Limbal Stem Cell Deficiency (LSCD): Diagnosis, Staging, and Ocular Surface Reconstruction
Özet
Limbal kök hücre yetmezliği (LKHY), limbal epitelyal kök hücrelerin kaybı veya işlev bozukluğu sonucu ortaya çıkan, konjonktivalizasyon, yüzeyel vaskülarizasyon, kronik inflamasyon ve ilerleyici görme kaybıyla karakterize, görmeyi tehdit eden bir oküler yüzey hastalığıdır. Bu bölümde LKHY'nin tanısı, konsensüse dayalı evrelemesi ve güncel oküler yüzey rekonstrüksiyon stratejileri yapılandırılmış bir yaklaşımla ele alınmaktadır. Limbal niş patofizyolojisi, kök hücre yetmezlik mekanizmaları ve "yüzey ekosistemi bozukluğu" kavramı tartışılmaktadır. Klinik muayenenin impresyon sitoloji, in vivo konfokal mikroskopi ve ön segment optik koherens tomografi (OKT) epitel haritalama ile birleştirildiği multimodal tanı yaklaşımı ve ayırıcı tanı sunulmaktadır. Evreleme, lateralite, tutulum yaygınlığı ve oküler yüzey risk faktörlerini vurgulayan uluslararası konsensüs çerçevesine dayanmaktadır. Tedavi ilkeleri, transplantasyon öncesi yüzey optimizasyonunu ön koşul olarak ele almaktadır. Tek taraflı hastalıkta birinci basamak seçenek olan otolog rekonstrüksiyon teknikleri (SLET, CLAU, CLET) ve iki taraflı olgularda sistemik immünsupresyon gerektiren allojenik yaklaşımlar (KLAL, lr-CLAL) incelenmektedir. Prognostik faktörler, komplikasyonlar, postoperatif izlem ve gelecek yönelimler de ele alınmaktadır.
Limbal stem cell deficiency (LSCD) is a sight-threatening ocular surface disorder resulting from the depletion or dysfunction of limbal epithelial stem cells, leading to conjunctivalization, superficial vascularization, chronic inflammation, and progressive visual loss. This chapter provides a structured overview of LSCD diagnosis, consensus-based staging, and contemporary ocular surface reconstruction strategies. The pathophysiology of the limbal niche, mechanisms of stem cell failure, and the concept of "surface ecosystem failure" are discussed. A multimodal diagnostic approach combining clinical examination with impression cytology, in vivo confocal microscopy, and anterior segment OCT epithelial mapping is outlined, along with key differential diagnoses. Staging follows the international consensus framework, emphasizing laterality, extent of involvement, and ocular surface risk factors. Management principles focus on preoperative surface optimization as a prerequisite to transplantation. Autologous reconstructive techniques (SLET, CLAU, CLET) are reviewed as first-line options for unilateral disease, while allogeneic approaches (KLAL, lr-CLAL) are discussed for bilateral cases requiring systemic immunosuppression. Prognostic factors, complication patterns, postoperative monitoring, and emerging therapeutic directions—including standardized cell manufacturing and pharmacological strategies—are also addressed.
Referanslar
Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JAP, et al. Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea. 2019; 38(3): 364-375. doi:10.1097/ICO.0000000000001820.
International Limbal Stem Cell Deficiency Working Group. Global Consensus on the Management of Limbal Stem Cell Deficiency. Cornea. 2020; 39(10): 1291-1302. doi:10.1097/ICO.0000000000002358.
Kenyon KR, Tseng SCG. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989; 96(5): 709-723.
Sangwan VS, Basu S, MacNeil S, Balasubramanian D. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. British Journal of Ophthalmology. 2012; 96(7): 931-934.
Basu S, Sureka SP, Shanbhag SS, et al. Simple Limbal Epithelial Transplantation: Long-Term Outcomes. Ophthalmology. 2016; 123(5): 1000-1010. doi:10.1016/j.ophtha.2015.12.042.
Holland EJ, Schwartz GS. The evolution of ocular surface transplantation for severe ocular surface disease and a review of immunosuppression strategies. Cornea. 2012; 31(7): 809-819.
Le Q, Xu J, Deng SX. The Diagnosis of Limbal Stem Cell Deficiency. The Ocular Surface. 2018; 16(1): 58-69.
Poli M, Janin H, Justin V, Auxenfans C, Burillon C, Damour O. Cytokeratin 13 as a diagnostic marker of limbal stem cell deficiency: evaluation by impression cytology. Investigative Ophthalmology & Visual Science. 2011; 52(5): 2749-2754.
Deng SX, Sejpal KD, Tang Q, et al. Characterization of limbal stem cell deficiency by in vivo laser scanning confocal microscopy: a microstructural approach. Archives of Ophthalmology. 2012; 130(4): 440-446.
Nubile M, Lanzini M, Miri A, Mastropasqua L. In vivo confocal microscopy and diagnosis of limbal stem cell deficiency. American Journal of Ophthalmology. 2013; 155(2): 220-232.
Liang L, et al. Corneal epithelial thickness measured using anterior segment optical coherence tomography as a diagnostic parameter for limbal stem cell deficiency. American Journal of Ophthalmology. 2020; 214: 1-10. doi:10.1016/j.ajo.2020.02.010.
Le Q, Chauhan T, Yung M, Tseng CH, Deng SX. Outcomes of Limbal Stem Cell Transplant: A Meta-analysis. JAMA Ophthalmology. 2020; 138(6): 660-670. doi:10.1001/jamaophthalmol.2020.1120.
Eslani M, Baradaran-Rafii A, Cheung AY, et al. Long-term outcomes of conjunctival limbal autograft in patients with unilateral limbal stem cell deficiency. The Ocular Surface. 2019; 17(4): 660-666.
