Genotoxicity, nitric oxide level modulation and cardio-protective potential of Kalanchoe Integra Var. Crenata (Andr.) Cuf Leaves in murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Advancement in cancer therapy has improved survival among patients. However, use of anticancer drugs like anthracyclines (e.g., doxorubicin) is not without adverse effects. Notable among adverse effects of doxorubicin (DOX) is cardiotoxicity, which ranges from mild transient blood pressure changes to potentially serious heart failure. Anecdotal reports suggest that Kalanchoe integra (KI) may have cardio-protective potential. AIMS OF THE STUDY: This study sought to determine the cardio-protective potential of KI against doxorubicin-induced cardiotoxicity and also examined any possible genotoxic potential of KI in selected organs. Additionally, the nitric oxide modulatory potential of KI was assessed. MATERIALS AND METHODS: The leaves of KI were collected, air-dried, pulverised and extracted using 70% ethanol. High-performance liquid chromatography (HPLC) fingerprinting was done for KI. Also, the single-cell gel electrophoresis assay (Comet assay) was employed to ascertain the genotoxic potential of KI. In assessment of cardio-protective potential of KI against doxorubicin-induced cardiotoxicity, a total of 42 female Sprague-Dawley rats were put into 7 groups (n = 6). Group I: vehicle control, received normal saline (1 mL/kg p.o) for 30 days. Group II: toxic control, received DOX (20 mg/kg i.p.) once on the 29th day. Group III: KI control, received KI (300 mg/kg p.o) for 30 days. Group IV: vitamin E control, received vitamin E (100 mg/kg p.o) for 30 days. Group V: KI treated-1, received KI (300 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VI: KI treated-2, received KI (600 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VII: vitamin E treated, received vitamin E (100 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Thirty-six (36) hours after last administration, rats were sacrificed. Blood samples were taken via cardiac puncture to determine levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), lactate dehydrogenase (LDH), enzymatic antioxidants such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Nitric oxide level was also determined. Hearts of rats in each group were excised and taken through histopathological examination. RESULTS: In the HPLC fingerprint analysis, 13 peaks were identified, and peak with retention time of 24.0 min had the highest peak area (3.223 x104 mAU). Comet assay showed that the KI extract was non-genotoxic. Pretreatment with KI protected rats against doxorubicin-induced cardiotoxicity as evidenced by the low levels of AST, ALT, ALP, CK and LDH compared with the controls (p < 0.05). SOD, CAT and GPX levels were also high for rats administered KI extracts, further showing that KI protected rats against doxorubicin-induced cardiotoxicity. KI also inhibited nitric oxide levels at 300 mg/kg and 600 mg/kg effective doses. Histological examination revealed that rats pretreated with KI showed no signs of abnormal myocardial fibres (shape, size and configuration). CONCLUSION: Ethanolic (70%) leaf extract of KI showed no genotoxic potential and possessed cardioprotective effects against doxorubicin-induced cardiotoxicity in Sprague-Dawley rats. KI also inhibited nitric oxide production, thus, a potential nitric oxide scavenger.

Do premorbid characteristics of home care clients predict delayed discharges in acute care hospitals: a retrospective cohort study in Ontario and British Columbia, Canada.

BACKGROUND: Improved identification of patients with complex needs early during hospitalisation may help target individuals at risk of delayed discharge with interventions to prevent iatrogenic complications, reduce length of stay and increase the likelihood of a successful discharge home. METHODS: In this retrospective cohort study, we linked home care assessment records based on the Resident Assessment Instrument for Home Care (RAI-HC) of 210 931 hospitalised patients with their Discharge Abstract Database records. We then undertook multivariable logistic regression analyses to identify preadmission predictive factors for delayed discharge from hospital. RESULTS: Characteristics that predicted delayed discharge included advanced age (OR: 2.72, 95% CI 2.55 to 2.90), social vulnerability (OR: 1.27, 95% CI 1.08 to 1.49), Parkinsonism (OR: 1.34, 95% CI 1.28 to 1.41) Alzheimer's disease and related dementias (OR: 1.27, 95% CI 1.23 to 1.31), need for long-term care facility services (OR: 2.08, 95% CI 1.96 to 2.21), difficulty in performing activities of daily living and instrumental activities of daily living, falls (OR: 1.16, 95% CI 1.12 to 1.19) and problematic behaviours such as wandering (OR: 1.29, 95% CI 1.22 to 1.38). CONCLUSION: Predicting delayed discharge prior to or on admission is possible. Characteristics associated with delayed discharge and inability to return home are easily identified using existing interRAI home care assessments, which can then facilitate the targeting of pre-emptive interventions immediately on hospital admission.

