Eye care is advancing at a rapid pace, and the Ophthalmology Times® EyeCon 2022 is the best place to discover opportunities in the field to bring home to your practice. 

Ophthalmology EyeCon 2022

RegeneRx Biopharmaceuticals Inc. said today that its U.S. joint venture (JV) partner and licensee, HLB Therapeutics (HLBT), is planning to expand its ophthalmic clinical development program with RGN-259 in two indications, neurotrophic keratopathy (NK) and dry eye disease (DED), beginning in November.

The trials will be sponsored by the U.S. JV, ReGenTree, LLC.

In a news release, the companies noted that RGN-259 is a sterile, preservative-free, eye drop developed to reduce damage and improve healing for various ophthalmic indications including dry eye syndrome and neurotrophic keratopathy.

To date, more than 1700 subjects have received RGN-259 indicating various degrees of efficacy in both DED and NK. RGN-259 has shown to be quick-acting, well-tolerated and does not have the documented side effects of other approved pharmaceutical products for these indications.

According the HLBT, it will run both DED and NK clinical development program simultaneously. In the case of DED, for which ReGenTree conducted a pre-BLA meeting in February this year, the company said it plans to apply for SPA (Special Protocol Assessment) to the FDA around this October. SPA is a program in which FDA specialists provide a sponsor (ReGenTree) with collaboration in setting up clinical protocols and statistical analysis plans.

The agreed clinical trial design with FDA is binding and this program will give the sponsor and FDA a clear understanding [of relevant trial criteria] by participating together at this stage of the clinical trial protocol development.

The company also noted in its news release that ReGenTree will start the two phase 3 trials for NK simultaneously [to meet the requirement of two independent phase 3 clinical trials necessary for FDA marketing approval].

HLBT also noted that ReGenTree will seek to confirm the efficacy observed in SEER-1 despite the very small number of subjects in that trial. Based on the results of the SEER-1 study, ReGenTree has developed a plan to enter into two phase 3 studies (SEER-2, SEER-3) simultaneously with 60 patients in each study. To this end, it plans to retain a contract research organization (CRO) very shortly and start recruitment of patients in November.

J.J. Finkelstein, RegeneRx's president and CEO, said the company was pleased to see that HLBT is moving forward with both NK and DED clinical trials with RGN-259.

“We believe our product candidate has significant potential as an important therapeutic modality for numerous ophthalmic disorders,” he said in a news release. “Accelerating NK clinical development by simultaneously conducting two trials will speed up the process while also working with the FDA under an SPA to refine our approach to DED. I believe this strategy indicates that HLBT is fully committed to RGN-259's clinical development in the field of ophthalmology.”

Articles

RegeneRx Biopharmaceuticals Inc. said its U.S. joint venture partner and licensee, HLB Therapeutics, will expand its ophthalmic clinical development program with RGN-259 in two indications, neurotrophic keratopathy and dry eye disease.

RegeneRx licensee to expand Phase 3 clinical trial program with RGN-259

A specific cell within the retina appears to be particularly good at housing Ebola and other viruses, new research has found.1

A highly infectious and lethal viral disease, Ebola was first observed 1976 and has since impacted thousands of humans and animals, primarily in Central Africa.

“Inflammation of the eye, known as uveitis, is very common following infection with Ebola and we know the cells within the iris, at the front of the eye, as well as the retina have the capacity to play a major role in uveitis and act as hosts for microorganisms,” says study senior author P Justine Smith, PhD, FARVO, a strategic professor in Eye and Vision Health at Flinders University. “However, what we didn’t know was which out of the two was most responsible in the case of Ebola.”

The study wasled by Flinders University and CSIRO’s Australian Centre for Disease Preparedness, used cells from human eyes donated from the SA Eye Bank to investigate the ability of iris and retinal pigment epithelial cells to be infected by Ebola.

According to a news release from Flinders University, cells were infected with Ebola virus, Reston virus (a type of 

 that does not cause disease in humans) or Zika virus (another type of virus, but one that also can cause uveitis), while some were left uninfected for the duration of the trial.

While both types of cells seemed to allow the Ebola virus to replicate, it was the retinal cells that showed much higher levels of infection.

“We also found similar results when looking at the cells infected with Reston virus and Zika virus,” Smith said in the release.

Moreover, Smith explained that patients with Ebola eye disease have characteristic retinal scars, suggesting the retinal pigment epithelium is involved in the disease, so this finding is consistent with what eye doctors are seeing in the clinic.

