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Effect of latanoprost as adjunctive therapy
Effect of latanoprost as adjunctive therapy Beatrice DesMarchais, * MD; Eugenio Candal, MD; Marc Weitzman, MD; M. Bruce Shields, MD ABSTRACT • RESUME Background: Latanoprost may be a useful adjunct in some patients receiving maxi mum tolerated medical therapy. We report our clinical experience with latano prost when added to one or two other glaucoma medications. Methods: Review of the charts of 53 patients with open-angle glaucoma whose intra ocular pressure (IOP) was uncontrolled with one or two glaucoma medications and who had latanoprost added as a second or third drug. Patients whose IOP decreased by 3 mm Hg or more were considered to be responders. Results: The shortest length of follow-up was 2.3 months (median 5.8 months). Latanoprost was given as a second medication to 35 patients, of whom 22 (63%) responded, with a mean IOP reduction of 6.1 mm Hg (standard deviation [SD] 2.73 mm Hg) (28.7% [SD 12. I0%]). Of the 18 patients to whom latanoprost was given as a third medication, I0 (56%) responded, with a mean IOP reduction of 6.3 mm Hg (SD 3.86 mm Hg) (24.5% [SD I0.12%]). Interpretation: Latanoprost provides additional IOP reduction in some patients with open-angle glaucoma when added to one or two other glaucoma medications. Contexte : Le latanoprost peut etre utile comme agent d'appoint therapeutique chez certains patients sous regime medical maximum. Nous rendons compte de notre experience clinique avec le latanoprost ajoute a un ou deux autres medicaments pour le glaucome. Methodes : Examen du dossier de 53 patients ayant un glaucome a angle ouvert, dont on n'avait pu maitriser la pression intraoculaire (PIO) avec un medica ment ou deux et auxquels on a ajoute le latanoprost comme deuxieme ou troisieme medicament. Nous avons estime que les patients dont la PIO avait baisse de 3 mm Hg ou plus avaient reagi de fa~on positive. Resultats : Nous avons suivi les patients pendant au mains 2,3 mois (moyenne 5,8 mois). Le latanoprost a ete administre comme deuxieme medicament a 35 patients, parmi lesquels 22 (63 %) ont reagi positivement, avec une baisse moyenne de la PIO de 6, I mm Hg (ecart type 2,73 mm Hg) (28,7 % [ecart type
From the Department of Ophthalmology and Visual Science, Yale Uni versity School of Medicine, New Haven, Conn. *Currently with the Centre d'ophtalmologie Saint-Georges, Chicoutimi, Que. Accepted for publication Feb. 12, 2000
214
Reprint requests to: Dr. M. Bruce Shields, Department of Ophthal mology and Visual Science, Yale University School of Medicine, 330 Cedar St., PO Box 208061, New Haven CT 06520-8061, USA; fax (203) 785-6123
Can} Ophtha/mo/ 2000;35:214-7
Latanoprost as adjunctive therapy-DesMarchais et al
Latanoprost as adjunctive therapy-DesMarchais et al 12, I0 %]). Parmi les 18 patients qui ont rec;:u le latanoprost com me troisieme medicament, I0 (56 %) ont reagi de fac;:on positive, avec une baisse moyenne de la PIO de 6,3 mm Hg (ecart type 3,86 mm Hg) (24,5 % [ecart type I 0, 12 %]).
Interpretation : Le latanoprost apporte une baisse additionnelle de la PIO chez certains patients ayant un glaucome a angle ouvert quand on l'ajoute a Un OU deux autres medicaments antiglaucomateux.
L
atanoprost, the isopropylester of prostaglandin F2a, has been shown to effectively lower the in traocular pressure (IOP). In several large clinical trials the IOP lowering with latanoprost as a single drug was concluded to be comparable or superior to that achieved with timolol. 1-4 Latanoprost was also found to be a useful adjunct in some patients receiving max imum tolerated medical therapy. 5•6 Because latano prost is still relatively new and has ocular side effects of uncertain significance, many physicians prefer to reserve its use as a second- or third-line drug. We report our clinical experience with latanoprost when added to one or two other glaucoma medications. METHODS
The study was carried out from July 1997 to January 1998. We reviewed the charts of consecutive patients with open-angle glaucoma, either chronic or with pseudoexfoliation, who were treated at the Glau coma Section, Yale Eye Center, New Haven, Conn., with latanoprost (Xalatan, Pharmacia & Upjohn, Mississauga, Ont.) as adjunctive therapy for at least 2 months. Only patients whose IOP had not reached the target level with one or two glaucoma medications and who had latanoprost added as a second or third drug were included. Patients who had undergone cataract surgery or trabeculectomy during the previous 6 months were excluded from the study. Age, race, IOP level and type of current glaucoma medication(s) were not exclusion factors. In all cases 0.005% latanoprost was prescribed for once-daily use at bedtime. Two IOP measurements obtained before latanoprost was added and the final two measurements during the study period were noted. The pressure was measured within approximately 3 hours of the same time of day. We used the average of the two measurements before the addition of latanoprost and of the two after the addition of latanoprost for analysis. The data for only one eye per patient were analysed; if both eyes were treated, the right eye was arbitrarily chosen for analy sis.
