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A Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa

A Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa Abstract • Objective. —To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa. Design. —Randomized, controlled, double-masked trial with 2×2 factorial design and duration of 4 to 6 years. Electroretinograms, visual field area, and visual acuity were measured annually. Setting. —Clinical research facility. Patients. —601 patients aged 18 through 49 years with retinitis pigmentosa meeting preset eligibility criteria. Ninety-five percent of the patients completed the study. There were no adverse reactions. Intervention. —Patients were assigned to one of four treatment groups receiving 15 000 IU/d of vitamin A, 15 000 IU/d of vitamin A plus 400 IU/d of vitamin E, trace amounts of both vitamins, or 400 IU/d of vitamin E. Main Outcome Measure. —Cone electroretinogram amplitude. Results. —The two groups receiving 15 000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage (P=.01). Among 354 patients with higher initial amplitudes, the two groups receiving 15 000 IU/d of vitamin A were 32% less likely to have a decline in amplitude of 50% or more from baseline in a given year than those not receiving this dosage (P=.01), while the two groups receiving 400 IU/d of vitamin E were 42% more likely to have a decline in amplitude of 50% or more from baseline than those not receiving this dosage (P=.03). While not statistically significant, similar trends were observed for rates of decline of visual field area. Visual acuity declined about 1 letter per year in all groups. Conclusions. —These results support a beneficial effect of 15 000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa. References 1. Leber T. Die Pigmentdegeneration der Netzhaut und mit ihr verwandte Erkränkungen In: Graefe A, Saemisch-Hess T, eds. Handbuch der gesammten Augenheilkunde . 2nd ed. Leipzig, Germany: W Engelmann; 1916;17:1076-1225. 2. Bell J. Retinitis pigmentosa and allied diseases of the eye . In: Pearson K, ed. Treasury of Human Inheritance . London, England: Cambridge University Press; 1922;2:1-28. 3. Ammann F, Klein D, Franceschetti A. Genetic and epidemiological investigation of pigmentary degeneration of the retina and allied disorders in Switzerland . J Neurol Sci . 1965;2:183-196.Crossref 4. Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa . Am J Hum Genet . 1980;32:223-235. 5. Bundy S, Crews SJ. Wishes of patients with retinitis pigmentosa concerning genetic counseling . J Med Genet . 1982;19:317-318.Crossref 6. Hu DN. Genetic aspects of retinitis pigmentosa in China . Am J Med Genet . 1982;12:51-56.Crossref 7. Bunker CH, Berson EL, Bromley WC, Hayes RB, Roderick TH. Prevalence of retinitis pigmentosa in Maine . Am J Ophthalmol . 1984;97:357-365. 8. Heckenlively JR. Retinitis Pigmentosa . Philadelphia, Pa: JB Lippincott; 1988. 9. Haim M, Holm NV, Rosenberg T. Prevalence of retinitis pigmentosa and allied disorders in Denmark . Acta Ophthalmol . 1992;70:178-186.Crossref 10. Berson EL. Retinitis pigmentosa: the Friedenwald Lecture . Invest Ophthalmol Vis Sci . 1993;34:1659-1676. 11. Mandelbaum J. Dark adaptation: some physiologic and clinical considerations . Arch Ophthalmol . 1941;26:203-239.Crossref 12. Sloan LL. Light sense in pigmentary degeneration of the retina . Arch Ophthalmol . 1942;28:613-631.Crossref 13. Berson EL. Visual function testing: clinical correlations . In: Tasman W, Jaeger E, eds. Duane's Foundations of Clinical Ophthalmology . Philadelphia, Pa: JB Lippincott; 1992;2:1-10. 14. Verhoeff FH. Microscopic observations in a case of retinitis pigmentosa . Arch Ophthalmol . 1931;5:392-407.Crossref 15. Cogan DG. Primary chorioretinal aberrations with night blindness: pathology . Trans Am Acad Ophthalmol Otolaryngol . 1950;54:629-661. 16. Karpe G. Basis of clinical electroretinography . Acta Ophthalmol . 