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Joseph Caprioli

Publications and source records attributed to Joseph Caprioli.

At least 37 records · Page 2Linked to original sources

Optic disk appearance in advanced age-related macular degeneration.

PURPOSE: To describe and quantify the appearance of the optic disk in patients with advanced age-related macular degeneration (ARMD). DESIGN: Retrospective comparative study. METHODS: A total of 316 charts were reviewed. From these, 45 subjects with advanced ARMD (defined as geographic atrophy or disciform scar) in at least one eye were enrolled. Patients with glaucoma or glaucoma visual field defects were excluded. The probability of glaucomatous optic nerve damage was scored by evaluation of stereoscopic optic disk photographs in a masked fashion, according to a predefined evaluation scale and measured with confocal ophthalmoscopy (Heidelberg Retinal Tomograph; HRT). The area of macular involvement was measured in units of disk area. The optic disk evaluation scores and HRT measurements of a group of eyes with a large area of ARMD were compared with their fellow eyes with smaller areas of ARMD. The correlations between the area of macular involvement with the optic disk evaluation scores and HRT measurements were analyzed. MAIN OUTCOME MEASURES: The optic disk evaluation scores and the HRT measurements between study groups. RESULTS: Eyes with larger areas of ARMD had optic disks that were more likely to be classified as glaucomatous by clinical evaluation (3.45 +/- 0.23 vs 3.05 +/- 0.18, P =.015) and by HRT imaging analysis (-0.995 +/- 0.423 vs -0.376 +/- 0.249, P =.030) than the fellow eyes with smaller areas of ARMD. For eyes with six or more disk areas of ARMD, larger areas of ARMD correlated with a higher cup/disk ratio (P =.022), smaller neuroretinal rim area (P =.022), and glaucomatous classification (P =.040) with HRT discriminant function analysis. CONCLUSIONS: Eyes with large areas of geographic or diskiform ARMD have optic disk structural alterations that resemble glaucomatous optic neuropathy. This should be taken into consideration when evaluating patients with ARMD for glaucomatous damage.

Aged↗

Visual field changes after cataract extraction: the AGIS experience.

PURPOSE: To test the hypothesis that cataract extraction in glaucomatous eyes improves overall sensitivity of visual function without affecting the size or depth of glaucomatous scotomas. DESIGN: Experimental study with no control group. METHODS: One hundred fifty-eight eyes (of 140 patients) from the Advanced Glaucoma Intervention Study with at least two reliable visual fields within a year both before and after cataract surgery were included. Average mean deviation (MD), pattern standard deviation (PSD), and corrected pattern standard deviation (CPSD) were compared before and after cataract extraction. To evaluate changes in scotoma size, the number of abnormal points (P < .05) on the pattern deviation plot was compared before and after surgery. We described an index ("scotoma depth index") to investigate changes of scotoma depth after surgery. RESULTS: Mean values for MD, PSD, and CPSD were -13.2, 6.4, and 5.9 dB before and -11.9, 6.8, and 6.2 dB after cataract surgery (P < or = .001 for all comparisons). Mean (+/- SD) number of abnormal points on pattern deviation plot was 26.7 +/- 9.4 and 27.5 +/- 9.0 before and after cataract surgery, respectively (P = .02). Scotoma depth index did not change after cataract extraction (-19.3 vs -19.2 dB, P = .90). CONCLUSIONS: Cataract extraction caused generalized improvement of the visual field, which was most marked in eyes with less advanced glaucomatous damage. Although the enlargement of scotomas was statistically significant, it was not clinically meaningful. No improvement of sensitivity was observed in the deepest part of the scotomas.

Aged↗

Variable corneal compensation improves discrimination between normal and glaucomatous eyes with the scanning laser polarimeter.

PURPOSE: The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes. DESIGN: Prospective, nonrandomized, comparative case series. PARTICIPANTS: Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes. TESTING: Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects. MAIN OUTCOME MEASURES: Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined. RESULTS: Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (P<0.021). When the discriminant functions were applied to a subset of patients with early visual field loss, areas under the ROC curve were 0.82 for the FCC and 0.90 for the VCC (P<0.016). CONCLUSION: Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

Adult↗

Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study.

