Optical coherence tomography of the optic nerve head detects acute changes in intracranial pressure.

We aimed to determine if there are measurable objective changes in the optic nerve head (ONH) immediately after cerebrospinal fluid (CSF) drainage in a prospective case-series of five patients undergoing a clinically indicated lumbar puncture (LP) for diagnosis of idiopathic intracranial hypertension. A Cirrus high-definition optical coherence tomography machine (Carl Zeiss Meditec, Dublin, CA, USA) was used to acquire images in the lateral decubitus position. Optic disc cube and high-definition line raster scans centered on the ONH were obtained immediately before and after draining CSF, while the patient maintained the lateral decubitus position. Measured parameters included retinal nerve fiber layer (RNFL) thickness, peripapillary retinal pigment epithelium/Bruch's membrane (RPE/BM) angulation, transverse neural canal diameter (NCD) and the highest vertical point of the internal limiting membrane from the transverse diameter (papillary height). The mean (±standard deviation) opening and closing CSF pressures were 34.3±11.8 and 11.6±3.3cmH2O, respectively. Mean RNFL thickness (pre LP: 196±105µm; post LP: 164±77µm, p=0.1) and transverse NCD (pre LP: 1985±559µm; post LP: 1590±228µm, p=2.0) decreased in all subjects, but with non-significant trends. The RPE/BM angle (mean change: 5.8±2.0degrees, p=0.003) decreased in all subjects. A decrease in papillary height was seen in three of five subjects (mean: pre LP: 976±275µm; post LP: 938±300µm, p=0.9). Our results show a measurable, objective change in the ONH after acute lowering of the lumbar CSF pressure, suggesting a direct link between the lumbar subarachnoid space and ONH regions, and its potential as a non-invasive method for monitoring intracranial pressures.

Clinical Validation of a Transcranial Doppler-Based Noninvasive Intracranial Pressure Meter: A Prospective Cross-Sectional Study.

BACKGROUND: Noninvasive intracranial pressure (ICP) measurement would represent a major advance for patients with neurological problems. The Vittamed ICP meter is an ultrasound-based device reported to have high agreement with lumbar puncture cerebrospinal fluid (CSF) pressure measurement. However, previous studies included mostly patients with normal levels of ICP. The purpose of our study was to perform an independent clinical validation study of a transcranial Doppler-based noninvasive ICP meter in patients anticipated to have a wide range of ICP. METHODS: In a prospective cross-sectional design, we simultaneously measured ICP with the Vittamed device and the invasive lumbar CSF pressure. The operator of each procedure was blinded to the result of the other method. Data were analyzed using Bland-Altman plots, Pearson correlation coefficients, and receiver operator characteristic curves. RESULTS: Twenty-four independent paired measurements of Vittamed and lumbar CSF pressure were obtained; with mean absolute difference between paired measures of 4.5 mmHg (standard deviation 3.1). The 95% limits of agreement were -10.5 to +11.0. The systematic bias (mean of paired differences) was negligible at 0.25 mmHg. The sensitivity, specificity, and area under the curve for ICP >20 mmHg were 0.73, 0.77, and 0.71, respectively. CONCLUSIONS: The Vittamed ICP meter had fair agreement with lumbar CSF pressure measurement. The wide limits of agreement would preclude using this version of the device as a stand-alone method for ICP determination, but may be useful if combined with other ICP screening methods. Ongoing improvements to the Vittamed hardware and software may lead to improvements in accuracy and clinical utility of this device.

A Circulating Biomarker Risk-Prediction Model Correlates with CHADS-2 Risk Score in Chronic Atrial Fibrillation.

