The University of Southern California Roski Eye Institute researchers and clinicians published the results of the National Eye Institute-funded Chinese American Eye Study, the largest ophthalmology study among those with Chinese ancestry living in the United States. The findings, published in JAMA Ophthalmology, point to critical interventions in the prevention and treatment of blinding eye diseases, such as age-related macular degeneration and diabetic retinopathy, among Chinese Americans.

Key findings of the CHES study point to a higher percentage (85 percent) of neovascular AMD than geographic atrophy AMD (15 percent). This is almost the opposite of what has been found in whites or other ethnic groups, who typically have the same percentage of AMD types or higher prevalence of dry AMD. The study also found the prevalence of AMD is higher among Chinese Americans as compared to the Chinese population living in urban/rural China, suggesting the influence of environmental or behavioral factors should be considered.

The other substantial finding in the study is the participants with diabetes (17.4 percent) were three times more likely than those without the disease to have significant visual impairment. This increase was found in the Chinese-American study participants with Type II diabetes who had cataracts or macular edema resulting in visual impairments. While 41 percent of these Chinese-American study participants had DR, this is a lower percentage than has been reported among Chinese people living in rural China (46 percent) and Latinos living in Los Angeles (48 percent). As well, Chinese Americans were found to have a lower reported rate of DR than Chinese residing in rural northern China, likely a result of their better access to diabetes screening and treatment.

Asian Americans are the fastest growing racial group in the United States, and Chinese Americans are the largest segment of this population, according to the latest U.S. Census. Rohit Varma, MD, MPH, interim dean of the Keck School of Medicine of USC and director of the USC Roski Eye Institute, was the study’s principal investigator and one of the world’s leading experts in population-based eye disease.

“This study sounds a clarion call for all eye care providers to be aware of the prevalence of wet AMD in those of Chinese ancestry and to provide the available treatments such as injections and laser therapies,” said Dr. Varma.
“And while not as prevalent as we see in the Latino community, we also need to be aware of addressing those Chinese Americans with diabetes to prevent DR and the onset of significant visual impairment.”

Dr. Varma added that the treatments for wet AMD are aimed at blocking the growth of new abnormal blood vessels in the eye and are widely available as opposed to the lack of therapy options for dry AMD, a diagnosis that is typically treated through health lifestyle changes.

“The study gives us unprecedented insights into the burden of eye disorders among this fast growing racial group in the United States. The findings will help inform preventive screening strategies and guide health-care resource planning,” said Maryann Redford, DDS, MPH, a program director for Collaborative Clinical Research at the National Eye Institute.

The CHES study involved more than 4,500 Chinese Americans age 50 or older living in Monterey Park, Calif. Almost all (98 percent) of the study participants were first-generation immigrants. The participants underwent comprehensive eye exams and interviews to assess risk factors for AMD and DR, including lifestyle factors such as smoking and daily diet. Photographs of the inside of the eyes were taken to also detect signs of these eye diseases.

 ASCRS Forms Research Council
The American Society of Cataract and Refractive Surgery recently announced the formation of the ASCRS Research Council, an internal department that will collaborate with ASCRS members and partners on research trials aimed toward improving patient care and quality of life.

The Research Council will be chaired by Douglas Rhee, MD, chair of the Case Western Reserve Department of Ophthalmology and Visual Sciences. “We recognize that some of the really important questions in clinical medicine will need extensive collaboration to answer,” said Dr. Rhee. “ASCRS is a leading organization in ophthalmology that is well-positioned to coordinate a multilateral effort between its academic and community membership and corporate and federal partners to investigate these immediately relevant clinical questions with scientific rigor.”

The council’s first study, which will examine the effects of enzymes/detergents on the anterior segment of the eye, is currently funded and underway. Led by Nick Mamalis, MD, director of the Intermountain Ocular Research Center in Salt Lake City, the study will explore whether enzymatic detergents used in cleaning ophthalmic surgical instruments can cause toxic anterior segment syndrome-like responses in a rabbit model. “Inspectors from the Centers for Medicare & Medicaid Services often require surgery centers or hospitals to strictly follow manufacturer’s directions for use in the cleaning and sterilization of surgical instruments that specify the use of enzymes/detergents,” said Dr. Mamalis, editor of the Journal of Cataract & Refractive Surgery. “We are very concerned that any residues of these materials on intraocular instruments may lead to TASS. It is important to study carefully the possible toxic effects of enzymes/detergents on the anterior segment of the eye in this animal model.”

The ability to engage with nearly 9,000 ASCRS-member ophthalmologists in the United States and abroad offers the research council a substantial advantage in the design and undertaking of future studies. “With access to thousands of domestic and international members, we have the numbers and geographical distribution to explore meaningful questions in a way that will ultimately benefit the patient,” said Kerry Solomon, MD, council member and incoming ASCRS president.

