{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:44Z","timestamp":1785432404506,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore National Medical Research Council Clinician Scientist Award Grant","award":["MOHCSAINV24jul-005"],"award-info":[{"award-number":["MOHCSAINV24jul-005"]}]},{"award":["MOHCSAINV24jul-005"],"award-info":[{"award-number":["MOHCSAINV24jul-005"]}],"id":[{"id":"https:\/\/ror.org\/04x3cxs03","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Clinician Scientist Individual Research Grant","award":["CSIRG24jul-010"],"award-info":[{"award-number":["CSIRG24jul-010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significanc: Neuropathic corneal pain is a debilitating condition characterized by ocular pain disproportionate to clinical signs, often resulting from peripheral and central sensitization of the corneal somatosensory pathway. Emerging evidence suggests that chronic involuntary muscle contraction in blepharospasm may lead to irritation of trigeminal afferents and corneal neurogenic inflammation, potentially predisposing patients to neuropathic corneal pain. Given its debilitating nature, early recognition can prevent the progression of neuropathic sequelae. This study examines the potential role of blepharospasm as a predisposing factor contributing to neuropathic corneal pain. Case Presentation: This retrospective case series describes three cases (median age: 50 years) of neuropathic corneal pain in association with blepharospasm and their clinical course following multimodal treatment over a median follow-up period of one year. Ocular surface was evaluated using slit-lamp biomicroscopy, while corneal nerve structure and morphology were assessed with in vivo confocal microscopy. All the three subjects presented with minimal ocular surface staining but disproportionate ocular pain characterized by burning sensation and photophobia. Proparacaine challenge testing was performed to determine the subtype of neuropathic corneal pain. Pain symptoms and quality of life were evaluated using the Ocular Pain Assessment Survey and Ocular Surface Disease Index questionnaires. In vivo confocal microscopy demonstrated characteristic corneal nerve abnormalities including reduced corneal nerve density, increased nerve tortuosity, and the presence of microneuromas. Treatment included oral Pregabalin or Gabapentin, topical lubricants, Cyclosporine 0.05% (1 case), and 20% autologous serum eye drops (1 case). Two of the three cases received four to five injections of botulinum toxin for blepharospasm, whereas one had undergone a single injection prior to review. All patients also received weekly periorbital quantum molecular resonance electrotherapy for two months. Improvements were observed across multiple domains of the Ocular Pain Assessment Survey and Ocular Surface Disease Index evaluation, including ocular pain, photophobia, non-ocular pain, and quality-of-life measures following multimodal treatment. The co-existence of blepharospasm and neuropathic corneal pain observed in our cases supports a possible association between chronic periocular muscle hyperactivity and corneal nociceptor sensitization. Proposed mechanisms include chronic trigeminal nerve irritation, neurogenic inflammation, and sensitization mediated by pro-inflammatory neuropeptides. Multimodal treatment targeting both motor hyperactivity and neuropathic pain pathways appeared to provide symptomatic relief, including the use of quantum molecular resonance electrotherapy, which might modulate pain pathways, block nociceptor neurotransmission, and accelerate corneal nerve regeneration. Given the complexity of the neural pathways responsible for ocular discomfort, further studies are required to elucidate the relationship between neuropathic corneal pain and blepharospasm in larger cohorts, as well as refine existing therapeutic approaches, including evaluating the therapeutic role of electrotherapy. Conclusions: Blepharospasm may represent a potential predisposing factor of neuropathic corneal pain. Early recognition and concurrent treatment of blepharospasm and neuropathic corneal pain can effectively relieve symptoms and improve quality of life. Adopting a multimodal treatment approach is therefore recommended.<\/jats:p>","DOI":"10.3390\/diagnostics16131974","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:14:12Z","timestamp":1782375252000},"page":"1974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropathic Corneal Pain and Blepharospasm: A Case Series"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhang Zhe","family":"Thia","sequence":"first","affiliation":[{"name":"Regenerative Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-0665","authenticated-orcid":false,"given":"Aya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Yu","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle Xin Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3986-6552","authenticated-orcid":false,"given":"Louis","family":"Tong","sequence":"additional","affiliation":[{"name":"Cornea & External Eye Disease, Singapore National Eye Centre, Singapore 169856, Singapore"},{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-0382","authenticated-orcid":false,"given":"Yu-Chi","family":"Liu","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"},{"name":"Cornea & External Eye Disease, Singapore National Eye Centre, Singapore 169856, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3109\/08820538.2015.1114853","article-title":"Understanding Neuropathic Corneal Pain\u2013Gaps and Current Therapeutic Approaches","volume":"31","author":"Goyal","year":"2016","journal-title":"Semin. 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