{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:33:22Z","timestamp":1771047202210,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vision"],"abstract":"<jats:p>Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive syndrome caused by loss-of-function mutations in the Neurotrophic Tyrosine Kinase Receptor 1 gene, characterized by recurrent episodes of infections and unexplained fever, anhidrosis, absence of reactions to noxious stimuli, intellectual disability, self-mutilating behaviors, and damage to many body organs, including the eyes. Main text: We systematically searched the Medline\/PubMed, Scopus, and Web of Science databases from their inception until March 2025 for papers describing the clinical manifestations of patients with CIPA. The inclusion criterion was papers reporting ocular manifestations of patients diagnosed with CIPA. We excluded non-English papers or those reporting ocular manifestations of patients diagnosed with syndromes other than CIPA. Also, we excluded review articles, clinical trials, gray literature, or any paper that did not report ocular manifestations of patients with CIPA or that reported patients with previous ocular surgeries. Out of 6243 studies, 28 were included in the final analysis, comprising 118 patients. The mean age was 7.37 years, and males represented 63.5% (n = 75). Of the patients, fifty-six had bilateral ocular manifestations. The most common ocular manifestations were the absence of corneal reflex in 56 patients (47.5%, bilateral in 56), whereas corneal ulcerations were the second most common manifestation in 46 patients (38.98%, bilateral in 8), followed by corneal opacity in 32 patients (27.11%, bilateral in 19). Topical lubricants, topical antibiotics, and lateral tarsorrhaphy were common management modalities for these patients. Absent corneal sensitivity, corneal ulcers, and corneal opacities, among other manifestations, are common ocular presentations in patients with CIPA. Conclusions: Self-mutilation, intellectual disability, decreased lacrimation, and absence of the corneal reflex are factors that may explain the development of these manifestations in CIPA. The early detection of these manifestations can improve patient conditions and prevent further complications, in addition to helping to guide the clinical diagnosis of CIPA in these patients.<\/jats:p>","DOI":"10.3390\/vision9030062","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T14:55:18Z","timestamp":1753109718000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ocular Manifestations in Congenital Insensitivity to Pain with Anhidrosis: A Window into a Rare Syndrome"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5363-8759","authenticated-orcid":false,"given":"Mohammed","family":"Baker","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0250-8938","authenticated-orcid":false,"given":"Kenda","family":"Abedal-Kareem","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4329-2977","authenticated-orcid":false,"given":"Sadeen","family":"Eid","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Alkhawaldeh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahya","family":"Albashaireh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihan","family":"Joulani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Bani Amer","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethar","family":"Hazaimeh","sequence":"additional","affiliation":[{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"},{"name":"Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center, Hidaka, Saitama 320-1298, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar F.","family":"Jbarah","sequence":"additional","affiliation":[{"name":"Medical Researcher, Neuropedia for Training and Scientific Research, Amman 11194, Jordan"},{"name":"Department of Cerebrovascular Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama 320-1298, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelwahab","family":"Aleshawi","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rami","family":"Al-Dwairi","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/brain\/106.2.373","article-title":"Not \u201cindifference to pain\u201d but varieties of hereditary sensory and autonomic neuropathy","volume":"106","author":"Dyck","year":"1983","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/ajmg.a.35803","article-title":"Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan","volume":"161","author":"Haga","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_3","first-page":"91","article-title":"Mutations in the trka\/high affinity ngf receptor gene in patients with congenital insensitivity to pain with anhidrosis","volume":"42","author":"Indo","year":"1997","journal-title":"Jpn. J. Hum. 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