- Email: [email protected]
Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy
Optometry (2006) 77, 177-179
Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy Shannon L. Steinhäuser, O.D. Prime Eye Care, Phoenix, Arizona KEYWORDS: Bimatoprost; High-density lipoproteins; Glaucoma; Prostaglandins; Side effects
Abstract BACKGROUND: The aim of this study is to report an adverse systemic response associated with topical bimatoprost therapy. CASE REPORT: An otherwise healthy 58-year-old woman with primary open-angle glaucoma was started on bimatoprost drops once a day. Bimatoprost is a structural analog of prostaglandin F2 ␣-ethanolamide (PGF2a), a class of compounds that in systemic form has been associated with alterations in serum lipid levels. The patient subsequently experienced a significant decrease in her high-density lipoprotein (HDL) serum levels, which subsequently returned to normal on discontinuation of bimatoprost. CONCLUSIONS: This is the first published report of a possible association between topical bimatoprost therapy and decreased serum HDL levels. Because of the significantly increased risk of cardiovascular disease and morbidity associated with low HDL levels, further study is strongly indicated. Optometry 2006;77:177-179
Background The emergence of prostaglandin analogs as monotherapy for glaucoma has enhanced intraocular pressure control and has had significant positive impact on glaucoma management. Less frequent dosing of prostaglandin analogs compared with other topical glaucoma medications has also likely resulted in improved compliance. Bimatoprost (Lumigan; Allergan Inc., Irvine, California) is a prostamide/prostaglandin analog that lowers intraocular pressure by increasing outflow through both the trabecular meshwork and uveoscleral routes.1 Despite the increased effectiveness and the potential for better compliance with this medication, side effects have remained a significant issue. Clinically recognized side effects include: hyperemia,2 deepening of the lid sulcus,3 cystoid macular edema,4 lash poliosis,5 trichomegaly and hypertrichosis,6,7 anterior uveitis,8 punctate keratitis,9 and increases in
Corresponding author: Shannon L. Steinhäuser, O.D., Prime Eye Care, 2423 West Dunlap, Suite 180, Phoenix, Arizona 85021. E-mail: [email protected]
pigmentation of periorbital skin10 and irides.11 This report describes the observation of a new and potentially serious systemic side effect of bimatoprost: lowering of the highdensity lipoprotein (HDL) serum levels.
Case report In May 2003, a 58-year-old white woman presented with a chief complaint of decreased distance vision. It had been approximately 20 years since her last comprehensive examination. She had no history of ocular disease, ocular injury, systemic disease, or medication use. She reported participating in a “vitamin study” over the last “couple years” that required comprehensive blood work every few months. On examination, her Goldmann intraocular pressures (IOPs) were 33 mmHg in the right eye (O.D.) and 30 mmHg in the left eye (O.S.) with an enlarged cup-to-disc ratio and evident notching. Humphrey 24-2 SITA-Fast results confirmed a corresponding inferior nasal visual field defect. The patient had primary open-angle glaucoma diagnosed and was started on bimatoprost at bedtime in both eyes (OU).
1529-1839/06/$ -see front matter © 2006 American Optometric Association. All rights reserved. doi:10.1016/j.optm.2006.02.001
178 Table
Optometry, Vol 77, No 4, April 2006 The subject’s cholesterol levels and ratios before, during, and after bimatoprost therapy
Date
Total cholesterol
HDL
LDL
Cholesterol to HDL ratio
Glaucoma treatment
May 2003 October 2003 January 2004 May 2004
230 237 221 221
63 39 24 51
146 155 138 123
3.7:1 6.1:1 9.2:1 4.3:1
None Bimatoprost Bimatoprost Betaxolol
IOP readings at 1-month followup were 28 mmHg O.D. and 27 mmHg O.S. with the patient admitting poor compliance. Intraocular pressures 1 month after were 22 mmHg OU; 3 months later they were 21 mmHg O.D. and 15 mmHg O.S. The patient telephoned in February 2004 inquiring if HDL levels could be affected by the bimatoprost drops. Her most recent blood work showed a decrease in her HDL levels of 24 mg/dL (HDL levels decreased from 63 mg/dL to 39 mg/dL) compared with laboratory tests conducted before bimatoprost was initiated (see Table). This decrease in HDL adversely affected her cholesterol-to-HDL ratios. Absent any lifestyle or health status changes likely to have affected her HDL level, bimatoprost became suspect. At a followup office visit in April 2004, her IOP was 17 mmHg OU, but her HDL level had dropped an additional 15 mg/dL (HDLs, 24 mg/dL). At this point, the bimatoprost was discontinued. Betaxolol ophthalmic suspension, a selective 1-adrenergic receptor antagonist, was initiated twice daily OU. Results of the patient’s laboratory tests conducted nearly 2 months after the bimatoprost was discontinued showed her HDL level up 27 mg/dL (HDLs, 51 mg/dL). The patient is currently being maintained on betaxolol ophthalmic suspension.
