The evolution of clinical guidelines for antimicrobial photodynamic therapy of skin.

Antimicrobial photodynamic therapy has become an important component in the treatment of human infection. This review considers historical guidelines, and the scientific literature to envisage what future clinical guidelines for treating skin infection might include. Antibiotic resistance, vertical and horizontal infection control strategies and a range of technologies effective in eradicating microbes without building up new resistance are described. The mechanism of action of these treatments and examples of their clinical use are also included. The research recommendations of NICE Guidelines on the dermatological manifestations of microbial infection were also reviewed to identify potential applications for PDT. The resistance of some microbes to antibiotics can be halted, or even reversed through the use of supplementary drugs, and so they are likely to persist as a treatment of infection. Conventional PDT will undoubtedly continue to be used for a range of skin conditions given existing healthcare infrastructure and a large evidence base. Daylight PDT may find broader antimicrobial applications than just Acne and Cutaneous Leishmaniasis, and Ambulatory PDT devices could become popular in regions where resources are limited or daylight exposure is not possible or inappropriate. Nanotheranostics were found to be highly relevant, and often include PDT, however, new treatments and novel applications and combinations of existing treatments will be subject to Clinical Trials.

The Effect of Biofeedback as a Psychological Intervention in Multiple Sclerosis: A Randomized Controlled Study.

BACKGROUND: Relaxation, mindfulness, social support, and education (RMSSE) have been shown to improve emotional symptoms, coping, and fatigue in multiple sclerosis (MS). Biofeedback was trialed as a psychological intervention, designed to improve self-control, in two groups of patients with MS. Both groups received RMSSE, and one group additionally received biofeedback. METHODS: Forty people with relapsing-remitting MS were recruited from three sites in Sydney, Australia. The mean disability score (Expanded Disability Status Scale; EDSS) was 2.41 ± 1.46 (95% confidence interval [CI], 1.46-3.36); the mean age in years was 45.9 ± 12.42 (95% CI, 41.92-49.87). Participants were randomly assigned to two active treatment groups (n = 20 per group). All participants received one 1-hour session per week for 3 weeks of RMSSE, while biofeedback equipment measured breathing rate and muscle tension. Members of one group used biofeedback screens to regulate physiological response. RESULTS: Whole-group pre- and post-treatment scores demonstrated a reduction of 38% for anxiety and 39% for depression scores (P = .007 and P = .009, respectively). A post-treatment comparison failed to demonstrate any significant difference between the two active treatment groups in anxiety and depression scores. The biofeedback group showed significant pre- to post-treatment improvement or trends toward improvement in anxiety, fatigue, and stress (P = .05, .02, and .03, respectively). Comparison of pre-post treatment results between groups showed improvements for the biofeedback group in breathing rate and muscle tension (P = .06 and .09). CONCLUSIONS: For relapsing-remitting MS patients receiving biofeedback in addition to RMSSE, there was a demonstrable reduction in anxiety, fatigue, and stress. There was also a trend toward significant reduction of breathing rate and muscle tension in favor of biofeedback.

Sensitivity and specificity of the step VEP in suspected functional visual acuity loss.

BACKGROUND/AIM: Early and accurate diagnosis of functional visual loss (FVL) allows optimum management. Visual evoked potentials (VEPs) offer a means of objectively estimating acuity and therefore could assist with early and accurate diagnosis. The aim of this study was to assess the sensitivity and specificity of the step VEP in diagnosing FVL. METHODS: A retrospective audit was conducted in 36 school-aged children presenting with reduced visual acuity and clinical suspicion of FVL. All had undergone step VEP testing as part of their investigation. Medical notes were reviewed, and where necessary, referring centres, general practitioners or electronic clinical portals were consulted to obtain longer-term outcome data. RESULTS: Twenty-seven of the 36 patients (75%) were classified as having had FVL: all had a normal step VEP spatial threshold. Nine patients (25 %) had an organic cause for their acuity loss, of whom seven had abnormal step VEP spatial thresholds: the other two patients had some functional overlay to their organic disease. The step VEP sensitivity was 78% (95% confidence interval 40-96%), and specificity was 100% (95% confidence interval 84-100%). CONCLUSION: The high specificity of the step VEP for FVL warrants increased suspicion of an organic cause should the step VEP spatial threshold be abnormal.

Real-time rapid acuity assessment using VEPs: development and validation of the step VEP technique.

PURPOSE: To develop a reference range of visual acuities corresponding to thresholds found using the step VEP method of rapid, objective visual acuity assessment by using steady state (ss)VEPs in normal adults. METHODS: Sixteen normal adults had visual acuity assessed five times with both the step VEP and with Glasgow Acuity Cards (GAC). Subjects were tested once without filters and with four different levels of optical filtering provided by Bangerter neutral-density filters. Acuity outcomes were compared by linear regression and Bland-Altman analysis. RESULTS: Step VEP and GAC acuities correlated highly (r(2) = 0.60, P = 0.000). GAC scores were predicted with the equation: acuity(GAC) = (0.9 x acuity(step VEP)) - 0.37. Step VEP acuity was 0.46 (95% CI: -0.13 to 1.06) logMAR units greater (poorer) than GAC acuities in these normal subjects. The disparity between test results did not vary with visual acuity. CONCLUSIONS: The step VEP provides a rapid, objective means of estimating visual acuity that can be related to acuity derived from a commonly used letter test.

Multifocal electroretinography as a predictor of maintenance of vision after photodynamic therapy for neovascular age-related macular degeneration.

