Ocular Surface Squamous Neoplasia: Epidemiology, Dıagnosis, And Evolving Therapeutic Strategies
Özet
Oküler yüzey skuamöz neoplazisi (OSSN), konjonktival intraepitelyal neoplaziden invaziv skuamöz hücreli karsinoma kadar uzanan ve oküler yüzeyin en sık görülen melanom dışı malignitesi olan bir spektrumu ifade eder. İnsidans, coğrafyaya göre değişir; ekvator kuşağında ultraviyole maruziyeti ve immünsupresyon (özellikle HIV) nedeniyle belirgindir. Onkojenik HPV enfeksiyonu, kronik oküler yüzey inflamasyonu ve kseroderma pigmentozum gibi DNA onarım bozuklukları da riski artırır. Klinik olarak OSSN genellikle limbal bölgede tek taraflı, jelatinöz, lökoplazik veya papilliform lezyon şeklinde, besleyici damarlarla birlikte görülür ve pterjiyum ya da kronik konjonktiviti taklit edebilir. Tanıda biomikroskopi ve histopatoloji esastır; impresyon sitolojisi, ön segment OKT ve in vivo konfokal mikroskopi, invaziv olmayan saptama ve tedavi izlemine katkı sağlar. Yönetim; yayılım ve histolojiye göre bireyselleştirilir: Lokalize olgularda kriyoterapi ile “dokunmasız” eksizyon temel yaklaşımdır ve yüzey rekonstrüksiyonu ile tamamlanabilir. Topikal interferon-α2b, mitomisin-C ve 5-florourasil; birincil, neoadjuvan veya adjuvan olarak etkilidir ve interferon genellikle en iyi tolere edilen seçenektir. İleri invazyon enükleasyon veya ekzenterasyon gerektirebilir; seçilmiş olgularda radyoterapi düşünülür. Nüks riski nedeniyle uzun dönem izlem şarttır. Yapay zekâ destekli görüntüleme, moleküler profilleme (p16/HPV, Ki-67, p53) ve kontrol noktası inhibitörleri, tanı ve tedavi doğruluğunu artırma potansiyeli taşır.
Referanslar
Lee, G. A., & Hirst, L. W. (1995). Ocular surface squamous neoplasia. Survey of Ophthalmology, 39(6), 429–450. https://doi.org/10.1016/S0039-6257(05)80105-2
Shields, C. L., & Shields, J. A. (2004). Ocular surface squamous neoplasia: The 2004 review. Survey of Ophthalmology, 49(1), 3–24. https://doi.org/10.1016/j.survophthal.2003.10.008
Gichuhi, S., Sagoo, M. S., Weiss, H. A., & Burton, M. J. (2013). Epidemiology of ocular surface squamous neoplasia in Africa. Tropical Medicine & International Health, 18(12), 1424–1433. https://doi.org/10.1111/tmi.12203
Basti, S., & Macsai, M. S. (2003). Ocular surface squamous neoplasia: A review. Cornea, 22(7), 687–704. https://doi.org/10.1097/00003226-200310000-00015
McKelvie, P. A., Daniell, M., McNab, A., Loughnan, M., & Santamaria, J. D. (2002). Squamous cell carcinoma of the conjunctiva: A series of 26 cases. British Journal of Ophthalmology, 86(2), 168–173. https://doi.org/10.1136/bjo.86.2.168
Patel, U., Karp, C. L., & Dubovy, S. R. (2021). Update on the management of ocular surface squamous neoplasia. Current Ophthalmology Reports, 9(1), 7–15. https://doi.org/10.1007/s40135-020-00260-y
Gichuhi, S., Macharia, E., Kabiru, J., Zindamoyen, A. M., Rono, H., Ollando, E., Wachira, J., Munene, R., Maina, J., Onyuma, T., Sagoo, M. S., Weiss, H. A., & Burton, M. J. (2016). Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: A randomised, double-blind, placebo-controlled trial. The Lancet Global Health, 4(6), e378–e385. https://doi.org/10.1016/S2214-109X(16)30052-3