“These retinal cells are good at eating things – called phagocytosis - and they play an essential part in the visual cycle by recycling our photoreceptors, so it makes sense that these cells would be a receptive haven for Ebola, as well as other viruses,” she noted.

According to the university, the researchers explained that the study demonstrates an important target cell for Ebola infection in the eye and suggests the potential for these cells to be monitored during acute viral infection to identify patients at highest risk of uveitis.

“Amongst other issues, including pain and blurred vision, uveitis can ultimately lead to vision loss, so it’s important we find ways to diagnose it as early as possible to enable swift treatment,” Smith concluded.

The work was supported by a grant from the National Health & Medical Research Council.

1 Shawn Todd, Yuefang Ma, Liam M. Ashander, Binoy Appukuttan, Michael Z. Michael, Timothy A. Blenkinsop, Steven Yeh, Glenn A. Marsh and Justine R. Smith

Ebola virus differentially infects human iris and retinal pigment epithelial cells. Frontiers in Virology

A team of investigators at Flinders University in Australia have found that a specific cell within the retina appears to be particularly good at housing Ebola and other viruses.

Eyes a haven for Ebola and other viruses

Self-Plugging needles provided a more targeted, self-plugging drug delivery. (Image courtesy of Terasaki Institute for Biomedical Innovation)

A team of investigators, including scientists from the Terasaki Institute for Biomedical Innovation (TIBI), has developed a novel, self-plugging microneedle for injecting therapeutics into the eyes, potentially solving one of the major challenges of treating eye diseases – accurate delivery of therapeutic drugs to the retina, while guarding against possible complications at the injection site.

According to the institute, in a recent study,

 investigators found preclinical evidence that this innovative, biodegradable microneedle, dip-coated with a therapeutic drug for release upon insertion into the eyeball, can also be equipped with a special hydrogel that simultaneously seals off the insertion hole. Additionally, this self-plugging microneedle can be fabricated with different needle lengths, so therapeutics can be precisely targeted and dispersed to retinal tissues or other areas within the eyeball.

“This novel improvement in drug delivery treatment can avoid problems associated with using needles to treat serious eye diseases,” Ali Khademhosseini, PhD, TIBI’s director and CEO and a co-author of the study, said in a news release from TIBI. “It is one of many simple, yet effective and impactful innovations from our institute, which is focused on translating biomedical engineering into clinical realities.”

The challenge – and need – for retinal drug delivery

The retina is a thin layer of cells that make up the inner lining of the very back of the eyeball. It enables vision by receiving light and converting it to signals that travel to the brain, which then interprets them as images.

As vital as it is to clear, crisp vision, the retina and its critical central portion, the macula, are also subject to different types of damage due to age, genetics, disease and other risk factors. This damage can cause symptoms ranging from distorted or seriously impaired vision to complete blindness and can be widespread among different populations. Indeed, age-related macular degeneration is the leading cause of irreversible vision loss in adults aged over 60, and diabetic retinopathy is the leading cause of blindness among U.S. working-aged adults aged 20 to 74 years.

According to TIBI, some forms of retinopathy can be treated by the injection of drugs into the eyeball using syringes and hypodermic needles. In this procedure, the injected drugs diffuse through the fluid within the eyeball to reach the damaged site. In many cases, multiple injections are needed over a prolonged period of time in order to protect their vision. In addition to this regimen being a hardship on patients, it introduces the risk of bacterial infection at the needle withdrawal site. It can also pose a risk for floating tumor cells in diseased eyes to escape through the puncture holes and migrate to other sites.

TIBI noted in its news release that in order to avoid these hurdles, implantable needles have been attempted for drug delivery. However, mechanical difficulties and navigation through the viscous fluid in the eyeball have hampered accurate needle placement and pose an additional risk of retinal damage. Other approaches involve polymer plugs to close the holes left by hypodermal needles, but this involves a separate step and time lag after injection.

According to TIBI, different types of microneedles, both in singular or patch form, have proven effective for drug delivery into different regions of the eye, with minimal puncture size and optimally targeted drug delivery. A collaborative team, including scientists from the Terasaki Institute for Biomedical Innovation, has built upon this technology by developing a novel, self-plugging microneedle for advanced injection treatment of the eyes.

The TIBI team utilized a precision fabrication method to create biodegradable, sharply-tipped, ultrathin microneedles of various lengths. This versatility in needle length allowed for a more controllable placement into the eyeball and more accurate drug delivery to the injury site; the fineness of the needles minimize incision size in the eyeball. The sharp end of the needle could be dip-coated with the therapeutic drug, with the needle releasing the drug upon insertion into the eyeball.