Discussion Cholesterol is a waxy substance produced by the liver that is also acquired through dietary consumption of animal products such as meats, poultry, fish, and dairy products. Cholesterol is necessary for the body to synthesize myelin, create cell membranes, and produce some hormones. However, the body produces sufficient endogenous cholesterol to obviate the need for additional dietary sources. The Third Report of the Expert panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults released in 200112 recommends that everyone age 20 and older have a fasting “lipoprotein profile” every 5 years. In cholesterol testing, total cholesterol, or serum cholesterol, is the sum of the HDLs, low-density lipoproteins (LDLs), and one-fifth triglycerides. The HDL and LDL cholesterol levels help practitioners assess the risk of a patient having a myocardial infarction or cerebrovascular accident. Total serum cholesterol level of less than 200 mg/dL is optimum. Total serum cholesterol level greater than 240 mg/dL reflects a two-fold greater risk for cardiovascular disease than a patient with total serum cholesterol less than 200 mg/dL.
LDLs, also known as “bad cholesterol,” contain more fat than protein, are unstable, and easily degrade. When excess LDL cholesterol circulates, rather than being cleared from the body, the LDLs adhere to the inner walls of arteries. These areas then attract fatty substances, blood clotting factors, and white blood cells, resulting in a thick, hard deposit or plaque that can clog the affected arteries. If a clot forms in one of these narrowed arteries in the heart or brain, it can cause myocardial infarction or cerebrovascular accident, respectively. An LDL cholesterol level of less than 100 mg/dL is considered optimum with less than 130 mg/dL being near optimal for most people. An LDL level of more than 160 mg/dL reflects an increased risk for cardiovascular disease. In contrast, HDL cholesterol is described as “good cholesterol.” HDLs are composed of more protein than fat and move easily through the blood. Because of their more stable nature, HDL cholesterol does not adhere to the walls of arteries and tends to carry cholesterol away from the arteries to the liver where it is excreted from the body. It is believed that HDL can remove excess cholesterol from existing plaques in arteries, thus slowing progression of vascular disease. HDL levels greater than 60 mg/dL are considered protective against cardiovascular disease, whereas levels less than 40 mg/dL pose a greater risk. Some physicians use a ratio of total serum cholesterol to HDLs to monitor a patient’s cholesterol-related cardiovascular risk. The ratio is obtained by dividing the HDL cholesterol level into the total cholesterol. An acceptable ratio is less than 5:1; the optimum ratio is 3.5:1.13 Bimatoprost (and all currently available topical prostaglandin analog medications) are structural analogs of prostaglandin F2 ␣-ethanolamide (PGF2a).14 Researchers have reported that systemic prostaglandin E1 lowers serum lipid levels of HDL cholesterol, HDL triglycerides, and HDL phospholipids15 and may even convert HDL to LDL.16 Systemic PGF2a lowered specifically HDL-cholesterol.17 Doses of bimatoprost reach peak blood concentrations 10 minutes after instillation and are undetectable within 90 minutes in most subjects. Bimatoprost is moderately distributed into body tissues, residing mainly in the plasma with 12% remaining unbound in the plasma.18 In this case, the patient’s HDL levels dropped, and her total serum cholesterol, LDL, and triglyceride levels remained relatively stable. The lowered HDL level
Steinhäuser
Clinical Care
and the effect on her total cholesterol-to-HDL ratio placed her in a high-risk category for cardiovascular disease. This patient’s response to both treatment and discontinuation of the PGF2a derivative, bimatoprost, strongly suggests that it may have been the cause of the decreased HDL levels observed. In addition to reports that PGF2a can cause a decrease in HDLs, both oral and topical nonselective -blockers have also been reported to decrease serum HDL levels.19 Nonselective -blockers and prostaglandin analogs, commonly prescribed glaucoma therapies individually, adjunctively, and soon to be released as a combination therapy, may increase the risk of cardiovascular disease by adversely affecting patients’ HDL levels. This may be of even greater significance because of the systemic health status of populations typically treated for glaucoma.
