Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Peripheral Nerve Disorders

Peripheral nerve disorders are caused by a range of different aetiologies. The range of causes include metabolic conditions such as diabetes, obesity and chronic kidney disease. Diabetic neuropathy may be associated with severe weakness and the loss of sensation, leading to gangrene and amputation in advanced cases. Recent studies have indicated a high prevalence of neuropathy in patients with chronic kidney disease, also known as uraemic neuropathy. Immune-mediated neuropathies including Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy may cause significant physical disability. As survival rates continue to improve in cancer, the prevalence of treatment complications, such as chemotherapy-induced peripheral neuropathy, has also increased in treated patients and survivors. Notably, peripheral neuropathy associated with these conditions may be chronic and long-lasting, drastically affecting the quality of life of affected individuals, and leading to a large socioeconomic burden. This review article explores some of the major emerging clinical and experimental therapeutic agents that have been investigated for the treatment of peripheral neuropathy due to metabolic, toxic and immune aetiologies

Review of referrals reveal the impact of referral content on the triage and management of ophthalmology wait lists

Objectives Many chronic eye conditions are managed within public hospital ophthalmology clinics resulting in encumbered wait lists. Integrated care schemes can increase system capacity. In order to direct implementation of a public hospital-based integrated eye care model, this study aims to evaluate the quality of referrals for new patients through information content, assess triage decisions of newly referred patients and evaluate the consistency of referral content for new patients referred multiple times. Design A retrospective and prospective review of all referral forms for new patients referred to a public hospital ophthalmology clinic between January 2016 and September 2017, and September 2017 and August 2018, respectively. Setting A referral-only public hospital ophthalmology clinic in metropolitan Sydney, Australia. Participants 418 new patients on existing non-urgent wait lists waiting to be allocated an initial appointment, and 528 patients who were newly referred. Primary and secondary outcome measures The primary outcome was the information content of referrals for new patients. The secondary outcomes were triage outcomes for new incoming referrals, and the number of new patients with multiple referrals. Results Of the wait-listed referrals, 0.2% were complete in referral content compared with 9.8% of new incoming referrals (p<0.001). Of new incoming referrals, 56.7% were triaged to a non-urgent clinic. Multiple referrals were received for 49 patients, with no change in the amount of referral content. Conclusions Most referrals were incomplete in content, leading to triage based on limited clinical information. Some new patients were referred multiple times with their second referral containing a similar amount of content as their first. Lengthy wait lists could be prevented by improving administrative processes and communication between the referral centre and referrers. The future implementation of an integrated eye care model at the study setting could sustainably cut wait lists for patients with chronic eye conditions

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research

AGE-RELATED EFFECTS OF INCREASING POSTURAL CHALLENGE ON EYE MOVEMENT ONSET LATENCIES TO VISUAL TARGETS

When a single light cue is given in the visual field, our eyes orient towards it with an average latency of 200 ms. If a second cue is presented at or around the time of the response to the first, a secondary eye movement occurs that represents a re-orientation to the new target. While studies have shown that eye movement latencies to ‘single-step’ targets may or may not be lengthened with age, secondary eye-movements (during ‘double-step’ displacements) are significantly delayed with increasing age. The aim of this study was to investigate if the postural challenge posed simply by standing (as opposed to sitting) results in significantly longer eye movement latencies in older adults compared to the young. Ten young (65 years) participated in the study. They were required to fixate upon a central target and move their eyes in response to 2 types of stimuli: 1) a single-step perturbation of target position either 15º to the right or left, and 2) a double-step target displacement incorporating an initial target jump to the right or left by 15º, followed after 200 ms, by a shift of target position to the opposite side (e.g., +15º then -15º). All target displacement conditions were executed in sit and stand positions with the participant at the same distance from the targets. Eye movements were recorded using electro-oculography. Older adults did not show significantly longer eye movement latencies than the younger adults for single-step target displacements, and postural configuration (stand compared to sit) had no effect upon latencies for either group. We categorised double-step trials into those during which the second light changed after or before the onset of the eye shift to the first light. For the former category, young participants showed faster secondary eye shifts to the second light in the standing position, while the older adults did not. For the latter category of double-step trial, young participants showed no significant difference between sit and stand secondary eye movement latencies, but older adults were significantly longer standing compared to sitting. The older adults were significantly longer than the younger adults across both postural conditions, regardless of when the second light change occurred during the eye shift to the first light. We suggest that older adults require greater time and perhaps attentional processes to execute eye movements to unexpected changes of target position when faced with the need to maintain standing balance. Keywords: Balance, Ageing, Gaze, Electro-oculography, Target perturbations

TFOS Lifestyle: Impact of nutrition on the ocular surface: TFOS Lifestyle Workshop: Nutrition report