As an innovative addition, the blunt end of the microneedle was affixed with an experimentally-optimized hydrogel plug, which could swell after needle injection and seal off the insertion hole.

The 2 microneedle coatings were examined microscopically and tested for strength before subjecting them to validation tests for drug delivery and sealing effectiveness. Initial 

tests using the drug-loaded microneedles demonstrated almost complete drug delivery over a 24 hour period; similar experiments using dye-loaded SPNs inserted into vials of pig eyeball fluid demonstrated dye release over a suitable distance for injection into the eyeball.

 experiments measuring the internal pressure of cultured pig eyeballs showed that there was almost no change in pressure after applications of SPNs, unlike the pressure drop obtained when non-plugging microneedles were applied. Examination of the tissue at the SPN application site confirmed firm attachment of the SPNs.

 experiments measured dye-tracked release from the SPNs into cultured rabbit and pig eyeballs. Tissue sections from these eyeballs revealed that dye distribution distance from the insertion site was directly proportional to needle length, demonstrating the spatially controllable drug delivery capabilities of the SPNs.

 on pig animal models. Seven days after application of dye-loaded SPNs to the pigs’ eyes, observation through the pigs’ corneas revealed that the SPNs were still firmly implanted and there was no needle deformation. Leakage tests using surgical sponges showed no leakage of eyeball fluid.

TIBI noted in the news release that tissue section staining of the eyeballs exhibited complete dye dispersal and deep penetration into retinal tissues. Notably, there were no signs of inflammation or tissue disruption at the application site.

This work was supported in part by a grant by the National Research Foundation of Korea (NRF), a grant funded by the Korean government (MSIT) (2021R1F1A105502211), and the Basic Science Research Program through the NRF, funded by the Ministry of Education (NRF-2017R1A6A3A04004741.

1 KangJu Lee, SeungHyun Park, Dong Hyun Jo, Chang Sik Cho, Ha Young Jang, Jiyeon Yi, Minkyung Kang, Jaeho Kim, Ho Yun Jung, Jeong Hun Kim, WonHyoung Ryu, and Ali Khademhosseini. Self-Plugging Microneedle (SPM) for Intravitreal Drug Delivery. 

. Published February 22, 2022. doi: 10.1002/adhm.202102599.

Self-plugging microneedles offer potential to improve delivery of drugs into the eye

LumiThera Inc. today announced detailed findings in its LIGHTSITE III, multi-center clinical trial in non-neovascular (dry) Age-Related Macular Degeneration (AMD) subjects treated with Photobiomodulation (PBM) using the Valeda Light Delivery System.

According to the company, LIGHTSITE III, a prospective, double-masked, randomly assigned, multi-center clinical trial, was conducted at 10 leading US retinal centers. The goal was to treat non-neovascular (dry) AMD subjects with PBM every four months for a duration of 24 months.

The company noted in a news release that 100 subjects were enrolled in a 2:1 ratio of PBM to sham in the treatment groups. The mean age was 75 years and mean dry AMD duration since diagnosis was 4.9 years prior to trial enrollment. Baseline best corrected visual acuity (BCVA) letter scores observed were a mean 

 0.7 in the sham and PBM treatment groups, respectively.

The majority of subjects were considered to have intermediate dry AMD. The analysis included 91 eyes in the PBM treatment group and 54 eyes in the sham treatment group in the modified intent to treat population.

The trial results demonstrated statistically significant improvement in the prespecified primary endpoint in BCVA at 13 months in the PBM treatment group over the sham-treatment group (p = 0.02). A sustained, mean increase in ETDRS letter score of ~5.5 letters from baseline was seen at the 13-month timepoint in PBM-treated subjects (p < 0.0001). In the PBM treatment group responders, 55% of the subjects showed a 

5 letter improvement on the standard EDTRS eye chart with a mean of 9.7 letters and 26% achieved a 

10 letter improvement with a mean of 12.8 letters.

In addition to improvements in BCVA, anatomical measurements in PBM-treated subjects demonstrated no significant increase in drusen pathology at 13 months compared to baseline while sham subjects continued to see numerical increases in drusen deposition. Drusen deposition is the hallmark pathology for diagnosis of dry AMD which leads to chronic inflammation and is associated with disease progression and cell loss. A negative correlation was observed between lower drusen volume pathology and improvement in BCVA with PBM (Spearman correlation, -0.3, p = 0.004).

