Week in Review: Number 33

Visual Impairment May Increase Risk of Dementia
A study using data from the World Health Organization's Study on Global Ageing and Adult Health (SAGE) found that older people with visual impairment were significantly more likely to suffer mild cognitive impairment (MCI), a potential precursor to dementia, which in turn is a major cause of disability and dependency among older individuals. Based on population data of 32,715 people older than 50 years of age from China, India, Russia, South Africa, Ghana and Mexico, the researchers found that people with visual impairment at both distance and near vision were 1.7 times more likely to suffer from mild cognitive impairment than those without visual impairment. Similarly, people with near visual impairment were 1.3 times more likely to suffer from mild cognitive impairment than those without. However, those individuals who reported only distance visual impairment did not appear to exhibit increased risk. The overall prevalence of mild cognitive impairment was 15.3% in the study sample, and 44% of the study population reported no visual impairment at all, suggesting that the connection to cognitive impairment is not strictly due to age. One of the authors comments, “Research now needs to focus on whether intervention to improve quality of vision can reduce the risk of mild cognitive impairment, and ultimately dementia. More work needs to be done to examine any possible causation, and what the reasons might be behind it.”

AI for the Diagnosis of Retinopathy of Prematurity
An artificial intelligence technology used in the United States to diagnose retinopathy of prematurity (ROP) was successfully applied in India, according to researchers at OHSU and Massachusetts General Hospital. Retinopathy of prematurity develops in premature infants who are given high levels of oxygen to sustain them after birth; the high amount of oxygen causes abnormal blood vessel growth in the retina, potentially leading to blindness. Retinopathy of prematurity affects 20,000 babies worldwide, especially in developing countries where there are fewer trained ophthalmologists. According to an earlier study published in JAMA Ophthalmology, the use of this technology to diagnose ROP via images showed a 91% accuracy rate compared to expertly trained ophthalmologists. The new study applied the algorithms to 1,253 eye exams from an ROP telemedicine program in India, and correctly identified 100% of severe cases requiring treatment. The researchers also report that their i-ROP DL system is less susceptible to racial bias by implementing a two-step process, first identifying blood vessel patterns in the original eye image, then turning the image into a black-and-white blood vessel map. It is this second image in black-and-white that is analyzed for ROP, the greyscale colors reducing ethnicity-related differences in retinal image appearance. The technology has been granted breakthrough status by the FDA in 2020 and is licensed to a company called Boston AI Labs for further development. The study authors conclude, "Integration of AI into ROP screening programs may lead to improved access to care for secondary prevention of ROP and may facilitate assessment of disease epidemiology and NCU resources."

RPE Proliferation as a Novel Cause of Uveal Coloboma
Colobomas are congenital ocular malformations resulting from the incomplete closure of the optic fissure during embryonic development. Although most commonly visualized as incomplete formation of the iris, colobomas can occur in a variety of ocular structures, including the lens, choroid, retina, optic disc, and eyelid. Depending on the eye tissue affected and the extent of malformation, colobomas can cause blindness. Prior research demonstrated that mutations in the gene encoding neurofibromin 2 (NF2), a tumor suppressor protein important in tissue development and regeneration, can cause colobomas, among other contributing causes. Researchers studying the role of the gene Nf2 found that silencing the gene in developing mouse eyes led to proliferation of the retinal pigment epithelium (RPE) in the optic fissure region, with RPE cells not forming a monolayer but multiple layers. The cellular crowding from RPE proliferation prevents the cells from transitioning to a cuboidal shape. This leads to improper alignment and orientation of the RPE cells, failure of optic fissure fusion/closure, and ultimately persistent coloboma. The researchers also note that, interestingly, these cells retain their RPE character, rather than transforming into other tissues of the retina. The authors write, "Our findings indicate that limiting proliferation particularly in the RPE layer is a critical mechanism during OF [optic fissure] closure." They hope that studying the underlying mechanism of RPE proliferation during development may help to understand factors preventing regeneration of adult RPE and inform therapeutics for RPE-related eye diseases.