For purposes of analysis, we classified the patients into two groups according to the number of glaucoma medications (one or two) in use before latanoprost was added. Patients whose IOP decreased by 3 mm Hg or more after the addition of latanoprost were considered to be responders, and those whose pressure increased, remained the same or decreased by less than 3 mm Hg were considered to be nonresponders. We compared the proportion of patients who re sponded in the two groups using the x2 test. RESULTS
A total of 53 patients were included in the study. Of the 53, 35 received latanoprost as a second glaucoma medication, and 18 received the agent as a third glau coma medication. The shortest length of follow-up after the addition of latanoprost was 2.3 months, and the median was 5.8 months. The mean age of the patients who received latano prost as a second medication was 71.7 (standard devi ation [SD] 11.65) years. There were 31 white and 4 black patients; 19 were men. Thirty-one patients had chronic open-angle glaucoma, and 4 had open-angle glaucoma with pseudoexfoliation. Twenty-seven pa tients were using a 13-blocker, seven were receiving dorzolamide, and one was receiving a cholinergic agent. The mean IOP before and after the addition of latanoprost is shown in Table 1. Of the 35 patients 22 (63%) responded to latanoprost therapy, with a mean decrease in IOP of 6.1 mm Hg (SD 2.73 mm Hg) (28.7% [SD 12.1 %]). The mean age of the patients who received latan oprost as a third medication was 69.5 (SD 16.35) years. There were 11 white and 7 black patients; 13 were women. Seventeen patients had chronic open angle glaucoma, and one had open-angle glaucoma with pseudoexfoliation. Fifteen patients were receiv ing a combination of a 13-blocker and dorzolamide, and three were receiving a 13-blocker and a cholinergic agent. The mean IOP before and after latanoprost was added is shown in Table 1. Ten patients (56%)
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Latanoprost as adjunctive therapy-DesMarchais et al
Table I-Results of adding latanoprost as second or third drug to the antiglaucoma regimen of 53 patients with chronic open-angle glaucoma or open-angle glaucoma with pseudoexfoliation*
Latanoprost given as
No. of patients
No. (and%) of responderst
Mean IOP (and SD), mm Hg, before addition of latanoprost, all patients
Second drug Third drug
35 18
22 (63) I0 (56)
19.6 (4.08) 23.2 (5.55)
Mean decrease in IOP (and SD), mm Hg, after addition of latanoprost All patients
Responders
3.8 (3.90) 2.2 (6.94)
6.1 (2.73) 6.3 (3.86)
*IOP = intraocular pressure, SD = standard deviation. tDefined as those with a decrease in IOP of 3 mm Hg or more after the addition of latanoprost.
