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In vivo confocal microscopy indicates an inverse relationship between the sub-basal corneal plexus and the conjunctivalisation in patients with limbal stem cell deficiency
  1. Manuel Caro-Magdaleno1,2,
  2. Asunción Alfaro-Juárez1,
  3. Jesús Montero-Iruzubieta1,2,
  4. Ana Fernández-Palacín3,
  5. Ana Muñoz-Morales1,
  6. Manuel Alberto Castilla-Martino1,
  7. Consuelo Spínola-Muñoz1,
  8. Enrique Rodríguez-de-la-Rúa1,2
  1. 1 U.G.C. Ophthalmology, Hospital Universitario Virgen Macarena and Virgen del Rocío, Seville, Spain
  2. 2 Department of Surgery, University of Seville, Seville, Spain
  3. 3 Department of Preventive Medicine and Public Health, University of Seville, Seville, Spain
  1. Correspondence to Dr Manuel Caro-Magdaleno, U.G.C. Ophthalmology, Hospital Universitario Virgen Macarena and Virgen del Rocío, Seville, Spain; mcaro79{at}


Background/aims Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification.

Methods We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity.

Results The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm2) was less (p<0.001) than in controls (20911±4142 µm/mm2). The SND, but not basal cell density, played a protective role against conjunctivalisation (OR, 0.069; 95% CI 0.008–0.619; p=0.01). An SND cut-off value of 17 215 µm/mm2 yielded a sensitivity and specificity of 95.5% and 90.6%, respectively, for LSCD diagnosis.

Conclusion The density of the corneal sub-basal nerve plexus was inversely related to conjunctivalisation in LSCD. Further studies are needed to verify this and to elucidate the directionality between these factors.

  • cornea
  • diagnostic tests/investigation
  • stem cells
  • neovascularisation
  • ocular surface
  • Confocal Microscopy
  • corneal nerve plexus
  • in vivo confocal microscopy
  • limbal stem cell deficiency

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  • Contributors Research design: MC-M, JM-I, AF-P and ER-d-l-R; data acquisition and/or research execution: MC-M, AA-J, JM-I, AF-P, AM-M, MAC-M, CS-M and ER-R; data analysis and/or interpretation: MC-M, AA-J, JM-I, AF-P and ER-d-l-R; manuscript preparation: all authors.

  • Funding Iniciativa Andaluza en Terapias Avanzadas (IATA). MC-M, JM-I and ER-d-l-R are members of RETICS OFTARED 'RD16/0008/0010', financed by the Instituto de Salud Carlos III, as part of the Plan Nacional I+D+i 2013-2016 and cofinanced by the European Union (FEDER/FSE) 'Una manera de hacer Europa'. IATA and RETICS OFTARED have sponsored the translation of this manuscript. None of the funders played an active role in the study design nor in the decision to submit this manuscript and do not have ultimate authority over any of these activities.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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