In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown.

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Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine.

Objective To incorporate recent research findings, expert consensus, and patient perspectives into updated guidance on the use of new acute and preventive treatments for migraine in adults. Background The American Headache Society previously published a Consensus Statement on the use of newly introduced treatments for adults with migraine. This update, which is based on the expanded evidence base and emerging expert consensus concerning postapproval usage, provides practical recommendations in the absence of a formal guideline. Methods This update involved four steps: (1) review of data about the efficacy, safety, and clinical use of migraine treatments introduced since the previous Statement was published; (2) incorporation of these data into a proposed update; (3) review and commentary by the Board of Directors of the American Headache Society and patients and advocates associated with the American Migraine Foundation; (4) consideration of these collective insights and integration into an updated Consensus Statement. Results Since the last Consensus Statement, no evidence has emerged to alter the established principles of either acute or preventive treatment. Newly introduced acute treatments include two small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (ubrogepant, rimegepant); a serotonin (5-HT1F ) agonist (lasmiditan); a nonsteroidal anti-inflammatory drug (celecoxib oral solution); and a neuromodulatory device (remote electrical neuromodulation). New preventive treatments include an intravenous anti-CGRP ligand monoclonal antibody (eptinezumab). Several modalities, including neuromodulation (electrical trigeminal nerve stimulation, noninvasive vagus nerve stimulation, single-pulse transcranial magnetic stimulation) and biobehavioral therapy (cognitive behavioral therapy, biofeedback, relaxation therapies, mindfulness-based therapies, acceptance and commitment therapy) may be appropriate for either acute and/or preventive treatment; a neuromodulation device may be appropriate for acute migraine treatment only (remote electrical neuromodulation). Conclusions The integration of new treatments into clinical practice should be informed by the potential for benefit relative to established therapies, as well as by the characteristics and preferences of individual patients.

The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice.

Inflammation is genetically implicated in Parkinson's disease.

Contact lenses are ocular prosthetic devices used by over 150 million people worldwide. Primary applications of contact lenses include vision correction, therapeutics, and cosmetics. Contact lens materials have significantly evolved over time to minimize adverse effects associated with contact lens wearing, to maintain a regular corneal metabolism, and to preserve tear film stability. This article encompasses contact lens technology, including materials, chemical and physical properties, manufacturing processes, microbial contamination, and ocular complications. The function and the composition of the tear fluid are discussed to assess its potential as a diagnostic media. The regulatory standards of contact lens devices with regard to biocompatibility and contact lens market are presented. Future prospects in contact lens technology are evaluated, with particular interest given to theranostic applications for in situ continuous monitoring the ocular physiology.

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Contact lens technology: from fundamentals to applications

Parkinson's disease (PD) is one of the common progressive neurodegenerative disorders with several motor and non-motor symptoms. Most of the motor symptoms may appear at a late stage where most of the dopaminergic neurons have been already damaged. In order to provide better clinical intervention and treatment at the onset of disease, it is imperative to find accurate biomarkers for early diagnosis, including prodromal diagnosis and preclinical diagnosis. At the same time, these reliable biomarkers can also be utilized to monitor the progress of the disease. In this review article, we will discuss recent advances in the development of PD biomarkers from different aspects, including clinical, biochemical, neuroimaging and genetic aspects. Although various biomarkers for PD have been developed so far, their specificity and sensitivity are not ideal when applied individually. So, the combination of multimodal biomarkers will greatly improve the diagnostic accuracy and facilitate the implementation of personalized medicine.

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Recent Advances in Biomarkers for Parkinson's Disease.

Tear levels of tumor necrosis factor-alpha in patients with Parkinson's disease

Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with Parkinson’s disease (PD) as a consequence of levodopa methylation via catechol-O-methyltransferase (COMT). Results from previous studies that assessed the effect of COMT inhibitors on levodopa-induced hyperhomocysteinemia are conflicting. We aimed to evaluate the effects of levodopa and entacapone on plasma Hcy levels. A hundred PD patients were enrolled to the study and divided into three treatment groups (group I: levodopa and/or dopamine agonists; group II: levodopa, entacapone, and/or a dopamine agonist; and group III: dopamine agonist alone). We measured the serum B12, folic acid, and Hcy levels in all patients. There were no statistically significant differences between groups in terms of modified Hoehn and Yahr stages, Unified Parkinson’s Disease Rating Scale II/III, Standardized Mini-Mental Test scores, and serum vitamin B12 and folic acid levels. Plasma median Hcy levels were found above the normal laboratory values in groups I and II, but they were normal in group III. However, there was no statistically significant difference in plasma Hcy levels between groups. Our results showed that levodopa treatment may cause a slight increase in the Hcy levels in PD compared with dopamine agonists and that COMT inhibitors may not have a significant effect on preventing hyperhomocysteinemia.

