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Low glutathione reductase and peroxidase activity791 in age-related macular degeneration BritishJournal ofOphthalmology 1994; 78: 791-794 Low glutathione reductase and peroxidase activity inSteven age-related macular degeneration M Cohen, Katherine L Olin, William J Feuer, Leonard Hjelmeland, Carl L Keen, Lawrence S Morse Steven M Cohen, Katherine L Olin, William J Feuer, Leonard Hjelmeland, Carl L Keen, Lawrence S Morse Patients and methods Abstract Age-related macular degeneration (ARMD) All patients examined in the UC Davis Departmay result from events initiated by reactive ment of Ophthalmology by the authors (LM and oxygen species. Blood samples from 18 SC) from September 1989 through September andconsidered methods for this study. Thirty six Abstract patients with ARMD and 18 similarly aged Patients 1992 were macular Age-related All patients examined thetheUC Davis degeneration (ARMD) Departcontrols were analysed for activities of impor- subjects were entered in into study based on the of Ophthalmology may from events reactive ment bystudy the authors by reductase (LM andby tant result antioxidants. Blood initiated glutathione was approved criteria listed below. This Blood 18 SC) September oxygen through September sampleswithfrom UC Davis, human1989 subjects committee. Subactivity species. was lower in patients ARMD the from 1992 ARMD were considered for this with and 18 patients study. Thirty six aged similarly or a compared with controls (p=0·03S). The activ- jects with diabetes, a major systemic disease, controls for activities of imporentered into basedexcluded on the studywere analysedperoxidase glutathione (p=0·18) and subjects ities of were visuallywere compromising eyethe disease listed below. This study was approved tant antioxidants. Blood glutathione by erythrocyte superoxide dismutasereductase (p=0·29) criteria from the study. Patients with visually significant was lower in patients ARMD UC Davis, committee. subjectsalong activity the twowith groups by a the were similar between cataracts werehuman also excluded with allSubindiwith taking a major The regresactiv- jects diabetes, compared systemic or a disease, viduals zinc supplements high or dose Student'swith two controls sample t(p=0035). test. Logistic ities of and visually glutathione compromising eye disease were peroxidase excluded (p=018) sion was used to determine which enzyme vitamin supplements. However, subjects taking the study. Patients dismutase with visually erythrocyte superoxide (p=029) activities were associated with ARMD after from a multivitamin supplement were notsignificant excluded. were similar cataracts between the two were also excluded withcontained all india along groups by adjusting for possible confounding variables: These multivitamin supplements viduals taking zinc or dose supplements high two t test. Student's sample Logistic regressmoking history, age, multivitamin use, and 100% to 200% of the recommended daily dietary supplements. takingC to determine which reductase was used disease. sion enzyme vitamin of vitaminHowever, A (5000 subjects IU), vitamin allowances cardiovascular Glutathione activities multivitamin were associated with ARMD after a (60 supplement mg), and vitamin E (30 were IU). I'not excluded. activity (p=O·OS) and glutathione peroxidase for variables: These multivitamin adjusting possible contained supplements confounding Patients included in the ARMD group had a activity (p=O·06S) were significantly associated to 200% multivitamin smoking the recommended history, age,analysis. use, andof 100% daily dietary The relation of 20/40 or worse and had to Snellen visualof acuity with ARMD by this cardiovascular of vitamin A (5000 IU), vitamin disease. and Glutathione reductase C glutathione reductase glutathione peroxi- allowances 10 ophthalmoscopically visible have at least and and vitamin activity (60 E (p=0.05) glutathione mg), peroxidase (30 IU).'9 dase activity to ARMD merits further study. macular drusen, characteristic pigmentary geoin the subretinal ARMD group had a Patientsatrophy, includedand/or activity (p=0 065) were associated graphic (BrJ Ophthalmoll994; 78: significantly 791-794) neovascular with ARMD by this analysis. The relation of Snellen visual of20/40 or worse and had to acuity membranes. Subjects whose visual loss may have glutathione reductase and glutathione peroxi- have least 10 ophthalmoscopically to a media opacityvisible were been atsecondary dase to ARMD merits further activity macular drusen, characteristic pigmentary geostudy. Age-related degeneration (ARMD) is a macular excluded. 