Ava K Bittner

Ashtanga-Based Yoga Therapy Increases the Sensory Contribution to Postural Stability in Visually-Impaired Persons at Risk for Falls as Measured by the Wii Balance Board: A Pilot Randomized Controlled Trial

Objective Persons with visual impairment (VI) are at greater risk for falls due to irreparable damage to visual sensory input contributing to balance. Targeted training may significantly improve postural stability by strengthening the remaining sensory systems. Here, we evaluate the Ashtanga-based Yoga Therapy (AYT) program as a multi-sensory behavioral intervention to develop postural stability in VI. Design A randomized, waitlist-controlled, single-blind clinical trial Methods The trial was conducted between October 2012 and December 2013. Twenty-one legally blind participants were randomized to an 8-week AYT program (n = 11, mean (SD) age = 55(17)) or waitlist control (n=10, mean (SD) age = 55(10)). AYT subjects convened for one group session at a local yoga studio with an instructor and two individual home-based practice sessions per week for a total of 8 weeks. Subjects completed outcome measures at baseline and post-8 weeks of AYT. The primary outcome, absolute Center of Pressure (COP), was derived from the Wii Balance Board (WBB), a standalone posturography device, in 4 sensory conditions: firm surface, eyes open (EO); firm surface, eyes closed (EC); foam surface, EO; and foam surface, EC. Stabilization Indices (SI) were computed from COP measures to determine the relative visual (SIfirm, SIfoam), somatosensory (SIEO, SIEC) and vestibular (SIV, i.e., FoamEC vs. FirmEO) contributions to balance. This study was not powered to detect between group differences, so significance of pre-post changes was assessed by paired samples t-tests within each group. Results Groups were equivalent at baseline (all p > 0.05). In the AYT group, absolute COP significantly increased in the FoamEO (t(8) = -3.66, p = 0.01) and FoamEC (t(8) = -3.90, p = 0.01) conditions. Relative somatosensory SIEO (t(8) = -2.42, p = 0.04) and SIEC (t(8) = -3.96, p = 0.01), and vestibular SIV (t(8) = -2.47, p = 0.04) contributions to balance increased significantly. As expected, no significant changes from EO to EC conditions were found indicating an absence of visual dependency in VI. No significant pre-post changes were observed in the control group (all p > 0.05). Conclusions These preliminary results establish the potential for AYT training to develop the remaining somatosensory and vestibular responses used to optimize postural stability in a VI population. Trial Registration www.ClinicalTrials.gov NCT01366677

Improving graph-based OCT segmentation for severe pathology in retinitis pigmentosa patients

Three dimensional segmentation of macular optical coherence tomography (OCT) data of subjects with retinitis pigmentosa (RP) is a challenging problem due to the disappearance of the photoreceptor layers, which causes algorithms developed for segmentation of healthy data to perform poorly on RP patients. In this work, we present enhancements to a previously developed graph-based OCT segmentation pipeline to enable processing of RP data. The algorithm segments eight retinal layers in RP data by relaxing constraints on the thickness and smoothness of each layer learned from healthy data. Following from prior work, a random forest classifier is first trained on the RP data to estimate boundary probabilities, which are used by a graph search algorithm to find the optimal set of nine surfaces that fit the data. Due to the intensity disparity between normal layers of healthy controls and layers in various stages of degeneration in RP patients, an additional intensity normalization step is introduced. Leave-one-out validation on data acquired from nine subjects showed an average overall boundary error of 4.22 μm as compared to 6.02 μm using the original algorithm.

Randomized Controlled Trial of Electro-stimulation Therapies to Modulate Retinal Blood Flow and Visual Function in Retinitis Pigmentosa

We examined changes in visual function and ocular and retinal blood flow (RBF) among retinitis pigmentosa (RP) participants in a randomized controlled trial of electro‐stimulation therapies.

Reduced Central Retinal Artery Blood Flow Is Related to Impaired Central Visual Function in Retinitis Pigmentosa Patients

