Three-Dimensional Disadvantage

Article: Three-Dimensional Disadvantage
Source: University of California, Santa Barbara, via ScienceDaily
Published: March 16, 2021

“We’re good at making technology, but sometimes we don’t really connect with it that well,” a senior author of the study comments, “And we don’t know that we don’t connect with it that well.” Researchers in the field of visual search recently conducted a study exploring how human vision processes 2D versus 3D images. The assumption in developing increasingly sophisticated imaging technologies is that detection success should increase with the additional information. However, this is not necessarily the case. The researchers found that we are actually worse at finding small targets in 3D image stacks than in single 2D images. According to the study, observers searching through 3D renderings had higher small target miss rates and significantly decreased decision confidence, though the observers also overestimated how much of the image they explored. Eye-tracking software, for example, showed that subjects conducting the 3D search were looking through only about half of the search area while reporting up to more than 80% image exploration.

This discrepancy lies in part in how we use central and peripheral vision. When searching through 2D images, observers tended to rely on their fovea, which offers the sharpest vision and is used for fixation, while they tended to rely on peripheral vision when searching through the composite images of 3D renderings, and move their eyes less. The combination of eye movement under-exploration, reliance on peripheral vision, and a bit of self-limiting search strategy on the part of radiologist participants in the study resulted in a high number of small target errors in 3D searches. The opposite was found for large targets, where detection improved in the 3D searches; this finding is consistent with use of peripheral vision. In illustrating the gaps between the availability of technology and how our eyes and brains process vision, the study is valuable in informing a better use of technology, for example, to use 2D images for small-target searches and 3D images for large-target searches. Additionally, implementing systems that don't possess these limitations, such as computer vision (e.g., deep learning neural networks), could improve detection success.

My rating of this study: ⭐⭐⭐

Lago MA, Jonnalagadda A, Abbey CK, et al. "Under-exploration of Three-Dimensional Images Leads to Search Errors for Small Salient Targets." Current Biology. 19 January 2021. https://doi.org/10.1016/j.cub.2020.12.029

Retinal Scans for Early Detection of Childhood Autism

Article: HK scientist develops retinal scan technology to identify early childhood autism
Source: Chinese University of Hong Kong, via Reuters
Published: March 15, 2021

A scientist in Hong Kong is developing a method to use retinal scans for early detection of childhood autism. The technology uses a high-resolution retinal camera and artificial intelligence software to analyze retinal fiber layers and blood vessels to detect markers of autism. When tested on 70 children, 46 with autism and 24 without, the technology could identify those children with autism 95.7% of the time. The study size is small and it is not clear as to the severity of autism detected; nonetheless, the results are very encouraging. From a scientific standpoint, autism is added to the expanding list of neurological and systemic conditions that are detectable by eye exam. From a clinical standpoint, such a study is a big step toward bringing awareness to autism detection and intervention. As the researchers report, there is a stigma associated with mental illness, in this case with autism. That stigma might be higher in Asia. What is especially pertinent about this study is that it applies to children, whose parents could be in denial of the fact that their child needs treatment. An objective measure of biomarkers, in conjunction with professional assessment, could help to convince parents to enroll their children in therapy programs more quickly.

My rating of this study: ⭐⭐🌸

Dry Eye Disease Affects Health Beyond Vision

Article: Dry eye disease negatively affects physical and mental health as well as vision
Source: University of Southampton, via ScienceDaily
Published: March 11, 2021

Dry eyes is a common multifactorial condition that affects millions of people, many of whom do not report their symptoms. Researchers in the U.K. conducted an online survey of 1000 people with dry eyes and compared them with 1000 people without the condition to explore how dry eyes affect quality of life. Unsurprisingly, they found that those with dry eye symptoms experienced worse quality of life. These effects extend beyond worse visual function and ocular discomfort to impact daily activities and work productivity for those with the most severe symptoms. The survey also revealed that those with dry eyes were also more likely to suffer anxiety and depression. The lead author of the study comments, “As well as confirming the impact on work and social lives we also discovered showed [sic] that the extent of the effects [is] consistent with the severity of symptoms. We also found that participants with dry eye disease symptoms were a lot more likely to suffer from other comorbidities...Whilst we cannot draw causal associations through this study, the presence of dry eye disease does appear to impact on an individual’s health and vision related quality of life.” Indeed a survey study design cannot untangle confounding factors that might underlie both dry eyes and systemic conditions, or naturally arise with age. However, interestingly, both groups in the study reported similar levels of screen time, though the group with dry eye symptoms also reported more exposure to environmental factors such as air conditioning, forced heating, or air pollution. Mitigating environmental factors could be helpful in addition to dry eye therapies.

My rating of this study: ⭐

Further reading: Go Deep on DED

Week in Review: Number 10

Unprecedented Imaging Resolution of the Retina
Imaging of the retina is limited by diffraction through apertures such as the pupil, which bends the light and essentially becomes a secondary source of waves. Diffraction limits image resolution. Additionally, the optics of refraction by the cornea and lens, such as transverse and longitudinal aberrations, further decrease image resolution. A team of researchers at the National Eye Institute developed a new adaptive optics technique called non-confocal split-detection to overcome some of these challenges for enhanced imaging of the photoreceptor mosaic of the retina. Interestingly, they did so by reducing the amount of light entering the eye, by strategically blocking the light in the center of a beam to form a hollow ring of light. Though this produced better transverse resolution of the retina, it also reduced axial resolution. The researchers compensated for this by blocking the light coming back from the retina using a sub-Airy disk, a tiny pinhole. The imaging tweak yielded 33% increase in transverse resolution and 13% improvement in axial resolution compared to traditional adaptive optics scanning light ophthalmoscopy. Unlike other methods of imaging that overcome the diffraction barrier by using more light, this technique reduces the amount of light to more safely image living human eyes. When applied to the eyes of five healthy volunteers (after theoretical simulations), the imaging technique could visualize "a circularly shaped subcellular structure in the center of cone photoreceptors that could not be clearly visualized previously." The enhanced resolution is particularly useful for imaging the cones tightly packed at the fovea as well as imaging the more numerous, but smaller, rods elsewhere. The researchers hope that this first step toward routine sub-diffraction imaging of subtleties and changes in size, shape, and distribution of photoreceptors will aid in early detection and intervention of retinal diseases.

Large Study Identified 50 New Genes for Eye Color
An international team of researchers conducted a genome-wide association study of the genes involved in eye color. The study comprising almost 195,000 people across Europe and Asia, the largest genetic study of its kind to date, identified 50 new genes for eye color. Additionally, the study found that eye color in Asians with different shades of brown is genetically similar to eye color in Europeans ranging from dark brown to light blue. While exploring the genetics of eye color might appear trivial on the surface, such a study has both societal and clinical relevance. As one of the senior authors states, “The findings are exciting because they bring us to a step closer to understanding the genes that cause one of the most striking features of the human faces, which has mystified generations throughout our history. This will improve our understanding of many diseases that we know are associated with specific pigmentation levels.” Clinically, this study contributes to a better understanding of eye diseases ranging from ocular albinism to uveal melanomas. Equally important to the basic sciences is the confirmation and further discovery that the genetic basis of a person's eye color are polygenic, much more so than previously thought. For simplicity, most of us were taught in grade school to consider eye color as an example of a simple monogenic (or bigenic) trait following Mendelian genetics, with brown being dominant over blue. Explorations into the topic in later years reveals a more complex picture with many other genes involved. Though the simplified conception of eye color will not likely leave the public eye anytime soon, the present study is valuable in providing a more nuanced expansion of that picture.

