If you’ve been to the eye doctor recently, chances are good that your visit did not include any kind of test that had to be run in a clinical laboratory. Most rudimentary eye tests, such as for glaucoma, can be performed right in the doctor’s office. But pathology — molecular pathology, in particular — is increasingly important for good eye care, says Dr Anita Chan, an ophthalmologist and trained pathologist at the Singapore National Eye Centre (SNEC), a division of the SingHealth cluster in the Singapore public health system.

Dr Chan began her career as an ophthalmologist, but recently took the time to be trained as a pathologist. This dual-track career has made her the first ophthalmologist-pathologist in Singapore. She currently serves as Head & Senior Consultant in the Ocular Inflammation & Immunology Department and Clinical Director of the Ophthalmic Pathology Department at SNEC, as well as Head of the Translational Ophthalmic Pathology Platform at the Singapore Eye Research Institute. Her ophthalmic pathology lab is one of the first of its kind in the Asia Pacific region.

Dr Chan aims to help her patients, and the field as a whole, by developing and implementing valuable new tests for eye care. But she also hopes that other pathologists will take an interest in ophthalmology so some of the more sophisticated, centralised labs in Southeast Asia could begin offering molecular tests for ocular conditions.

Because these tests must be performed on extremely low-volume samples, many pathology laboratories cannot run them simply because of limited workflows in place. That leaves ophthalmologists in Southeast Asia in a bad position when handling ocular cancers, such as eye melanomas, as they must either send these samples to Australia or the United States at higher costs, or not offer important tests to their patients.

Pathology tests for ophthalmology patients

One reason for the rising interest in molecular tests for eye conditions is a relatively recent development in ophthalmology: the ability to safely and routinely take samples of intraocular fluid from patients. Now that this can be done in eye centres all around the world, the procedure has opened the doors for a broad array of new test options.

For example, PCR testing can now be performed to diagnose eye infections. Since eye samples tend to be too small to culture using traditional methods, ophthalmic pathologists have focused on established techniques such as PCR for ocular use. These PCR tests, which can be combined or multiplexed, reduce the sample volume required per test. Such techniques have made a huge difference in the ability to diagnose viral, bacterial or parasitic eye infections, which are common throughout Asia.

“We use the same downstream testing methods as any lab,” Dr Chan told Lab Insights. “Any lab can do this as long as they’re not intimidated by the sample volume.”

On the horizon: single-cell testing

The advent of single-cell profiling technologies has been a breakthrough for ocular conditions. Dr Chan recently developed a sequencing-based, single-cell test for intraocular lymphoma. The test was validated with residual clinical samples that had already been processed by the pathology lab; there was so little sample remaining that most cases yielded just 10 to 20 cells, she said. But that’s enough to search for genetic markers commonly seen in this particular cancer.

“It’s mindboggling to realize that we only need 10 cells,” she said. This form of cancer is especially hard to diagnose with conventional techniques, but the single-cell method should improve the diagnosis rate and lead to more targeted therapies for patients.

The test, currently used for research only in Dr Chan’s lab, is expected to be developed into a diagnostic assay that any qualified clinical lab could use. Already, the team has vetted key factors needed for commercial use, such as which fixative to use with fluid samples for best performance when shipped to a central laboratory (they chose the same fixative used for liquid Pap smears). Already, Dr Chan has worked with samples sent from Myanmar and Vietnam, in addition to the original samples collected in Singapore.

How to get involved

Any clinical laboratory can begin offering molecular pathology tests for ocular samples. If you’re interested, here’s how to get started.

1. Team up with an ophthalmologist. You don’t need to be an ophthalmologist-pathologist like Dr Chan, but “you really need to understand the clinical aspect,” she said. Talk to an eye doctor in your health system to understand how molecular tests could best contribute to his or her practice, or check out ophthalmologic literature to get up to speed on the tests they often use.

2. Embrace small samples. “Small samples are a big problem,” Dr Chan said. “Labs tend to be hesitant to work with such small volumes.” But as centralised laboratories adopt single-cell technologies for other applications, they may find that those sample prep workflows will also make it feasible to work with ocular samples. Even smaller labs committed to providing ocular tests can implement the techniques needed for processing low-volume samples.

3. Train at other labs. Labs such as Dr Chan’s are happy to host pathologists from other facilities and offer training on how to work with small samples. If that’s not an option, Dr Chan regularly visits labs in other countries to help teams across Asia get up and running with ocular testing.

“It’s important that we set up the same capacity for ophthalmologic testing in Asia that we see in Europe or the U.S.,” Dr Chan said. “This would allow us to develop tests that cater to the needs of an Asian population in terms of genetic differences as well as disease spectrum.”