PURPOSE: To investigate the risk factors associated with visual field (VF) progression in the Advanced Glaucoma Intervention Study (AGIS) with pointwise linear regression (PLR) analysis of serial VFs. DESIGN: Prospective, multicenter, randomized clinical trial. PARTICIPANTS: Five hundred nine eyes of 401 patients from the AGIS with a baseline VF score of or=7 VF examinations, and >or=3 years of follow-up were selected. MAIN OUTCOME MEASURE: Visual field progression. METHODS: This is a cohort study of patients enrolled in a prospective randomized clinical trial (AGIS). Worsening of a test location on PLR analysis was defined as a change of threshold sensitivity of >or=1.00 decibels a year, with P<or=0.01. Visual field progression was defined as worsening of at least 2 test locations within a Glaucoma Hemifield Test cluster with PLR analysis. Multivariate logistic regression was used to determine risk factors associated with VF worsening. Intraocular pressure (IOP) fluctuation was defined as standard deviation of the IOP at all visits after the initial surgery. RESULTS: The mean (+/- standard deviation) follow-up time and baseline AGIS score were 7.4 (+/-1.7) years and 7.7 (+/-4.4), respectively. Visual field progression was detected with PLR analysis in 151 eyes (30%). Older age at the initial intervention (P = 0.0012; odds ratio [OR], 1.30; 95% confidence interval [CI], 1.11-1.50), larger IOP fluctuation (P = 0.0013; OR, 1.31; 95% CI, 1.12-1.54), increasing number of glaucoma interventions (P = 0.01; OR, 1.74; 95% CI, 1.14-2.64), and longer follow-up (P = 0.02; OR, 1.19; 95% CI, 1.03-1.38) were associated with increased odds of VF progression. When regression analyses were repeated in eyes with and without a history of cataract extraction, IOP fluctuation was the only variable to be consistently associated with VF progression. CONCLUSION: Both increasing age and greater IOP fluctuation increase the odds of VF progression by 30% (for each 5-year increment in age and 1-mmHg increase in IOP fluctuation). The higher risk conferred by IOP fluctuation was consistently observed in eyes with and without a history of cataract extraction.

Adult↗

Optical coherence tomography to detect and manage retinal disease and glaucoma.

PURPOSE: To review basic principles of optical coherence tomography, and to describe its use in the diagnosis and management of retinal diseases and glaucoma. DESIGN: Perspective. METHODS: Literature review. RESULTS: Optical coherence tomography is a noninvasive imaging technique that has been used increasingly to diagnose and manage a variety of retinal diseases and glaucoma. Optical coherence tomography (OCT) is based on the principal of Michelson interferometry. Interference patterns produced by low coherence light reflected from retinal tissues and a reference mirror are processed into an "A-scan" signal. Multiple A-scan signals are aligned to produce a two-dimensional image that can be thought of as a form of "in vivo histology." Optical coherence tomography has been used to identify macular holes, to differentiate macular holes from simulating lesions, to identify lamellar macular holes, macular cysts, vitreomacular traction, subretinal fluid, pigment epithelial detachment, and choroidal neovascularization. It can be used to identify and quantify macular edema, and to measure retinal thickness changes in response to therapy. Macular thickness measurements determined by OCT correlate well with visual acuity and with leakage observed by fluorescein angiography. Optical coherence tomography is an accurate and reproducible method to measure retinal nerve fiber layer thickness. Particularly, when used in combination with other optic nerve imaging techniques, it can be used to differentiate glaucomatous eyes from normal eyes. Despite its usefulness, OCT has its limitations. Optical coherence tomography equipment is expensive, and not all insurance companies reimburse this procedure. Image quality is dependent on operator technique and can be degraded in the presence of media opacity. Change analysis software for glaucoma applications is not fully developed, and there is a scarcity of age, gender, and race-specific normative data upon which to compare eyes with retinal disease and glaucoma. In the next few years, it is likely that the role of OCT as a method to diagnose and manage retinal disease and glaucoma will be further defined, and many of the current limitations will be overcome. CONCLUSIONS: Optical coherence tomography is a useful imaging technique to diagnose and manage a variety of retinal diseases and glaucoma. Care is needed to avoid artifacts and image misinterpretation.