β-Amyloid Accumulation in RPE Lysosomes
Researchers in the U.K. recently published a study linking age-related macular degeneration (AMD) with the accumulation of β-amyloid proteins in the lysosomes of retinal pigment epithelial (RPE) cells. Beta amyloid is a hallmark of Alzheimer's disease, so this study also makes a connection between Alzheimer's and AMD, guided by prior research findings that donor eyes from patients who had suffered from AMD showed high levels of β-amyloid in their retinas. In their particular mouse model, the researchers were able to introduce β-amyloid to the mouse eyes, which subsequently developed retinal pathology similar to AMD in humans, without the use of transgenic mice. Though the lead researcher states that reducing the use of transgenic animals improves animal welfare, mouse models were still used, with the greatest practical benefit being a reduction in time to produce. More importantly, the researchers also used in vitro cell models to investigate the effect of β-amyloid on RPE cells. They found that β-amyloid accumulated in RPE cell lysosomes, and once invaded by β-amyloid, there were 20% fewer lysosomes available to perform recycling of photoreceptor discs, a necessary daily clean up process for vision at the cellular level. The experiments also found that once β-amyloid entered RPE cells, 85% of these toxic proteins remained in the lysosomes (rather than are cleared away) and accumulate over time. The finding of β-amyloid accumulation in RPE cells, thus linking AMD and Alzheimer's disease, seems to be a new connection that could guide additional anti-amyloid therapy pathways for both diseases.

Soft Contact Lenses for Electroretinograms
“Since the first conceptual invention by Leonardo da Vinci, there has been a great desire to utilize contact lenses for eye-wearable biomedical platforms,” reported a lead investigator of a project at Purdue University to engineer soft contact lenses with biosensors for improved patient comfort in electroretinograms. How this project differs from current corneal sensors is the seamless integration of ultrathin, stretchable biosensors with commercial soft contact lenses via “an electrochemical anchoring mechanism,” thus bypassing obstacles presented by the rigid planar surfaces of most electronics. As with electroretinogram sensors, these contact lenses would measure electrophysiological retinal activity from the corneal surface of human eyes; however, the contacts are an improvement over current sensors in both signal quality and patient comfort, that is, avoiding the need for a topical anesthetic or a speculum. It is tempting to imagine these contact lenses as the kind that could detect biomarkers of ocular diseases in the tear film, but this isn't quite that kind of project. Rather, it is an improved corneal interface for electroretinogram sensors using the more comfortable vehicle of the ubiquitous commercial soft contact lens. That being said, the fact that electronics could be so intimately integrated into the soft, curved surface of soft contact lenses is a big step forward for engineering of other biosensors for monitoring of ocular diseases.

Corneal Reflections Tell the Difference
This study lies at the intersection between computer science and optics. The slang term deepfake  usually refers to visual media that has been edited to replace the person in the original photo or video with another person, often a public figure, in a way that makes it look authentic; the "deep" in deepfake likely refers to deep learning algorithms. Computer scientists are looking into how the optics of the cornea can help to differentiate authentic photos from deepfakes. Because the cornea is foremost a transparent refracting surface, one often forgets that it is also a reflective surface, a convex mirror producing upright, virtual, minified images of the world. Because the two eyes are seeing and reflecting the same thing, the two images should be similar, for example, in shape and color. This is distinguished from the reflections seen in deepfake photos and videos, which are often generated by combining many images and thus produce corneal reflections that are not similar. By comparing the corneal reflections between the two eyes, the investigators' algorithm was reported to be 94% effective at telling the difference between authentic and deepfake portrait-like photos. In order for the tool to work, however, it requires that the photos have a reflected light source, that the original image not have been edited, and that there are two eyes to compare with one another. Additionally, the algorithm only compares differences at the level of pixels rather than broader shapes. Nonetheless, it is an interesting computer science application of corneal optics.

In Other News
(1) Pilocarpine to treat presbyopia submitted for FDA approval (Related)
(2) Visual attention in the immature brain of infants
(3) What your eyes can tell you about your health

Unprecedented Imaging Resolution of the Retina

Article: Researchers Set New Resolution Record for Imaging the Human Eye
Source: The Optical Society, via ScienceDaily
Article: NIH-led team sets new bar in retinal imaging
Source: National Eye Institute
Published: March 11, 2021

Imaging of the retina is limited by diffraction through apertures such as the pupil, which bends the light and essentially becomes a secondary source of waves. Diffraction limits image resolution. Additionally, the optics of refraction by the cornea and lens, such as transverse and longitudinal aberrations, further decrease image resolution. A team of researchers at the National Eye Institute developed a new adaptive optics technique called non-confocal split-detection to overcome some of these challenges for enhanced imaging of the photoreceptor mosaic of the retina. Interestingly, they did so by reducing the amount of light entering the eye, by strategically blocking the light in the center of a beam to form a hollow ring of light. Though this produced better transverse resolution of the retina, it also reduced axial resolution. The researchers compensated for this by blocking the light coming back from the retina using a sub-Airy disk, a tiny pinhole. The imaging tweak yielded 33% increase in transverse resolution and 13% improvement in axial resolution compared to traditional adaptive optics scanning light ophthalmoscopy. Unlike other methods of imaging that overcome the diffraction barrier by using more light, this technique reduces the amount of light to more safely image living human eyes. When applied to the eyes of five healthy volunteers (after theoretical simulations), the imaging technique could visualize "a circularly shaped subcellular structure in the center of cone photoreceptors that could not be clearly visualized previously." The enhanced resolution is particularly useful for imaging the cones tightly packed at the fovea as well as imaging the more numerous, but smaller, rods elsewhere. The researchers hope that this first step toward routine sub-diffraction imaging of subtleties and changes in size, shape, and distribution of photoreceptors will aid in early detection and intervention of retinal diseases.

My rating of this study: ⭐⭐⭐⭐⭐

Further reading: Do you 'need' or just 'want' that new diagnostic imaging device?

Large Study Identified 50 New Genes for Eye Color

Article: 50 new genes for eye colour
Source: King's College London, via ScienceDaily
Published: March 11, 2021

An international team of researchers conducted a genome-wide association study of the genes involved in eye color. The study comprising almost 195,000 people across Europe and Asia, the largest genetic study of its kind to date, identified 50 new genes for eye color. Additionally, the study found that eye color in Asians with different shades of brown is genetically similar to eye color in Europeans ranging from dark brown to light blue. While exploring the genetics of eye color might appear trivial on the surface, such a study has both societal and clinical relevance. As one of the senior authors states, “The findings are exciting because they bring us to a step closer to understanding the genes that cause one of the most striking features of the human faces, which has mystified generations throughout our history. This will improve our understanding of many diseases that we know are associated with specific pigmentation levels.” Clinically, this study contributes to a better understanding of eye diseases ranging from ocular albinism to uveal melanomas. Equally important to the basic sciences is the confirmation and further discovery that the genetic basis of a person's eye color are polygenic, much more so than previously thought. For simplicity, most of us were taught in grade school to consider eye color as an example of a simple monogenic (or bigenic) trait following Mendelian genetics, with brown being dominant over blue. Explorations into the topic in later years reveals a more complex picture with many other genes involved. Though the simplified conception of eye color will not likely leave the public eye anytime soon, the present study is valuable in providing a more nuanced expansion of that picture.

My rating of this study: ⭐⭐⭐⭐

Further reading: Eye color: the myth

Corneal Reflections Tell the Difference

Article: How to spot deepfakes? Look at light reflection in the eyes
Source: University of Buffalo, via Technology Networks
Published: March 10, 2021

This study lies at the intersection between computer science and optics. The slang term deepfake  usually refers to visual media that has been edited to replace the person in the original photo or video with another person, often a public figure, in a way that makes it look authentic; the "deep" in deepfake likely refers to deep learning algorithms. Computer scientists are looking into how the optics of the cornea can help to differentiate authentic photos from deepfakes. Because the cornea is foremost a transparent refracting surface, one often forgets that it is also a reflective surface, a convex mirror producing upright, virtual, minified images of the world. Because the two eyes are seeing and reflecting the same thing, the two images should be similar, for example, in shape and color. This is distinguished from the reflections seen in deepfake photos and videos, which are often generated by combining many images and thus produce corneal reflections that are not similar. By comparing the corneal reflections between the two eyes, the investigators' algorithm was reported to be 94% effective at telling the difference between authentic and deepfake portrait-like photos. In order for the tool to work, however, it requires that the photos have a reflected light source, that the original image not have been edited, and that there are two eyes to compare with one another. Additionally, the algorithm only compares differences at the level of pixels rather than broader shapes. Nonetheless, it is an interesting computer science application of corneal optics.

