Conjunctival Intraepithelial Neoplasia (CIN)
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Conjunctival Intraepithelial Neoplasia (CIN)

Conjunctival Intraepithelial Neoplasia (CIN) is classified as a rare type of ocular surface disease that is characterized by the abnormal growth of epithelial dysplastic cells in the conjunctiva. Protheragen provides diagnostics and therapeutics development services for CIN as well as for disorders of the ocular surface using advanced technologies and their expertise.

Overview of Conjunctival Intraepithelial Neoplasia (CIN)

Conjunctival Intraepithelial Neoplasia (CIN) pertains to a condition that is pathologically characterized by a pre-malignant condition with dysplastic developments restricted to the epithelial level of the conjunctiva. It covers a spectrum of lesions from mild dysplastic changes up to carcinoma in situ (CIS), which, if untreated, can progress to invasive squamous cell carcinoma. CIN is regarded as the most prevalent tumor of the ocular surface, with its incidence being roughly 1.9 per 100,000 population.

Pathologically, primary and recurrent pterygium presented fibrovascular tissue, basophilic solar elastosis, fibrosis, and chronic inflammation.Fig.1 Histopathological case of CIN. (Hung K. H., et al., 2020)

The disease often starts at the limbus and can lead to corneal and fornix involvement. Among the risk factors for CIN are overexposure to Ultraviolet B (UV-B) including outdoor work, light skin, weak immunity, and Human Papillomavirus (HPV) especially types 16 and 18.

Diagnostic Methods for Conjunctival Intraepithelial Neoplasia (CIN)

  • Histopathological Examination
    The grading for CIN histopathology is based on the degree of dysplastic alterations within the epithelium which ranges from mild dysplasia (lower third of the epithelial layer) to carcinoma in situ (full thickness). This method is accurate, but it is invasive, and diagnosis depends heavily on the pathologist's opinion.
  • Cytological Techniques
    Methods such as impression and impression cytology are non-invasive cytological techniques that evaluate the spare surface cells of the eye with the aim of identifying any dysplastic alterations. Even though these techniques do not supplant histopathology, they offer quick, minimally invasive sorting for CIN where biopsy is not immediately possible.
  • Immunohistochemical Staining
    The examined markers HIF-1α and HIF-2α were underexpressed in CINs and thus not helpful in providing a diagnosis. In contrast, ProExC could serve as a prognostic marker as a greater intensity of staining was associated with recurrence and progression toward squamous cell carcinoma.

Therapeutics Development for Conjunctival Intraepithelial Neoplasia (CIN)

Topical Chemotherapy

Agents such as mitomycin C and 5-fluorouracil are widely utilised in the management of CIN. Mitomycin C inhibits the synthesis of DNA, effectively treating dysplastic cells with minimal systemic side effects. 5-Fluorouracil is a pro-drug that inhibits thymidylate synthetase and consequently inhibits DNA synthesis. Their potent effects, delivered directly to the skin, ensure that the target lesion is treated; however, prolonged use can lead to inflammation of the ocular surface.

Interferon Therapy

Interferon alpha-2b (IFN-α2b) is an effective therapeutic for CIN when used as a subconjunctival injection or when it is applied topically. It has many attributes such as efficacy against proliferation, immune enhancement, and activation of cytotoxic cells for dysplastic tissue. Compared to the typical chemotherapy therapeutics, IFN-α2b has significantly reduced side effects. One case report described the use of IFN-α2b for a conjunctival tumour which resulted in complete resolution and sustained remission over a year.

Our Services

At Protheragen, we provide diagnostic and therapeutic services for Conjunctival Intraepithelial Neoplasia or CIN. We have vast knowledge and experience when it comes to CIN therapeutics, including but not limited to, early detection, diagnosis, and novel therapeutic development.

Diagnostics Development

  • Karyotype Analysis Service
  • Omics Analysis Service
  • Biomarker Development Service
  • Artificial Intelligence Service

Therapeutic Development

  • Small Molecule Drug
  • Cell Therapy
  • Gene Therapy
  • Therapeutic Antibody
  • Therapeutic Peptide
  • Therapeutic Protein

Preclinical Research

  • Pharmacodynamics Study Services
  • Pharmacokinetics Study Services
  • Drug Safety Evaluation Services

Disease Models

  • DMBA Induction Mouse Models
  • Surgical Induction Non-human Primate Models
  • Human Papillomavirus Infection Rabbit Models
  • 3D Cell Cultures

Protheragen's preclinical research services are designed to support the development of novel diagnostics and therapeutics for CIN. Our state-of-the-art facilities and expert team provide comprehensive support for preclinical studies, from in vitro assays to animal models. If you are interested in our services, please feel free to contact us.

References

  • Hung, Kuo-Hsuan, et al. "Clinical demographics of pterygium excision and prevalence of conjunctival intraepithelial neoplasia: a 15-year review." International Ophthalmology 40 (2020): 1781-1788.
  • Nuessle, Simone, et al. "HIF-1α, HIF-2α, and ProExC: diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia?." Graefe's Archive for Clinical and Experimental Ophthalmology 258 (2020): 2023-2030.