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Healio
BySteven T. Simmons, MD
November 15, 2005
9 min read
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Assessing glaucoma treatment

BySteven T. Simmons, MD
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After diagnosing a patient with glaucoma, individualized treatment plans must be developed. This begins with setting a target IOP.

Setting target pressures

The target IOP is an important part of treatment and should be tailored to the individual patient. No single IOP level is safe for all patients. Primary considerations for establishing a target IOP include the severity of glaucoma damage, IOP at which damage occurred and risk factors for progression such as age, race, family history and central corneal thickness (CCT). All patients lose retinal ganglion cells (RGCs) with age, but, at some level of IOP, an individual with glaucoma begins to lose RGCs exponentially. Target IOP should be set just below that threshold, which varies with each individual. Target IOP should also be dynamic, reviewed at each visit and adjusted over the course of treatment depending on the patient’s status and effectiveness of treatment.2,3

Steven T. Simmons, MD [photo]
Steven T. Simmons, MD

Glaucoma experts agree that lipids are the safest and most effective medications available but disagree on which lipid is most effective.

A number of guidelines have been proposed for recommending an initial target IOP.1,2,4,5For glaucoma patients and suspects in whom treatment is needed, published guidelines recommend reducing baseline IOP by 20% to 30%. For high-risk patients, guidelines recommend reducing IOP by at least 30%.1,2,4,5

Canadian guidelines recommend a minimum target IOP of less than 25 mm Hg with at least a 20% reduction from baseline for glaucoma suspects requiring treatment; less than 21 mm Hg with at least a 20% reduction from baseline for patients with early glaucoma; less than 18 mm Hg with at least a 30% reduction from baseline for patients with moderate glaucoma; and less than 15 mm Hg with at least a 30% reduction from baseline for patients with advanced/severe glaucoma.6These minimal guidelines are then further reduced for each risk factor (i.e., age, CCT, family history, vasospastic diseases) an individual patient has.

A panel of 18 American glaucoma specialists recommended similar initial target IOP (Table).7Greater pressure reductions than previously thought may be needed to minimize the risk of glaucoma progression in newly diagnosed patients, and very low target IOPs are needed in patients with advanced glaucoma.

Table
A panel of 18 glaucoma specialists recommended guidelines for setting initial target pressures similar to guidelines previously published. These target IOP ranges should be adjusted throughout treatment.7

Achieving target IOPs

Achieving target IOP is critical. Failing to achieve the target IOP may lead to an increased risk of vision loss. Studies have shown, however, that glaucoma may be undertreated relative to IOP control standards established in recent clinical trials.8In a surveillance study of 395 patients with primary open-angle glaucoma, IOP was inadequately controlled at follow-up visits. In patients with mild glaucoma, IOP was greater than 22 mm Hg at 34.1% of visits and greater than 24 mm Hg at 21.1% of visits. In patients with moderate to severe glaucoma, IOP was greater than 19 mm Hg at 47.9% of visits and greater than 21 mm Hg at 30.4% of visits. In addition, therapy was not changed at half of the visits in which the IOP was greater than 30 mm Hg.8

A change in therapy should be considered for patients who fail to reach target IOP at even a small percentage of visits. Primary medical therapy serves as the foundation, and adjunctive therapy should be built onto it. It is critical to establish the strongest foundation before resorting to adjunctive therapy.

The goals of primary medical therapy include achieving the lowest IOP using a single agent; providing a high response rate with few to no nonresponders; maintaining consistent diurnal pressure lowering; and obtaining compliance and adherence by meeting patients’ goals and expectations.

Achieving the lowest IOP using a single agent

When choosing primary therapy, every 1 mm Hg that IOP is lowered matters.9-12An expert panel recommends first-line therapy with once-daily hypotensive lipid therapy.7Glaucoma experts agree that lipids are the safest and most effective medications available but disagree on which lipid is most effective.

Seven prospective, randomized, investigator-masked, direct-comparison studies of Lumigan (bimatoprost, Allergan), Xalatan (latanoprost, Pfizer) and Travatan (travoprost, Alcon) have been performed, with variations in duration, patient selection and characteristics, and methods of data analysis.

