In the medical management of patients with glaucoma, we are not short of options. In 2002, Realini and Fechtner published an article1 titled "56,000 ways to treat glaucoma." In the article they described the number of possible treatment regimens a given patient could be treated with from monotherapy to maximum therapy if one examines all of the possible combinations and concentrations. Amazingly, this number does not include fixed combinations or generic equivalents and of course we do have at least one new molecule available since that time.
Should we try our glaucoma patients on all 56,000 options before picking the treatment that is best for them? Purists will argue that we should indeed always adjust a medical regimen one medication at a time in order to understand the individual contribution of that agent from an efficacy and safety standpoint. While the reasoning is very sound, there are problems with this approach. To begin with, each agent tends to have its own unique side effect profile, and when faced with an adverse event, it is typically possible to determine the offending agent, even when multiple agents are initiated at the same time (for example, some agents are simply more likely to cause hyperemia than others). Furthermore, there is evidence that when several glaucoma medications are combined, the side effect profile is not always equal to (and may be better than) the sum of its parts.2 Furthermore, a series of investigations by Realini and others have convincingly demonstrated that there is enough noise and variability in a given pressure response to a medication that a single observation of pressure change after starting a medication may have limited value, as inter-visit IOP fluctuation is often large enough to mimic the effects of an eye drop.3,4
There are other downsides to adjusting medical regimen and one agent at a time. The patient may need to return more frequently which may have costs including time away from work, parking costs, and office co-pay. Furthermore, changing or adjusting agents may result in medication purchased by the patient being discarded prior to its completion and confusion regarding medication scheduling and usage.
On the other hand, FDA approved fixed combination medications have, by definition, been demonstrated to be more efficacious than either component by itself. Side effect profiles have either been shown to be simply additive, or slightly better than one might expect from adding the two individual components. Most importantly, using more efficacious agents routinely will on average result in better IOP control for a population of patients.
The reality of medicinal glaucoma management is that some patients will be controlled with medications and some will not. By being aggressive with IOP lowering initially (especially in higher-risk patients), the physician may be able to identify non-responders more quickly, and deliver the appropriate laser or incisional treatment earlier in the disease process.
1. Realini T, Fechtner RD. 56,000 ways to treat glaucoma. Ophthalmology. 2002;109:1955-6.
2. Realini T1, Barber L, Burton D. Frequency of asymmetric intraocular pressure fluctuations among patients with and without glaucoma. Ophthalmology. 2002;109:1367-71.
3. Higginbotham EJ, Feldman R, Stiles M, Dubiner H; Fixed Combination Investigative Group. Latanoprost and timolol combination therapy vs monotherapy: one-year randomized trial. Arch Ophthalmol. 2002;120:915-22.
4. Bhorade AM, Gordon MO, Wilson B, Weinreb RN, Kass MA; Ocular Hypertension Treatment Study Group. Variability of intraocular pressure measurements in observation participants in the ocular hypertension treatment study. Ophthalmology. 2009;116:717-24.
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.