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Latanoprost and clinically significant cystoid macular edema after uneventful phacoemulsification with intraocular lens implantation
Latanoprost and clinically significant cystoid macular edema after uneventful phacoemulsification with intraocular lens implantation Patrick C. Yeh, MD, Saras Ramanathan, MD Purpose: To elucidate an association between latanoprost and clinically significant cystoid macular edema (CME) in patients after uneventful phacoemulsification with intraocular lens implantation. Setting: Bergman Eye Center, Department of Ophthalmology, The University of Chicago Hospitals, Chicago, Illinois, USA. Methods: One hundred forty-five consecutive patients (162 eyes) who had phacoemulsification from July 1999 to December 2000 were retrospectively reviewed to determine which patients developed CME. Patients with a history of inflammation and pseudoexfoliation, previous intraocular procedures, or current intraoperative complications were excluded from the study. All cases of CME were diagnosed on the basis of a fundus examination showing typical CME accompanied by a decrease in visual acuity. Upon diagnosis, latanoprost was discontinued and ketorolac was prescribed. The data were analyzed using the Fisher exact test. Of the records reviewed, 134 patients (151 eyes) were included in the study; 11 eyes were excluded secondary to intraoperative complications, a history of ocular inflammation, or both. Among the patients included, 12 were receiving latanoprost preoperatively. Results: Four cases of CME were identified; all 4 patients were taking latanoprost. Latanoprost was discontinued in 8 patients 1 week preoperatively, and none of them developed CME. Therefore, in this series, only patients receiving latanoprost developed CME after uneventful cataract surgery. This difference was statistically significant. In addition, all cases of CME resolved upon discontinuation of latanoprost and administration of ketorolac. Conclusions: This retrospective study shows a clinical association between latanoprost use and postoperative CME after uneventful phacoemulsification. Given the absence of other coexisting risk factors for CME, this series suggests latanoprost is a significant etiologic factor for the development of postoperative CME. J Cataract Refract Surg 2002; 28:1814 –1818 © 2002 ASCRS and ESCRS
L
atanoprost has become a popular agent for the treatment of elevated intraocular pressure (IOP) and glaucoma since its approval by the U.S. Food and Drug Administration in June 1996. Previously known as
Accepted for publication January 19, 2002. Reprint requests to Saras Ramanathan, MD, Department of Ophthalmology & Visual Science, The University of Chicago, 5841 South Maryland Avenue, MC 2114, Chicago, Illinois 60637, USA. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
PhXA41, latanoprost is an isopropyl ester prodrug of 17-phenyl substituted prostaglandin F2␣ that effectively lowers IOP by enhancing uveoscleral outflow.1 Despite its efficacy in lowering IOP, a few ocular side effects associated with latanoprost are known from early studies. These include increased iris pigmentation and mild anterior segment inflammation.2–5 Since its widespread clinical use, several additional ocular side effects have been reported including hypertrichosis and 0886-3350/02/$–see front matter PII S0886-3350(02)01334-2
LATANOPROST AND CME AFTER UNEVENTFUL PHACOEMULSIFICATION
increased eyelash pigmentation,6,7 iritis,8 anterior uveitis,9 choroidal effusion,10 and cystoid macular edema (CME).8,11–15 Although several animal pharmacokinetic studies suggest that topically applied drugs, including prostaglandin F␣, distribute to the retina and choroid,16 –20 the use of topical latanoprost was never shown to induce disruption of the blood–aqueous barrier (BAB) or blood– retinal barrier (BRB) in early studies of experimental animals and human eyes.21–26 However, a later study demonstrated that latanoprost can accelerate BAB disruption, leading to angiographic CME in the early postoperative period in pseudophakic patients.27 The temporal relationships between the use of latanoprost and development of CME and the resolution of CME after cessation of the drug in complicated eyes that are phakic, aphakic, or pseudophakic were also demonstrated in a recent case series.15 These studies all provide evidence suggesting a clinical association between latanoprost and CME. In this retrospective observational case series, we evaluated whether there is a clinical association between latanoprost use and visually significant CME after uneventful phacoemulsification and intraocular lens (IOL) implantation.
