Glaucoma experiences transformative growth as a subspecialty

By Vanessa Caceres, Reviewed by Kuldev Singh, MD, MPH

Glaucoma is experiencing a renaissance with promise in a greater number of therapies, exciting research, and the brightest talent being attracted to the profession, according to Kuldev Singh, MD, MPH.

Dr. Singh made an analogy to the European Renaissance-a period of intellectual enlightenment from the 14^th century to the 17^th century-to glaucoma’s current renaissance. Before the European Renaissance, the Middle Ages represented a bleak period in history when wars, famine, and the lack of progress by those with power hindered the advancement of the arts and sciences.

Dr. Singh is professor of ophthalmology and director, Glaucoma Service, Stanford University School of Medicine, Palo Alto, CA.

As was the case with literature, art, and physics, the renaissance in ophthalmology arrived for different subspecialties at different times. The introduction of innovations, such as intraocular lenses and phacoemulsification, initially were met with skepticism, but ultimately prevailed due to the conviction of the innovators.

While Dr. Singh acknowledged the advances in perimetry and imaging as critical to the “Glaucoma Renaissance,” he focused on glaucoma therapeutics. The introduction of new pharmacologic agents, the evolution of cataract surgery as a glaucoma procedure, refinements in trabeculectomy, and the introduction of adjunctive antimetabolite drugs contributed to improved patient care. These advances were followed a few years later by the breakthrough innovation of micro-invasive glaucoma surgery (MIGS), according to Dr. Singh.

Glaucoma renaissance men

Dr. Singh pointed out that as with the European Renaissance, a few individuals were critical to the field moving forward. He particularly praised the work of two, now-deceased clinician scientists: Carl Camras, MD, and Thom Zimmerman, MD, as pioneers in bringing about the Glaucoma Renaissance.

Dr. Camras performed work that ultimately led to the development of prostaglandin analogs–although he had to partner with a European-based company because of the lack of initial interest from corporate partners in the United States.

Dr. Zimmerman, besides giving the specialty timolol as a treatment to lower intraocular pressure (IOP), was among the first clinicians to pose the idea of a safer, non-penetrating operation for glaucoma–deep sclerectomy. This was the stimulus for further research that influenced the MIGS revolution, Dr. Singh said.

While for most of the 20^th century, glaucoma was considered a field with few safe and effective surgical treatment options, today, there are up to 17 distinct ways to lower IOP without medications, said Dr. Singh.

Recent drug approvals

Although most recent glaucoma innovations have been in the surgical sector, there are novel classes, particularly the rho kinase inhibitors, that will be available soon. There are also numerous drug-delivery vehicles under development, but progress in this space has been slower than expected.

Another force contributing to glaucoma’s renaissance has been the tremendous ophthalmic leadership at the FDA, Dr. Singh said. Malvina Eydelman, MD, director, Division of Ophthalmic and Ear, Nose and Throat Devices, and Wiley Chambers, MD, deputy director, Division of Transplant & Ophthalmology Products at the FDA’s Center for Drug Evaluation and Research, have provided insight on what is required to  expedite innovation. Both have been active participants in major ophthalmic conferences as well as other initiatives. Dr. Singh added.

Dr. Singh provided the example of a workshop prior to the 2014 American Glaucoma Society meeting. During that workshop, glaucoma physicians discussed guidelines for MIGS clinical trials with Dr. Eydelman’s team at the Center for Devices and Radiologic Health (CDER). The following year, the FDA published a leap-frog guidance document to provide a roadmap for innovators in the MIGS field.

The collaboration also funded a bicoastal initiative through the Centers for Excellence in Regulatory Science and Innovation (CERSI) at the Johns Hopkins University and the University of California, San Francisco/Stanford University to develop patient preference and patient-related outcome tools that allow patients to be heard in the innovation process.

Reviewing compliance issues

Dr. Singh also addressed areas where further work was needed to improve the care of glaucoma patients, including medication compliance as well as compliance with appointments–the latter being a surrogate for disease surveillance.

Patients getting their eyes checked regularly is as important as continuing to take their  medications, according to data presented by Dr. Singh and colleagues, including Shan Lin, MD, at San Francisco General Hospital.

“Only 25% to 50% of people in the United States who have glaucoma know that they have it,” Dr. Singh said. “Many who are under care are noncompliant.”

While only a small percentage of affected individuals go blind from glaucoma, it is not possible to prospectively separate those who will do well from those who will do poorly. IOP is clearly a risk factor and lowering IOP helps, but there are patients with high IOP who do better than expected and others with low IOP who go blind from glaucomatous disease.

Regular follow-up is critical to distinguish the few who are destined to do poorly and need aggressive therapy from many others who are at lower risk of vision loss.

“There is a lot of ‘glaucoma light’ in the offices of ‘suburban’ practitioners, particularly in Caucasian populations,” Dr. Singh said. “Tertiary glaucoma providers, if not careful, can end up living in a bubble where they believe everyone with glaucoma needs very low IOP.”

Dr. Singh concluded by pointing out that many patients have a false sense of security about taking glaucoma medications if they think that good compliance means they don’t need to see an ophthalmologist on a regular basis.

“The data from San Francisco General suggests that showing up regularly for appointments is at least equally important,” Dr. Singh said. “Even patients who never miss their medications may continue to show disease progression and need more aggressive intervention, such as laser or surgical therapy. You can’t perform a trabeculectomy for a patient who needs it if they don’t show up.”

Kuldev Singh, MD, MPH

e. kuldev.singh@stanford.edu

This article was adapted from Dr. Singh’s American Glaucoma Society Subspecialty Day Lecture that he delivered during the Glaucoma Subspecialty Day, held prior to the 2017 American Academy of Ophthalmology meeting. Dr. Singh is a consultant for Aerie Pharmaceuticals, Alcon Laboratories, Glaukos, Ivantis, and other pharmaceutical companies.