Archives of Ophthalmology

Pérez-Santonja, Juan J.;Sakla, Hani F.;Alió, Jorge L.

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160011001pmid: 9230822

Abstract Objective: To investigate changes in the human corneal endothelium after excimer laser in situ keratomileusis for the correction of high myopia. Methods: Preoperative and serial postoperative specular microscopy of the central corneal endothelium was performed on 31 patients (45 eyes) (group A) who underwent laser in situ keratomileusis for the correction of myopia ranging from −8.25 to −18.50 diopters. Twenty-one patients (30 eyes) were contact lens wearers (group B), and 10 patients (15 eyes) had never worn contact lenses (group C). The central endothelium was analyzed for cell density, coefficient of variation in cell size, and hexagonality. The preoperative data were compared with those obtained 3, 6, and 12 months after surgery in all groups. Results: In group A, the postoperative mean cell density increased significantly (2.3%) at 6-month follow-up (P=.04); the coefficient of variation decreased at all follow-ups (P<.001); and the percentage of hexagonal cells increased at all follow-ups (P<.05). In group B, there was a significant postoperative increase in cell density at the 3- (2.36%) and 6-month (3.74%) follow-ups (P<.05); the coefficient of variation decreased at all follow-ups (P<.001); and the hexagonality was also significantly higher at all follow-ups than it was before treatment (P<.05). In group C, no significant differences in mean cell density or morphometric indexes were found between preoperative and postoperative values. Conclusions: Laser in situ keratomileusis caused no damage to the central corneal endothelium. The postoperative improvements in endothelial cell density and morphometric indexes are related to postoperative discontinuation of contact lens use. References 1. Pallikaris IG, Siganos DS. Excimer laser in situ keratomileusis and photorefractive keratectomy for correction of high myopia . J Refract Surg . 1994;10:498-510. 2. Maldonado-Bas A, Onnis R. Excimer laser in situ keratomileusis for myopia . J Refract Surg . 1995;11( (suppl) ):229-233. 3. Fiander DC, Tayfour F. Excimer laser in situ keratomileusis in 124 myopic eyes . J Refract Surg . 1995;11( (suppl) ):234-238. 4. Kremer FB, Dufek M. Excimer laser in situ keratomileusis . J Refract Surg . 1995;11( (suppl) ):244-247. 5. Güell JL, Muller A. Laser in situ keratomileusis (LASIK) for myopia from −7 to −18 diopters . J Refract Surg . 1996;12:222-228. 6. Marshall J, Trokel S, Rothery S, Schubert H. An ultrastructural study of corneal incisions induced by an excimer laser at 193 nm . Ophthalmology . 1985;92:749-758.Crossref 7. Koch JW, Lang GK, Naumann GO. Endothelial reaction to perforating and non-perforating excimer laser excisions in rabbits . Refract Corneal Surg . 1991;7:214-222. 8. Del Pero R, Gigstad J, Roberts A, et al. A refractive and histopathological study of excimer laser keratectomy in primates . Am J Ophthalmol . 1990;109:419-429. 9. Pérez-Santonja JJ, Meza J, Moreno E, García-Hernández MR, Zato MA. Short-term corneal endothelial changes after photorefractive keratectomy , J Refract Surg . 1994;10( (suppl) ):194-198. 10. Amano S, Shimizu K. Corneal endothelial changes after excimer laser photorefractive keratectomy . Am J Ophthalmol . 1993;116:692-694. 11. Cennamo G, Rosa N, Guida E, Del Prete A, Sebastiani A. Evaluation of corneal thickness and endothelial cells before and after excimer laser photorefractive keratectomy . J Refract Surg . 1994;10:137-141. 12. Carones F, Brancato R, Venturi E, Morico A. The corneal endothelium after myopic excimer laser photorefractive keratectomy . Arch Ophthalmol . 1994;112:920-924.Crossref 13. Mardelli PG, Piebenga LW, Matta CS, Hyde LL, Gira J. Corneal endothelial status 12 to 55 months after excimer laser photorefractive keratectomy . Ophthalmology . 1995;102:544-549.Crossref 14. Trocmé SD, Mack KA, Gill KS, Gold DH, Milstein BA, Bourne WM. Central and peripheral endothelial cell changes after excimer laser photorefractive keratectomy for myopia . Arch Ophthalmol . 1996;114:925-928.Crossref 15. Rao G, Waldron W, Aquavella J. Morphology of graft endothelium and donor age . Br J Ophthalmol . 1980;64:523-527.Crossref 16. MacRae SM, Matsuda M, Rich LF. The effect of radial keratotomy on the corneal endothelium . Am J Ophthalmol . 1985;100:538-542. 17. Dehm EJ, Puliafito CA, Adler CM, Steinert RF. Corneal endothelial injury in rabbits following excimer laser ablation at 193 and 248 nm . Arch Ophthalmol . 1986;104:1364-1368.Crossref 18. Fantes FE, Hanna KD, Waring III GO, Pouliquen Y, Thompson KP, Savoldelli M. Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys . Arch Ophthalmol . 1990;108:665-675.Crossref 19. Hirst LW, Auer C, Cohn J, Tseng SC, Khodadoust AA. Specular microscopy of hard contact lens wearers . Ophthalmology . 1984;91:1147-1150.Crossref 20. MacRae SM, Matsuda M, Yee R, Shellans S. The effect of contact lenses on the corneal endothelium . Invest Ophthalmol Vis Sci . 1985;26( (suppl) ):275.

Schuman, Joel S.;Horwitz, Barry;Choplin, Neil T.;David, Robert;Albracht, Diane;Chen, Kuankuan