Twenty-two patients included in the study had openangle glaucoma. Twelve were receiving latanoprost preoperatively for primary open-angle glaucoma. Other antiglaucoma medications used by the patients were combinations of timolol (Timoptic-XE威) (10 patients), dorzolamide hydrochloride and timolol maleate (Cosopt威) (5 patients), brimonidine tartrate (Alphagan威) (4 patients), betaxolol hydrochloride (Betoptic威) (2 patients), pilocarpine (2 patients), and dorzolamide hydrochloride (Trusopt威) (1 patient). No patient was on phospholine iodide, known to increase the risk of CME.28 Under retrobulbar or topical anesthesia, all surgeries were performed using a temporal clear corneal incision and the divide-and-conquer phacoemulsification technique. All patients received an AcrySof威 MA60BM acrylic IOL (Alcon). Postoperatively, patients were examined at 1 day, 1 week, and 1 month. A standard postoperative drug regimen was prescribed that included prednisolone acetate 1% 4 times a day, ofloxacin 4 times a day, and tobramycin– dexamethasone ointment at bedtime. The ofloxacin and tobramycin– dexamethasone were discontinued at 1 week and the prednisolone, at 3 weeks. Cases in which anterior segment inflammation required more than this regimen of steroid use were excluded from the study. Clinically significant CME was diagnosed at the 1-month postoperative visit on the basis of characteristic findings on ocular fundus examination. All diagnoses were made or confirmed by the same surgeon (S.R.). The Fisher exact test was used for statistical analysis.
Patients and Methods
Results
This retrospective review comprised 162 eyes of 145 consecutive patients who had phacoemulsification by 1 surgeon (S.R.) or under her direct supervision at The University of Chicago Hospitals from July 1999 to December 2000. The patients were reviewed to determine a possible association between preoperative latanoprost use and the development of postoperative CME. An effort was made to exclude patients who might have other known reasons to develop CME. Patients with a history intraocular surgery, uveitis, or pseudoexfoliation were excluded. Patients whose current phacoemulsification surgery involved vitreous loss or excessive intraoperative manipulations such as mechanical pupil stretch or iris prolapse were also excluded. Of the 134 patients in the study, 68 (51%) had hypertension and 28 (21%) had insulin-dependent or non-insulindependent diabetes mellitus. Eighteen patients (13%) had both hypertension and diabetes. Other systemic diseases included hypothyroidism (10 patients, 7.5%), arthritis (9 patients, 7%), asthma (7 patients, 5%), coronary artery disease (5 patients, 4%), systemic lupus erythematosis (3 patients, 2%), hypercholesterolemia (3 patients, 2%), and gout (1 patient, 1%).
Four patients (3%) developed postoperative clinically significant CME 1 month after surgery. None of these patients had diabetes mellitus or any systemic or ocular inflammatory disease. All patients diagnosed with CME had a loss of at least 3 lines of Snellen visual acuity from the 1-week examination. In 2 cases, acuity decreased from 20/40 to 20/200, in 1 cases from 20/60 to 20/200, and in 1 case from 20/80 to 20/200. Upon diagnosis of CME, the latanoprost was discontinued and ketorolac was prescribed to the affected eye 4 times a day. Because of anecdotal reports of an association between latanoprost and CME and the development of CME in this patient population, latanoprost was deliberately discontinued in 8 patients 1 week preoperatively. None of these patients developed clinical CME after cataract surgery. In the 4 patients who continued to receive latanoprost because they had not been asked to discontinue the drug or because they had forgotten to do
J CATARACT REFRACT SURG—VOL 28, OCTOBER 2002
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LATANOPROST AND CME AFTER UNEVENTFUL PHACOEMULSIFICATION
so, all developed postoperative CME. This difference was statistically significant (P ⫽ .003, Fisher exact test). At subsequent follow-up visits, the 4 cases of CME resolved completely with discontinuation of the latanoprost and treatment with ketorolac. The visual acuity returned to the 1-week postoperative value within 1 month of the onset of treatment.