78: Ophthalmol 1994; 791-794) (BrJ and/orconsisted subretinal neovascular graphic atrophy, leading cause of irreversible vision loss in the The control group of subjects who have whose visual loss mayvisible Subjects United States, United Kingdom, and other membranes. had fewer than two ophthalmoscopically to each a media secondary were developed nations. l -6 This disease affects been macular drusen in eye andopacity an associated excluded. Age-related macular degeneration (ARMD) is a 20-30% of people over the age of 75. 17 Since this Snellen visual acuity of 20/30 or better in both leading irreversible The control vision loss in the eyes. subjects towho sectioncause of the of population is expected to increase these consisted patients of presented the Most ofgroup United had United fewer than two visible States, and other Kingdom, ophthalmoscopically dramatically during the next century, ARMD is a clinic with refractive problems. nations."' druseninintheeach andasked an associated developed disease affects macular eyewere Participants study a standard of severe and growing public health problem This 20-30% of people over the age of 75. 7 Since this in both of 20/30 orhistory better questionacuityThis 8 Although questions. patient series ofvisual proportions. some risk factors for Snellen section of the is population Most of these expected to increase the eyes. patients presented ARMD have been identified, its cause remains naire focused on previously identified risktofactors the next century, clinic with refractive dramatically ARMDofisthe a during problems. An improved understanding unknown. 19-12 for ARMD.· Each subject had visual acuity health in thecorrection, public of severe asked a standard and growing Participants study wereslit-lamp aetiology andproblem pathogenesis of ARMD at the testing with best examinaproportions.8 Although some risk factors series of This for questions. patient history questioncellular and biochemical level is crucial to devel- tion noting any media opacities, and applanation ARMD have beentreatment identified,and its cause focused on risk factors remains previously oping improved hopefully even naire The fundus identified was examined in all tonometry. University of California, ' 12 An improved understanding ofthe for unknown. ARMD.9 visual acuity Davis, Sacramento, USA prevention of this disease. subjects usingEach eithersubject contact had or non-contact lens and suggested aetiology pathogenesis ARMD with best Fundus the testing examinacorrection, slit-lamp were It has been thatof ARMD mayatresult biomicroscopy. photographs taken Department of cellular biochemical is crucial to develnoting any media opacities, and applanation Ophthalmology in partand from a cascadelevel of events initiated by tion in most patients and fluorescein angiography was SMCohen oping improved treatment and hopefully The even fundus examined in all tonometry. of University California, 7' 13 14 These reactive done only when clinicallywas reactive oxygen species. indicated. LSMorse USA Davis, Sacramento, of thismay disease. prevention contact or non-contact oxygen species damage lipids in the outer subjects of examination, venous bloodlens was At theusing timeeither L Hjelmeland It has been suggested that ARMD result biomicroscopy. may Fundus photographs were taken Department of of photoreceptors and lead to progressegments drawn into a heparinised tube free from trace Department of Nutrition Ophthalmology insive from a cascade events part initiated by inelement most patients and fluorescein was of the of retinal pigment epithedeterioration contamination. Those angiography that processed the M Cohen S KLOlin 9 314 These reactive reactive oxygen species.7 done when indicated. only clinically CLKeen L S Morse lium (RPE).