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160017002pmid: 9230823

Abstract Objective: Brimonidine tartrate is a highly selective α2-agonist. This study investigates the safety and efficacy of 0.2% brimonidine administered twice daily for 1 year in patients with glaucoma or ocular hypertension. Methods: The study design was a multicenter, double-masked, randomized, parallel-group, active-controlled comparison clinical trial. Subjects instilled 0.2% brimonidine or 0.5% timolol maleate twice daily for 12 months. Subjects were examined at baseline, week 1, and months 1, 2,3,6, 9, and 12. A subset of subjects was examined at week 2. Results: Of 443 subjects enrolled in this study, 374 met the entry criteria; 186 received brimonidine and 188 received timolol. Brimonidine-treated subjects showed an overall mean peak reduction in intraocular pressure (IOP) of 6.5 mm Hg; timolol-treated subjects had a mean peak reduction in IOP of 6.1 mm Hg. Brimonidine lowered mean peak IOP significantly more than timolol at week 2 and month 3 (P<.03); no significant difference was observed between the groups for this variable at other visits throughout the 1-year course of the study. No evidence of tachyphylaxis was seen in either group. Allergy was seen in 9% of subjects treated with brimonidine. Dry mouth was more common in the brimonidine-treated group than in the timolol-treated group (33.0% vs 19.4%), but complaints of burning and stinging were more common in the timolol-treated group (41.9%) than in the brimonidine-treated patients (28.1%). Headache, fatigue, and drowsiness were similar in the 2 groups. In general, the tolerance to medication was acceptable. Conclusions: Brimonidine is safe and effective in lowering IOP in glaucomatous eyes. Brimonidine provides a sustained long-term ocular hypotensive effect, is well tolerated, and has a low rate of allergic response. References 1. Burke J, Schwartz M. Preclinical evaluation of brimonidine . Surv Ophthalmol . 1996;41( (suppl) ):S9-S18.Crossref 2. Jampel HD, Robin AL, Quigley HA, Pollack JP. Apraclonidine: a one-week dose-response study . Arch Ophthalmol . 1988;106:1069-1073.Crossref 3. Robin AL. Short-term effects of unilateral 1% apraclonidine therapy . Arch Ophthalmol . 1988;106:912-915.Crossref 4. Abrams DA, Robin AL, Crandall AS, et al. A limited comparison of apraclonidine's dose response in subjects with normal or increased intraocular pressure . Am J Ophthalmol . 1989;109:230-237. 5. Robin AL, Ritch R, Shin DH, et al. The short-term effect of apraclonidine hydrochloride when added to maximum tolerated medical therapy . Am J Ophthalmol . 1995;120:423-432. 6. Wilkerson M, Lewis RA, Shields MB. Follicular conjunctivitis associated with apraclonidine . Am J Ophthalmol . 1991;111:105-106. 7. Nagasubramanian S, Hitchings RA, Demailly P, et al. Comparison of apraclonidine and timolol in chronic open-angle glaucoma: a three-month study . Ophthalmology . 1993;100:1318-1323.Crossref 8. Stewart WC, Ritch R, Shin DH, et al. The efficacy of apraclonidine as an adjunct to timolol therapy . Arch Ophthalmol . 1995;113:287-292.Crossref 9. Robin AL. Questions concerning the role of apraclonidine in the management of glaucoma . Arch Ophthalmol . 1995;113:712-713.Crossref 10. Butler P, Mannschreck M, Lin S, Hwang I, Alvarado J. Clinical experience with the long-term use of 1% apraclonidine: incidence of allergic reactions . Arch Ophthalmol . 1995;113:293-296.Crossref 11. Burke JA, Potter DE. The ocular effects of relatively selective α-agonist (UK 14,304-18) in cats, rabbits, and monkeys . Curr Eye Res . 1986;5:665-676.Crossref 12. David R, Walters TR, Sargent JB, et al. The safety and efficacy of brimonidine tartrate 0.08%, 0.2%, 0.35%, and 0.5% in normotensive subjects . Eur J Ophthalmol . 1995;5( (suppl 2A) ):156. Abstract. 13. Derick RJ, Robin AL, Walters TR, et al. Brimonidine tartrate: a one month dose response study . Ophthalmology . 1997;104:131-136.Crossref 14. Barnebey HS, Robin AL, Zimmerman TJ, et al. The efficacy of brimonidine in decreasing elevations in intraocular pressure after laser trabeculoplasty . Ophthalmology . 1993;100:1083-1088.Crossref 15. David R, Spaeth GL, Clevenger CE, et al. Brimonidine in the prevention of intraocular pressure-elevation following argon laser trabeculoplasty . Arch Ophthalmol . 1993;111:1387-1390.Crossref 16. The Brimonidine-ALT Study Group. Effect of brimonidine 0.5% on intraocular pressure spikes following 360° argon laser trabeculoplasty . Ophthalmic Surg Lasers . 1995;26:404-409. 17. Toris CB, Camras CB, Yablonski ME. Effects of brimonidine on aqueous humor dynamics in human eyes . Arch Ophthalmol . 1995;113:1514-1517.Crossref 18. Rosenthal AL, Walters T, Berg E, et al. A comparison of the safety and efficacy of brimonidine 0.2%, BID versus TID, in subjects with elevated intraocular pressure . Invest Ophthalmol Vis Sci . 1996;37( (suppl) ):S1102. Abstract. 19. Milliken GA, Johnson DE. Analysis of Messy Data . New York, NY: Van Nostrand Reinhold Co; 1984:138-156, 323-375. 20. Snedecor GW, Cochran WG. Statistical Methods . 7th ed. Ames: The Iowa State University Press; 1980:83-96, 208-210. 21. Landis RJ, Heyman ER, Koch GG. Average partial association in three-way contingency tables: a review and discussion of alternative tests . Int Stat Rev . 1978;46:237-254.Crossref 22. Choplin NT, the Brimonidine Study Group. Visual field results from a one year multicenter randomized double masked study comparing brimonidine tartrate to timolol maleate in the treatment of ocular hypertension and glaucoma . Invest Ophthalmol Vis Sci . 1996;37( (suppl) ):S510. Abstract. 23. Bulter PJ, Jones B. Incidence of characteristics of allergic reactions to apraclonidine 0.5% . Invest Ophthalmol Vis Sci . 1996;37( (suppl) ):S201. Abstract. 24. Pineyro A, Gross RL, Orengo-Nania S. Long term experience with apraclonidine 0.5% (lopidine) in clinical practice . Invest Ophthalmol Vis Sci . 1996;37( (suppl) ): S1100. Abstract. 25. Nordlund JR, Pasquale LR, Robin AL, et al. A comparison of the cardiovascular and pulmonary effects of brimonidine 0.20%, timolol 0.5% and betaxolol suspension 0.25% . Arch Ophthalmol . 1995;113:77-83.Crossref

Stewart, William C.;Sine, Cheryl;Cate, Elin;Minno, George E.;Hunt, Hurshell H.