My rating of this study: ⭐⭐

Soft Contact Lenses for Electroretinograms

Article: Soft contact lenses eyed as new solutions to monitor ocular diseases
Source: Purdue University, via ScienceDaily
Published: March 10, 2021

“Since the first conceptual invention by Leonardo da Vinci, there has been a great desire to utilize contact lenses for eye-wearable biomedical platforms,” reported a lead investigator of a project at Purdue University to engineer soft contact lenses with biosensors for improved patient comfort in electroretinograms. How this project differs from current corneal sensors is the seamless integration of ultrathin, stretchable biosensors with commercial soft contact lenses via “an electrochemical anchoring mechanism,” thus bypassing obstacles presented by the rigid planar surfaces of most electronics. As with electroretinogram sensors, these contact lenses would measure electrophysiological retinal activity from the corneal surface of human eyes; however, the contacts are an improvement over current sensors in both signal quality and patient comfort, that is, avoiding the need for a topical anesthetic or a speculum. From the news article headline, it is tempting to imagine these contact lenses as the kind that could detect biomarkers of ocular diseases in the tear film, but this isn't quite that kind of project. Rather, it is an improved corneal interface for electroretinogram sensors using the more comfortable vehicle of the ubiquitous commercial soft contact lens. That being said, the fact that electronics could be so intimately integrated into the soft, curved surface of soft contact lenses is a big step forward for engineering of other biosensors for monitoring of ocular diseases.

Personal commentary: This is an example of a collaborative research project between engineering and optometry. The bulk of the biomedical engineering contribution came from Purdue University. The clinical application component came from a professor of optometry at Indiana University. This makes sense intuitively when working with contact lenses, but it's also a rare instance of optometric research being reported, albeit only peripherally, in general science news. Finally, additional mechanical engineering involvement came from the University of Virginia.

My rating of this study: ⭐⭐⭐

β-Amyloid Accumulation in RPE Lysosomes

Article: New study links protein causing Alzheimer’s disease with common sight loss
Source: University of Southampton, via ScienceDaily
Published: March 10, 2021

Researchers in the U.K. recently published a study linking age-related macular degeneration (AMD) with the accumulation of β-amyloid proteins in the lysosomes of retinal pigment epithelial (RPE) cells. Beta amyloid is a hallmark of Alzheimer's disease, so this study also makes a connection between Alzheimer's and AMD, guided by prior research findings that donor eyes from patients who had suffered from AMD showed high levels of β-amyloid in their retinas. In their particular mouse model, the researchers were able to introduce β-amyloid to the mouse eyes, which subsequently developed retinal pathology similar to AMD in humans, without the use of transgenic mice. Though the lead researcher states that reducing the use of transgenic animals improves animal welfare, mouse models were still used, with the greatest practical benefit being a reduction in time to produce. More importantly, the researchers also used in vitro cell models to investigate the effect of β-amyloid on RPE cells. They found that β-amyloid accumulated in RPE cell lysosomes, and once invaded by β-amyloid, there were 20% fewer lysosomes available to perform recycling of photoreceptor discs, a necessary daily clean up process for vision at the cellular level. The experiments also found that once β-amyloid entered RPE cells, 85% of these toxic proteins remained in the lysosomes (rather than are cleared away) and accumulate over time. The finding of β-amyloid accumulation in RPE cells, thus linking AMD and Alzheimer's disease, seems to be a new connection that could guide additional anti-amyloid therapy pathways for both diseases.

My rating of this study: ⭐⭐⭐

Week in Review: Number 9

Eye Doctors Save Lives
Researchers at the University of Michigan Health conducted a meta-analysis of 17 studies consisting of 48,000 people collectively to investigate the association between visual disability and risk of all-cause mortality on a global scale. They found that the risk of mortality was 29% higher for participants with mild vision impairment, compared to normal vision, and that the risk increased to 89% among those with severe vision impairment. Most of these cases, such as cataracts and unmet need for glasses, can be prevented or corrected. The study compliments the researchers' earlier work highlighting the impact of vision impairment on health and well-being. One of the investigators states, “It’s important these issues are addressed early on because losing your vision affects more than just how you see the world; it affects your experience of the world and your life. This analysis provides an important opportunity to promote not only health and well-being, but also longevity by correcting, rehabilitating, and preventing avoidable vision loss across the globe.”

Engineering Photovoltaic Retinal Prostheses
While efforts at retinal regeneration and retinal transplant are ongoing, another line of research looks into artificial vision using retinal prostheses. Engineers in Switzerland have created a prototype of one such retinal prosthesis and their preliminary tests in a virtual reality program are encouraging. The research team used two parameters to evaluate their system: image resolution and field of vision. The POLYRETINA implant contains 10,500 electrodes, each of which produces one dot of light. Patients would need to learn to interpret the signals from the array of electrodes, similar to recognizing constellations in the pattern of stars in the night sky. The researchers investigated number of electrodes and spacing to provide enough image resolution while keeping the electrodes spaced far enough apart to distinguish one dot from another. Their virtual reality program determined that 10,500 was a good amount of electrodes, and that each electrode stimulated a different part of the retina. In their system, adding more electrodes would not improve image resolution. The second parameter they investigated was field of vision. Tests of field-of-vision angles between 5 degrees and 45 degrees found that 35 degrees is the saturation point for stable object perception. This retinal prosthesis is still a long ways from clinical trials, but the project provides a look into the parameters that engineers consider in designing a system for artificial vision.

Neurological Agreement in Color Perception
This article from general science news is extra special in that the authors of the news article are also the authors of the research. The research was aimed at answering the question of color perception, both the purpose of color perception and the physiological agreement of color perception, from a neuroscience perspective. Two studies were discussed. In one study, by a different research team, participants were shown real-world stimuli illuminated by low-pressure-sodium lights (similar to the kind found in parking garages). The yellow light (perhaps any colored light) prevents the retina from properly encoding color. The participants could still recognize objects, such as fruits, but those fruits appeared unappetizing. The participants could still recognized faces, though those faces looked green and sick. The researchers think that when normal color perception expectations are violated, this sends an error signal to the brain to interpret the situation as amiss, that there is something wrong. In other words, such studies confirm that color perception encodes meaning.

But what about individual variations in perception of color? There is of course the physical basis of color in the wavelengths of visible light. But is one person's perception of red the same as another person's? In the second study, conducted by the authors, magnetoencephalography  (MEG) was used to measure participants' brain wave activity in response to different color relationships. Note that the study design does not answer the much tougher question of whether responses to specific colors are similar across people. Rather, it is a measure of responses to color relationships, such as a person's perception of the relationship between red and orange. The MEG results showed that a person's neurological response to more closely similar colors, such as light green and dark green, is more similar than the response to less closely similar colors, such as yellow and brown. Furthermore, these relationships are preserved across people. As the authors conclude, “Physiological measurements are unlikely to ever resolve metaphysical questions such as 'what is redness?' But the MEG results nonetheless provide some reassurance that color is a fact we can agree on.”