Discussion Since its first clinical description by Irvine29 about half a century ago, CME remains the most common cause of decreased vision associated with cataract surgery. However, despite numerous clinical and laboratory investigations, its incidence continues to be variable and its pathogenesis remains obscure.30 Macular edema occurs when intravascular fluid entry exceeds the retinal tissue compliance and the rate of fluid removal from the perivascular interstitium, resulting in cystic fluid collection in the outer plexiform and inner nuclear layers of the retina. Disruptions in the integrity of both the inner and outer portions of the BRB may be involved in the process. Although the pathogenesis is most likely multifactorial, many investigators agree that inflammation, including endogenous chemical mediators such as prostaglandins, is the major etiologic factor in the development of CME after cataract surgery.27,31–36 Latanoprost, a prostaglandin analog, has become one of the more favored antiglaucoma medications. Since its approval and widespread clinical use, latanoprost has been associated with a variety of side effects, including CME. There have been several well-documented case series of CME temporally related to latanoprost therapy.8,10 –15 All reported cases of latanoprostassociated CME occurred in patients with coexisting ocular and/or systemic conditions that may place eyes at risk for the development of latanoprost-associated CME. These conditions include a history of CME or anterior uveitis, epiretinal membrane, vein occlusion, complicated cataract surgery, presence of an anterior chamber IOL, and diabetes mellitus.15 In our retrospective review of a cohort of patients after uneventful phacoemulsification, only 3% developed clinically significant CME. All who developed it were receiving latanoprost for primary open-angle glaucoma. Resolution of the CME was observed in all cases after the latanoprost was discontinued and ketorolac 1816
treatment initiated. Of the patients who were prophylactically taken off the latanoprost before surgery, none developed postoperative CME. Although the number of patients receiving latanoprost was small, the Fisher exact test revealed a significant clinical association between the use of latanoprost and the development of clinical postoperative CME. Of note is that none of our 4 patients who developed CME had coexisting ocular or systemic conditions, such as uveitis and diabetes mellitus, associated with an altered BRB. Latanoprost therapy has been associated with CME in glaucoma patients and plays an indirect role in the incidence of angiographic CME in postoperative pseudophakic patients.15,27 In our study, despite its retrospective nature and relatively small patient sample, we found a temporal relationship between latanoprost use and the development of early postoperative CME after uneventful cataract surgery. Resolution of the edema with discontinuation of latanoprost and administration of ketorolac suggests that the process is reversible. More important, the absence of other coexisting ocular and systemic risk factors for CME in our patients further suggests latanoprost is an important etiologic factor in the development of early postoperative CME. Given a large armamentarium of antiglaucoma agents and a tendency of IOP reduction after cataract extraction,37–38 our protocol has been to discontinue latanoprost before surgery to avoid this unwanted complication after otherwise uneventful phacoemulsification. We would be interested to see the results of a larger cohort of patients in whom the relationship of latanoprost use and postoperative CME was studied. Ideally, a large prospective double-masked trial in which angiograms were performed in all patients would elucidate and clarify such a relationship. In light of increasing anecdotal evidence and the results of retrospective trials such as this study, this issue bears further investigation.
References 1. Toris CB, Camras CB, Yablonski ME. Effects of PhXA41, a new prostaglandin F2␣ analog, on aqueous humor dynamics in human eyes. Ophthalmology 1993; 100:1297–1304 2. Alm A, Camras CB, Watson PG. Phase III latanoprost studies in Scandinavia, the United Kingdom and the United States. Surv Ophthalmol 1997; 41(suppl 2): S105–S110
