This activity is supported by an unrestricted grant from Bausch + Lomb.
This activity is supported by an unrestricted grant from Bausch + Lomb.
Optometry is a profession dedicated to preserving and enhancing vision. Therefore, there may be no higher calling for optometrists than to prevent vision compromise or loss in people who are at risk for, or who have glaucoma.
As reported in the November 2017 issue of Primary Care Optometry News, American Optometric Association President Christopher J. Quinn, OD, addressed the Optometric Glaucoma Society during its meeting held just before the 2017 American Academy of Optometry meeting in Chicago, and made quite clear that “Glaucoma is a serious public health problem in this country. Optometry is the solution … Glaucoma is a disease that this profession should own.”
Robert D. Fechtner, MD, concurred, stating “There’s no way to take care of this epidemic, except through partnership. The optometric portion of care is the largest portion."
Although modulating IOP (no medications are available yet to “treat" glaucoma), is reasonably straightforward, the greatest challenge is in making the diagnosis. This challenge includes not missing glaucomatous optic neuropathy in patients presenting with IOPs in the normal range.
Historically, IOP has been the rudder steering further workup. This is a grossly inadequate algorithmic approach, because a large subset of glaucoma or glaucoma suspect patients do not present with elevated IOP. Medicolegal surveillance clearly shows that, by far, the most common reason doctors of optometry are successfully sued is for failure to diagnose. Virtually 100% of such cases could be avoided if greater attention is paid to the nuanced study of the optic nerve head.
Complicating this situation is the realization that many people experience their highest IOP outside of traditional office hours. Therefore technology, such as the Icare HOME tonometer may facilitate our ability to uncover missed ocular hypertension patients.
Rather than the IOP being the finding that causes us to pursue a comprehensive glaucoma evaluation, our diagnostic approach needs to quickly shift to an attentive study of the optic nerve head. This is best accomplished with a magnified stereoscopic evaluation of this tissue.
Considering that the only known approach to halting or slowing optic nerve atrophy is reducing IOP, we want to focus on the issue of critical medical management. As is reasonably well understood, the physiologic internal ocular plumbing is quite simple: aqueous humor is produced by the nonpigmented epithelium of the ciliary body and drained through the trabecular meshwork and, to a lesser extent, the uveoscleral tissue. It is also understood that the weak links in aqueous flow are the outflow pathways. Thus, the primary focus of pharmacologic intervention is enhancing aqueous outflow.
However, two commonly used and effective drug classes — nonselective beta-adrenergic receptor blockers and carbonic anhydrase inhibitors — reduce aqueous production as their mode of action. Alpha-adrenergic receptor agonists have somewhat dual mechanisms of action by both inhibiting aqueous production and enhancing unconventional (uveoscleral) outflow.
Pilocarpine, a parasympathomimetic agent, now minimally used because of the largely aggravating ocular adverse effects, nicely enhances conventional (trabecular) outflow by stimulating the contraction of the longitudinal muscles of the ciliary body, thus enlarging the trabecular pores.
The most efficacious class of IOP-lowering medicines, the prostaglandins, stimulates extracellular matrix metalloproteinases in the uveoscleral tissues to make them more porous, thus enhancing aqueous outflow through these unconventional (uveoscleral) tissues.
For historical perspective, the modern era of glaucoma medicines began in 1978, with the advent of timolol (Figure 16). Initially, timolol was administered twice daily, but further research found that once-daily administration shortly after awakening worked as well or nearly as well as twice-daily administration.
Figure 16. Timolol ophthalmic solution.
It was nearly 2 more decades until the prostaglandins (beginning with Xalatan [latanoprost, Pfizer]) entered the market, which relegated timolol (and numerous other beta-blockers) largely to second-tier status. Latanoprost had exclusive status until other prostaglandin competitors entered the market a few years later.
It has since been another 2 decades, and now a new generation of a nitric oxide-donating prostaglandin is available for the care of our patients. The options for medical reduction in human IOP are now more numerous than ever and require us to gain a keener understanding of how all these drugs best play a role in the enduring care of our patients.
