new research topics in ophthalmology

Eye care: Taking electroretinography to the next level with a soft multi-electrode system

Eye diseases are becoming more prevalent worldwide, partly because of the aging population, but also because of our greatly increased screen time compared to previous generations. Considering our use of displays will most likely keep rising due to technologies such as virtual and augmented reality, we must improve our diagnostic techniques for the early detection and monitoring of ocular diseases.

Among the arsenal of tools ophthalmologist have at their disposal, electroretinography (ERG) still holds much-untapped potential. Simply put, ERG consists of taking measurements of the electrical potentials generated by neurons and other cells in the retina from the surface of the cornea. Many ocular diseases cause abnormalities in a person's ERG signals, including glaucoma, retinitis pigmentosa, and diabetic retinopathy. Although many types of ERG measurement devices exist, few ERG electrodes can measure multiple localized ERG signals from different regions of the retina at the same time. In most cases, such measurements are performed using electrodes placed on hard contact lenses. This makes the procedure more complex, expensive, and particularly uncomfortable for the patient.

Against this background, a research team led by Professor Takeo Miyake from the Graduate School of Information, Production and Systems at Waseda University, Japan, set out to develop a new type of soft ERG multi-electrode system to overcome these issues. Their latest study, published in Advanced Materials Technologies on May 7, 2024, describes their findings. It was co-authored by Saman Azhari from the Graduate School of Information, Production and Systems at Waseda University, as well as Atsushige Ashimori and Kazuhiro Kimura from the Department of Ophthalmology at Yamaguchi University.

The proposed system utilizes a commercially available soft disposable contact lens. The researchers first immersed this contact lens in a solution containing the monomer 3,4-ethylenedioxythiophene (EDOT). They then placed carefully designed gold mesh electrodes with their respective connecting wires onto the inner surface of the contact lens. By circulating a current through the solution containing EDOT, the monomers formed an entangled polymer called PEDOT, which adhered well to the contact lens and fixated the gold components.

A key advantage of this approach is that the PEDOT layer can be overoxidized by using a DC voltage under dry condition, thereby forming a highly insulating layer on the collecting wire. This insulation is critical to ensure different retinal signals flowing through the gold wires do not interfere with one another or with signals originating from other regions of the eye. By carefully designing the gold mesh of the electrodes to spread currents during overoxidation process, the PEDOT encapsulating the mesh region does not overoxidize, thus ensuring good electrical contact with the eye.

The result of this innovative process is a flexible and highly transparent multi-electrode system for ERG measurements that is just as comfortable as commercial disposable contact lenses. The researchers carefully examined the optoelectrical properties of their multi-electrodes and also conducted some experiments on rabbits, as Miyake comments: "Our device was used in animal experiments, confirming its biocompatibility and suggesting a correlation between the location of the electrodes and the intensity of the recorded ERG signals. In other words, our design could enable precise spatial measurements of multiple ERG signals simultaneously."

Taken together, the findings of this study would help us better understand and diagnose ocular diseases. "The use of augmented and virtual reality devices is growing quickly, and the precise and continuous monitoring of eye conditions will become a necessity," remarks Miyake. "A smart contact lens such as the one developed in this work could be connected to a local network to transmit the eye's health condition to an ophthalmologist or healthcare specialist while the user is performing their daily routine. Such systems could prevent irreparable damage to the eyes."

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Materials provided by Waseda University . Note: Content may be edited for style and length.

Journal Reference :

• Lunjie Hu, Saman Azhari, Qianyu Li, Hanzhe Zhang, Atsushige Ashimori, Kazuhiro Kimura, Takeo Miyake. Multi‐Electrode Electroretinography with Transparent Microelectrodes Printed on a Soft and Wet Contact Lens . Advanced Materials Technologies , 2024; DOI: 10.1002/admt.202400075

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On October 18, 2021, five faculty from the Department of Ophthalmology shared their cutting-edge research on a range of eye diseases and topics, including the depth and breadth of our clinical trials, advanced eye imaging techniques, a retinal prosthesis for age-related macular degeneration, artificial intelligence in glaucoma, and curing treatable blindness throughout the world. To view a recording of all five talks, click on the first link below. To view the talk of an individual faculty member, click on that faculty member’s name below.

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·  Diana Do, MD: Clinical Trials

·  Alfredo Dubra, PhD: Advanced Imaging of the Eye

·  Daniel Palanker, PhD: Retinal Prosthesis for AMD

·  Sophia Wang, MD: Artificial Intelligence in Glaucoma

·  Geoff Tabin, MD: Curing Treatable Blindness Globally

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The Department of Ophthalmology and Visual Sciences offers medical students and residents a variety of research opportunities. Please browse the basic science, translational and clinical research projects currently underway below.