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3. Wistrand PJ, Stjernschantz J, Olsson K. The incidence and time-course of latanoprost-induced iridial pigmentation as a function of eye color. Surv Ophthalmol 1997; 41(suppl 2):S129 –S138 4. Watson PG. Latanoprost; two years’ experience of its use in the United Kingdom; the Latanoprost Study Group. Ophthalmology 1998; 105:82–87; discussion by JA Alvarado, 87 5. Camras CB, Alm A, Watson P, Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy; efficacy and safety after 1 year of treatment in 198 patients; the Latanoprost Study Group. Ophthalmology 1996; 103:1916 –1924 6. Wand M. Latanoprost and hyperpigmentation of eyelashes. Arch Ophthalmol 1997; 115:1206 –1209 7. Johnstone MA. Hypertrichosis and increased pigmentation of eyelashes and adjacent hair in the region of the ipsilateral eyelids of patients treated with unilateral topical latanoprost. Am J Ophthalmol 1997; 124:544 –547 8. Warwar RE, Bullock JD, Ballal D. Cystoid macular edema and anterior uveitis associated with latanoprost use; experience and incidence in a retrospective review of 94 patients. Ophthalmology 1998; 105:263–268 9. Fechtner RD, Khouri AS, Zimmerman TJ, et al. Anterior uveitis associated with latanoprost. Am J Ophthalmol 1998; 126:37–41 10. Rowe JA, Hattenhauer MG, Herman DC. Adverse side effects associated with latanoprost. Am J Ophthalmol 1997; 124:683–685 11. Avakian A, Renier SA, Butler PJ. Adverse effects of latanoprost on patients with medically resistant glaucoma. Arch Ophthalmol 1998; 116:679 –680 12. Heier JS, Steinert RF, Frederick AR Jr. Cystoid macular edema associated with latanoprost use. Arch Ophthalmol 1998; 116:680 –682 13. Gaddie IB, Bennett DW. Cystoid macular edema associated with the use of latanoprost. J Am Optom Assoc 1998; 69:122–128 14. Wardrop DRA, Wishart PK. Latanoprost and cystoid macular oedema in a pseudophake. (letter) Br J Ophthalmol 1998; 82:843–844 15. Moroi SE, Gottfredsdottir MS, Schteingart MT, et al. Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension. Ophthalmology 1999; 106:1024 –1029 16. Bito LZ, Baroody RA. The ocular pharmacokinetics of eicosanoids and their derivatives: 1. Comparison of ocular eicosanoid penetration and distribution following the topical application of PGF2␣, PGF2␣-1-methyl ester, and F2␣-1-isopropyl ester. Exp Eye Res 1987; 44:217–226 17. Schoenwald RD, Deshpande GS, Rethwisch DG, Barfknecht CF. Penetration into the anterior chamber via the conjunctival/scleral pathway. J Ocul Pharmacol Ther 1997; 13:41–59
18. Green K, Bowman K, Luxenberg MN, Friberg TR. Penetration of topical indomethacin into phakic and aphakic rabbit eyes. Arch Ophthalmol 1983; 101:284 –288 19. Chen CC, Anderson J, Shackleton M, Attard J. The disposition of bunolol in the rabbit eye. J Ocul Pharmacol 1987; 3:149 –157 20. Acheampong AA, Breau A, Shackleton M, et al. Comparison of concentration-time profiles of levobunolol and timolol in anterior and posterior ocular tissues of albino rabbits. J Ocul Pharmacol Ther 1995; 11:489 –502 21. Toris CB, Camras CB, Yablonski ME, Brubaker RF. Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous barrier function. Surv Ophthalmol 1997; 41(suppl 2):S69 –S75 22. Kosaka T. [The effects of long term topically applied prostaglandins on aqueous protein concentration and the rabbit ciliary process]. [Japanese] Nippon Ganka Gakkai Zasshi 1994; 98:435–442 23. Kosaka T. The effects of prostaglandins on the bloodretinal barrier. Nippon Ganka Gakkai Zasshi 1995; 99: 412–419 24. Hoyng PFJ, Rulo AH, Greve EL, et al. Fluorescein angiographic evaluation of the effect of latanoprost treatment on blood-retinal barrier integrity: a review of studies conducted on pseudophakic glaucoma patients and on phakic and aphakic monkeys. Surv Ophthalmol 1997; 41(suppl 2):S83–S88 25. Ziai N, Dolan JW, Kacere RD, Brubaker RF. The effects on aqueous dynamics of PhXA41, a new prostaglandin F2␣ analogue, after topical application in normal and ocular hypertensive human eyes. Arch Ophthalmol 1993; 111:1351–1358 26. Hotehama Y, Mishima HK. Clinical efficacy of PhXA34 and PhXA41, two novel prostaglandin F2␣-isopropyl ester analogues for glaucoma treatment. Jpn J Ophthalmol 1993; 37:259 –269 27. Miyake K, Ota I, Maekubo K, et al. Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema in early postoperative pseudophakias. Arch Ophthalmol 1999; 117:34 –40 28. Halperin LS, Goldman HB. Cystoid macular edema associated with topical echthiophate iodide. Ann Ophthalmol 1993; 25:457–458 29. Irvine SR. A newly defined vitreous syndrome following cataract surgery; interpreted according to recent concepts of the structure of the vitreous. Am J Ophthalmol 1953; 36:599 –619 30. Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc 1998; 96:557–634 31. Miyake K, Sugiyama S, Norimatsu I, Ozawa T. Aqueous prostaglandins in persistent cystoid macular edema sec-
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32.