Shared Mutations in Skin & Conjunctival Melanomas
Researchers in the U.K. studying how ultraviolet radiation contributes to cutaneous melanomas found that the same genes that cause these skin cancers also cause a rarer form of melanoma of the eye, namely, conjunctival melanoma, of the mucous membrane that lines the sclera of the eye and inner lids. In particular, the researchers applied whole genome sequencing to 10 samples of conjunctival melanomas and found UVR-associated single base substitution signature 7 (SBS7) genetic mutations in 9 of the conjunctival melanomas, as compared to 1 sample of conjunctival melanoma and 8 samples of other mucosal melanomas that did not show these features related to ultraviolet radiation. They argue that SBS7 dominance in mucosal melanoma is a better indicator of UVR-exposure than tumor site. Furthermore, they found that ultraviolet radiation-induced conjunctival melanomas contain the same cancer mutations in the BRAF and NRAS genes. This contrasts with earlier understanding that the KIT and SF3B1 mutations are more common in mucosal melanomas and the BRAF and NRAS mutations are more common in cutaneous melanomas. Although uveal melanomas, another rare melanoma of the eye, are less related to ultraviolet radiation, the researchers report that their findings complement an earlier study showing that ultraviolet exposure can present SBS7 predominance if it arises on the iris. A common driver of both cutaneous and conjunctival melanoma, the researchers argue, facilitates the application of therapies developed primarily for cutaneous melanoma in the context of ocular melanomas, such as the BRAF inhibitor vemurafenib used to treat skin melanoma. The lead author of the study comments, “Our work shows the importance of delving into the underlying biology in rare cancers, which could identify new tailored treatment avenues for people. In this case we have identified mutations in a rare type of eye cancer that could be targeted by drugs used to treat skin cancer.”

Effects of Dual Sensory Impairment in Women & Men
Two studies from researchers in the U.K. examined the effects of vision, hearing, and dual sensory impairment or loss in women and men, with attention to gender differences. The survey data in the first study, from a database of 23,089 adults in the Spanish National Health Survey, showed that women were between 2 and 2.5 times as likely as men to report experiencing depression and anxiety. Compared to women without sensory impairment, women with dual sensory impairment were almost 3.5 times more likely to report depression or anxiety. Compared to men with no sensory impairment, men with dual sensory loss were almost 2.8 times more likely to report depression and almost 1.8 times as likely to report anxiety. Finally, as expected, dual sensory loss was associated with higher levels of depression and anxiety compared to single sensory loss. In this study, although both genders report experiencing mental health effects, the association was stronger in women. The lead author of the study comments, "This highlights the importance of interventions to address vision and hearing loss, especially in women. Some sensory loss is preventable or treatable, and clearly these issues are taking their toll not just on physical health, but mental health too."

In a second study, using the same Spanish National Health Survey database, the same lead researcher explored associations between physical inactivity and obesity in women and men with vision, hearing , and dual sensory impairment or loss. They found that in people with vision loss, the likelihood of obesity was about 1.4 times higher than those who did not report vision loss. Furthermore, in people with vision loss, the prevalence of obesity was roughly 1.5 times higher in inactive men than in inactive women. Again, as expected, those with combined hearing and vision impairment were more likely to experience inactivity and obesity compared to those with single sensory impairment. The researchers note that although women were overall less physically active than men, an association between physical inactivity and obesity was found in men but not in women. Similar to interventions for depression and anxiety, they conclude that active steps should be taken to reduce the risk of weight gain in people with sensory impairments.

Attentional Blink Phenomenon in Infants
Spatial and temporal attention are primary cognitive processes that enable higher order thinking. Spatial attention is an aspect of visual working memory that develops dramatically during the first year of life and has been previously demonstrated to be similar between infants and adults. Researchers were curious to know whether the temporal element of visual working memory was also similar between adults and preverbal infants. They explored this question through testing the attentional blink effect, a temporal limitation in processing visual information when perception of images occurs less than half a second apart. In other words, if two images occur less than 500 ms apart, visual working memory would "blink" and not register the perception of one of the images. The sample comprised of forty 7- to 8-month-old infants, who were presented with rapid serial visual streams of two female faces as targets at a rate of 100 ms per image and temporally separated by either 200 ms or 800 ms. The scientists took advantage of infants' preferential looking at novelty to identify whether the infants could perceive an image. They found that the babies could identify targets at 800 ms, but not identify targets at 200 ms. They could consolidate items into visual working memory at the longer lag, within a second, but not at the shorter lag of less than half a second. In other words, for targets that were temporally separated by less than half a second, the infants demonstrated attentional blink. Like the similarities between adult and infant spatial visual attention, this study points to similar patterns in temporal visual attention, and the same temporal limitations, between adults and infants that take place as early as within the first year of life. The researchers argue that in addition to being the first study to demonstrate attentional blink in preverbal infants, study of this phenomenon is also relevant as it relates to consciousness.

In Other News
(1) Serious visual impairment declines among older Americans
(2) Added features in VR headset-based vision testing
(3) How newborn mammals dream the world they're entering (Related)