Nitric oxide-induced autophagy and the activation of activated protein kinase pathway protect against apoptosis in human dental pulp cells.

AIM: To investigate the role of nitric oxide (NO)-induced autophagy in human dental pulp cells (HDPCs) and the involvement of AMP-activated protein kinase (AMPK) pathway. METHODOLOGY: The MTT assay was used to determine the cytotoxic effect of the NO donor sodium nitroprusside (SNP) in HDPCs. Apoptosis was detected by means of the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and apoptosis- or autophagy-related signal molecules were observed by Western blot analysis. Acidic autophagolysosomal vacuoles were stained with acridine orange to detect autophagy in the presence of 3-methyladenine (3MA) used to inhibit autophagy. To explore the mechanism underlying autophagy and its protective role against apoptosis, compound C, the chemical AMPK inhibitor, was used. Statistical analysis was performed using Student's t-test or analysis of variance (anova) followed by the Student-Newman-Keuls test (P < 0.05). RESULTS: SNP decreased viability of the HDPCs in a dose- and time-dependent manner. Exposing the HDPCs to SNP increased the levels of p62 and LC3-II, the typical markers of autophagy, and increased the number of acidic autophagolysosomal vacuoles, indicating the appearance of autophagy as detected by acridine orange staining (P < 0.05). Pre-treatment with 3MA decreased cell viability but increased cleaved poly(ADP-ribose) polymerase (PARP) and caspase-3, apoptosis indicators, in the SNP-treated HDPCs (P < 0.05). SNP activated AMPK/ULK signalling, whilst the inhibition of AMPK by compound C enhanced apoptotic cell death induced by SNP in the HDPCs (P < 0.05). CONCLUSION: NO induced autophagy with AMPK activation, which plays a role in the survival of HDPCs against NO-induced apoptosis.

Efficacy of rhBMP-2/Hydroxyapatite on Sinus Floor Augmentation: A Multicenter, Randomized Controlled Clinical Trial.

The aim of this randomized single-blinded active-controlled clinical study was to evaluate the early efficacy of low-dose Escherichia coli-derived recombinant human bone morphogenetic protein 2 (rhBMP-2) soaked with hydroxyapatite granules (BMP-2/H) as compared with an inorganic bovine bone xenograft (ABX) in maxillary sinus floor augmentation. In a total of 127 subjects who were enrolled at 6 centers, maxillary sinus floors were augmented with 1 mg/mL of rhBMP-2 (0.5 to 2.0 mg per sinus) and BMP-2/H (0.5 to 2.0 g; n = 65) or with ABX alone (0.5 to 2.0 g; n = 62). Core biopsies were obtained 3 mo after the augmentation surgery and were analyzed histomorphometrically. The mean new bone formation with BMP-2/H and ABX augmentation was 16.10% ± 10.52% and 8.25% ± 9.47%, respectively. The BMP-2/H group was noninferior to the ABX group; the lower limit of the 1-sided 97.5% confidence interval for the difference between the 2 groups was calculated as 4.33%, which was greater than the prespecified noninferiority margin of -3.75%. An additional test with the Wilcoxon rank-sum test with a 2-sided 5% significance level showed that bone formation between the 2 groups was significantly different (P < 0.0001). The soft tissue and residual graft areas showed no significant differences between the groups. With regard to safety, no significant difference between the 2 groups was observed; there was no significant increase in the amount of rhBMP-2 antibody in the serum after BMP-2/H grafting. Our study suggested that low-dose Escherichia coli-derived rhBMP-2 with hydroxyapatite was effective in early stages for enhanced bone formation after maxillary sinus floor augmentation without harmful adverse events (Clinicaltrials.gov NCT01634308).

Relationship between retinal nerve fibre layer measurements and retinal sensitivity by scanning laser polarimetry with variable and enhanced corneal compensation.

AIM: To evaluate the relationship between retinal sensitivity and the retinal nerve fibre layer (RNFL) measurements by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in a homogenous group of Asian eyes. METHODS: The presence of atypical birefringence pattern (ABP) on the peripapillary SLP-VCC was determined by the subjective evaluation and the objective criteria of software-provided typical scan score (TSS) <80. RNFL parameters were measured by both VCC and ECC techniques, and the visual field was examined. The relationships between retinal sensitivity and RNFL measurements were sought globally and regionally with linear and logarithmic regression analysis. Coefficients of the determination for VCC and ECC techniques were compared. RESULTS: Seventy-two eyes were classified as having normal birefringence pattern (NBP) and 53 eyes were classified as having ABP. In eyes with ABP, R2 values for the association between retinal sensitivity and RNFL measurements were 0.06-0.24 with VCC, whereas they were 0.21-0.48 with ECC. In eyes with NBP, R2 values for the association between retinal sensitivity and RNFL measurements were 0.14-0.35 with VCC, whereas they were 0.22-0.43 with ECC. The association of RNFL measurements with retinal sensitivity was significantly better with ECC than with VCC in nine out of 16 regression models in eyes with ABP, whereas only three models showed better associations with ECC in eyes with NBP (p<0.05). CONCLUSIONS: The associations of RNFL measurements on the routine SLP printouts with corresponding retinal sensitivity were stronger with the ECC algorithm compared with VCC in Asian eyes with ABP.