Let us take a more detailed look at each of these drug classes and develop a more fine-tuned appreciation for their strengths and weaknesses. We will start with the most commonly prescribed class, the prostaglandins. As we shared above, when prostaglandins entered the market in the mid-1990s, this drug class was the single most beneficial contribution to our modest glaucoma armamentarium that had been made in decades. Xalatan then, and generic latanoprost now, is the most commonly prescribed prostaglandin. Despite containing 0.02% benzalkonium chloride (BAK), latanoprost is the most tolerable medication of this class. Its new mechanism of action of enhancing uveoscleral outflow by potentiating resident extracellular matrix metalloproteinases within the uveosclera, thus making the tissue more porous, was revolutionary.
Generally, traditional prostaglandins reduce IOP by about 30% and have mild conjunctival hyperemia as the most common adverse effect. In phase 3 studies on prostaglandins, two things were learned:
Although prostaglandins are best used in the evenings, compliance is enhanced when patients can most consistently remember to instill them. Therefore, if a patient reports that he or she takes all medications with breakfast, then the prostaglandin can also be administered at this habituated time. These medicines work almost as efficiently when taken in the morning, so if this is the time of greatest likelihood for compliance, then morning dosing is fine.
Although uncommon, patients with hazel-colored irides can sustain generalized darkening of these tissues, which is usually only a concern when treating patients with unilateral glaucoma. Even more uncommon is periorbitopathy (Figure 17), which represents a decrease in the population of adipose tissues in the orbit, thus causing a deepening of the superior sulcus, and occasionally an enophthalmic appearance. When reflected against their sight-saving benefits, these adverse effects are relatively inconsequential.
Figure 17. This patient developed periorbitopathy after a few years on a prostaglandin.
Some years later, Travatan Z (travoprost, Alcon), which is BAK-free, and Lumigan (bimatoprost, Allergan) entered the market, followed by tafluprost (Zioptan, Akorn), which is the only preservative-free prostaglandin, a few years later (Figure 18). Like latanoprost, tafluprost is stored under refrigeration until dispensed to the patient.
Figure 18. Latanprost, travoprost (Travatan Z), bimatoprost (Lumigan) and tafluprost (Zioptan) ophthalmic solutions.
The prostaglandin market had a quiescent period for several years until November 2017, when Vyzulta (latanoprostene bunod 0.024%, Bausch + Lomb) broke the silence (Figure 19).
Figure 19. Latanoprostene bunod (Vyzulta).
This totally new, single-entity, dual-action upgrade to the first-generation prostaglandins raises the efficacy to a higher level. The latanoprostene bunod molecule is cleaved into two distinct entities by resident esterases in the anterior eye tissues. Two compounds result from this cleaving: latanoprost acid (the metabolically active form of latanoprost) and butanediol mononitrate, which is subsequently metabolized into nitric oxide, which is thought to relax the smooth muscles of the trabecular meshwork, thereby enhancing conventional (trabecular) outflow. In phase 2 studies, latanoprostene bunod reduced IOP an additional 1.23 mm Hg beyond that of first-generation latanoprost.
The FDA-approved package insert states that Vyzulta is indicated for “the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension.” Note that it does not say for “elevated” intraocular pressure but simply for “reduction of intraocular pressure,” thus acknowledging (planned or unplanned) that many patients have normal-pressure glaucoma or are glaucoma suspects. The package insert further shares that, “the IOP-lowering effect of Vyzulta is up to 7 to 9 mm Hg.”
Like latanoprost, Vyzulta is stored under refrigeration long-term at the pharmacy; however, once dispensed to the patient, it can be kept at room temperature for several weeks. Vyzulta is approved for once-daily use (preferably instilled in the evening). This medication is approved for persons ages 16 and older. Mild conjunctival hyperemia was observed in about 6% of study patients. Vyzulta is preserved with 0.02% BAK (just like latanoprost).
We have been using Vyzulta in these four scenarios:
Preventing Vision Loss: Importance of Optometry
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