BACKGROUND: Inflammation and oxidative stress have been linked to the origin and persistence of atrial fibrillation (AF). CHADS-2 scoring system is a risk stratification schema well validated in prognostication of stroke in AF. We evaluated the association of markers of oxidative stress and inflammation with CHADS-2 scores in chronic AF patients. METHODS: CHADS-2 scores were calculated for 64 subjects with chronic AF. Serum markers of inflammation [C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α)] and of oxidative stress [Derivatives of reactive oxygen metabolites (DROMs) and isoprostanes (IsoPs)] were measured. RESULTS: Twenty subjects were categorized as 0 (no risk), 24 as 1 (intermediate risk) and 20 as 2 (severe risk) based on their CHADS-2 scores. High sensitivity-CRP (CHADS-2 0=40.0%, 1=70.0%, 2=90.0%; p=0.003) and DROMs (CHADS-2 0=45%, 1=78%, 2=80%; p=0.04) were positively associated with the CHADS-2 risk score. Subjects with intermediate to severe CHADS-2 risk retained significant associations with abnormal hs-CRP (OR: 5.3, 95%CI: 1.1-25.0) and DROMs (adjusted OR: 6.7, 95%CI: 1.2-38.8) after adjusting for gender and hypertension. In a multiple logistic interaction model, there was no significant interaction between hs-CRP and DROMs in their association with CHADS-2 risk categories (p=0.64). A biomarker risk-model, combining hs-CRP and DROMs, correlated well with the CHADS-2 risk categories (r= 0.49, p<0.001). CONCLUSIONS: A biomarker risk-model using a combination of hs-CRP and DROMs correlates well with CHADS-2 risk scores in chronic AF. Either or both of these markers may add predictive power to future stroke risk prediction models.

A novel mutation in the ABCA1 gene causing an atypical phenotype of Tangier disease.

Tangier disease is a rare autosomal-recessive disorder caused by mutation in the ATP binding cassette transporter 1 (ABCA1) gene. Typically, Tangier disease manifests with symptoms and signs resulting from the deposition of cholesteryl esters in nonadipose tissues; chiefly, in peripheral nerves leading to neuropathy and in reticulo-endothelial organs, such as liver, spleen, lymph nodes, and tonsils, causing their enlargement and discoloration. An association with early cardiovascular disease can be variable. We describe a patient with a unique phenotype of Tangier disease from a novel splice site mutation in the ABCA1 gene that is associated with a central nervous system presentation resembling multiple sclerosis, and the presence of premature atherosclerosis.

Widespread systemic embolization with isolated tricuspid valve endocarditis.

Concurrent systemic and pulmonary septic emboli from isolated right-sided infective endocarditis are rare. One mechanism described is that of intrapulmonary shunting. We describe a case of widespread pulmonary and systemic septic embolization with sequelae in an intravenous drug user with concomitant chronic hepatitis C infection and discuss possible mechanisms involved in the pathogenesis.

Short-duration transient visual evoked potential for objective measurement of refractive errors.

This study examined effects of uncorrected refractive errors (RE) in a short-duration transient visual evoked potential (SD t-VEP) system and investigated their role for objective measurement of RE. Refractive errors were induced by means of trial lenses in 35 emmetropic subjects. A synchronized single-channel EEG was recorded for emmetropia, and each simulated refractive state to generate 21 VEP responses for each subject. P100 amplitude (N75 trough to P100 peak) and latency were identified by an automated post-signal processing algorithm. Induced hypermetropia and myopia correlated strongly with both P100 amplitude and latency. To minimize the effect of baseline shift and waveform fluctuations, a VEP scoring system, based on software-derived P100 latency, amplitude and waveform quality, was used to estimate the RE. Using the VEP scores, a single VEP response had a high sensitivity and specificity for discerning emmetropia, small RE (<2 diopter) within a 2 diopter range and large RE (2-14 diopter) within a 4 diopter range. The VEP scoring system has a potential for objective screening of RE and for a more accurate 3-step objective refraction.

Large blood transfusion as a rare cause of ventricular fibrillation.

Large blood transfusions are common in clinical practice. Though several complications have been described with this procedure, cardiac arrhythmias occur uncommonly in this setting. We describe a case of a previously healthy 17-year-old girl who developed wide-complex ventricular tachycardia rapidly culminating in a ventricular fibrillation cardiac arrest several hours following an uneventful large-volume blood transfusion. Hypomagnesemia was detected on postcardiac arrest investigations. A review of this life-threatening complication and discussion on the ways to prevent it are presented.

Use of amniotic membrane graft in glaucoma shunt surgery.