The advance to later stage disease pathology such as the neovascular (wet) form or the development of geographic atrophy (GA), i.e., loss of retinal tissue in naïve patients was evaluated. The % conversion of dry AMD to the wet form was 1.8% for sham, 5.4% for PBM and 8.3% for the non-study eye groups at month 13. A few patients had GA (9 eyes at screening), and were distributed evenly between 5 PBM and 4 sham eyes at baseline. At month 13, 6 additional eyes progressed with new GA identified. Overall, a total of five of 55 sham eyes progressed to new GA (9.1%) versus only 1 of 93 PBM eyes progressed to new GA (1.1%) at month 13.

"The subjects had good starting vision with approximately 70% having between 20/32 to 20/40 vision.

According to Diana Do, MD, and Quan Dong Nguyen, MD, MSc, FARVO, both professors of ophthalmology and members of the Retina Division at the Byers Eye Institute at Stanford University, a clinical site for the LIGHTSITE III trial, study subjects were only enrolled in the study if their vision was 20/32 to 20/100 and no evidence of GA in the central macula.

“Intermediate dry AMD patients have pathology and visual impairment consistent with earlier stages in the disease and have not lost retinal tissue by progressing to GA,” the pair noted in the news release. “Thus there is an opportunity to improve their vision while retinal tissue is still viable. Therapy with PBM using the Valeda Light Delivery System may serve a significant unmet need for many of our patients with dry AMD who now have the potential to improve their visual acuity with treatment”

Moreover, René Rückert, MD, MBA, chief medical officer of LumiThera, pointed out in the news release that the safety results from the LIGHTSITE III trial through the 13-month timepoint were positive.

“We now have patients that have exited the 2 year study,” Rückert explained. “We will continue to follow all patients for the full 24 months for safety. To date, the results are consistent with a very favorable safety profile and a non-invasive treatment that can target patients earlier in disease.”

Eleonora Lad, MD, PhD, an associate professor and director of ophthalmology clinical research at Duke UniversityMedical Center, a participating site, moted that a non-invasive approach such as PBM treatment with the light delivery system could have a potential impact on the quality of life for dry AMD patients.

“We have many patients that would be excited to benefit from any treatment that recovers or improves vision,” she said in the news release.

Glenn Jaffe, MD, Robert Machemer Professor of Ophthalmology and chief, Vitreoretinal Division and director of the Duke Reading Center, pointed out that the clinical results show improvements in vision.

What is further interesting is the lack of drusen deposit in the PBM treated group, and potentially less patient conversions to wet form of disease,” Jaffe noted in a statement. “Patient progression to new GA was also evaluated and was less in the PBM group, and while the new GA progression numbers are small in this study group, all outcomes point in favor for PBM as a novel approach to treat dry AMD patients earlier in disease.”

Clark Tedford, PhD, president and CEO of LumiThera, pointed out in the news release that the study supports that PBM treatments can improve visual acuity.

“Our commercial and clinical trial experience has demonstrated an excellent safety and clinical benefit profile and we plan on submitting a PMA to the FDA for U.S. approval,” Tedford noted.

LumiThera Inc. noted that the trial results demonstrated statistically significant improvement in the prespecified primary endpoint in BCVA at 13 months in the PBM treatment group over the sham-treatment group. 

LIGHTSITE III trial data demonstrates improvement in vision in intermediate dry AMD

Sheryl brings a wealth of editorial experience to MJH Life Sciences’ Eye Care Network, having engaged with the readers and the greater ophthalmic community of 

for more than 20 years. As Group Editorial Director, Sheryl’s purview extends across the print and digital network of 

Ophthalmology Times, Ophthalmology Times Europe, Modern Retina 

 Prior to ophthalmology, Sheryl previously covered the fields of audiology and confectionery science/technology/manufacturing.

Sheryl is also passionate about the mission, vision and values of Ophthalmic World Leaders (OWL) and recently completed her term on its Board of Directors. She continues to volunteer as Editor-in-Chief of the organization’s 

Magazine. In 2013, she was honored with the group’s inaugural Rising Star Award.

In addition, she has served as a judge for 

 Health Care Heroes Awards program as well as the Jesse H. Neal National Business Journalism Awards.

William L. Soscia, MD, explains how the Center for Sight participates in Mission Cataract and will perform 100 to 200 cataract surgery cases for free for patients who may not have insurance. He also discusses the various opportunities that patients have available to them to be less dependent on glasses after cataract surgery.

Videos

As ophthalmologists observe Cataract Awareness Month this June, William L. Soscia, MD, medical director at Center for Sight, in Sarasota, Florida, focuses on the importance of having excellent vision for safety and everyday functions. 