PURPOSE: To investigate the role of multifocal electroretinography (mfERG) in predicting the outcome of photodynamic therapy (PDT) for neovascular age-related macular degeneration (AMD). METHODS: Participants underwent refraction protocol VA assessment using the ETDRS logMAR chart at 1 m, Contrast Sensitivity (CS) using the Pelli-Robson chart at 1 m, fundus fluorescein angiography (FA) and mfERGs in response to 19 segments. Response to PDT was binary (1 = the loss of less than 15 letters at 12 months, 0 = the loss of 15 letters or more) and was used as the dependent variable for logistic regression analysis. RESULTS: Logistic regression modelling identified mfERG central segment amplitude, lesion size on FA, VA and CS as predictors of outcome (P = 0.05, 0.02, 0.01, 0.03). The model is stable and has excellent discriminability. CONCLUSION: The outcomes of this study are particularly relevant to patients in the UK who are sometimes treated with PDT alone. A larger prospective study would facilitate development of an index to predict outcome of future treatments for AMD.

Deficits in the electroretinogram in neovascular age-related macular degeneration and changes during photodynamic therapy.

PURPOSE: To describe the deficits in four electroretinography (ERG) modalities in patients with neovascular age-related macular degeneration (AMD). To describe the changes in these parameters during a course of verteporfin photodynamic therapy (PDT). METHODS: Pattern (PERG), multifocal (mfERG) (19 segment simplified test protocol), flash ERG and flicker ERG were performed in patients with active neovascular AMD before PDT and compared to fellow eye controls using paired t-tests. Changes in ERG parameters during the 12 month treatment course were visualised using 95% confidence intervals of the median difference. The statistical significance of any changes was quantified using Wilcoxon signed ranks tests. RESULTS: Fifty patients were recruited and followed. At presentation all ERG amplitudes were reduced with greater reductions in focal as opposed to global test protocols (P < 0.05). Over the 12 month course of PDT, PERG P50 amplitude showed a general downward trend and latency remained unchanged. mfERG p1 amplitude density showed an upward trend at six months before returning to baseline by 12 months. mfERG ring 2 amplitude density was significantly increased at 12 months compared to baseline (P = 0.010). Flicker ERG latency was significantly increased at six months compared to baseline (P = 0.015). DISCUSSION: The simplified mfERG protocol was tolerated by this patient group, however, they found the full test protocol demanding. Large deficits in the retinal ERG function occur in neovascular AMD and involve retinal locations adjacent to as well as overlying choroidal neovascularisation (CNV). After PDT there is an improvement in electro-retinal function in retinal locations overlying the CNV.

Rapid detection of threshold VEPs.

OBJECTIVE: To determine whether a one-dimensional (1D) Laplacian analysis detects steady-state visual evoked potentials (ssVEPs) faster than the standard O(z)-F(z) montage and to establish the optimum position of Laplacian reference electrodes. METHODS: Twenty-two normal adults were shown reversing checks ranging from 1.5' to 60'. Three electrode montages were investigated: O(z)-F(z), LO-F(z) and a 1D Laplacian analysis of 3 occipital electrodes (2O(z)-(RO+LO)). RO and LO were placed symmetrically and horizontally about O(z). Five different locations for RO and LO were investigated. Recordings were analysed in the frequency domain and the presence (and detection time, DT) or absence of a ssVEP defined statistically. Effects of individual, reference electrode site and check size on DT and phase differences between recording montages were investigated. RESULTS: Laplacian analysis detected ssVEPs to small (3') checks faster than O(z)-F(z), by 12.3 and 4.1s on average with Laplacian reference electrodes at 15 and 20% of half-head circumference, respectively. The optimum position of reference electrodes was governed by the instantaneous spatial spread of the response and the noise coherence between midline and lateral electrodes. CONCLUSIONS: A 1D Laplacian analysis can reduce the time to statistical detection of ssVEPs compared to the traditional O(z)-F(z) recording for stimuli near the normal acuity threshold of adults. This in turn could be used to minimise the length of a VEP acuity assessment.

Faster and more sensitive VEP recording in children.

PURPOSE: In the difficult-to-test paediatric population, shorter test procedures are desirable. This study investigates whether Laplacian analysis of a three occipital-electrode montage detects steady-state VEPs (ssVEPs) more often or faster in children than a conventional montage, and if so, in which age groups. METHODS: Steady-state VEPs (7.78 reversals/s; checkerboard stimulus) to various checksizes (60-3', 0.07-14 cpd equivalent) were recorded from 80 normal children aged from 1 month to 13 years and 19 adults. Active occipital electrodes were placed at Oz and symmetrically either side at 15% of the subject's half-head circumference (right occipital and left occipital, RO and LO). The Laplacian analysis used 2Oz-(RO+LO) instead of the conventional Oz-Fz. Fourier analysis and a circular T2 statistic was used to determine VEP detection time (DT). The number of responses detected overall by each analysis method and the effects of age and checksize on DT differences between analysis methods were investigated. RESULTS: The Laplacian analysis detected more VEPs than the conventional Oz-Fz (95 versus 84%, p = 0.001) in children's age groups. The Laplacian analysis also provided faster response detection to 3' checks in all subjects over the age of five, and to 6' and 9' in 7-9-year-olds. CONCLUSION: A Laplacian analysis offers increased sensitivity and faster VEP detection over conventional (Oz-Fz) recording in children over five for threshold-sized VEPs. Simultaneous use of both conventional (Oz-Fz) VEP recording and a Laplacian analysis in all patient ages is likely to give faster, more accurate VEP assessments.