Conclusions New glaucoma therapies have afforded practitioners increased efficacy and improved patient compliance. However, clinicians must be cognizant of potentially serious side effects even with these seemingly innocuous medications. The decreased HDL levels observed in this patient may have been an atypical, isolated occurrence, exacerbated by vitamin therapy or may possibly represent a common, yet overlooked, complication. This is the first published report of a possible association between topical bimatoprost therapy and decreased serum HDL levels. Whether this finding occurs only with bimatoprost, possibly because of its ten-fold higher concentration compared with other prostaglandin analogs, is unknown. Because of the significantly increased risk of cardiovascular disease and morbidity associated with low HDL levels, further investigation of the possible impact of topical prostaglandin and prostaglandin/nonselective -blocker combination therapies on changes in serum cholesterol levels is indicated. Additionally, the effects of vitamin therapies on the pharmacodynamics of prostaglandins may also warrant further investigation.
Disclaimer The author has no financial or proprietary interest in any of the products or competitor products mentioned.
179
References 1. Christiansen GA, Nau CB, McLaren JW, et al. Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma. Ophthalmology 2004;111(9):1658-62. 2. Leal BC, Medeiros FA, Medeiros FW, et al. Conjunctival hyperemia associated with bimatoprost use: a histopathologic study. Am J Ophthalmol 2004;138(2):310-3. 3. Peplinski LS, Albiani Smith K. Deepening of lid sulcus from topical bimatoprost therapy. Optom Vis Sci 2004;81(8):574-7. 4. Carrillo MM, Nicolela MT. Cystoid macular edema in a low-risk patient after switching from latanoprost to bimatoprost. Am J Ophthalmol 2004;137(5):966-8. 5. Chen CS, Wells J, Craig JE. Acquired trichomegaly of the eyelashes and hypertrichosis induced by bimatoprost. J Eur Acad Dermatol Venereol 2004;18(5):644-5. 6. Herane M, Urbina F. Topical prostaglandin F(2alpha) analog induced poliosis. Am J Ophthalmol 2004;137(5):965-6. 7. Hart J, Shafranov G. Hypertrichosis of vellus hairs of the malar region after unilateral treatment with bimatoprost. Am J Ophthalmol 2004; 137(4):756-7. 8. Packer M, Fine IH, Hoffman RS. Bilateral nongranulomatous anterior uveitis associated with bimatoprost. J Cataract Refract Surg 2003; 29(11):2242-3. 9. Stewart WC, Stewart JA, Jenkins JN, et al. Corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy subjects. J Glaucoma 2003;12(6):475-9. 10. Herndon LW, Williams RD, Wand M, et al. Increased periocular pigmentation with ocular hypotensive lipid use in African Americans. Am J Ophthalmol 2004;137(4):783. 11. Stjernschantz JW, Albert DM, Hu DN, et al. Mechanism and clinical significance of prostaglandin-induced iris pigmentation. Surv Ophthalmol 2002;47 (Suppl 1):S162-75. 12. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97. 13. American Heart Association. http://www.americanheart.org/ presenter.jhtml?identifier⫽183. Last accessed September 15, 2004. 14. Woodward DF, Phelps RL, Krauss AH, et al. Bimatoprost: a novel antiglaucoma agent. Cardiovasc Drug Rev 2004;22(2):103-20. 15. Dionyssiou-Asteriou A, Triantafyllou A, Lekakis J, et al. Influence of prostaglandin E1 on high density lipoprotein-fraction lipid levels in rats. Biochem Med Metab Biol 1986;36(1):114-7. 16. Muzia GI, Korobkova EN, Bergel’son LD. Effect of prostaglandins on lipid transfer between high- and low-density lipoproteins in human plasma. Biokhimiia 1988;53(4):643-8. 17. Dionyssiou-Asteriou A, Triantafyllou A, Kalofoutis A. Changes in serum lipids in rats treated with PGF2 alpha. Biochem Med Metab Biol 1990;44(1):13-7. 18. Lumigan package insert. Allergan, Inc. Irvine, California, August 2002. 19. Stewart WC, Osterman J. Serum lipid physiology and the influence of glaucoma medications. Surv Ophthalmol 1998;43(3):233-44.
Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy Shannon L. Steinhäuser, O.D. Prime Eye Care, Phoenix, Arizona KEYWORDS: Bimatoprost; High-density lipoproteins; Glaucoma; Prostaglandins; Side effects
Abstract BACKGROUND: The aim of this study is to report an adverse systemic response associated with topical bimatoprost therapy. CASE REPORT: An otherwise healthy 58-year-old woman with primary open-angle glaucoma was started on bimatoprost drops once a day. Bimatoprost is a structural analog of prostaglandin F2 ␣-ethanolamide (PGF2a), a class of compounds that in systemic form has been associated with alterations in serum lipid levels. The patient subsequently experienced a significant decrease in her high-density lipoprotein (HDL) serum levels, which subsequently returned to normal on discontinuation of bimatoprost. CONCLUSIONS: This is the first published report of a possible association between topical bimatoprost therapy and decreased serum HDL levels. Because of the significantly increased risk of cardiovascular disease and morbidity associated with low HDL levels, further study is strongly indicated. Optometry 2006;77:177-179
Background The emergence of prostaglandin analogs as monotherapy for glaucoma has enhanced intraocular pressure control and has had significant positive impact on glaucoma management. Less frequent dosing of prostaglandin analogs compared with other topical glaucoma medications has also likely resulted in improved compliance. Bimatoprost (Lumigan; Allergan Inc., Irvine, California) is a prostamide/prostaglandin analog that lowers intraocular pressure by increasing outflow through both the trabecular meshwork and uveoscleral routes.1 Despite the increased effectiveness and the potential for better compliance with this medication, side effects have remained a significant issue. Clinically recognized side effects include: hyperemia,2 deepening of the lid sulcus,3 cystoid macular edema,4 lash poliosis,5 trichomegaly and hypertrichosis,6,7 anterior uveitis,8 punctate keratitis,9 and increases in
Corresponding author: Shannon L. Steinhäuser, O.D., Prime Eye Care, 2423 West Dunlap, Suite 180, Phoenix, Arizona 85021. E-mail: [email protected]
pigmentation of periorbital skin10 and irides.11 This report describes the observation of a new and potentially serious systemic side effect of bimatoprost: lowering of the highdensity lipoprotein (HDL) serum levels.
Case report In May 2003, a 58-year-old white woman presented with a chief complaint of decreased distance vision. It had been approximately 20 years since her last comprehensive examination. She had no history of ocular disease, ocular injury, systemic disease, or medication use. She reported participating in a “vitamin study” over the last “couple years” that required comprehensive blood work every few months. On examination, her Goldmann intraocular pressures (IOPs) were 33 mmHg in the right eye (O.D.) and 30 mmHg in the left eye (O.S.) with an enlarged cup-to-disc ratio and evident notching. Humphrey 24-2 SITA-Fast results confirmed a corresponding inferior nasal visual field defect. The patient had primary open-angle glaucoma diagnosed and was started on bimatoprost at bedtime in both eyes (OU).
1529-1839/06/$ -see front matter © 2006 American Optometric Association. All rights reserved. doi:10.1016/j.optm.2006.02.001
178 Table
Optometry, Vol 77, No 4, April 2006 The subject’s cholesterol levels and ratios before, during, and after bimatoprost therapy
Date
Total cholesterol
HDL
LDL
Cholesterol to HDL ratio
Glaucoma treatment
May 2003 October 2003 January 2004 May 2004
230 237 221 221
63 39 24 51
146 155 138 123
3.7:1 6.1:1 9.2:1 4.3:1
None Bimatoprost Bimatoprost Betaxolol
IOP readings at 1-month followup were 28 mmHg O.D. and 27 mmHg O.S. with the patient admitting poor compliance. Intraocular pressures 1 month after were 22 mmHg OU; 3 months later they were 21 mmHg O.D. and 15 mmHg O.S. The patient telephoned in February 2004 inquiring if HDL levels could be affected by the bimatoprost drops. Her most recent blood work showed a decrease in her HDL levels of 24 mg/dL (HDL levels decreased from 63 mg/dL to 39 mg/dL) compared with laboratory tests conducted before bimatoprost was initiated (see Table). This decrease in HDL adversely affected her cholesterol-to-HDL ratios. Absent any lifestyle or health status changes likely to have affected her HDL level, bimatoprost became suspect. At a followup office visit in April 2004, her IOP was 17 mmHg OU, but her HDL level had dropped an additional 15 mg/dL (HDLs, 24 mg/dL). At this point, the bimatoprost was discontinued. Betaxolol ophthalmic suspension, a selective 1-adrenergic receptor antagonist, was initiated twice daily OU. Results of the patient’s laboratory tests conducted nearly 2 months after the bimatoprost was discontinued showed her HDL level up 27 mg/dL (HDLs, 51 mg/dL). The patient is currently being maintained on betaxolol ophthalmic suspension.