How quality vision builds a foundation for safety and everyday activities

Bausch + Lomb Corp. today announced that the U.S. Centers for Medicare and Medicaid Services (CMS) has issued a permanent, product specific J-Code J3299 for triamcinolone acetonide injectable suspension (Xipere)

According to a news release, the code will become effective for provider billing on July 1, 2022. J-Codes are reimbursement codes used by both commercial insurers and government payers to quickly identify therapies that are administered by a health care professional incident to the office visit.

“At Bausch + Lomb we are committed to bringing new and innovative therapies to market that benefit eye care professionals and the patients they serve. This not only applies to the development of new therapies, but also making these therapies accessible once they become available,” Yolande Barnard, senior vice president and general manager, U.S. Pharmaceuticals, Bausch + Lomb, said in a statement. “The issuance of the permanent J-Code will help facilitate access to Xipere for Americans suffering from macular edema associated with uveitis and help streamline the reimbursement process.”

According to the news release, triamcinolone acetonide injectable suspensionwas approved by the FDA on October 25, 2021, and is the first and only therapy available in the United States that utilizes the suprachoroidal space to treat patients suffering from macular edema associated with uveitis, which is the leading cause of vision loss in people with uveitis, a form of eye inflammation.

 It became commercially available in March.

Physicians interested in attending a training session can register at 

https://www.xipere.com/hcp/xipere-training

Massa, H., Pipis, S. Y., Adewoyin, T., Vergados, A., Patra, S., & Panos, G. D. (2019). Macular edema associated with non-infectious uveitis: pathophysiology, etiology, prevalence, impact and management challenges. Clinical ophthalmology (Auckland, N.Z.), 13, 1761–1777. 

XIPERE® [prescribing information]. Alpharetta, GA: Clearside Biomedical, Inc.; 2021.

The U.S. Centers for Medicare and Medicaid Services code is effective July 1 and will enhance access to Xipere, the only therapy available in the United States for suprachoroidal use in the treatment of macular edema associated with uveitis. 

Bausch + Lomb receives permanent J-Code for triamcinolone acetonide injectable suspension 

Retinitis pigmentosa, a degenerative genetic disease of the eye, is characterized by progressive vision loss, usually leading to blindness. In some patients, structural defects in the photoreceptor cells have been observed, but the molecular mechanisms involved are not understood.

A team from the University of Geneva (UNIGE), in collaboration with the University of Lausanne (UNIL), has identified the essential role played by a molecular zipper formed by four proteins. The absence of this zipper leads to cell death in retinal cells. This discovery could lead to the development of therapeutic approaches for 

According to a news release form the University of Geneva, retinitis pigmentosa

 is the most common hereditary retinal disease in humans, with a prevalence of one in every 4000 people worldwide. The first symptoms usually appear between the ages of 10 and 20 with a loss of night vision. Thereafter, the visual field narrows into a “tunnel vision” to finally lead to blindness around the age of 40. This disease is characterized by a degeneration of the light sensitive cells, the photoreceptors.


The university noted in the release that these specialized neuronal cells of the retina are responsible for the conversion of light into a nerve signal. The outer segment of the cell is made up of stacks of discs on which the light-sensitive pigments are located. The inner segment contains all the metabolic machinery essential to the functioning of the cell and is linked to the outer segment by the connecting cilium.

Mutations in the genes of four proteins located in this connecting cilium are all associated with retinal pathologies presenting degeneration of photoreceptors. These four proteins had been identified by the laboratory of Paul Guichard, PhD, and Virginie Hamel, PhD, of the Department of Molecular and Cellular Biology of the Faculty of Science. They are located in centrioles, cylindrical structures made of microtubules and present in all animal cells.


“In the centriole, these proteins ensure the cohesion of the different microtubules by acting like a zipper. We wondered if they did not play the same role in the tubular structures of the connecting cilium”, explained Hamel, last author of the study, said in the release.

Observations with unprecedented precision

Thanks to an expansion microscopy technique optimized by the group of Hamel and Guichard, which allow cells to be inflated without deforming them, the scientists were able to observe retinal tissue with a resolution never achieved. The biologists focused on the structure of connecting cilia from mice that had - or did not have - a mutation in the gene for one of the four mentioned proteins.

These observations were conducted at different life stages.

“In the absence of the mutation, we found that these proteins ensure, just as we had previously seen in centrioles, the cohesion between microtubules by forming a zipper that closes as development proceeds,” Olivier Mercey, researcher in the Department of Molecular and Cellular Biology and first author of the study, said in the release.