Diagnostic Techniques, Ophthalmological↗

Baerveldt-350 implant versus Ahmed valve for refractory glaucoma: a case-controlled comparison.

PURPOSE: To compare the efficacy of intraocular pressure (IOP) control of the Baerveldt-350 implant with tube ligature and the Ahmed valve in patients with refractory glaucoma. PATIENTS AND METHODS: Four hundred seventy glaucoma drainage device procedures from July 1995 to July 2001 (6 years) were reviewed retrospectively. Thirty-two cases of Baerveldt-350 implantation performed in patients with glaucoma refractory to medical treatment and filtering procedures, without previous drainage device or cyclodestructive procedures, and with a minimum of 1-year follow-up were identified. Thirty-two cases of Ahmed valve implantation were matched case by case with 32 Baerveldt-350 cases for age, race, gender, glaucoma subtype, previous ocular history, preoperative IOP, and surgeon who performed the implantation. The two groups were compared for IOP control, visual outcome, complication rate, and surgical success rate. Surgical success rate was defined as an IOP reduction greater than or equal to 30% and final IOP more than 5 mm Hg and less than 22 mm Hg, without devastating complications. RESULTS: Over a follow-up period of 1 year, no statistically significant differences were detected between the Baerveldt-350 implant versus Ahmed valve for IOP control (12.1 +/- 5.3 mm Hg vs. 13.6 +/- 5.6 mm Hg respectively, at a power of 90% to detect a difference of 3.2 mm Hg between the two groups and P = 0.05), surgical success rate (65.6% vs. 65.6% respectively, complete and qualified combined), postoperative hypotony rate (37.5% vs. 34.4% respectively), and visual acuity changes of more than 1 line in Snellen visual acuity (43.3% vs. 29.0% respectively). CONCLUSION: In a case-controlled comparison, the Baerveldt-350 implant and the Ahmed valve had similar IOP control and surgical outcomes in patients with refractory glaucoma at 1-year follow-up.

Adult↗

Relationship between visual field sensitivity and retinal nerve fiber layer thickness as measured by scanning laser polarimetry.

PURPOSE: To evaluate the strength and pattern of the relationship between visual field (VF) sensitivity and retinal nerve fiber layer (RNFL) thickness measurements by scanning laser polarimetry (SLP). METHODS: Fifty-four eyes of 54 normal subjects (age, 42 +/- 15 years; VF mean deviation [MD], -0.69 +/- 1.01 dB) and 51 eyes of 51 glaucoma patients (age, 66 +/- 14 years; VF MD, -6.92 +/- 5.43 dB) were imaged with an SLP using fixed corneal compensation (FCC) and variable corneal compensation (VCC). VF sensitivity was recorded in the dB and the 1/L scales. Linear and logarithmic relationships were sought globally and in six VF sectors. Relationships of VF and RNFL thickness with age were sought in normal subjects. RESULTS: Both VF sensitivity and RNFL thickness declined with age (as determined by the regression slope): -0.13% (P = 0.0005) and -0.64% (P = 0.0001) per year for dB and 1/L VF sensitivity, respectively, and -0.25% (P = 0.003) per year for VCC RNFL thickness. FCC RNFL thickness was not statistically significantly related to age. The relationship of VF sensitivity to VCC global (R(2) = 0.49) and sectoral (R(2) = 0.00-0.47) RNFL thickness was greater than for FCC global (R(2) = 0.12) and sectoral (R(2) = 0.00-0.21) RNFL thickness. Relationships were curvilinear with the dB scale, with logarithmic regression of dB VF sensitivity against RNFL thickness being significantly better than linear regression. Logarithmic regression of 1/L VF sensitivity against RNFL thickness was no better than linear regression for all sectors. There was no relationship between VF sensitivity and RNFL thickness in the temporal peripapillary RNFL sector. CONCLUSIONS: The strength of the structure/function relationships compare well with previous reports in the literature. The relationships were curvilinear with the dB scale and linear with the 1/L scale, and were much stronger with VCC than with FCC RNFL thickness measurements.

