Amy C. Nau

Top-down influence on the visual cortex of the blind during sensory substitution.

Visual sensory substitution devices provide a non-surgical and flexible approach to vision rehabilitation in the blind. These devices convert images taken by a camera into cross-modal sensory signals that are presented as a surrogate for direct visual input. While previous work has demonstrated that the visual cortex of blind subjects is recruited during sensory substitution, the cognitive basis of this activation remains incompletely understood. To test the hypothesis that top-down input provides a significant contribution to this activation, we performed functional MRI scanning in 11 blind (7 acquired and 4 congenital) and 11 sighted subjects under two conditions: passive listening of image-encoded soundscapes before sensory substitution training and active interpretation of the same auditory sensory substitution signals after a 10-minute training session. We found that the modulation of visual cortex activity due to active interpretation was significantly stronger in the blind over sighted subjects. In addition, congenitally blind subjects showed stronger task-induced modulation in the visual cortex than acquired blind subjects. In a parallel experiment, we scanned 18 blind (11 acquired and 7 congenital) and 18 sighted subjects at rest to investigate alterations in functional connectivity due to visual deprivation. The results demonstrated that visual cortex connectivity of the blind shifted away from sensory networks and toward known areas of top-down input. Taken together, our data support the model of the brain, including the visual system, as a highly flexible task-based and not sensory-based machine.

A standardized obstacle course for assessment of visual function in ultra low vision and artificial vision.

We describe an indoor, portable, standardized course that can be used to evaluate obstacle avoidance in persons who have ultralow vision. Six sighted controls and 36 completely blind but otherwise healthy adult male (n=29) and female (n=13) subjects (age range 19-85 years), were enrolled in one of three studies involving testing of the BrainPort sensory substitution device. Subjects were asked to navigate the course prior to, and after, BrainPort training. They completed a total of 837 course runs in two different locations. Means and standard deviations were calculated across control types, courses, lights, and visits. We used a linear mixed effects model to compare different categories in the PPWS (percent preferred walking speed) and error percent data to show that the course iterations were properly designed. The course is relatively inexpensive, simple to administer, and has been shown to be a feasible way to test mobility function. Data analysis demonstrates that for the outcome of percent error as well as for percentage preferred walking speed, that each of the three courses is different, and that within each level, each of the three iterations are equal. This allows for randomization of the courses during administration.

Successful tactile based visual sensory substitution use functions independently of visual pathway integrity

Purpose: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort). Methods: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). Results: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p ≤ 0.025) in the bilateral optic radiations and some visual association connections between all three groups. No relationship was found between FA and functional performance with the BrainPort. Discussion: All subjects showed performance improvements using the BrainPort irrespective of nature and duration of blindness. Definite brain areas with significant microstructural integrity changes exist among PB, AB, and NC, and these variations are most pronounced in the visual pathways. However, the use of sensory substitution devices is feasible irrespective of microstructural integrity of the primary visual pathways between the eye and the brain. Therefore, tongue based devices devices may be usable for a broad array of non-sighted patients.

Acanthamoeba keratitis associated with tap water use during contact lens cleaning: manufacturer guidelines need to change.

Abstract: Contact lens–associated Acanthamoeba keratitis continues to be a significant cause of visual morbidity in the United States. Although exposure to water sources while wearing lenses has been a known risk factor for infection for decades, this behavior in several contact lens hygiene protocols continues to prevail. In this review, we surveyed the currently available contact lens cleaning solutions for both soft and rigid gas-permeable contact lenses and reviewed the cleaning instructions of the available solutions. Discrepancies between clinician recommendations and written instructions on a solution packages continues to persist, and we advocate a revision in current manufacturer guidelines to include explicit warnings against use of tap or distilled water sources for cleaning contact lenses or their storage cases.

Contact lens fitting and long-term management for the Boston keratoprosthesis.