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Homocysteine Levels in Parkinson’s Disease: Is Entacapone Effective?

Cutaneous allodynia may be observed in patients with migraine and this reflects the central sensitization of the trigeminal neurons. We aimed to investigate the frequency of cutaneous allodynia in patients with episodic migraine and to compare clinical characteristics of migraine patients with and without allodynia. One hundred and eighty-six consecutive patients with episodic migraine attacks were prospectively included in the study. The cutaneous allodynia symptoms that occurred during headache attacks were documented using a questionnaire for assessing cephalic and extracephalic cutaneous allodynia. One hundred and fourteen patients (61.3 %) were observed to develop allodynia during migraine attacks and the ratio of the female gender was found higher among the patients with allodynia (p < 0.001). Migraine disease duration was longer (p = 0.004) and accompanying nausea and phonophobia were more common (p = 0.003 and p = 0.005, respectively) in the patients with allodynia. Menstrually related migraine was found to be associated with both allodynia (p = 0.049) and its severity (p = 0.003). The results of present study revealed that cutaneous allodynia was rather frequent in episodic migraine, particularly in patients having longer disease duration. Higher frequency of allodynia in women and its association with menstrually related migraine may be related to the effects of hormonal factors on cutaneous pain thresholds and central sensitization. Association of nausea and phonophobia with allodynia may be interpreted as the common pathways are shared in the development of these symptoms.

Cutaneous allodynia in patients with episodic migraine.

Vestibular-evoked myogenic potentials (VEMP), short-latency electromyographic responses elicited by acoustic stimuli, evaluate the function of vestibulocollic reflex and may give information about brainstem function. The aim of the present study is to evaluate the potential contribution of VEMP to the diagnosis of multiple sclerosis (MS). Fifty patients with MS and 30 healthy control subjects were included in this study. The frequency of VEMP p1–n1 and n2–p2 waves; mean p1, n1, n2, and p2 latency; and mean p1–n1 and n2–p2 amplitude were determined. The relation between clinical and imaging findings and VEMP parameters was evaluated. The p1–n1 and n2–p2 waves were more frequently absent in MS than in control subjects [p1–n1 wave absent: MS, 25 (25 %) ears; control, 6 (10 %) ears; P ≤ 0.02] [n2–p2 wave absent: MS, 44 (44 %) ears; control, 7 (12 %) ears; P ≤ 0.001]. The mean p1–n1 amplitude was lower in MS than in control subjects (MS, 19.1 ± 7.2 μV; control, 23.3 ± 7.4 μV; P ≤ 0.002). A total of 24/50 (48 %) MS patients had VEMP abnormalities (absent responses and/or prolonged latencies). VEMP abnormalities were more frequent in patients with than without vestibular symptoms (P ≤ 0.02) and with brainstem functional system score (FSS) ≥1 than FSS = 0 (P ≤ 0.02). In patients with MS, absence of p1–n1 wave was more frequent in patients with than without vestibular symptoms [absence of p1–n1 wave: vestibular symptoms, 9 (45 %) ears; no vestibular symptoms, 16 (20 %) ears; P ≤ 0.03] and patients with Expanded Disability Status Scale (EDSS) score ≥5.5 [absence of p1–n1 wave: EDSS ≥5.5, 7 (70 %) ears; EDSS <5.5, 18 (20 %) ears; P ≤ 0.001]. Abnormal VEMP may be noted in MS patients, especially those with vestibular symptoms and greater disability. The VEMP test may complement other studies for diagnosis and follow-up of patients with MS.

Hayat Güven

Papers

Tear levels of tumor necrosis factor-alpha in patients with Parkinson's disease

Homocysteine Levels in Parkinson’s Disease: Is Entacapone Effective?

Cutaneous allodynia in patients with episodic migraine.

Vestibular-evoked myogenic potentials, clinical evaluation, and imaging findings in multiple sclerosis.

Epilepsy and headaches: Further evidence of a link