· 15 Others propose that circulating blood and performed the assays were masked to in the oxygen damage the chorioAt subjects' outer the time of venous bloodblood was examination, LDepartment Hjelmeland of reactivespecies oxygenmay species couldlipids damage the diagnoses. Aliquots of whole Biostatistics, the Bascom of and lead to segments photoreceptors drawn progresinto a tube free from trace heparinised Department of Nutrition capillaris and lead to ARMD. 13 Deficiencies of were stored at - 70°C for subsequent analysis of sive KPalmer L Olin Eye Institute, deterioration of the retinal pigment epithecontamination. that processed the select trace elements, such as zinc, have also been element glutathione peroxidase Those and glutathione reductase Miami, USA C L Keen lium (RPE).9'5inOthers that circulating and performed the assays to W J Feuer implicated the propose vision loss caused by blood activities. The remaining bloodwere was masked centrifuged of Department reactive oxygen species could damage the choriothe of whole blood subjects' diagnoses. Aliquots ARMD.I6--18 Correspondence to: at 1700 g for 20 minutes, and plasma fractions the Bascom Biostatistics, Lawrence S Morse, MD, and leadwetoreport capillaris Deficiencies of were ARMD.'3 for subse'quent -70°C of analysiswere Accordingly, the results of a casewerestored storedat at - 70°C. Red cell lysates Palmer Eye Institute, Department of select trace such as have also elements, zinc, been and glutathione glutathione peroxidase USA Miami, Ophthalmology, UC Davis, control study of patients with ARMD aimed at prepared by diluting packed red bloodreductase cells with Alhambra Boulevard, W1603 J Feuer in thealterations vision inloss implicated caused by activities. blood was remaining centrifuged detecting possible enzyme activities an equal The volume of distilled, deionised water, Sacramento, CA 95816, USA. to: '8 ARMD.' Correspondence atmixing 1700 gand for 20 minutes, and fractions plasma which have critical roles in cellular defence 1700 g; the supercentrifuging at AcceptedSfor publication Lawrence Morse, MD, - 70°C. the results of a case- were Accordingly, report celluntil were lysates 15 June 1994 of against reactivewe oxygen species Department natesstored were atstored at Red - 70°C used for Ophthalmology, UC Davis, 1603 Alhambra Boulevard, Sacramento, CA 95816, USA. Accepted for publication 15 June 1994 control study of patients with ARMD aimed at detecting possible alterations in enzyme activities which have critical roles in cellular defence against reactive oxygen species prepared by diluting packed red blood cells with an equal volume of distilled, deionised water, mixing and centrifuging at 1700 g; the supernates were stored at - 70°C until used for Downloaded from bjo.bmj.com on March 19, 2013 - Published by group.bmj.com Cohen, Olin, Feuer, Hjelmeland, Hielmeland, Keen, Morse 792 determining erythrocyte superoxide dismutase activity. Analytical grade chemicals and reagents were purchased from Sigma Chemical Co (St Louis, MO, USA) unless otherwise noted. Blood glutathione peroxidase activity was measured accord20) and ing to the methods of Lawrence and Burk Burk20) Jensen. 21 Selenium dependent Agergaard and Jensen.2' glutathione peroxidase activity was measured by using 55 mM hydrogen peroxide in the assay system. Blood glutathione reductase activity was measured as described by Rogers and Augusteyn. 22 Following the extraction of haemoglobin teyn.22 from the red cell lysates, superoxide dismutase activity was determined according to Marklund and Marklund.23 Marklund. 