Hematological changes and nitric oxide levels accompanying high-dose artemether-lumefantrine administration in male guinea pigs: Effect of unsweetened natural cocoa powder.

BACKGROUND: Unsweetened natural cocoa powder (UNCP), prepared after removal of the cocoa butter, is a common beverage in Ghana. It possesses antimalarial prophylactic property and has a beneficial effect on blood components. AIM: The aim of this study was to determine whether regular dietary supplement of UNCP mitigates high-dose (HD) artemether-lumefantrine (A-L)-induced hematological disorders and to determine the effect on nitric oxide (NO) levels. MATERIALS AND METHODS: Adult male guinea pigs (300 g - 350 g) were randomly divided into 5 groups of 6 guinea pigs each. Among the 5 groups, 3 groups were treated with UNCP (300, 900, and 1500 mg/kg body weight) for 14 days. A-L (75 mg/kg) was administered from the 12th to 14th day. One of the remaining 2 groups received distilled water only, i.e., vehicle control group (VCG) while the other received 75 mg/kg A-L only, i.e., negative control group (NCG). Blood samples from all groups were obtained by cardiac puncture (day 15) followed by hematological and NO analysis. RESULTS: A-L reduced white blood cells (WBC) by 31.87%, lymphocyte count by 45.99%, hemoglobin by 11.72%, hematocrit by 18.56%, and platelet count by 33.08% in the NCG. Administration of various doses of UNCP increased WBC and lymphocyte count (P > 0.05) compared to the NCG. UNCP and A-L combination caused an increase in NO levels when compared to the VCG. CONCLUSION: Regular consumption of UNCP by guinea pigs increases plasma NO and restores some hematological disorders induced by a 3-day HD A-L administration.

Efficacy, safety, and survival rates of IOP-lowering effect of phacoemulsification alone or combined with canaloplasty in glaucoma patients.

PURPOSE: To evaluate efficacy and survival rates of intraocular pressure (IOP)-lowering effect obtained with phacoemulsification (phaco) alone or in combination with canaloplasty (PCP) in patients with open-angle glaucoma (OAG). METHODS: Retrospective chart review of consecutive cases at the Department of Ophthalmology, Indiana University. Visual acuity (VA), IOP, number of medications (Meds), failures, and survival rates of IOP-lowering effect were analyzed. Inclusion criteria were: patients older than 18 years with OAG and cataract. Exclusion criteria were: no light perception vision, prior glaucoma surgery, chronic uveitis, angle-closure glaucoma, and advanced-stage or end-stage OAG. Failure criteria were: IOP>21 mm Hg or <20% reduction, IOP<6 mm Hg, further glaucoma surgeries, and loss of light perception vision. RESULTS: Thirty-seven patients underwent phaco and 32 patients had PCP. Follow-up was 21.8±10.1 versus 18.8±9.6 months for phaco and PCP, respectively (P=0.21). Age (y) (74.7±9.8 vs. 76.1±8.3, P=0.54), sex (P=81), and laser status (P=0.75) were similar between the groups. Preoperatively, mean±SD logMAR VA (0.5±0.7 vs. 0.5±0.5, P=0.77), IOP (16.2±4.6 vs. 18.2±5.1, P=0.13), and Meds (1.4±1.1 vs. 1.3±0.7, P=0.75) were similar for phaco and PCP, respectively. At 24-month phaco (n=17) and PCP (n=11), respectively, mean±SD were: logMAR VA 0.2±0.2 versus 0.4±0.7, P=0.29; IOP 14.1±4.0 versus 12.9±3.8, P=0.43; and Meds 1.5±1.2 versus 0.3±0.5, P=0.005. Rates of successful IOP lowering without medications for phaco versus PCP at 12 months were 34% versus 75%, respectively (P=0.003). CONCLUSIONS: A combination of canaloplasty with phaco results in a decreased number of glaucoma medications and increased survival rate of IOP-lowering effect compared with phaco alone.