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160023003pmid: 9230824

Abstract Objective: To evaluate the daily cost of β-blocker therapy among commercially available products. Methods: Ten different β-adrenergic blocker preparations, each in 10-mL bottles (except Timoptic-XE [Merck brand of timolol maleate gel-forming solution], which was in a 5-mL bottle), were acquired from a local pharmacy. Each of 10 subjects dispensed 10 drops from each bottle onto an analytical scale. The mean drop volume for each preparation was then calculated. The fill volume of each bottle and the amount of each medicine that was wasted upon dispensing also were determined. Additionally, 60 pharmacies in the United States were randomly chosen to determine the average cost of each preparation studied. Based on all data obtained, an average daily cost of each medicine was calculated. Results: The generic formulation of timolol maleate (Falcon) ($0.55) and Betimol (Ciba Vision Ophthalmics brand of timolol hemihydrate) ($0.57) demonstrated the lowest cost per day of therapy. In contrast, Betoptic-S (Alcon brand of betaxolol hydrochloride) ($1.60) and Betagan (Allergan brand of levobunonol hydrochloride) ($1.35) had the highest daily cost of therapy. Ocupress (Otsuka America brand of carteolol hydrochloride) had the smallest drop volume (31 μL) and Timoptic-XE had the highest (49 pL). Most preparations were close to their stated bottle fill volume. The amount of wasted medicine varied and was least with Ocupress (27%) and greatest with Betoptic-S (54%). The mean pharmacy price for a 10-mL bottle was lowest for OptiPranolol (Bausch & Lomb brand of metipranolol) ($25.51) and Betimol ($28.28); Betoptic-S ($44.80) and Betagan ($43.67) were the most expensive. Conclusion: Although all commercially available β-adrenergic blockers effectively lower intraocular pressure, one differential factor between medicines is cost, which may be influenced by the price at the pharmacy, volume of medication per bottle, drop size, and medicine wastage. References 1. Dubiner HB, Hill R, Kaufman H, et al. Timolol hemihydrate vs timolol maleate in ocular hypertension and open-angle glaucoma . Am J Ophthalmol . 1996;121:522-528. 2. Beehler CC, Stewart WC, MacDonald DK, et al. A comparison of the ocular hypotensive efficacy of twice-daily 0.25% levobunolol to 0.5% timolol in patients previously treated with 0.5% timolol . J Glaucoma . 1992;1:237-242.Crossref 3. Stewart WC, Shields MB, Allen RC, et al. A three-month comparison of 1% and 2% carteolol and 0.5% timolol in open-angle glaucoma . Graefes Arch Clin Exp Ophthalmol . 1991;229:258-261.Crossref 4. Serle JB, Lustgarten JS, Podos SM. A clinical trial of metipranolol, a noncardioselective beta-adrenergic antagonist, in ocular hypertension . Am J Ophthalmol . 1991;112:302-307. 5. Laurence J, Holder D, Vogel R, et al. A double-masked, placebo-controlled evaluation of timolol in a gel vehicle . J Glaucoma . 1993;2:177-182.Crossref 6. Hartenbaum D, Stek M, Haggert B, et al. Quantitative and cost evaluation of three antiglaucoma beta-blocker agents: Timoptic-XE® versus two generic levobunolol products . Am J Managed Care . 1996;2:157-162. 7. Ball SF, Schneider E. Cost of β-adrenergic receptor blocking agents for ocular hypertension . Arch Ophthalmol . 1992;110:654-657.Crossref 8. Connors KA. A Textbook of Pharmaceutical Analysis . New York, NY: John Wiley & Sons Inc; 1967:260-267. 9. Stewart WC, Castelli WP. Systemic side effects of topical β-adrenergic blockers . Clin Cardiol . 1996;19:691-697.Crossref 10. Lederer CM Jr, Harold RE. Drop size of commercial glaucoma medications . Am J Ophthalmol . 1986;101:691-694. 11. Sorenson SJ, Abel SR. Drop size of ocular carteolol hydrochloride . Am J Hosp Pharm . 1994;51:1470-1473. 12. Wandel T, Fishman D, Novack GD, Kelley E, Chen KS. Ocular hypotensive efficacy of 0.25% levobunolol instilled once daily . Ophthalmology . 1988;95:252-255.Crossref 13. Rakofsky SI, Melamed S, Cohen JS, et al. A comparison of the ocular hypotensive efficacy of once-daily and twice daily levobunolol treatment . Ophthalmology . 1989;96:8-11.Crossref