Newton, R. (1996). A review of the aetiology of squamous cell carcinoma of the conjunctiva. British Journal of Cancer, 74(10), 1511–1513. https://doi.org/10.1038/bjc.1996.581
Gichuhi, S., Macharia, E., Kabiru, J., Zindamoyen, A. M., Rono, H., Ollando, E., Wachira, J., Munene, R., Onyuma, T., Jaoko, W. G., Sagoo, M. S., Weiss, H. A., & Burton, M. J. (2016). Risk factors for ocular surface squamous neoplasia in Kenya: A case-control study. Tropical Medicine & International Health, 21(12), 1522–1530. https://doi.org/10.1111/tmi.12792
Ateenyi-Agaba, C., Franceschi, S., Wabwire-Mangen, F., Arslan, A., Othieno, E., Binta-Kahwa, J., van Doorn, L. J., Kleter, B., Quint, W., & Weiderpass, E. (2010). Human papillomavirus infection and squamous cell carcinoma of the conjunctiva. British Journal of Cancer, 102(2), 262–267. https://doi.org/10.1038/sj.bjc.6605466
Galor, A., Karp, C. L., Chhabra, S., Barnes, S., & Alfonso, E. C. (2010). Topical interferon alpha 2b eye-drops for treatment of ocular surface squamous neoplasia: A dose comparison study. British Journal of Ophthalmology, 94(5), 551–554. https://doi.org/10.1136/bjo.2008.153197
Kalamkar, C., & Radke, N. (2016). Bilateral ocular surface squamous neoplasia in a child with xeroderma pigmentosum. BMJ Case Reports, 2016, bcr2016215814. https://doi.org/10.1136/bcr-2016-215814
Gichuhi, S., Ohnuma, S., Sagoo, M. S., & Burton, M. J. (2014). Pathophysiology of ocular surface squamous neoplasia. Experimental Eye Research, 129, 172–182. https://doi.org/10.1016/j.exer.2014.10.015
El-Abaseri, T. B., Putta, S., & Hansen, L. A. (2006). Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis, 27(2), 225–231. https://doi.org/10.1093/carcin/bgi220
Kiire, C. A., & Dhillon, B. (2006). The aetiology and associations of conjunctival intraepithelial neoplasia. British Journal of Ophthalmology, 90(1), 109–113. https://doi.org/10.1136/bjo.2005.077305
McGee-Avila, J. K., & Mbulaiteye, S. M. (2024). Conjunctival squamous cell carcinoma in people with HIV in South Africa: Time to renew efforts for novel oncogenic virus discovery? Journal of the National Cancer Institute, 116(2), 186–188. https://doi.org/10.1093/jnci/djad147
Birkholz, E. S., Goins, K. M., Sutphin, J. E., Kitzmann, A. S., & Wagoner, M. D. (2011). Treatment of ocular surface squamous cell intraepithelial neoplasia with and without mitomycin C. Cornea, 30(1), 37–41. https://doi.org/10.1097/ICO.0b013e3181d43ac6
Chauhan, S., Sen, S., Sharma, A., Tandon, R., Kashyap, S., Pushker, N., Vanathi, M., & Sharma, N. (2014). American Joint Committee on Cancer staging and clinicopathological high-risk predictors of ocular surface squamous neoplasia: A study from a tertiary eye center in India. Archives of Pathology & Laboratory Medicine, 138(11), 1488–1494. https://doi.org/10.5858/arpa.2013-0353-OA
Karp, C. L., Moore, J. K., & Rosa, R. H., Jr. (2001). Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b. Ophthalmology, 108(6), 1093–1098. https://doi.org/10.1016/S0161-6420(01)00577-2
Nolan, G. R., Hirst, L. W., Wright, R. G., & Bancroft, B. J. (1994). Application of impression cytology to the diagnosis of conjunctival neoplasms. Diagnostic Cytopathology, 11(3), 246–249. https://doi.org/10.1002/dc.2840110309
