A collaborative biomedical engineering team from Bascom Palmer Eye Institute and Florida International University has developed what it calls a breakthrough retinal imaging technology that could help clinicians diagnose and assess the extent of vision loss in patients with a wide range of conditions.

After three years of work, the Bascom Palmer and FIU researchers successfully tested the first visible-light optical coherence tomography (VIS-OCT) technology for imaging rhodopsin, the light-sensing molecule contained in the retinal photoreceptors that convert light signals to neuronal signals sent to the brain.

Shuliang Jiao, PhD, an associate professor in the department of biomedical engineering at FIU and a Bascom Palmer alumnus, led the project. He designed and built the first VIS-OCT capable of imaging rhodopsin, and is the senior author of an article describing the novel VIS-OCT technology, “Depth-resolved rhodopsin molecular contrast imaging for functional assessment of photoreceptors,” published recently in Scientific Reports. The research was supported by grants from the National Institutes of Health.

Tan Liu, PhD, a postdoctoral associate in the FIU biomedical engineering program, was first author of the paper. Co-authors were Bascom Palmer professors of ophthalmology Rong Wen, MD, PhD, and Byron L. Lam, MD, the Robert Z. and Nancy J. Greene Chair in Ophthalmology; and Carmen A. Puliafito, MD, MBA, dean of the Keck School of Medicine of the University of Southern California. Dr. Puliafito was one of the pioneers in the development of OCT.

“OCT has been used extensively in ophthalmology clinics,” said Dr. Jiao. “Our work shows the new technology can be used to construct an accurate map showing the distribution of rhodopsin—a functional biomarker of the rod photoreceptors in the retina. We now are working on making this imaging equipment more patient-friendly to move it into the clinical setting.”

Dr. Jiao added that the VIS-OCT-created map could help determine the effectiveness of treatments in retinal disorders that affect the photoreceptors. For example, the progressive loss of photoreceptors in patients with hereditary retinal degeneration can be objectively measured and documented for clinical care and evaluation of treatments.

“This technology can be used to monitor disease progression for retinitis pigmentosa, age-related macular degeneration and other retinal diseases,” said Dr. Lam, a physician-scientist who specializes in photoreceptor degeneration. “It can also be used to objectively measure the outcomes for treatments and clinical trials of new therapies,” he added. Dr. Wen, a photoreceptor cell biologist, believes VIS-OCT technology will also be useful to study future photoreceptor regeneration, including transplant stem cell-derived photoreceptors, gene therapies, neuroprotection therapies using neurotrophic factors and other neuroprotective agents.

“The rapid development in regenerative medicine to restore vision has raised a hope that regeneration of photoreceptors and restoration of photoreceptor function will become reality in the near future,” he said. “When the time comes, this technology will be used to see whether the new photoreceptors are functional.”

This work started three years ago when Drs. Jiao, Wen and Lam were seeking an objective way to measure the function of photoreceptors in patients. The prototype rhodopsin VIS-OCT is an important step toward clinical application of the new technology.

Outdoor Activity Combats Myopia In Young Children
The addition of a
daily outdoor activity class at school for three years for children in Guangzhou, China, resulted in a reduction in the rate of myopia, according to a study in the September 15 issue of JAMA.

Myopia has reached epidemic levels in young adults in some urban areas of East and Southeast Asia. In these areas, 80 to 90 percent of high school graduates now have myopia. Myopia also appears to be increasing, more slowly, in populations of European and Middle Eastern origin. Currently, there is no effective intervention for preventing onset. Recent studies have suggested that time spent outdoors may prevent the development of myopia, according to background information in the article.

Mingguang He, MD, PhD, of Sun Yat-sen University, Guangzhou, and colleagues conducted a study in which children in grade one from 12 primary schools in Guangzhou (six intervention schools [n=952 students]; six control schools [n=951 students]), were assigned to one additional 40-minute class of outdoor activities, added to each school day, and parents were encouraged to engage their children in outdoor activities after school hours, especially during weekends and holidays (intervention schools); or children and parents continued their usual pattern of activity (control schools). The average age of the children was 6.6 years.

The three-year cumulative incidence rate of myopia was 30.4 percent (259 cases among 853 eligible participants) in the intervention group and 39.5 percent (287 cases among 726 eligible participants) in the control group. Cumulative change in spherical equivalent refraction (myopic shift) after three years was significantly less in the intervention group than in the control group.

“Our study achieved an absolute difference of 9.1 percent in the incidence rate of myopia, representing a 23 percent relative reduction in incident myopia after three years, which was less than the anticipated reduction,” the authors write. “However, this is clinically important because small children who develop myopia early are most likely to progress to high myopia, which increases the risk of pathological myopia. Thus a delay in the onset of myopia in young children, who tend to have a higher rate of progression, could provide disproportionate long-term eye health benefits. Further studies are needed to assess long-term follow-up of these children and the generalizability of these findings.”