23 Haemoglobin concentrations were determined by the cyanomethaemoglobin colorimetric procedure (Sigma Diagnostic Kit No 525). Results are presented as the mean (SEM). p Values were computed with Student's two sample tt test. Backward stepwise multiple logistic regression was used to determine what variables were significantly related to the subjects' disease status. Variables were removed from models if their maximum likely p values were greater than or equal to 01. 0·1. p Values were calculated with maximum likelihood methods while confidence intervals were obtained from asymptotic standard errors. Enzyme activities were fitted as continuous variables. Table 1I Historical profile ofpatients with age-related macular degeneration (ARMD) and controls Control No(%) No (%) ARMD No(%) 18 74 (60--96) (60-96) 11 (61) 4 (22) 4 (22) 10 (59) 6(35) 6 (35) 6 (35) 3 (17) 3 (17) 11 (61) 18 (100) Total patients Average age (range) Ever smoked Currently smokes Stroke Hypertension Angina Myocardial infarct Multivitamin (currently) Family history of ARMD Female White 18 76 (68-87) 9 (50) 2 (11) 2 (11) 8 (44) 2 (11) 0(0) 0 (0) 7 (39) 11 (6) 8 (44) 18 (100) Table 2 Examination profile ofpatients with age-related macular degeneration (ARMD) and controls ARMD Control Visual acuity, right eye* 20/80 20/20 20/20 Visual acuity, left eye 20/200 20/20 Visual acuity, worse eye 20/20 20/300 Visual acuity, better eye 20/60 20/20 Hglt Intraocular pressure, right eye (mm Hg)t (0 9) 16 (0 6) 15 (0'9) (0'6) Intraocular pressure, left eye (mm Hg)t (0 9) 15 (0 6) 16 (0'9) (0'6) Systolic blood pressure (mm Hg)t 134 (4) 140 (5) Diastolic blood pressure (mm Hg)t 77 (2) 75 (2) Pseudophakia:j: Pseudophakia: 55 (28) 2 (11) Blue irist iris:j: 77 (39) 11 (61) * * Values are expressed as geometric mean of standard Snellen units. ' t Values are expressed expressed as mean (SEM). (SEM). No (%). t:j:No(%). Table 3 Blood antioxidant enzyme activities 'Fable ARMD Hb-')') . Erythrocyte superoxide dismutase (units mg HbBlood glutathione reductase (nmol NADPH oxidised min-' mg Hb-') Blood glutathione peroxidase (nmol NADPH oxidised min-'mgHb-') min-' mgHb-') Values are expressed as mean (SEM). p Values are from two sample Student's tI test. lest. Control Control 0 930 (0'04) (0-04) 0·930 0-884 (0'02) (0 02) 0·884 p Value 0-29 o· 29 3-81 HI (0-39) (0' 39) 5 09 (0 43) 5·09 (0'43) 0-035 0'035 10-3 10'3 (0 72) (0'72) 11 5 11'5 (0-54) (0'54) 0-18 0·18 Results Historical profiles of ARMD and control subjects are presented in Table 1. The mean age of the control group was 74 years, ranging from 60 to 96; the mean age of the ARMD group was 76 years, ranging from 68 to 87. Results from the clinical examination are presented in Table 2. Subjects in the ARMD group had poor visual acuity with a geometric mean Snellen visual acuity of 20/80 right eye, 20/200 left eye. In contrast, the control group had excellent visual acuity with a geometric mean Snellen visual acuity of 20/20 in both eyes. Comparing right eyes, left eyes, better eyes, or worse eyes geometric mean visual acuity was significantly poorer in the ARMD group than in controls (p<O·OOl). (p<0O001). There was no difference in degree of lens opacity between the ARMD group and controls. Five (28%) ARMD patients compared with two (11%) controls were bilaterally pseudophakic. Results of antioxidant enzyme activities are presented in Table 3. Glutathione reductase activity was significantly lower in ARMD subjects compared with controls (p=0·035). (p=0035). The actIVItIeS activities of glutathione peroxidase and erythrocyte superoxide dismutase were similar between the two groups. Logistic regression was used to determine which of the antioxidant enzyme activities were associated with disease status after adjusting for possible confounding variables: smoking history, age, multivitamin use, and cardiovascular factors including stroke, hypertension, angina, myocardial infarction. All six patients with myocardial infarction were in the ARMD group (significant by two tailed Fisher's exact test, p=0'019) so these cases were excluded from the p=0-019) logistic regression analysis. The only variables which were found to be significantly related to disease status by logistic regression