Study of retinal nerve fibre layer thickness in eyes with high tension glaucoma and hemifield defect.

AIM: To quantitatively evaluate retinal nerve fibre layer (RNFL) difference in areas of apparently normal appearing visual field in eyes with high tension glaucoma (HTG) and hemifield defects using scanning laser polarimetry. METHODS: 40 eyes from 40 patients with HTG with superior or inferior hemifield defects based on the Humphrey field analyser (HFA) underwent RNFL thickness measurements. 20 normal eyes from 20 subjects matched in age and refractive error were selected as a control group. The RNFL thickness was measured with a scanning laser polarimeter. Mean RNFL thickness was evaluated in four quadrants (superior, inferior, nasal, and temporal). A superior or inferior quadrant in the defined ring of scanning laser polarimetry corresponds to inferior or superior hemifield in HFA. RESULTS: The mean RNFL thickness in the unaffected quadrant (the quadrant corresponding to the hemifield with apparently normal visual field based on HFA) of the HTG group was significantly thinner than the average RNFL thickness of the corresponding quadrant of the control eyes. The RNFL thickness of the unaffected quadrant in the eyes with HTG was reduced and statistically similar to that of the affected quadrant. Symmetry, calculated as the ratio of superior to inferior RNFL thickness, showed no statistical difference between the study and control group. CONCLUSION: Changes in RNFL are present in the apparently normal hemifield in the eyes with HTG. The thickness of the RNFL is reduced symmetrically in both superior and inferior quadrants based on the GDx parameters.

Reproducibility of scanning laser polarimetry (GDx) of peripapillary retinal nerve fiber layer thickness in normal subjects.

PURPOSE: To assess the reproducibility of measurement of retinal nerve fiber layer (RNFL) thickness among subjects using the GDx Nerve Fiber Analyzer (NFA). METHODS: One eye of each of five young and healthy volunteers was imaged by three newly trained technicians (R.-H.P, K.-R.K., and S.-T.K.). Each volunteer was scanned six consecutive times for five independent times within a 1-month period. One composite image was selected out of three best images per session. Intra- and interoperator reproducibilities were calculated and the influence of placement of measurement ellipse by a single operator on interobserver reproducibility was also investigated. RESULTS: Mean coefficients of variation for total integral value of RNFL were 3.67 +/- 1.47%, 3.86 +/- 2.13%, and 4.16 +/- 1.97%, respectively for the three technicians. Interoperator variability was not statistically significant (P = 0.075), and the difference was even less if a single ellipse drawn by one operator was used in all measurements (P = 0.1528) by repeated-measures analysis of variance (ANOVA). CONCLUSIONS: The results suggest that GDx NFA may provide acceptable intraoperator as well as interoperator reproducibility among Asian eyes.

Short-term effect of mitomycin-C augmented trabeculectomy on axial length and corneal astigmatism.

PURPOSE: To evaluate the short-term effect of trabeculectomy with adjunctive mitomycin-C (MMC) on corneal astigmatism and axial length. SETTING: Asan Medical Center, University of Ulsan, Department of Ophthalmology, Seoul, Korea. METHODS: Eighteen consecutive eyes of 16 patients having trabeculectomy with adjunctive MMC were prospectively analyzed. Intraocular pressure (IOP) and axial length were evaluated preoperatively and 1, 3, 6, and 12 months postoperatively. Postoperative changes in corneal astigmatism were evaluated using vector analysis. RESULTS: The overall mean induced astigmatism showed with-the-rule change up to 3 months postoperatively followed by an against-the-rule shift. The mean axial length was significantly less postoperatively and changed throughout the 12 month follow-up. There was a positive correlation between postoperative axial length and IOP. Eyes with higher preoperative IOP had a greater decrease in axial length after trabeculectomy with MMC. CONCLUSION: The induced corneal astigmatism after trabeculectomy with MMC was long lasting, although less than that in previous studies. The change in axial length after surgery was significant, especially in eyes with a high preoperative IOP. The decrease in axial length persisted throughout the follow-up.

Increases in intraocular pressure during hemodialysis in eyes during early postvitrectomy period.

