Impression Cytology on Conjunctiva and Cornea in Dry Eye Patients Establishes a Correlation between Squamous Metaplasia and Dry Eye Clinical Severity

Abstract

Purpose To obtain deeper knowledge of the cellular transition in squamous metaplasia, and to look for a correlation between the clinical grade of severity of dry eye and the grade of squamous metaplasia of the corneal and conjunctival epithelium, studied by impression cytology. Methods A total of 143 patients with dry eye disorders of different grades of clinical severity and 33 control subjects of matched age and sex were studied. Symptoms, clinical tests (including Schirmer test, slit-lamp examination, break-up time, rose Bengal staining, vanishing lacunar sulci, and neovascularization), and tear osmolarity were used to establish the diagnosis of dry eye. The subjects were classified into six clinical grades, grade 0 indicating normal and grades 1 to 5 progressively more severe dry eye. Impression cytology specimens were taken from the central cornea and different areas of the conjunctiva of one eye from all patients. A morphologic and morphometric study of the photographs obtained by light microscopy showed cell size, nuclear size, nuclear-cytoplasmic ratio (N:C) in nonsecretory epithelial cells, and density of goblet cells. Results Morphometric and morphologic studies of the ocular surface cells indicated significant differences, mainly in cell sizes, nuclear alterations, and the N:C ratio, in nonsecretory epithelial cells of the conjunctiva and cornea, and in goblet cell densities from the conjunctiva, between the clinically normal eyes and those with the five grades of clinical severity of dry eye, with different degrees of squamous metaplasia. Conclusions A morphologic and morphometric analysis of the ocular surface from patients with dry eye obtained by impression cytology led us to draft a new grading system containing one normal level and five levels of squamous metaplasia. This new grading system is based on a significant decrease in the number of goblet cells with less periodic acid-Schiff-hematoxylin-positive staining, an increase in nonsecretory cell size, more marked cell separation, a lower N:C ratio, and an increase in nuclear alterations. The clinical severity of the dry eye correlates with these alterations.