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials

BCLA CLEAR Presbyopia:Epidemiology and impact

The global all-ages prevalence of epidemiologically-measured 'functional' presbyopia was estimated at 24.9% in 2015, affecting 1.8 billion people. This prevalence was projected to stabilise at 24.1% in 2030 due to increasing myopia, but to affect more people (2.1 billion) due to population dynamics. Factors affecting the prevalence of presbyopia include age, geographic location, urban versus rural location, sex, and, to a lesser extent, socioeconomic status, literacy and education, health literacy and inequality. Risk factors for early onset of presbyopia included environmental factors, nutrition, near demands, refractive error, accommodative dysfunction, medications, certain health conditions and sleep. Presbyopia was found to impact on quality-of-life, in particular quality of vision, labour force participation, work productivity and financial burden, mental health, social wellbeing and physical health. Current understanding makes it clear that presbyopia is a very common age-related condition that has significant impacts on both patient-reported outcome measures and economics. However, there are complexities in defining presbyopia for epidemiological and impact studies. Standardisation of definitions will assist future synthesis, pattern analysis and sense-making between studies

Contact lens wear and dry eyes: challenges and solutions

© 2017 Markoulli and Kolanu. The number of contact lens wearers worldwide has remained relatively stable over the past decade, despite the investment that has gone into contact lens technology. This is largely because 10%-50% of wearers dropout of contact lens wear within 3 years of commencement; the most common reason cited being contact lens discomfort (CLD). Of the symptoms reported, sensation of dry eye is the most common. Given the outcome of reduced wearing time, increased chair time, and ultimate contact lens discontinuation, the challenge is to identify the warning signs of CLD early on. Clinically detectable changes such as conjunctival staining, conjunctival indentation, conjunctival epithelial flap formation, lid wiper epitheliopathy, Demodex blepharitis, and meibomian gland dysfunction have been linked to CLD, highlighting the need to perform regular aftercare visits to identify these changes. At a cellular level, conjunctival metaplasia and reduced goblet cell density have been linked to CLD, leading to a downstream effect on the tear film breakup time of contact lens wearers. These factors suggest a strong link between CLD and friction, raising the need to target this as a means of minimizing CLD. The purpose of this review is to identify the clinical signs that relate to CLD as a means of earlier detection and management in order to combat contact lens dropout

Contact lens wear and dry eyes: challenges and solutions

Maria Markoulli,&nbsp;Sailesh Kolanu School of Optometry and Vision Science, University of New South Wales, Sydney, NSW, Australia Abstract: The number of contact lens wearers worldwide has remained relatively stable over the past decade, despite the investment that has gone into contact lens technology. This is largely because 10%&ndash;50% of wearers dropout of contact lens wear within 3 years of commencement; the most common reason cited being contact lens discomfort (CLD). Of the symptoms reported, sensation of dry eye is the most common. Given the outcome of reduced wearing time, increased chair time, and ultimate contact lens discontinuation, the challenge is to identify the warning signs of CLD early on. Clinically detectable changes such as conjunctival staining, conjunctival indentation, conjunctival epithelial flap formation, lid wiper epitheliopathy, Demodex blepharitis, and meibomian gland dysfunction have been linked to CLD, highlighting the need to perform regular aftercare visits to identify these changes. At a cellular level, conjunctival metaplasia and reduced goblet cell density have been linked to CLD, leading to a downstream effect on the tear film breakup time of contact lens wearers. These factors suggest a strong link between CLD and friction, raising the need to target this as a means of minimizing CLD. The purpose of this review is to identify the clinical signs that relate to CLD as a means of earlier detection and management in order to combat contact lens dropout. Keywords: contact lens discomfort, dry eye disease, lid wiper epitheliopathy, tear film biomarkers, meibomian gland dysfunctio

Filaggrin Expression in the Lid Margin During Contact Lens Wear.

AIM: To investigate the expression of the keratinization-related protein, filaggrin, in the lid margin epithelium of contact lens (CL) wearers compared with nonwearers. METHODS: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience; previous CL wearers; and nonwearers as controls. Impression cytology samples were collected from the lid wiper (LW) area of the central upper lid margin. After fixing, an equal, random sample was selected from each group (n=13) for immunocytochemistry analysis using antihuman primary anybody (mouse filaggrin), then stained with secondary antibody (fluorescein isothiocyanate-conjugated donkey anti-mouse immunoglobulin G horseradish peroxidase) to detect filaggrin. Imaging was performed with the 3i-Vivo 2-photon microscope equipped with a Zeiss 20×-objective and SlideBook-reader software. RESULTS: Sixty-five samples from 65 participants (37 women; mean age±SD: 25.1±4.1 years) were collected. Filaggrin was detected in all 65 randomly selected immunostained marginal epithelium samples. All samples were similar in showing patchy areas of filaggrin immunostaining, regardless of CL wear, symptoms or epithelium morphology. Because the filaggrin immunostaining showed similar patterns across almost all the observed samples, comparison between subject groups was impractical. The presence of filaggrin in the healthy LW was additionally confirmed by an independent laboratory. CONCLUSION: Filaggrin expression seems to be a normal part of epithelial cell differentiation in the lid margin and may not be a useful keratinization/stress biomarker in the marginal epithelium. Investigating other keratinization biomarkers that are not detected in the normal mucocutaneous junction/LW may help to understand the keratinization nature of LW epithelium changes in CL wearers