33.
34.
35.
36.
ondary to vitreous incarceration: effects of pars plana vitrectomy. Jpn J Ophthalmol 1980; 24:335–345 Miyake K, Sugiyama S, Norimatsu I, Ozawa T. Prevention of cystoid macular edema after lens extraction by topical indomethacin (III). Radioimmunoassay measurement of prostaglandins in the aqueous during and after lens extraction procedures. Albrecht von Graefes Arch Klin Exp Ophthalmol 1978; 209:83–88 Neufeld AH, Jampol LM, Sears ML. Aspirin prevents the disruption of the blood-aqueous barrier in the rabbit eye. Nature 1972; 238:158 –159 Peyman GA, Bennett TO, Vlchek J. Effects of intravitreal prostaglandins on retinal vasculature. Ann Ophthalmol 1975; 7:279 –288 Tsukahara S, Kohda N. [The effects of prostaglandins on the blood-ocular barrier: II. Blood-retinal barrier]. [Japanese] Acta Soc Ophthalmol Jpn 1977; 81:193–198 Podos SM. Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. Trans Am Ophthalmol Soc 1976; 74:637–660
1818
37. Jahn CE. Reduced intraocular pressure after phacoemulsification and posterior chamber intraocular lens implantation. J Cataract Refract Surg 1997; 23:1260 – 1264 38. Link S, Haring G, Hedderich J. Einfluss der phakoemulsifikation und Implantation auf den Intraokulardruck bei Patienten mit und ohne Offenwinkelglaukom. Ophthalmologe 2000; 97:402–406 From the Department of Ophthalmology and Visual Science, The University of Chicago, Chicago, Illinois, USA. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Ft. Lauderdale, Florida, USA, April 2001, and the Symposium on Cataract, IOL and Refractive Surgery, San Diego, California, USA, April 2001. Supported in part by a grant from Research to Prevent Blindness, Inc. None of the authors has a financial or proprietary interest in any material or method mentioned
J CATARACT REFRACT SURG—VOL 28, OCTOBER 2002
L
atanoprost has become a popular agent for the treatment of elevated intraocular pressure (IOP) and glaucoma since its approval by the U.S. Food and Drug Administration in June 1996. Previously known as
Accepted for publication January 19, 2002. Reprint requests to Saras Ramanathan, MD, Department of Ophthalmology & Visual Science, The University of Chicago, 5841 South Maryland Avenue, MC 2114, Chicago, Illinois 60637, USA. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
PhXA41, latanoprost is an isopropyl ester prodrug of 17-phenyl substituted prostaglandin F2␣ that effectively lowers IOP by enhancing uveoscleral outflow.1 Despite its efficacy in lowering IOP, a few ocular side effects associated with latanoprost are known from early studies. These include increased iris pigmentation and mild anterior segment inflammation.2–5 Since its widespread clinical use, several additional ocular side effects have been reported including hypertrichosis and 0886-3350/02/$–see front matter PII S0886-3350(02)01334-2
LATANOPROST AND CME AFTER UNEVENTFUL PHACOEMULSIFICATION
increased eyelash pigmentation,6,7 iritis,8 anterior uveitis,9 choroidal effusion,10 and cystoid macular edema (CME).8,11–15 Although several animal pharmacokinetic studies suggest that topically applied drugs, including prostaglandin F␣, distribute to the retina and choroid,16 –20 the use of topical latanoprost was never shown to induce disruption of the blood–aqueous barrier (BAB) or blood– retinal barrier (BRB) in early studies of experimental animals and human eyes.21–26 However, a later study demonstrated that latanoprost can accelerate BAB disruption, leading to angiographic CME in the early postoperative period in pseudophakic patients.27 The temporal relationships between the use of latanoprost and development of CME and the resolution of CME after cessation of the drug in complicated eyes that are phakic, aphakic, or pseudophakic were also demonstrated in a recent case series.15 These studies all provide evidence suggesting a clinical association between latanoprost and CME. In this retrospective observational case series, we evaluated whether there is a clinical association between latanoprost use and visually significant CME after uneventful phacoemulsification and intraocular lens (IOL) implantation.
