The Placebo Effect

      Abstract

      Placebos have been traditionally regarded as deceptive therapies and have not been understood in the broader context of social symbols and of interpersonal factors that surround the healing process itself. Although the power of inert substances to heal is well recognized, the placebo effect also influences the outcome of conventional therapies. The role of the placebo in modern medicine is poorly defined because of a lack of a common understanding of what the placebo effect is and because of the negative connotions associated with its use. The response rate to placebo varies by illness. The natural course of disease and patient or physician bias can be misinterpreted as a placebo response. In research, the placebo effect is therapeutic noise to be removed by placebo-controlled trials. Few studies are designed to measure the placebo response rate directly. Placebos are a reminder of how little is known about mind-body interaction. The placebo effect may be one of the most versatile and underused therapeutic tools at the disposal of physicians.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Survey of Ophthalmology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Loteprednol Etabonate Postoperative Inflammatory Study Group 2
        A double-masked, placebo-controlled evaluation of 0.5% loteprednol etabonate in the treatment of postoperative inflammation.
        Ophthalmology. 1998; 105: 1780-1786
        • Herpetic Eye Diseas Study Group
        Acyclovir for the prevention of recurrent herpes simplex virus eye disease.
        N Engl J Med. 1998; 339: 300-306
        • Pharmacological Therapy for Macular Degeneration Study Group
        Interferon alfa-2A is ineffective for patients with choroidal neovascularization secondary to age related macular degeneration.
        Arch Ophthalmol. 1997; 115: 865-872
        • Herpetic Eye Disease Study Group
        A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis.
        Arch Ophthalmol. 1997; 115: 703-712
        • The Studies of Ocular Complications of AIDS Research Group, AIDS Clinical Trial Group
        MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.
        Arch Ophthalmol. 1997; 115: 1528-1536
        • Herpetic Eye Disease Study Group
        A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus.
        Arch Ophthalmol. 1996; 114: 1065-1072
        • Endophthalmitis Vitrectomy Study Group
        Results of the Endophthalmitis Vitrectomy Study.
        Arch Ophthalmol. 1995; 113: 1479-1496
        • Ischemic Optic Neuropathy Decompression Trial Research Group
        Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful.
        JAMA. 1995; 272: 625-632
        • Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion
        The Central Vein Occlusion Study Group M Report.
        Ophthalmology. 1995; 102: 1425-1433
        • 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
      1. Kefauver-Harris Amendments of October 10, 1962 to Food, Drug and Cosmetic Act. Code Federal Regulation.

      2. Federal Register 35:7250, 1970

      3. Dietary Supplement Health and Education Act of 1994, Public Law 103–417

        • Abelson M.B.
        Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model.
        Ann Allergy Asthma Immunol. 1998; 81: 211-218
        • Abelson M.B.
        • Spitalny L.
        Combined analysis of two studies using the conjunctival allergen challenge model to evaluate olopatadine hydrochloride, a new ophthalmic antiallergic with dual activity.
        Am J Ophthalmol. 1998; 125: 797-804
        • Ader R.
        The role of conditioning in pharmacotherapy.
        in: Harrington A. The Placebo Effect An Interdisciplinary Exploration. Harvard University Press, Cambridge1997
        • Ader R.
        • Cohen N.
        Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus.
        Science. 1982; 215: 1534-1536
        • Ambersom Jr, J.B.
        • McMahon B.T.
        • Pinner M.A.
        A clinical trial of sanocrysin in pulmonary tuberculosis.
        Am Rev Tuberculosis. 1931; 24: 401-435
        • Andren L.
        • Wadevik H.
        • Kutti H.
        • Hansson L.
        • et al.
        Stress and platelet activation.
        Acta Haematol. 1983; 70: 302-306
        • Angell M.
        • Kassirer J.P.
        Alternative medicine—the risks of untested and unregulated remedies.
        N Engl J Med. 1998; 339: 839-841
        • Archer T.P.
        • Leier C.V.
        Placebo treatment in congestive heart failure.
        Cardiology. 1992; 81: 125-133
        • Asbell P.
        • Howes J.
        A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis.
        CLAO J. 1997; 23: 31-36
        • Assil K.K.
        • Massry G.
        • Lehmann R.
        • et al.
        Control of ocular inflammation after cataract extraction with rimexolone 1% ophthalmic suspension.