BACKGROUND AND OBJECTIVE: To determine the safety and efficacy of amniotic membrane graft in glaucoma drainage device surgery. PATIENTS AND METHODS: Institutional retrospective case series of 44 patients undergoing glaucoma drainage device implantation with use of 300-µm thick amniotic membrane as a patch graft. Endpoints assessed were tube exposure, graft thinning, graft clarity, graft-related infection, and inflammation. RESULTS: A total of 41 (93%) eyes had an uneventful course over a mean follow-up of 22 ± 3 months (range: 17 to 28 months). Tube exposure and hypotony each occurred in one eye and were successfully treated with a tube revision using double pericardial and amniotic membrane patch graft. The translucency of amniotic membrane graft enabled good visualization of the occluding suture when performing laser suture lysis in 16 eyes. Sequential anterior segment optical coherence tomography showed stable amniotic membrane graft thickness with a change from low to moderate reflectivity in the subconjunctival-graft bilayer. CONCLUSION: Amniotic membrane graft offers good tectonic support and allows direct visualization of the underlying tube.

Atherosclerotic coronary heart disease-epidemiology, classification and management.

Atherosclerotic coronary heart disease (CHD) is a major health problem worldwide. Epidemiological studies have identified the role of several modifiable and non-modifiable risk factors in the pathogenesis of CHD. Aggressive risk modification has led to a significant improvement in the morbidity and mortality from CHD. However, there is a growing need to identify better modalities of risk prediction in CHD. Many of these newer risk markers, currently under evaluation, are based on the newer concept that atherosclerosis is more than merely a problem of lipid imbalance. There has been a recent shift in the paradigm towards inflammation and oxidative stress as the key drivers in the pathophysiology of atherosclerosis and its complications. Further understanding of this complex interplay of lipid and inflammatory factors is likely to pave way to a better understanding of this disease and its myriad complications.

Corneal hysteresis and visual field asymmetry in open angle glaucoma.

PURPOSE: To investigate the association between corneal biomechanical parameters and asymmetric primary open angle glaucoma (POAG) using the Ocular Response Analyzer (ORA). METHODS: In a prospective cross-sectional study, ORA parameters were measured in 117 POAG patients with asymmetric visual fields (VF). The asymmetry in VF was defined as a five point difference between the eyes using the Advanced Glaucoma Intervention Study (AGIS) scoring system. Subjects with previous intraocular or refractive surgery, ocular comorbidities and diabetes were excluded. RESULTS: In worse eyes, mean AGIS scores were significantly higher (8.1 ± 4.3 vs. 1.0 ± 1.6; P < 0.001) and mean corneal hysteresis (CH) was significantly lower (8.2 ± 1.9 vs. 8.9 ± 1.9 mm Hg; P < 0.001). Median ORA-corrected intraocular pressure was higher in the worse eyes (IOP(cc), 17.4 mm Hg vs. 16.9 mm Hg; P < 0.001). Worse eyes had a slightly lower mean corneal resistance factor (P = 0.04) and more myopic mean spherical equivalent (P = 0.02). No difference was seen in the central corneal thickness (CCT; P = 0.63) and Goldmann applanation tonometry (GAT; P = 0.32). On multivariate analysis, only CH retained an association with the worse eye (odds ratio, 25.9; 95% confidence interval, 10.1-66.5). ROC curves showed that only CH and IOP(cc) had a discriminative ability for the eye with worse VF (AUC, 0.82 and 0.70, respectively). CONCLUSIONS: Asymmetric POAG was associated with asymmetry in ORA parameters but not in CCT and GAT. Lower CH was associated with worse eyes independently of its effect on IOP measurement and had the best discriminability for the eye with the worse VF.

Sequential glaucoma implants in refractory glaucoma.