Adult↗

Prediction of visual field progression in glaucoma.

PURPOSE: To determine the probability of future glaucomatous visual field (VF) progression with clinical and perimetric data. METHODS: One hundred sixty-one eyes of patients (161) enrolled in the Advanced Glaucoma Intervention Study (AGIS) with >or=8 years of follow-up and a baseline VF score <or=16 were selected. VF progression at 8 years was determined with point-wise linear regression (PLR) analysis, using a two-omitting algorithm. The course of VF series over the first 4 years of follow-up was quantified by an index, the sum of slopes, which is the sum of all slopes of VF thresholds with P < 0.05 when PLR was performed on the 4-year data. The following parameters were included in a logistic regression model to predict 8-year outcomes from the first 4 years of follow-up: intervention sequence, age, AGIS VF score, mean IOP, IOP fluctuation, and sum of slopes. RESULTS: Sixty-four (40%) eyes progressed after 8 years as determined by PLR analysis. Two parameters were predictive of subsequent VF progression, as identified at 8 years (predictive power: 76%): more negative sum of slopes (i.e., faster or more extensive deterioration; P < 0.001) and older age at 4 years (P = 0.049). When sum of slopes alone was used to predict outcomes at 8 years, the predictive power was the same. CONCLUSIONS: The VF sum of slopes can be used to estimate the probability of subsequent VF worsening with reasonable, clinically useful accuracy. This probability may be combined with other clinical information for more effective clinical predictions and treatment decisions.

Aged↗

2-Deoxy-D-glucose protects retinal ganglion cells against excitotoxicity.

Caloric restriction mimicked by administration of 2-deoxy-D-glucose (2DG) has been shown to protect cerebral neurons against ischemia and excitotoxicity. This study examined the protective effects of pretreatment with 2DG on retinal neurons in N-methyl-D-aspartate (NMDA) excitotoxicity in rats. There was a significantly reduced number of TUNEL-labeled cells in the retinal ganglion cell layer 18 h after intravitreal injection of NMDA with 2DG pretreatment. At 7 days after NMDA, 2DG pretreatment significantly preserved neurons in the retinal ganglion cell layer and reduced immunoreactivity of glial fibrillary acidic proteins in retinas. Our findings demonstrate that caloric restriction mimicked by 2DG protects retinas from NMDA excitotoxicity.

Animals↗

Hyperthermic pre-conditioning protects retinal neurons from N-methyl-D-aspartate (NMDA)-induced apoptosis in rat.

Glutamate-induced excitotoxicity is associated with a selective loss of retinal neurons after retinal ischemia and possibly in glaucoma. Since heat shock protein (HSP) 70 is known to play a protective role against ischemic neuronal injury, which is also linked to excitotoxicity, we studied the expression of inducible (HSP72) and constitutive (HSC70) forms of HSP70 in apoptosis of retinal ganglion cells (RGCs) after intravitreal injection of 8 nmoles N-methyl-D-aspartate (NMDA), a glutamate receptor agonist. Approximately 18 h after NMDA injection, there were increased numbers of TUNEL-positive cells and cells with elevated HSP72 immunoreactivity in the retinal ganglion cell layer (RGCL), but there were no noticeable changes in HSC70 immunoreactivity. These HSPs positive cells were also Thy-1 positive, a marker for RGCs. Hyperthermic pre-conditioning, which is known to induce HSPs, given 6 or 12 h prior to NMDA injection ameliorated neuronal loss in the RGCL as counted 7 days after NMDA injection but pre-conditioning at 18 h prior to NMDA injection did not have any ameliorative effect. Quercetin, an inhibitor of HSP synthesis, abolished the ameliorative effect of hyperthermic pre-conditioning. Pre-conditioning elevated HSP72 but not HSC70 immunoreactivity and reduced the number of TUNEL-positive cells in the RGCL at 18 h. Our results suggest that intravitreal injection of NMDA induces an up-regulation of HSP72 in a time-dependent manner but not HSC70 in RGCs, indicating a stress response of HSP72 in RGCs and other inner retinal neurons after exposure to NMDA. Hyperthermic pre-conditioning given within a therapeutic window is neuroprotective to the retina against NMDA-induced excitotoxicity, likely by inhibiting apoptosis through the modulation of HSP72 expression.