        J Cataract Refract Surg. 1997; 23: 750-757
        • Beck R.W.
        • Cleary P.A.
        • Anderson Jr, M.M.
        • et al.
        A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis.
        N Engl J Med. 1992; 326: 581-588
        • Beecher H.K.
        Surgery as placebo.
        JAMA. 1961; 176: 1102-1107
        • Beecher H.K.
        Increased stress and effectiveness of placebos and “active” drugs.
        Science. 1960; 132: 91-92
        • Beecher H.K.
        Powerful placebo.
        JAMA. 1955; 159: 1602-1606
        • Benson H.
        • Epstein M.D.
        The placebo effect.
        JAMA. 1975; 232: 1225-1227
        • Benson H.
        • McCallie Jr, D.P.
        Angina pectoris and the placebo effect.
        N Engl J Med. 1979; 300: 1424-1429
        • Binder H.J.
        • Cocco A.
        • Crossley R.J.
        Cimetidine in the treatment of duodenal ulcer.
        Gastroenterology. 1978; 74: 380-388
        • Biswas N.R.
        • Beri S.
        • Das G.K.
        • Mongre P.K.
        Comparative double-blind multicentric randomised placebo controlled clinical trial of a herbal preparation of eye drops in some ocular ailments.
        J Indian Med Assoc. 1996; 94: 101-102
        • Brenner M.H.
        • Curbow B.
        • Javitt J.C.
        Vision change and quality of life in the elderly.
        Arch Ophthalmol. 1993; 111: 680-685
        • Brody H.
        The lie that heals.
        Ann Intern Med. 1982; 97: 112-118
        • Brody H.
        The doctor as therapeutic agent.
        in: Harrington A. The Placebo Effect An Interdisciplinary Exploration. Harvard University Press, Cambridge1997
        • Brody H.
        Placebo effect.
        in: White L. Tursky B. Schwartz G.E. Placebo Theory, Research, and Mechanisms. Guilford Press, New York1985
        • Brown W.A.
        The placebo effect.
        JAMA. 1997; 278: 1291-1292
        • Brown W.A.
        • Johnson M.F.
        • Chen M.G.
        Clinical features of depressed patients who do and do not improve with placebo.
        Psychiatry Res. 1992; 41: 203-204
        • Brunner R.
        • Widder R.A.
        • Fischer R.A.
        Clinical efficacy of haemorheological treatment using plasma exchange, selective adsorption and membrane differential filtration in maculopathy, retinal vein occlusion and uveal effusion syndrome.
        Transfus Sci. 1996; 17: 493-498
        • Bunker J.P.
        • Hinkley D.
        • McDermott W.V.
        Surgical innovation and its evaluation.
        Science. 1978; 200: 937-941
        • Centofanti M.
        • Schiavone M.
        • Lambiase A.
        Efficacy of mipragoside ophthalmic gel in vernal keratoconjunctivitis.
        Eye. 1996; 10: 422-424
        • Chaput de Saintonge D.M.
        • Herxheimer A.
        Harnessing placebo effects in health care.
        Lancet. 1994; 344: 995-998
        • Chaturvedi N.
        • Sjolie A.K.
        • Stephenson J.M.
        Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes.
        Lancet. 1998; 351: 28-31
        • Chitkara D.K.
        • Jayamanne D.G.
        • Griffiths P.G.
        • Fsadni M.G.
        Effectiveness of topical diclofenac in relieving photophobia after pupil dilation.
        J Cataract Refract Surg. 1997; 23: 740-744
        • Ciprandi G.
        • Buscaglia S.
        • Catrullo A.
        Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti-allergic activity.
        Clin Exp Allergy. 1997; 27: 182-191
        • Clark P.I.
        • Leaverton P.E.
        Scientific and ethical issues in the use of placebo controls in clinical trials.
        Annu Rev Public Health. 1994; 15: 19-38
        • Cobb L.A.
        • Thomas G.I.
        • Dillard D.H.
        • et al.
        An evaluation of internal-mammary-artery ligation by a double-blinded technique.
        N Engl J Med. 1959; 260: 1115-1118
        • Cohen J.S.
        • Greff L.J.
        • Novack G.D.
        • Wind B.E.
        A placebo-controlled, double-masked evaluation of mitomycin C in combined glaucoma and cataract procedures.
