Filtering bleb structure associated with long-term intraocular pressure control after amniotic membrane-assisted trabeculectomy.

PURPOSE/AIM: To determine whether amniotic membrane transplantation (AMT) at trabeculectomy affects intrableb structures and which intrableb parameters are significantly correlated with the long-term intraocular pressure (IOP) control. MATERIALS AND METHODS: Enrolled were 64 eyes of 56 glaucoma patients who underwent trabeculectomy without (36 eyes) or with (28 eyes) AMT. Bleb structure was evaluated by ultrasound biomicroscopy (UBM) at least one year after surgery. IOP control was defined as good when the eyes had a more than 30% decrease in the preoperative IOP and an IOP value <18 mmHg if the preoperative IOP was higher than 21 mmHg. Logistic regression analyses were conducted to identify factors significantly associated with IOP control. RESULTS: Intervals between surgery and the timing of the UBM examinations (median; 2.5 years) and the overall frequency of good IOP control (28/36 in the eyes without AMT and 17/28 in those with AMT; chi-square test, P = 0.2276) were similar in the two groups. The eyes with AMT had a significantly lower number of type H (high reflective) or L (low reflective) blebs and a higher number of type E (encapsulated) blebs compared to those without AMT (P < 0.0001). Among independent variables, which included age, sex, glaucoma type, lens status, the number of ocular hypotensives, and previous intraocular surgeries, only type F (flattened) bleb in eyes without AMT (P = 0.0008, odds ratio [OR] = 0.0256) and no or limited intrableb fluid-filled space in eyes with AMT were significantly associated with poor IOP control (P = 0.0026, OR = 0.0111, and 0.0071, 0.0167, respectively). CONCLUSIONS: Intrableb structures after trabeculectomy alone versus AMT-assisted trabeculectomy were distinct. The bleb wall reflectivity in the former and the extent of the subconjunctival fluid-filled space in the latter were factors associated with long-term IOP control.

Comparison of mean deviation with AGIS and CIGTS scores in association with structural parameters in glaucomatous eyes.

OBJECTIVE: To evaluate which of the 3 clinically used visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. METHODS: In 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD> or =-6 dB; moderate, -12 dB< or =MD<-6 dB; advanced, MD<-12 dB). RESULTS: Among structure-function relationships in all subjects, the highest correlation determination (R) was MD with RNFLT (=0.298). CIGTS score showed better R than MD or AGIS score with rim area, but these values were not higher than any R with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. CONCLUSIONS: No clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.

Association of optic disc configuration and clustered visual field sensitivity in glaucomatous eyes with hemifield visual field defects.

PURPOSE: To compare the morphologic alterations between upper and lower sectors of the optic nerve head (ONH) in eyes with primary open-angle glaucoma (POAG) that have hemifield visual field defects and to evaluate the correlation between this sectoral ONH damage and visual field sensitivity loss within the corresponding clustered test points of standard automated perimetry. METHODS: Visual field testing with Humphrey Field Analyzer and imaging with Heidelberg Retina Tomograph (HRT) were performed in 87 eyes from 87 Japanese patients with POAG and 150 eyes from 150 normal subjects. Global and segmental HRT topographic parameters were compared among POAG patients with superior hemifield defects, those with inferior hemifield defects, and controls. The correlation between the sectoral HRT measurements and the sum of total deviation values in the corresponding clustered visual field test points was analyzed in the 2 POAG groups. RESULTS: The HRT measurements in both POAG groups were significantly different from those of controls, not only in the sectors corresponding to abnormal hemifield, but also in the sectors corresponding to the normal visual hemifield. There was a linear correlation between the sectoral HRT parameters and clustered visual field sensitivities in the affected hemifield areas. CONCLUSIONS: The present study indirectly supports the notion that the relationship between structural and functional damage of glaucomatous optic neuropathy is not linear when evaluated with the currently available techniques and instruments.

Regional relationship between retinal nerve fiber layer thickness and corresponding visual field sensitivity in glaucomatous eyes.

OBJECTIVE: To establish the structure-function relationship between peripapillary retinal nerve fiber layer (RNFL) thickness and visual field (VF) test points in standard automated perimetry. METHODS: We included 213 eyes with open-angle glaucoma and VF loss in this cross-sectional study. Correlations between individual VF sensitivity at 52 test points and peripapillary RNFL thickness divided into 16 sectors were calculated. The RNFL thickness was measured by Stratus optical coherence tomography. A new VF cluster map corresponding to RNFL sectors was generated by grouping the VF test points with the highest relation to each RNFL sector. RESULTS: The VF sensitivity at each test point was significantly correlated with the sectoral RNFL thickness. The highest coefficient of determination (R(2)) for a superotemporal RNFL sector and VF sensitivity at an inferotemporal test point (9 degrees temporal and 15 degrees inferior from the center) in standard automated perimetry was 0.500 (P < .001). Clustered VF test points most highly related to the RNFL sectors were asymmetrically located between the upper and lower hemifields. A newly developed map revealed significant structure-function relationships. CONCLUSIONS: We describe an association between VF sensitivity at test points and sectoral RNFL thickness. Nine clustered VF test points corresponding to 9 RNFL regions were demonstrated from the structure-function relationships.