Animals↗

Neural networks to identify glaucomatous visual field progression.

PURPOSE: To describe a method to determine progression of glaucoma based on visual field thresholds. DESIGN: Observational retrospective longitudinal cohort study. METHODS: A back propagation neural network with three hidden layers was developed with commercial software. Visual field data from 80 patients who participated in the Advanced Glaucoma Intervention Study (AGIS) were used. Glaucomatous visual field progression was defined as a change of 4 or more units in the AGIS score, confirmed by at least two sequential subsequent tests. Inputs to the neural network consisted of threshold measurements from 55 visual field locations from the baseline examination and each follow-up examination. The data set was randomized so the sequence of examinations would not influence the training or testing of the neural network. Two thirds of the randomized data were used for training and the remaining one third for testing. RESULTS: The mean age of 80 patients enrolled in AGIS at initial examination was 67.4 (+/- 7.3 standard deviation [SD]) years. The average follow-up period was 7.2 (+/-2.3 SD) years and the mean duration between examinations was 0.46 (+/- 0.39 SD) years. The neural network estimated the probability of progression for each baseline and follow-up comparison with an average sensitivity of 86% and specificity of 88%. The area under the receiver operating characteristic (ROC) curve was 0.92, with a sensitivity of 86% at the 80% specificity level and a sensitivity of 91% at the 90% specificity level. CONCLUSIONS: From analysis of AGIS data, progression of glaucoma could be detected from visual field thresholds with a neural network.

Aged↗

Evaluation of the hypertensive phase after insertion of the Ahmed Glaucoma Valve.

PURPOSE: To investigate the postoperative hypertensive phase (HP) in patients undergoing glaucoma drainage implant surgery. DESIGN: Interventional case series. METHODS: A retrospective chart review of 156 consecutive eyes (139 patients) who underwent placement of an Ahmed Glaucoma Valve (AGV) with a follow-up of >or=3 months was performed. Main outcome measures were occurrence and resolution of the HP and intraocular pressure (IOP) control. The HP was defined as IOP > 21 mm Hg during the first 3 months after surgery. Resolution of the HP was defined as an IOP < 22 mm Hg and an IOP reduction of 3 mm Hg with the same or fewer number of glaucoma medications. RESULTS: An HP was observed in 88 eyes (56%). It occurred after a mean of 5.0 weeks (median, 4 weeks; range, 1-13 weeks) with an average (+/- standard deviation) peak IOP of 30.1 (+/- 7.5) mm Hg. Resolution of the HP occurred in 19 of 68 eyes (28%) with available data. Eyes with an HP had a higher mean IOP and needed more medications 6 to 12 months after surgery than eyes without an HP (17.2 +/- 5.6 vs 14.3 +/- 5.8 mm Hg; P =.012 and 1.7 +/- 1.2 vs 0.3 +/- 0.6 medications; P <.001, respectively). CONCLUSION: A hypertensive phase occurs frequently after implantation of the AGV. However, it resolves in only a minority of eyes. The majority of eyes with an HP have no significant improvement of IOP control and continue to require the same number of glaucoma medications as they did during the HP.

Adolescent↗

Evaluating several sources of variability for standard and SWAP visual fields in glaucoma patients, suspects, and normals.

