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William C. Stewart, MD,
Jennifer S. Rhodes, BS,
and Jessica N. Leech, BS
Charleston, S.C. |
More than five years ago, latanoprost (Xalatan, Pharmacia) was introduced to reduce the intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension. Since then, the F2a prostaglandin has become the leading individual selling medicine for this disease. Last year, two new medications were released, bimatoprost (Lumigan, Allergan) and travoprost (Travatan, Alcon), which appear to have structural similarities to those of latanoprost.
A potentially important difference, however, in the molecular formula among these three medicines is that bimatoprost and travoprost both contain a double bond at the C13 – C14 position. This bond remains saturated in latanoprost. This may be important because, as Johan Stjernschantz noted during the development of latanoprost, the double-bond at this position tends to be associated with conjunctival hyperemia.1,2 Accordingly, in a recent double-masked, three-period crossover trial in healthy individuals, bimatoprost and travoprost demonstrated more conjunctival hyperemia than latanoprost.3 However, it is still unclear from a direct comparative study in patients with glaucoma whether differences in conjunctival hyperemia exist among these three medicines. Also unclear is what clinical significance conjunctival hyperemia has beyond a cosmetic defect.
To help further clarify this question, we developed a survey that evaluated the clinical appearance and significance of conjunctival hyperemia associated with latanoprost, bimatoprost and travoprost. Physicians were selected randomly from the American Academy of Ophthalmology membership book. The survey was faxed to a total of 505 physicians. If no response was obtained, the survey was faxed again one week later. Sixty-one (12 percent) surveys were returned. Not every physician answered every question.
Prescribing Habits
All respondents indicated they prescribed latanoprost in clinical practice while four physicians did not prescribe bimatoprost, and 13 did not prescribe travoprost. Beyond a perceived lack of experience with these new medications specific reasons for not prescribing the two newer medicines were red eyes with bimatoprost (n=2) and efficacy problems with travoprost (n=3).
Clinical Impact of Red Eye
The responding physicians observed conjunctival hyperemia in 11.3 percent (±15.2) of patients treated with latanoprost, 30.3 percent (±24.7) with bimatoprost and 22.6 percent (±23.3) with travoprost (P=0.001).* When present, the average severity of redness was: 1.5 (±0.6) for latanoprost; 2.5 (±0.8) for bimatoprost; and 2.1 (±0.8) for travoprost. (Grade 1=minimal, 2=mild, 3=moderate, 4=severe) (P=0.001).** Thirty-two of 61 responding physicians noted additional symptoms associated with red eye among all the medicines, including pain, dryness, tearing and photophobia. Statistical differences among groups for these symptoms were not found, except pain was greater with bimatoprost (P=0.02).
| Table 1. Reported Severity of Dry Eye |
|
Minimal |
Mild |
Moderate |
Severe |
| Xalatan |
31 |
23 |
3 |
0 |
| Travatan |
10 |
18 |
16 |
0 |
| Lumigan |
8 |
15 |
26 |
3 |
Further, many physicians also noted that the conjunctival hyperemia with these medicines was often associated with worsening of concomitant ocular conditions. There was no difference among the three medicines in the extent of aggravating dry eye or blepharitis, but physicians noted that bimatoprost caused more worsening of ocular allergy than latanoprost or travoprost (P=0.0094).**
Impact on Practice
Responding physicians indicated that they had received extra telephone calls from their patients due to conjunctival hyperemia in 3.2 percent (±4.2) of patients for latanoprost, 15.4 percent (±19.4) for bimatoprost, and 7.8 percent (±10.1) for travoprost (P=0.001).* Physicians had to schedule extra office visits because of conjunctival hyperemia in 2.5 percent (±4.3) of patients for latanoprost, 19.2 percent (±2.6) for bimatoprost, and 6.1 percent (±11.1) for travoprost (P=0.0005).* Further, there was a difference among the medicines in the percentage of patients who had to be discontinued because of conjunctival hyperemia. This occurred in 5.2 percent (±9.9) of patients for latanoprost, 18.7 percent (±26.3) for bimatoprost, and 12.3 percent (±19.2) for travoprost (P=0.001).*
This survey indicates that conjunctival hyperemia, both in incidence and severity, appears to be highest with bimatoprost and lowest with latanoprost, but may be noticed with all three prostaglandin-related medicines. Further, the conjunctival hyperemia may be associated with other symptoms including pain, dryness, tearing and photophobia. The pain appears worse with bimatoprost. In addition, worsening of other concomitant ocular diseases has been noticed with conjunctival hyperemia. The extent and the associated worsening of allergy were greatest with bimatoprost and least with latanoprost.
Conjunctival hyperemia may impact a clinical practice. Physicians in this survey experienced extra phone calls, office visits and the need to discontinue patients after prescribing latanoprost, bimatoprost or travoprost because of the conjunctival hyperemia. The impact on the practice, however, appeared greatest with bimatoprost and least with latanoprost.
Direct, quantitative, prospective comparative trials are needed to evaluate the clinical impact of conjunctival hyperemia in patients with primary open-angle glaucoma or ocular hypertension. In addition, clinical trials might help discern any real clinical or pharmacoeconomic impact from conjunctival hyperemia on the physician’s practice related to latanoprost, bimatoprost and travoprost.
(* = ANOVA test. ** = Chi square test)
Dr. Stewart is director of medical affairs at Pharmaceutical Research Corp. and a clinical professor of ophthalmology at the University of South Carolina School of Medicine. Ms. Leech is the research manager and Ms. Rhodes, a research assistant at PRC. The authors have no financial interest in the products and received no support for the study, though Dr. Stewart receives research grants from all three manufacturers.
1. Stjernschantz JW. From PGF2_-Isopropyl Ester to Latanoprost: A review of the development of Xalatan. The proctor lecture. Invest Ophthalmol Vis Sci 2001;42:1134-1145.
2. Stjernschantz JW. Phenyl substituted prostaglandin analogues for glaucoma treatment. Drugs of the Future 1992;17(8):691-704.
3. Albritton AE, Stewart JA, Leech JN, Jackson AL, Stewart WC. Conjunctival hyperemia with latanoprost travoprost and bimatoprost. Invest Ophthalmol Vis Sci. 2002;43: in press.
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