Week in Review: Number 3

Kamuvudines for the Treatment of Advanced AMD
Jayakrishna Ambati, MD, professor of ophthalmology and founding director at the Center for Advanced Vision Science at the University of Virginia, recently published a study in Proceedings of the National Academy of Sciences showing the strong correlation between patients taking nucleoside reverse transcriptase inhibitors (NRTIs), FDA-approved anti-HIV drugs, and reduced risk of developing advanced dry macular degeneration. This observational study is extraordinarily robust, applying "big data archeology" to four different health insurance databases comprising more than 100 million American. The data of reduced risk was found in all of the databases, approximately 40% reduced risk overall, which is a significant finding. An earlier study by Ambati's team published in Nature Communications showed that the use of NRTIs is associated with a 30% reduced risk of developing type 2 diabetes, providing an estimate for the team's further studies into the effect of NRTIs and kamuvudines (less toxic derivatives) on degenerative diseases that involve inflammasome activation, including macular degeneration such as in the present study, but also multiple sclerosis and Alzheimer's disease. Given the robust data on the effect of these drugs that are already FDA-approved to treat HIV in humans, the drugs have great potential to be repurposed for off-label use in the treatment of advanced macular degeneration. While there are eye vitamins following the AREDS2 formulas to promote eye health in some forms and stages of dry macular degeneration, there is as yet no therapeutic treatment for the disease at this point. As Ambati states, “A clinical trial of these inflammasome-inhibiting drugs is now warranted."

Increased Prevalence of Myopia in Young Children during COVID-19 Quarantine
Myopia, or near-sightedness, is a growing concern in some parts of the world, recently being studied in detail in East Asian countries such as China. The current prospective study examined the refractive error of 123,535 children aged 6 to 13 years from 10 elementary schools in Feicheng, China over 6 consecutive years, ending in July 2020. While the researchers found a shift toward myopia in children ages 6 to 8 studied between 2015 and 2019, what was most striking about the results was the increased prevalence of myopia during 2020, when schools were closed due to the COVID-19 pandemic and school children transitioned to online learning. Though the majority of cases were mild at an average of -0.3 diopters of myopic shift, the prevalence of myopia in 2020 was higher than the highest prevalence in 2015 to 2019 for students ages 6 (21.5% vs 5.7%), 7 (26.2% vs 16.2%), and 8 (37.2% vs 27.7%). There was no increased prevalence of myopia in children ages 9 to 13 despite longer durations of online learning. With a topic this complex and new, the researchers added the appropriate remarks about limitations of the study before offering a cautious suggestion toward evidence of cause being decreased time spent outdoors, especially during the younger ages when the eyes are still developing. A commentary in the article and in the same journal adds, however, that "older children's eyesight may not have changed much because they were already accustomed to spending less time outdoors and more time on screens and doing close-up work before the pandemic began," suggesting that the shift is not necessarily progressive.

Remyelinating Drug in an MS Mouse Model
Multiple sclerosis (MS) is an autoimmune condition that affects the myelin sheath surrounding and insulating neuronal axons, resulting in demyelination and reduced signal transmission. Where MS is relevant to eye care is in its effect on the optic nerve carrying visual information from the retina to the brain. The current study investigated the use of a drug, an estrogen receptor ligand called indazole chloride (IndCl), in remyelinating afferent neurons of the visual pathway in a mouse model of MS. As measured by functional assay to determine the visual electrical signal and immunohistochemistry to examine the visual pathway, the researchers found that the mice that received the drug, even as tested at peak disease, showed improvement in myelination, with visual function improving by about 50%. It's important to keep in mind that the research is in animal models at this stage. However, given that current therapies for multiple sclerosis are only aimed at reducing inflammation and do not necessarily provide recovery of visual function, the potential of a remyelinating drug that confers neuroprotection and reversal of damage is encouraging.

Ocular Effects of Prion Disease
Prion diseases are neurodegenerative diseases due to misfolded proteins and usually affect the brain. Because the retina is an extension of the brain, many neurodegenerative diseases also have ocular manifestations. In this study, scientists at the NIH's National Institute of Allergy and Infectious Diseases investigated the mechanism of prion diseases on the eye's photoreceptors using a mouse model of scrapie, a prion disease common to sheep and goats. Previously, the researchers found that prion-induced retinal damage in mice and human photoreceptors resembled that of retinitis pigmentosa. In the current study, they further isolated the location of that damage to the cilia and ribbon synapses of rod photoreceptors. By interfering with transport and critical synapses, prion aggregates may provide an early mechanism of damage to the photoreceptors. The findings in this study provide a new level of detail to the association between prion disease and retinal damage.

Vitamin C for Microvascular Health
This study comes from the field of dentistry, but contains relevance to eye care in the shared assessment of microvascular health as early indications of systemic health. The authors conducted a literature review of 15 clinical trials involving 1,140 participants and data from 8,210 U.S. residents surveyed in the Centers for Disease Control and Prevention’s Health and Nutrition Examination Survey. They found a correlation between bleeding diseases, such as bleeding in the gums and in the retina, and low levels of vitamin C in the bloodstream. Furthermore, in individuals with low vitamin C plasma levels, the researchers found that increasing daily intake of vitamin C helped to reverse the bleeding issues. This study is particularly relevant to dentistry in the sense of appropriate recommendation upon presentation of bleeding gums. Whereas the predominant recommendation is better brushing and flossing, this study calls attention to the need to consider additional causes of the bleeding, causes that could point to microvascular and systemic health concerns such as nutrient deficiency. Since the eyes and their retinal vasculature are accessible windows to systemic health, the findings of this study are helpful to eye care in calling attention to additional considerations when there is bleeding in the eye. It is a reminder to address the underlying cause of the condition, and it is a reminder of the importance of good nutrition to maintaining good health.

In Everyday News
1) What to look for when buying sunglasses for eye protection
2) A case of tattoo-associated uveitis (Further reading)
3) Visual system evolution in primates