1945;24( (suppl) ):84. 17. Bjork A, Karpe G. The electroretinogram in retinitis pigmentosa . Acta Ophthalmol . 1951;29:361-376.Crossref 18. Henkes HE, van der Tweel LH, van der Gon JJD. Selective amplification of the electroretinogram . Ophthalmologica . 1956;132:140-150.Crossref 19. Armington JC, Gouras P, Tepas DI, Gunkel RD. Detection of the electroretinogram in retinitis pigmentosa . Exp Eye Res . 1961;1:74-80.Crossref 20. Berson EL, Sandberg MA, Rosner B, Birch DG, Hanson AH. Natural course of retinitis pigmentosa over a three-year interval . Am J Ophthalmol . 1985;99:240-251. 21. Andréasson SOL, Sandberg MA, Berson EL. Narrow-band filtering for monitoring low-amplitude cone electroretinograms in retinitis pigmentosa . Am J Ophthalmol . 1988;105:500-503. 22. Biro I. Therapeutic experiments in cases of retinitis pigmentosa . Br J Ophthalmol . 1939;23:332-342.Crossref 23. Gordon DM. The treatment of retinitis pigmentosa with special reference to the Filatov method . Am J Ophthalmol . 1947;30:565-580. 24. Campbell DA, Harrison R, Tonks EL. Retinitis pigmentosa: vitamin A serum levels in relation to clinical findings . Exp Eye Res . 1964;3:412-426.Crossref 25. Chatzinoff A, Nelson E, Stahl N, Clahane A. Eleven-cis vitamin A in the treatment of retinitis pigmentosa: a negative study . Arch Ophthalmol . 1968;80:417-419.Crossref 26. Bergsma DR, Wolf ML. A therapeutic trial of vitamin A in patients with pigmentary retinal degeneration: a negative study . In: Landers MA, Wolbarsht ML, Laties AM, Dowling JE, eds. Retinitis Pigmentosa . New York, NY: Plenum Publishing Corp; 1976:197-209. 27. Katznelson LA, Khoroshilova-Maslova IP, Eliseyeva RF. A new method of treatment of retinitis pigmentosa/pigmentary abiotrophy . Ann Ophthalmol . 1990;22:167-172. 28. Duke-Elder S, Dobrie JH. System of ophthalmology . In: Duke-Elder S, ed. Diseases of the Retina . St Louis, Mo: CV Mosby Co; 1967;10:574-622. 29. Dowling JE, Wald G. The biological function of vitamin A acid . Proc Natl Acad Sci U S A . 1960;46:587-608.Crossref 30. Dowling JE, Gibbons IR. The effect of vitamin A deficiency on the fine structure of the retina . In: Smelser G, ed. The Structure of the Eye . Orlando, Fla: Academic Press Inc; 1961:85-99. 31. Berson EL. Nutrition and retinal degenerations: vitamin A, taurine, ornithine, and phytanic acid . Retina . 1982;2:236-255.Crossref 32. Robison WG, Kuwabara T, Bieri JG. The roles of vitamin E and unsaturated fatty acids in the visual process . Retina . 1982;2:263-281.Crossref 33. Berson EL, Gouras P, Hoff M. Temporal aspects of the electroretinogram . Arch Ophthalmol . 1969;91:207-217.Crossref 34. Berson EL. Retinitis pigmentosa and allied retinal diseases: electrophysiologic findings . Trans Am Acad Ophthalmol Otolaryngol . 1976;81:659-666. 35. Gouras P, Carr RE, Gunkel RD. Retinitis pigmentosa in abetalipoproteinemia: effects of vitamin A . Invest Ophthalmol Vis Sci . 1971;10:784-793. 36. Bishara S, Merin S, Cooper M, Azizi E, Delpre G, Deckelbaum RJ. Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinemia . Br J Ophthalmol . 1982;66:767-770.Crossref 37. Weight by Height and Age for Adults 18 to 74 Years . Washington, DC: US Dept of Health, Education, and Welfare; 1979. Vital and Health Statistics, ser 11, No. 208. 38. Willett WC, Stampfer MJ, Underwood BA, Speizer FE, Rosner B, Hennekens CH. Validation of a dietary questionnaire with plasma carotenoid and α-tocopherol levels . Am J Clin Nutr . 1983;38:631-639. 39. Bieri JG, Tolliver TJ, Catignani GL. Simultaneous determination of α-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography . Am J Clin Nutr . 1979;32:2143-2149. 40. Willett WC, Sampson L, Browne ML, et al. The use of a self-administered questionnaire to assess diet four years in the past . Am J Epidemiol . 1988;127:188-199. 41. Ferris FL, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research . Am J Ophthalmol . 1982;94:91-96. 