ABSTRACT Purpose: We evaluated the test-retest repeatability of blood flow velocities in the retrobulbar central retinal artery (CRA) and explored whether reduced blood flow is related to the degree of visual function loss in retinitis pigmentosa (RP) patients with wide range of disease severity. Materials and Methods: We measured CRA peak systolic velocity (PSV) and end diastolic velocity (EDV) to calculate mean flow velocity (MFV) in 18 RP patients using color Doppler imaging with spectral flow Doppler (GE Logiq7 ultrasound) twice in each eye at each of two visits within a month. At each of these two visits, we measured ETDRS visual acuity (VA), quick Contrast Sensitivity Function (qCSF), Goldmann visual fields (GVF), 10–2 Humphrey visual fields (HVF), and dark-adaptation at 5° from fixation with the AdaptDx; multifocal electroretinography (mfERG) was obtained at a single visit. Results: Mean coefficients of variation for PSV, EDV and MFV were 16.1–19.2% for within-visit measurements and 20.1–22.4% for between-visit measures. Across patients, greater visual function loss assessed with VA (p = 0.04), extinguished versus measurable amplitude in ring 1 for mfERG (p = 0.001), and cone-only versus rod function with the AdaptDx (p = 0.002) were statistically significantly correlated with reduced MFV in the CRA when included a multilevel multivariate regression model along with the qCSF and HVF results, which all together accounted for 47% of the total variance in MFV. GVF log retinal areas (V4e and III4e; p = 0.30 and p = 0.95, respectively) and measurable far peripheral vision during GVF testing (p = 0.66) were not significantly related to MFV. Conclusions: MFV in the CRA decreased with impaired central vision due to loss of both rod and cone function, had good test-retest repeatability, and may serve as a biomarker outcome to determine the potential physiological basis for improvements in RP clinical trials of therapies with indirect effects on blood flow to the retina.

Response to Re: A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients

EDITOR: We are grateful for Mr. Curtis’ comments, which gives us an opportunity to provide further clarifications. In reading our previous report, one should bear in mind that clinical trials are conducted in a series of steps called phases. In phase I, such as our pilot study of electro-acupuncture for retinitis pigmentosa, researchers test a new intervention in a small group to evaluate safety and determine estimates of effect size. Previous phase I trials for orphan retinal diseases, such as retinitis pigmentosa, have included very small samples without a placebo control. If phase I trials demonstrate safety and support study hypotheses, then later phase trials will include larger numbers of subjects and a control group. In his letter, Curtis raises the concern that the subjects with retinitis pigmentosa in our phase 1 trial may have experienced placebo effects, as they were actively seeking an intervention to help with their otherwise untreatable visual loss. He also suggests that heat lamps applied to the stomach, as in our pilot study, may enhance placebo effects but gives no reference or scientific support for this statement. The occurrence of placebo effects following acupuncture is indeed a possibility and an unavoidable factor in any clinical trial. This is precisely why we reported previously the need for future controlled trials, have now identified an appropriate sham intervention and are currently conducting an NIH-funded placebocontrolled trial of electro-acupuncture for retinitis pigmentosa (clinicaltrials.gov: NCT02086890). Curtis claims there are learning effects for visual field and scotopic tests but references a study of frequency doubling perimetry in people without ocular disease and without previous experience with visual field testing. Previously, we addressed this issue by referencing studies indicating no learning effects for these tests in a retinitis pigmentosa population with previous visual field experience. It was important to use a ‘large’ test battery (n = 4) in our initial exploratory study, as we did not know which of the many aspects of visual loss in retinitis pigmentosa might be affected by acupuncture. Curtis commented that it is possible to obtain significant positives by chance when using a large number of tests in a small sample. For this reason, we did not apply any statistical tests to detect significance in our data. Instead, we determined the proportion of patients with improvements outside the 95 per cent confidence interval reported previously for testretest variability in retinitis pigmentosa. Exceeding this interval is highly suggestive that the change is not likely due to chance or usual variability. Beyond the placebo effect, Curtis believes there are no plausible hypotheses to support changes in anatomical structures or physiological processes after treatment with acupuncture; however, there is evidence from a published, controlled study using electro-acupuncture in rats with retinitis pigmentosa-like degeneration, which found increased retinal nerve growth factor and brain-derived neurotrophic factor, as well as preserved outer nuclear layer retinal thickness. We did not claim to have adequate power to demonstrate effectiveness with our initial small sample. Power to show a significant effect is dependent on the magnitude of the effect size and variability of the outcome measure; these parameters alone determine the required sample size. These factors will vary according to the study population, outcome measure and intervention. Therefore, one cannot make the conjecture that an equivalent review of acupuncture research would reveal that a sample size of 70 to 80 subjects would be inadequately powered to detect effects, as in the homeopathy review referenced by Curtis. We welcome suggestions and comments and urge readers to keep an open mind. It is true that older reports of clinical acupuncture outcomes in retinitis pigmentosa are bereft of scientific approaches. With the use of a standardised treatment and evaluation protocol, consisting of validated measures of vision, we firmly believe that our previous and current studies will help to break from that legacy.