International Coalition Classifies 25 Subtypes of Uveitis

Article: International coalition classifies 25 subtypes of uveitis, an inflammatory eye disease
Source: National Eye Institute
Published: June 7, 2021

The Standardization of Uveitis Nomenclature (SUN) Working Group, an international coalition of uveitis experts, developed classification criteria for 25 of the most common types of uveitis. Collectively describing over 30 eye diseases characterized by inflammation of the eye, these diseases together comprise the fifth leading cause of blindness in the United States, according to the National Eye Institute. Such inflammation can be seen in structures beyond the uvea, depending on the type of disease, and have different causes, courses, prognoses, and treatment needs. As the project lead comments, "The agreement among uveitis experts on the diagnosis of individual diseases was modest at best." Until recently, the classification of uveitis was based on the primary location of inflammation, such as anterior and posterior uveitis, or intermediate uveitis and panuveitis. To help them identify the important characteristics that distinguished each disease, the team first used informatics to standardize language used to describe the individual diseases, followed by formal consensus techniques among nine uveitis experts reviewing 5,766 cases (averaging 100-250 of each uveitis type), and finally applied machine learning to the 4,046 cases that had at least 75% agreement among the expert reviewers. The overall performance of the criteria was over 90% within uveitic class. Such a classification system would greatly enhance research efforts in "epidemiological studies, translational studies, pathogenesis research, outcomes research, and clinical trials," says the project lead, and "hopefully will yield better disease-specific approaches to diagnosis and treatment."

My rating of this study: ⭐⭐⭐

The Standardization of Uveitis Nomenclature (SUN) Working Group. "Development of Classification Criteria for the Uveitides." American Journal of Ophthalmology.  228:96-105. 9 April 2021. https://doi.org/10.1016/j.ajo.2021.03.061

Echolocation Training in Blind and Sighted People

Article: Can echolocation help people with vision loss?
Source: Durham University (U.K.), via Technology Networks
Published: June 3, 2021

Researchers in the U.K. investigated factors that influence learning a new sensory skill, in this case click-based echolocation, in both blind and sighted individuals. Specifically, they wanted to determine whether blindness and age affected learning of the new auditory skill. The study involved 14 sighted participants and 12 blind participants, ranging from 21 to 79 years of age, over a 10-week training program. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life. "We found that both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training," the authors report, "Importantly, neither age nor blindness was a limiting factor in participants’ rate of learning (i.e. their difference in performance from the first to the final session) or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing." The results suggest that neither age nor level of vision was a limiting factor in learning click-based echolocation. Though there is the possibility of a perceived stigma surrounding making the required clicks in social environments, the findings in this group of participants indicate that both blind and sighted people were confident to use it in social situations. Currently, click-based echolocation is not taught as part of mobility training and rehabilitation for blind people, though based on surveys of improved independence and well-being in blind individuals, introducing training in this sensory modality should be considered.

My rating of this study: ⭐⭐

Norman LJ, Dodsworth C, Foresteire D, et al. "Human click-based echolocation: Effects of blindness and age, and real-life implications in a 10-week training program." PLOS ONE.  16(6):e0252330. 2 June 2021. https://doi.org/10.1371/journal.pone.0252330

Both Active & Sham Play Improve Visuo-Motor Skills

Article: Scientists use video games to shed light on the link between motor activity and vision
Source: City College of New York in PsyPost, via Technology Networks
Published: June 3, 2021

Alpha desynchronization over motor cortex
during active and sham play

Vision guides movement. But input from the motor cortex may also guide the visual system. To explore the connection, the authors designed an experiment with three scenarios: (1) "active play" of a racing video game with traditional hand controls, (2) "sham play" in which participants were made to believe they were controlling the video game with their brain activity, (3) and "passive viewing" of a prerecorded playback of the video game. Because movement (both real and imagined) also produces increased attention that could affect changes in visual processing, the authors developed a second study in which participants were asked to count the appearance of specific images on the screen while passively viewing the game. Electroencephalography (EEG) of alpha-band (8–12 Hz) activity, which appear before performing motor tasks, showed reduced correlation during passive viewing, but no difference between active and sham play, indicating recruitment of the motor cortex despite the absence of overt movement. Counting showed weak evidence, less than statistical significance, that attention was not responsible for the observed differences. The latter finding are likely due to the very small sample size of only 24 participants, of which only one-third were assigned to the sham task. Despite this limitation, the study provides some evidence for the effect of both active and sham play in eliciting visual evoked potentials as compared to passive viewing in support of the view that visual signals are enhanced during movement. That is, motion might also guide vision. Future studies with larger population sizes would provide greater statistical significance.