42. Miller S, Sandberg MA. Cone electroretinogram change during light adaptation in retinitis pigmentosa . Invest Ophthalmol Vis Sci . 1991;32:2536-2541. 43. Broich CR, Gerber LE, Erdman JW Jr. Determination of lycopene α- and β-carotene and retinyl esters in human serum by reversed-phase high performance chromatography . Lipids . 1983;18:253-258.Crossref 44. Armitage P. Statistical Methods in Medical Research . New York, NY: John Wiley & Sons Inc; 1971. 45. Wilson C, Pollack MR, Harris AD. Diet in the treatment of infective hepatitis . Lancet . 1946;1:881-883.Crossref 46. Chalmers TC, Eckhardt RD, Reynolds WE, et al. The treatment of acute infectious hepatitis: controlled studies on the effect of diet, rest, and physical reconditioning on the acute course of the disease and on the incidence of relapses and residual abnormalities . J Clin Invest . 1955;34:1165-1235.Crossref 47. Stampfer MJ, Buring JE, Willett W, Rosner B, Eberlein K, Hennekens CH. The 2×2 factorial design: its application to a randomized trial of aspirin and carotene in U.S. physicians . Stat Med . 1985;4:111-116.Crossref 48. Rosner B. Multivariate methods in ophthalmology with application to other paired data situations . Biometrics . 1984;40:1025-1035.Crossref 49. Glynn R, Rosner B. Accounting for the correlation between fellow eyes in regression analysis . Arch Ophthalmol . 1992;110;381-387.Crossref 50. Peto R, Pike M, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient . Br J Cancer . 1977;35:1-39.Crossref 51. Dubach UC, Rosner B, Pfister E. Epidemiologic study of abuse of analgesics containing phenacetin: renal morbidity and mortality (1968-1979) . N Engl J Med . 1983;308:357-362.Crossref 52. Miller RE. Survival Analysis . New York, NY: John Wiley & Sons Inc; 1971. 53. Rosner B. Fundamentals of Biostatistics . 3rd ed. Boston, Mass: Duxbury Press; 1989. 54. Snedecor G, Cochran WG. Statistical Methods . 7th ed. Ames: Iowa State University Press; 1980. 55. Fleiss JL. Statistical Methods for Rates and Proportions . New York, NY: John Wiley & Sons Inc; 1981. 56. Bauernfeind JC. The Safe Use of Vitamin A: A Report of the International Vitamin A Consultative Group (IVACG) . Washington, DC: The Nutrition Foundation; 1980. 57. Hathcock JN, Hattan DG, Jenkins MY, McDonald JT, Sundareson PR, Wilkening VL. Evaluation of vitamin A toxicity . Am J Clin Nutr . 1990;52:183-202. 58. Dryja TP, McGee TL, Reichel E, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa . Nature . 1990;343:364-366.Crossref 59. Sung C-H. Davenport CM, Hennessey JC, et al. Rhodopsin mutations in autosomal dominant retinitis pigmentosa . Proc Natl Acad Sci U S A . 1991;88:6481-6485.Crossref 60. Dryja TP, Hahn LB, Cowley GS, McGee TL, Berson EL. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa . Proc Natl Acad Sci U S A . 1991;88:9370-9374.Crossref 61. Farrar GJ, Kenna P, Jordan SA, et al. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa . Nature . 1991;354:478-480.Crossref 62. Kajiwara K, Hahn L, Mukai S, Travis GH, Berson EL, Dryja TP. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa . Nature . 1991;354:480-483.Crossref 63. Rosenfeld PJ, Cowley GS, McGee TL, Sandberg MA, Berson EL, Dryja TP. A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa . Nat Genet . 1992;1:209-213.Crossref 64. McLaughlin ME, Sandberg MA, Berson EL, Dryja TP. Recessive mutations in the gene encoding the β-subnit of rod phospho diesterase in patients with retinitis pigmentosa. Nat Genet. In press. 65. Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C. Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases . Gastroenterology . 1991;100:1701-1709. 66. Goodman DS. Vitamin A and retinoids in health and disease . N Engl J Med . 1984;310:1023-1031.Crossref 67. Blomhoff R, Green MH, Berg T, Norum KR. Transport and storage of vitamin A . Science . 1990;250:399-404.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

A Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa

