In vivo confocal microscopy indicates an inverse relationship between the sub-basal corneal plexus and the conjunctivalisation in patients with limbal stem cell deficiency

Br J Ophthalmol. 2019 Mar;103(3):327-331. doi: 10.1136/bjophthalmol-2017-311693. Epub 2018 May 18.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Count
  • Conjunctival Diseases / diagnostic imaging
  • Conjunctival Diseases / pathology*
  • Cornea / innervation*
  • Corneal Diseases / diagnostic imaging
  • Corneal Diseases / pathology*
  • Epithelium, Corneal / diagnostic imaging
  • Epithelium, Corneal / pathology*
  • Female
  • Humans
  • Limbus Corneae / diagnostic imaging
  • Limbus Corneae / pathology*
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Ophthalmic Nerve / diagnostic imaging
  • Ophthalmic Nerve / pathology*
  • ROC Curve
  • Sensitivity and Specificity
  • Slit Lamp Microscopy
  • Stem Cells / pathology*