Classification of Limbal Stem Cell Deficiency Using Clinical and Confocal Grading

Abstract

Purpose: To grade the severity of limbal stem cell deficiency (LSCD) based on the extent of clinical presentation and central corneal basal epithelial cell density (BCD).

Methods: This is a retrospective observational comparative study of 48 eyes of 35 patients with LSCD and 9 eyes of 7 normal subjects (controls). Confocal images of the central cornea were acquired. A clinical scoring system was created based on the extent of limbal and corneal surface involvement. LSCD was graded as mild, moderate, and severe stages based on the clinical scores. The degree of BCD reduction was given a score of 0 to 3.

Results: Compared with BCD in controls, BCD decreased by 23.0%, 40.4%, and 69.5% in the mild, moderate, and severe stages of LSCD classified by the clinical scoring system, respectively. The degree of BCD reduction was positively correlated with larger limbal and corneal surface involvement and when the central visual axis was affected (all P ≤ 0.0005). Mean corrected distance visual acuity logarithm of the minimum angle of resolution was 0.0 ± 0.0 in control eyes, 0.2 ± 0.5 in mild LSCD, 0.6 ± 0.4 in moderate LSCD, and 1.6 ± 1.1 in severe LSCD (P < 0.0001). There was a significant correlation between a higher clinical score and corrected distance visual acuity logarithm of the minimum angle of resolution (rho = 0.82; P < 0.0001) and a greater decrease in BCD (rho = -0.78; P < 0.0001).

Conclusions: A clinical scoring system was developed to assess the extent of clinical presentation of LSCD. A classification system to grade the severity of LSCD can be established by combining the BCD score with the clinical score.

Figure 1:

Representative diagram of the limbal stem cell deficiency clinical grading system. Limbus involvement in clock hours (top panel), cornea surface area (middle panel) and visual axis involvement (bottom panel) criteria are shown. Slit lamp photo of an eye with a total score of 6 points, classified as the moderate stage of limbal stem cell deficiency (far right panel).

Figure 2:

Box and whisker plot of the central cornea basal cell density (cells/mm², left panel) and corrected distant visual acuity in LogMAR (right panel) in the control group and in patients with mild, moderate, and severe limbal stem cell deficiency. The central cornea basal cell density and corrected distant visual acuity in all patients with limbal stem cell deficiency was significantly less than that in the controls. Asterisk denotes P < 0.0001.

Figure 3.

Representative confocal images of corneal basal epithelial cells in normal and limbal stem cell deficiency (LSCD). Basal epithelial cells are compact and have clear cell-cell junction in normal eye (top left panel). The size of the epithelial cells is slightly larger in LSCD with confocal grade 1 (top right panel) and cells became metaplastic in grade 2 (bottom left panel). In grade 3, cells with normal corneal epithelial cell morphology are not detected (bottom right panel).