A novel mutation in FBN1 gene in autosomal dominant Marfan syndrome and macular degeneration in a Chinese consanguineous family.

AIM: To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome (MFS) phenotype and an unusual bilateral macular degeneration. METHODS: Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals. RESULTS: In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation (c.3932A>G, p.Y1311C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls. CONCLUSION: A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome.

Rosiglitazone inhibits TGF-ß 1 induced activation of human Tenon fibroblasts via p38 signal pathway.

PURPOSE: Transdifferentiation of human Tenon fibroblasts to myofibroblasts and subsequent deposition of extracellular matrix is a key step in the scarring after glaucoma filtration surgery. The p38 signaling pathway plays an important role in cell proliferation and differentiation, and its upstream regulators and downstream molecules are widely distributed in the eye. We aimed to investigate the role of p38 in the activation of Tenon fibroblasts and that of the anti-fibrotic mechanism of rosiglitazone in the modulation of the p38 signaling pathway. METHODS: Cultured Tenon fibroblasts were stimulated with transforming growth factor (TGF)-ß1. Activation of p38 was examined by western blot analysis. Rosiglitazone and blocking of the p38 signaling pathway by SB203580 were used to antagonize stimulation by TGF-ß1. Fibroblast motility was examined by wound closure assay; alpha-smooth muscle actin, connective tissue growth factor, and collagen type I were determined by qPCR and western blot. Expression and localization of alpha-smooth muscle actin were determined by immunofluorescence staining. RESULTS: Phosphorylated p38 was upregulated in fibroblasts stimulated with TGF-ß1, and this effect was substantially inhibited by rosiglitazone. Proliferation and migration of fibroblasts were suppressed by rosiglitazone and SB203580. Expression of alpha-smooth muscle actin, connective tissue growth factor, and collagen type I were decreased at the mRNA and protein levels by rosiglitazone and SB203580. However, the inhibitory effect of SB203580 on transcription and protein expression was weaker than that of rosiglitazone. Similar phenomena were found on immunofluorescence microscopy of alpha-smooth muscle actin. CONCLUSIONS: The p38 signaling pathway mediates the TGF-ß1-induced transdifferentiation of human Tenon fibroblasts to myofibroblasts. Rosiglitazone can exert anti-fibrotic activity by interfering with the TGF-ß/p38 signaling pathway and might be useful for modulating scar formation after glaucoma filtration surgery.

[Ocular surface injury resulted from topical anti-glaucoma medications: prevention and cure].

The accumulating evidences from experimental and clinical studies suggested that the ocular surface could be injured by topical anti-glaucoma medications. The ocular surface injury not only caused dry eyes, red eye, eye itching, photophobia and other discomforts, but also increased the risk of failure of glaucoma surgery in patients. The commonly used preservative Benzalkonium Chloride (BAK) plays an important role in ocular surface damage and its side effects are dose- and time-dependent, particularly, in the combined medications. Topical application of preservative BAK could result in the damage of epithelial cells and endothelial cells, and also affect the central corneal thickness. Prevention of ocular injury should be seriously taken into consideration in the anti-glaucoma medical treatment. Development of complex preparations, preservative-free and/or novel preservative preparations for glaucoma therapy may provide a promising approach in the prevention of ocular surface injury.

Repeatability and agreement of CCT measurement in myopia using entacam and ultrasound pachymetry.