Optic nerve diffusion tensor imaging parameters and their correlation with optic disc topography and disease severity in adult glaucoma patients and controls.

PURPOSE: To evaluate optic nerve diffusion tensor imaging (DTI) parameters in glaucoma patients and controls, and to correlate DTI parameters with the rim area obtained with Heidelberg retina tomography (HRT) and with the severity of glaucomatous damage using the Glaucoma Staging System. DESIGN: Pilot study. METHODS: Twenty-seven patients with glaucoma and 12 control subjects underwent DTI and HRT imaging. Main outcome measures included: fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, HRT rim area, and Glaucoma Staging System stage. RESULTS: In group comparison, mean diffusivity (1.33 vs. 0.91 µm/ms, P=0.0002), axial diffusivity (1.70 vs. 1.43 µm/ms, P=0.036), and radial diffusivity (1.24 vs. 0.71 µm/ms, P<0.0001) were significantly higher and fractional anisotropy (0.21 vs. 0.44, P<0.0001) was significantly lower in the glaucoma compared with those of control subjects. In glaucoma patients, mean, axial, and radial diffusivities increased and fractional anisotropy decreased as rim area decreases and the Glaucoma stage increased (P<0.05). However, there were no statistically significant differences in the DTI parameters when adjacent pairs of stages were compared (P>0.05). CONCLUSIONS: DTI may be a useful technique for detection and evaluation of glaucomatous damage in the optic nerve, particularly for patients in whom conventional imaging and perimetry are not possible. Future studies are needed to evaluate how DTI parameters change longitudinally with glaucomatous damage within the visual pathways and address cerebrospinal fluid partial volume effects in diffusion tensor quantification, especially for patients with advanced glaucoma stage.

Update on the role of alpha-agonists in glaucoma management.

Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine-timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

The location of the inferior and superior temporal blood vessels and interindividual variability of the retinal nerve fiber layer thickness.

PURPOSE: To determine if adjusting for blood vessel (BV) location can decrease the intersubject variability of retinal nerve fiber layer (RNFL) thickness measured with optical coherence tomography (OCT). SUBJECTS AND METHODS: One eye of 50 individuals with normal vision was tested with OCT and scanning laser polarimetry (SLP). The SLP and OCT RNFL thickness profiles were determined for a peripapillary circle 3.4 mm in diameter. The midpoints between the superior temporal vein and artery (STva) and the inferior temporal vein and artery (ITva) were determined at the location where the vessels cross the 3.4 mm circle. The average OCT and SLP RNFL thicknesses for quadrants and arcuate sectors of the lower and upper optic disc were obtained before and after adjusting for BV location. This adjustment was carried out by shifting the RNFL profiles based upon the locations of the STva and ITva relative to the mean locations of all 50 individuals. RESULTS: Blood vessel locations ranged over 39 (STva) and 33 degrees (ITva) for the 50 eyes. The location of the leading edge of the OCT and SLP profiles was correlated with the location of the BVs for both the superior [r=0.72 (OCT) and 0.72 (SLP)] and inferior [r=0.34 and 0.43] temporal vessels. However, the variability in the OCT and SLP thickness measurements showed little change due to shifting. After shifting, the difference in the coefficient of variation ranged from -2.1% (shifted less variable) to +1.7% (unshifted less variable). CONCLUSIONS: The shape of the OCT and SLP RNFL profiles varied systematically with the location of the superior and inferior superior veins and arteries. However, adjusting for the location of these major temporal BVs did not decrease the variability for measures of OCT or SLP RNFL thickness.

Uveitis-glaucoma-hyphema syndrome and corneal decompensation in association with cosmetic iris implants.