Lindén, Christina;Alm, Albert

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160027004pmid: 9230825

Abstract Objective: To investigate if a pronounced ciliary muscle contraction, induced by physostigmine salicylate, can abolish the ocular hypotensive effect of latanoprost, a prostaglandin analogue, via inhibition of the uveoscleral outflow. Design: A randomized, crossover study that was double-masked for latanoprost. Physostigmine was the second factor in a 22 factorial experiment. Participants: A total of 20 male and female healthy volunteers (median age, 25 years; age range, 17-30 years). Interventions: Between 7 am and 7 pm, 1 drop of physostigmine salicylate (8 mg/mL) was instilled in 1 eye every other hour. At 8 am, 1 drop of either latanoprost (50 mg/L or placebo was instilled in both eyes. This protocol was repeated a second time with latanoprost administered to previously placebo-treated eyes and vice versa. Main Outcome Measures: Intraocular pressure differences were measured with Goldmann applanation tonometry hourly for 13 hours. Results: Latanoprost reduced the intraocular pressure significantly at 3 to 12 hours after application with a maximal effect at 8 hours after the administration of the dose. The reduction that was obtained with physostigmine administered every other hour was more pronounced, was observed at 1 hour after the administration of the first dose, and increased throughout the day. A significant interaction was seen between 3 and 6 PM (ie, at 7-10 hours after application of latanoprost). Conclusions: Latanoprost and physostigmine have a mainly additive ocular hypotensive effect. Thus, high doses of physostigmine did not abolish the eye pressure-lowering effect of latanoprost, but some interaction was seen at low intraocular pressures. It was concluded that any mechanical effect on the uveoscleral flow achieved with physostigmine is short-lasting compared with the effect obtained with latanoprost, and that latanoprost and miotics can be combined. References 1. Camras CB, Bito LZ, Eakins KE. Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits . Invest Ophthalmol Vis Sci . 1977;16:1125-1134. 2. Bito LZ, Draga A, Blanco J, Camras CB. Long-term maintenance of reduced intraocular pressure by daily or twice daily topical application of prostaglandins to cat or rhesus monkey eyes . Invest Ophthalmol Vis Sci . 1983;24:312-319. 3. Lee P-Y, Podos SM, Severin C. Effect of prostaglandin F2α on aqueous humor dynamics of rabbit, cat, and monkey . Invest Ophthalmol Vis Sci . 1984;25:1087-1093. 4. Giuffrè G. The effects of prostaglandin F2α in the human eye . Graefes Arch Clin Exp Ophthalmol . 1985;222:139-141.Crossref 5. Alm A, Villumsen J. PhXA34, a new potent ocular hypotensive drug: a study on dose-response relationship and on aqueous humor dynamics in healthy volunteers . Arch Ophthalmol . 1991;109:1564-1568.Crossref 6. Alm A, Stjernschantz J, the Scandinavian Latanoprost Study Group. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning: a comparison with timolol . Ophthalmology . 1995;102:1743-1752.Crossref 7. Watson P, Stjernschantz 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;103:126-137.Crossref 8. Camras CB, the United States Latanoprost Study Group. Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six-month, masked, multicenter trial in the United States . Ophthalmology . 1996;103:138-147.Crossref 9. Crawford K, Kaufman PL. Pilocarpine antagonizes prostaglandin F2α-induced ocular hypotension in monkeys: evidence for enhancement of uveoscleral outflow by prostaglandin F2α . Arch Ophthalmol . 1987;105:1112-1116.Crossref 10. Crawford K, Kaufman PL, Gabelt BT. Effects of topical PGF2α on aqueous humor dynamics in cynomolgus monkeys . Curr Eye Res . 1987;6:1035-1044.Crossref 11. Nilsson SFE, Samuelsson M, Bill A, Stjernschantz J. Increased uveoscleral outflow as a possible mechanism of ocular hypotension caused by prostaglandin F2α-1-isopropylester in the cynomolgus monkey . Exp Eye Res . 1989;48:707-716.Crossref 12. Kerstetter JR, Brubaker RF, Wilson SE, Kullerstrand LJ, Prostaglandin F2α-1-isopropylester lowers intraocular pressure without decreasing aqueous humor flow . Am J Ophthalmol . 1988;105:30-34. 13. Villumsen J, Alm A. Prostaglandin F2α-isopropylester eye drops: effects in normal human eyes . Br J Ophthalmol . 1989;73:419-426.Crossref 14. Ziai N, Dolan JW, Kacere RD, Brubaker RF. The effects on aqueous dynamics of PhXA41, a new prostaglandin F2α analogue, after topical application in normal and ocular hypertensive human eyes . Arch Ophthalmol . 1993;111:1351-1358.Crossref 15. Toris CB, Camras CB, Yablonski ME. Effects of PhXA41, a new prostaglandin F2α analog, on aqueous humor dynamics in human eyes . Ophthalmology . 1993;100:1297-1304.Crossref 16. Bill A. The aqueous humor drainage mechanism in the cynomolgus monkey (Macaca irus) with evidence for unconventional routes . Invest Ophthalmol Vis Sci . 1965;4:911-919. 17. Bill A. Aqueous humor dynamics in monkeys (Macaca irus and Cercopithecus ethiops) . Exp Eye Res . 1971;11:195-206.Crossref 18. Bill A, Wålinder PE. The effects of pilocarpine on the dynamics of aqueous humor in a primate (Macaca irus) . Invest Ophthalmol Vis Sci . 1966;5:170-175. 19. Bill A. Effects of atropine and pilocarpine on aqueous humour dynamics in cynomolgus monkeys (Macaca irus) . Exp Eye Res . 1967;6:120-125.Crossref 20. Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes . Exp Eye Res . 1971;12:275-281.Crossref 21. Millar JC, Kaufman PL. PGF2α/pilocarpine interactions on IOP and accommodation in monkeys . Exp Eye Res . 1995;54:677-683.Crossref 22. Villumsen J. Effect of the prostaglandin F2α analogue PhXA41 in human eyes treated with timolol and pilocarpine. In: Effects in Human Eyes of Topical Prostaglandin F2α-Isopropylester and 17-Phenyl Substituted Analogues of Prostaglandin F2α-Isopropylester. Umeå, Sweden: Umeå University Medical Dissertations; 1992. New Series publication 336-ISBN 91-7174-652-8, section 6. 23. Friström B, Nilsson SEG. Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine: a study on patients with elevated intraocular pressure . Arch Ophthalmol . 1993;111:662-665.Crossref 24. Hogg RV, Ledolter J. Experiments with two or more factors . In: Engineering Statistics . New York, NY: Macmillan Publishing Co Inc; 1987:227-237. 25. Lütjen-Drecoll E, Tamm E. Morphological study of the anterior segment of cynomolgus monkey eyes following treatment with prostaglandin F2α . Exp Eye Res . 1988;47:761-769.Crossref 26. Neider MW, Crawford K, Kaufman PL, Bito LZ. In vivo videography of the rhesus monkey accommodative apparatus: age-related loss of ciliary muscle response to central stimulation . Arch Ophthalmol . 1990;108:69-74.Crossref 27. Croft MA, Oyen MJ, Gange SJ, Fisher MR, Kaufman PL. Aging effects on accommodation and outflow facility responses to pilocarpine in humans . Arch Ophthalmol . 1996;114:586-592.Crossref 28. Villumsen J, Alm A. PhXA34—a prostaglandin F2α analogue: effect on intraocular pressure in patients with ocular hypertension . Br J Ophthalmol . 1992;76:214-217.Crossref 29. Hotehama Y, Mishima HK. Clinical efficacy of PhXA34 and PhXA41, two novel prostaglandin F2α-isopropyl ester analogues for glaucoma treatment . Jpn J Ophthalmol . 1993;37:259-269. 30. The Pharmaceutical Society of Great Britain. In: Reynolds JEF, ed. Martindale: the Extra Pharmacopoeia . 31st ed. London, England: The Pharmaceutical Society of Great Britain; 1993:1118-1119. 31. Krishna N, Leopold IH. The effect of BC-48 (demecarium bromide) on normal rabbit and human eyes . Am J Ophthalmol . 1960;49:270-277. 32. Drance SM, Carr F. Effects of phospholine-iodide (217MI) on intraocular pressure in man . Am J Ophthalmol . 1960;49:470-474. 33. Berggren L. Individual responsiveness to topical pilocarpine and the effects of variations in application technique . Acta Ophthalmol . 1985;63:642-646.Crossref 34. Ethier CR, Coloma FM, de Kater AW, Allingham RR. Retroperfusion studies of the aqueous outflow system, II: studies in human eyes . Invest Ophthalmol Vis Sci . 1995;36:2466-2475. 35. Mäepea O, Bill A. The pressures in the episcleral veins, Schlemm's canal and the trabecular meshwork in monkeys: effects of changes in intraocular pressure . Exp Eye Res . 1989;49:645-663.Crossref 36. Zeimer RC, Gieser DK, Wilensky JT, Noth JM, Mori MM, Odunukwe EE. A practical venomanometer: measurement of episcleral venous pressure and assessment of the normal range . 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1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160035005pmid: 9230826