AIM: To evaluate the repeatability of central corneal thickness (CCT) measurement by entacam, and agreement of CCT measured by Pentacam and ultrasound pachymetry (USP) in Chinese myopia. Thereby investigate the possibility of Pentacam as a substitute for USP in CCT measurement before refractive surgery. The effects of corneal curvature measured by Pentacam on CCT were also evaluated. METHODS: One hundred and forty-eight right eyes of 148 individual with myopia were included in this study. Three successive Pentacam CCT measurements followed by 10 successive ultrasound pachymetry were carried out in the 148 eyes. Mean of CCT taken by each device was calculated for comparison. According to the CCT measured by USP, all the 148 eyes were divided into 3 groups: <520µm, 520-560µm, >560µm. For all eyes and each group the CCT obtained by Pentacam and USP were compared. Anterior corneal curvature of the 148 eyes was also adopted for correlation analysis with CCT obtained by ultrasound pachymetry. In addition, CCT measurement using 60 random selected Scheimpflug images was performed by 3 skilled investigators at different time, and this was repeated for 3 times by a forth investigator to assess repeatability of Pentacam CCT measurement using Scheimpflug images. RESULTS: Intraclass correlation coefficient (ICC) analysis revealed high intraobserver repeatability (ICC=0.994, F=158.60, P<0.001) for CCT measurement by Pentacam. The interobserver (ICC=0.998, F=494.73, P<0.001) and intraobserver (ICC=0.997, F=383.98, P<0.001) repeatability for Pentacam CCT measurements using Scheimpflug images were also excellent. There was high positive correlation between the CCT values measured by Pentacam and ultrasound pachymetry (r=0.963, P<0.001). Bland-altman plots showed that the Pentacam underestimate the CCT by 8.02µm compared with ultrasouond pachymetry. The differences between Pentacam and USP increased as the CCT readings by USP increased (Pentacam vs USP: slope=-0.04, P<0.05). The 95% upper and lower limits of agreement between CCT values obtained from the two devices were +9.33µm and -25.37µm. No significant association could be found between CCT and anterior corneal curvature. CONCLUSION: Inter- and intraobserver variability for CCT measurements by Pentacam was considerably below clinically significant levels. CCT of myopia obtained by Scheimpflug camera, Pentacam, were highly correlated to that by ultrasound pachymetry. However, the values obtained are not directly interchangeable between Pentacam and ultrasound pachymetry as the 95% limits of agreement are relatively wide. Pentacam can be a useful instrument for measuring CCT in candidates to refractive surgery in clinic.

Assessment of intraocular pressure measured by Reichert Ocular Response Analyzer, Goldmann Applanation Tonometry, and Dynamic Contour Tonometry in healthy individuals.

AIM: To investigate the accuracy of intraocular pressure (IOP) as measured by a Reichert Ocular Response Analyzer (ORA), as well as the relationship between central corneal thickness (CCT) and IOP as measured by ORA, Goldmann applanation tonometry (GAT), and dynamic contour tonometry (DCT). METHODS: A total of 158 healthy individuals (296 eyes) were chosen randomly for measurement of IOP. After CCT was measured using A-ultrasound (A-US), IOP was measured by ORA, GAT, and DCT devices in a randomized order. The IOP values acquired using each of the three tonometries were compared, and the relationship between CCT and IOP values were analyzed separately. Two IOP values, Goldmann-correlated IOP value (IOPg) and corneal-compensated intraocular pressure (IOPcc), were got using ORA. Three groups were defined according to CCT: 1) thin cornea (CCT<520µm); 2) normal-thickness cornea (CCT: 520-580µm); and 3) thick cornea (CCT>580µm) groups. RESULTS: In normal subjects, IOP measurements were 14.95±2.99mmHg with ORA (IOPg), 15.21±2.77mmHg with ORA (IOPcc), 15.22±2.77mmHg with GAT, and 15.49±2.56mmHg with DCT. Mean differences were 0.01±2.29mmHg between IOPcc and GAT (P>0.05) and 0.28±2.20mmHg between IOPcc and DCT (P>0.05). There was a greater correlation between IOPcc and DCT (r=0.946, P=0.000) than that between IOPcc and GAT (r=0.845, P=0.000). DCT had a significant correlation with GAT (r=0.854, P=0.000). GAT was moderately correlated with CCT (r=0.296, P<0.001), while IOPcc showed a weak but significant correlation with CCT (r=-0.155, P=0.007). There was a strong negative correlation between CCT and the difference between IOPcc and GAT(r=-0.803, P=0.000), with every 10µm increase in CCT resulting in an increase in this difference of 0.35mmHg. The thick cornea group (CCT>580µm) showed the least significant correlation between IOPcc and GAT (r=0.859, P=0.000); while the thin cornea group (CCT<520µm) had the most significant correlation between IOPcc and GAT (r=0.926, P=0.000). The correlated differences between IOPcc and DCT were not significant in any of the three groups (P>0.05). CONCLUSION: Measurement of IOP by ORA has high repeatability and is largely consistent with GAT measurements. Moreover, the ORA measurements are affected only to a small extent by CCT, and are likely to be much closer to the real IOP value than GAT.

Diagnosis and treatment of myopic traction maculopathy.

In recent years, the broad application of optical coherence tomography and vitrectomy, combined with research efforts in maculopathy in high myopia have provided many achievements, such as the new classification of myopic traction maculopathy (MTM). Here, we review the latest developments in the diagnosis and treatment of MTM, including its conception, clinical characteristics, pathogenesis, clinical stages, and the options for surgical treatment.