Research Topic: Corneal endothelial health judged by endothelial image analysis

Description.

Endothelium is critical for dehydrating the cornea and keeping it clear. With loss of its barrier and pump function, the cornea swells and corneal transplantation may be needed.

Changes in the number, shape and size of the cells may predict loss of function.

Key Research Question/Hypothesis 

Effect of drugs, surgery, devices, and preservation media on the endothelium.

Images of the endothelium captured with either a specular or confocal microscope that can take repeated pictures of the endothelial cells non-invasively in patients. Once images are captured, they can be analyzed with special software in the Cornea Image Analysis Reading Center (CIARC) of the Department.

Student learn these techniques working with both patients and technicians, depending on the project.

Ongoing projects.

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Image analysis studies in CIARC approved; ongoing projects have IRB approval. If launching a new project, IRB approval will need to be obtained.

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Research Topic: Retinopathy of Prematurity and other Pediatric Studies

Effect of low birth weight on the eye’s development.

Data analysis, chart review.

Several ongoing projects—long-term data collection.

Current study has IRB approval. Any new studies will need IRB approval.

Excellent; the data base study has been presented at ARVO and is in preparation for publication in a major pediatric journal.

Dr. Faruk Orge

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Research Topic: Cholesterol and function of the retina

Cholesterol is essential for life in mammal. Yet, if it is chronically in excess, it is a risk factor for cardiovascular and Alzheimer's disease and likely age-related macular degeneration.

To delineate the putative link between cholesterol and age-related macular degeneration.

Characterization of retinal function of mice deficient in different enzymes involved in cholesterol elimination. Animals are assessed by optical coherence tomography, electroretinography, fluorescein angiography and optomotor response.

Students learn these techniques working with post-doctoral researchers responsible for these projects.

All studies are approved by the IACUC.

Dr. Irina Pikuleva

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Research Topic: Contact Lens Related Complications

Ongoing clinical trials related to corneal infiltrative events associated with daily or extended wear of soft contact lenses. Fungal and bacterial biofilm-contact lens models and susceptibility to contact lens care products.

Assessment of sub-clinical corneal inflammation with confocal microscopy. Assessment of bacterial endotoxin and relationship to infiltrative events with soft lenses.

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Other corporate-funded work may or may not allow authorship.

Dr. Loretta Szcztoka-Flynn

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Research Topic: Mechanisms of retinal degenerations

How do mutations in the light receptor rhodopsin cause retinal degenerations like retinitis pigmentosa? How does the retina protect against oxidative stresses that can lead to retinal degenerations such as retinitis pigmentosa and age-related macular degeneration?

A multi-disciplinary approach is employed that includes biochemistry, molecular biology, animal models and biophysics.

All animal studies have approved IACUC protocols.

Excellent with track record of publications in major journals and presentations at national and international conferences.

Information about the laboratory can be found by browsing the Park Lab webpage.

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May 13, 2024

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

Junk food marketing on videogame livestreaming platforms increases purchases and consumption among teens, study finds

by European Association for the Study of Obesity

Food and drink advertisements on videogame livestreaming platforms (VGLSPs) like Twitch are associated with more positive attitudes towards, and purchases and intake of, unhealthy foods that are high in fat, salt and/or sugar (HFSS) like energy drinks among adolescents aged 18 or younger, according to new research presented at this year's European Congress on Obesity (ECO) in Venice, Italy (12–15 May).

The concerning findings prompt researchers to call for stronger regulations on digital marketing of unhealthy foods to young people on these platforms, where there is currently no effective regulation and minimal efforts to control it.

Although the causes of obesity are complex, junk food marketing is associated with overweight and obesity in young people of all ages. As major users of digital media, adolescents (aged 12–18 years) are particularly exposed to their potential benefits and harms.

VGLSPs are a growing form of digital media where individuals can watch streamed videogame footage and communicate via a live chat. They can be accessed via PC, tablets, mobiles, and gaming consoles.

The top VGLSPs globally at the time of the research were Twitch (with 77% of the market share by hours watched), YouTube Gaming (15%), and Facebook Gaming Live (7%). However, a relatively new platform, Kick, has now replaced Facebook Gaming in third spot. The use of VGLSPs is rapidly growing with nearly 30 billion hours of content viewed on the top three platforms in 2023.

Because VGLSPs are popular with young people, they offer an opportunity for food and drink brands seeking to engage with teenagers.