responded to latanoprost therapy, with a mean decrease in IOP of 6.3 mm Hg (SD 3.86 mm Hg) (24.5% [SD 10.12% ]). The proportion of responders did not differ signifi cantly between the two groups (p = 0.75). However, the small sample yielded a power of 4.5% with a z value of 1.64. INTERPRETATION
Several large studies have shown the !OP-lowering efficacy of 0.005% latanoprost when used once daily as a single drug: the mean efficacy reported was 33.7%, 1 27% 2 and 35%. 3 In these trials very few patients were withdrawn from the study because of uncontrolled IOP while receiving latanoprost (21149, 1 0/128 2 and 1/1163). When the agent was used as an adjunct to existing glaucoma medical therapy, the pro portion of patients with good additional IOP reduction was less impressive. When administered with timolol, once-daily latanoprost lowered the IOP by at least 15% in 21 of 25 patients. 6 It lowered the IOP by an additional 14% when combined with cholinergic ago nists7 and by 15% with carbonic anhydrase inhibitors. 8 As an adjunct to maximum tolerated medical therapy, latanoprost was associated with additional IOP reduc tion of at least 20% in 44.4% of patients at 1 month. 5 The discrepancy in the results between primary and adjunctive therapy may relate to differences in base line IOP, as is true with all glaucoma medications. Our findings show that latanoprost is effective in some patients when added to one or two existing glau coma medications, including 13-blockers, topical car bonic anhydrase inhibitors and cholinergic agonists. The responder group, defined as patients with a de crease in IOP of 3 mm Hg or more, had a mean reduc
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tion in IOP of 28.7% when latanoprost was used as a second medication and 24.5% when it was used as a third medication. It is of interest that the mean IOP reduction among the responders in our study was similar regardless of whether the agent was given as a second- or a third line drug. Our sample was too small to determine whether response or nonresponse was significantly associated with existing glaucoma therapy or any pa tient feature. The clinical impression, however, is that about two-thirds of patients respond and one-third do not respond. There were no apparent risk factors in our study to predict into which group an individual patient might fall. Although we do not advocate the routine use of three or more medications in the treatment of patients with open-angle glaucoma, there are times when this regimen may be in the patient's best interest. In some of these cases latanoprost may be useful adjunctive therapy, not only as a second-line drug but also when added as a third drug. ~ This study was supported in part by unrestricted grants from Research to Prevent Blindness, Inc., and the Connecticut Lions Eye Research Foundation. REFERENCES
1. Watson P, Stjemschantz J, the Latanoprost Study Group. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension. Ophthalmology 1996; 103: 126-36. 2. Camras CB, the United States Latanoprost Study Group. Comparison of latanoprost and timolol in patients with ocu lar hypertension and glaucoma. Ophthalmology 1996;103: 138-48. 3. Alm A, Stjemschantz J, the Scandinavian Latanoprost Study Group. Effects on intraocular pressure and side ef
Latanoprost as adjunctive therapy-DesMarchais et al fects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Ophthalmology 1995; 102: 1743-52. 4. Camras CB, Alm A, Watson P, Stjemschantz J, the Latanoprost Study Groups. Latanoprost, a prostaglandin analog, for glaucoma therapy. Ophthalmology 1996;103: 1916-24. 5. Patelska B, Greenfield D, Liebmann J, Wand M, Kushnick H, Ritch R. Latanoprost for uncontrolled glaucoma in a compassionate case protocol. Am J Ophthalmol 1997;124: 279-86. 6. Alm A, Widengard I, Kjellgren D, SOderstrom M, Fristrom B, Heijl A, et al. Latanoprost administered once daily caused
a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol. Br J Ophthalmol 1995;79:12-6. 7. Fristrom B, Nilsson SEG. Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. Arch Ophthalmol 1993;111:662-5. 8. Rulo AH, Greve EL, Hoyng PFJ. Additive ocular hypoten sive effect of latanoprost and acetazolamide. A short-term study in patients with elevated intraocular pressure. Oph thalmology 1997;104:1503-7. Key words: open-angle glaucoma, latanoprost, medical treat ment, multiple drugs
IN THE NEXT ISSUE • DANS LE PROCHAIN NUMERO
Guidelines for screening for retinopathy of prematurity Information needs for vision loss prevention strategies
CAN J OPHTHALMOL-VOL 35, NO. 4, 2000
217
From the Department of Ophthalmology and Visual Science, Yale Uni versity School of Medicine, New Haven, Conn. *Currently with the Centre d'ophtalmologie Saint-Georges, Chicoutimi, Que. Accepted for publication Feb. 12, 2000
214
Reprint requests to: Dr. M. Bruce Shields, Department of Ophthal mology and Visual Science, Yale University School of Medicine, 330 Cedar St., PO Box 208061, New Haven CT 06520-8061, USA; fax (203) 785-6123
Can} Ophtha/mo/ 2000;35:214-7
Latanoprost as adjunctive therapy-DesMarchais et al
Latanoprost as adjunctive therapy-DesMarchais et al 12, I0 %]). Parmi les 18 patients qui ont rec;:u le latanoprost com me troisieme medicament, I0 (56 %) ont reagi de fac;:on positive, avec une baisse moyenne de la PIO de 6,3 mm Hg (ecart type 3,86 mm Hg) (24,5 % [ecart type I 0, 12 %]).
Interpretation : Le latanoprost apporte une baisse additionnelle de la PIO chez certains patients ayant un glaucome a angle ouvert quand on l'ajoute a Un OU deux autres medicaments antiglaucomateux.