On the other hand, when the gene for this protein is mutated, although the structure of the microtubules appears normal in the first days, the microtubules gradually become less and less attached to each other. In adulthood, the affected mice have microtubules that are no longer “zipped” together at all and eventually collapse, leading to cell death of the photoreceptors.

Restoring the “molecular zipper” to prevent cell death

According to the university, this work, supported by the European Research Council (ERC) and the Pro Visu Foundation, has led to a better understanding at the molecular and structural level of 

 which allows to consider therapeutic treatments that act upstream of cell degeneration.


“By injecting the protein into patients suffering from certain types of 

, we can imagine that the molecular zipper could be restored to ensure the structural integrity of the microtubules of the connecting cilia, thus preventing the death of photoreceptor cells,” Guichard concluded. “We are evaluating this approach in collaboration with our colleagues from UNIL and the Jules-Gonin Ophthalmic Hospital, Yvan Arsenijevic and Corinne Kostic.”

Olivier Mercey, PhD; Paul Guichard, PhD; et al. The connecting cilium inner scaffold provides a structural foundation that protects against retinal degeneration. 

 published June 16, 2022. doi 10.1371.journal.pbio.3001649

A team led by researchers from the University of Geneva has identified a molecular mechanism that causes degeneration of the eye’s photoreceptors, which can lead to blindness.


A new hope for a therapy against retinitis pigmentosa

Can the eyes can help understand the brain? (Image courtesy of Per Jansen/University of South Australia)

It is frequently said that ‘the eyes tell it all’, but regardless of what their outward expression may be, the eyes also could signal neurodevelopmental disorders such as ASD and ADHD according to research from 

In what is considered by the University of South Australia as the first study of its kind,

 investigators have found that recordings from the retina could identify distinct signals for both attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), providing a potential biomarker for each condition.

 (ERG) - a diagnostic test that measures the electrical activity of the retina in response to a light stimulus - researchers found that children with ADHD showed higher overall ERG energy, whereas children with ASD showed less ERG energy.

, PhD, a research optometrist at Flinders University, noted that the preliminary findings indicate promising results for improved diagnoses and treatments in the future.

“ASD and ADHD are the most common neurodevelopmental disorders diagnosed in childhood. But as they often share similar traits, making diagnoses for both conditions can be lengthy and complicated,” Constable said in the news release. “Our research aims to improve this.”

Constable noted in the release that by exploring how signals in the retina react to light stimuli, investigators hope to develop more accurate and earlier diagnoses for different neurodevelopmental conditions.

“Retinal signals have specific nerves that generate them, so if we can identify these differences and localize them to specific pathways that use different chemical signals that are also used in the brain, then we can show distinct differences for children with ADHD and ASD and potentially other neurodevelopmental conditions,” he explained in the release.

Moreover, Constable pointed out in the release that the study delivers preliminary evidence for neurophysiological changes that not only differentiate both ADHD and ASD from typically developing children, but also evidence that they can be distinguished from each other based on ERG characteristics.

 (ADHD) is a neurodevelopmental condition characterized by being overly active, struggling to pay attention, and difficulty controlling impulsive behaviors. 

 (ASD) is also a neurodevelopmental condition where children behave, communicate, interact, and learn in ways that are different from most other people.

Co-researcher and expert in human and artificial cognition at the University of South Australia, Fernando Marmolego-Ramos, PhD, said the research has potential to extend across other neurological conditions.

“Ultimately, we are looking at how the eyes can help us understand the brain,” Marmolejo-Ramos explained.

While further research is needed to establish abnormalities in retinal signals that are specific to these and other neurodevelopmental disorders, Marmolejo-Ramos noted that what the investigators have observed so far shows that they are on the precipice of something amazing.

“It is truly a case of watching this space; as it happens, the eyes could reveal all,” he said.

According to the University of South Australia, the research was conducted in partnership with 

Great Ormond Street Hospital for Children

Fernando Marmolego-Ramos, PhD, Paul Constable, PhD; Discrete Wavelet Transform Analysis of the Electroretinogram in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder. 

. Published June 6, 2022. doi: 10.3389.fnins.2022.890461

Investigators have found that recordings from the retina could identify distinct signals for both attention deficit hyperactivity disorder and autism spectrum disorder, providing a potential biomarker for each condition.

When it comes to ADHD and ASD, the eyes could reveal all

A team of investigators from the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) has found that there is a bidirectional association between chronic kidney disease (CKD) and glaucoma. This is possibly due to underlying common risk factors such as diabetes and hypertension.

