Frank Eperjesi

Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers

Ocular barriers and the poor water solubility of drug candidates present a number of problems for the development of ocular drug delivery systems. Recently, the emergence of lipid-based nanocarriers has provided a viable means of enhancing the bioavailability of ophthalmic formulations. A number of these formulations have been found to be clinically active and several others are currently undergoing clinical trials. In this review, the advantages of lipid-based nanocarriers as non-invasive topical ocular drug delivery systems are presented. Many systems, including emulsions, liposomes, cubosomes, niosomes and other lipid-based nanocarriers, are reviewed.

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.

Visual Hallucinations in the Psychosis Spectrum and Comparative Information From Neurodegenerative Disorders and Eye Disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications.

Nutritional supplementation for type 2 diabetes: a systematic review

The role of nutritional supplementation is of increasing interest with regard to ocular disease. Randomised controlled trials have demonstrated the effectiveness of supplementation for age‐related macular degeneration, and formulations are now being developed for use by people with diabetes and diabetic retinopathy. The aim of this review was to synthesise the evidence for use of nutritional supplementation in type 2 diabetes. MEDLINE and EMBASE databases were searched using a systematic approach. Only double‐masked randomised controlled trials were selected. A total of 50 trials were identified as suitable for inclusion. The potential role of alpha‐lipoic acid, chromium, folic acid, isoflavones, magnesium, Pycnogenol®, selenium, vitamin C, vitamin E, and zinc in the treatment of type 2 diabetes is discussed. The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors. Chromium was the most studied supplement, accounting for 16 of the 50 trials. A majority of the trials found a positive effect of chromium on fasting plasma glucose. Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures, but only when combined with soy proteins. Vitamin E is reported to reduce oxidative stress at levels of 200 mg day−1 or more.

Measuring macular pigment optical density in vivo: a review of techniques

BackgroundMacular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in vivo.MethodA systematic literature search was undertaken to identify all available papers that have used in vivo MPOD techniques. The papers were reviewed, and all relevant information was incorporated into this article.ResultsMeasurement of MPOD is achievable with a wide range of techniques, which are typically categorized into one of two groups: psychophysical (requiring a response from the subject) or objective (requiring minimal input from the subject). The psychophysical methods include heterochromatic flicker photometry and minimum motion photometry. The objective methods include fundus reflectometry, fundus autofluorescence, resonance Raman spectroscopy and visual evoked potentials. Even within the individual techniques, there is often much variation in how data is obtained and processed.ConclusionThis review comprehensively details the procedure, instrumentation, assumptions, validity and reliability of each MPOD measurement technique currently available, along with their respective advantages and disadvantages. This leads us to conclude that development of a commercial instrument, based on fundus reflectometry or fundus autofluorescence, would be beneficial to macular pigment research and would support MPOD screening in a clinical setting.

Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials

Age‐related macular degeneration (AMD) is the leading cause of severe vision loss in the developed world. The lack of effective treatment modalities, coupled with evidence supporting an oxidative pathogenesis, has increased interest in the potential preventative role of nutritional supplementation.

Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease: a randomized controlled trial

Objective:The aim of the study is to determine the effect of lutein combined with vitamin and mineral supplementation on contrast sensitivity in people with age-related macular disease (ARMD).Design:A prospective, 9-month, double-masked randomized controlled trial.Setting:Aston University, Birmingham, UK and a UK optometric clinical practice.Subjects:Age-related maculopathy (ARM) and atrophic age-related macular degeneration (AMD) participants were randomized (using a random number generator) to either placebo (n=10) or active (n=15) groups. Three of the placebo group and two of the active group dropped out.Interventions:The active group supplemented daily with 6 mg lutein combined with vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured using the Pelli–Robson chart, for which the study had 80% power at the 5% significance level to detect a change of 0.3 log units.Results:The CS score increased by 0.07±0.07 and decreased by 0.02±0.18 log units for the placebo and active groups, respectively. The difference between these values is not statistically significant (z=−0.903, P=0.376).Conclusion:The results suggest that 6 mg of lutein supplementation in combination with other antioxidants is not beneficial for this group. Further work is required to establish optimum dosage levels.

A review of the management of 323 consecutive patients seen in a specific learning difficulties clinic

Visual correlates of specific learning difficulties (SpLD) include: binocular instability, low amplitude of accommodation, and Meares–Irlen Syndrome. Meares–Irlen Syndrome describes asthenopia and perceptual distortions which are alleviated by using individually prescribed coloured filters. Data from 323 consecutive patients seen over a 15 month period in an optometric clinic specialising in SpLD are reviewed. Visual symptoms and headaches were common. 48% of patients were given a conventional optometric intervention (spectacles, orthoptic exercises) and 50% were issued with coloured filters, usually for a trial period. 40% of those who were given orthoptic exercises were later issued with coloured overlays. 32% of those who were issued with coloured overlays were ultimately prescribed Precision Tinted lenses. Approximately half the sample were telephoned more than a year after the last clinical appointment. More than 70% of those who were prescribed Precision Tints were still wearing them daily, and results for this intervention compared favourably with data for non‐tinted spectacles. The data suggest that many people with SpLD need optometric care and that the optometrist needs to be skilled in orthoptic techniques and cognisant of recent research on coloured filters.

Do tinted lenses or filters improve visual performance in low vision? A review of the literature.

This is a review of studies that have investigated the proposed rehabilitative benefit of tinted lenses and filters for people with low vision. Currently, eye care practitioners have to rely on marketing literature and anecdotal reports from users when making recommendations for tinted lens or filter use in low vision. Our main aim was to locate a prescribing protocol that was scientifically based and could assist low vision specialists with tinted lens prescribing decisions. We also wanted to determine if previous work had found any tinted lens/task or tinted lens/ocular condition relationships, i.e. were certain tints or filters of use for specific tasks or for specific eye conditions. Another aim was to provide a review of previous research in order to stimulate new work using modern experimental designs. Past studies of tinted lenses and low vision have assessed effects on visual acuity (VA), grating acuity, contrast sensitivity (CS), visual field, adaptation time, glare, photophobia and TV viewing. Objective and subjective outcome measures have been used. However, very little objective evidence has been provided to support anecdotal reports of improvements in visual performance. Many studies are flawed in that they lack controls for investigator bias, and placebo, learning and fatigue effects. Therefore, the use of tinted lenses in low vision remains controversial and eye care practitioners will have to continue to rely on anecdotal evidence to assist them in their prescribing decisions. Suggestions for future research, avoiding some of these experimental shortcomings, are made.

Rehabilitation in Charles Bonnet syndrome: a review of treatment options

People with vision loss sometimes experience visual hallucinations associated with Charles Bonnet syndrome. The appearance of these hallucinations often causes anxiety for the sufferer and can be difficult for the attending eye care professional to manage. A review of the literature highlighted a range of visual, pharmacological and social management regimes that may alleviate these hallucinations, albeit using small samples in uncontrolled trials. Eye care practitioners should be aware of methods of rehabilitation in Charles Bonnet syndrome that may lead to resolution of the visual hallucinations.