Blood biomarkers for assessment of mitochondrial dysfunction: An expert review.

Although mitochondrial dysfunction is the known cause of primary mitochondrial disease, mitochondrial dysfunction is often difficult to measure and prove, especially when biopsies of affected tissue are not available. In order to identify blood biomarkers of mitochondrial dysfunction, we reviewed studies that measured blood biomarkers in genetically, clinically or biochemically confirmed primary mitochondrial disease patients. In this way, we were certain that there was an underlying mitochondrial dysfunction which could validate the biomarker. We found biomarkers of three classes: 1) functional markers measured in blood cells, 2) biochemical markers of serum/plasma and 3) DNA markers. While none of the reviewed single biomarkers may perfectly reveal all underlying mitochondrial dysfunction, combining biomarkers that cover different aspects of mitochondrial impairment probably is a good strategy. This biomarker panel may assist in the diagnosis of primary mitochondrial disease patients. As mitochondrial dysfunction may also play a significant role in the pathophysiology of multifactorial disorders such as Alzheimer's disease and glaucoma, the panel may serve to assess mitochondrial dysfunction in complex multifactorial diseases as well and enable selection of patients who could benefit from therapies targeting mitochondria.

Cost-effectiveness of early detection and treatment of ocular hypertension and primary open-angle glaucoma by the ophthalmologist.

PURPOSE: To determine the most cost-effective case-finding strategy for the ophthalmologist to detect and treat ocular hypertension (OH) and primary open-angle glaucoma (POAG) at an early stage to prevent blindness. DESIGN: A Markov cost-effectiveness simulation model. METHODS: Three case-finding strategies are analysed and compared. The simulated cohort consists of all initial patients of at least 40 years old visiting an ophthalmic practice. All patients undergo ophthalmoscopy, but tonometry is routinely performed to: (1) all initial patients, (2) high-risk patients only, or (3) no one. The population characteristics are based on data of 1000 initial patients. Transition probabilities are taken from the literature. The (direct) costs of diagnosis and treatment represent those for the Netherlands. The time-horizon of the model is 20 years. An annual discount rate of 4% is used. MAIN OUTCOME MEASURES: Costs, proportion of patients becoming blind, years of blindness. RESULTS: The costliest strategy (1) leads to least blindness. The incremental cost-effectiveness ratio, which shows extra costs per year of vision saved in comparison to the cheapest strategy (3), is lower for strategy (1) than for strategy (2). It amounts to euro1707, not including extra costs due to blindness (eg associated with the use of disability facilities). When such costs exceed euro1707 per patient per year, which is most likely, then strategy (1) becomes cost saving. CONCLUSION: It is most cost-effective to routinely perform tonometry to all initial ophthalmic patients to prevent blindness due to glaucoma.

Non-invasive assessment of ocular pharmacokinetics using Confocal Raman Spectroscopy.

A Laser Scanning Confocal Raman Spectroscopy (LSCRS) system was applied for the non-invasive quantification of the transport of a drug through the rabbit cornea in vivo. Employing LSCRS, the changes in the amplitude of a drug-specific Raman signal were assessed over time in the tearfilm and corneal epithelium of the living rabbit eye (n = 6), after topical application of 25 microL Trusopt 2%. This allowed for quantification of pharmacokinetic variables. The effect of the drug on corneal hydration was also monitored. LSCRS demonstrated adequate sensitivity and reproducibility, for continuous real-time monitoring of the Trusopt concentration. Each concentration-time curve had a bi-phasic trend; the rapid initial phase (t<8 min.) corresponds to the nonproductive losses of Trusopt from the tears (k10 = 0.24+/-0.04 min(-1), and the slower later phase (t>20 min.) is the result of transfer of the drug from the corneal epithelium to the stroma (k23 = 0.0047+/-0.0004 min(-1). Drug absorption into the corneal epithelium occurred at a rate of k12 = 0.034+/-0.006 min(-1). Trusopt caused an acute dehydrating effect, with a maximum decrease in corneal hydration of approximately 15% at approximately 60 min. following application of the drug. LSCRS has the specificity, sensitivity, reproducibility and spatial resolution for employment as a potentially valuable tool for the study of ocular pharmacokinetics.