Biopsy of the conjunctiva in dry eye patients establishes a correlation between squamous metaplasia and dry eye clinical severity

Abstract

Purpose: The aim of this work was to evaluate the different grades of squamous metaplasia of the conjunctiva during the clinical course of dry eye syndrome, detecting the most characteristic morphological and morphometric changes by biopsy in order to provide a diagnostic classification.

Methods: The conjunctiva was studied under light microscopy by conventional histological methods and by morphometric analysis in 165 patients and in 33 controls. Patients were classified according to the Schirmer 1 test, break-up time, rose Bengal staining, osmolarity and impression cytology. The epithelium and connective tissue, with their different cells and other structures, were studied.

Results: The conjunctiva in dry eye patients showed progressive stratification, hyperplasia, hypertrophy and cellular flattening, with loss of goblet cell density and mucous layer. We found five pathological grades of squamous metaplasia and one normal grade. Clear nuclear alterations (indentation and binucleation) were found in the early grades of dry eye syndrome, but pyknotic nuclei and anucleated cells were only seen in the most severe grades. The smallest epithelial cells were found in the control group and their size increased with the severity of the dry eye syndrome. From the earliest stages to the most severe cases, increases in cellular separation were observed. There was also an increase in the number of inflammatory cells. Blood and lymphatic vessels showed alterations only in the most severe cases.

Conclusions: This is the first grading system proposed for biopsy evaluation of the ocular surface in dry eye patients. These morphological and morphometric studies alone were able, even in the earliest phases of dry eye, to detect the squamous metaplasia that progresses from the surface of the epithelium to the connective tissue. This degenerative or adaptative cellular process was characterized mainly by marked increases in the stratification, epithelial cellular size and a general loss of goblet cells.