        Ophthalmology. 1996; 103: 1934-1942
        • Coppes M.J.
        • Anderson R.A.
        • Egeler R.M.
        • Wolff J.R.
        Alternative therapies for the treatment of childhood cancer (letter).
        N Engl J Med. 1998; 339: 846-847
        • Crawshaw R.
        Lying.
        in: Bulger R.J. In Search of the Modern Hippocrates. University of Iowa Press, Iowa City1987
        • De Bustros S.
        Vitrectomy for prevention of macular holes.
        Ophthalmology. 1994; 101: 1055-1060
        • Derick R.J.
        • Robin A.L.
        • Walters T.R.
        • et al.
        Brimonidine tartrate.
        Ophthalmology. 1997; 104: 131-136
        • Dhume V.G.
        • Agshikar N.V.
        • Diniz R.S.
        Placebo-induced side effects in healthy volunteers.
        Clinician. 1975; 39: 289-290
        • Diehl H.S.
        • Baker A.B.
        • Cowan D.W.
        Cold vaccines.
        JAMA. 1938; 111: 1168-1173
        • Dimond E.G.
        • Kittle C.F.
        • Crockett J.E.
        Comparison of internal mammary ligation and sham operation for angina pectoris.
        Am J Cardiol. 1960; 5: 483-486
        • Donzis P.B.
        • Factor J.S.
        Visual field loss resulting from cervical chiropractic manipulation.
        Am J Ophthalmol. 1997; 123: 851-852
        • Drake Jr, M.E.
        Saline activation of pseudoepileptic seizures.
        Clin Electroencephalogr. 1985; 16: 171-176
        • Dunlop D.M.
        • Henderson T.L.
        • Inch R.S.
        A survey of 17,301 prescriptions on Form E. C. 10.
        BMJ. 1952; 1: 292-293
        • Egan C.A.
        • Hodge D.O.
        • McLaren J.W.
        • Bourne W.M.
        Effect of dorzolamide on corneal endothelial function in normal human eyes.
        Invest Ophthalmol Vis Sci. 1998; 39: 23-29
        • Eisenberg D.M.
        • Kessler R.C.
        • Foster C.
        Unconventional medicine in the United States.
        N Engl J Med. 1993; 328: 246-252
        • Evans B.J.
        • Evans B.V.
        • Jordahl-Moroz J.
        • Nabee M.
        Randomized double-masked placebo-controlled trial of a treatment for congenital nystagmus.
        Vision Res. 1998; 38: 2193-2202
        • Evans F.J.
        Expectancy, therapeutic instructions, and the placebo response.
        in: White L. Tursky B. Schwartz G.E. Placebo Theory, Research, and Mechanisms. Guilford Press, New York1985
        • Feke G.T.
        • Yoshida A.
        • Ogasawara H.
        • et al.
        Retinal blood flow increases following short-term aspirin usage in type I diabetics with no or minimal retinopathy.
        Ophthalmic Res. 1996; 28: 108-116
        • Feman S.S.
        • Leonard-Martin T.C.
        • Redman J.R.
        The Vanderbilt Classification System in the evaluation of diabetic retinopathy patients treated with Alredase.
        Trans Am Ophthalmol Soc. 1996; 94: 433-450
        • Ferro J.F.
        • de Pablos M.
        • Logrono M.J.
        • et al.
        Postoperative contamination after using vancomycin and gentamicin during phacoemulsification.
        Arch Ophthalmol. 1997; 115: 165-170
        • Fisher P.
        • Ward A.
        Complementary medicine in Europe.
        BMJ. 1994; 309: 107-111
        • Fontanarosa P.H.
        • Lundberg G.D.
        Complementary, alternative, unconventional, and integrative medicine.
        Arch Fam Med. 1998; 7: 18-19
        • Fontanarosa P.H.
        • Lundberg G.D.
        Alternative medicine meets science.
        JAMA. 1998; 280: 1618-1619
        • Friedlaender M.H.
        • Howes J.
        A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis.
        Am J Ophthalmol. 1997; 123: 455-464
        • Frucht-Pery J.
        • Solomon A.
        • Siganos C.S.
        • et al.
        Treatment of inflamed pterygium and pinguecula with topical indomethacin 0.1% solution.