My rating of this study: ⭐

Ki JJ, Parra LC and Dmochowski JP. "Visually evoked responses are enhanced when engaging in a video game." European Journal of Neuroscience.  52(12):4695-4708. December 2020. https://doi.org/10.1111/ejn.14924

Week in Review: Number 19

Optogenetics & Vision: Interview with José-Alain Sahel
Review of Optology earlier highlighted media coverage of a breakthrough story of the first clinical application of optogenetics to restore partial vision to a patient with terminal retinitis pigmentosa. An interview with the lead author of the study, José-Alain Sahel, in CNRS News  published this week takes a closer look at the research behind the scenes. Originally developed to study neural circuits of the brain, Sahel explains that a colleague's work applying the technique to the circuits of the retina prompted the idea to apply optogenetics to visual impairment. "This project required a lot of time and a great deal of tenacity," he revealed, "Although some of our colleagues thought this project was ludicrous, we held our course because we knew it made sense."

The challenges the team faced over the twelve years of the project included choosing the right proteins for the right type of cell, determining how they could be stimulated effectively, and developing visual rehabilitation protocols for patients. The researchers first explored injecting the proteins in bipolar cells, then in dormant photoreceptors. Though the latter experiments were successful at reactivating dormant cones, the proteins could not be sufficiently strongly expressed in these cells; work continues to be done in this area. They next turned their attention to retinal ganglion cells, which naturally react to light with melanopsin. Responsible for regulating circadian rhythm, melanopsin nonetheless responds too slowly for a strategy to stimulate vision. Sahel's team tested green fluorescent proteins before colleagues suggested channelrhodopsin (CrimsonR), which responds to low-energy amber light that they were looking for. The next obstacle was creating a projection system to stimulate the CrimsonR proteins. Because the application is rather unique, they set up a company, GenSight Biologics, to develop both the gene therapy and the equipment for its application. Finally, they collaborated with a platform called StreetLab to train the patients to use the light-stimulating goggles in real-life conditions. Sahel adds, "Our research is carried out in close collaboration with the patients, who play an active role in our work. We are convinced that in terms of rehabilitation, close ties between actors, developers and users are essential."

Reducing Light Exposure and Neuronal Activity Decreases Risk of Optic Glioma, in Mice
Seeing, hearing, thinking all require brain activity. But for those at risk, the normal day-to-day activity of neurons can drive the formation and growth of brain tumors, such as optic gliomas in this case. Since the neurons of the optic nerve become active when exposed to light, the researchers wanted to investigate whether reducing exposure to light could decrease neuronal activity and thereby limit tumor formation. Using a mouse model of neurofibromatosis type 1 (NF1), they found that mice with Nf1 mutations raised under normal lighting developed tumors, while those kept in the dark during a critical period of development did not. Additional experiments narrowed down the critical window to age 6 to 12 weeks in these mice. None of the mice reared in the dark during that time frame developed tumors by 24 weeks of age. Limited effect was seen beyond the critical window; when the tumors have already formed, placing the mice into darkness slowed tumor growth but did not shrink them. In both mice with Nf1 mutations and in tissue samples of people with low-grade brain tumors, tumor formation was associated with abnormally high levels of a protein called neuroligin 3. In mouse studies, blocking the protein with a drug or eliminating the protein through genetic modification resulted in fewer and smaller tumors. Understanding risk factors for tumor formation can help guide preventative strategies. As one of the senior authors states, “[N]ow that we know these brain tumors are caused by exposure to light and neuronal activity, we can start thinking of next-gen prevention strategies. Maybe we can give kids cool sunglasses to wear with filters or lenses to block out certain wavelengths of light, or repurpose drugs that suppress excessive neuronal activity, and protect these kids from developing brain tumors and losing their sight.”

Larger Pupils are Correlated with Higher Fluid Intelligence and Attention Control
New research finds a possible link between baseline pupil size and individual difference in cognitive ability. Beyond reacting to light intensity, pupils also indicate arousal, interest, and mental effort. Curious about the connection between pupil dilations as an indicator of mental effort, the researchers wanted to investigate whether pupil size was also a measure of intelligence. The study involved 500 participants aged 18 to 35, whose pupils were measured with an eye tracker while they stared at a blank computer screen for up to four minutes. These participants then performed tests in fluid intelligence (the capacity to reason through new problems), working memory capacity (the ability to remember information over a period of time), and attention control (the ability to focus attention amid distractions and interference). After controlling for age-related decreases in pupil size, the researchers found that larger baseline pupil size was correlated with better performance in fluid intelligence and attention control and, to a lesser degree, working memory capacity in all but the brightest lighting conditions. They hypothesize that people with larger pupils at rest have greater regulation of activity by the locus coeruleus, a nucleus situated in the upper brain stem that is responsible for releasing norepinephrine as well as regulating a range of neural processes such as perception, attention, learning and memory. Though more research is needed to determine why larger pupils are correlated with higher fluid intelligence and attention control, studies such as this provide a better glimpse through that proverbial "window of the soul."