PURPOSE: To report a case and management of uveitis-glaucoma-hyphema (UGH) syndrome and corneal decompensation associated with cosmetic iris implants. DESIGN: Interventional case report. SETTINGS: Department of Ophthalmology, University of Minnesota School of Medicine. PATIENTS: A 29-year-old man presented with bilateral redness, severe pain, photophobia, and reduction in visual acuity. Examination revealed intraocular pressure (IOP) of 38 mm Hg and 40 mm Hg right and left eye respectively, bilateral conjunctival injection 3+, epithelial corneal edema, microhyphema, cells 3+ to 4+ and flare 2+, bilateral cosmetic iris implants, and surgical peripheral iridectomies. The patient was diagnosed with UGH syndrome and corneal decompensation associated with cosmetic iris implants. INTERVENTION: Immediate medical management of inflammation and elevated IOP, anterior segment imaging, specular microscopy, Humphrey 24-2 visual field (VF) testing; following failed conservative management, combined trabeculectomy and removal of the iris implants. MAIN OUTCOME MEASURES: Anterior chamber inflammation and microhyphema, IOP, and corneal edema. RESULTS: Anterior segment imaging demonstrated bilateral implant-iris apposition and implant-angle structures apposition. Specular microscopy demonstrated a significant reduction of the number of endothelial cells. VF test demonstrated a right superior arcuate scotoma and a normal left VF. Following surgical treatment IOP normalized and inflammation and microhyphema subsided. However, mild corneal edema persisted. CONCLUSION: Cosmetic iris implantation may lead to UGH syndrome and corneal decompensation. Therefore, its use should be reserved for patients with significant medical indications, and avoided in patients with intact natural iridies, until more short-term and long-term safety data are available.

HRT III glaucoma probability score and Moorfields regression across the glaucoma spectrum.

OBJECTIVE: To compare the agreement, sensitivity, and specificity of the Heidelberg Retina Tomograph III Glaucoma Probability Score (GPS) and Moorfields Regression Analysis (MRA) across the spectrum of glaucomatous visual field (VF) loss. DESIGN: Retrospective observational study. METHODS: Data from 247 glaucoma patients and 142 controls who underwent standard achromatic perimetry (SITA-SAP) and Heidelberg Retina Tomograph III imaging within 6 months were analyzed. Sensitivity, specificity, agreement, and discrimination capability of MRA and GPS were assessed. RESULTS: Age-adjusted specificity was 92% and 93% and sensitivity was 76.88 and 80.85 for GPS and MRA, respectively. Sensitivity for early VF loss [mean deviation (MD) < -5 dB] (N=81) was 66.64% and 69.82%, for moderate VF loss (-5 dB -15 dB) (N=62) was 87.70% and 86.48% (GPS and MRA, respectively). Age-specific receiver operating characteristics ranged from 0.89 to 0.92 and from 0.87 to 0.90 (GPS and MRA, respectively). Kappa ranged from 0.64 to 0.77. CONCLUSIONS: Specificity for MRA and GPS was similar and agreement was good. GPS offered slightly higher age-specific receiver operating characteristic. GPS, which does not require contour line placement, may have a potential role in screening for severe glaucomatous damage.

Blood vessel contributions to retinal nerve fiber layer thickness profiles measured with optical coherence tomography.

PURPOSE: To understand better the influence of retinal blood vessels (BVs) on the interindividual variation in the retinal nerve fiber layer (RNFL) thickness measured with optical coherence tomography (OCT). SUBJECTS AND METHODS: RNFL thickness profiles were measured by OCT in 16 control individuals and 16 patients. The patients had advanced glaucoma defined by abnormal disc appearance, abnormal visual fields, and a mean visual field deviation worse than -10 dB. RESULTS: In general, the OCT RNFL thickness profiles showed 4 local maxima, with the peak amplitudes in the superior and inferior regions occurring in the temporal (peripapillary) disc region. There was considerable variability among individuals in the location of these maxima. However, the 4 maxima typically fell on, or near, a major BV with the temporal and inferior peaks nearly always associated with the main temporal branches of the superior and inferior veins and arteries. In the patients' hemifields with severe loss (mean visual field deviation worse than -20 dB), the signals associated with the major BVs were in the order of 100 to 150 microm. CONCLUSIONS: The variation in the local peaks of the RNFL profiles of controls correlates well with the location of the main temporal branches of the superior and inferior veins and arteries. This correspondence is, in part, due to a direct BV contribution to the shape of the OCT RNFL and, in part, due to the fact that BVs develop along the densest regions of axons. Although the overall BV contribution was estimated to be relatively modest, roughly 13% of the total peripapillary RNFL thickness in controls, their contribution represents a substantial portion locally and increases in importance with disease progression.