        Cornea. 1997; 16: 42-47
        • Ghanchi F.D.
        • Khan M.Y.
        Sublingual lorazepam as premedication in peribulbar anesthesia.
        J Cataract Refract Surg. 1997; 23: 1581-1584
        • Giede-Tuch C.
        • Westhoff M.
        • Zarth A.
        Azelastine eye-drops in seasonal allergic conjunctivitis or rhinoconjunctivitis.
        Allergy. 1998; 53: 857-862
        • Gigliotti F.
        • Hendley J.O.
        • Morgan J.
        • et al.
        Efficacy of topical antibiotic therapy in acute conjunctivitis in children.
        J Pediatr. 1984; 104: 623-626
        • Gilbert J.P.
        • McPeek B.
        • Mosteller F.
        Statistics and ethics in surgery and anesthesia.
        Science. 1977; 198: 684-689
        • Gillies M.C.
        • Garrett S.K.
        • Shina S.M.
        • et al.
        Topical interferon alpha 2b for corneal haze after excimer laser photorefractive keratectomy.
        J Cataract Refract Surg. 1996; 22: 891-900
        • Gotzsche P.C.
        Is there logic in the placebo (see comments)?.
        Lancet. 1994; 344: 925-926
        • Gould B.A.
        • Mann S.
        • Davies A.B.
        • et al.
        Does placebo lower blood pressure?.
        Lancet. 1981; 2: 1377-1381
        • Gracely R.H.
        • Dubner R.
        Reliability and validity of verbal descriptor scales of painfulness.
        Pain. 1987; 29: 175-185
        • Greenberg L.M.
        • Roth S.
        Differential effects of abrupt versus gradual withdrawal of chlorpromazine in hospitalized chronic schizophrenic patients.
        Am J Psychiatry. 1966; 123: 221-226
        • Grevert P.
        • Goldstein A.
        Placebo analgesia, naloxone, and the role of endogenous opioids.
        in: White L. Tursky B. Schwartz G.E. Placebo Theory, Research, and Mechanisms. Guilford Press, New York1985
        • Grover S.
        • Fishman G.A.
        • Fiscella R.G.
        • Adelman A.E.
        Efficacy of dorzolamide hydrochloride in the management of chronic cystoid macular edema in patients with retinitis pigmentosa.
        Retina. 1997; 17: 222-231
        • Guyatt G.
        • Sackett D.
        • Taylor D.W.
        • et al.
        Determining optimal therapy.
        N Engl J Med. 1986; 314: 889-892
        • Guyatt G.H.
        • Keller J.L.
        • Jaeschke R.
        • et al.
        The n of 1 randomized controlled trial.
        Ann Intern Med. 1990; 112: 293-299
        • Hahn R.A.
        The nocebo phenomenon.
        in: Harrington A. The Placebo Effect An Interdisciplinary Exploration. Harvard University Press, Cambridge1997
        • Hedner J.
        • Svedmyr N.
        • Lunde H.
        • Mandahl A.
        The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma.
        Surv Ophthalmol. 1997; 41: S111-S115
        • Hettinger M.E.
        • Gill D.J.
        • Robin J.B.
        • et al.
        Evaluation of diclogenac sodium 0.1% ophthalmic solution in the treatment of ocular symptoms after bilateral radial keratotomy.
        Cornea. 1997; 16: 406-413
        • Hingorani M.
        • Moodaley L.
        • Calder V.L.
        • et al.
        A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis.
        Ophthalmology. 1998; 105: 1715-1720
        • Houston W.R.
        The doctor himself as a therapeutic agent.
        Ann Intern Med. 1938; 11: 1416-1425
        • Imboden J.B.
        Psychosomatic medicine.
        in: Harvey A.M. Johns R.J. Owens A.H. Ross R.S. The Principles and Practice of Medicine. Appleton-Century-Crofts, New York1968
        • Jackson W.B.
        • Easterbrook W.M.
        • Connolly W.E.
        • Leers W.D.
        Treatment of blepharitis and blepharoconjunctivitis.
        Can J Ophthalmol. 1982; 17: 153-156
        • Jacobs J.J.
        Building bridges between two worlds.
        Acad Med. 1995; 70: 40-41
        • Jenkin C.D.
        Recent evidence supporting psychologic and social risk factors for coronary disease.