Discussion Cholesterol is a waxy substance produced by the liver that is also acquired through dietary consumption of animal products such as meats, poultry, fish, and dairy products. Cholesterol is necessary for the body to synthesize myelin, create cell membranes, and produce some hormones. However, the body produces sufficient endogenous cholesterol to obviate the need for additional dietary sources. The Third Report of the Expert panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults released in 200112 recommends that everyone age 20 and older have a fasting “lipoprotein profile” every 5 years. In cholesterol testing, total cholesterol, or serum cholesterol, is the sum of the HDLs, low-density lipoproteins (LDLs), and one-fifth triglycerides. The HDL and LDL cholesterol levels help practitioners assess the risk of a patient having a myocardial infarction or cerebrovascular accident. Total serum cholesterol level of less than 200 mg/dL is optimum. Total serum cholesterol level greater than 240 mg/dL reflects a two-fold greater risk for cardiovascular disease than a patient with total serum cholesterol less than 200 mg/dL.
LDLs, also known as “bad cholesterol,” contain more fat than protein, are unstable, and easily degrade. When excess LDL cholesterol circulates, rather than being cleared from the body, the LDLs adhere to the inner walls of arteries. These areas then attract fatty substances, blood clotting factors, and white blood cells, resulting in a thick, hard deposit or plaque that can clog the affected arteries. If a clot forms in one of these narrowed arteries in the heart or brain, it can cause myocardial infarction or cerebrovascular accident, respectively. An LDL cholesterol level of less than 100 mg/dL is considered optimum with less than 130 mg/dL being near optimal for most people. An LDL level of more than 160 mg/dL reflects an increased risk for cardiovascular disease. In contrast, HDL cholesterol is described as “good cholesterol.” HDLs are composed of more protein than fat and move easily through the blood. Because of their more stable nature, HDL cholesterol does not adhere to the walls of arteries and tends to carry cholesterol away from the arteries to the liver where it is excreted from the body. It is believed that HDL can remove excess cholesterol from existing plaques in arteries, thus slowing progression of vascular disease. HDL levels greater than 60 mg/dL are considered protective against cardiovascular disease, whereas levels less than 40 mg/dL pose a greater risk. Some physicians use a ratio of total serum cholesterol to HDLs to monitor a patient’s cholesterol-related cardiovascular risk. The ratio is obtained by dividing the HDL cholesterol level into the total cholesterol. An acceptable ratio is less than 5:1; the optimum ratio is 3.5:1.13 Bimatoprost (and all currently available topical prostaglandin analog medications) are structural analogs of prostaglandin F2 ␣-ethanolamide (PGF2a).14 Researchers have reported that systemic prostaglandin E1 lowers serum lipid levels of HDL cholesterol, HDL triglycerides, and HDL phospholipids15 and may even convert HDL to LDL.16 Systemic PGF2a lowered specifically HDL-cholesterol.17 Doses of bimatoprost reach peak blood concentrations 10 minutes after instillation and are undetectable within 90 minutes in most subjects. Bimatoprost is moderately distributed into body tissues, residing mainly in the plasma with 12% remaining unbound in the plasma.18 In this case, the patient’s HDL levels dropped, and her total serum cholesterol, LDL, and triglyceride levels remained relatively stable. The lowered HDL level
Steinhäuser
Clinical Care
and the effect on her total cholesterol-to-HDL ratio placed her in a high-risk category for cardiovascular disease. This patient’s response to both treatment and discontinuation of the PGF2a derivative, bimatoprost, strongly suggests that it may have been the cause of the decreased HDL levels observed. In addition to reports that PGF2a can cause a decrease in HDLs, both oral and topical nonselective -blockers have also been reported to decrease serum HDL levels.19 Nonselective -blockers and prostaglandin analogs, commonly prescribed glaucoma therapies individually, adjunctively, and soon to be released as a combination therapy, may increase the risk of cardiovascular disease by adversely affecting patients’ HDL levels. This may be of even greater significance because of the systemic health status of populations typically treated for glaucoma.