Abstract Background: Interferon alfa-2a has been shown to be effective as an antiangiogenic agent for several systemic human angiogenic disorders and has shown antiangiogenic activity in the laboratory. Objective: To evaluate the safety and efficacy of interferon alfa-2a for the treatment of choroidal neovascularization secondary to age-related macular degeneration. Methods: A randomized, placebo-controlled, parallel, multicenter double-blind trial was performed at 45 ophthalmic centers worldwide. Four hundred eighty-one patients were randomly assigned to 4 treatment groups: placebo or interferon alfa-2a (Roferon-A), 1.5, 3.0, or 6.0 million international units (MIU). Visual acuity testing, clinical examination, fluorescein angiography, and indocyanine green angiography were evaluated, with the primary end point being a comparison of the number of patients who experienced a loss of 3 lines or more of vision at 1 year. Results: At 52 weeks, 40 (38%; 95% confidence interval, 29%-48%) of 105 placebo-treated patients had lost at least 3 lines of vision (with 12% unavailable for follow-up), compared with 142 (50%; 95% confidence interval, 44%-55%) of 286 in the 3 active treatment groups combined. The difference in proportions was not statistically significant. However, a pairwise comparison of these proportions for the placebo group vs the group that received interferon alfa-2a, 6 MIU (with 26% unavailable for follow-up), showed a statistically significant difference in favor of the placebo group (P=.02) and a nearly significant difference for the placebo vs the 1.5-MIU group (P=.05) (with 16% unavailable for follow-up), again favoring the placebo group. The 3-MIU group (with 22% unavailable for follow-up) did not show a statistically significant difference in pairwise comparison (P=.48), suggesting that a dose-response relationship was not evident. Conclusion: Interferon alfa-2a provides no benefit as a treatment for choroidal neovascularization secondary to age-related macular degeneration and may be associated with a poorer visual outcome when given at a dose of 6 MIU. However, the absence of a clear dose-response relationship raises the possibility that the observed differences result from chance. References 1. Macular Photocoagulation Study Group. Argon laser photocoagulation for senile macular degeneration: results of a randomized clinical trial . Arch Ophthalmol . 1992;100:912-918. 2. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration: results of a randomized clinical trial . Arch Ophthalmol . 1991;109:1220-1231.Crossref 3. Freund KB, Yannuzzi LA, Sorenson JA. Age-related macular degeneration of choroidal neovascularization . Am J Ophthalmol . 1993;115:786-791. 4. Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration . Arch Ophthalmol . 1990;108:825-831.Crossref 5. Sorenson JA, Yannuzzi LA, Shakin JL. Recurrent subretinal neovascularization . Ophthalmology . 1985;92:1059-1074.Crossref 6. Brouty-Boye D, Zetter B. Inhibition of cell motility by interferon . Science . 1980;108:516-518.Crossref 7. Friesel R, Komariya A, Maciag T. Inhibition of endothelial cell proliferation by gamma interferon . J Cell Biol . 1987;104:689-696.Crossref 8. Sidky Y, Borden E. Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced responses . Cancer Res . 1987;47:5155-5161. 9. Miller JW, Stinson WG, Folkman J. Regression of iris neovascularization with systemic alfa-interferon . Ophthalmology . 1993;100:9-14.Crossref 10. White CW, Sonheimer HM, Crouch EC, Wilson H, Fan LL. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a . N Engl J Med . 1989;320:1197-1200.Crossref 11. Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa 2a therapy for life-threatening hemangiomas of infancy . N Engl J Med . 1992;326:1456-1463.Crossref 12. Krown SE, Real FX, Vadhan-Raj S, et al. Kaposi's sarcoma and the acquired immune deficiency syndrome: treatment with recombinant interferon alfa and analysis of prognostic factors . Cancer . 1986;57( (suppl 8) ):1662-1665.Crossref 13. Guyer DR, Adamis AP, Gragoudas ES, Folkman J, Slakter JS, Yannuzzi LA. Systemic antiangiogenic therapy for choroidal neovascularization: what is the role of interferon alfa? Arch Ophthalmol . 1992;110:1383-1384.Crossref 14. Engler CB, Sander B, Krofoed P, Larsen M, Vinding R, Lund-Anderson H. Interferon alfa-2a treatment of patients with subfoveal neovascular macular degeneration: a pilot investigation . Acta Scand Ophthalmol . 1993;71:27-31.Crossref 15. Fung WE. Interferon alfa-2a for treatment of age-related macular degeneration . Am J Ophthalmol . 1991;112:349-350. 16. Thomas MA, Ibanez HE. Interferon alfa-2a in the treatment of subfoveal choroidal neovascularization . Am J Ophthalmol . 1993;115:563-568. 17. Poliner LS, Tornambe PE, Michelson PE, Heitzmann JG. Interferon alfa-2a for subfoveal neovascularization in age-related macular degeneration . Ophthalmology . 1993;100:1417-1424.Crossref 18. Kirkpatrick JP, Dick AD, Forrester JV. Clinical experience with interferon alfa-2a for exudative age-related macular degeneration . Br J Ophthalmol . 1993;77:766-770.Crossref 19. Gillies MC, Sarks JP, Beaumont PE, et al. Treatment of choroidal neovascularization in age-related macular degeneration with interferon alfa-2a and alfa-2b . Br J Ophthalmol . 1993;77:759-765.Crossref 20. Lewis ML, Davis J, Chuang E. Interferon alfa-2a in the treatment of exudative age-related macular degeneration . Graefes Arch Clin Exp Ophthalmol . 1993;231:615-618.Crossref 21. Guyer DR, Tiedeman J, Yannuzzi LA, et al. Interferon associated retinopathy . Arch Ophthalmol . 1993;1 11:350-356.Crossref

Fong, Donald S.;Segal, Paul P.;Myers, Frank;Ferris, Frederick L.;Hubbard, Larry D.;Davis, Matthew D.

