Experimentally induced dry eye produces ocular surface inflammation and epithelial disease.
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Biomedical subjects
Stephen C Pflugfelder
Publications and source records attributed to Stephen C Pflugfelder.
Corneal thickness indices discriminate between keratoconus and contact lens-induced corneal thinning.
PURPOSE: To evaluate two indices generated from measurements obtained from the Orbscan Corneal Topography System (CTS; Orbscan, Inc., Salt Lake City, UT) to distinguish contact lens-induced corneal thinning from keratoconus. The corneal thickness index (CTI) was used to compare central and peripheral corneal thicknesses. The discriminant function 1 (DF1) was used to evaluate corneal thickness and central keratometry measurements. DESIGN: Case-control study. PARTICIPANTS: Fifty-four patients with keratoconus or suspected keratoconus, 75 contact lens wearers, and 67 normal controls. METHODS: In the initial model-building study, the central and peripheral corneal thickness and central keratometry (K) readings were evaluated retrospectively in 1 eye each of 23 patients with clinically defined keratoconus, 31 contact lens wearers, and 43 normal patients with the Orbscan CTS. Two methods (corneal thickness index [CTI] and discriminant function 1 [DF1]) were evaluated for their efficacy in classifying these conditions. The CTI was designed as the ratio between mean peripheral corneal thickness and the central corneal thickness, and the formula for the DF1 was as follows: DF1 = 0.044 x central thickness - 0.030 x nasal thickness + 9.210 x CTI - 0.157 x Max K - 8.9. In the subsequent validation study, the results were verified in a separate group of keratoconus patients (n = 23), keratoconus suspects (n = 8), contact lens wearers (n = 44), and normal patients (n = 24). MAIN OUTCOME MEASURES: Corneal thickness index (CTI) and discriminant function 1 (DF1). RESULTS: The corneal thickness in patients with keratoconus and contact lens wearers was significantly thinner than that of normal eyes in the central and eight peripheral measured sites (P < 0.001). The corneal thickness in contact lens wearers was significantly greater than in keratoconus patients in the inferotemporal (P = 0.013), inferior (P = 0.003), and central (P < 0.001) sites and was borderline different in the superior site (P = 0.07). In the model-building study, the CTI in keratoconus patients (1.28 +/- 0.15) was significantly greater than in contact lens-wearing (1.10 +/- 0.03; P < 0.001) and normal eyes (1.09 +/- 0.04; P < 0.001). The CTI was not significantly different between normal and contact lens-wearing eyes (P = 0.68). A CTI value of 1.16 or more showed a sensitivity of 91% and specificity of 99% in differentiating keratoconus from contact lens-wearing and normal eyes. The DF1 value was significantly lower in keratoconic eyes than in contact lens-wearing and normal eyes. A DF1 value of -0.6 showed a 96% sensitivity and 99% specificity in differentiating keratoconus from contact lens-wearing and normal eyes. Similar results were obtained in the validation study. CONCLUSIONS: Corneal thickness indices generated from the Orbscan CTS appear to be sensitive and specific for diagnosing keratoconus. These indices may prove to be clinically useful parameters for distinguishing keratoconus from contact lens-induced corneal thinning.
Adult↗
A mouse model of keratoconjunctivitis sicca.
PURPOSE: To evaluate the effects of pharmacologic inhibition of aqueous tear production and desiccating environmental stress on aqueous tear production, tear clearance, corneal epithelial permeability, and conjunctival epithelial morphology, proliferation, and conjunctival goblet cell differentiation. METHODS: Aqueous tear production was inhibited by applying transdermal scopolamine (scop) patches to the depilated midtail of female MC, CBA mice. Desiccating environmental stress was created by placing mice in a hood with a continuous airflow blower. Aqueous tear production and volume, tear clearance, and corneal barrier function were compared in four experimental groups: untreated control mice, mice placed in the blower hood, mice treated with a scop patch, and mice treated with a scop patch and blower hood (scop patch + blower). Cotton threads were used to evaluate aqueous tear production and volume. Tear clearance was assessed by fluorometric measurement of collected tear fluid 15 minutes after instillation of 1% sodium fluorescein. Corneal epithelial barrier function was assessed by fluorometric measurement of carboxyfluorescein uptake. Conjunctival morphology and goblet cell density were evaluated in stained histologic sections. Conjunctival epithelial proliferation was assessed by bromodeoxyuridine (BrdU) labeling. RESULTS: Significant decreases in cotton thread wetting and tear clearance were observed in mice treated with a scop patch (P < 0.001) or with a scop patch and blower desiccation (P < 0.001), with a greater reduction in tear clearance in the latter group. Significantly increased corneal carboxyfluorescein uptake was noted in the scop patch group compared with untreated mice (P = 0.05) and in the scop patch + blower group compared with all the other groups (P < 0.0001). Changes in conjunctival epithelial morphology and a significant decrease in conjunctival goblet cell density (P < 0.001) were observed in the scop patch + blower group compared with the untreated control group. The number of proliferating conjunctival epithelial cells was significantly greater in the scop patch + blower group. CONCLUSIONS: Pharmacologic inhibition of tear production in mice is accompanied by ocular surface epithelial changes resembling human keratoconjunctivitis sicca (KCS) that are exacerbated by desiccating environmental stress. Cholinergic stimulated tear production appears to be essential for maintaining a healthy ocular surface.
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