Twenty-two patients included in the study had openangle glaucoma. Twelve were receiving latanoprost preoperatively for primary open-angle glaucoma. Other antiglaucoma medications used by the patients were combinations of timolol (Timoptic-XE威) (10 patients), dorzolamide hydrochloride and timolol maleate (Cosopt威) (5 patients), brimonidine tartrate (Alphagan威) (4 patients), betaxolol hydrochloride (Betoptic威) (2 patients), pilocarpine (2 patients), and dorzolamide hydrochloride (Trusopt威) (1 patient). No patient was on phospholine iodide, known to increase the risk of CME.28 Under retrobulbar or topical anesthesia, all surgeries were performed using a temporal clear corneal incision and the divide-and-conquer phacoemulsification technique. All patients received an AcrySof威 MA60BM acrylic IOL (Alcon). Postoperatively, patients were examined at 1 day, 1 week, and 1 month. A standard postoperative drug regimen was prescribed that included prednisolone acetate 1% 4 times a day, ofloxacin 4 times a day, and tobramycin– dexamethasone ointment at bedtime. The ofloxacin and tobramycin– dexamethasone were discontinued at 1 week and the prednisolone, at 3 weeks. Cases in which anterior segment inflammation required more than this regimen of steroid use were excluded from the study. Clinically significant CME was diagnosed at the 1-month postoperative visit on the basis of characteristic findings on ocular fundus examination. All diagnoses were made or confirmed by the same surgeon (S.R.). The Fisher exact test was used for statistical analysis.
Patients and Methods
Results
This retrospective review comprised 162 eyes of 145 consecutive patients who had phacoemulsification by 1 surgeon (S.R.) or under her direct supervision at The University of Chicago Hospitals from July 1999 to December 2000. The patients were reviewed to determine a possible association between preoperative latanoprost use and the development of postoperative CME. An effort was made to exclude patients who might have other known reasons to develop CME. Patients with a history intraocular surgery, uveitis, or pseudoexfoliation were excluded. Patients whose current phacoemulsification surgery involved vitreous loss or excessive intraoperative manipulations such as mechanical pupil stretch or iris prolapse were also excluded. Of the 134 patients in the study, 68 (51%) had hypertension and 28 (21%) had insulin-dependent or non-insulindependent diabetes mellitus. Eighteen patients (13%) had both hypertension and diabetes. Other systemic diseases included hypothyroidism (10 patients, 7.5%), arthritis (9 patients, 7%), asthma (7 patients, 5%), coronary artery disease (5 patients, 4%), systemic lupus erythematosis (3 patients, 2%), hypercholesterolemia (3 patients, 2%), and gout (1 patient, 1%).
Four patients (3%) developed postoperative clinically significant CME 1 month after surgery. None of these patients had diabetes mellitus or any systemic or ocular inflammatory disease. All patients diagnosed with CME had a loss of at least 3 lines of Snellen visual acuity from the 1-week examination. In 2 cases, acuity decreased from 20/40 to 20/200, in 1 cases from 20/60 to 20/200, and in 1 case from 20/80 to 20/200. Upon diagnosis of CME, the latanoprost was discontinued and ketorolac was prescribed to the affected eye 4 times a day. Because of anecdotal reports of an association between latanoprost and CME and the development of CME in this patient population, latanoprost was deliberately discontinued in 8 patients 1 week preoperatively. None of these patients developed clinical CME after cataract surgery. In the 4 patients who continued to receive latanoprost because they had not been asked to discontinue the drug or because they had forgotten to do
J CATARACT REFRACT SURG—VOL 28, OCTOBER 2002
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LATANOPROST AND CME AFTER UNEVENTFUL PHACOEMULSIFICATION
so, all developed postoperative CME. This difference was statistically significant (P ⫽ .003, Fisher exact test). At subsequent follow-up visits, the 4 cases of CME resolved completely with discontinuation of the latanoprost and treatment with ketorolac. The visual acuity returned to the 1-week postoperative value within 1 month of the onset of treatment.
