibitors for the Treatment of Cystic Macular Lesions in Children with X-Linked Juvenile Retinoschisis","volume":"57","author":"Verbakel","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.oret.2023.12.003","article-title":"Efficacy of Carbonic Anhydrase Inhibitors on Cystoid Fluid Collections and Visual Acuity in Patients with X-Linked Retinoschisis","volume":"8","author":"Hensman","year":"2024","journal-title":"Ophthalmol. Retin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1056\/NEJMoa2515953","article-title":"Subretinal Gene Therapy for X-Linked Retinoschisis","volume":"394","author":"Liang","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40123-017-0077-7","article-title":"A Review of Subthreshold Micropulse Laser and Recent Advances in Retinal Laser Technology","volume":"6","author":"Su","year":"2017","journal-title":"Ophthalmol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gaw\u0119cki, M. (2019). Micropulse Laser Treatment of Retinal Diseases. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020242"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"729792","DOI":"10.1155\/2015\/729792","article-title":"Sublethal Photothermal Stimulation with a Micropulse Laser Induces Heat-Shock Protein Expression in ARPE-19 Cells","volume":"2015","author":"Inagaki","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10034","DOI":"10.1038\/s41598-019-46515-y","article-title":"Sub-Threshold Micropulse Laser Treatment Reduces Inflammatory Biomarkers in Aqueous Humour of Diabetic Patients with Macular Edema","volume":"9","author":"Midena","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1097\/IAE.0000000000002356","article-title":"Changes of Aqueous Humor M\u00fcller-Cell Biomarkers in Patients with Diabetic Macular Edema after Subthreshold Micropulse Laser Treatment","volume":"40","author":"Midena","year":"2020","journal-title":"Retina"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1007\/s12325-017-0559-y","article-title":"A Review of Subthreshold Micropulse Laser for Treatment of Macular Disorders","volume":"34","author":"Scholz","year":"2017","journal-title":"Adv. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"525","DOI":"10.2147\/OPTH.S232202","article-title":"532-nm Subthreshold Micropulse Laser for the Treatment of Chronic Central Serous Retinopathy","volume":"14","author":"Sousa","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1097\/ICB.0000000000001472","article-title":"X-Linked Juvenile Retinoschisis Associated with an RS1 In-Frame Deletion and Bilateral Central Serous Chorioretinopathy","volume":"18","author":"Zenteno","year":"2024","journal-title":"Retin. Cases Brief Rep."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7093\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:49:22Z","timestamp":1789390162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,13]]},"references-count":19,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187093"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187093","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,13]]}}}