Week in Review: Number 35

Robotic White Cane for Assistive Navigation
Although many advances have been made in navigation assistive devices for the blind and visually impaired, the white cane remains the most functional and reliable navigation tool for most people who are visually impaired. A project co-funded by the National Institutes of Health’s National Eye Institute (NEI) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) sought to improve upon this century-old technology with modern electronics. As the lead author of the study explains, while GPS-based applications have revolutionized navigation in outdoor settings, helping the blind find their way around in large spaces inside buildings can present challenges, a gap he hopes to close through his robotic white cane. These improvements include the integration of a color 3D camera, an inertial measurement sensor, and an on-board computer, whose software can be paired with a building’s architectural blueprints or floorplans to guide users to destinations using auditory and sensory cues. The color depth camera, in particular, uses infrared light (similar to the front-facing camera of most smartphones) to determine the distance between the user and other physical objects. This information is processed by the onboard computer, which then maps the user's location onto the building's architectural drawings to alert the user to obstacles. The project lead adds, “The rolling tip on our robotic cane can guide you to turn at just the right point and exactly the right number of degrees, whether it’s 15 degrees or 90. This version can also alert you to overhanging obstacles, which a standard white cane cannot.” The robotic white cane is still in development to slim down some of its features for regular use. Nonetheless, the ability to switch between the automated mode and the simpler, non-robotic mode could provide additional independence for people who are blind or visually impaired without losing the time-tested attributes of the traditional white cane.

Eyeglasses to Boost Academic Performance in School
Researchers at Johns Hopkins University Wilmer Eye Institute and School of Education conducted a large clinical study, the most robust study in the U.S. to date on the impact of glasses on education. Vision for Baltimore was a project launched by Johns Hopkins researchers in 2016 in an effort to address the acute need for vision care among the city’s public school students. In addition to providing more than $1 million in support, Johns Hopkins works closely with the program team to provide technical assistance. In the five years, the program has tested the vision of more than 64,000 students and distributed more than 8,000 pairs of glasses. Now in its sixth year, Vision for Baltimore is operated and funded in partnership with the Johns Hopkins schools of Education and Medicine, Baltimore City Public Schools, the Baltimore City Health Department, eyewear brand Warby Parker, and national nonprofit Vision To Learn. The study, a three-year randomized clinical trial, analyzed the performance of 2,304 students in grades 3 to 7 who received screenings, eye examinations and eyeglasses from Vision for Baltimore, looking in particular at their scores on standardized reading and math tests over 1 and 2 years. They found significant improvements in math scores in the elementary school grades, and improvements in reading scores in the first year. The researchers encourage sustained use of glasses to maintain gains in academic achievement thereafter. As the senior author of the study states, “We rigorously demonstrated that giving kids the glasses they need helps them succeed in school...[and] has major implications for advancing health and educational equity all across the country.” Johns Hopkins President Ron Daniels adds, “These results validate the dedication of all of the program’s committed partners, from the principals, staff and teachers across Baltimore City schools to the optometrists at Vision to Learn and the school vision advocates from Johns Hopkins. Looking forward, we hope to work with our state and city leaders to ensure that this impactful program has sustainable funding for years to come.”

Blue Widefield SLO to Evaluate Diabetic Retinopathy
In a retrospective study, researchers in Japan examined blue widefield scanning laser ophthalmoscopy (SLO) in the evaluation of non-perfusion areas (ischemia) and retinal thinning in diabetic retinopathy (DR). This method follows earlier imaging techniques using fluorescein angiography (FA) and multicolor widefield SLO, which uses laser light in simultaneous red, green, and blue wavelengths. The researchers found that the blue images captured by conventional SLO could reveal hyporeflective areas in the retina indicative of damage, and sought to explore this finding further in widefield SLO. The retrospective observational case series compared blue widefield SLO with fluorescein angiography in 90 patients with diabetes; in individuals with diabetic retinopathy, retinal morphology was further examined with optical coherence tomography (OCT). The senior author of the study explains, “We found that the hyporeflective areas in the blue widefield SLO images appeared to correspond with areas of ischemia in the fluorescein angiogram images of patients with DR. We were pleased to find that the rate of concordance was high.” Scanning laser ophthalmoscopy, however, is advantageous in that it is non-invasive compared to fluorescein angiography, which uses an intravenous dye. Furthermore, they found that the ischemic areas correspond with retinal thinning. As another researcher comments, “It’s possible that the blue wavelength of light can pass more easily through these thinned areas of the retina, which present as hyporeflective areas in the SLO images." Given its non-invasive nature and wider field of view, now enhanced with the detection of ischemia and retinal thinning via the blue wavelength, blue widefield SLO could offer new advantages in the detection and evaluation of diabetic retinopathy.

