Corneal intraepithelial neoplasia: in vivo confocal microscopic study with histopathologic correlation

To ascertain in vivo confocal microscopic features of corneal/conjunctival intraepithelial neoplasia (CIN) and correlate these with histology of the same lesions.

Observational case series with evaluation of diagnostic technology.

Four patients with unilateral CIN (3 men and 1 woman) were examined with the Heidelberg Retina Tomograph II (HRT II) Rostock Cornea Module (RCM) confocal microscope before, during, and after treatment. Corneal epithelial samples were taken by alcohol delamination technique in 2 patients, while impression cytology (IC) samples were obtained in the other 2 patients. Morphometric analysis of confocal and histologic images was carried out and the findings correlated. Four controls (all men, 2 with limbal stem cell deficiency, 1 with a limbal lesion, and 1 with diffuse keratoconjunctival proliferation) were similarly examined. Two of these had biopsy for histologic examination. Main outcome measures comprised the degree of correlation between histology and confocal microscopic features of CIN.

Dysplastic cellular changes were noticed on histopathology and correlated well with confocal microscopy, corresponding to the different corneal epithelial layers. Bright nucleoli within huge nuclei and ill-defined cell borders were a feature of the basal epithelium on histopathology and confocal microscopy. Subbasal corneal nerves were not visualized on confocal microscopy in areas affected by CIN. These features disappeared in response to treatment cycles as the basal epithelium reverted to its normal pattern, as seen by confocal microscopy.

Confocal microscopy findings highly correlate with histologic features in CIN. Confocal microscopic features of CIN as defined in this study will enable a reliable diagnosis in a noninvasive manner. Confocal microscopy will also allow real-time monitoring of the condition during treatment.