L
atanoprost, the isopropylester of prostaglandin F2a, has been shown to effectively lower the in traocular pressure (IOP). In several large clinical trials the IOP lowering with latanoprost as a single drug was concluded to be comparable or superior to that achieved with timolol. 1-4 Latanoprost was also found to be a useful adjunct in some patients receiving max imum tolerated medical therapy. 5•6 Because latano prost is still relatively new and has ocular side effects of uncertain significance, many physicians prefer to reserve its use as a second- or third-line drug. We report our clinical experience with latanoprost when added to one or two other glaucoma medications. METHODS
The study was carried out from July 1997 to January 1998. We reviewed the charts of consecutive patients with open-angle glaucoma, either chronic or with pseudoexfoliation, who were treated at the Glau coma Section, Yale Eye Center, New Haven, Conn., with latanoprost (Xalatan, Pharmacia & Upjohn, Mississauga, Ont.) as adjunctive therapy for at least 2 months. Only patients whose IOP had not reached the target level with one or two glaucoma medications and who had latanoprost added as a second or third drug were included. Patients who had undergone cataract surgery or trabeculectomy during the previous 6 months were excluded from the study. Age, race, IOP level and type of current glaucoma medication(s) were not exclusion factors. In all cases 0.005% latanoprost was prescribed for once-daily use at bedtime. Two IOP measurements obtained before latanoprost was added and the final two measurements during the study period were noted. The pressure was measured within approximately 3 hours of the same time of day. We used the average of the two measurements before the addition of latanoprost and of the two after the addition of latanoprost for analysis. The data for only one eye per patient were analysed; if both eyes were treated, the right eye was arbitrarily chosen for analy sis.
For purposes of analysis, we classified the patients into two groups according to the number of glaucoma medications (one or two) in use before latanoprost was added. Patients whose IOP decreased by 3 mm Hg or more after the addition of latanoprost were considered to be responders, and those whose pressure increased, remained the same or decreased by less than 3 mm Hg were considered to be nonresponders. We compared the proportion of patients who re sponded in the two groups using the x2 test. RESULTS
A total of 53 patients were included in the study. Of the 53, 35 received latanoprost as a second glaucoma medication, and 18 received the agent as a third glau coma medication. The shortest length of follow-up after the addition of latanoprost was 2.3 months, and the median was 5.8 months. The mean age of the patients who received latano prost as a second medication was 71.7 (standard devi ation [SD] 11.65) years. There were 31 white and 4 black patients; 19 were men. Thirty-one patients had chronic open-angle glaucoma, and 4 had open-angle glaucoma with pseudoexfoliation. Twenty-seven pa tients were using a 13-blocker, seven were receiving dorzolamide, and one was receiving a cholinergic agent. The mean IOP before and after the addition of latanoprost is shown in Table 1. Of the 35 patients 22 (63%) responded to latanoprost therapy, with a mean decrease in IOP of 6.1 mm Hg (SD 2.73 mm Hg) (28.7% [SD 12.1 %]). The mean age of the patients who received latan oprost as a third medication was 69.5 (SD 16.35) years. There were 11 white and 7 black patients; 13 were women. Seventeen patients had chronic open angle glaucoma, and one had open-angle glaucoma with pseudoexfoliation. Fifteen patients were receiv ing a combination of a 13-blocker and dorzolamide, and three were receiving a 13-blocker and a cholinergic agent. The mean IOP before and after latanoprost was added is shown in Table 1. Ten patients (56%)
CAN J OPHTHALMOL-VOL 35, NO. 4, 2000
215
Latanoprost as adjunctive therapy-DesMarchais et al
Table I-Results of adding latanoprost as second or third drug to the antiglaucoma regimen of 53 patients with chronic open-angle glaucoma or open-angle glaucoma with pseudoexfoliation*
Latanoprost given as
No. of patients
No. (and%) of responderst
Mean IOP (and SD), mm Hg, before addition of latanoprost, all patients
Second drug Third drug
35 18
22 (63) I0 (56)
19.6 (4.08) 23.2 (5.55)
Mean decrease in IOP (and SD), mm Hg, after addition of latanoprost All patients
Responders
3.8 (3.90) 2.2 (6.94)
6.1 (2.73) 6.3 (3.86)
*IOP = intraocular pressure, SD = standard deviation. tDefined as those with a decrease in IOP of 3 mm Hg or more after the addition of latanoprost.