        N Engl J Med. 1976; 294: 1033-1038
        • Jentzen J.M.
        • Amatuzio J.
        • Peterson G.F.
        Complications of cervical manipulation.
        J Forensic Sci. 1987; 32: 1089-1094
        • Johnson A.G.
        Surgery as a placebo.
        Lancet. 1994; 344: 1140-1142
        • Johnson L.N.
        • Could T.J.
        • Krohel G.B.
        Effect of levodopa and carbidopa on recovery of visual function in patients with nonarteritic anterior ischemic optic neuropathy of longer than six months duration.
        Am J Ophthalmol. 1996; 121: 77-83
        • Katz J.
        • Gilbert D.
        • Quigley H.A.
        • Sommer A.
        Estimating progression of visual field loss in glaucoma.
        Ophthalmology. 1997; 104: 1017-1025
        • Kienle G.S.
        • Kiene H.
        The powerful placebo effect.
        J Clin Epidemiol. 1997; 50: 1311-1318
        • Kienle G.S.
        • Kiene H.
        Placebo effect and placebo concept.
        Alternative Therap Health Med. 1996; 2: 39-54
        • Klockgether-Radke A.
        • Neumann S.
        • Neumann P.
        • et al.
        Ondansetron, droperidol and their combination for the prevention of post-operative vomiting in children.
        Eur J Anaesthesiol. 1997; 14: 362-367
        • Ko R.J.
        Adulterants in Asian patent medicines (letter).
        N Engl J Med. 1998; 339: 847
        • Krakoff L.R.
        • Dziedzic S.
        • Man S.J.
        • et al.
        Plasma epinephrine concentration in healthy men.
        J Am Coll Cardiol. 1985; 5: 352-356
        • Kruger A.
        • Matulla B.
        • Wolzt M.
        • et al.
        Short-term oral pentoxifylline use increases choroidal blood flow in patients with age-related macular degeneration.
        Arch Ophthalmol. 1998; 116: 27-30
        • Laporte J.R.
        • Figueras A.
        Placebo effects in psychiatry.
        Lancet. 1994; 344: 1206-1209
        • Larson E.B.
        • Ellsworth A.J.
        • Oas J.
        Randomized clinical trials in single patients during a 2-year period.
        JAMA. 1993; 270: 2708-2712
        • Lasagna L.
        • Laties V.G.
        • Dohan J.L.
        Further studies on the “pharmacology” of a placebo administration.
        J Clin Invest. 1958; 37: 533-557
        • Leber P.
        The placebo control in clinical trials (a view from the FDA).
        Psychopharmacol Bull. 1986; 22: 30-32
        • Lehrman N.S.
        Pleasure heals.
        Arch Intern Med. 1993; 153: 929-934
        • Leslie A.
        Ethics and the practice of placebo therapy.
        Am J Med. 1954; 16: 854-862
        • Levine J.D.
        • Gordon N.C.
        • Fields H.L.
        The mechanism of placebo analgesia.
        Lancet. 1978; 2: 654-657
        • Leys M.J.
        • van Slycken S.
        • Nork T.M.
        • Odom J.V.
        Acetazolamide affects performance on the Nagel II anomaloscope.
        Graefes Arch Clin Exp Ophthalmol. 1996; 234: S193-S197
        • LoVecchio F.
        • Curry S.C.
        • Bagnasco T.
        Butyrolactone-induced central nervous system depression after ingestion of RenewTrient, a dietary supplement (letter).
        N Engl J Med. 1998; 339: 847-848
        • Lowinger P.
        • Dobie S.
        What makes placebos work? A study of placebo response rates.
        Arch Gen Psychiatry. 1969; 20: 84-88
        • Mabey D.
        • Whitworth J.A.
        • Eckstein M.
        • et al.
        The effects of multiple doses of ivermectin on ocular onchocerciasis.
        Ophthalmology. 1996; 103: 1001-1008
        • MacLennan A.H.
        • Wilson D.H.
        • Taylor A.W.
        Prevalence and cost of alternative medicine in Australia.
        Lancet. 1996; 347: 569-573
      4. Margo CE: Recurrent episcleritis and emotional stress (letter). Arch Ophthalmol 102:821, 824, 1984

        • McGraw B.F.
        • Hemberger J.A.
        • Smith A.L.