Shanbhag SS, Chodosh J, Saeed HN. Simple limbal epithelial transplantation (SLET): Review of indications, surgical technique, outcomes, and future directions. International Journal of Ophthalmology. 2019; 12(11): 1689-1696.
Vazirani J, Basu S, Kenia H, et al. Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation. American Journal of Ophthalmology. 2014; 157(3): 584-590.e1-2. doi:10.1016/j.ajo.2013.11.011.
Rama P, Di Rocco A, et al. Cultivated limbal epithelial transplantation. Current Opinion in Ophthalmology. 2017; 28(4): 387-393.
Sangwan VS, Basu S, Vemuganti GK, et al. Clinical outcomes of xeno-free autologous cultivated limbal epithelial transplantation: a 10-year study. British Journal of Ophthalmology. 2011; 95(11): 1525-1529. doi:10.1136/bjophthalmol-2011-300352.
Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. Limbal stem-cell therapy and long-term corneal regeneration. The New England Journal of Medicine. 2010; 363(2): 147-155. doi:10.1056/NEJMoa0905955.
Liang L, Sheha H, Li J, Tseng SCG. Long-term outcomes of keratolimbal allograft transplantation in patients with severe ocular surface disorders. Archives of Ophthalmology. 2009; 127(11): 1425-1430.
Daya SM, Ilari L. Living-related conjunctival limbal allograft for the treatment of stem cell deficiency. Ophthalmology. 2001; 108(1): 126-133.
Referanslar
Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JAP, et al. Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea. 2019; 38(3): 364-375. doi:10.1097/ICO.0000000000001820.
International Limbal Stem Cell Deficiency Working Group. Global Consensus on the Management of Limbal Stem Cell Deficiency. Cornea. 2020; 39(10): 1291-1302. doi:10.1097/ICO.0000000000002358.
Kenyon KR, Tseng SCG. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989; 96(5): 709-723.
Sangwan VS, Basu S, MacNeil S, Balasubramanian D. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. British Journal of Ophthalmology. 2012; 96(7): 931-934.
Basu S, Sureka SP, Shanbhag SS, et al. Simple Limbal Epithelial Transplantation: Long-Term Outcomes. Ophthalmology. 2016; 123(5): 1000-1010. doi:10.1016/j.ophtha.2015.12.042.
Holland EJ, Schwartz GS. The evolution of ocular surface transplantation for severe ocular surface disease and a review of immunosuppression strategies. Cornea. 2012; 31(7): 809-819.
Le Q, Xu J, Deng SX. The Diagnosis of Limbal Stem Cell Deficiency. The Ocular Surface. 2018; 16(1): 58-69.
Poli M, Janin H, Justin V, Auxenfans C, Burillon C, Damour O. Cytokeratin 13 as a diagnostic marker of limbal stem cell deficiency: evaluation by impression cytology. Investigative Ophthalmology & Visual Science. 2011; 52(5): 2749-2754.
Deng SX, Sejpal KD, Tang Q, et al. Characterization of limbal stem cell deficiency by in vivo laser scanning confocal microscopy: a microstructural approach. Archives of Ophthalmology. 2012; 130(4): 440-446.
Nubile M, Lanzini M, Miri A, Mastropasqua L. In vivo confocal microscopy and diagnosis of limbal stem cell deficiency. American Journal of Ophthalmology. 2013; 155(2): 220-232.
Liang L, et al. Corneal epithelial thickness measured using anterior segment optical coherence tomography as a diagnostic parameter for limbal stem cell deficiency. American Journal of Ophthalmology. 2020; 214: 1-10. doi:10.1016/j.ajo.2020.02.010.
Le Q, Chauhan T, Yung M, Tseng CH, Deng SX. Outcomes of Limbal Stem Cell Transplant: A Meta-analysis. JAMA Ophthalmology. 2020; 138(6): 660-670. doi:10.1001/jamaophthalmol.2020.1120.
Eslani M, Baradaran-Rafii A, Cheung AY, et al. Long-term outcomes of conjunctival limbal autograft in patients with unilateral limbal stem cell deficiency. The Ocular Surface. 2019; 17(4): 660-666.
Shanbhag SS, Chodosh J, Saeed HN. Simple limbal epithelial transplantation (SLET): Review of indications, surgical technique, outcomes, and future directions. International Journal of Ophthalmology. 2019; 12(11): 1689-1696.
Vazirani J, Basu S, Kenia H, et al. Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation. American Journal of Ophthalmology. 2014; 157(3): 584-590.e1-2. doi:10.1016/j.ajo.2013.11.011.
Rama P, Di Rocco A, et al. Cultivated limbal epithelial transplantation. Current Opinion in Ophthalmology. 2017; 28(4): 387-393.
Sangwan VS, Basu S, Vemuganti GK, et al. Clinical outcomes of xeno-free autologous cultivated limbal epithelial transplantation: a 10-year study. British Journal of Ophthalmology. 2011; 95(11): 1525-1529. doi:10.1136/bjophthalmol-2011-300352.
Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. Limbal stem-cell therapy and long-term corneal regeneration. The New England Journal of Medicine. 2010; 363(2): 147-155. doi:10.1056/NEJMoa0905955.
Liang L, Sheha H, Li J, Tseng SCG. Long-term outcomes of keratolimbal allograft transplantation in patients with severe ocular surface disorders. Archives of Ophthalmology. 2009; 127(11): 1425-1430.
Daya SM, Ilari L. Living-related conjunctival limbal allograft for the treatment of stem cell deficiency. Ophthalmology. 2001; 108(1): 126-133.