Intra-observer and inter-observer reliability and reproducibility of slit-lamp-adapted optical coherence tomography for evaluation of anterior chamber depth and central corneal thickness.

BACKGROUND AND OBJECTIVE: To evaluate the intra-observer and inter-observer reproducibility of anterior chamber depth (ACD) and central corneal thickness (CCT) measurements taken by slit-lamp-adapted optical coherence tomography (SL-OCT) and to evaluate concordance of CCT and ACD values obtained by SL-OCT with gold standard devices. PATIENTS AND METHODS: Three images of each eye were taken by two different operators using SL-OCT. ACD and CCT values obtained by each operator were determined and compared to one another and to ultrasonic pachymetry (CCT) and axial OCT biometry (ACD) values obtained by a third, masked operator. Intra-observer and inter-operator reproducibility was assessed using the intraclass correlation coefficient (ICC). RESULTS: Forty-one eyes of healthy subjects were enrolled. Mean CCT was 0.556 +/- 0.020, 0.557 +/- 0.019, and 0.532 +/- 0.032 and mean ACD was 3.12 +/- 0.36, 3.13 +/- 0.38, and 3.50 +/- 0.44 for operators 1, 2, and 3, respectively (P < .001, for both CCT and ACD). Intra-operator reproducibility for CCT (ICC of 0.948 to 0.995) and ACD (ICC of 0.972 to 0.987) was excellent. CONCLUSION: SL-OCT provides highly reproducible measures for both CCT and ACD. SL-OCT yields higher values for CCT compared to ultrasonic pachymetry and lower values for ACD compared to axial OCT biometry. Caution should be taken when extrapolating these data into clinical practice until the differences between SL-OCT, axial OCT biometry, and ultrasonic pachymetry can be further elucidated.

Comparison of diagnostic accuracy of Heidelberg Retina Tomograph II and Heidelberg Retina Tomograph 3 to discriminate glaucomatous and nonglaucomatous eyes.

PURPOSE: To compare the diagnostic accuracy of the Moorfields regression analysis (MRA), parameters, and glaucoma probability score (GPS) from Heidelberg Retinal Tomograph (HRT) 3 (Heidelberg Engineering, Heidelberg, Germany) with MRA and parameters from HRT II in discriminating glaucomatous and healthy eyes in subjects of African and European ancestry. DESIGN: Case-control institutional setting. METHODS: Seventy-eight glaucoma patients (44 of African ancestry, 34 of European ancestry) and 89 age-matched controls (46 of African ancestry, 33 European ancestry), defined by visual fields and self-reported race were included. Imaging was obtained with HRT II, and data were exported to a computer with the HRT 3 software using the same contour line. Area under the receiver operating characteristic (ROC) curves (AUCs), sensitivity, and specificity were evaluated for the entire group, the African ancestry group, and the European ancestry group separately. Mean disk area was compared between correctly and incorrectly diagnosed eyes by each technique. RESULTS: Disk, cup, and rim areas from HRT 3 were lower than HRT II (P < .0001). AUC (sensitivity at 95% specificity) was 0.85 (54%) for vertical cup-to-disk ratio (VCDR) HRT 3, 0.84 (45%) for VCDR HRT II, and 0.81 (44%) for GPS at the temporal sector. MRA HRT 3 showed greater sensitivity but lower specificity than HRT II for the entire group, the African ancestry group, and the European ancestry group. GPS classification had the lowest specificity. Glaucomatous eyes incorrectly classified by GPS had smaller mean disk area (P = .0002); control eyes incorrectly classified had greater mean disk area (P = .015). CONCLUSIONS: VCDR from HRT 3 showed higher sensitivity than HRT II and GPS for the entire group and for those of African ancestry and of European ancestry separately. Sensitivity of MRA improved in HRT 3 with some trade-off in specificity compared with MRA of HRT II. GPS yielded erroneous classification associated to optic disk size.

Detecting visual function abnormalities using the Swedish interactive threshold algorithm and matrix perimetry in eyes with glaucomatous appearance of the optic disc.