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American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1993.01090060049022
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Abstract

Abstract • Objective. —To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa. Design. —Randomized, controlled, double-masked trial with 2×2 factorial design and duration of 4 to 6 years. Electroretinograms, visual field area, and visual acuity were measured annually. Setting. —Clinical research facility. Patients. —601 patients aged 18 through 49 years with retinitis pigmentosa meeting preset eligibility criteria. Ninety-five percent of the patients completed the study. There were no adverse reactions. Intervention. —Patients were assigned to one of four treatment groups receiving 15 000 IU/d of vitamin A, 15 000 IU/d of vitamin A plus 400 IU/d of vitamin E, trace amounts of both vitamins, or 400 IU/d of vitamin E. Main Outcome Measure. —Cone electroretinogram amplitude. Results. —The two groups receiving 15 000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage (P=.01). Among 354 patients with higher initial amplitudes, the two groups receiving 15 000 IU/d of vitamin A were 32% less likely to have a decline in amplitude of 50% or more from baseline in a given year than those not receiving this dosage (P=.01), while the two groups receiving 400 IU/d of vitamin E were 42% more likely to have a decline in amplitude of 50% or more from baseline than those not receiving this dosage (P=.03). While not statistically significant, similar trends were observed for rates of decline of visual field area. Visual acuity declined about 1 letter per year in all groups. Conclusions. —These results support a beneficial effect of 15 000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa. References 1. Leber T. Die Pigmentdegeneration der Netzhaut und mit ihr verwandte Erkränkungen In: Graefe A, Saemisch-Hess T, eds. Handbuch der gesammten Augenheilkunde . 2nd ed. Leipzig, Germany: W Engelmann; 1916;17:1076-1225. 2. Bell J. Retinitis pigmentosa and allied diseases of the eye . In: Pearson K, ed. Treasury of Human Inheritance . London, England: Cambridge University Press; 1922;2:1-28. 3. Ammann F, Klein D, Franceschetti A. Genetic and epidemiological investigation of pigmentary degeneration of the retina and allied disorders in Switzerland . J Neurol Sci . 1965;2:183-196.Crossref 4. Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa . Am J Hum Genet . 1980;32:223-235. 5. Bundy S, Crews SJ. Wishes of patients with retinitis pigmentosa concerning genetic counseling . J Med Genet . 1982;19:317-318.Crossref 6. Hu DN. Genetic aspects of retinitis pigmentosa in China . Am J Med Genet . 1982;12:51-56.Crossref 7. Bunker CH, Berson EL, Bromley WC, Hayes RB, Roderick TH. Prevalence of retinitis pigmentosa in Maine . Am J Ophthalmol . 1984;97:357-365. 8. Heckenlively JR. Retinitis Pigmentosa . Philadelphia, Pa: JB Lippincott; 1988. 9. Haim M, Holm NV, Rosenberg T. Prevalence of retinitis pigmentosa and allied disorders in Denmark . Acta Ophthalmol . 1992;70:178-186.Crossref 10. Berson EL. Retinitis pigmentosa: the Friedenwald Lecture . Invest Ophthalmol Vis Sci . 1993;34:1659-1676. 11. Mandelbaum J. Dark adaptation: some physiologic and clinical considerations . Arch Ophthalmol . 1941;26:203-239.Crossref 12. Sloan LL. Light sense in pigmentary degeneration of the retina . Arch Ophthalmol . 1942;28:613-631.Crossref 13. Berson EL. Visual function testing: clinical correlations . In: Tasman W, Jaeger E, eds. Duane's Foundations of Clinical Ophthalmology . Philadelphia, Pa: JB Lippincott; 1992;2:1-10. 14. Verhoeff FH. Microscopic observations in a case of retinitis pigmentosa . Arch Ophthalmol . 1931;5:392-407.Crossref 15. Cogan DG. Primary chorioretinal aberrations with night blindness: pathology . Trans Am Acad Ophthalmol Otolaryngol . 1950;54:629-661. 16. Karpe G. Basis of clinical electroretinography . Acta Ophthalmol . 