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160043006pmid: 9230827

Abstract Objective: To describe the characteristics of and risk factors for subretinal fibrosis (SRF) in patients with diabetic macular edema. Patients and Methods: A total of 109 eyes (in 96 persons) with SRF, defined as a mound or sheet of gray to white tissue beneath the retina at or near the center of the macula, were identified during the Early Treatment Diabetic Retinopathy Study, which is a randomized clinical trial of photocoagulation and aspirin treatment in patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. The patients and the ocular characteristics of these 109 eyes, all of which had clinically significant macular edema, were compared with those of 5653 eyes in which clinically significant macular edema, but not SRF, was observed during the trial. Results: In 9 of 109 eyes, the development of SRF may have been directly related to focal photocoagulation. Seventy-four percent of the eyes in which SRF developed had very severe hard exudates in the macula prior to the development of SRF, while this level of hard exudates was seen in only 2.5% of the eyes with clinically significant macular edema in which SRF did not develop (P<.001). Of the 264 eyes with this level of hard exudates at baseline (n=29) or during follow-up (n=235), SRF developed in 30.7% of the eyes, while this complication developed in only 0.05% of 5498 eyes with clinically significant macular edema without this level of hard exudates. Conclusions: Subretinal fibrosis is an infrequent complication of diabetic macular edema. Although it has been reported to be associated with photocoagulation burn intensity, in only 9 of 109 eyes in which SRF developed was it located adjacent to a photocoagulation-related scar (among 4823 eyes that received focal photocoagulation for treatment of macular edema). The strongest risk factor for the development of SRF is very severe hard exudate. References 1. Chandra SR, Bresnick GH, Davis MD, Miller SA, Myers F. Choroidovitreal neovascular ingrowth after photocoagulation for proliferative diabetic retinopathy . Arch Ophthalmol . 1980;98:1593-1599.Crossref 2. Wallow I, Johns K, Barry P, Chandra S, Bindley C. Chorioretinal and choriovitreal neovascularization after photocoagulation for proliferative diabetic retinopathy . Ophthalmology . 1985;92:523-532.Crossref 3. Varley MP, Frank E, Purnell EW. Subretinal neovascularization after focal argon laser for diabetic macular edema . Ophthalmology . 1988;95:567-573.Crossref 4. Berger AR, Boniuk I. Bilateral subretinal neovascularization after focal argon laser photocoagulation for diabetic macular edema . Am J Ophthalmol . 1989;108:88-90. 5. Lewis H, Schachat AP, Haimann MH, et al. Choroidal neovascularization after laser photocoagulation for diabetic macular edema . Ophthalmology . 1990;97:503-511.Crossref 6. Begg IS, Rootman J. Clinico-pathological study of an organized plaque in exudative diabetic maculopathy . Can J Ophthalmol . 1976;11:197-202. 7. Sigurdsson R, Begg IS. Organized macular plaques in exudative diabetic maculopathy . Br J Ophthalmol . 1980;64:392-397.Crossref 8. ETDRS Research Group. Early Treatment Diabetic Retinopathy Study design and baseline patient characteristic: ETDRS report number 7 . Ophthalmology . 1991;98:741-756.Crossref 9. Chew EY, Klein ML, Ferris FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy: ETDRS report 22 . Arch Ophthalmol . 1996;114:1079-1084.Crossref 10. Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema: ETDRS report No. 2 . Ophthalmology . 1987;94:761-774.Crossref 11. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema: ETDRS report No. 4 . Int Ophthamol Clin . 1987;27:263-333.

Polk, Timothy D.;Gass, J. Donald M.;Green, W. Richard;Novak, Michael A.;Johnson, Mark W.

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160048007pmid: 9230828

Abstract Objective: To describe the clinicopathologic features of a previously unreported retinal dystrophy. Methods: Fourteen members of a single family were examined. The medical records of 2 additional family members were reviewed. Pathologic examination was performed on 2 eyes of 1 affected patient. Results: Five individuals were identified with a retinal dystrophy characterized by a glistening inner retinal surface throughout the posterior pole. Visual loss occurred in 3 affected patients in later life owing to superficial polycystic retinal edema and retinal folds. Electroretinographic testing revealed a selective diminution of the b wave. Pathologic examination revealed an abnormal internal limiting membrane with schisis cavities in the inner retina. Endothelial cell swelling, pericyte degeneration, and basement membrane thickening were present in retinal capillaries. Conclusions: A previously unreported sheen retinal dystrophy is described. Pedigree analysis suggests an autosomal dominant mode of inheritance. A primary defect in Müller cells is the suspected, but unproved, cause. No effective treatment for the associated visual loss is known. The term familial internal limiting membrane dystrophy is proposed to describe this condition. References 1. O'Donnell FE, Welch RB. Fenestrated sheen macular dystrophy: a new autosomal dominant maculopathy . Arch Ophthalmol . 1979;97:1292-1296.Crossref 2. Slagsvold JE. Fenestrated sheen macular dystrophy: a new autosomal dominant maculopathy . Acta Ophthalmol . 1981;59:683-688. 3. Daily MJ, Mets MB. Fenestrated sheen macular dystrophy . Arch Ophthalmol . 1984;102:855-856.Crossref 4. Sneed SR, Sieving PA. Fenestrated sheen macular dystrophy . Am J Ophthalmol . 1991;112:1-7. 5. Foos RY. Vitreoretinal juncture: topographical variations . Invest Ophthalmol . 1972;11:801-808. 6. Green WR. The retina . In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook . 4th ed. Philadelphia, Pa: WB Saunders Co; 1996;2:673-674, 1124-1128. 7. Hogan MJ. The vitreous, its structure, and relation to the ciliary body and retina . Invest Ophthalmol . 1963;2:418-445. 8. Newman EA, Frishman LJ. The b-wave . In: Heckenlively JR, Arden GB, eds. Principles and Practice of Clinical Electrophysiology of Vision . St Louis, Mo: Mosby-Year Book Inc; 1991;101-111. 9. Carlson EC. Human retinal capillary basement membrane leaflets are morphologically distinct: a correlated TEM and SEM analysis . Exp Eye Res . 1989;49:967-981.Crossref 10. Gass JDM, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis: update of classification and follow-up study . Ophthalmology . 1993;100:1536-1546.Crossref 11. Yanoff M, Rahn EK, Zimmerman LE. Histopathology of juvenile retinoschisis . Arch Ophthalmol . 1968;79:49-53.Crossref 12. Hirose T, Wolf E, Hara A. Electrophysiological and psychophysical studies in congenital retinoschisis of X-linked recessive inheritance . Doc Ophthalmol Proc Ser . 1977;13:173-184. 13. Peachey NS, Fishman GA, Derlacki DJ, Brigell MG. Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis . Arch Ophthalmol . 1987;105:513-516.Crossref 14. Condon GP, Brownstein S, Wang NS, Kearns JA, Ewing CC. Congenital hereditary (juvenile X-linked) retinoschisis: histopathologic and ultrastructural findings in three eyes . Arch Ophthalmol . 1986;104:576-583.Crossref 15. Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction . Ophthalmology . 1992;99:753-759.Crossref 16. Renie WA. Fundamentals of genetics . In: Renie WA, ed. Goldberg's Genetic and Metabolic Eye Disease . 2nd ed. Boston, Mass: Little Brown & Co; 1986:11-12, 14-15. 17. Gass JDM. Stereoscopic Atlas of Macular Diseases . 3rd ed. St Louis, Mo: CV Mosby Co; 1987:676-683, 694-713. 18. Smiddy WE, Green WR, Michels RG, de la Cruz Z. Ultrastructural studies of vitreomacular traction syndrome . Am J Ophthalmol . 1989;107:177-185. 19. Smiddy WE, Maguire AM, Green WR, et al. Idiopathic epiretinal membranes: ultrastructural characteristics and clinicopathologic correlation . Ophthalmology . 1989;96:811-821.Crossref 20. Gass JDM. Stereoscopic Atlas of Macular Diseases . 2nd ed. St Louis, Mo; CV Mosby Co; 1977:153.