As lead author Dr. Rebecca Evans from the University of Liverpool explains, "Endorsement deals for prominent streamers on Twitch can be worth many millions of dollars, and younger people, who are attractive to advertisers, are moving away from television to these more interactive forms of entertainment. These deals involve collaborating with brands and promoting their products, including foods that are high in fats, salt and/or sugar."

To study this possibility, Dr. Evans and her University of Liverpool colleagues investigated the extent and nature of food marketing via VGLSPs, and its impact on eating behavior in teenagers.

They started by conducting a content analysis to examine the extent and nature of food cues displayed in 52 Twitch videos (52 hours of video content) uploaded to the platform during October 2020 to September 2021 by three influencers popular with adolescents.

Then they systematically reviewed the evidence for a link between exposure to digital game-based (e.g., in-game advertising, advergames) or influencer food marketing (two key techniques used on VGLSPs), and food-related outcomes (attitudes, preferences, purchase, consumption) in young people (aged 18 years or younger).

They went on to survey 490 young people (average age 17 years, 30% female, 76% white, recruited via social media, schools, and a youth research panel) to further explore the link between recall of food marketing on top VGLSPs (i.e., Twitch, YouTube Gaming, and Facebook Gaming Live) and relevant food-related outcomes. Participants were asked about their age, gender, ethnicity, VGLSP viewing habits, their recall of food marketing on VGLSPs, and their food and drink attitudes, preferences, purchase, and consumption of marketed foods.

Finally, the researchers conducted a lab-based randomized controlled trial to explore associations between HFSS food marketing via a mock Twitch stream and subsequent snack intake.

In total, 91 young people (average age 18 years, 69% female, 81% white) took part in an experiment in which they viewed a mock Twitch stream containing either an advert (an image overlaid on the video featuring a brand logo and product) for an unhealthy snack brand or a non-food brand.

Participants were told that they would be completing a memory task about what happened in the stream, to disguise study aims. They then had a "snack break" during which they were offered the branded snack from the stream and a supermarket brand version of the snack. They were also asked about their age, gender, ethnicity, and VGLSP viewing habits.

Viewers exposed to 52 minutes of food advertising every hour

Overall, the analyses found that food cues on Twitch appeared at an average rate of 2.6 every hour, and the average duration of each cue was 20 minutes.

Overall, this amounts to 52 minutes of exposure per hour (including overlapping exposure from multiple food cues on-screen at the same time). Most (71%) of the cues were for HFSS foods, and among these, energy drinks were the most featured category, accounting for 62%. Most food cues (81%) were branded (e.g., an image overlaid on the video featuring a food brand logo) and only 2% had an advertising disclosure.

Most food cues appeared as either product placement (44%) or looping images (41%), and several features that would appeal to adolescents (e.g., tie-ins, logos, offers, slogans) were used. The nature of this advertising means that it is always visible on screen (i.e., viewers cannot "skip" or "close" it).

Familiarity with junk-food ads influences adolescents' unhealthy diet

The researchers also found that the digital game-based marketing was associated with more positive attitudes and greater preferences toward marketed food and drink brands, with young people twice as likely to prefer these products. Additionally, influencer and digital game-based marketing were associated with eating more HFSS food post-marketing exposure (~37 additional kcals in one sitting).

Further analyses found that recall of HFSS food marketing on VGLSPs was associated with more positive attitudes towards advertised HFSS food categories (e.g., fast food, energy drinks ), and in turn purchases and consumption of marketed HFSS foods.

Nevertheless, in the randomized trial, acute exposure to HFSS food marketing in a mock Twitch stream was not associated with immediate consumption of unhealthy foods. This may be because participants were only exposed to one type of advert (a static image), and this was presented in isolation (i.e., no other adverts were present). However, the more time young people reported spending watching VGLSPs each week, the more of the marketed snack they ate, suggesting that habitual exposure is impactful.

According to Dr. Evans, "Our findings provide crucial new information on the extent, nature, and impacts of HFSS food marketing via VGLSPs on young people 's eating behavior. The high level of exposure to digital marketing of unhealthy food could drive excess calorie consumption and weight gain, particularly in adolescents who are more susceptible to advertising. It is important that digital food marketing restrictions encompass innovative and emerging digital media such as VGLSPs."

The authors acknowledge that some of their findings show observational differences rather than evidence of cause and effect, and cannot be generalized to all teenagers. They also note that some of the findings are based on a self-reported survey of viewing and eating habits that can lead to problems of recall and bias, which could have affected the results.

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New treatment could reverse hair loss caused by an autoimmune skin disease

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Researchers at MIT, Brigham and Women’s Hospital, and Harvard Medical School have developed a potential new treatment for alopecia areata, an autoimmune disorder that causes hair loss and affects people of all ages, including children.