Discussion Since its first clinical description by Irvine29 about half a century ago, CME remains the most common cause of decreased vision associated with cataract surgery. However, despite numerous clinical and laboratory investigations, its incidence continues to be variable and its pathogenesis remains obscure.30 Macular edema occurs when intravascular fluid entry exceeds the retinal tissue compliance and the rate of fluid removal from the perivascular interstitium, resulting in cystic fluid collection in the outer plexiform and inner nuclear layers of the retina. Disruptions in the integrity of both the inner and outer portions of the BRB may be involved in the process. Although the pathogenesis is most likely multifactorial, many investigators agree that inflammation, including endogenous chemical mediators such as prostaglandins, is the major etiologic factor in the development of CME after cataract surgery.27,31–36 Latanoprost, a prostaglandin analog, has become one of the more favored antiglaucoma medications. Since its approval and widespread clinical use, latanoprost has been associated with a variety of side effects, including CME. There have been several well-documented case series of CME temporally related to latanoprost therapy.8,10 –15 All reported cases of latanoprostassociated CME occurred in patients with coexisting ocular and/or systemic conditions that may place eyes at risk for the development of latanoprost-associated CME. These conditions include a history of CME or anterior uveitis, epiretinal membrane, vein occlusion, complicated cataract surgery, presence of an anterior chamber IOL, and diabetes mellitus.15 In our retrospective review of a cohort of patients after uneventful phacoemulsification, only 3% developed clinically significant CME. All who developed it were receiving latanoprost for primary open-angle glaucoma. Resolution of the CME was observed in all cases after the latanoprost was discontinued and ketorolac 1816
treatment initiated. Of the patients who were prophylactically taken off the latanoprost before surgery, none developed postoperative CME. Although the number of patients receiving latanoprost was small, the Fisher exact test revealed a significant clinical association between the use of latanoprost and the development of clinical postoperative CME. Of note is that none of our 4 patients who developed CME had coexisting ocular or systemic conditions, such as uveitis and diabetes mellitus, associated with an altered BRB. Latanoprost therapy has been associated with CME in glaucoma patients and plays an indirect role in the incidence of angiographic CME in postoperative pseudophakic patients.15,27 In our study, despite its retrospective nature and relatively small patient sample, we found a temporal relationship between latanoprost use and the development of early postoperative CME after uneventful cataract surgery. Resolution of the edema with discontinuation of latanoprost and administration of ketorolac suggests that the process is reversible. More important, the absence of other coexisting ocular and systemic risk factors for CME in our patients further suggests latanoprost is an important etiologic factor in the development of early postoperative CME. Given a large armamentarium of antiglaucoma agents and a tendency of IOP reduction after cataract extraction,37–38 our protocol has been to discontinue latanoprost before surgery to avoid this unwanted complication after otherwise uneventful phacoemulsification. We would be interested to see the results of a larger cohort of patients in whom the relationship of latanoprost use and postoperative CME was studied. Ideally, a large prospective double-masked trial in which angiograms were performed in all patients would elucidate and clarify such a relationship. In light of increasing anecdotal evidence and the results of retrospective trials such as this study, this issue bears further investigation.
References 1. Toris CB, Camras CB, Yablonski ME. Effects of PhXA41, a new prostaglandin F2␣ analog, on aqueous humor dynamics in human eyes. Ophthalmology 1993; 100:1297–1304 2. Alm A, Camras CB, Watson PG. Phase III latanoprost studies in Scandinavia, the United Kingdom and the United States. Surv Ophthalmol 1997; 41(suppl 2): S105–S110
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37. Jahn CE. Reduced intraocular pressure after phacoemulsification and posterior chamber intraocular lens implantation. J Cataract Refract Surg 1997; 23:1260 – 1264 38. Link S, Haring G, Hedderich J. Einfluss der phakoemulsifikation und Implantation auf den Intraokulardruck bei Patienten mit und ohne Offenwinkelglaukom. Ophthalmologe 2000; 97:402–406 From the Department of Ophthalmology and Visual Science, The University of Chicago, Chicago, Illinois, USA. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Ft. Lauderdale, Florida, USA, April 2001, and the Symposium on Cataract, IOL and Refractive Surgery, San Diego, California, USA, April 2001. Supported in part by a grant from Research to Prevent Blindness, Inc. None of the authors has a financial or proprietary interest in any material or method mentioned
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