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160055008

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1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160056009

Abstract Objective: To describe the clinical characteristics and survival experience of a prospectively followed up group of patients with small choroidal melanoma. Methods: The Collaborative Ocular Melanoma Study (COMS) is a set of clinical trials designed to compare the role of radiotherapy and enucleation in the treatment of medium and large-size choroidal melanoma. From December 1986 to August 1989, patients with small choroidal melanoma, not large enough to be eligible for the COMS clinical trials, were offered participation in a nonrandomized prospective follow-up study. Small choroidal melanomas were defined as 1.0 to 3.0 mm in apical height and at least 5.0 mm in basal diameter. A total of 204 patients were enrolled in the study. Patients were followed up annually through August 1989. Two additional assessments of treatment status and mortality were conducted in 1993-1994 and 1995-1996. The median length of follow-up was 92 months. Eight percent of patients were treated at the time of study enrollment and an additional 33% were treated during follow-up. Results: Twenty-seven patients have died; 6 deaths were reported by the clinical center as due to metastatic melanoma. The Kaplan-Meier estimate of 5-year all-cause mortality was 6.0% (95% confidence interval, 2.7%-9.3%) and 8-year all-cause mortality was 14.9% (95% confidence interval, 9.6%-20.2%). Conclusions: Otherwise healthy patients, average age of 60 years, without a previous diagnosis of malignant disease who have small choroidal lesions judged to be melanoma have a low risk of dying within 5 years. References 1. Karcioglu ZA, Gordon RA, Karcioglu GL. Tumor seeding in ocular fine needle aspiration biopsy . Ophthalmology . 1985;92:1763-1767.Crossref 2. Shields JA, Shields CL, Donoso LA. Management of posterior uveal melanoma . Surv Ophthalmol . 1991;36:161-195.Crossref 3. Shields JA, McDonald PR. Improvements in the diagnosis of posterior uveal melanomas . Arch Ophthalmol . 1974;97:259-264.Crossref 4. Collaborative Ocular Melanoma Study Group. Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma Study: COMS Report No. 1 . Arch Ophthalmol . 1990;108:1268-1273.Crossref 5. Robertson DM, Campbell RJ. Errors in the diagnosis of malignant melanoma of the choroid . Am J Ophthalmol . 1979;87:269-275. 6. Davidorf FH, Letson AD, Weiss ET, Levine E. Incidence of misdiagnosed and unsuspected choroidal melanomas: a 50-year experience . Arch Ophthalmol . 1983;101:410-412.Crossref 7. McLean IW, Foster WD, Zimmerman LE. Uveal melanoma: location, size, cell type, and enucleation as risk factors in metastasis . Hum Pathol . 1982;13:123-132.Crossref 8. Straatsma BR, Fine SL, Earle JD, Hawkins BS, Diener-West M, McLaughlin JA, the Collaborative Ocular Melanoma Study Research Group. Enucleation versus plaque irradiation for choroidal melanoma . Ophthalmology . 1988;95:1000-1004.Crossref 9. Gass JDM. Observation of suspected choroidal and ciliary body melanomas for evidence of growth prior to enucleation . Ophthalmology . 1980;87:523-528.Crossref 10. Augsburger JJ. Is observation really appropriate for small choroidal melanomas . Trans Am Ophthalmol Soc . 1993;91:147-168. 11. Butler P, Char DH, Zarbin M, Kroll S. Natural history of indeterminate pigmented choroidal tumors . Ophthalmology . 1994;101:710-716.Crossref 12. Shields JA, Shields CL, Kiratli H, Cater JR, De Potter P. Metastatic risk factors for small choroidal melanocytic lesions: are we waiting too long? Presented at The Macula Society: Scientific Program. The Eighteenth Annual Scientific Meeting; February 25,1995; Palm Beach Gardens, Fla. Page 126. 13. Davidorf FH, Lang JR: The natural history of malignant melanoma of the choroid: small vs large tumors . Trans Am Acad Ophthalmol Otolaryngol . 1975;79:310-320. 14. Zimmerman LE, McLean IW. Montgomery Lecture, 1975: changing concepts of the prognosis and management of small malignant melanomas of the choroid . Trans Ophthalmol Soc U K . 1975;95:487-494. 15. Hagler WS, Jarrett WH, Killian JH. The use of the 32P test in the management of malignant melanoma of the choroid: a five-year follow-up study . Trans Am Acad Ophthalmol Otolaryngol . 1977;83:49-60. 16. Packard RBS. Pattern of mortality in choroidal malignant melanoma . Br J Ophthalmol . 1980;64:565-575.Crossref 17. Seddon JM, Albert DM, Lavin PT, Robinson N. A prognostic factor study of disease-free interval and survival following enucleation for uveal melanoma . Arch Ophthalmol . 1983;101:1894-1899.Crossref 18. Shammas HF, Blodi FC. Prognostic factors in choroidal and ciliary body melanomas . Arch Ophthalmol . 1977;95:63-69.Crossref 19. Thomas JV, Green WR, Maumenee AE. Small choroidal melanomas: a long-term follow-up study . Arch Ophthalmol . 1979;97:861-864.Crossref 20. McLean IW, Foster WD, Zimmerman LE. Prognostic factors in small malignant melanomas of choroid and ciliary body . Arch Ophthalmol . 1977;95:48-58.Crossref 21. Barr CC, Sipperley JO, Nicholson DH. Small melanomas of the choroid . Arch Ophthalmol . 1978;96:1580-1582.Crossref 22. Greer CH, Buckley C, Buckley J, Ramsay R, La Nauze J. An Australian choroidal melanoma survey: factors affecting survival following enucleation . Aust J Ophthalmol . 1981;9:255-261.Crossref 23. Diener-West M, Hawkins BS, Markowitz JM, Schachat AP. A review of mortality from choroidal melanoma, II: a meta-analysis of 5-year mortality rates following enucleation, 1966 through 1988 . Arch Ophthalmol . 1992;110:245-250.Crossref 24. Collaborative Ocular Melanoma Study Group. Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study: COMS Report No. 3 . Control Clin Trials . 1993;14:362-391.Crossref 25. Collaborative Ocular Melanoma Study. COMS Manual of Procedures . Springfield, Va: National Technical Information Service; January 1995. PB95-179693. 26. Collaborative Ocular Melanoma Study. COMS Study Forms Book . Springfield, Va: National Technical Information Service; May 1991; PB91-217315. 27. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations . J Am Stat Assoc . 1958;53:457-481.Crossref 28. Davidorf FH, Pajka JT, Makley TA, Kartha MK. Radiotherapy for choroidal melanoma: an 18-year experience with radon . Arch Ophthalmol . 1987;105:352-355.Crossref 29. Lommatzsch PK. Results after β-irradiation (106Ru/106Rh) of choroidal melanomas: twenty years' experience . Am J Clin Oncol . 1987;10:146-151.Crossref 30. Shields CL, Shields JA, Kiratli H, De Potter P, Cater JR. Risk factors for growth and metastasis of small choroidal melanocytic lesions . Ophthalmology . 1995;102:1351-1361.Crossref

Grossniklaus, Hans E.;Albert, Daniel M.;Green, W. Richard;Conway, Brian P.;Hovland, Kenneth R.