OBJECTIVE: To compare the ability of 24-2 frequency-doubling perimetry (FDP-Matrix) with standard automated perimetry with the Swedish interactive threshold algorithm (SAP-SITA) in detection of visual function abnormalities in patients with glaucomatous-appearing optic discs (GAOD). METHODS: This observational case-control study included 80 patients with GAOD and 54 control subjects diagnosed by masked assessment of optic disc stereoscopic photographs. Abnormal visual function at SAP-SITA and FDP-Matrix testing required consistent abnormalities in 2 visual field examinations, determined using the glaucoma hemifield test outside 99% normal limits, pattern standard deviation outside 95% normal limits, or 3 contiguous points in the pattern deviation probability plot outside 95% normal limits (at least 1 P<1%) within the same hemifield. RESULTS: The FDP-Matrix and SAP-SITA detected abnormal visual function in 51% and 44%, respectively, of GAOD eyes (P = .26), and both perimetry techniques identified 11% of healthy eyes as abnormal. Agreement between FDP-Matrix and SAP-SITA was moderate (kappa = 0.49), as only 35% of GAOD eyes and 2% of healthy eyes had both visual field test results flagged as abnormal. CONCLUSIONS: The FDP-Matrix detected abnormal visual function in more eyes with GAOD than did SAP-SITA, although this difference was not significant. Each visual field test tended to identify different subsets of eyes with GAOD as abnormal. Combination of these perimetry techniques may improve the detection of visual function abnormalities in patients with glaucoma.

Effect of glaucomatous damage on repeatability of confocal scanning laser ophthalmoscope, scanning laser polarimetry, and optical coherence tomography.

PURPOSE: To determine and compare the effect of the severity of glaucomatous damage on the repeatability of retinal nerve fiber layer (RNFL) thickness with GDx-VCC (variable corneal compensation) and StratusOCT (optical coherence tomography; both produced by Carl Zeiss Meditec, Inc., Dublin, CA), and optic nerve head (ONH) topography with HRT-II (retinal tomograph; Heidelberg Engineering GmbH, Heidelberg, Germany) and StratusOCT. METHODS: With each of these techniques, two measurements were obtained from 41 eyes of 41 control subjects and 98 glaucomatous eyes (37 patients with early, 29 with moderate, and 32 with severe field loss). To evaluate test-retest variability at each stage, limits of agreement (Bland-Altman plots) and repeatability coefficients (RCs) were obtained from pairs of measurements. Comparisons of within-subject variances were used to compare repeatability of GDx-VCC versus StratusOCT for global RNFL and HRT-II versus StratusOCT for global ONH topography. Effects from age, visual acuity, and lens status were also included in the analysis as covariates. RESULTS: Test-retest variability of RNFL using GDx-VCC and StratusOCT were consistent through all stages of disease severity. Repeatability results of GDx-VCC were better than those of StratusOCT, except in severe cases. Test-retest variability of ONH topography using HRT-II and StratusOCT increased with increasing disease severity for rim area, cup area, and cup-to-disc (C/D) area ratio. In contrast, vertical C/D ratio from HRT-II, and horizontal C/D ratio from StratusOCT showed stable test-retest variability through all stages. Regardless of disease severity, repeatability results of HRT-II were better than those of StratusOCT. CONCLUSIONS: GDx-VCC and HRT-II showed better repeatability than StratusOCT. Although test-retest variability increased with disease severity for rim area, the variability for vertical C/D ratio (HRTII) and global RNFL (GDx-VCC) was stable across disease severity. These parameters, rather than rim area, may be more useful in detection of progression in patients with glaucoma who have more advanced field loss.