Intraocular pressure lowering effect of once daily versus once weekly latanoprost instillation in the same normal individuals.

This study tested whether once weekly instillation of latanoprost exerts the similar IOP lowering effect as once daily instillation in the same individuals. Latanoprost was administered on right eyes of eight healthy male volunteers once daily first for 24 days, which was followed by the 31-day washout and the subsequent once weekly instillation for another 24 days. The mean baseline IOP was 12.06 +/- 1.50 (range, 10.0 to 14.0) mmHg, whereas the mean IOP during once daily treatment was 9.87 +/- 1.71 mmHg, which was significantly lower than the former (p=0.025). The mean washout IOP was 12.56 +/- 2.16 mmHg, which was similar to the baseline IOP. The mean IOP during once weekly instillation of latanoprost was 11.34 +/- 1.51 mmHg, which was not statistically different from the washout IOP. Four of the 8 subjects showed 15% or more reduction in IOP both during once daily and once weekly instillations, two of whom were overlapped. Since the magnitude of the IOP reduction with once daily use was higher than that with once weekly use even in the responders, the current protocol of once daily instillation should be respected.

Nipradilol protects rat retinal ganglion cells from apoptosis induced by serum deprivation in vitro and by diabetes in vivo.

PURPOSE: To investigate if nipradilol has an anti-apoptotic effect in serum-deprived RGC-5 cells and in the streptozotocin-induced diabetic rat retina. METHODS: Apoptosis was quantified by activated caspase-3 immunohistochemistry or terminal dUTP nick end-labeling assay. RESULTS: Nipradilol dose-dependently suppressed apoptosis in a protein kinase A- and G-dependent manner and counteracted glutamate-induced calcium entry in the RGC-5 cells and reduced apoptotic cells in the retinal ganglion cell layer of 4- and 12-week diabetic retinas compared to controls when instilled for 5 days. Removal of the nitric oxide moiety from nipradilol blocked these effects. CONCLUSIONS: Nipradilol protects RGCs from apoptosis induced by serum-deprivation in vitro and by diabetes in vivo. The NO-related signaling pathway mediates the anti-apoptotic ability of nipradilol.

Long-term results of amniotic membrane transplantation-assisted bleb revision for leaking blebs.

BACKGROUND: To report long-term results of amniotic membrane transplantation (AMT)-assisted bleb revision for intractable late-onset bleb leak. METHODS: Retrospective medical record review of six consecutive patients who underwent AMT-assisted bleb revision for late-onset bleb leak at the Kobe University hospital between December 2001 and March 2004. RESULTS: The median (range) of age was 60 (20-77) years. All patients had a history of trabeculectomy with adjunctive use of 0.4 mg/ml mitomycin C. The median (range) of interval between the prior trabeculectomy and bleb leak was 15 (4-54) months. Preoperative intraocular pressure (IOP) was lower than 10 mmHg in two cases, while it was 25 mmHg or higher in three patients, who had a localized, ischemic, thin-wall leaking bleb circumscribed with extensively scarred tissue. The median (range) of follow-up after the AMT-assisted bleb revision was 49 (41-67) months. Postoperative IOP was well controlled in all patients without medication or with a maximum of three glaucoma medications. No patients presented recurrence of the bleb leak or AMT-related complications during entire follow-up. All patients showed at final visit a diffuse bleb which extended posteriorly beyond the conjunctival incision line. CONCLUSION: AMT-assisted bleb revision successfully treated intractable late-onset bleb leak. Further comparative studies are needed to confirm the present result.

cAMP-responsive element binding protein mediates a cGMP/protein kinase G-dependent anti-apoptotic signal induced by nitric oxide in retinal neuro-glial progenitor cells.