Nanji, A. A., Sayyad, F. E., Galor, A., Dubovy, S., & Karp, C. L. (2015). High-resolution optical coherence tomography as an adjunctive tool in the diagnosis of corneal and conjunctival pathology. The Ocular Surface, 13(3), 226–235. https://doi.org/10.1016/j.jtos.2015.02.001
Alzahrani, Y. A., Alahmadi, A. S., Alahmadi, A. M., Alsarhani, W. K., & Alzahrani, Y. M. (2022). Diagnostic tools for ocular surface squamous neoplasia: A review. Frontiers in Oncology, 12, 955449. https://doi.org/10.3389/fonc.2022.955449
Napora, C., Cohen, E. J., Genvert, G. I., Presson, A. C., Arentsen, J. J., Eagle, R. C., & Laibson, P. R. (1990). Factors associated with conjunctival intraepithelial neoplasia: A case-control study. Ophthalmic Surgery, 21(1), 27–30. https://doi.org/10.3928/1542-8877-19900101-07
El-Hadad, C., Zaghloul, M. S., Farid, M., Khafagy, W., & Ezzat, A. (2014). Conjunctival squamous cell carcinoma: Clinicopathological characteristics, treatment outcomes, and prognostic factors. Clinical Ophthalmology, 8, 79–86. https://doi.org/10.2147/OPTH.S54588
Mittal, R., Rathore, A., Meel, R., Singh, P., Dahiya, R., Pushker, N., Bajaj, M. S., Sen, S., & Kashyap, S. (2019). Ocular surface squamous neoplasia: An overview of pathogenesis, molecular biology, clinical features, diagnosis and management. Indian Journal of Ophthalmology, 67(9), 1389–1399. https://doi.org/10.4103/ijo.IJO_1240_19
Nagata, K., Maruyama, F., Araki-Sasaki, K., Nakajima, A., & Ogata, N. (2014). Immunohistochemical expression of EGFR and Ki-67 in ocular surface squamous neoplasia. PLOS ONE, 9(4), e93164. https://doi.org/10.1371/journal.pone.0093164
Galor, A., Feuer, W., Lee, Y., Dubovy, S., Kovalyshyn, I., & Karp, C. L. (2018). Tumor size and clinical outcomes for ocular surface squamous neoplasia: A proposal for the American Joint Committee on Cancer staging system. Ophthalmology, 125(6), 859–868. https://doi.org/10.1016/j.ophtha.2017.12.020
Erie, J. C., Campbell, R. J., & Liesegang, T. J. (1986). Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology, 93(2), 176–183. https://doi.org/10.1016/S0161-6420(86)33764-3
Shields, J. A., Shields, C. L., & De Potter, P. (1997). Surgical approach to conjunctival tumors. Archives of Ophthalmology, 115(6), 808–815. https://doi.org/10.1001/archopht.1997.01100150810025
Tabin, G., Levin, S., Snibson, G., Loughnan, M., Taylor, H., & McCarty, C. (2005). Late recurrences and the necessity for long-term follow up in corneal and conjunctival intraepithelial neoplasia. Cornea, 24(3), 297–300. https://doi.org/10.1097/01.ico.0000151496.93372.64
Kiire, C. A., Srinivasan, S., & Karp, C. L. (2010). Ocular surface squamous neoplasia. International Ophthalmology Clinics, 50(3), 35–46. https://doi.org/10.1097/IIO.0b013e3181e246e5
El-Hadad, C., Abdelbaky, S. H., Eltanamly, R. M., & Ezzat, W. F. (2021). Prognostic factors for orbital exenteration, local recurrence, metastasis, and death from disease in conjunctival squamous cell carcinoma. Ophthalmic Plastic and Reconstructive Surgery, 37(3), 279–285. https://doi.org/10.1097/IOP.0000000000001814
Nanji, A. A., Sayyad, F. E., & Karp, C. L. (2013). Topical chemotherapy for ocular surface squamous neoplasia. Current Opinion in Ophthalmology, 24(4), 336–342. https://doi.org/10.1097/ICU.0b013e3283622a13