Correlations between retinal nerve fiber layer and visual field in eyes with nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To evaluate correlations between retinal nerve fiber layer (RNFL) thickness with visual field (VF) sensitivities in eyes with nonartertic anterior ischemic optic neuropathy (NAION). DESIGN: Case-control study in an academic, institutional setting. METHODS: One eye from 21 patients with NAION and 32 healthy participants were included in this prospective study. Humphrey visual field (HVF) sensitivities were obtained from standard achromatic HVF test (24-2 SITA). RNFL was measured with scanning laser polarimetry (SLP, GDx-VCC) and optical coherence tomography (OCT, StratusOCT). Correlations were evaluated between RNFL and sensitivities from global, hemifields, and regional locations of the VF pertinent to the RNFL distribution. A total of 15 NAION eyes had inferior altitudinal HVF defects, and their global and regional RNFL was compared with that of control eyes. The main outcome measure was correlation between HVF sensitivities and RNFL. RESULTS: Correlations of global, hemifield, and sectorial HVF sensitivities with RNFL were greater when RNFL was measured with OCT than with SLP, except for nasal and inferonasal sectors. RNFL thickness was far lower in the hemiretinas corresponding to the relative unaffected hemifield in eyes with altitudinal VF defect compared with controls. CONCLUSIONS: In patients with NAION, RNFL measured by OCT provided better correlation to HVF changes than SLP did. Both instruments showed decreased RNFL in NAION eyes with altitudinal VF defects compared with control eyes, demonstrating loss of RNFL even in sectors of the optic disk that corresponded to relatively unaffected hemifield, suggesting greater damage beyond the extent estimated by VF methods.

Comparison of the Moorfields classification using confocal scanning laser ophthalmoscopy and subjective optic disc classification in detecting glaucoma in blacks and whites.

OBJECTIVE: To compare the diagnostic accuracy of the Moorfields regression classification (MRC) and subjective optic disc evaluation in discriminating early to moderate glaucomatous from nonglaucomatous eyes. DESIGN: Cross-sectional observational study. PARTICIPANTS: Two hundred thirty-three patients with glaucoma and 216 normal subjects were included in the analysis. Racial groups were defined by self-description. METHODS: All subjects underwent confocal scanning laser ophthalmoscopy, stereophotography, and standard perimetry. Glaucoma was defined by visual field defect alone and confirmed with a second visual field test. Stereo photographs were graded as either normal or glaucomatous appearing in a masked fashion by 2 independent graders and adjudicated by a third grader in cases of disagreement. Mean disc area was compared between patients correctly and incorrectly diagnosed with either technique. MAIN OUTCOME MEASURES: Sensitivity and specificity of MRC and subjective evaluation of stereophotographs in the detection of glaucomatous visual field loss. RESULTS: With the MRC, the sensitivity and specificity were higher using the 95% cutoff than using the 99.9% cutoff. Classification based on subjective photo assessment had a greater agreement with the diagnosis of glaucoma than the MRC for blacks (MRC, sensitivity = 62.5%, specificity = 93.2%; Photo, sensitivity = 76.5%, specificity = 91.5%) and whites (MRC, sensitivity = 67.0%, specificity = 92.2%; photo, sensitivity = 78.4%, specificity = 91.9%). Disc area was significantly larger in patients incorrectly diagnosed with the MRC (P = 0.0289). CONCLUSIONS: Subjective optic disc grading by glaucoma specialists outperformed the MRC with the HRT II in both black and white subjects. Both subjective and objective diagnostic methods were associated with similar sensitivity and specificity between racial groups. The MRC was more likely to provide an incorrect diagnosis in subjects with larger optic discs.

Discrimination between glaucomatous and nonglaucomatous eyes using quantitative imaging devices and subjective optic nerve head assessment.

PURPOSE: To compare the diagnostic ability of the confocal scanning laser ophthalmoscope (HRT-II; Heidelberg Engineering, Heidelberg, Germany), scanning laser polarimeter (GDx-VCC; Carl Zeiss Meditec, Inc., Dublin, CA), and optical coherence tomographer (StratusOCT, Carl Zeiss Meditec, Inc.) with subjective assessment of optic nerve head (ONH) stereophotographs in discriminating glaucomatous from nonglaucomatous eyes. METHODS: Data from 79 glaucomatous and 149 normal eyes of 228 subjects were included in the analysis. Three independent graders evaluated ONH stereophotographs. Receiver operating characteristic curves were constructed for each technique and sensitivity was estimated at 80% of specificity. Comparisons of areas under these curves (aROC) and agreement (kappa) were determined between stereophoto grading and best parameter from each technique. RESULTS: Stereophotograph grading had the largest aROC and sensitivity (0.903, 77.22%) in comparison with the best parameter from each technique: HRT-II global cup-to-disc area ratio (0.861, 75.95%); GDx-VCC Nerve Fiber Indicator (NFI; 0.836, 68.35%); and StratusOCT retinal nerve fiber layer (RNFL) thickness (0.844, 69.62%), ONH vertical integrated rim area (VIRA; 0.854, 73.42%), and macular thickness (0.815, 67.09%). The kappa between photograph grading and imaging parameters was 0.71 for StratusOCT-VIRA, 0.57 for HRT-II cup-to-disc area ratio, 0.51 for GDX-VCC NFI, 0.33 for StratusOCT RNFL, and 0.28 for StratusOCT macular thickness. CONCLUSIONS: Similar diagnostic ability was found for all imaging techniques, but none demonstrated superiority to subjective assessment of the ONH. Agreement between disease classification with subjective assessment of ONH and imaging techniques was greater for techniques that evaluate ONH topography than with techniques that evaluate RNFL parameters. A combination of subjective ONH evaluation with RNFL parameters provides additive information, may have clinical impact, and deserves to be considered in the design of future studies comparing objective techniques with subjective evaluation by general eye care providers.