        • Schroeder J.S.
        Variability of exercise performance during long-term placebo treatment.
        Clin Pharmacol Ther. 1981; 30: 321-327
        • Mikawa K.
        • Nishina K.
        • Maekawa N.
        • et al.
        Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery.
        Can J Anaesth. 1997; 44: 95-98
        • Morselli P.L.
        • Garattini S.
        Monosodium glutamate and the Chinese restaurant syndrome.
        Nature. 1970; 227: 611-612
        • Moses L.E.
        The series of consecutive cases as a device for assessing outcomes of intervention.
        N Engl J Med. 1984; 311: 705-710
        • Murali S.
        • Uretsky B.F.
        • Kolesar J.A.
        • et al.
        The acute effect of an oral inotropic placebo on the exercise capacity of patients with chronic cardiac failure.
        Chest. 1988; 94: 262-266
        • Novack D.H.
        Therapeutic aspects of the clinical encounter.
        J Gen Intern Med. 1987; 2: 346-355
        • Obermayer M.
        Psychocutaneous Medicine. Charles C Thomas, Springfield, IL1955
        • Olness K.
        • Ader R.
        Conditioning as an adjunct in the pharmacotherapy of lupus erythematosus.
        Dev Behav Pediatr. 1992; 13: 124-125
        • Pepper O.H.P.
        A note on placebo.
        Ann J Pharm. 1945; 117: 409-412
        • Price D.D.
        • Fields H.L.
        The contribution of desire and expectation to placebo analgesia; Implications for new research strategies.
        in: Harrington A. The Placebo Effect. An Interdisciplinary Exploration. Harvard University Press, Cambridge1997
        • Quaranta L.
        • Pasquini L.
        • Cassamali M.
        • et al.
        Ocular hypotensive effect of sublingual administration of timolol.
        Int Ophthalmol. 1996; 20: 49-51
        • Racz P.
        • Ruzsonyi Nagy Z.T.
        • et al.
        Around-the-clock intraocular pressure reduction with once-daily application of latanoprost by itself or in combination with timolol.
        Arch Ophthalmol. 1996; 114: 268-273
        • Reich J.
        The effect of personality on placebo response in panic patients.
        J Nerv Ment Dis. 1990; 178: 699-702
        • Richer S.
        Multicenter ophthalmic and nutritional age-related macular degeneration study, part 2.
        J Am Optom Assoc. 1996; 67: 30-49
        • Roberts A.H.
        The powerful placebo revisited.
        Mind Body Med. 1995; 1: 35-44
        • Robertson D.M.
        • Ilstrup D.
        Direct, indirect, and sham laser photocoagulation in the management of central serous chorioretinopathy.
        Am J Ophthalmol. 1983; 95: 457-466
        • Robin A.L.
        • Ramkrishnan R.
        • Krishnadas R.
        • et al.
        A long-term dose-response study of mitomycin in glaucoma filtration surgery.
        Arch Ophthalmol. 1997; 115: 969-974
        • Rosenzweig P.
        • Brohier S.
        • Zipfel A.
        The placebo effect in healthy volunteers.
        Clin Pharmacol Ther. 1993; 54: 578-583
        • Rossetti L.
        • Bujtar E.
        • Castoldi D.
        • et al.
        Effectiveness of diclofenac eyedrops in reducing inflammation and the incidence of cystoid macular edema after cataract surgery.
        J Cataract Refract Surg. 1996; 22: 794-799
        • Rossetti L.
        • Marchetti I.
        • Orzalesi N.
        Randomized clinical trials on medical treatment of glaucoma.
        Arch Ophthalmol. 1993; 111: 96-103
        • Rothman K.J.
        • Michels K.B.
        The continuing unethical use of placebo controls (see comments).
        N Engl J med. 1994; 331: 394-398
        • Rulo A.H.
        • Greve E.L.
        • Geijssen H.C.
        • Hoyng P.F.
        Reduction of intraocular pressure with treatment of latanoprost once daily in patients with normal-pressure glaucoma (see comments).
        Ophthalmology. 1996; 103: 1276-1282
        • Sabbah A.
        • Marzetto M.
        Azelastine eye drops in the treatment of seasonal allergic conjunctivitis or rhinoconjunctivitis in young children.
        Curr Med Res Opin. 1998; 14: 161-170
        • Sackett D.L.