Sripawadkul, W., Reyes-Capo, D., Zein, M., Wylegala, A., Albayyat, G., Galor, A., & Karp, C. L. (2023). Long-term study of topical interferon α-2b eye drops as primary treatment of ocular surface squamous neoplasia. The Ocular Surface, 28, 108–114. https://doi.org/10.1016/j.jtos.2022.12.009
Frucht-Pery, J., Rozenman, Y., & Pe’er, J. (1997). Mitomycin C therapy for corneal intraepithelial neoplasia. American Journal of Ophthalmology, 124(3), 303–309. https://doi.org/10.1016/S0002-9394(14)70814-6
Joag, M. G., Sise, A., Murillo, J. C., Sayed-Ahmed, I. O., Wong, J. R., Bouchard, C. S., Karp, C. L., & Galor, A. (2016). Topical 5-fluorouracil 1% as primary treatment for ocular surface squamous neoplasia. Ophthalmology, 123(7), 1442–1448. https://doi.org/10.1016/j.ophtha.2016.02.034
Kozma, K., Dömötör, Z. R., Csutak, A., Szabó, L., Hegyi, P., Erőss, B., Helyes, Z., Molnár, Z., Dembrovszky, F., & Szalai, E. (2022). Topical pharmacotherapy for ocular surface squamous neoplasia: Systematic review and meta-analysis. Scientific Reports, 12(1), 14221. https://doi.org/10.1038/s41598-022-18545-6
Shields, C. L., Ramasubramanian, A., Mellen, P. L., & Shields, J. A. (2012). Intraocular invasion of conjunctival squamous cell carcinoma in five patients. Ophthalmology, 119(3), 558–563. https://doi.org/10.1016/j.ophtha.2011.08.036
Borella, Y., Lumbroso, L., Lévy, C., Gardrat, S., Klijanienko, J., Malaise, D., Dendale, R., Cassoux, N., & Matet, A. (2024). Intraocular invasion by conjunctival squamous cell carcinoma: Clinical presentation, histopathological findings, and outcome. Ocular Oncology and Pathology, 10(1), 32–42. https://doi.org/10.1159/000531983
Rathi, S. G., Ganguly Kapoor, A., & Kaliki, S. (2018). Ocular surface squamous neoplasia in HIV-infected patients: Current perspectives. HIV/AIDS (Auckland), 10, 33–45. https://doi.org/10.2147/HIV.S120517
Gurnani, B., & Kaur, K. (2025). Ocular surface squamous neoplasia. In StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK573082/
Tsatsos, M., Delimitrou, C., Tsinopoulos, I., & Ziakas, N. (2025). Update in the diagnosis and management of ocular surface squamous neoplasia (OSSN). Journal of Clinical Medicine, 14(5), 1699. https://doi.org/10.3390/jcm14051699
Gokharu, S., Arya, D., Chauhan, D., & Das, S. (2025). Ocular surface squamous neoplasia masquerades: Clinical profile and outcome. Indian Journal of Ophthalmology, 73(Suppl 3), S405–S409. https://doi.org/10.4103/IJO.IJO_3391_23
Greenfield, D. S., Jiang, Y., Madu, A., Hernandez-Aya, L. F., Sun, W., Karp, C. L., Dubovy, S. R., Lee, R. K., & Galor, A. (2025). Deep learning-based differentiation of ocular surface squamous neoplasia from pterygium and pinguecula using anterior segment optical coherence tomography. American Journal of Ophthalmology, 268, 45–54. https://doi.org/10.1016/j.ajo.2024.10.012
Ramberg, I. M. S. (2022). Human papillomavirus-related neoplasia of the ocular adnexa. Acta Ophthalmologica, 100(Suppl 272), 3–33. https://doi.org/10.1111/aos.15244
Esmaeli, B. (2023). Immune checkpoint inhibitor therapy for orbital and ocular adnexal squamous cell carcinomas: International Society of Ocular Oncology President’s Lecture, 2022. Investigative Ophthalmology & Visual Science, 64(7), 29. https://doi.org/10.1167/iovs.64.7.29