Study topics will be considered and vetted by the ASCRS Research Council, and all research will adhere to the strictest scientific rigor. “We understand the importance of proper study design, data collection and review,” said Dr. Rhee. “Our goal is to produce relevant, useful data that can directly influence ophthalmic practice and patient care.”
Researchers Devise ‘Mini-Retinas’
Stem cell science has progressed so that researchers can now share recipes for making human retinas. The first protocols enabled the generation of retinal cells in laboratory plates and more recently as complex tissue in the form of tiny eye-like cups. Researchers in Germany now have another efficient way to make 3-D retina organoids, which mimic the organ’s tissue organization, from mouse or human stem cells. Their version of “mini-retinas,” published online on March 31 by Stem Cell Reports, offers new perspectives on retina growth, injury and repair.

“The goal isn’t just to make the closest thing next to a real retina, but also to possibly harness the flexibility of the system to create more diverse ways of studying retina tissue,” says senior author Mike Karl of the German Center for Neurodegenerative Diseases. “We need to respect that each protocol is a new beast with different tastes, wrappings and purposes.”

Stem cell technologies have the potential to develop therapies for the treatment of diseases such as age-related blindness, and as clinical researchers work to apply the cells into new therapies, stem cell biologists such as Dr. Karl have been working to understand the regeneration of neurons from lower vertebrates to humans, which can aid regenerative medicine in more indirect ways.

For example, the 3-D retinal organoids developed in Dr. Karl’s lab (an effort led by first author Manuela Völkner) efficiently replicate the formation of the retina. This specifically includes the light-detecting cone cells, which now can be produced in high quantities in their mini-retinas. Cone photoreceptors, which are responsible for high acuity and color vision, are the most precious retinal cell type with regard to potential future cell replacement therapies in patients affected by retinal degeneration.

Dr. Karl and colleagues’ comparative studies on pluripotent stem cell-derived human and mouse retina organoids and mouse retina in vivo support the power of the new organoid protocol. “Tissue heterogeneity is a major challenge in organoid systems, and here our work provides new insight, which will help to develop specific organoid-based models, specifically to reliably study retinal disease mechanisms,” says Dr. Karl.

“Even with our new additions to existing organoid systems, we have not yet reached that tipping point of robustness that we need for people without the expertise to grow these models,” says Dr. Karl. “By working out the details, we also hope to help those who are not developmentally or stem cell-minded to just go and study what they want.”

The Karl Lab’s change to the mini-retina protocol involves cutting a retina organoid grown from stem cells into three pieces at an early stage of eye development. Each of these pieces, which look like little half moons, eventually grows into the full suite of cells found in the retina, thereby increasing the yield of retinal organoids up to fourfold compared to previous protocols. A trisection also spurs the surviving organoids to grow to reach sizes similar to uncut organoids. These mini-retinas swim around in the dish and because they’re not attached to a surface, better reflect the structure of retinal tissue during development.

The next objective is to make his 3-D “mini-retinas” even more complex, perhaps by bringing in blood vessels, as well as to use the organoids to study regeneration and the function of different neural cell types—specifically, from the human retina.

Preventing Neuropathy in KPro Cases
Researchers from Massachusetts Eye and Ear/Harvard Medical School have identified inflammatory factors that cause optic neuropathy following implantation of a keratoprosthesis —similar to what glaucoma patients experience, without the rise of pressure in the eye—and have shown that blocking one of those factors, tumor necrosis factor alpha, successfully halts the development of optic nerve damage in a mouse model. Their findings, published online in Investigative Ophthalmology and Visual Science, shed light on the underlying process responsible for optic neuropathy in KPro patients and also suggest a new pathway for preventing optic nerve damage in patients who receive the KPro implant.

“We used a mouse model of the KPro to, first of all, identify the inflammatory factors that cause damage to the eye, and then we also quantified the amount of nerve cell death in the back of the eye that mediates the optic neuropathy, and, lastly, we looked at blocking these factors with antibodies,” said Reza Dana, MD, MSc, MPH, director of the Cornea and Refractive Surgery Service at Massachusetts Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School. “We found that the KPro leads to high levels of TNFa, and that by blocking TNFa, we can prevent the nerve damage.”

With more than 1,000 KPro surgeries performed annually, and with new technologies being developed to increase the number of patients who may benefit, the KPro is a clear, plastic artificial cornea often used to replace diseased corneas in patients prone to rejecting biological tissues. The vast majority of KPro recipients report good vision initially, and then later experience a progression of optic neuropathy.

To better understand these responses in the eyes of KPro recipients, the researchers studied the effects of keratoprosthesis implantation in an animal model. They found that the mice can develop damage to the optic nerve despite normal pressure in the eye following KPro surgery and identified TNFa and IL-1 as inflammatory factors involved in this process, with high levels of TNFa mediating the damage to the optic nerve. The findings represent the first proof of concept regarding the role of TNFa as a result of keratoprosthesis surgery damaging the optic nerve.

“Now we have a much more mechanistic understanding of the mediator behind this clinical presentation,” Dr. Dana said. “Future studies are needed to prove that TNFa blocking can be therapeutic in humans, but in the meantime, this new knowledge clarifies the pathway to cell death of the optic nerve following KPro surgery.”  REVIEW