David Hutton

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.”

This article originally appeared on Ophthalmology Times.

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

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

Articles

A team of investigators has found that there is a bidirectional association between chronic kidney disease and glaucoma.

Glaucoma and Chronic Kidney Disease Have More in Common than Previously Thought

With diabetes the leading cause of new, preventable cases of blindness in working aged adults in the United States, medical experts are now suggesting patients have dilated eye examinations after their first diabetes diagnosis.

Despite this medical advice from the American Academy of Ophthalmology, the American Academy of Optometry and the American Diabetes Association, only about 48% of diabetic patients receive the exam regularly.

A new University of Houston study, published in the journal 

,1 may explain significant racial and ethnic disparities that connect the numbers of those who undergo eye examinations and the prevalence of diabetic eye complications.

“Among diabetic patients, Whites were more likely to receive routine diabetic eye exams than minorities (66.1% vs. 55.5%). Moreover, compared to Hispanics, Whites reported a higher participation rate in clinical services and diabetes self-management education," Jieni Li, lead author of the paper and doctoral student in the lab of Sang Kyu Cho, PhD, assistant professor of pharmaceutical health outcomes and policy at the UH College of Pharmacy, said in a release. Wendy Harrison, OD, PhD, FAAO, an associate professor at the College of Optometry, rounds out the research team.

“The rate of diabetic eye complications ranged from about 12% to almost 19% in the U.S. among diabetic patients from 2009 to 2018. Hispanics had the highest prevalence of diabetic eye complications, followed by African Americans and Whites,” Li explained.

The team analyzed 10 years of survey data from 8080 diabetic patients in the 2009-2018 Medical Expenditures Panel Survey administered by the Agency for Healthcare Research and Quality. The survey is nationally representative of non-institutionalized civilians capturing their health care utilization and costs.

“Li’s research not only documents the burden of diabetic eye complications at a national level, but also identifies why racial and ethnic minorities are disproportionately affected,” Cho said.

In 2010, the National Eye Institute reported that Hispanics who were 50 and older had a higher prevalence of diabetic retinopathy (DR) (8.0%) than African Americans (5.4%) and whites (5.1%). Between 2010 and 2050, the number of Hispanics with DR is expected to triple, from 1.2 million to 5.3 million.

On the other hand, the prevalence of DR in whites is expected to remain relatively stable during the same period. (5.2 million to 6.4 million).
Several studies have assessed racial and ethnic disparities in the prevalence and disease management among diabetic patients, but literature that focuses on patients with diabetic eye complications and up-to-date information is limited.

“Because diabetic eye complications are consequences of poorly managed diabetes over time, such racial/ethnic disparities in the prevalence of diabetic eye complications are likely entrenched in a more profound systemic inequality in health care access,” said Harrison.

“Given the disparities in diabetic eye complications among minorities, health care providers and policymakers should promote interventions and education programs accordingly to prevent and reduce the development of eye complications,” Cho concluded.

In a separate study, investigators have found that racial and ethnic minorities with glaucoma are facing higher cost-related barriers to medication, which remained after controlling for socioeconomic factors.

The cross-sectional study of 3826 patients with glaucoma found significantly higher odds of self-reported difficulty affording medication were observed among non-Hispanic African American and Hispanic individuals compared with non-Hispanic White individuals.

“Being a chronic disease that frequently requires access to health care, close follow-up, and sometimes complicated and expensive medical and surgical regimens, glaucoma outcomes are often tied to socioeconomic factors, which are invariably linked with race and ethnicity in the US,” wrote Sally L. Baxter, MD, MSc, Shiley Eye Institute, University of California, San Diego, an author of the study.

The goal of the study was to determine cost-related barriers to medication adherence by race and ethnicity in a nationwide cohort of patients with glaucoma.

Disparity in diabetic eye complications among racial/ethnic minorities: An analysis of the 2009-2018 United States medical expenditure panel survey.

Published online April 2022. doi:10.1016/j.deman.2022.100070

A University of Houston study found that minorities have fewer eye exams, higher instances of disease. 

Examining Eye Care Disparities in Diabetes

A new study has found that depression could exasperate symptoms of chronic dry eye disease.

However, investigators point out that the exact reasons behind the link are not immediately known. Could depression drive the severity of dry eye disease, or do chronic eye symptoms fuel depression?

Ultimately, investigators maintain that there is a link between severe dry eye and depression, and it is important for ophthalmologists and patients to be aware of the potential connection.

Dry eye affects around 16 million Americans, according to the US National Eye Institute. But the condition ranges widely in its severity: Many people have milder dry eye -- from staring at computers all day, for example -- and it can be managed with over-the-counter eye drops and frequent screen breaks.

Other people have severe symptoms, sometimes associated with certain autoimmune conditions, like Sjogren’s syndrome or rheumatoid arthritis.

Past studies have shown that people with chronic dry eye have a higher-than-average rate of depression. The new study—published March 10 in 

—shows a correlation between depression and more-severe dry eye symptoms and signs.

According to investigators, the study found that of 535 adults with dry eye disease, those who screened positive for depression generally had worse eye symptoms throughout the one-year study.

However, the study cannot identify the cause of the depression, senior researcher Gui-shuang Ying, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, said in a statement. The relationship could go in either direction, he said.