PURPOSE: To quantify factors affecting test-retest variability of threshold measurements over a series of 3 serial visual fields (VF). DESIGN: Prospective comparative observational study. PARTICIPANTS: Forty-one normals, 10 suspects and 35 stable glaucoma patients. METHODS: All subjects performed 3 standard and 3 short-wavelength automated perimetry (SWAP) VFs. At each VF location, severity (defined as age-corrected total deviation) and test-retest variability (TRV), defined as the standard deviation of 3 serial threshold values, were calculated. A multiple regression model (constructed separately for standard VF and SWAP) incorporated 13 factors: severity, location, eccentricity, study group, diagnosis, superior versus inferior hemifield, nasal versus temporal hemifield, one-versus-two thresholds, age, mean pupil size, pupil size variability, between-subject variation, and residual variation. MAIN OUTCOME MEASURES: Variability in threshold sensitivity VF values. RESULTS: Mean TRV (+/- standard deviation) for normal, suspect and glaucoma eyes, respectively, was: 1.28 +/- 0.87, 1.53 +/- 1.04 and 2.20 +/- 1.79 dB for standard VF, and 1.87 +/- 1.35, 1.86 +/- 1.24 and 2.68 +/- 1.85 dB for SWAP. The contribution of each factor to the model for standard VF and SWAP (SWAP in parentheses) were: severity 15.5% (6.9%); location 2.7% (4.1%); eccentricity 1.1% (0.64%); diagnosis 2.9% (5.9%); "superior versus inferior" hemifield 0.17% (1.7%); "nasal versus temporal" hemifield 0.06% (0.02%); one-versus-two thresholds 0.04% (0.16%); age 0.1% (0.06%); mean pupil size 0.59% (0.1%); pupil size variability 3.2% (2.8%); between-subject 8.0% (13.5%) and residual variation 61.0% (66.6%). Excluding between-subject and residual variation, the 11-factor model was able to account for less than one third of the variability seen in both standard VF and SWAP. CONCLUSIONS: Severity of defect and between subject variation exerted the largest effect on TRV. However, even if all 11 factors could be adjusted for, it would reduce the magnitude of TRV by only 30%. More work is needed to reduce the remaining variability inherent in psychophysical testing and to better understand the intrinsic physiological variability present both in healthy and diseased eyes. It is possible that a larger number of VFs used for the calculation of TRV might further reduce the magnitude of the remaining variability found in this study.

Adult↗

Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model.

PURPOSE: To study the effects of geranylgeranylacetone (GGA) on the expression of inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal ganglion cells (RGCs) in a rat model of glaucoma. METHODS: Adult Wistar rats were given intraperitoneal injections of GGA at 200 mg/kg daily. Western blot analysis and immunohistochemical staining for HSP72 and HSC70 were performed after 1, 3, and 7 days of treatment with GGA. After 7 days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation 5 days after intracameral injection of india ink. After the first laser photocoagulation, GGA was administered twice a week. RGC survival was evaluated after 5 weeks of elevated IOP. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of elevated IOP. Quercetin, an inhibitor of HSP expression, was also administered to a separate group. RESULTS: There was increased expression of HSP72 in RGCs at 3 and 7 days after administration of GGA, but HSC70 was unchanged. After 5 weeks of elevated IOP, there was a 27% +/- 6% loss of RGCs. The administration of GGA significantly reduced the loss of RGCs, lessened optic nerve damage, decreased the number of TUNEL-positive cells in the RGC layer, and increased HSP72. Quercetin abolished these protective effects. CONCLUSIONS: These results demonstrate that systemic administration of GGA protects RGCs from glaucomatous damage in a rat model and suggest a novel pathway for neuroprotection in patients with glaucoma.

Animals↗

Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model.

PURPOSE: To study the effects of geranylgeranylacetone (GCA) on the expression of inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal ganglion cells (RGCs) in a rat model of glaucoma. METHODS: Adult Wistar rats were given intraperitoneal injections of GGA, 200 mg/kg daily. Western blot analysis and immunohistochemical staining for HSP72 and HSC70 were performed after 1, 3, and 7 days of GGA administration. After 7 days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation 5 days after intracameral injection of india ink. After the first laser photocoagulation, CGA was given twice a week. RGC survival was evaluated after 5 weeks of IOP elevation. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of IOP elevation. Quercetin, an inhibitor of HSP expression, was also administered to a separate group. RESULTS: There was increased expression of HSP72 in RGCs at 3 and 7 days after GGA administration, but HSC70 was unchanged. After 5 weeks of IOP elevation, there was 27% +/- 6% loss of RGCs. The administration of GGA significantly reduced the loss of RGCs, lessened optic nerve damage, decreased the number of TUNEL-positive cells in the RGC layer, and increased HSP72. Quercetin administration abolished these protective effects. CONCLUSIONS: These results demonstrate that systemic administration of GGA protects RGCs from glaucomatous damage in a rat model and suggest a novel pathway for neuroprotection for patients with glaucoma.