1997 Archives of Ophthalmology

doi: 10.1001/archopht.1997.01100160064010pmid: 9230830

Abstract Objective: To describe 2 enucleated eyes of patients enrolled in the Collaborative Ocular Melanoma Study that contained primary choroidal melanoma with clear cell features. Methods: During a 9-year period, 1493 eyes enucleated as part of the Collaborative Ocular Melanoma Study routinely processed for histologic examination were evaluated by the pathology review committee (H.E.G, D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were identified and immunostained for S100 protein and HMB 45. Portions of the tumors were processed for electron microscopic examination. Results: Results of electron microscopic examination of both tumors displayed malignant melanoma (mixed cell type with many malignant cells with clear cytoplasm). The cytoplasm of the clear cells stained with periodic acid-Schiff and failed to stain when pretreated with diastase. Results of immunohistochemical stains in both tumors were positive for S100 protein and HMB 45 in the tumor cells. Results of electron microscopic examination showed that the cytoplasm of the clear cells contained scattered glycogen granules, premelanosomes, and melanosomes. Conclusion: These cases represent a clear cell variant of malignant melanoma of the choroid. This tumor should not be confused with metastatic clear cell carcinoma to the choroid. References 1. The Collaborative Ocular Melanoma Study Group. Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study: COMS report No. 3 . Control Clin Trials . 1993;14:362-391.Crossref 2. Albert DM, Green WR, Grossniklaus HE, Diener-West M for the Collaborative Ocular Melanoma Study Group. Histopathologic review of 1,091 uveal melanomas . Invest Ophthalmol Vis Sci . 1994;35( (suppl) ):1925. Abstract. 3. The Collaborative Ocular Melanoma Study Group. Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma Study: COMS report No. 1 . Arch Ophthalmol . 1990;108:1268-1273.Crossref 4. 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Clear cell carcinoma of the ovary: light and electron microscopic studies . CA Cancer J Clin . 1977;40:3019-3029. 11. Chesky VE, Hellwig CA, Barbosa E. Clear cell tumors of the thyroid . Surgery . 1957;42:282-289. 12. Unni KK, Dahlin DC, Beabout JW, Sim FH. Chondrosarcoma: clear cell variant . J Bone Joint Surg Am . 1976;58:676-683. 13. Kurman RJ, Norris HJ. Mesenchymal tumors of the uterus, VI: epithelioid smooth muscle tumors including leiomyoblastoma and clear cell leiomyoma: a clinical and pathologic analysis of 26 cases . CA Cancer J Clin . 1976;37:1853-1865. 14. Becker NH, Soifer I. Benign clear cell tumor ('sugar tumor') of the lung . CA Cancer J Clin . 1971;27:712-719. 15. Donath K, Seifert G, Schmitz R. Zur Diagnose und Ultrastruktur des tubularen Spechelgancarcinoms: Epithelial-myoepitheliales Schaltstuckcarcinoma . Virchows Arch . 1972;356:16-31.Crossref 16. Haas JE, Bonadio JF, Beckwith JB. Clear cell sarcoma of the kidney with emphasis on ultrastructural studies . CA Cancer J Clin . 1984;54:2978-2987. 17. Enzinger FM. Clear cell sarcoma of the tendons and aponeuroses: an analysis of 21 cases . CA Cancer J Clin . 1965;18:1163-1174. 18. Enzinger FM, Weiss SW. Malignant tumors of uncertain histogenesis . In: Enzinger FM, Weiss SW, eds. Soft Tissue Tumors . St Louis, Mo: Mosby-Year Book Inc; 1988:929-965. 19. Zimmerman LE. Malignant melanoma of the uveal tract . In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook . Philadelphia, Pa: WB Saunders Co; 1985-1986:2072-2139. 20. Messmer EM, Hoops JP, Stefani FH. Signet ring malignant melanoma of the choroid . Invest Ophthalmol Vis Sci . 1996;37( (suppl) ):244. Abstract. 21. Callender GR. Malignant melanotic tumors of the eye: a study of histologic types in 111 cases . Trans Am Acad Ophthalmol Otolaryngol . 1931;36:131-142. 22. McLean IW, Zimmerman LE, Evans RM. Reappraisal of Callender's spindle A type of malignant melanoma of the choroid and ciliary body . Am J Ophthalmol . 1978;86:557-564. 23. Grossniklaus HE, Green WR. Uveal tumors . In: Garner A, Klintworth GK, eds. Pathobiology of Ocular Disease: A Dynamic Approach . 2nd ed. New York, NY: Marcel Dekker Inc; 1994:1423-1477. 24. McLean IW, Burnier MN, Zimmerman LE, Jakobiec FA. Tumors of the eye and ocular adnexa . In: Rosai J, Sobin LH, eds. Atlas of Tumor Pathology . Washington, DC: Armed Forces Institute of Pathology; 1994:189-190. 25. Pfaffenbach DD, Green WR, Maumenee AE. Balloon cell nevus of the conjunctiva . Arch Ophthalmol . 1972;87:192-195.Crossref 26. Saornil MA, Egan KM, Gragoudas ES, Seddon JM, Walsh SM, Albert DM. Histopathology of proton-beam irradiated vs enucleated uveal melanomas . Arch Ophthalmol . 1992;110:1112-1118.Crossref 27. Taylor HB, Norris HJ. Lipid cell tumors of the ovary . Cancer . 1967;20:1953-1962.Crossref 28. Ramos CV, Taylor HB. Lipid-rich carcinoma of the breast: a clinicopathologic analysis of 13 examples . Cancer . 1974;33:812-819.Crossref 29. LiVolsi VA, Brooks JJ, Soslow R, Johnson BL, Elder DE. Signet cell melanocytic lesions . Mod Pathol . 1992;5:515-520. 30. Chung EB, Enzinger FM. Malignant melanoma of the soft parts: a reassessment of clear cell sarcoma . Am J Surg Path . 1983;7:405-413.Crossref 31. Fletcher JA. Translocation (12;22)(q13-14; q12) is a nonrandom aberration in soft tissue clear cell sarcoma . Genes Chromosomes Cancer . 1992;5:184. Abstract.Crossref 32. NCI Surveillance, Epidemiology and End Results Web site. Available at: http://www-seer.ims.nci.nih.gov/cgi-bin/imagemap.USASEI. 33. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to the eye, part I: incidence in 213 adult patients with generalized malignancy . Am J Ophthalmol . 1967;63:723-726. 34. Ferry AP, Font RL. Carcinoma metastatic to the eye and orbit, I: a clinicoathologic study of 227 cases . Arch Ophthalmol . 1974;92:276-286.Crossref