For most patients with this type of hair loss, there is no effective treatment. The team developed a microneedle patch that can be painlessly applied to the scalp and releases drugs that help to rebalance the immune response at the site, halting the autoimmune attack.

In a study of mice, the researchers found that this treatment allowed hair to regrow and dramatically reduced inflammation at the treatment site, while avoiding systemic immune effects elsewhere in the body. This strategy could also be adapted to treat other autoimmune skin diseases such as vitiligo, atopic dermatitis, and psoriasis, the researchers say.

“This innovative approach marks a paradigm shift. Rather than suppressing the immune system, we’re now focusing on regulating it precisely at the site of antigen encounter to generate immune tolerance,” says Natalie Artzi, a principal research scientist in MIT’s Institute for Medical Engineering and Science, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, and an associate faculty member at the Wyss Institute of Harvard University.

Artzi and Jamil R. Azzi, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, are the senior authors of the new study , which appears in the journal Advanced Materials . Nour Younis, a Brigham and Women’s postdoc, and Nuria Puigmal, a Brigham and Women’s postdoc and former MIT research affiliate, are the lead authors of the paper.

The researchers are now working on launching a company to further develop the technology, led by Puigmal, who was recently awarded a Harvard Business School Blavatnik Fellowship.

Direct delivery

Alopecia areata, which affects more than 6 million Americans, occurs when the body’s own T cells attack hair follicles, leading the hair to fall out. The only treatment available to most patients — injections of immunosuppressant steroids into the scalp — is painful and patients often can’t tolerate it.

Some patients with alopecia areata and other autoimmune skin diseases can also be treated with immunosuppressant drugs that are given orally, but these drugs lead to widespread suppression of the immune system, which can have adverse side effects.

“This approach silences the entire immune system, offering relief from inflammation symptoms but leading to frequent recurrences. Moreover, it increases susceptibility to infections, cardiovascular diseases, and cancer,” Artzi says.

A few years ago, at a working group meeting in Washington, Artzi happened to be seated next to Azzi (the seating was alphabetical), an immunologist and transplant physican who was seeking new ways to deliver drugs directly to the skin to treat skin-related diseases.

Their conversation led to a new collaboration, and the two labs joined forces to work on a microneedle patch to deliver drugs to the skin. In 2021, they reported that such a patch can be used to prevent rejection following skin transplant. In the new study, they began applying this approach to autoimmune skin disorders.

“The skin is the only organ in our body that we can see and touch, and yet when it comes to drug delivery to the skin, we revert to systemic administration. We saw great potential in utilizing the microneedle patch to reprogram the immune system locally,” Azzi says.

The microneedle patches used in this study are made from hyaluronic acid crosslinked with polyethylene glycol (PEG), both of which are biocompatible and commonly used in medical applications. With this delivery method, drugs can pass through the tough outer layer of the epidermis, which can’t be penetrated by creams applied to the skin.

“This polymer formulation allows us to create highly durable needles capable of effectively penetrating the skin. Additionally, it gives us the flexibility to incorporate any desired drug,” Artzi says. For this study, the researchers loaded the patches with a combination of the cytokines IL-2 and CCL-22. Together, these immune molecules help to recruit regulatory T cells, which proliferate and help to tamp down inflammation. These cells also help the immune system learn to recognize that hair follicles are not foreign antigens, so that it will stop attacking them.

Hair regrowth

The researchers found that mice treated with this patch every other day for three weeks had many more regulatory T cells present at the site, along with a reduction in inflammation. Hair was able to regrow at those sites, and this growth was maintained for several weeks after the treatment ended. In these mice, there were no changes in the levels of regulatory T cells in the spleen or lymph nodes, suggesting that the treatment affected only the site where the patch was applied.

In another set of experiments, the researchers grafted human skin onto mice with a humanized immune system. In these mice, the microneedle treatment also induced proliferation of regulatory T cells and a reduction in inflammation.

The researchers designed the microneedle patches so that after releasing their drug payload, they can also collect samples that could be used to monitor the progress of the treatment. Hyaluronic acid causes the needles to swell about tenfold after entering the skin, which allows them to absorb interstitial fluid containing biomolecules and immune cells from the skin.

Following patch removal, researchers can analyze samples to measure levels of regulatory T cells and inflammation markers. This could prove valuable for monitoring future patients who may undergo this treatment.

The researchers now plan to further develop this approach for treating alopecia, and to expand into other autoimmune skin diseases.

The research was funded by the Ignite Fund and Shark Tank Fund awards from the Department of Medicine at Brigham and Women’s Hospital.

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