Gold-Infused Contact Lenses for Color Vision Correction
Researchers at the American Chemical Society have created a prototype of a contact lens using gold nanoparticles to correct red-green color vision deficiencies. Previously, colorblindness-correcting contact lenses using dyes as filters (to shift the color confusion curve and thereby enhance contrast between colors) had the problem of leaching the dyes. The advantage of using gold to produce the color filter is that gold is inert. For a quotidian example, one can recall the culinary use of gold leaf in more elegant dishes to add artistic flare, though the gold is not metabolized by the body in any way. The use of gold nanoparticles to produce a color-filtering rosy tint is also not surprising given the artistic use of gold particles to impart a red color to stained or blown glass. The rosy tint of the gold-infused contact lenses were matched with the wavelength profile of existing dyed contact lenses for correction of red-green color vision deficiency. The researchers found that 40 nm-wide gold nanoparticles were the most effective, as the particles did not clump or filter more color than necessary. Because gold is inert to the body, there is a lot of potential with this line of research, so it will be interesting to see its performance in real eyes.

Retinal Ischemic Lesions and Risk of Heart Disease
Researchers from the Shiley Eye Institute at UC San Diego recently published a small study to investigate the correlation between retinal ischemic perivascular lesions (RIPLs) and risk of cardiovascular disease. The microvasculature of the retina is a window to the health of larger vessels and organs in the body, so the research team sought to determine if it could serve as a biomarker of cardiovascular disease. They compared a cohort of 84 individuals with heart disease with 76 healthy individuals through chart review of ocular coherence tomography (OCT) findings between July 2014 and July 2019. An increased number of RIPLs was observed in the eyes of individuals with heart disease, which the researchers correlate with increased risk of heart disease. The study references the atherosclerotic cardiovascular disease (ASCVD) risk score calculator, the national guideline developed by the American College of Cardiology, as the guideline for assessing risk of cardiovascular events such as heart attack and stroke. The researchers found a positive correlation between the number of RIPLs in a patient’s eye and their ASCVD risk score. This study offers an interesting approach to the connection between retinal microvasculature and cardiovascular health. The population size is small and the study design and inferences are indirect. Nonetheless, it is a reminder of the eye's unique window to help reduce risk of disease in the rest of the body.

In Other News
(1) NEI launches data portal for macular degeneration research
(2) Vision impairment expected to rise in future decades
(3) The history of eye charts

Engineering Photovoltaic Retinal Prostheses

Article: Retinal Prostheses Poised to Provide Artificial Vision to the Blind
Source: Genetic Engineering & Biotechnology News
Article: Retinal Implants Give Artificial Vision to Blind People
Source: École Polytechnique Fédérale de Lausanne (Switzerland), via Technology Networks
Published: March 8, 2021 / March 15, 2021

While efforts at retinal regeneration and retinal transplant are ongoing, another line of research looks into artificial vision using retinal prostheses. Engineers in Switzerland have created a prototype of one such retinal prosthesis and their preliminary tests in a virtual reality program are encouraging. The research team used two parameters to evaluate their system: image resolution and field of vision. The POLYRETINA implant contains 10,500 electrodes, each of which produces one dot of light. Patients would need to learn to interpret the signals from the array of electrodes, similar to recognizing constellations in the pattern of stars in the night sky. The researchers investigated number of electrodes and spacing to provide enough image resolution while keeping the electrodes spaced far enough apart to distinguish one dot from another. Their virtual reality program determined that 10,500 was a good amount of electrodes, and that each electrode stimulated a different part of the retina. In their system, adding more electrodes would not improve image resolution. The second parameter they investigated was field of vision. Tests of field-of-vision angles between 5 degrees and 45 degrees found that 35 degrees is the saturation point for stable object perception. This retinal prosthesis is still a long ways from clinical trials, but the project provides a look into the parameters that engineers consider in designing a system for artificial vision.

My rating of this study: ⭐⭐⭐

Further reading: Retinal Prosthesis Aids Multisensory Perception

Eye Doctors Save Lives

Article: Vision Impairment is Associated with Mortality
Source: University of Michigan Health, via ScienceDaily
Published: March 5, 2021

Researchers at the University of Michigan Health conducted a meta-analysis of 17 studies consisting of 48,000 people collectively to investigate the association between visual disability and risk of all-cause mortality on a global scale. They found that the risk of mortality was 29% higher for participants with mild vision impairment, compared to normal vision, and that the risk increased to 89% among those with severe vision impairment. Most of these cases, such as cataracts and unmet need for glasses, can be prevented or corrected. The study compliments the researchers' earlier work highlighting the impact of vision impairment on health and well-being. One of the investigators states, “It’s important these issues are addressed early on because losing your vision affects more than just how you see the world; it affects your experience of the world and your life. This analysis provides an important opportunity to promote not only health and well-being, but also longevity by correcting, rehabilitating, and preventing avoidable vision loss across the globe.”

Personal commentary: Living in a privileged country such as the U.S. causes us to sometimes forget the unmet need of millions of people across the globe who live with visual impairment and even blindness. As the study points out, four out of five cases of visual disability are due to cataracts and unmet need for glasses, both of which are preventable or correctable. I remember the first time reading a similar article to this and making the connection that eye doctors save lives. We often don't realize it because, again, we live in a country such as the U.S. But looking through an often blurrier and smudgier global lens reminds us of the difference in experience that people in different countries or situations face. There is no shortage of need anywhere, but it explains why historically, I have preferred to engage in (what used to be at one point, monthly) mission trips to Mexico. This is why if asked where I want to focus my attention, it would be cataracts. Note that the two leading causes of global visual need are refractive and, comparatively, simple. We should celebrate the life-saving work of all eye doctors, both the ones who help us forget that we would have vision and health problems otherwise and the ones working to bring clear vision to those in need globally.

My rating of this study: ⭐⭐⭐🌸

Further reading: Understanding the molecular mechanisms underlying cataract development

Neurological Agreement in Color Perception

Article: Do you see red like I see red?
Source: The Conversation, via Knowable Magazine
Published: February 5, 2021

This article from general science news is extra special in that the authors of the news article are also the authors of the research. The research was aimed at answering the question of color perception, both the purpose of color perception and the physiological agreement of color perception, from a neuroscience perspective. Two studies were discussed. In one study, by a different research team, participants were shown real-world stimuli illuminated by low-pressure-sodium lights (similar to the kind found in parking garages). The yellow light (perhaps any colored light) prevents the retina from properly encoding color. The participants could still recognize objects, such as fruits, but those fruits appeared unappetizing. The participants could still recognized faces, though those faces looked green and sick. The researchers think that when normal color perception expectations are violated, this sends an error signal to the brain to interpret the situation as amiss, that there is something wrong. In other words, such studies confirm that color perception encodes meaning.

But what about individual variations in perception of color? There is of course the physical basis of color in the wavelengths of visible light. But is one person's perception of red the same as another person's? In the second study, conducted by the authors, magnetoencephalography  (MEG) was used to measure participants' brain wave activity in response to different color relationships. Note that the study design does not answer the much tougher question of whether responses to specific colors are similar across people. Rather, it is a measure of responses to color relationships, such as a person's perception of the relationship between red and orange. The MEG results showed that a person's neurological response to more closely similar colors, such as light green and dark green, is more similar than the response to less closely similar colors, such as yellow and brown. Furthermore, these relationships are preserved across people. As the authors conclude, “Physiological measurements are unlikely to ever resolve metaphysical questions such as 'what is redness?' But the MEG results nonetheless provide some reassurance that color is a fact we can agree on.”

My rating of this article: ⭐⭐🌸

See also: Tetrachromacy: the women with superhuman vision (Related)

Gold-Infused Contacts for Color Vision Correction

Article: Color blindness-correcting contact lenses
Source: American Chemical Society, via ScienceDaily  and Technology Networks
Published: March 3, 2021

Researchers at the American Chemical Society have created a prototype of a contact lens using gold nanoparticles to correct red-green color vision deficiencies. Previously, colorblindness-correcting contact lenses using dyes as filters (to shift the color confusion curve and thereby enhance contrast between colors) had the problem of leaching the dyes. The advantage of using gold to produce the color filter is that gold is inert. For a quotidian example, one can recall the culinary use of gold leaf in more elegant dishes to add artistic flare, though the gold is not metabolized by the body in any way. The use of gold nanoparticles to produce a color-filtering rosy tint is also not surprising given the artistic use of gold particles to impart a red color to stained or blown glass. The rosy tint of the gold-infused contact lenses were matched with the wavelength profile of existing dyed contact lenses for correction of red-green color vision deficiency. The researchers found that 40 nm-wide gold nanoparticles were the most effective, as the particles did not clump or filter more color than necessary. Because gold is inert to the body, there is a lot of potential with this line of research, so it will be interesting to see its performance in real eyes.

