In all likelihood, the invention and commercialization of the prostaglandin analog therapeutic class has been one of the greatest advances in glaucoma care over the past century.
The prostaglandin analogs are dosed once daily, work both day and night, are unsurpassed in terms of single agent efficacy, and have essentially no significant systemic side effects, a perfect fit for the ophthalmologist and patient.
But prostaglandin analogs are not for everyone. The Achilles' heel of the prostaglandin analog class has been, and remains, conjunctival hyperemia. While this side effect is not harmful to the eye, it presents cosmetic issues for many patients and can mimic infection and inflammation (decreasing the value of these agents in the postoperative period). The warning label for the PGA class indicates that these agents may not be ideal for patients with uveitis, herpetic keratitis, or macular edema. While paucity of clinical publications describing these side effects would indicate that they are relatively rare, PGAs are generally avoided in patients with these conditions.
Other cosmetic considerations with the prostaglandin analog class can be significant for some patients, including eyelid hyperemia, eyelash growth, periorbitopathy, and eyelid pigmentation, not to mention the potential for iris color change. The side effects are more noticeable if the treatment is unilateral, and occur more commonly in patients who have these features (e.g., eyelid pigmentation or long, dark eyelashes) at baseline.
What is one to do when PGA therapy needs to be replaced? The temptation is to try to cling to once-a-day dosing and to utilize a beta blocker such as timolol. However, single agent beta blocker therapy is less efficacious than most members of the prostaglandin analog class.
If the patient’s glaucoma severity puts them at significant risk for functional impairment due to disease progression, a fixed-combination agent would be a better choice. These agents generally contain aqueous suppressants, so the alternative mechanism may be beneficial for PGA nonresponders. While there is no hard data to back this up, the overwhelming majority of glaucoma surgeons would choose a fixed-combination agent over a prostaglandin analog as the first medication to restart after a partially successful filtration surgery. The range of intraocular pressure lowering for fixed-combination therapy is generally in line with the prostaglandin analog class. Generally, fixed-combination medications fit in where the PGA class fails, with lower rates of hyperemia, better surface tolerability, and no induced cosmetic periocular changes, apart from the occasional allergy.
Not surprisingly, the use of fix combination therapies for glaucoma has been growing in recent years. This therapeutic approach likely demonstrates a growing need for straightforward yet efficacious therapies as an alternative to or in addition to the PGA class.
Dr. Nathan M. Radcliffe is the director of the glaucoma service and a clinical assistant professor at
New York Univeristy Langone Ophthalmology Associates and is a cataract and glaucoma surgeon at
the New York Eye Surgery Center.