Conclusions New glaucoma therapies have afforded practitioners increased efficacy and improved patient compliance. However, clinicians must be cognizant of potentially serious side effects even with these seemingly innocuous medications. The decreased HDL levels observed in this patient may have been an atypical, isolated occurrence, exacerbated by vitamin therapy or may possibly represent a common, yet overlooked, complication. This is the first published report of a possible association between topical bimatoprost therapy and decreased serum HDL levels. Whether this finding occurs only with bimatoprost, possibly because of its ten-fold higher concentration compared with other prostaglandin analogs, is unknown. Because of the significantly increased risk of cardiovascular disease and morbidity associated with low HDL levels, further investigation of the possible impact of topical prostaglandin and prostaglandin/nonselective -blocker combination therapies on changes in serum cholesterol levels is indicated. Additionally, the effects of vitamin therapies on the pharmacodynamics of prostaglandins may also warrant further investigation.
Disclaimer The author has no financial or proprietary interest in any of the products or competitor products mentioned.
179
References 1. Christiansen GA, Nau CB, McLaren JW, et al. Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma. Ophthalmology 2004;111(9):1658-62. 2. Leal BC, Medeiros FA, Medeiros FW, et al. Conjunctival hyperemia associated with bimatoprost use: a histopathologic study. Am J Ophthalmol 2004;138(2):310-3. 3. Peplinski LS, Albiani Smith K. Deepening of lid sulcus from topical bimatoprost therapy. Optom Vis Sci 2004;81(8):574-7. 4. Carrillo MM, Nicolela MT. Cystoid macular edema in a low-risk patient after switching from latanoprost to bimatoprost. Am J Ophthalmol 2004;137(5):966-8. 5. Chen CS, Wells J, Craig JE. Acquired trichomegaly of the eyelashes and hypertrichosis induced by bimatoprost. J Eur Acad Dermatol Venereol 2004;18(5):644-5. 6. Herane M, Urbina F. Topical prostaglandin F(2alpha) analog induced poliosis. Am J Ophthalmol 2004;137(5):965-6. 7. Hart J, Shafranov G. Hypertrichosis of vellus hairs of the malar region after unilateral treatment with bimatoprost. Am J Ophthalmol 2004; 137(4):756-7. 8. Packer M, Fine IH, Hoffman RS. Bilateral nongranulomatous anterior uveitis associated with bimatoprost. J Cataract Refract Surg 2003; 29(11):2242-3. 9. Stewart WC, Stewart JA, Jenkins JN, et al. Corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy subjects. J Glaucoma 2003;12(6):475-9. 10. Herndon LW, Williams RD, Wand M, et al. Increased periocular pigmentation with ocular hypotensive lipid use in African Americans. Am J Ophthalmol 2004;137(4):783. 11. Stjernschantz JW, Albert DM, Hu DN, et al. Mechanism and clinical significance of prostaglandin-induced iris pigmentation. Surv Ophthalmol 2002;47 (Suppl 1):S162-75. 12. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97. 13. American Heart Association. http://www.americanheart.org/ presenter.jhtml?identifier⫽183. Last accessed September 15, 2004. 14. Woodward DF, Phelps RL, Krauss AH, et al. Bimatoprost: a novel antiglaucoma agent. Cardiovasc Drug Rev 2004;22(2):103-20. 15. Dionyssiou-Asteriou A, Triantafyllou A, Lekakis J, et al. Influence of prostaglandin E1 on high density lipoprotein-fraction lipid levels in rats. Biochem Med Metab Biol 1986;36(1):114-7. 16. Muzia GI, Korobkova EN, Bergel’son LD. Effect of prostaglandins on lipid transfer between high- and low-density lipoproteins in human plasma. Biokhimiia 1988;53(4):643-8. 17. Dionyssiou-Asteriou A, Triantafyllou A, Kalofoutis A. Changes in serum lipids in rats treated with PGF2 alpha. Biochem Med Metab Biol 1990;44(1):13-7. 18. Lumigan package insert. Allergan, Inc. Irvine, California, August 2002. 19. Stewart WC, Osterman J. Serum lipid physiology and the influence of glaucoma medications. Surv Ophthalmol 1998;43(3):233-44.