analysis were glutathione reductase activity (p=005) (p=0'05) and glutathione peroxidase activity (p=0·065). (p=0065). The odds ratios associating decreased enzyme activities with ARMD were 1'63 1 63 (95% confidence interval=1 0 to 2'8) 2-8) for glutathione reductase interval = 1'0 1 36 (95% confidence interval=1 interval = 1·0 and 1'36 0 to 2-0) for glutathione peroxidase. Discussion Given that the prevalence of ARMD is strongly correlated with age, it is reasonable to speculate that the deterioration of the neurosensory macula, the RPE, and the choriocapillaris in ARMD may be secondary to mechanisms associated with the aging process. While the process of aging is poorly understood, several theories have been proposed to help explain events leading to decrease viability and eventually death in a seemingly time programmed manner. One of the leading theories of aging links damage caused by reactive oxygen species to several known aging processes.24 processes. 24 Reactive oxygen species are molecules which contain an unpaired electron making them highly reactive. This high reactivity leads to toxic effects on more stable molecules. Reactive oxygen species are produced in all tissues during aerobic metabolism and they can also be formed by photochemical reactions. 525 IS 2S Since the Downloaded from bjo.bmj.com on March 19, 2013 - Published by group.bmj.com Low glutathione reductase and peroxidase activity in age-related macular degeneration retina is metabolically very active, exposed to high oxygen concentrations, and exposed to focused light energy, it is subject to high concentrations of reactive oxygen species. Some of the toxic effects that these reactive molecules have no healthy surrounding tissues are a decline in cellular function caused by reduced enzyme activities, increased error rates in nucleic acid metabolism, damaged membranes, and accumulation of undigestible deformed cellular material in lysosomes. lysosomes.2"25 In the eye, antioxidant damage is correlated with senile cataract and exudative macular 2627 We did not include any patient degeneration. degeneration.2627 in this study with a visually significant cataract. The higher incidence of pseudophakia in the ARMD group (28%) compared with controls (11 ( 11 %), however, may imply that ARMD subjects developed more visually significant cataracts than controls. Although several large epidemiological .studies have investigated the relation between senile cataract and ARMD, their association remains controversial.9-12 controversial.9'2 14'4 The body has several defences against damage induced by reactive oxygen species. In this study, we focused our attention on three enzymes, erythrocyte superoxide dismutase, glutathione reductase, and glutathione peroxidase, which serve key functions in the elimination of reactive oxygen species. We found no difference in activity of erythrocyte superoxide dismutase in ARMD subjects versus controls. We did, however, find significantly low blood actlvitIes in ARMD glutathione reductase activities patients compared with controls. In addition, a multiple logistic regression analysis showed that ARMD patients were more likely to have lower levels of both glutathione reductase and glutathione peroxidase. Glutathione peroxidase can reduce hydrogen peroxide and a variety of organic peroxides using glutathione as an electron donor.24 Therefore, low glutathione peroxidase activity may render patients with ARMD susceptible to damage from reactive oxygen species. Glutathione peroxidase activity is dependent on selenium. Interestingly, a recent case control study found a borderline association between ARMD and low serum selenium concentrations; however, no such association was found in the Eye Disease Casereport. 2728 Control Study report.27 28 Recently, a decreased glutathione reductase activity in lens epithelial cells was shown to be associated with senile cataract.29 cataract. 