Novel mutations in PDE6B causing human retinitis pigmentosa.

AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa (RP). METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated with retinal diseases were scanned with capture next generation sequencing (CNGS) approach. Two heterozygous mutations in PDE6B were confirmed in the pedigree by Sanger sequencing subsequently. The carrier frequency of PDE6B mutations of reported PDE6B mutations based on the available two public exome databases (1000 Genomes Project and ESP6500 Genomes Project) and one in-house exome database was investigated. RESULTS: We identified compound heterozygosity of two novel nonsense mutations c.1133G>A (p.W378X) and c.2395C>T (p.R799X) in PDE6B, one reported causative gene for RP. Neither of the two mutations in our study was presented in three exome databases. Two mutations (p.R74C and p.T604I) in PDE6B have relatively high frequencies in the ESP6500 and in-house databases, respectively, while no common dominant mutation in each of the database or across all databases. CONCLUSION: We demonstrates that compound heterozygosity of two novel nonsense mutations in PDE6B could lead to RP. These results collectively point to enormous potential of next-generation sequencing in determining the genetic etiology of RP and how various mutations in PDE6B contribute to the genetic heterogeneity of RP.

Ten-year results of a randomized controlled trial comparing 0.02% mitomycin C and limbal conjunctival autograft in pterygium surgery.

OBJECTIVE: To compare the long-term outcome of pterygium surgery and the long-term effect on endothelial counts after mitomycin C (MMC) or limbal conjunctival autograft (LCAU) in pterygium surgery. DESIGN: We performed a 10-year follow-up study of a randomized controlled trial. PARTICIPANTS: A total of 115 eyes of 114 patients with primary pterygium were treated with intraoperative MMC (n = 63) or LCAU transplants (n = 52). A total of 76 patients completed the current 10-year long-term follow-up (47 in the MMC group, 29 in the LCAU group). METHODS: This is a follow-up study of a randomized controlled trial of a cohort of 114 patients in 2 groups that was performed at the Prince of Wales Hospital 10 years ago: group 1, intraoperative 0.02% MMC for 5 minutes; group 2, LCAU. Consecutive patients enrolled in the original study (recruitment began in February 2001) were invited back for a detailed clinical examination to document the long-term outcome of both surgical groups. MAIN OUTCOME MEASURES: The main outcome measures included the recurrence rate, residual conjunctival bed status, complications, and corneal endothelial cell density (ECD) differences. RESULTS: A total of 115 eyes of 114 patients were enrolled and randomized in our previous study. For the current study, 76 of the 114 patients (47 in the MMC group, 29 in the LCAU group) were contacted, whereas 18 patients were lost to follow-up and 20 patients had died. The mean follow-up period was 138 ± 2 months in the MMC group and 137 ± 2 months in the LCAU group. Twelve of 47 patients (25.5%) in the original MMC group and 2 of 29 patients (6.9%) in the LCAU group had recurrent pterygium (P = 0.021). The mean ECD was 2,39 2 ± 342 cells/mm(2) in the MMC group and 2,390 ± 388 cells/mm(2) in the LCAU group (P = 0.978). There was no significant difference in the ECD between the operated eyes and the fellow eyes in both groups (P = 0.926 MMC, P = 0.468 LCAU). No other significant ocular complications were observed in either group at the 10-year postoperative follow-up. CONCLUSIONS: Limbal conjunctival autograft was more effective than intraoperative MMC in minimizing pterygium recurrence at the 10-year follow-up. Treatment with intraoperative MMC was not associated with long-term corneal endothelial cell loss.

Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China.

BACKGROUND: Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain (DPNP) in the United States, European Union, and many other countries. This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain. METHODS: This double-blind, randomized, placebo-controlled, flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory (BPI) 24-hour average pain severity ratings ≥ 4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks. Dose adjustments of duloxetine or matching placebo were based upon investigator's judgment of clinical response. Change from baseline to endpoint in BPI average pain was the primary efficacy outcome. Secondary outcome measures included BPI-severity and -Interference, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, EuroQol: 5 Dimensions, Athens Insomnia Scale, and safety measures. RESULTS: Of 215 patients randomized, 88.4% and 82.1% of patients in placebo and duloxetine groups, respectively, completed the study. Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups (P = 0.124). Duloxetine- treated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1, 2, and 4 (P = 0.004, P = 0.009, and P = 0.006, respectively), but not at weeks 8 (P = 0.125) and 12 (P = 0.107). Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement, Clinical Global Impression of Severity, area under the curve for pain relief, BPI-severity pain right now, and BPI-interference walking ability. Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction on the Brief Pain Inventory average pain score relative to placebo. Duloxetine-treated patients reported nausea, somnolence, anorexia, and dysuria significantly more than placebo. CONCLUSIONS: Although the primary study endpoint was not achieved, the overall observed response pattern suggests the efficacy of duloxetine in the treatment of Chinese patients with diabetic peripheral neuropathic pain. The safety profile for duloxetine is similar to that reported in other global trials.