Objectives: To examine the types of contact lenses used as bandage lenses in the postoperative management of patients with Boston type 1 keratoprosthesis (K-Pro). We examined the lens parameters, the number of trial lenses used to achieve successful fit, and lens replacement schedule. The strategies to achieving a successful fit in these complex patients are reviewed. Methods: This was a single-center, retrospective chart review of patients who had undergone implantation of the Boston keratoprosthesis in 1 or more eyes from January 2006 to December 2011. Patients included male and female subjects aged 18 years or older who had been fit with bandage contact lenses as part of their postoperative management. Results: Twenty-two eyes of 15 patients met the criteria for this review. The age range was 30 to 90 years. There were eight men and seven women. The average number of lenses to achieve a successful fit varied from 1 to 8, with an average of 2.22 trial lenses used per patient. By 6 months after the surgery, 12 K-Pro eyes showed visual acuity of 20/200 or better, with 7 of those eyes attaining better than 20/80 best-corrected Snellen distance acuity. Conclusions: Our results show that it is often necessary to use custom contact lenses for K-Pro patients. Management of poor tear film quality, protein deposition, inflammation, lens replacement schedule, and antibiotic resistance are related considerations.

Demographic Characteristics and Prescribing Patterns of Scleral Lens Fitters: The SCOPE Study

Objectives: This study reports demographic characteristics of scleral lens providers and indications for scleral lens prescription as assessed by a worldwide online survey. Methods: The Scleral Lenses in Current Ophthalmic Practice: an Evaluation (SCOPE) study group designed the online survey regarding current scleral lens prescription and management practices. The Mayo Clinic Survey Research Center administered the survey, which was open from January 15 to March 31, 2015. Data from 989 responses were collated by the Survey Research Center and deidentified before analysis. Responses of individuals who had fit at least five patients with scleral lenses were analyzed in detail. Results: Most lens fitters were men (61%, n=800). Of survey respondents, 29% were 25 to 34 years; 22%, 35 to 44 years; 22%, 45 to 54 years; and 26%, more than 55 years (n=806). For 29% of all respondents, professional training was completed between 2009 and 2014 (n=804). Most (54%) fit their first patient between 2010 and 2015, with the earliest lens fit reported in 1956 (n=634). Most respondents (63%) worked primarily in private, group, or retail practice (n=811). Scleral lenses were most often prescribed for corneal irregularity (74%), followed by ocular surface disease (16%) and uncomplicated refractive error (10%) (n=673). Conclusions: Eye care providers of all ages are fitting scleral lenses. The number of individuals who fit this lens modality has increased during the past decade. Scleral lenses are being fit by providers in a wide range of practice settings. Most scleral lenses are prescribed for corneal irregularity.

Use of sensory substitution devices as a model system for investigating cross-modal neuroplasticity in humans

Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans. Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life (Kupers and Ptito, 2014). More recent studies explored what happens to the visual pathways in the context of acquired blindness. This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly. Our lab and others have demonstrated compromised visual pathway integrity in those with peri-natal and acquired blindness (Schoth et al., 2006; Chan et al., 2012; Li et al., 2013; Lee et al., 2014; Dietrich et al., 2015; Ho et al., 2015; Reislev et al., 2015). Additional studies have begun to examine the changes occurring with certain disease states: patients suffering from retinitis pigmentosa, optic neuritis, and glaucoma, all so far demonstrate deterioration of the white matter tract architecture as a function of disease severity (Garaci et al., 2009; Gabilondo et al., 2014; Ohno et al., 2015). This evidence indicates that the visual system as a whole is profoundly susceptible to degeneration even with small amounts of vision loss. On the surface, these investigations appear to have negative implications for vision restoration efforts. Yet, parallel studies which examine the phenomenon of cross-modal plasticity suggest that a remodeling of the central nervous system is possible, such that areas of the brain which have been deprived of normal afferent input are able to reconstitute themselves to be receptive to alternative sensory channels (Merabet and Pascual-Leone, 2010; Kupers and Ptito, 2014). The literature includes several examples of investigations which show that the visual cortex will react to tactile and auditory stimuli in the blind but will be less readily recruited in sighted patients (Merabet and Pascual-Leone, 2010). Moreover, cross-modal interactions have been demonstrated well beyond the traditional “critical period” and into late adulthood, albeit perhaps in a less robust fashion (Sadato et al., 2002; Bedny et al., 2012; Collignon et al., 2013). The notion that the adult brain is still capable of significant structural and functional remodeling after vision loss provides opportunities to restore vision through mechanical or biological means.