1945;24( (suppl) ):84. 17. Bjork A, Karpe G. The electroretinogram in retinitis pigmentosa . Acta Ophthalmol . 1951;29:361-376.Crossref 18. Henkes HE, van der Tweel LH, van der Gon JJD. Selective amplification of the electroretinogram . Ophthalmologica . 1956;132:140-150.Crossref 19. Armington JC, Gouras P, Tepas DI, Gunkel RD. Detection of the electroretinogram in retinitis pigmentosa . Exp Eye Res . 1961;1:74-80.Crossref 20. Berson EL, Sandberg MA, Rosner B, Birch DG, Hanson AH. Natural course of retinitis pigmentosa over a three-year interval . Am J Ophthalmol . 1985;99:240-251. 21. Andréasson SOL, Sandberg MA, Berson EL. Narrow-band filtering for monitoring low-amplitude cone electroretinograms in retinitis pigmentosa . Am J Ophthalmol . 1988;105:500-503. 22. Biro I. Therapeutic experiments in cases of retinitis pigmentosa . Br J Ophthalmol . 1939;23:332-342.Crossref 23. Gordon DM. The treatment of retinitis pigmentosa with special reference to the Filatov method . Am J Ophthalmol . 1947;30:565-580. 24. Campbell DA, Harrison R, Tonks EL. Retinitis pigmentosa: vitamin A serum levels in relation to clinical findings . Exp Eye Res . 1964;3:412-426.Crossref 25. Chatzinoff A, Nelson E, Stahl N, Clahane A. Eleven-cis vitamin A in the treatment of retinitis pigmentosa: a negative study . Arch Ophthalmol . 1968;80:417-419.Crossref 26. Bergsma DR, Wolf ML. A therapeutic trial of vitamin A in patients with pigmentary retinal degeneration: a negative study . In: Landers MA, Wolbarsht ML, Laties AM, Dowling JE, eds. Retinitis Pigmentosa . New York, NY: Plenum Publishing Corp; 1976:197-209. 27. Katznelson LA, Khoroshilova-Maslova IP, Eliseyeva RF. A new method of treatment of retinitis pigmentosa/pigmentary abiotrophy . Ann Ophthalmol . 1990;22:167-172. 28. Duke-Elder S, Dobrie JH. System of ophthalmology . In: Duke-Elder S, ed. Diseases of the Retina . St Louis, Mo: CV Mosby Co; 1967;10:574-622. 29. Dowling JE, Wald G. The biological function of vitamin A acid . Proc Natl Acad Sci U S A . 1960;46:587-608.Crossref 30. Dowling JE, Gibbons IR. The effect of vitamin A deficiency on the fine structure of the retina . In: Smelser G, ed. The Structure of the Eye . Orlando, Fla: Academic Press Inc; 1961:85-99. 31. Berson EL. Nutrition and retinal degenerations: vitamin A, taurine, ornithine, and phytanic acid . Retina . 1982;2:236-255.Crossref 32. Robison WG, Kuwabara T, Bieri JG. The roles of vitamin E and unsaturated fatty acids in the visual process . Retina . 1982;2:263-281.Crossref 33. Berson EL, Gouras P, Hoff M. Temporal aspects of the electroretinogram . Arch Ophthalmol . 1969;91:207-217.Crossref 34. Berson EL. Retinitis pigmentosa and allied retinal diseases: electrophysiologic findings . Trans Am Acad Ophthalmol Otolaryngol . 1976;81:659-666. 35. Gouras P, Carr RE, Gunkel RD. Retinitis pigmentosa in abetalipoproteinemia: effects of vitamin A . Invest Ophthalmol Vis Sci . 1971;10:784-793. 36. Bishara S, Merin S, Cooper M, Azizi E, Delpre G, Deckelbaum RJ. Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinemia . Br J Ophthalmol . 1982;66:767-770.Crossref 37. Weight by Height and Age for Adults 18 to 74 Years . Washington, DC: US Dept of Health, Education, and Welfare; 1979. Vital and Health Statistics, ser 11, No. 208. 38. Willett WC, Stampfer MJ, Underwood BA, Speizer FE, Rosner B, Hennekens CH. Validation of a dietary questionnaire with plasma carotenoid and α-tocopherol levels . Am J Clin Nutr . 1983;38:631-639. 39. Bieri JG, Tolliver TJ, Catignani GL. Simultaneous determination of α-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography . Am J Clin Nutr . 1979;32:2143-2149. 40. Willett WC, Sampson L, Browne ML, et al. The use of a self-administered questionnaire to assess diet four years in the past . Am J Epidemiol . 1988;127:188-199. 41. Ferris FL, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research . Am J Ophthalmol . 1982;94:91-96. 