Screen Time, Sleep Quality, and Myopia
Research led by an optometrist in Australia investigated the link between sleep quality and myopia. The findings indicate that people with near-sightedness have lower production of melatonin and more delayed circadian rhythms, compared to those with normal vision. The study involved a small cohort—18 myopes and 14 emmetropes—of university students, with endogenous melatonin levels measured through saliva and urine samples. The differences in sleep patterns in myopes compared to emmetropes include being more likely to go to bed later (i.e., be "night owls"), taking longer to fall asleep, and sleeping for shorter periods of time. Other research in the field suggest a link between excessive screen use and the onset of the condition in young children, with cases of myopia on the rise globally. As the researcher says, "A lot of digital devices emit blue light, which can suppress the production of melatonin and cause delay in circadian rhythms at night, resulting in delayed and poor sleep...Adequate sleep is critical for learning, memory, sustained attention, academic performance at school, and general wellbeing of children during the early development...It is important to limit the exposure to digital devices in children, particularly at night, for ensuring good sleep and healthy vision." He next plans to study light exposure at night, melatonin production, and circadian rhythms during childhood, when risk of developing myopia is highest.

Screen Time and Myopia During COVID-19
An article in the Wall Street Journal  summarizes key points about the link between myopia and increased screen time during the COVID-19 pandemic, as reported by several ophthalmologists. One theory suggests that when children engage in prolonged near work, such as on screens or reading books, the eye becomes used to near focus, which may cause lengthening of the eyeball, leading to myopia. Less time spent outdoors also contributes to the growing rates of myopia, as time spent outdoors often accompanies looking farther away (rather than near). Finally, the natural lighting of outdoor environments could also play a role in preventing myopia. The article touches upon an often cited study published in JAMA Ophthalmology  reporting overall increased rates of myopia among more than 120,000 homebound children in China. Doctors in the U.S. are seeing similar trends in their clinics, including trends toward high myopia (that is, myopia greater than six diopters), which puts these kids at increased risk of vision-threatening eye problems such as myopic degeneration and retinal detachment later in life. Alongside myopia, doctors also report more cases of digital eye strain during the pandemic, with symptoms including blurry vision, headaches and eye fatigue. One of the ophthalmologists interviewed has conducted a small survey during the first five months of this year among 110 children, ages 10 to 17, who had virtual schooling ranging from 3 to 10 hours. The data is preliminary and yet to be published, though the article reports that symptoms found include "eye aches, headaches, words moving around a page, blurry and double vision, and losing their place when they read, tearing and burning, rubbing eyes more often, dryness, and the sensation of a foreign body in the eye." Lastly, the pandemic has caused more complaints of dry eyes, especially among adults and associated with mask-wearing and reduced blink rate from screen use.

In Other News:
(1) The use of optogenetics in neuroscience
(2) Controlling brain states with rays of light
(3) J&J develops reshaping contact lenses for childhood myopia

Optogenetics & Vision: Interview with José-Alain Sahel

Article: How optogenetics has restored partial sight to a blind patient
Source: French National Center for Scientific Research, CNRS News
Published: June 23, 2021

Optogenetic response measured ex vivo in
a primate’s retina when presented with a symbol

Review of Optology earlier highlighted media coverage of a breakthrough story of the first clinical application of optogenetics to restore partial vision to a patient with terminal retinitis pigmentosa. An interview with the lead author of the study, José-Alain Sahel, in CNRS News  published this week takes a closer look at the research behind the scenes. Originally developed to study neural circuits of the brain, Sahel explains that a colleague's work applying the technique to the circuits of the retina prompted the idea to apply optogenetics to visual impairment. "This project required a lot of time and a great deal of tenacity," he revealed, "Although some of our colleagues thought this project was ludicrous, we held our course because we knew it made sense."