Scleral Lens Prescription and Management Practices: The SCOPE Study

Objectives: To assess current scleral lens prescription and management practices by conducting an international online survey of eye care providers. Methods: The SCOPE (Scleral Lenses in Current Ophthalmic Practice: an Evaluation) study group designed and administered an online survey regarding current scleral lens prescription and management practices. The survey was open from January 15 to March 31, 2015, and generated 723 responses from individuals who had fit at least 5 patients with scleral lenses. Results: Respondents (n=663) prescribed scleral lenses that ranged from 15 to 17 mm in diameter (65%), smaller than 15 mm (18%), and larger than 18 mm (17%). More than 50 lens designs were identified. Average daily wearing time of 11.8 hr was consistent across 651 respondents, and 475/651 (73%) recommended midday removal on some, most, or all days. Most respondents recommended nonpreserved saline to fill the bowl of the lens before application (single-use vials, 392/653 [60%]; bottled products, 372/653 [57%]). A hydrogen peroxide-based disinfection system was the most commonly recommended care product (397/651 [61%]). Conclusions: A reasonable degree of consensus exists regarding some aspects of scleral lens prescription and management (average lens diameter, daily wearing time, and use of nonpreserved products for lens application). Further study is needed to develop evidence-based guidelines for scleral lens prescription and management.

Dexamethasone diffusion across contact lenses is inhibited by Staphylococcus epidermidis biofilms in vitro.

Purpose: This study was designed to measure the impact of bacterial biofilms on diffusion of an ocular therapeutic through silicone hydrogel bandage lenses in vitro. Methods: An assay was designed to study the passage of a commonly used steroid, dexamethasone, through silicone hydrogel soft contact lenses. Diffused dexamethasone was measured using a spectrophotometer over a period of 18 hours and quantified using a standard curve. This assay was performed with control and Staphylococcus epidermidis biofilm-coated contact lenses comprised of lotrafilcon A and methafilcon. Biofilms were formed in brain heart infusion broth supplemented with D-glucose. Results: The presented data validate a simple in vitro model that can be used to measure the penetration of a topical therapeutic through silicone hydrogel soft contact lenses. Using this model, we measured a reduction in dexamethasone diffusion up to 88% through S. epidermidis biofilm-coated silicone hydrogel lenses compared with control lenses. Conclusions: The results of this in vitro study demonstrate that bacterial biofilms impede dexamethasone diffusion through silicone hydrogel contact lenses and warrant future studies regarding the clinical benefit of using ocular therapeutics in the setting of bandage contact lens use for corneal epithelial defects.

Effects of acute peripheral/central visual field loss on standing balance

Vision impairments such as age-related macular degeneration (AMD) and glaucoma are among the top risk factors for geriatric falls and falls-related injuries. AMD and glaucoma lead to loss of the central and peripheral visual fields, respectively. This study utilized a custom contact lens model to occlude the peripheral or central visual fields in healthy adults, offering a novel within-subject approach to improve our understanding of the etiology of balance impairments that may lead to an increased fall risk in patients with visual field loss. Two dynamic posturography tests, including an adapted version of the Sensory Organization Test and a virtual reality environment with the visual scene moving sinusoidally, were used to evaluate standing balance. Balance stability was quantified by displacement and time-normalized path length of the center of pressure. Nine young and eleven older healthy adults wore visual field occluding contact lenses during posturography assessments to compare the effects of acute central and peripheral visual field occlusion. The results found that visual field occlusion had greater impact on older adults than young adults, specifically when proprioceptive cues are unreliable. Furthermore, the results suggest that both central and peripheral visions are important in postural control; however, peripheral vision may be more sensitive to movement in the environment.