Personal commentary: The beginning of the source news article asks the reader to imagine seeing the world in tones of gray. While it is tempting to associate grayed out vision with "colorblindness," complete absence of color vision (monochromacy) is extremely rare. Most people who are labeled "colorblind" have anomalous color vision perception due to different wavelength sensitivity of a genetic mutation to one of their cones. This means they see a shift in color vision, not a complete absence of it. Only if there is existing color vision perception could lenses that selectively filter wavelengths of light be effective at enhancing color contrasts. The rest of the article addresses red-green color vision deficiency, the most common type being anomalous deuterochromacy, caused by an x-linked genetic mutation to the "green" cones responsible for detecting "medium" wavelengths of light. Because these mutations, though categorized by the cones they affect, are individual to the person, one could also think of color vision deficiencies and color vision perception as a personal experience, resulting in differences in improvement for different people with (even the same type of) color vision deficiency. The ideal lens would thus be customized to the individual's color vision.

My rating of this study: ⭐⭐

Further reading: Blue-Light Filtering Lenses Do Not Reduce Computer Eye Strain
Further reading: Agreement. But modulating blue light can help with circadian rhythm.

Retinal Ischemic Lesions and Risk of Heart Disease

Article: Heart Disease is in the Eye of the Beholder
Source: University of California, San Diego, via ScienceDaily
Published: March 2, 2021

Researchers from the Shiley Eye Institute at UC San Diego recently published a small study to investigate the correlation between retinal ischemic perivascular lesions (RIPLs) and risk of cardiovascular disease. The microvasculature of the retina is a window to the health of larger vessels and organs in the body, so the research team sought to determine if it could serve as a biomarker of cardiovascular disease. They compared a cohort of 84 individuals with heart disease with 76 healthy individuals through chart review of ocular coherence tomography (OCT) findings between July 2014 and July 2019. An increased number of RIPLs was observed in the eyes of individuals with heart disease, which the researchers correlate with increased risk of heart disease. The study references the atherosclerotic cardiovascular disease (ASCVD) risk score calculator, the national guideline developed by the American College of Cardiology, as the guideline for assessing risk of cardiovascular events such as heart attack and stroke. The researchers found a positive correlation between the number of RIPLs in a patient’s eye and their ASCVD risk score. This study offers an interesting approach to the connection between retinal microvasculature and cardiovascular health. The population size is small and the study design and inferences are indirect. Nonetheless, it is a reminder of the eye's unique window to help reduce risk of disease in the rest of the body.

My rating of this study: ⭐

Further reading: Wild and Woolly: Take a closer look at how cotton wool spots manifest

Week in Review: Number 8

Axonal Regeneration after Silencing a Cytokine Gene
Researchers at Yale University recently identified 40 genes involved in preventing axonal regeneration in the central nervous system in a mouse model. By suppressing those genes, especially the gene for the cytokine interleukin-22 (IL-22), they were able to regenerate retinal ganglion cell axons in a mouse model of glaucoma (by optic nerve crush). The study itself seeks to investigate the larger topic of CNS nerve regeneration, and in this case uses the convenient model of the optic nerve. The authors state, “Reduced IL-22 drives concurrent activation of signal transducer and activator of transcription 3 and dual leucine zipper kinase pathways and upregulation of multiple neuron-intrinsic regeneration-associated genes.” In other words, suppressing this cytokine gene led to favorable expression of regenerative genes. This kind of discovery was facilitated by the advent of DNA cutting technologies, such as the viral-driven short hairpin RNAs used in these experiments; another DNA cutting technology most of us have heard of by now would be CRISPR-Cas9. These gene editing tools allow researchers to observe the function of a gene by silencing it, by rendering the gene nonfunctional through cutting its DNA sequence. The researchers also noted that identifying multiple genes suggests multiple molecular pathways, which could be useful for both multiplexed gene editing (a more efficient method of gene editing) and interventional therapeutics.

Genome-Wide Association Study of Keratoconus
An international team of researchers from the UK, the US, the Czech Republic, the Netherlands, Australia, Austria and Singapore recently conducted a genome-wide association study of keratoconus. The observation that keratoconus is more common in people with an affected relative led scientists to consider a genetic link. The present study compared the full genome of 4,669 people with keratoconus to that of 116,547 people without keratoconus, a larger sample size than in previous studies for the condition in question. The team found an association between keratoconus and defects in corneal collagen matrix integrity. They also found possible abnormalities in the cell differentiation pathways of corneal cells in keratoconus. Though the sample population severely lacks ethnic diversity, a not uncommon situation, the data still contributes to collective knowledge overall. The researchers hope that the genetic information can help pinpoint a biological mechanism for the disease, in turn guiding early detection and intervention. Currently, the only treatment for keratoconus (short of corneal transplant) is corneal crosslinking. Genetics, and other methods for early detection, could help initiate therapy before the disease progresses to affect vision.

Macrophages of the Human Eye Come into Focus
Macrophages are immune cells present in all ocular tissues. On the surface of the retina they look and act like microglia, the "sentinels of the central nervous system." The present study using ocular coherence tomography (OCT) and adaptive optics (for enhanced image resolution) is the first to visualize these cells in real time in the eyes of living humans. The imaging technique allowed the researchers to pinpoint the location of retinal macrophages. For example, they discovered that in healthy eyes, the macrophages were densely distributed in the periphery of people's retinas and sparsely found near/at the fovea. The researchers hypothesized that the relative absence of macrophages at the fovea is related to retinal development, wherein photoreceptors migrate to what becomes the fovea, and the inner layers of the retina (such as the ganglion cell layer and nerve fiber layer) move aside for clearer light transmission. The role of macrophages is to clean up cellular debris from the inner retinal layers, which are absent at the fovea, and thus might explain macrophages' absence there. The researchers also found that in glaucoma, macrophages gather in areas of active disease. If these changes can be visualized and monitored over time, they could be an avenue of research as a biomarker of disease activity and severity.

AI Models for the Study of Motion Perception
Researchers at the University of Cambridge have developed an artificial neural network to study motion perception. Called MotionNet, this computer network simulates a particular type of visual processing known as the reverse phi phenomenon. In the phi phenomenon, which most of us are familiar with in the form of animated films, dark spots appearing in succession give the illusion of motion. In the more perplexing reverse phi phenomenon, if the second point becomes light rather than dark, then we perceive the motion as moving in the opposite direction; instead of perceiving the sequence moving "forward," we perceive it as moving "backward" (keeping in mind that directions are relative). The MotionNet system seems to faithfully replicate the mistakes that human brains make with regard to the reverse phi illusion, but has the advantage of being able to be examined and tested in detail. The researchers found, for example, that the reverse phi illusion triggered "neurons" in their system that were tuned to the direction opposite of the actual movement. The system also revealed information about the speed of movement and spacing of dots on the effect of motion perception. Studying optical illusions has consequential implications for patient care beyond scholarly interest. For example, in previous work, the researchers showed that neurons in our brain are biased towards slow speeds, so when visibility is low we tend to think that objects are moving more slowly than they actually are. These findings are thus applicable to real-world scenarios, such as accurately gauging the speed of moving objects when driving in low visibility conditions. The MotionNet artificial neural network is a model wherein preliminary experiments could provide insights for more focused studies in subsequent biological models and human subjects.

