Decade ahead to bring momentous advances in glaucoma care

By Cheryl Guttman Krader

The next 5 to 10 years will be a period of remarkable research discoveries for glaucoma and their translation into enhanced patient care, said Robert N. Weinreb, MD.

“Glaucoma research has a number of areas that will be transformative and will dramatically change our clinical practice,” said Dr. Weinreb, chairman of ophthalmology, director of the Shiley Eye Center and the Hamilton Glaucoma Center, University of California, San Diego.

Looking forward to what is next in glaucoma, Dr. Weinreb discussed improvements in risk-prediction and risk-modification strategies, increased knowledge of glaucoma pathophysiology, the advent of 24-hour IOP monitoring, and advanced technologies for structural and functional imaging.

A broadened understanding of glaucoma’s genetic associations is one of the first events on the horizon, and the information will be valuable in helping clinicians better determine an individual’s risk for becoming functionally impaired. To date, there is only limited information about genetic variations associated with glaucoma. However, it is expected that this will change with findings from ongoing studies, including research being funded by the National Eye Institute and others.

“Not all patients progress along the glaucoma continuum to the stage where they become functionally impaired,” Dr. Weinreb said. “In the future, we will incorporate findings from genetic analyses in our risk calculators to identify patients who are at highest risk for progression. Equipped with that information, we can best allocate limited resources for healthcare.”

Increased understanding of the mechanisms of glaucomatous optic nerve damage is also forthcoming, as multiple laboratories elucidate the role of the microcirculation, immune system, and the milieu of inflammatory cytokines associated with glaucoma. More complete articulation of the mechanisms of optic nerve damage will also provide a foundation for developing more effective glaucoma treatment, Dr. Weinreb added.

24-hour IOP monitoring

The advent of 24-hour, IOP-monitoring systems will transform glaucoma patient care in the near future because it will allow clinicians to better define target IOPs and to treat patients more effectively. One such device, a contact lens-based system (Triggerfish, Sensimed) that detects changes in corneal curvature as a surrogate for IOP, is currently available in Europe. Other implantable devices that measure IOP directly are in development (Implandata and AcuMEMS) and are in clinical trials.

“Today, we make management decisions based on a single IOP measurement taken during office hours, but the patient’s IOP may be different at other times during the day,” Dr. Weinreb pointed out. “With 24-hour, IOP monitoring, we can better understand the impact of IOP, and we will also be able to determine if our treatment target should be based on IOP peak, 24-hour mean, or fluctuation over 24 hours or a longer period.”

Dr. Weinreb said that over the next 5 to 10 years, devices will be available that adjust therapy based on continuous monitoring of IOP. “Such devices might synchronize drug release with peaks of IOP or open conduits to allow aqueous outflow,” he added.

Diagnostic technologies

According to Dr. Weinreb, use of diagnostic technologies for assessing features of individual retinal ganglion cells (RGCs), as well as the entire visual pathway, may also become part of clinical glaucoma practice within the next decade. Modalities, such as functional magnetic resonance imaging, are already being used in research studies investigating glaucoma-related damage, recognizing that glaucoma is not just an eye disease but a neurodegenerative condition affecting the brain as well.

Neuroprotective strategies are also on the horizon with cell-based strategies likely to be the earliest to become available. Dr. Weinreb noted that studies are underway evaluating the use of neurotrophic growth factor-releasing cells for rescuing damaged RGCs. Eventually, with the use of pluripotent stem cells induced from the patient’s own skin fibroblasts, optic nerve regeneration may become a reality.

On the topic of glaucoma risk factors, Dr. Weinreb looked ahead to more information about the role of cerebrospinal fluid pressure (CSF). He cited recent research that identified translamina cribosa pressure difference (IOP minus intracranial pressure) as a powerful predictor for glaucomatous damage in both high pressure and normal tension disease, and noted that the information raises interesting ideas about novel strategies for treating glaucoma based on modulating intracranial pressure.

Finally, Dr. Weinreb said ophthalmologists should expect new information about lifestyle modifications that can be beneficial for glaucoma.

“It is remarkable how few studies have been done on potentially modifiable risk factors like smoking, diet, obesity, and exercise,” he noted.  “Just like cardiologists do today, I predict that in the future, we will discuss with our patients smoking cessation, altering diet, losing weight, and increasing physical activity.”

Dr. Weinreb added that research conducted by his group and others show that reservatrol or other substances, such as coenzyme Q10, enhance mitochondrial function, and he speculated that these substances provided as supplements or in items such as red wine might enhance current glaucoma treatments.