PURPOSE: To evaluate the efficacy of a second glaucoma implant in eyes with prior glaucoma implant surgery and inadequate intraocular pressure (IOP) control. DESIGN: Retrospective observational cohort study. METHODS: Patients undergoing a second glaucoma implant surgery from 1996 to 2008 were included. Outcome measures included visual acuity, IOP, glaucoma medication use, and complications. Success was defined as IOP < 21 mm Hg (criterion 1) and IOP < 17 mm Hg (criterion 2), with at least 25% reduction in IOP and no prolonged hypotony. RESULTS: Forty-three eyes (43 patients) had a mean follow-up of 32.6 +/- 21.6 months. Life-table analysis demonstrated success rates of 93%, 89%, and 83% using criterion 1 and 83%, 75%, and 75% using criterion 2 at 1, 2, and 3 years, respectively. At last follow-up, mean IOP (13.6 +/- 4.6 vs 24.7 +/- 7.5 mm Hg; P < .001) and mean number of medications (1.4 +/- 1.2 vs 3.9 +/- 1.2; P < .001) were lower following the second implant. There was no difference in preoperative and most recent logarithm of the minimal angle of resolution (logMAR) visual acuities (0.86 +/- 0.13 vs 1.1 +/- 0.13; P = .07). The most frequently used second implants were similar in percentage IOP reduction (Baerveldt implant, 45 +/- 19%; Ahmed valve, 40 +/- 18%; P = .4). CONCLUSIONS: A second glaucoma implant may effectively lower IOP in eyes with refractory glaucoma.

Hydrophilic acrylic intraocular lens exchange: Five-year experience.

PURPOSE: To evaluate clinical outcomes of opacified SC60B-0UV intraocular lens (IOL) (MDR, Inc.) and clear SC60B-0UV IOL exchange. SETTING: Department of Ophthalmology, Queen's Hospital, Burton-on-Trent, United Kingdom. METHODS: In a prospective audit, 149 patients with 152 SC60B-0UV hydrophilic acrylic IOLs were monitored over 5 years. Perioperative complications were evaluated. The best spectacle-corrected visual acuity, subjective quality of vision, and VF-14 scores were compared preoperatively and postoperatively. RESULTS: Ninety-eight IOLs developed opacification; 52 IOLs were exchanged between February 1999 and October 2004. The lens exchange procedure was uneventful in 39 eyes (75%). Perioperative complications included zonular dehiscence and posterior capsule rupture in 12 eyes (23.1%), total capsule-IOL extraction in 4 eyes (7.7%), iridodialysis in 3 eyes (5.8%), hyphema in 2 eyes (3.8%), and retained haptics in 5 eyes (9.6%). The mean logMAR visual acuity and mean VF-14 scores improved significantly after IOL exchange (P < .01). Forty-seven patients (90.4%) reported improvement in the subjective quality of vision after IOL exchange. However, after the exchange, visual acuity worsened in 5 patients (9.6%) and subjective quality of vision worsened in 3 patients (5.8%); the VF-14 scores decreased in 5 (14.7%) of the 34 patients tested. CONCLUSIONS: Visual function and quality of life were better after IOL exchange. However, poor outcomes in some patients mandate an extensive informed consent procedure for clear IOL exchange.

Early post-phacoemulsification hypotony as a risk factor for intraocular contamination: in vivo model.

PURPOSE: To observe cataract wound dynamics and determine the risk for intraocular contamination under induced conditions of early postoperative hypotony after anterior chamber decompression for high intraocular pressure (IOP) spikes after uneventful phacoemulsification surgery. SETTING: Department of Ophthalmology, Queen's Hospital, Burton-on-Trent, United Kingdom. METHODS: In a prospective case series, 30 patients were treated with anterior chamber decompression for elevated IOP (>35 mm Hg) 1 to 2 hours after uneventful phacoemulsification through clear corneal temporal incisions. A drop of 2% fluorescein was instilled in the conjunctival sac before aqueous release to study the ocular fluid movements during and after the decompression procedure. The patterns of fluorescein movement were observed and photographed under cobalt blue light. RESULTS: Fluorescein staining of the entire corneal tunnel was observed in all 30 eyes after decompression. An immediate fluorescein flare was observed in the anterior chamber after aqueous release in 24 eyes (80%) (P<.001). Observations over several seconds after decompression found a frank influx of fluorescein-stained fluid into the anterior chamber in 12 eyes (40%) (P<.001), giving rise to an "inverse Seidel's test." An intermittent ingress of fluorescein-stained fluid continued for several minutes after the procedure in 6 eyes (20%) (P<.05). CONCLUSIONS: An incompetence of clear corneal cataract wound with intraocular contamination was observed during the period of induced hypotony after anterior chamber decompression in the early post-phacoemulsification period.