CKD involves the gradual loss of kidney function in filtering blood, with evidence of kidney damage for more than 3 months.

 Glaucoma is a condition where there is a build-up of pressure in the eye, resulting in damage to the optic nerve. It affects around 3% of people over 40 in Singapore and its incidence increases with age.

 Poorly controlled glaucoma can eventually lead to permanent loss of vision.

As our population ages, more are at risk of developing chronic diseases such as CKD and glaucoma. The number of Singaporeans diagnosed with CKD has increased significantly from about 4.3 daily new cases in 2011, to about 5.7 daily new cases in 2019, with no sign of abating. There are currently more than 8,500 dialysis patients in Singapore.

The kidney and the eye are two organs located in separate parts of the body that are not intuitively thought to be associated. They are involved in different systems and perform different functions. The team, however, found that patients with baseline CKD have a 18% higher risk of incident glaucoma. The risk of incident glaucoma increased to 42% in patients with CKD due to diabetes. This association was more prevalent among patients of East Asian ethnicity, including Singaporeans. Reversely, patients with glaucoma have more than 3.6 times higher risk of incident CKD after 10-15 years of follow-up.

Possible explanations for the association include the two diseases sharing common risk factors, such as diabetes, hypertension and cardiovascular disease, as well as common disease processes such as renin-angiotensin system (RAS) dysfunction – in which, a hormonal system is unable to regulate blood pressure, fluid and electrolyte balance, and other functions in the body, other disease processes also include oxidative stress, and inflammation. Causal mechanisms may also play a role in the presence of both diseases, as CKD results in fluid overload and accumulation of toxic metabolites, disturbing the osmotic pressure in the eye, and at the same time accelerating arteriosclerosis, which is the hardening of the walls of the blood vessels, causing microvascular compromise.

Though these findings are still insufficient to conclude a cause-and-effect relationship between CKD and glaucoma, they draw attention to the complex interplay of factors between disease states. They also emphasize the importance of reducing risk factors such as diabetes and hypertension that are implicated in multiple health problems.

 was published in June. The team comprises NUS Medicine fifth-year student Faye Ng, third-year student Harris Song, and newly-minted doctors, Benjamin Tan, MD, and Teo Chong Boon, MD, along with Cheng Ching-Yu, MD, PhD, MPH, from the Department of Ophthalmology at NUS Medicine and clinical associate professor Boey Pui Yi, MBBS, from the Glaucoma Department, Singapore National Eye Centre, Singapore, and Emmett Wong, MD, from the Division of Nephrology, Department of Medicine at the National University Hospital, Singapore.

“We are grateful for the opportunity to work with brilliant mentors who provided their clinical knowledge and expertise to this research,” Ng said in a statement. “They encouraged us to reflect on how we can leverage our research findings to impact population health, translating science into actionable perspectives and insights. Our research has shown the importance of paying attention to the complex interplay between disease states such as CKD and glaucoma, and the need to advocate for preventive health to improve overall health and well-being, countering the rise in chronic diseases.”

Cheng, supervisor of the research team, applauds the efforts of the team on discovering this significant finding.

“The team has been hard at work trying to discover the associations between seemingly different organs,” Cheng concluded. “Eventually, we hope that this research will add on to the narrative in educating the public that they need to pay closer attention to their chronic health risks, because it is crucial for the entire physiology of the body to work in tandem to ensure good health.”

1 https://www.kidney-international.org/article/S0085-2538(15)50698-4/fulltext

2 https://www.straitstimes.com/singapore/health/local-studies-find-link-between-myopia-and-glaucoma

https://www.straitstimes.com/opinion/forum/forum-vital-to-do-more-upstream-to-prevent-or-delay-kidney-failure

4 Faye Yu Ci Ng, Benjamin Kye Jyn Tan, Harris Jun Jie Muhammad Danial Song, Chong Boon Tan, Chong Boon Teo, Emmett Tsc Yeung Wong, Pui Yi Boey, et al. Bidirectional association between glaucoma and chronic kidney disease: A systematic review and meta-analysis. eClinicalMedicine, published June, 2022; doi: 10.1016/j.eclinm.2022.101498

A team of investigators from the Yong Loo Lin School of Medicine at the National University of Singapore has found that there is a bidirectional association between chronic kidney disease and glaucoma.

Researchers discover glaucoma and chronic kidney disease have more in common than what meets the eye

: The views expressed in this blog are those of their respective contributor and do not represent the views of 

A world-renowned cataract surgeon recently told me, “Both Jim Carrey and Leonardo DiCaprio are actors, but they don’t try out for the same roles; likewise, you don’t have to do what I do. I’m Jim Carrey, you be Leonardo.”