The challenges the team faced over the twelve years of the project included choosing the right proteins for the right type of cell, determining how they could be stimulated effectively, and developing visual rehabilitation protocols for patients. The researchers first explored injecting the proteins in bipolar cells, then in dormant photoreceptors. Though the latter experiments were successful at reactivating dormant cones, the proteins could not be sufficiently strongly expressed in these cells; work continues to be done in this area. They next turned their attention to retinal ganglion cells, which naturally react to light with melanopsin. Responsible for regulating circadian rhythm, melanopsin nonetheless responds too slowly for a strategy to stimulate vision. Sahel's team tested green fluorescent proteins before colleagues suggested channelrhodopsin (CrimsonR), which responds to low-energy amber light that they were looking for. The next obstacle was creating a projection system to stimulate the CrimsonR proteins. Because the application is rather unique, they set up a company, GenSight Biologics, to develop both the gene therapy and the equipment for its application. Finally, they collaborated with a platform called StreetLab to train the patients to use the light-stimulating goggles in real-life conditions. Sahel adds, "Our research is carried out in close collaboration with the patients, who play an active role in our work. We are convinced that in terms of rehabilitation, close ties between actors, developers and users are essential."

My rating of this article: ⭐⭐⭐

Larger Pupils are Correlated with Higher Fluid Intelligence and Attention Control

Article: Pupil Size Is a Marker of Intelligence
Source: Scientific American, via JCAHPO and AOA
Published: June 2, 2021

New research finds a possible link between baseline pupil size and individual difference in cognitive ability. Beyond reacting to light intensity, pupils also indicate arousal, interest, and mental effort. Curious about the connection between pupil dilations as an indicator of mental effort, the researchers wanted to investigate whether pupil size was also a measure of intelligence. The study involved 500 participants aged 18 to 35, whose pupils were measured with an eye tracker while they stared at a blank computer screen for up to four minutes. These participants then performed tests in fluid intelligence (the capacity to reason through new problems), working memory capacity (the ability to remember information over a period of time), and attention control (the ability to focus attention amid distractions and interference). After controlling for age-related decreases in pupil size, the researchers found that larger baseline pupil size was correlated with better performance in fluid intelligence and attention control and, to a lesser degree, working memory capacity in all but the brightest lighting conditions. They hypothesize that people with larger pupils at rest have greater regulation of activity by the locus coeruleus, a nucleus situated in the upper brain stem that is responsible for releasing norepinephrine as well as regulating a range of neural processes such as perception, attention, learning and memory. Though more research is needed to determine why larger pupils are correlated with higher fluid intelligence and attention control, studies such as this provide a better glimpse through that proverbial "window of the soul."

My rating of this study: ⭐⭐

Tsukahara JS and Engle RW. "Is baseline pupil size related to cognitive ability? Yes (under proper lighting conditions)." Cognition.  211:104643. June 2021. https://doi.org/10.1016/j.cognition.2021.104643

Screen Time and Myopia During COVID-19

Article: The Pandemic Made Kids’ Eyesight Worse, Doctors Say
Source: Wall Street Journal, via AAO
Published: June 1, 2021

An article in the Wall Street Journal  summarizes key points about the link between myopia and increased screen time during the COVID-19 pandemic, as reported by several ophthalmologists. One theory suggests that when children engage in prolonged near work, such as on screens or reading books, the eye becomes used to near focus, which may cause lengthening of the eyeball, leading to myopia. Less time spent outdoors also contributes to the growing rates of myopia, as time spent outdoors often accompanies looking farther away (rather than near). Finally, the natural lighting of outdoor environments could also play a role in preventing myopia. The article touches upon an often cited study published in JAMA Ophthalmology  reporting overall increased rates of myopia among more than 120,000 homebound children in China. Doctors in the U.S. are seeing similar trends in their clinics, including trends toward high myopia (that is, myopia greater than six diopters), which puts these kids at increased risk of vision-threatening eye problems such as myopic degeneration and retinal detachment later in life. Alongside myopia, doctors also report more cases of digital eye strain during the pandemic, with symptoms including blurry vision, headaches and eye fatigue. One of the ophthalmologists interviewed has conducted a small survey during the first five months of this year among 110 children, ages 10 to 17, who had virtual schooling ranging from 3 to 10 hours. The data is preliminary and yet to be published, though the article reports that symptoms found include "eye aches, headaches, words moving around a page, blurry and double vision, and losing their place when they read, tearing and burning, rubbing eyes more often, dryness, and the sensation of a foreign body in the eye." Lastly, the pandemic has caused more complaints of dry eyes, especially among adults and associated with mask-wearing and reduced blink rate from screen use.

My rating of this article: ⭐