It can be easy to see how severe dry eye symptoms could affect people's mental well-being, said Yi Zhou, a medical student at Penn who also worked on the study.

"On the other hand," Zhou said in the statement, "there are studies suggesting that people with depression may have changes in how they perceive pain."

Moreover, depression can also have a major impact on lifestyle habits. If a person with depression is spending more time in front of TV and computer screens, for example, that could worsen dry eye symptoms, the researchers said.

Then there's a third possibility: Shared underlying factors might contribute to both depression and dry eye disease, said Anat Galor, MD, of the Bascom Palmer Eye Institute at the University of Miami, who wrote an editorial published with the findings.

The findings are based on 535 dry eye patients enrolled in a clinical trial testing omega-3 fatty acid supplements for easing the condition. At the outset, and 6 and 12 months later, the participants completed standard mental health questionnaires. Anywhere from 13% to 17% of patients screened positive for depression at one of those time points.

Overall, there was a correlation between depression and more severe eye symptoms -- even after the researchers took some other factors into account, such as whether patients had autoimmune disease.

Many medications, including antidepressants, can have dry eye as a side effect. But in this study, there was no link between antidepressant use and dry eye severity -- only depression itself.

One question is whether inflammation could be a culprit, since inflammation has been implicated in the disease process of both dry eye and depression.

The researchers were able to delve into that by looking at markers of inflammation in study patients' tear samples: They did not find any correlation between depression and those inflammatory markers.

However, Zhou said, that does not discount a role of inflammation. It's still possible that systemic inflammation, rather than inflammation at the eye's surface, could help explain the connection between depression and severe dry eye.

Whatever the mechanisms, the findings highlight a connection between dry eye severity and mental well-being. And it's important for health care providers to be aware of it, the researchers said.

If, for example, a patient's dry eye symptoms are worse than the clinical signs of the disease, it might be appropriate to do a mental health screening, Zhou said.

Investigators noted that additional study is needed to elucidate the relationship. The study was funded by the US National Institutes of Health.

Yi Zhou, BA; James Murrough, MD, PhD; Yinxi Yu, MS, et al. Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study.

Published online March 10, 2022. doi:10.1001/jamaophthalmol.2022.0140

While investigators have found a link between dry eye and depression, the exact reasons behind the link are not immediately known.

Depression May Exacerbate Symptoms of Chronic Dry Eye 

The FDA has approved the first generic of cyclosporine ophthalmic emulsion (Restasis) 0.05% single-use vials of eye drops to increase tear production in patients with dry eye disease.

According to a news release, tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.

The generic version is sponsored by Mylan Pharmaceuticals. The company is part of Viatris. There are no remaining legal or regulatory barriers, and the company said in a release that it is launching immediately.

Sally Choe, PhD, director of the Office of Generic Drugs in FDA’s Center for Drug Evaluation and Research, pointed out in the news release that restasis has been approved for use in the U.S. for nearly 20 years, but until today, there was no approved generic product of this drug.

“Today’s approval reflects the FDA’s continued commitment to advancing patient access to lower-cost, high-quality generic drug products that are as safe and effective as their brand name counterparts,” she said in a statement. “Supporting development and expanding opportunities to bring complex generic drugs to the market is a major focus of our efforts to help improve competition and help lower drug prices.”

Cyclosporine ophthalmic emulsion is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca, also known as dry eye. Dry eye disease is a common condition that occurs when a patient's tears are unable to provide adequate lubrication for their eyes. Tears can be inadequate and unstable for many reasons, but the instability can lead to discomfort, inflammation and potential damage of the eye's surface.

The most common side effect reported in the clinical trials for cyclosporine ophthalmic emulsion was ocular burning. Other reactions included conjunctival hyperemia (dilation and redness of blood vessels in the eye), discharge, epiphora (excessive watering of the eye), eye pain, foreign body sensation (the sensation of having something in your eye), pruritus (itchy skin), stinging and visual disturbance (most often blurring).

"I am pleased that Viatris has received the first FDA approval for generic Restasis after working for nearly a decade not only to develop a more affordable product but also to remove all barriers to entry and achieve patient access,” Viatris President Rajiv Malik said in a statement. “We are also proud to add another first to our growing list of industry-setting scientific achievements in bringing to market complex and difficult-to-manufacture products."

Viatris Developed Markets President Tony Mauro said the approval of generic Restasis reinforces the company’s “ongoing commitment to deliver innovative solutions and increase access to more affordable treatment options for patients.”

“We look forward to quickly bringing this important product to millions of Americans with chronic dry eye disease,” he said in a statement.

According to the FDA, applicants must submit appropriate data and information to demonstrate that generic drug products meet the FDA’s rigorous approval standards, ensuring that generic drug products are safe, effective and meet the same high-quality standards as their brand name counterparts.

The development of complex generics may be more difficult due to, for example, their complex active ingredient formulation or route of delivery. As a result, many complex drugs lack generic competition. The FDA has taken a multifaceted approach to encourage development of complex generics through the Generic Drug User Fee Amendments (GDUFA) program.

Cyclosporine ophthalmic emulsion is indicated to increase tear production in patients with dry eye. 