responded to latanoprost therapy, with a mean decrease in IOP of 6.3 mm Hg (SD 3.86 mm Hg) (24.5% [SD 10.12% ]). The proportion of responders did not differ signifi cantly between the two groups (p = 0.75). However, the small sample yielded a power of 4.5% with a z value of 1.64. INTERPRETATION
Several large studies have shown the !OP-lowering efficacy of 0.005% latanoprost when used once daily as a single drug: the mean efficacy reported was 33.7%, 1 27% 2 and 35%. 3 In these trials very few patients were withdrawn from the study because of uncontrolled IOP while receiving latanoprost (21149, 1 0/128 2 and 1/1163). When the agent was used as an adjunct to existing glaucoma medical therapy, the pro portion of patients with good additional IOP reduction was less impressive. When administered with timolol, once-daily latanoprost lowered the IOP by at least 15% in 21 of 25 patients. 6 It lowered the IOP by an additional 14% when combined with cholinergic ago nists7 and by 15% with carbonic anhydrase inhibitors. 8 As an adjunct to maximum tolerated medical therapy, latanoprost was associated with additional IOP reduc tion of at least 20% in 44.4% of patients at 1 month. 5 The discrepancy in the results between primary and adjunctive therapy may relate to differences in base line IOP, as is true with all glaucoma medications. Our findings show that latanoprost is effective in some patients when added to one or two existing glau coma medications, including 13-blockers, topical car bonic anhydrase inhibitors and cholinergic agonists. The responder group, defined as patients with a de crease in IOP of 3 mm Hg or more, had a mean reduc
216
CAN J OPHTHALMOL-VOL. 35, NO. 4, 2000
tion in IOP of 28.7% when latanoprost was used as a second medication and 24.5% when it was used as a third medication. It is of interest that the mean IOP reduction among the responders in our study was similar regardless of whether the agent was given as a second- or a third line drug. Our sample was too small to determine whether response or nonresponse was significantly associated with existing glaucoma therapy or any pa tient feature. The clinical impression, however, is that about two-thirds of patients respond and one-third do not respond. There were no apparent risk factors in our study to predict into which group an individual patient might fall. Although we do not advocate the routine use of three or more medications in the treatment of patients with open-angle glaucoma, there are times when this regimen may be in the patient's best interest. In some of these cases latanoprost may be useful adjunctive therapy, not only as a second-line drug but also when added as a third drug. ~ This study was supported in part by unrestricted grants from Research to Prevent Blindness, Inc., and the Connecticut Lions Eye Research Foundation. REFERENCES
1. Watson P, Stjemschantz J, the Latanoprost Study Group. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension. Ophthalmology 1996; 103: 126-36. 2. Camras CB, the United States Latanoprost Study Group. Comparison of latanoprost and timolol in patients with ocu lar hypertension and glaucoma. Ophthalmology 1996;103: 138-48. 3. Alm A, Stjemschantz J, the Scandinavian Latanoprost Study Group. Effects on intraocular pressure and side ef
Latanoprost as adjunctive therapy-DesMarchais et al fects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Ophthalmology 1995; 102: 1743-52. 4. Camras CB, Alm A, Watson P, Stjemschantz J, the Latanoprost Study Groups. Latanoprost, a prostaglandin analog, for glaucoma therapy. Ophthalmology 1996;103: 1916-24. 5. Patelska B, Greenfield D, Liebmann J, Wand M, Kushnick H, Ritch R. Latanoprost for uncontrolled glaucoma in a compassionate case protocol. Am J Ophthalmol 1997;124: 279-86. 6. Alm A, Widengard I, Kjellgren D, SOderstrom M, Fristrom B, Heijl A, et al. Latanoprost administered once daily caused
a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol. Br J Ophthalmol 1995;79:12-6. 7. Fristrom B, Nilsson SEG. Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. Arch Ophthalmol 1993;111:662-5. 8. Rulo AH, Greve EL, Hoyng PFJ. Additive ocular hypoten sive effect of latanoprost and acetazolamide. A short-term study in patients with elevated intraocular pressure. Oph thalmology 1997;104:1503-7. Key words: open-angle glaucoma, latanoprost, medical treat ment, multiple drugs
IN THE NEXT ISSUE • DANS LE PROCHAIN NUMERO
Guidelines for screening for retinopathy of prematurity Information needs for vision loss prevention strategies
CAN J OPHTHALMOL-VOL 35, NO. 4, 2000
217