Agreement in assessing cup-to-disc ratio measurement among stereoscopic optic nerve head photographs, HRT II, and Stratus OCT.

PURPOSE: To compare the level of agreement between subjective and objective methods in estimating horizontal and vertical cup-to-disc ratios (HCDR and VCDR, respectively) to determine if objective techniques may be used as surrogates for subjective cup-to-disc (CDR) estimation. METHODS: Fifty-one glaucoma patients and 49 control subjects underwent full ophthalmic examination, stereoscopic optic nerve head photographs (ONHPs), confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomography II [HRT II]), and optical coherence tomography (Stratus OCT). The intraclass correlation coefficient (ICC) and Bland Altman plots were used to assess the agreement across the three methods. Repeated measures analysis of variance (ANOVA), Tukey adjustment, and pairwise P values were used to compare the HCDR and VCDR estimates between three clinicians who reviewed photos, Stratus OCT, and HRT II. RESULTS: For the clinicians, the agreement in subjectively assessed HCDR and VCDR was substantial (ICC=0.84 and 0.85, respectively), and for all three methods, overall agreement was good (ICC=0.75 and 0.77 for the HCDR and VCDR, respectively). Stratus OCT provided the largest overall mean+/-SD HCDR (0.68+/-0.14) and VCDR (0.62+/-0.13). The smallest overall mean+/-SD HCDR was provided by ONHP (0.32+/-0.16), and the smallest overall mean+/-SD VCDR was provided by HRT II (0.26+/-0.20). Repeated measures ANOVA test demonstrated significant differences across the three methods for glaucomatous (P=0.0017 and 0.0016, HCDR and VCDR, respectively) and normal (P=0.0001 for both HCDR and VCDR) eyes. Tukey adjustment demonstrated specific statistical differences between pairs of methods. CONCLUSIONS: Although the overall agreement between various methods was good, the mean estimates were statistically different. Additional studies are needed to evaluate the sources of variability, their level of significance, and longitudinal agreement between various methods of the CDR estimation.

Secondary acute angle-closure glaucoma associated with vitreous hemorrhage after ruptured retinal arterial macroaneurysm.

PURPOSE: To report acute angle-closure glaucoma in a patient with dense vitreous hemorrhage due to a ruptured retinal arterial macroaneurysm. DESIGN: Interventional case report. METHODS: A male patient presented with severe pain and decreased vision in his right eye, nausea, and vomiting. Visual acuity was hand motions, intraocular pressure was 64 mm Hg, and light reflex was not detected in the right eye. The patient underwent comprehensive ophthalmologic examination and appropriate medical and surgical management. RESULTS: Examination of the right eye revealed a shallow anterior chamber and closed angle; ultrasound confirmed the presence of vitreous hemorrhage. After intensive medical treatment and subsequent pars plana vitrectomy with laser treatment to the ruptured retinal macroaneurysm, pain in the right eye subsided, visual acuity improved to 20/25, and intraocular pressure decreased to 20 mm Hg. CONCLUSION: We are unaware of previous clinical reports of this finding and could find no reference to it in a computerized search utilizing MEDLINE. In our patient the pressure stabilized and the vision improved after medical and surgical management.