Tetrodotoxin Explored as a Treatment for Amblyopia
Amblyopia results when there are underdeveloped connections between the eye and the brain, and can have etiologies ranging from congenital cataracts to strabismus (an eye misalignment), to anisometropia (unequal refractive state), all of which prevent the affected eye from resolving clear images to form the necessary neural connections. The predominant view is that there is a critical period during childhood after which amblyopia cannot be reversed, even after the underlying etiology is corrected. Aside from behavioral approaches, clinicians have relied on "patching" of the unaffected eye with the thought that the affected eye would form stronger synapses with the brain. This "patching" can be a physical patch over the eye, the same concept of which is retained in more recent uses of atropine eye drops to blur vision in the unaffected eye. Neuroscientists exploring ways to reverse amblyopia have found success in a novel approach, namely, by injection of tetrodotoxin (TTX), which temporarily (reversibly) anesthetizes the retina of the unaffected eye. Experiments in two animal models (mice and cats) have produced "an unequaled profile of recovery" in the amblyopic eye even after the critical period. This recovery was seen in every animal they tested. At the neurological level, synapses that are weak wither in a process known as "long-term depression." However, the researchers explain that temporarily, but completely, suspending visual input creates a condition in which the synaptic connections can fully restrengthen, as if being “rebooted.”

In an earlier study from 2016, the researchers showed that they could reverse amblyopia by anesthetizing both retinas. In the present study, they were able to limit the effect of TTX to the retina of only the non-amblyopic eye. Additionally, the current study was conducted in mature amblyopic animals that were not responsive to other forms of treatment. The scientists even observed that neurons that shrink with amblyopia regained normal size after treatment. Finally, in addition to improving vision in the amblyopic eye (i.e., reversing amblyopia), visual responses recovered to normal levels in the eye that received the TTX in every animal tested, demonstrating no lasting negative effects. It should be noted that a major difference between this approach and prior variations of "patching" is in the complete inactivation of vision that triggers strengthening of synapses in the affected eye. The researchers will pursue further studies to explore tetrodotoxin as an option for adults who suffer from amblyopia. As co-lead author of the study remarks, “I am hopeful and optimistic that this study can provide a pathway for a new and more effective approach to amblyopia treatment. I am very proud to have been part of this rewarding collaboration.”

Case Report: Direct Voluntary Control of Pupil Size
Pupil contriction and dilation are controlled by the autonomic nervous system, a process that was once thought to be automatic in response to stimuli, such as light/darkness, arousing emotions, or mental effort. While indirect voluntary control of pupil size in response to imaginary light has been documented in the literature—for example, imagining a "sunny sky" or a "dark room" resulted in pupillary constriction and dilation, respectively—directly controlling the iris sphincter and dilator musculature was thought to be impossible. That is, until a psychology student in Germany approached his professor, one of the researchers, about his unusual ability to "tremble" his eyeballs. Known by his initials D.W., the student reports, "Constricting the pupil feels like gripping, tensing something; making it larger feels like fully releasing, relaxing the eye." Interestingly, D.W. described having initially practiced the ability by focusing in front of or behind an object, not unlike the miosis and mydriasis that occurs as a result of convergence and divergence of the eyes, respectively. According to the authors, "[I]t seems plausible that [D.W.] could have learned to gain control over the pupillary response by decoupling pupil size changes from accommodation and vergence in the near triad." After a while, D.W. states that all he needed to do to change his pupil size was to concentrate, noting that he doesn't have to imagine bright or dark environments.

The researchers performed a variety of tests, such as measuring the voltage on the skin as a proxy for mental effort, to rule out indirect ways of controlling pupil size. They then measured D.W.'s dilation of pupil diameter to be around 0.8 mm and constriction of pupil diameter to be around 2.4 mm. Moreover, even closer than his near point of accommodation or NPA (that is, the distance at which accommodation is maximal, at which a small object held in front of the eye, such as the tip of a pen, cannot be clearly resolved), D.W. could voluntarily constrict his pupils further. The authors report, "Even at maximal accommodation, [D.W.] voluntarily constricted his pupil without changing vergence and could improve visual acuity by >6 diopters." Task-based functional magnetic resonance imaging (fMRI) showed increased activity in brain areas responsible for volitional impulses, in this case, the dorsolateral prefrontal cortex, adjacent premotor areas, and supplementary motor area. And although the researchers cannot elucidate any connections between these cortical areas and the sympathetic or parasympathetic pathways that ultimately control autonomic pupillary reactions, nor can they definitively rule out that D.W. was using indirect strategies to change his pupil size, they found no evidence of such from the tests they performed. Accordingly, they conclude that this is the first reported case of direct voluntary control of pupil size.

In Other News
(1) How a robot's gaze can affect human decision-making (Related) (Related)
(2) New England College of Optometry to launch hybrid training program
(3) Look to ophthalmology for a glimpse of telemedicine's future