42. Miller S, Sandberg MA. Cone electroretinogram change during light adaptation in retinitis pigmentosa . Invest Ophthalmol Vis Sci . 1991;32:2536-2541. 43. Broich CR, Gerber LE, Erdman JW Jr. Determination of lycopene α- and β-carotene and retinyl esters in human serum by reversed-phase high performance chromatography . Lipids . 1983;18:253-258.Crossref 44. Armitage P. Statistical Methods in Medical Research . New York, NY: John Wiley & Sons Inc; 1971. 45. Wilson C, Pollack MR, Harris AD. Diet in the treatment of infective hepatitis . Lancet . 1946;1:881-883.Crossref 46. Chalmers TC, Eckhardt RD, Reynolds WE, et al. The treatment of acute infectious hepatitis: controlled studies on the effect of diet, rest, and physical reconditioning on the acute course of the disease and on the incidence of relapses and residual abnormalities . J Clin Invest . 1955;34:1165-1235.Crossref 47. Stampfer MJ, Buring JE, Willett W, Rosner B, Eberlein K, Hennekens CH. The 2×2 factorial design: its application to a randomized trial of aspirin and carotene in U.S. physicians . Stat Med . 1985;4:111-116.Crossref 48. Rosner B. Multivariate methods in ophthalmology with application to other paired data situations . Biometrics . 1984;40:1025-1035.Crossref 49. Glynn R, Rosner B. Accounting for the correlation between fellow eyes in regression analysis . Arch Ophthalmol . 1992;110;381-387.Crossref 50. Peto R, Pike M, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient . Br J Cancer . 1977;35:1-39.Crossref 51. Dubach UC, Rosner B, Pfister E. Epidemiologic study of abuse of analgesics containing phenacetin: renal morbidity and mortality (1968-1979) . N Engl J Med . 1983;308:357-362.Crossref 52. Miller RE. Survival Analysis . New York, NY: John Wiley & Sons Inc; 1971. 53. Rosner B. Fundamentals of Biostatistics . 3rd ed. Boston, Mass: Duxbury Press; 1989. 54. Snedecor G, Cochran WG. Statistical Methods . 7th ed. Ames: Iowa State University Press; 1980. 55. Fleiss JL. Statistical Methods for Rates and Proportions . New York, NY: John Wiley & Sons Inc; 1981. 56. Bauernfeind JC. The Safe Use of Vitamin A: A Report of the International Vitamin A Consultative Group (IVACG) . Washington, DC: The Nutrition Foundation; 1980. 57. Hathcock JN, Hattan DG, Jenkins MY, McDonald JT, Sundareson PR, Wilkening VL. Evaluation of vitamin A toxicity . Am J Clin Nutr . 1990;52:183-202. 58. Dryja TP, McGee TL, Reichel E, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa . Nature . 1990;343:364-366.Crossref 59. Sung C-H. Davenport CM, Hennessey JC, et al. Rhodopsin mutations in autosomal dominant retinitis pigmentosa . Proc Natl Acad Sci U S A . 1991;88:6481-6485.Crossref 60. Dryja TP, Hahn LB, Cowley GS, McGee TL, Berson EL. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa . Proc Natl Acad Sci U S A . 1991;88:9370-9374.Crossref 61. Farrar GJ, Kenna P, Jordan SA, et al. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa . Nature . 1991;354:478-480.Crossref 62. Kajiwara K, Hahn L, Mukai S, Travis GH, Berson EL, Dryja TP. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa . Nature . 1991;354:480-483.Crossref 63. Rosenfeld PJ, Cowley GS, McGee TL, Sandberg MA, Berson EL, Dryja TP. A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa . Nat Genet . 1992;1:209-213.Crossref 64. McLaughlin ME, Sandberg MA, Berson EL, Dryja TP. Recessive mutations in the gene encoding the β-subnit of rod phospho diesterase in patients with retinitis pigmentosa. Nat Genet. In press. 65. Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C. Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases . Gastroenterology . 1991;100:1701-1709. 66. Goodman DS. Vitamin A and retinoids in health and disease . N Engl J Med . 1984;310:1023-1031.Crossref 67. Blomhoff R, Green MH, Berg T, Norum KR. Transport and storage of vitamin A . Science . 1990;250:399-404.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Jun 1, 1993

References