DR Screenings For Kids May Be Delayed
A new study has
found that the occurrence of advanced forms of a diabetic eye disease remains low among children living with diabetes, regardless of how long they have had the disease or their ability to keep blood sugar levels controlled. Researchers are therefore recommending that most children with type 1 diabetes delay annual diabetic retinopathy screenings until age 15, or five years after their diabetes diagnosis, whichever occurs later. Their findings were published online in Ophthalmology.

It is well-established that early detection and timely treatment of diabetic retinopathy reduces vision loss in adults, and some physician organizations recommend screening children for diabetic retinopathy annually starting at an early age—after age 9, or from three to five years after diagnosis. However, the value of screening children has not been clearly documented and the prevalence of severe diabetic retinopathy among the young has been unclear.

Researchers based at the Children’s Hospital of Philadelphia and the Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania began to question current diabetic retinopathy screening guidelines for children. They were concerned that these annual exams may create an excessive financial and logistical burden for families and the health care system.

The researchers conducted a retrospective study of 370 children under age 18 with type 1 and type 2 diabetes. Some of the study participants had blood sugar levels three times that of a person without diabetes. All had received at least one diabetic eye disease screening exam between 2009 and 2013, but none were found to have diabetic retinopathy.

The researchers then examined the data that led to the current screening guidelines. They discovered that previous studies reported a diabetic retinopathy prevalence rate between 0 and 28 percent among children studied, but the majority of the cases were very mild and thus would not qualify for treatment. They also found that the youngest person reported to have severe diabetic retinopathy was between 15 and 19 years old, and five to six years was the shortest reported duration of having diabetes before developing severe diabetic retinopathy.

In light of the available evidence, the researchers recommend that screenings for children with type 1 diabetes could begin at a later age than previously recommended.

“Many of our young patients with diabetes diligently come in every year for screenings that consistently show no sign of the disease,” said Gil Binenbaum, MD, MSCE, co-author of the study and attending surgeon in the ophthalmology division at Children’s Hospital. “Of course, that’s good news for them, and it is very important to have annual eye exams once the risk of vision loss develops. But, is it worth the burden on the family and the health-care system if evidence shows that diabetic retinopathy doesn’t reach a treatable stage until years later?”

Researchers say exceptions should be made for children with type 2 diabetes and those identified by their endocrinologists as having high risk for diabetic complications. They should start diabetic retinopathy screenings upon diagnosis, similar to adults with type 2 diabetes, since many type 2 diabetes patients live with the disease uncontrolled before they are diagnosed. Because there is limited published researched on children with type 2 diabetes and diabetic retinopathy, researchers noted that a retinopathy screening examination upon diagnosis is their recommendation for those patients until additional data showing otherwise is available.

The American Academy of Ophthalmology currently recommends that people with type 1 diabetes have annual screenings for diabetic retinopathy beginning five years after the onset of their disease, and that those with type 2 diabetes should have an examination at the time of diagnosis and at least once a year thereafter.

Shiley Group: New Target to Prevent & Treat Glaucoma
Scientists at the University
of California, San Diego, School of Medicine have elucidated a genetic interaction that may prove key to the development and progression of glaucoma.

The findings, published online in Molecular Cell, suggest a new therapeutic target for treating the disease.

Primary open-angle glaucoma affects more than 3 million Americans, primarily after the age of 50, with intraocular pressure and age being the leading risk factors. Genetics also plays a role. Recent genome-wide association studies have identified two genes—SIX1-SIX6 and p16INK4a—as strongly associated with POAG. SIX6 is required for proper eye development. p16INK4a irreversibly arrests cell growth, or senescence.

Principal investigator Kang Zhang, MD, PhD, professor of ophthalmology and chief of ophthalmic genetics at Shiley Eye Institute at UC San Diego Health, and colleagues report that some variants of SIX6 boost expression of p16INK4a, which in turn accelerates senescence and death of retinal ganglion cells. “We also show that high IOP in glaucoma increases expression of p16INK4a, making it a key integrator of inherent genetic and environmental risk factors that can result in glaucoma,” said Dr. Zhang.

The findings suggest that inhibiting p16INK4a could offer a new therapeutic approach for glaucoma, currently treated by IOP-lowering drugs. “Although lowering IOP can slow worsening of the disease, it does not stop it and prevent further cell death or possible blindness,” said co-author Robert N. Weinreb, MD, distinguished professor of ophthalmology and director of Shiley Eye Institute.

The authors note that earlier studies in mouse models have shown that selective elimination of p16INK4a-positive senescent cells can prevent or delay age-related tissue deterioration.

According to the UC San Diego team, the next step is to conduct preclinical studies to assess the efficacy and safety of antisense oligonucleotides—strands of synthesized DNA or RNA that can prevent transfer of genetic information—which might inhibit p16INK4a expression and prevent worsening of glaucoma. “If they are effective, we may contemplate a human clinical trial in the future,” Dr. Zhang said.  REVIEW