Windows of the Brain: Retinal Screening for Early Detection of Neurodegenerative Diseases
This article is an example of coverage about eye care that appears in everyday news, in this case in the Washington Post, to inform the public and patients about the importance of being vigilant about their health in general and their eye health in particular. This article addresses the value of early detection in neurodegenerative diseases, such as Alzheimer's and Parkinson's, to improve treatment outcomes or interpersonal arrangements. Progress in retinal screening has great potential to provide a noninvasive and relatively inexpensive window to neurological health. The article highlights three projects toward this goal. The first by neuroscientist Maya Koronyo-Hamaoui at Cedar-Sinai visualizes beta amyloid plaques, a hallmark of Alzheimer's disease, through ingested curcumin (a compound in turmeric), which has high affinity for beta amyloid and shows up on retinal exam (with the right fluorescence-detecting equipment). The second project by biomedical engineer Ruogu Fang at the University of Florida uses smartphone fundus photography and artificial intelligence algorithms to screen photos of the microvasculature of the retina, on the premise that there is strong correlation between hypoxia and neuronal death characteristic of both Alzheimer's and Parkinson's. In a third project that also uses a neural network and ocular coherence tomography (OCT), vitreoretinal surgeon Sharon Fekrat at Duke University found that thinning of the retina's ganglion cell layer is highly predictive of Alzheimer's diagnosis. These techniques are not flawless, since the association between biomarkers and disease is complex. Nonetheless, with increasing sensitivity, they undoubtedly become more valuable tools in the diagnostics armamentarium.

In Other News
(1) Eyeless C. elegans perceives colors (Related)
(2) Probing the mysteries of ophthalmic migraines
(3) Photokeratitis risk in UV light disinfection

Axonal Regeneration after Silencing a Cytokine Gene

Article: Neurons Regenerated through Suppression of Regeneration-Thwarting Genes
Source: Genetic Engineering & Biotechnology News  and Yale University, via NEI
Published: March 2, 2021

Researchers at Yale University recently identified 40 genes involved in preventing axonal regeneration in the central nervous system in a mouse model. By suppressing those genes, especially the gene for the cytokine interleukin-22 (IL-22), they were able to regenerate retinal ganglion cell axons in a mouse model of glaucoma (by optic nerve crush). The study itself seeks to investigate the larger topic of CNS nerve regeneration, and in this case uses the convenient model of the optic nerve. The authors state, “Reduced IL-22 drives concurrent activation of signal transducer and activator of transcription 3 and dual leucine zipper kinase pathways and upregulation of multiple neuron-intrinsic regeneration-associated genes.” In other words, suppressing this cytokine gene led to favorable expression of regenerative genes. This kind of discovery was facilitated by the advent of DNA cutting technologies, such as the viral-driven short hairpin RNAs used in these experiments; another DNA cutting technology most of us have heard of by now would be CRISPR-Cas9. These gene editing tools allow researchers to observe the function of a gene by silencing it, by rendering the gene nonfunctional through cutting its DNA sequence. The researchers also noted that identifying multiple genes suggests multiple molecular pathways, which could be useful for both multiplexed gene editing (a more efficient method of gene editing) and interventional therapeutics.

My rating of this study: ⭐⭐⭐

Genome-Wide Association Study of Keratoconus

Article: Genetic study uncovers hidden pieces of eye disease puzzle 
Source: University of Leeds, via ScienceDaily
Published: March 1, 2021

An international team of researchers from the UK, the US, the Czech Republic, the Netherlands, Australia, Austria and Singapore recently conducted a genome-wide association study of keratoconus. The observation that keratoconus is more common in people with an affected relative led scientists to consider a genetic link. The present study compared the full genome of 4,669 people with keratoconus to that of 116,547 people without keratoconus, a larger sample size than in previous studies for the condition in question. The team found an association between keratoconus and defects in corneal collagen matrix integrity. They also found possible abnormalities in the cell differentiation pathways of corneal cells in keratoconus. Though the sample population severely lacks ethnic diversity, a not uncommon situation, the data still contributes to collective knowledge overall. The researchers hope that the genetic information can help pinpoint a biological mechanism for the disease, in turn guiding early detection and intervention. Currently, the only treatment for keratoconus (short of corneal transplant) is corneal crosslinking. Genetics, and other methods for early detection, could help initiate therapy before the disease progresses to affect vision.

My rating of this study: ⭐⭐⭐

Macrophages of the Human Eye Come into Focus

Article: Macrophages of the Human Eye Come into Focus
Source: The Scientist
Published: March 1, 2021

Macrophages are immune cells present in all ocular tissues. On the surface of the retina they look and act like microglia, the "sentinels of the central nervous system." The present study using ocular coherence tomography (OCT) and adaptive optics (for enhanced image resolution) is the first to visualize these cells in real time in the eyes of living humans. The imaging technique allowed the researchers to pinpoint the location of retinal macrophages. For example, they discovered that in healthy eyes, the macrophages were densely distributed in the periphery of people's retinas and sparsely found near/at the fovea. The researchers hypothesized that the relative absence of macrophages at the fovea is related to retinal development, wherein photoreceptors migrate to what becomes the fovea, and the inner layers of the retina (such as the ganglion cell layer and nerve fiber layer) move aside for clearer light transmission. The role of macrophages is to clean up cellular debris from the inner retinal layers, which are absent at the fovea, and thus might explain macrophages' absence there. The researchers also found that in glaucoma, macrophages gather in areas of active disease. If these changes can be visualized and monitored over time, they could be an avenue of research as a biomarker of disease activity and severity.

My rating of this study: ⭐⭐⭐

Windows of the Brain: Retinal Screening for Early Detection of Neurodegenerative Diseases

Article: Our eyes may provide early warning signs of Alzheimer’s and Parkinson’s
Source: Washington Post, via The Scientist
Published: February 27, 2021

This article is an example of coverage about eye care that appears in everyday news, in this case in the Washington Post, to inform the public and patients about the importance of being vigilant about their health in general and their eye health in particular. This article addresses the value of early detection in neurodegenerative diseases, such as Alzheimer's and Parkinson's, to improve treatment outcomes or interpersonal arrangements. Progress in retinal screening has great potential to provide a noninvasive and relatively inexpensive window to neurological health. The article highlights three projects toward this goal. The first by neuroscientist Maya Koronyo-Hamaoui at Cedar-Sinai visualizes beta amyloid plaques, a hallmark of Alzheimer's disease, through ingested curcumin (a compound in turmeric), which has high affinity for beta amyloid and shows up on retinal exam (with the right fluorescence-detecting equipment). The second project by biomedical engineer Ruogu Fang at the University of Florida uses smartphone fundus photography and artificial intelligence algorithms to screen photos of the microvasculature of the retina, on the premise that there is strong correlation between hypoxia and neuronal death characteristic of both Alzheimer's and Parkinson's. In a third project that also uses a neural network and ocular coherence tomography (OCT), vitreoretinal surgeon Sharon Fekrat at Duke University found that thinning of the retina's ganglion cell layer is highly predictive of Alzheimer's diagnosis. These techniques are not flawless, since the association between biomarkers and disease is complex. Nonetheless, with increasing sensitivity, they undoubtedly become more valuable tools in the diagnostics armamentarium.