BACKGROUND AND OBJECTIVES: To identify risk factors for intraocular pressure (IOP) increases during hemodialysis (HD) in the early postoperative period following pars plana vitrectomy (PPV). PATIENTS AND METHODS: Comparisons of 36 vitrectomized eyes of 22 diabetics undergoing maintenance HD with those of 138 eyes of 69 nonoperated patients. Serial IOPs were measured before PPV, after PPV/before dialysis, and during dialysis. Serum osmolarity and blood pressure were also recorded. RESULTS: In 20 of 36 operated eyes (55.6%) and 18 of 138 nonoperated eyes (13.0%) IOP was increased (> or =4 mm Hg) during HD. In the operated group, marked increases (> or =7 mm Hg) were noted in 9 eyes and ocular pain in 5 eyes. Eyes with pre-existing outflow obstruction and/or acute postoperative outflow compromise carried high risks. No correlation with changes in serum osmolarity or blood pressure was found. CONCLUSION: Monitoring of IOP during HD seems warranted when diabetics with pre-existing outflow obstruction and/or postoperative outflow compromise, undergo HD following PPV.

Increased eyelid pigmentation associated with use of latanoprost.

PURPOSE: To report increased eyelid pigmentation as an adverse side effect associated with topical latanoprost. METHOD: Case report. A 62-year-old Korean woman with normal-tension glaucoma developed bilateral increased eyelid skin pigmentation 4 months after beginning treatment with latanoprost in both eyes. Clinical examinations were performed, and external photographs were taken. RESULT: Latanoprost was discontinued. Periodic examinations revealed that the eyelid skin pigmentation gradually diminished 1 month after the cessation of the drug, and decrease in pigmentation continued over 4 months of follow-up. CONCLUSION: An increase in eyelid skin pigmentation is a possible complication of topical latanoprost therapy, and the cessation of the drug can result in loss of induced pigmentation in humans.

Clinical results of Ahmed glaucoma valve implantation in refractory glaucoma with adjunctive mitomycin C.

OBJECTIVE: To study the surgical outcome and complications of Ahmed glaucoma valve (AGV) implantation with mitomycin C (MMC) in refractory glaucoma. PATIENTS AND METHODS: The authors retrospectively reviewed the records of 40 eyes in 37 consecutive patients who underwent combined AGV with MMC (0.4 mg/mL; 5 minutes). All patients had a minimum of 6 months of follow-up. Outcome measures were best corrected visual acuity, intraocular pressure (IOP), the number of medications, success rates, and the incidence of complications. RESULTS: The Kaplan-Meier life table analysis revealed that the probabilities of surgical success based on our success criteria at 1 year and 2 years postoperatively were 80% and 77%, respectively. Postoperative IOP was significantly lower at all follow-up intervals. At the final visit fewer glaucoma medications were used (2.5 vs 0.7, preoperative vs postoperative). The most frequent complication was hypotony (17%). CONCLUSION: In this retrospective case series with relatively short follow-ups, AGV implantation with mitomycin C in refractory glaucoma appears to be effective without increased complication rates.

The immediate effect of bilateral superior obliuqe tenotomy on primary position horizontal binocular alignment.

PURPOSE: To evaluate the effect on primary position horizontal binocular alignment of superior oblique tenotomy for A-pattern exotropia with bilateral superior oblique overaction using new surgical and anesthesia techniques. SUBJECTS AND METHODS: We performed intraoperatively adjustable horizontal strabismus surgery under topical anesthesia in 6 cases of A-pattern exotropia. After adjusting the horizontal deviation nearly to orthotropia in primary position, we measured the angle of horizontal deviation in up-, primary, and downgaze positions. This was followed by bilateral superior oblique tenotomy and remeasurement of the horizontal deviation in the same 3 positions. Postoperatively we remeasured the deviation at one day, one month and three months. RESULTS: There was no immediate change in the horizontal deviation in primary position in 2 of the 6 patients, and 3-8 delta of immediate esotropic shift in 4 of the 6 patients (average 3.3 delta) after bilateral superior oblique tenotomy. At 3 months postop' the small esotropia noted at the immediate postop' measurement became orthotropic. There was a tendency of increased exotropic shift or becoming exotropic in those patients with slight exotropia or orthotropia at the immediate postop' measurement. But these shifts were minimal. CONCLUSION: When combined surgery of superior oblique and horizontal muscle is planned for A-pattern exotropia, the effect of bilateral superior oblique tenotomy on the primary position horizontal binocular alignment can be disregarded.

Penetrating keratoplasty for pseudophakic bullous keratopathy associated with semiflexible, closed-loop anterior chamber intraocular lenses.

We performed penetrating keratoplasty on 32 eyes that developed pseudophakic bullous keratopathy associated with closed-loop anterior chamber intraocular lenses. All lenses were exchanged at the time of keratoplasty. Seventeen patients received anterior chamber intraocular lenses and 15 patients had a posterior chamber lens sutured to the iris or sclera. Postoperatively, 13 of 32 eyes (41%) achieved a visual acuity of 20/100 or better, and 27 of 32 eyes (84%) had a clear graft. A high incidence of cystoid macular edema (eight cases), and graft rejection (seven cases) resulted in marked visual loss.