        The competing objectives of randomized trials (editorial).
        N Engl J Med. 1980; 303: 1059-1060
        • Sadiq S.A.
        • Fielding K.
        • Vernon S.A.
        The effect of timolol drops on respiratory function.
        Eye. 1998; 12: 417-418
        • Sadiq S.A.
        • Vernon S.A.
        Sublingual timolol—an alternative to topical medication in glaucoma?.
        Br J Ophthalmol. 1996; 80: 532-535
        • Sawada A.
        • Kitazawa Y.
        • Yamamoto T.
        • Okabe I.
        • Ichien K.
        • et al.
        Prevention of visual field defect progression with brovincamine in eyes with normal-tension glaucoma.
        Ophthalmology. 1996; 103: 283-288
        • Schendel S.A.
        • Stephanides M.
        Treatment of periorbital edema with human corticotropin-releasing factor after blepharoplasty.
        J Am Coll Surg. 1996; 182: 226-232
        • Scherer W.J.
        • Mielke D.L.
        • Tidwell P.E.
        • Hauber F.A.
        Effect of latanoprost on intraocular pressure following cataract extraction.
        J Cataract Refract Surg. 1998; 24: 964-967
        • Scuderi P.E.
        • Weaver Jr, R.G.
        • James R.L.
        • et al.
        A randomized, double-blinded, placebo-controlled comparison of droperidol, ondansetron, and metoclopramide for the prevention of vomiting following outpatient strabismus surgery in children.
        J Clin Anesth. 1997; 9: 551-558
        • Shapiro A.K.
        A contribution to the history of the placebo effect.
        Behav Sci. 1960; 5: 109-135
        • Shin D.H.
        • Frenkel R.E.
        • David R.
        • Cheetham J.K.
        Effect of topical anti-inflammatory treatment on the outcome of laser trabeculoplasty.
        Am J Ophthalmol. 1996; 122: 349-354
        • Sibille M.
        • Deigat N.
        • Olagnier V.
        • et al.
        Adverse events in phase one studies.
        Eur J Clin Pharmacol. 1992; 42: 389-393
        • Slifman N.R.
        • Obermeyer W.R.
        • Aloi B.K.
        • et al.
        Contamination of botanical dietary supplements by Digitalis lanata.
        N Engl J Med. 1998; 339: 806-811
        • Solomon K.D.
        • Stewart W.C.
        • Hunt H.H.
        • et al.
        Intraoperative intracameral carbachol in phacoemulsification and posterior chamber lens implantation.
        Am J Ophthalmol. 1998; 125: 36-43
        • Sprio H.
        Placebo, patients and physicians.
        in: Bulger R.J. In Search of the Modern Hippocrates. University of Iowa Press, Iowa City1987
        • Spodick D.H.
        Numerators without denominators.
        JAMA. 1975; 232: 35-36
        • Sterk C.C.
        • Renzenbrink-Bubberman A.C.
        • van Best J.A.
        The effect of 1% apraclonidine on intraocular pressure after cataract surgery.
        Ophthalmic Surg Lasers. 1998; 29: 472-475
        • Stewart R.
        • Horwitz B.
        • Howes J.
        • et al.
        Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation.
        J Cataract Refract Surg. 1998; 24: 1480-1489
      5. Stobbe M: Sugar-pill surgery fires ethics debate. Tampa Tribune, December 12, 1998

        • Strahlman E.
        • Tipping R.
        • Vogel R.
        A six-week dose-response study of the ocular hypotensive effect of dorzolamide with a one-year extension.
        Am J Ophthalmol. 1996; 122: 183-194
        • Stur M.
        • Tittl M.
        • Reitner A.
        • Meisinger V.
        Oral zinc and the second eye in age-related macular degeneration.
        Invest Ophthalmol Vis Sci. 1996; 37: 1225-1235
        • Suchman A.L.
        • Ader R.
        Classic conditioning and placebo effects in crossover studies.
        Clin Pharmacol Ther. 1992; 52: 372-377
        • Sullivan L.J.
        • McCurrach F.
        • Lee S.
        • et al.
        Efficacy and safety of 0.3% carbomer gel compared to placebo in patients with moderate-to-severe dry eye syndrome.
        Ophthalmology. 1997; 104: 1402-1408
        • Swartzman L.C.