My rating of this study: ⭐⭐

AI Models for the Study of Motion Perception

Article: Artificial ‘brain’ reveals why we can’t always believe our eyes
Source: University of Cambridge, via Technology Networks
Published: February 25, 2021

Researchers at the University of Cambridge have developed an artificial neural network to study motion perception. Called MotionNet, this computer network simulates a particular type of visual processing known as the reverse phi phenomenon. In the phi phenomenon, which most of us are familiar with in the form of animated films, dark spots appearing in succession give the illusion of motion. In the more perplexing reverse phi phenomenon, if the second point becomes light rather than dark, then we perceive the motion as moving in the opposite direction; instead of perceiving the sequence moving "forward," we perceive it as moving "backward" (keeping in mind that directions are relative). The MotionNet system seems to faithfully replicate the mistakes that human brains make with regard to the reverse phi illusion, but has the advantage of being able to be examined and tested in detail. The researchers found, for example, that the reverse phi illusion triggered "neurons" in their system that were tuned to the direction opposite of the actual movement. The system also revealed information about the speed of movement and spacing of dots on the effect of motion perception. Studying optical illusions has consequential implications for patient care beyond scholarly interest. For example, in previous work, the researchers showed that neurons in our brain are biased towards slow speeds, so when visibility is low we tend to think that objects are moving more slowly than they actually are. These findings are thus applicable to real-world scenarios, such as accurately gauging the speed of moving objects when driving in low visibility conditions. The MotionNet artificial neural network is a model wherein preliminary experiments could provide insights for more focused studies in subsequent biological models and human subjects.

My rating of this study: ⭐⭐

See also: Reverse phi motion in fruit flies

Week in Review: Number 7

International Team Identifies 127 Glaucoma Genes in Large Genome-Wide Association Study
An international team of researchers recently identified 44 new gene loci and confirmed 83 previously known gene loci reported to be linked with glaucoma in a large genome-wide association study comparing the genes of 34,179 people with the disease to 349,321 control subjects. It is the largest study of its kind to date and the first cross-ancestry glaucoma genome-wide association study to include data of people from Europe, Africa, and Asia (in addition to data from people of European, African, and Asian ancestry). While glaucoma is an eye disease that predominantly affects people with African and Asian ancestry, previous studies have looked mostly at the genes of people of European ancestry. By gathering data from such a large and diverse pool of subjects, this cross-ancestry study improves upon the fine-mapping of causal variants linked with glaucoma as well as provides new avenues of research, via the newly identified genes, that could implicate previously unknown biological processes leading to the disease. In other words, the exceptionally large size and diversity provided by this study improves the precision of genetic associations of the disease.

RUNX1 Inhibition as Treatment for CNV
In this study, researchers affiliated with Harvard Medical School explored the use of a Runt-related transcription factor 1 (RUNX1) inhibitor, with and without the anti–vascular endothelial growth factor (VEGF) aflibercept (Eylea), for the treatment of choroidal neovascularization (CNV) in exudative age-related macular degeneration (wet AMD). RUNX1 has previously been linked with CNV pathogenesis, that is, it seems to be involved in not only angiogenesis but also in the inflammation and fibrosis leading to CNV. Inhibition of RUNX1 thus provides a novel and intriguing approach to address the problem of incomplete response in anti-VEGF therapy. The researchers used a mouse model of CNV to test intravitreal injection of saline, aflibercept, the RUNX1 inhibitor Ro5-3335, and a combination of Ro5-3335 and aflibercept. They found that a single intravitreal injection of Ro5-3335 alone significantly decreased the CNV lesion size seven days after induction of the CNV lesions, and that the combination of Ro5-3335 and aflibercept was more effective at reducing vascular leakage than aflibercept alone. One of the researchers states, “RUNX1 inhibitors hold significant promise to complement or replace anti-VEGF therapies for patients in which anti-VEGF therapy is no longer effective, and with the potential to be administered topically it could be transformative in the field.” Because many eye diseases involve neovascularization, RUNX1 inhibition has great potential to be applicable to diseases ranging from wet AMD and diabetic retinopathy to retinopathy of prematurity and retinal vein occlusion.

An Oxidized Ketocholesterol and Wet AMD
Researchers at the Moran Eye Center at the University of Utah Health are using a mouse model to investigate how an oxidized form of cholesterol, called oxysterol 7-ketocholesterol (7KC), contributes to the fibrosis of choroidal endothelial cells (CECs) that eventually lead to a neovascular age-related macular degeneration (wet AMD) that is poorly responsive to anti-VEGF therapy. The ketocholesterol accumulates in Bruch's membrane, cause changes in the CECs, which then invade the neural retina and lead to enlarged lesions and fibrosis. These lesions and fibrosis account for 40% of poor vision in neovascular AMD. What is particularly interesting about this study is that it suggests a link between 7KC, choroidal fibrosis in neovascular AMD, and poor response to anti-VEGF treatment. Up to 50% of patients who undergo anti-VEGF therapy stop responding to the therapy long-term. In addition to research into novel therapeutics, studies such as this point to a potential explanation for the failure of therapy and provide an avenue of research to interfere with the process and potentially improve treatment outcomes.

Investigations in Intravitreal AAV Gene Therapies
This is an interesting study as a follow up to the article about AAV gene therapies by researchers at the Wyss Institute at Harvard University, as this study also addresses the topic of AAV gene therapy, in this case with a focus on intravitreal injection. As with the Wyss Institute study, the researchers note the limitations of subretinal injection, which prompted further investigation of vector delivery intravitreally. The news article itself is short, and the only section that discusses methods states, "Further studies on three animal models [mice, dogs and non‐human primates] confirmed the efficacy of the procedure, and experiments on human retinal tissue grown in culture confirmed that the vectors can infect photoreceptors and other retinal cells. Finally, initial results of experiments on a mouse model of achromatopsia (complete lack of color vision) suggested that the procedure is capable of restoring some degree of daylight vision." With regard to intraocular inflammation, two of the five dogs used in the study developed inflammation events, which the researchers hypothesized was in response to the enhanced green fluorescent protein (eGFP) rather than the vector capsid, without detailed explanation. In either case, though a good addition to the archive of knowledge about intravitreal gene therapies, the study still shows that this method has not surmounted the obstacle of inflammation if vectors are delivered intravitreally. The approach would probably have been more novel had it been published prior to the study by the Wyss Institute.

Eye Care Beyond Blindness
This study brings up a valid point for consideration. Because sight is such a valued sense modality, its absolute loss is an understandable emphasis and justification for advancing research and treatments for eye diseases. Both news articles and journal articles focus on keywords associated with blindness. A research group in the U.K. wants to call attention to the much greater proportion of people who are afflicted by eye disease that comes short of robbing them of vision, but nonetheless presents difficulties both for the individual and for the health care system overall. For example, the paper notes that while 8 million people around the world have moderate to severe visual impairment or blindness from glaucoma, around 76 million people around the world have the condition. Similarly, diabetic retinopathy has caused 4.4 million to be blind or have moderate to severe vision impairment, but around 160 million people have the condition. In short, stages of eye disease that involve moderate or severe visual impairment and blindness represent merely the tip of the iceberg of the plethora of eye conditions that need attention. Said researcher is leading a call for a UK-wide sensory health survey to provide robust data to inform health services. Reports like these provide a glimpse into differences in health care systems in different countries and the mentalities and emphases resulting from those different systems. On the one hand, one might ask, "Are not conjunctivitis, sore eyes or dry eyes the topics of ubiquitous discussions already?" On the other hand, to see a call for a survey to inform health services is an interesting public health perspective.

Investigating Sound Waves for IOP Measurement
Glaucoma is indeed a very complex constellation of disease states, and accurate measurement of intraocular pressure (IOP) is equally complex. Many would argue that even methods of IOP measurement in clinical settings, including the gold standard of Goldmann applanation tonometry, have limitations. Alternatives to provide around-the-clock IOP monitoring, such as through contact lenses, have been proposed but so far lack translatability to patient care. The present study is another such project, in a very early stage of engineering, that seeks to approach the problem from the perspective of soundwaves. One of the researchers states, “We discovered a relationship between the internal pressure of an object and its acoustic reflection coefficient. With further investigation into eye geometry and how this affects the interaction with soundwaves, it is possible to use a smartphone to accurately measure IOP from the comfort of the user’s home.” IOP measurement is one of those problems that is easier to talk about than it is to solve, but projects like these, with further development, could contribute to methods to monitor eye pressures around the clock.