These three lipids — bimatoprost, latanoprost and travoprost — have different mechanisms of action. Latanoprost and travoprost are prostaglandin analogues derived from arachidonic acid. Both are prodrugs activated by corneal enzymes, and they bind prostaglandin receptors. Available data suggest that these prostaglandins reduce IOP by increasing uveoscleral outflow.13In contrast, bimatoprost is a prostamide analogue derived from anandamide. An active drug, bimatoprost does not bind to any known receptor. Available data indicate bimatoprost reduces IOP by increasing both trabecular and uveoscleral outflow.14

Studies comparing latanoprost and travoprost revealed that the medications were equally efficacious in lowering IOP. Both studies showed that latanoprost took longer, 6 weeks, to achieve peak efficacy and was most effective at 8 a.m., while travoprost maintained a more consistent diurnal IOP.14,15

In studies comparing bimatoprost and travoprost, bimatoprost lowered IOP about 1 mm Hg more than travoprost.15,17In a 12-week trial, IOP levels at 8 a.m. were reduced statistically more in bimatoprost-treated patients than in travoprost-treated patients.15In the 6-month trial, bimatoprost provided larger mean IOP reductions than travoprost at each time point.17

Data from published clinical studies comparing bimatoprost and latanoprost in patients with elevated IOP indicate that IOP lowering was superior with bimatoprost.18-20In a 30-day study comparing bimatoprost with latanoprost, bimatoprost provided greater mean IOP reduction than latanoprost at all time points, especially in midday and afternoon time points.

In a 3-month study with baseline differences not statistically significant, mean IOP was significantly lower (up to 1 mm Hg at noon and 4 p.m.) with bimatoprost than with latanoprost. There was no statistically significant difference between the two therapies at 8 a.m. or 8 p.m.19

In a 12-week study, bimatoprost produced a consistently lower, although not statistically significant, mean IOP than latanoprost.15In a 6-month study conducted by Robert Noecker, MD, and colleagues, mean IOP reductions from baseline were significantly greater with bimatoprost than latanoprost at each time point (P < .025) (Figure 1), and mean changes from baseline were 1.2 mm Hg to 2.2 mm Hg greater with bimatoprost than latanoprost (P < .004).20In all comparisons, bimatoprost provided greater IOP lowering than latanoprost, with the most statistical difference between therapies occurring in the midday and afternoon time points.

Figure 1
In a study conducted by Robert J. Noecker, MD, and colleagues, mean change in IOP from baseline IOP was consistently greater with bimatoprost than latanoprost.20

Achieving a high response rate

Patients do not always respond to initial therapy. In Dr. Noecker’s study, four out of five patients achieved a 20% reduction in IOP with bimatoprost, while three out of five responded to this degree with latanoprost.20In comparing bimatoprost with travoprost, Louis B. Cantor, MD, and colleagues found that 77% of patients achieved a 20% IOP reduction with bimatoprost, while 62% of patients on travoprost reached this goal.

So what should an ophthalmologist do when initial therapy does not reach the 20% reduction? Should the patient be switched to another primary therapy, or should adjunctive therapy be added?

The goal should be to reach the target IOP with the minimal number of medications possible, so switching to a more effective medication may be the best course of action. The benefits of monotherapy include improved patient compliance, decreased cost and increased safety. It has been shown that even within a class of medications an individual patient may respond to one while not another. In a prospective, randomized study of 15 patients with less than 10% IOP decrease in eyes after 2 months of treatment with latanoprost, 13 patients achieved a 20% or greater IOP reduction with bimatoprost.22Mean IOP in those patients was 24.1 mm Hg when treated with latanoprost vs. 18.1 mm Hg when treated with bimatoprost (P < .001).22Subsequently, if one lipid does not achieve that 20% goal, the physician should try another lipid prior to leaving this class of medication or prior to turning to adjunctive therapy.

Minimizing pressure variation over time

IOP fluctuation is a risk factor for glaucomatous progression and visual field loss,11,23,24and it is important that IOP remain consistently 18 mm Hg or less.20,25In studies, lower circadian IOP was found in patients treated with bimatoprost than in those treated with timolol or latanoprost (P < .003)25,26and bimatoprost provided more effective diurnal control than latanoprost.19,20,25Data in a paper presented at the 2005 annual meeting of the American Society of Cataract and Refractive Surgery showed that 24.6% of patients on latanoprost had at least a 4 mm Hg median diurnal fluctuation over a 6-month period compared with 10% of patients taking bimatoprost (Figure 2).25

Figure 2
Over a 6-month follow-up, diurnal IOP fluctuations of at least 4 mm Hg occurred in a greater percentage of patients taking latanoprost than bimatoprost.25

Conclusion

Therapies must be tailored to suit individual patients, and consistent IOP control is crucial. Primary therapy is a vital step toward achieving that target IOP. Primary therapy serves as the strong foundation, the goals of which are to achieve the lowest IOP possible using a single agent; to provide a high response rate; to maintain consistent IOP; and to obtain good patient compliance.

