{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:38:06Z","timestamp":1772858286107,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recep Tayyip Erdogan University Development","award":["02025008022720"],"award-info":[{"award-number":["02025008022720"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Although methylphenidate is a first-line pharmacological agent in the treatment of Attention-Deficit\/Hyperactivity Disorder (ADHD), its long-term effects on ocular tissues, particularly the corneal endothelium, remain poorly understood. Given the cornea\u2019s metabolic sensitivity, subclinical changes may occur even in the absence of overt ophthalmologic symptoms. This study aims to evaluate the impact of six-month methylphenidate treatment on corneal endothelial morphology and intraocular pressure (IOP) in pediatric patients with ADHD. Methods: This prospective observational study included 100 treatment-naive children with ADHD and 100 age- and sex-matched healthy controls. All participants underwent comprehensive ophthalmologic assessment at baseline. In the ADHD group, follow-up evaluations were performed after six months of methylphenidate therapy. Endothelial cell density (ECD), average cell area (AVE), standard deviation (SD), coefficient of variation (CV), hexagonality index (6A), central corneal thickness (CCT), and IOP were measured using specular microscopy and corneal topography. ADHD symptom severity was evaluated using the Turgay DSM-IV-Based Rating Scale. Results: Significant reductions in ECD and increases in CCT, CV, AVE, and SD were observed following treatment (p &lt; 0.001). IOP also showed a statistically significant increase while remaining within normal physiological limits. Weak but significant correlations were found between inattention scores and ECD (r = 0.222), and between inattention and corneal volume (r = \u22120.248). Conclusions: Chronic methylphenidate use may be associated with measurable changes in corneal endothelial microstructure and IOP in children with ADHD. These findings highlight the need for routine ophthalmologic monitoring during stimulant therapy and underscore the importance of further large-scale, long-term studies exploring the neuro-ophthalmologic implications of pediatric psychopharmacological treatment.<\/jats:p>","DOI":"10.3390\/diagnostics15182368","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T09:32:32Z","timestamp":1758187952000},"page":"2368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alterations in Corneal Morphology and Thickness Associated with Methylphenidate Treatment in Children with Attention-Deficit\/Hyperactivity Disorder"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-8190","authenticated-orcid":false,"given":"Fatma","family":"Sumer","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-0043","authenticated-orcid":false,"given":"Merve","family":"Yazici","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1176\/appi.ps.20220334","article-title":"DSM-5-TR: Rationale, Process, and Overview of Changes","volume":"74","author":"First","year":"2023","journal-title":"Psychiatr. Serv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15020","DOI":"10.1038\/nrdp.2015.20","article-title":"Attention-deficit\/hyperactivity disorder","volume":"1","author":"Faraone","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3390\/pediatric13030050","article-title":"Does Methylphenidate Work in Children and Adolescents with Attention Deficit Hyperactivity Disorder?","volume":"13","author":"Ribeiro","year":"2021","journal-title":"Pediatr. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.eye.6702240","article-title":"Visual function and ocular features in children and adolescents with attention deficit hyperactivity disorder, with and without treatment with stimulants","volume":"21","author":"Aring","year":"2007","journal-title":"Eye"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/cap.2022.0074","article-title":"Short-Term Vision-Related Ocular Side Effects of Treatment with Dexmethylphenidate for Attention-Deficit\/Hyperactivity Disorder","volume":"32","author":"Fainberg","year":"2022","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/15569527.2024.2303442","article-title":"Evaluation of corneal endothelial cell morphology off and on treatment by specular microscopy in children and adolescents with attention deficit hyperactivity disorder","volume":"43","author":"Koc","year":"2024","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1097\/ICO.0000000000001941","article-title":"Corneal Edema Associated With Systemic Dopaminergic Agents","volume":"38","author":"Mancera","year":"2019","journal-title":"Cornea"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.4103\/ijo.IJO_2966_21","article-title":"Does methylphenidate treatment affect functional and structural ocular parameters in patients with attention deficit hyperactivity disorder?\u2014A prospective, one year follow-up study","volume":"70","author":"Atilla","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/pch\/pxz012","article-title":"Visual disorders with psychostimulants: A paediatric case report","volume":"24","author":"Soyer","year":"2019","journal-title":"Paediatr. Child Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jaapos.2015.04.005","article-title":"The effects of methylphenidate on refraction and anterior segment parameters in children with attention deficit hyperactivity disorder","volume":"19","author":"Noval","year":"2015","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S1726-4901(09)70335-1","article-title":"Methylphenidate (Ritalin)-associated Cataract and Glaucoma","volume":"69","author":"Lu","year":"2006","journal-title":"J. Chinese Med. Assoc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s10792-025-03471-z","article-title":"An examination of the ocular effects of methylphenidate used in children and adolescents diagnosed with attention-deficit hyperactivity disorder","volume":"45","author":"Uzlu","year":"2025","journal-title":"Int. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.jaapos.2013.06.005","article-title":"The possible association of attention deficit hyperactivity disorder with undiagnosed refractive errors","volume":"17","author":"Fabian","year":"2013","journal-title":"J. AAPOS"},{"key":"ref_14","unstructured":"Turgay, A. (1994). Disruptive Behavior Disorders Child and Adolescent Screening and Rating Scales for Children, Adolescents, Parents and Teachers, Integrative Therapy Institute Publication."},{"key":"ref_15","first-page":"132","article-title":"An attempt to develop a test battery for attention deficit hyperactivity disorder and disruptive behavioral disorders","volume":"8","author":"Ercan","year":"2001","journal-title":"J. Child Adolesc. Ment. Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4103\/ijo.IJO_574_20","article-title":"Specular microscopy in clinical practice","volume":"69","author":"Chaurasia","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/bjo.84.7.692","article-title":"Reassessment of the corneal endothelial cell organisation in children","volume":"84","author":"Doughty","year":"2000","journal-title":"Br. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.bbi.2017.10.016","article-title":"Impact of developmental exposure to methylphenidate on rat brain\u2019s immune privilege and behavior: Control versus ADHD model","volume":"68","author":"Cardoso","year":"2018","journal-title":"Brain. Behav. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.2174\/157015908787386069","article-title":"Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate","volume":"6","author":"Engert","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wu, F., Zhao, Y., and Zhang, H. (2022). Ocular Autonomic Nervous System: An Update from Anatomy to Physiological Functions. Vision, 6.","DOI":"10.3390\/vision6010006"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"804","DOI":"10.14348\/molcells.2014.0167","article-title":"Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons","volume":"37","author":"Kim","year":"2014","journal-title":"Mol. Cells"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jtos.2024.08.003","article-title":"Evolution of therapeutic strategy based on oxidant-antioxidant balance for fuchs endothelial corneal dystrophy","volume":"34","author":"Wu","year":"2024","journal-title":"Ocul. Surf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.euroneuro.2018.12.007","article-title":"Effect of chronic methylphenidate treatment on hippocampal neurovascular unit and memory performance in late adolescent rats","volume":"29","author":"Cardoso","year":"2019","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110623","DOI":"10.1016\/j.neuropharm.2025.110623","article-title":"Methylphenidate triggers retinal oxidative stress and mitochondrial dysfunction under physiological conditions but has beneficial effects in inflammatory settings","volume":"279","author":"Sanches","year":"2025","journal-title":"Neuropharmacology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1177\/0960327120940357","article-title":"Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy","volume":"40","author":"Kong","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.preteyeres.2010.03.001","article-title":"Preservatives in eyedrops: The good, the bad and the ugly","volume":"29","author":"Baudouin","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5301\/ejo.5000220","article-title":"Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients","volume":"23","author":"Rossi","year":"2013","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/sj.eye.6700559","article-title":"Biology of the corneal endothelium in health and disease","volume":"17","author":"Bourne","year":"2003","journal-title":"Eye"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.exer.2011.08.014","article-title":"Proliferative capacity of corneal endothelial cells","volume":"95","author":"Joyce","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0161-6420(82)34746-6","article-title":"The corneal endothelium. Normal and pathologic structure and function","volume":"89","author":"Waring","year":"1982","journal-title":"Ophthalmology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1037\/0021-843X.111.2.279","article-title":"The persistence of attention-deficit\/hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder","volume":"111","author":"Barkley","year":"2002","journal-title":"J. Abnorm. Psychol."},{"key":"ref_32","first-page":"105","article-title":"What We Know About ADHD and Driving Risk: A Literature Review, Meta-Analysis and Critique","volume":"15","author":"Jerome","year":"2006","journal-title":"J. Can. Acad. Child Adolesc. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1017\/S003329170500471X","article-title":"The age-dependent decline of attention deficit hyperactivity disorder: A meta-analysis of follow-up studies","volume":"36","author":"Faraone","year":"2006","journal-title":"Psychol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S2215-0366(18)30269-4","article-title":"Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis","volume":"5","author":"Cortese","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"P184","DOI":"10.1016\/j.ophtha.2017.09.032","article-title":"Pediatric Eye Evaluations Preferred Practice Pattern\u00ae: I. Vision Screening in the Primary Care and Community Setting; II. Comprehensive Ophthalmic Examination","volume":"125","author":"Wallace","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e20192528","DOI":"10.1542\/peds.2019-2528","article-title":"Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit\/hyperactivity disorder in children and adolescents","volume":"144","author":"Wolraich","year":"2019","journal-title":"Pediatrics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/09273970500455436","article-title":"The relationship between convergence insufficiency and ADHD","volume":"13","author":"Granet","year":"2005","journal-title":"Strabismus"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1097\/00006324-200312000-00014","article-title":"Validity and Reliability of the Revised Convergence Insufficiency Symptom Survey in Children Aged 9 to 18 Years","volume":"80","author":"Borsting","year":"2003","journal-title":"Optom. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1167\/iovs.05-1139","article-title":"The balance between corneal transparency and edema: The proctor lecture","volume":"47","author":"Edelhauser","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1113\/jphysiol.1972.sp009737","article-title":"The location of the fluid pump in the cornea","volume":"221","author":"Maurice","year":"1972","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1001\/archopht.126.10.1336","article-title":"Randomized clinical trial of treatments for symptomatic convergence insufficiency in children","volume":"126","author":"Scheiman","year":"2008","journal-title":"Arch. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e1141","DOI":"10.1111\/aos.14172","article-title":"Visual information processing skills are associated with academic performance in Grade 2 school children","volume":"97","author":"Hopkins","year":"2019","journal-title":"Acta Ophthalmol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/18\/2368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:34Z","timestamp":1760035654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/18\/2368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":42,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15182368"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15182368","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]}}}