Morphological changes in the meibomian glands of patients with phlyctenular keratitis: a multicenter cross-sectional study

Summary of 13 patients with phlyctenular keratitis. (XLSX 11 kb

Increased Tear Fluid Production as a Compensatory Response to Meibomian Gland Loss A Multicenter Cross-sectional Study

PurposeTo compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non–Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects.DesignMulticenter, cross-sectional, observational case series.ParticipantsForty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years).MethodsOcular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmer's test.Main Outcome MeasuresOcular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmer's test value.ResultsThe ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmer's test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmer's test value only in the MGD group (ρ = 0.508, P = 8.3×10−6).ConclusionsAn increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD

Pretranscriptional Regulation of Tgf-β1 by PI Polyamide Prevents Scarring and Accelerates Wound Healing of the Cornea After Exposure to Alkali

Corneal alkali burns are a serious clinical problem that often leads to permanent visual impairment. In this process, transforming growth factor (Tgf)-β1 is upregulated and involved in the response to corneal injury and the process of corneal stromal scarring. To develop an efficient compound to inhibit Tgf-β1 in the cornea, we designed GB1201, a pyrrole–imidazole (PI) polyamide targeting rat Tgf-β1 gene promoter to the activator protein-1 (AP-1) binding site. GB1201 showed a high binding affinity to the target DNA sequence in the gel mobility shift and Biacore assays. GB1201 significantly inhibited the rat Tgf-β1 gene promoter activity in HEK (human embryonic kidney) 293 cells in a concentration-dependent manner. Topically administrated GB1201 was distributed immediately to the nuclei of all cell layers of the cornea and remained for 24 hours. A corneal alkali burn model in rats was used to evaluate the therapeutic efficacy of GB1201. GB1201 suppressed the upregulation of Tgf-β1 in the burned cornea, both in the mRNA and protein levels. Moreover, daily treatment with GB1201 for a week significantly improved the corneal tissue wound healing, reduced corneal stromal scarring, and prevented corneal haze formation. Our data suggest that PI polyamide may open new opportunities for therapeutic intervention in the treatment of chemically burned corneas