The hypotensive lipids are the most effective primary agents available to achieve these goals. The role of the ophthalmologist is to find the right medication that reaches these goals for each patient that they treat.

References

  1. European Glaucoma Society.Terminology and Guidelines for Glaucoma, 2nd ed. Savona, Italy: Editrice DOGMA; 2003.
  2. American Academy of Ophthalmology. Preferred Practice Pattern: Primary Open-Angle Glaucoma. 2003. Available at http://www.aao.org/aao/education/library/ppp/upload/Primary-Open-Angle-Glaucoma_pdf. Last accessed Sept. 12, 2005.
  3. American Academy of Ophthalmology. Preferred Practice Pattern: Primary Open-Angle Glaucoma Suspects. 2002. Available at http://www.aao.org/aao/education/library/ppp/upload/Primary-Open-Angle-Glaucoma-Suspect_pdf. Last accessed Sept. 12, 2005.
  4. South East Asia Glaucoma Interest Group. Asia Pacific Glaucoma Guidelines. Sydney, Australia: 2003-2004.
  5. Tuulonen A, Airaksinen PJ, Erola E, et al. The Finnish evidence-based guideline for open-angle glaucoma. Acta Ophthalmol Scand. 2003;81:3; 81:3-18.
  6. Damji KF, Behki R, Wang L, for the Target IOP Workshop participants. Canadian perspectives in glaucoma management: setting target intraocular pressure range. Can J Ophthalmol. 2003;38:189-197.
  7. Coleman AL, et al. In Glaucoma Disease Management Guide. 2003:201-215.
  8. Fremont AM, Lee PP, Mangione CM, et al. Patterns of care for open-angle glaucoma in managed care. Arch Ophthalmol. 2003;121; 121(6):777-783.
  9. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.
  10. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120; 120(6):701-713.
  11. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130(4):429-440.
  12. Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126; 126(4):498-505.
  13. Gross RL. Current medical management of glaucoma. In: Yanoff M, Duker JS, eds. Ophthalmology. 2nd ed. St. Louis, Mo.: Mosby; 2004:1543-1552.
  14. Netland PA, Landry T, Sullivan EK, et al. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001;132(4):472-484.
  15. Parrish RK, Palmberg P, Sheu WP; XLT Study Group. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evaluator multicenter study. Am J Ophthalmol. 2003;135(5):688-703.
  16. Camras CB. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2002;133(5):732; author reply 732-733.
  17. Cantor LB, Wu Dunn D, Cortes A, Hoop J, Knotts S. Ocular hypotensive efficacy of bimatoprost 0.03% and travoprost 0.004% in patients with glaucoma or ocular hypertension. Surv Ophthalmol. 2004:49(Suppl 1):S12-S18.
  18. DuBiner H, Cooke D, Dirks M, Stewart WC, VanDenburgh AM, Felix C. Efficacy and safety of bimatoprost in patients with elevated intraocular pressure: a 30-day comparison with latanoprost. Surv Ophthalmol. 2001;45(Suppl 4):S353-S360.
  19. Gandolfi S, Simmons ST, Sturm R, Chen K, VanDenburgh AM; Bimatoprost Study Group 3. Three-month comparison of bimatoprost and latanoprost in patients with glaucoma and ocular hypertension. Adv Ther. 2001;18(3):110-121.
  20. Noecker RS, Dirks MS, Choplin NT, Bernstein P, Batoosingh AL, Whicup SM; Bimatoprost/Latanoprost Study Group. A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Am J Ophthalmol. 2003;135(1):55-63.
  21. Bournias TE, et al. Poster 4503, presented at the annual meeting of the Association for Research in Vision and Ophthalmology; April 25-29, 2004; Fort Lauderdale, Fla.
  22. Gandolfi SA, Cimino L. Effect of bimatoprost on patients with primary open-angle glaucoma or ocular hypertension who are nonresponders to latanoprost. Ophthalmology. 2003;110:609-614.
  23. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943-1953.
  24. Nouri-Mahdavi K, Hoffman D, Coleman AL, et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111(9):1627-1635.
  25. Simmons S. Presented at the annual meeting of the American Society of Cataract and Refractive Surgery; April 16-20, 2005; Washington, D.C.
  26. Walters TR, DuBiner HB, Carpenter SP, Khan B, VanDenburgh AM; Bimatoprost Circadian IOP Study Group. 24-hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, randomized, comparative clinical trial. Surv Ophthalmol. 2004;49(Suppl 1):S26-S35.
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