In Other News
(1) Attention modulated by projections between frontal and visual cortices
(2) Heterochromia and iris color changes (Related)
(3) Eye drops to correct presbyopia

An Oxidized Ketocholesterol and Wet AMD

Article: Research Points to New Hope for Treatment-Resistant AMD
Source: University of Utah Health, via NEI
Published: February 26, 2021

Researchers at the Moran Eye Center at the University of Utah Health are using a mouse model to investigate how an oxidized form of cholesterol, called oxysterol 7-ketocholesterol (7KC), contributes to the fibrosis of choroidal endothelial cells (CECs) that eventually lead to a neovascular age-related macular degeneration (wet AMD) that is poorly responsive to anti-VEGF therapy. The ketocholesterol accumulates in Bruch's membrane, cause changes in the CECs, which then invade the neural retina and lead to enlarged lesions and fibrosis. These lesions and fibrosis account for 40% of poor vision in neovascular AMD. What is particularly interesting about this study is that it suggests a link between 7KC, choroidal fibrosis in neovascular AMD, and poor response to anti-VEGF treatment. Up to 50% of patients who undergo anti-VEGF therapy stop responding to the therapy long-term. In addition to research into novel therapeutics, studies such as this point to a potential explanation for the failure of therapy and provide an avenue of research to interfere with the process and potentially improve treatment outcomes.

My rating of this study: ⭐⭐⭐

See also: New therapeutic approach may help treat age-related macular degeneration effectively

Investigating Sound Waves for IOP Measurement

Article: Smartphones could help to prevent glaucoma blindness
Source: University of Birmingham, via ScienceDaily
Published: February 25, 2021

Glaucoma is indeed a very complex constellation of disease states, and accurate measurement of intraocular pressure (IOP) is equally complex. Many would argue that even methods of IOP measurement in clinical settings, including the gold standard of Goldmann applanation tonometry, have limitations. Alternatives to provide around-the-clock IOP monitoring, such as through contact lenses, have been proposed but so far lack translatability to patient care. The present study is another such project, in a very early stage of engineering, that seeks to approach the problem from the perspective of sound waves. One of the researchers states, “We discovered a relationship between the internal pressure of an object and its acoustic reflection coefficient. With further investigation into eye geometry and how this affects the interaction with sound waves, it is possible to use a smartphone to accurately measure IOP from the comfort of the user’s home.” IOP measurement is one of those problems that is easier to talk about than it is to solve, but projects like these, with further development, could contribute to methods to monitor eye pressures around the clock.

Personal commentary: This article, also from the U.K., seems to be a perfect example of what the previous article in the blog was referring to. The study itself is in a very early theoretical stage with a mechanical eye model, and yet the news article uses keywords such as "prevent glaucoma blindness."

My rating of this study: ⭐

Further reading: Pressure May Be Reduced for 1 Hour or More After Biomechanically-Corrected Tonometry

Eye Care Beyond Blindness

Article: Rapidly rising levels of sight loss are ‘tip of the iceberg’
Source: Anglia Ruskin University, via ScienceDaily
Published: February 24, 2021

This study brings up a valid point for consideration. Because sight is such a valued sense modality, its absolute loss is an understandable emphasis and justification for advancing research and treatments for eye diseases. Both news articles and journal articles focus on keywords associated with blindness. A research group in the U.K. wants to call attention to the much greater proportion of people who are afflicted by eye disease that comes short of robbing them of vision, but nonetheless presents difficulties both for the individual and for the health care system overall. For example, the paper notes that while 8 million people around the world have moderate to severe visual impairment or blindness from glaucoma, around 76 million people around the world have the condition. Similarly, diabetic retinopathy has caused 4.4 million to be blind or have moderate to severe vision impairment, but around 160 million people have the condition. In short, stages of eye disease that involve moderate or severe visual impairment and blindness represent merely the tip of the iceberg of the plethora of eye conditions that need attention. Said researcher is leading a call for a UK-wide sensory health survey to provide robust data to inform health services. Reports like these provide a glimpse into differences in health care systems in different countries and the mentalities and emphases resulting from those different systems. On the one hand, one might ask, "Are not conjunctivitis, sore eyes or dry eyes the topics of ubiquitous discussions already?" On the other hand, to see a call for a survey to inform health services is an interesting public health perspective.

My rating of this study: ⭐🌸

International Team Identifies 127 Glaucoma Genes in Large Genome-Wide Association Study

Article: International Team Identifies 127 Glaucoma Genes in Largest Study of Its Kind
Source: Massachusetts Eye and Ear, via NEI
Published: February 24, 2021

An international team of researchers recently identified 44 new gene loci and confirmed 83 previously known gene loci reported to be linked with glaucoma in a large genome-wide association study comparing the genes of 34,179 people with the disease to 349,321 control subjects. It is the largest study of its kind to date and the first cross-ancestry glaucoma genome-wide association study to include data of people from Europe, Africa, and Asia (in addition to data from people of European, African, and Asian ancestry). While glaucoma is an eye disease that predominantly affects people with African and Asian ancestry, previous studies have looked mostly at the genes of people of European ancestry. By gathering data from such a large and diverse pool of subjects, this cross-ancestry study improves upon the fine-mapping of causal variants linked with glaucoma as well as provides new avenues of research, via the newly identified genes, that could implicate previously unknown biological processes leading to the disease. In other words, the exceptionally large size and diversity provided by this study improves the precision of genetic associations of the disease.

Personal commentary: It is a lovely coincidence that this article appears chronologically right after the previous one in the blog as an example of the value of international collaboration in the collective effort of research. This particular research team comprised of contributions from researchers in Australia, the United Kingdom, the Netherlands, Finland, Germany, Singapore, Japan, Nigeria, Ghana, South Africa, Switzerland, Tanzania and the United States. Where possible, my commentaries are scheduled by date of publication of the source article, but I am always happily surprised when these coincidences in sequence speak by and for themselves.

My rating of this study: ⭐⭐⭐⭐⭐

Investigations in Intravitreal AAV Gene Therapies

Article: Improved vectors for ocular gene therapy
Source: University of Munich, via ScienceDaily  and Technology Networks
Published: February 22, 2021

This is an interesting study as a follow up to the article about AAV gene therapies by researchers at the Wyss Institute at Harvard University, as this study also addresses the topic of AAV gene therapy, in this case with a focus on intravitreal injection. As with the Wyss Institute study, the researchers note the limitations of subretinal injection, which prompted further investigation of vector delivery intravitreally. The news article itself is short, and the only section that discusses methods states, "Further studies on three animal models [mice, dogs and non‐human primates] confirmed the efficacy of the procedure, and experiments on human retinal tissue grown in culture confirmed that the vectors can infect photoreceptors and other retinal cells. Finally, initial results of experiments on a mouse model of achromatopsia (complete lack of color vision) suggested that the procedure is capable of restoring some degree of daylight vision." With regard to intraocular inflammation, two of the five dogs used in the study developed inflammation events, which the researchers hypothesized was in response to the enhanced green fluorescent protein (eGFP) rather than the vector capsid, without detailed explanation. In either case, though a good addition to the archive of knowledge about intravitreal gene therapies, the study still shows that this method has not surmounted the obstacle of inflammation if vectors are delivered intravitreally. The approach would probably have been more novel had it been published prior to the study by the Wyss Institute.

Personal commentary: I know I get a bit of critique for including articles and research from lesser known (often international) universities in this archive, for example, comparing research by the University of Munich alongside that of Harvard. The blog is not only for dissemination of information, but also for my own practice in seeing it and examining it. This is why it is a review and why I include my own ratings of the studies. I am aware that research funded by the NEI, for example, is much more robust. But I see no harm in reviewing research from lesser known sources.

My rating of this study: ⭐⭐

Further reading: Tool offers ultra-rapid cooling for intravitreal injections