        • Burkell J.
        Expectations and the placebo effect in clinical drug trials.
        Clin Pharmacol Ther. 1998; 64: 1-7
        • Thomas K.B.
        The placebo in general practice.
        Lancet. 1994; 344: 1066-1067
        • Tseng S.H.
        • Chen F.K.
        A randomized clinical trial of combined topical-intracameral anesthesia in cataract surgery.
        Ophthalmology. 1998; 105: 2007-2011
        • Turner J.A.
        • Deyo R.A.
        • Loeser J.D.
        • et al.
        The importance of placebo effects in pain treatment and research.
        JAMA. 1994; 271: 1609-1614
        • Tutton M.K.
        • Cherry P.M.
        • Ray P.S.
        • Fsadni M.G.
        Efficacy and safety of topical diclofenac in reducing ocular pain after excimer photorefractive keratectomy.
        J Cataract Refract Surg. 1996; 22: 536-541
        • Umetsuki M.H.
        • Kotegawa T.
        • Nakamura K.
        • et al.
        Temporal variation in the effects of ophthalmic timolol on cardiovascular and respiratory functions in healthy men.
        J Clin Pharmacol. 1997; 37: 58-63
        • Ustundag C.
        • Diestelhorst M.
        Efficacy of argon laser trabeculoplasty.
        Graefes Arch Clin Exp Ophthalmol. 1997; 235: 354-358
        • Vajpayee R.B.
        • Dhakal B.P.
        • Gupta S.K.
        • et al.
        Evaluation of topical 0.03% flurbiprofen drops in the treatment of herpetic stromal keratitis.
        Aust N Z J Ophthalmol. 1996; 24: 131-135
        • Vanlandingham B.D.
        • Maus T.L.
        • Brubaker R.F.
        The effect of dorzolamide on aqueous humor dynamics in normal human subjects during sleep.
        Ophthalmology. 1998; 105: 1537-1540
      6. Vayssairat M, Baudot N, Sainte-Beuve C: Why does placebo improve severe limb ischaemia (letter)? 1:356, 1988

        • Vener D.F.
        • Carr A.S.
        • Sikich N.
        • et al.
        Dimenhydrinate decreases vomiting after strabismus surgery in children.
        Anesth Analg. 1996; 82: 728-731
        • Verma S.
        • Corbett M.C.
        • Marshall J.
        A prospective, randomized, double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy.
        Ophthalmology. 1995; 102: 1918-1924
        • Voudouris N.J.
        • Peck C.L.
        • Coleman G.
        Conditioned response models of placebo phenomena.
        Pain. 1989; 38: 109-116
        • Walczak T.S.
        • Williams D.T.
        • Berten W.
        Utility and reliability of placebo infusion in the evaluation of patients with seizures.
        Neurology. 1994; 44: 394-399
        • Wall P.D.
        The placebo effect.
        Pain. 1992; 51: 1-3
        • Wayman L.L.
        • Larsson L.I.
        • Maus T.L.
        • Brubaker R.F.
        Additive effect of dorzolamide on aqueous humor flow in patients receiving long-term treatment with timolol.
        Arch Ophthalmol. 1998; 116: 1438-1440
        • Weiner M.
        • Weiner G.J.
        The kinetics and dynamics of responses to placebo.
        Clin Pharmacol Ther. 1996; 60: 247-254
        • Whitcup S.M.
        • Csaky K.G.
        • Podgor M.J.
        A randomized, masked, cross-over trial of acetazolamide for cystoid macular edema in patients with uveitis (see comments).
        Ophthalmology. 1996; 103: 1054-1063
        • Widengard I.
        • Mandahl A.
        • Tornquist P.
        • Wistrand P.J.
        Colour vision and side-effects during treatment with methazolamide.
        Eye. 1995; 9: 130-135
        • Wolf S.
        Effects of suggestion and conditioning on the action of chemical agents in human subjects.
        J Clin Invest. 1950; 29: 100-109
        • Woods J.R.
        • Williams J.G.
        • Tavel M.
        The two-period crossover design in medical research.
        Ann Intern Med. 1989; 110: 560-566
        • Zimmerman L.E.
        • McLean I.W.
        • Foster W.D.
        Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells?.
        Br J Ophthalmol. 1978; 98: 71-77