Nitric oxide (NO) is cytoprotective to certain types of neuronal cells. The neuroprotective ability of NO in the retina was reportedly mediated by the cyclic GMP (cGMP) to protein kinase G (PKG) pathway. Cyclic AMP-responsive element binding protein (CREB) plays an essential role in the NO/cGMP/PKG-mediated survival of rat cerebellar granule cells. We tested whether CREB transduces the NO/cGMP/PKG anti-apoptotic cascade in R28 neuro-glial progenitor cells. Apoptosis was induced in R28 cells by serum deprivation for 24 h. Varying concentrations of two NO donors, sodium nitroprusside (SNP) and nipradilol, were added to medium with or without an NO scavenger, a soluble guanylyl cyclase inhibitor, or a PKG inhibitor. The cells were immunostained against activated caspase-3 and counterstained with Hoechst 33258. Apoptosis was quantified by counting activated caspase-3 positive or pyknotic cells. SNP and nipradilol rescued R28 cells from apoptosis in a dose-dependent manner, at an optimal concentration of 1.0 microM and 10 microM, respectively. Higher concentrations were cytotoxic. The NO scavenger and the inhibitors decreased the anti-apoptotic effect of the NO donors. Intracellular cGMP levels were increased after exposure to SNP and nipradilol. Western blotting showed that both NO donors increased CREB phosphorylation, which was blocked when pre-exposed to the inhibitors. Transfection with a dominant negative CREB construct defective of phosphorylation at Ser-133 interfered with the anti-apoptotic activity of SNP. These results indicate that CREB at least in part mediates the cGMP/PKG-dependent anti-apoptotic signal induced by NO in R28 cells.

Quantification of retinal nerve fiber layer thickness reduction associated with a relative afferent pupillary defect.

BACKGROUND: A relative afferent pupillary defect (RAPD) is known to develop only when more than 25% of retinal ganglion cells are ablated in monkeys' eyes. However, there was no prior study to estimate biometrically the degree of retinal nerve fiber layer (RNFL) thickness reduction leading to the development of RAPD in live human eyes. The purpose of this study was to examine the correlation between the amount of RNFL thickness reduction and the depth of a clinically detectable RAPD in patients with unilateral optic atrophy. METHODS: Enrolled were 20 patients with optic atrophy of various etiologies. We quantified RAPD by performing the swinging flashlight test with log-scaled neutral density filters placed over the unaffected eye. Average RNFL thickness was measured by OCT3000 with the average RNFL thickness program. Linear regression analysis was used in assessing the relationship between RAPD and the ratio of affected to unaffected average RNFL thickness. RESULTS: The mean of average RNFL thickness was 95.6+/-17.3 microm in the unaffected eyes and 50.7+/-19.3 microm in the affected eyes (P<0.001). Regression analysis between RAPD and the ratio of affected to unaffected average RNFL thickness revealed a correlation coefficient R2=0.48 (P=0.0007). The regression line intersected the y-axis at 0.77. CONCLUSIONS: RAPD was not clinically detected until at least approximately 25% of the retinal nerve fibers were lost when compared with the unaffected eyes. Substantial retinal ganglion cell damage is required for the development of RAPD.

Comparison of confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography to discriminate ocular hypertension and glaucoma at an early stage.

BACKGROUND: The aim was to compare the ability of confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT) to discriminate eyes with ocular hypertension (OHT), glaucoma-suspect eyes (GS) or early glaucomatous eyes (EG) from normal eyes. METHODS: Ocular hypertension, GS, and EG were defined as normal disc with intraocular pressure >21 mmHg, glaucomatous disc without visual field loss, and glaucomatous disc accompanying the early glaucomatous visual filed loss respectively. Ninety-three normal eyes, 26 OHT, 55 GS, and 67 EG were enrolled. Optic disc configuration was analyzed by CSLO (version 3.04), whereas retinal nerve fiber layer thickness was analyzed by SLP (GDx-VCC; version 5.3.2) and OCT-1 (version A6X1) in each individual. The measurements were compared in the four groups of patients. Receiver operating characteristic curve (ROC) and area under the curve (AUC) discriminating OHT, GS or EG from normal eyes were compared for the three instruments. RESULTS: Most parameters in GS and EG eyes showed significant differences compared with normal eyes. However, there were few significant differences between normal and OHT eyes. No significant differences were observed in AUCs between SLP and OCT. In EG eyes, the greatest AUC parameter in OCT (inferior--120; 0.932) had a higher AUC than that in CSLO (vertical cup/disc ratio; 0.845; P=0.017). In GS, the greatest AUC parameter in OCT (average retinal nerve fiber layer [RNFL] thickness; 0.869; P=0.002) and SLP (nerve fiber indicator [NFI]; 0.875; P=0.002) had higher AUC than that in CSLO (vertical cup/disc ratio; 0.720). CONCLUSIONS: Three instruments were useful in identifying GS and EG eyes. For glaucomatous eyes with or without early visual field defects, SLP and OCT performed similarly or had better discriminating abilities compared with CSLO.