Animals↗

Development of a novel reference plane for the Heidelberg retina tomograph with optical coherence tomography measurements.

PURPOSE: To develop an ideal reference plane for the Heidelberg Retina Tomograph (HRT) with the assistance of optical coherence tomography (OCT) measurements of the mean retinal nerve fiber layer (RNFL) thickness. PATIENTS AND METHODS: The mean RNFL thickness was measured with OCT in eyes with early glaucoma (n = 50) and age-matched normal eyes (n = 40) at a circle as close as possible to the disc margin without touching it. Glaucomatous eyes were enrolled from chronic open-angle glaucoma patients with reproducible glaucomatous visual field defects with standard automated perimetry. One eye of each patient was randomly selected. A new reference plane was defined as located posteriorly from the mean height of the contour line by the amount of mean RNFL thickness measured with the OCT. Receiver-operating characteristic (ROC) curves were generated to compare the ability of parameters obtained with the conventional and the new reference plane to differentiate glaucomatous eyes from normal eyes. The same analysis was performed for early glaucomatous eyes with myopic refractive errors (n = 25). RESULTS: The areas under the ROC curves (AUCs) were greater for rim area, rim area/disc area, and rim volume with the new reference plane compared with those with the conventional reference plane, but they were not significantly different. When the same analysis was performed for myopic glaucomatous eyes, the AUCs for rim area, rim area/disc area, and rim volume with the new reference plane were greater than those with the conventional reference plane ( = 0.002, 0.010, and 0.034, respectively). CONCLUSION: A novel reference plane for the HRT defined by OCT measurements may improve the ability of the HRT to detect early glaucoma, especially in eyes with tilted discs.

Adult↗

Comparison of optic nerve imaging methods to distinguish normal eyes from those with glaucoma.

PURPOSE: To compare the ability of qualitative assessment of optic nerve head stereophotographs (ONHPs), confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT) to distinguish normal eyes from those with early to moderate glaucomatous visual field defects. METHODS: Eighty-nine eyes (63 normal, 63 age-matched with glaucoma) of 89 subjects more than 40 years of age were studied. Receiver operating characteristic (ROC) curves were generated from discriminant analysis of CSLO, SLP, and OCT measurements and from ONHP scores. Sensitivity at 80% and specificity at 90% were calculated. Differences between individual methods and combinations of methods were assessed for statistical significance. Agreement on categorization between methods (kappa) was assessed. RESULTS: The average visual field mean deviation (MD +/- SD) in patients with glaucoma was -3.9 +/- 2.2 dB, and the average pattern standard deviation (PSD) was 4.7 +/- 3.4 dB. In normal subjects the average MD was 0.1 +/- 0.9 dB and the average PSD was 1.5 +/- 0.3 dB. Optimal sensitivities, specificities, and areas under ROC curves were, respectively: ONHP (0.94, 0.87, 0.93), CSLO (0.84, 0.90, 0.92), SLP (0.89, 0.87, 0.94), and OCT (0.82, 0.84, 0.88). Best agreement on categorization (kappa) was between ONHPs and CSLO (0.70). The ROC area for the combination of methods was 0.99, higher than for any method alone. The ROC area for the combination of methods was significantly better than the CLSO rim area (P = 0.012) and the OCT retinal nerve fiber layer (RNFL) thickness (P = 0.002). CONCLUSIONS: The quantitative methods CSLO, SLP, and OCT were no better than qualitative assessment of disc ONHPs by experienced observers at distinguishing normal eyes from those with early to moderate glaucoma. A combination of the imaging methods significantly improves this capability.

Diagnostic Techniques, Ophthalmological↗