In a profession that values super subspecialization, combined with a society that pigeonholes physicians into corners, I often felt I didn’t fit into one job title with my varied passions and cross interests.

“It's hard to be what you can’t see.” While this phrase often refers to racial and gender representation, I also believe it expands to career possibilities. If you’ve never been exposed to careers beyond the 9-5 clinic model, it's hard to see how medicine can accommodate physicians with varied talents. You may come to think you are not capable of various roles because they are not in your vocabulary of possibilities.

My parents are Indian immigrants (I can probably stop here for all South Asian descendants),and while there were expectations for strong academics, we were told you were defined by your career, and you only picked one. So, if you had a passion in art, music, or writing, it was a nice hobby that could be indulged by your physician income, but it always stayed on the backburner. And while I grew up with some of these labels, my parents instilled in us a belief that I could accomplish anything with determination and hard work.

As a young child, I witnessed my parents exemplify the value of service to others through their generosity to help those locally and abroad. I helped gather medical supplies for war torn refugees and visited mobile clinics in farm villages in India. I grew up understanding the impact of philanthropy and how it could be used for larger institutional programs.

After residency, I became aware of public health advocacy programs focused on health equity. I learned how to use my professional status to advocate for policies that helped both un- and underinsured members of our local communities. After several years in practice, I was able to understand how my surgical skills could help in relief camps in underserved countries. This has grown into a passion to give back in terms of not only cataract camps, but sustainable skills transfer opportunities and educational programs with local NGOs.

Research and teaching were a natural offshoot of my global health work. As physicians, the “see one, teach one, do one” adage often comes full circle in academic medicine where we are involved with teaching not only residents, but medical students and undergraduates. It’s a natural step for physicians to be on faculty at local medical schools or have some academic appointment.

My research interests further expanded to include biopharmaceutical and medical devices development. Working on the execution of clinical trials has been an incredible opportunity to advance science and reach thousands of lives, as opposed to one patient every 15 minutes. I see the full scope of drugs and devices from conception to safety and finally in my operating room.

I used to hide some of my many interests, feeling it wasn't relevant to patient care, or brushed it off as "just my volunteer work." When those around me were comparing cataract case numbers, I was meticulously logging details about supplied needed for upcoming medical relief camps. While some were overscheduling patients during their lunch hour, I was on advocacy calls to senators trying to lobby for health care access and advocating for food program expansion to alleviate food insecurity. I've settled into my interests, and instead of putting them on a backburner or treating them as a side gig, I've combined them into building my portfolio career.

The Leonardo reference initially referred to a particular actor, but it made me think of Leonardo da Vinci. Despite his fame and accomplishments in art, he epitomized the “Renaissance man” with exploration in anatomy, zoology, geology , optics, and hydrodynamics. In the East, one of the most famous multitalented physicians was Ibn Sina (Avicenna). In addition to medicine, his writings included philosophy, astronomy, geography, geology, psychology, logic, mathematics, physics, and poetry. 

These renaissance ideals celebrated persons with many talents or areas of knowledge. Yet somehow modern society has labeled those of us with varied passions and talents as unfocused or undedicated, when in fact the opposite is true. It's because we are so dedicated to our values, we focus our talents in ensuring we use 

I say this all to emphasize that we don't have to be definted by others' expectations. If i want to have a 6 day a week practice, great, go for it. If, on the other hand, I want to spend my time in relief work and nonprofits and only work 3 days, that, too, is a valuable option. Or, if I want to reach thousands of patients and oversee global cutting-edge clinical trials and see patients and operate a couple days a week, fantastic.

I can be a surgeon, an educator, a researcher, a writer, and a philanthropist. We can all be Leonardos, and so much more.

Zaiba Malik, MD, is a board-certified ophthalmologist specializing in comprehensive, cataract, and global ophthalmology. Dr. Malik has been serving as Assistant Clinical Professor in the Surgery Department at Wright State University Boonshoft School of Medicine since 2008. She can be contacted at: zmalik01@gmail.com

In a profession that values super subspecialization, combined with a society that pigeonholes physicians into corners, I often felt I didn’t fit into one job title with my varied passions and cross interests. 

When it comes to ADHD and ASD, the eyes could reveal all

Researchers discover glaucoma and chronic kidney disease have more in common than what meets the eye

Blog: I’ll be Leonardo and so much more

Ophthalmology EyeCon 2022

SAP Content