29 Although glutathione reductase is not directly an antioxidant, its proper function is essential to the maintenance of available reduced glutathione, a potent scavenger of reactive oxygen species. Following its reaction with a reactive oxygen species, glutathione is oxidised and subsequently returned to its reduced state by glutathione reductase.24 Low. reductase. 24 Low glutathione reductase activity can occur for at least two reasons. Firstly, genetic variants of the enzyme exist with variable activity. These variations have been quantified in several populations and range in prevalence prevalence from 0·3% to 03% to 22%.30 Secondly, riboflavin deficient individuals 22%." are are characterised by lower than normal glutathione reductase activity.3' activity. 31 The Eye Disease Case-Control Study pre- 793 793 sented evidence that antioxidant blood levels may be associated with a decreased risk of developing neovascular ARMD. ARMD.2727 Similarly, our data would suggest that individuals with low glutathione reductase activity and glutathione peroxidase activity are at increased risk of developing ARMD. Despite current evidence that decreased activity of blood antioxidant enzyme activity is associated with ARMD, it is premature to recommend the use of antioxidant vitamin supplements for patients with ARMD. The AgeRelated Eye Disease Study is conducting a long term randomised clinical trial to evaluate the effect of vitamin and mineral supplements on the development of ARMD. Supported in part by a grant in aid from Fight for Sight, Inc, Research Division of the National Society to Prevent Blindness, and NIH grant DK35747. SUTV OphthalI1 Framingham Eye Study. Macular degeneration. Surv mol 1980; 24 (Suppl): 428-57. 2 Ghafour 1M, IM, Allan D, Foulds WS. Common causes of blindness and visual handicap in the west of Scotland. Brj Br] Ophthalmol1983; Ophthalmol 1983; 67: 209-13. 3 Grey RH, Burns-Cox CJ, Hughes A. Blind and partial sight registration in Avon. Br] BrJr Ophthalmol1989; Ophthalmol 1989; 73: 88-94. 4 MacDonald AE. Causes of blindness in Canada. Can Med Assoc] 1965; 92: 264-79. AssocJ7 55 Rosenberg T. Prevalence of blindness caused by senile macular degeneration in Greenland. Arctic Med Res 1987; 46: 64-70. 6 Thompson JR, Du L, Rosenthal AR. Recent trends in the registration of blindness and partial sight in Leicestershire. Br] Ophthalmol1989; Ophthalmol 1989; 73: 95-9. Brj 7 Young RW. Pathophysiology of age-related macular degeneration. SUTV Surv Ophthalmol1987; Ophthalmol 1987; 31: 291-306. 8 Johnson ML. Aging of the United States population. Dermatologic Clinics 1986; 4: 371-7. 9 Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MO. Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Am] Epidemiol1988; Nutrition Examination Survey. Am J Epidemiol 1988; 128: 700-10. 10 Ferris FL. Senile macular degeneration: review of epidemiAm] Epidemiol Epidemio11983; ologic features. Amj 1983; 118: 132-51. II 11 Hyman LG, Lilienfield AM, Ferris FL, Fine SL. Senile Am] Epidemiol macular degeneration: a case-control study. AmJ 1983; 118: 213-27. 12 West SK, Rosenthal FS, Bressler NM, Bressler SB, Munoz B, Fine SL, et al. Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol 1989; 107: 875-9. 13 Gottsch JD, Pou S, Bynoe LA, Rosen GM. Hematogenous photosensitization: a mechanism for the development of agerelated macular degeneration. Invest Ophthalmol Vis Sci 1990; 31: 1674-82. 14 Taylor HR. Ultraviolet radiation and the eye: an epidemiologic study. Trans Am Ophthalmol Soc 1989; 98: 802-53. IS Young RW. Solar radiation and age-related macular degenera15 . tion. Surv SUTV Ophthalmol Ophthalmol1988; 252-{;9. 1988; 32: 252-69. 16 Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol 1988; 106: 192-8. 106:192-8. 17 Weiter JJ. Macular degeneration: is there a nutritional compoOphthalmol1988; nent? Arch Ophthalmol 1988; 106: 183-4. 18 Silverstone BZ, Landau L, Berson D, Sternbuch J. Zinc and copper metabolism in patients with senile macular degeneraOphthalmol1985; tion. Ann Ophthalmol 1985; 17: 419-22. 19 National Academy of Sciences. Recommended Daily Dietary Allowances: designed for the maintenance of good nutrition of practically all healthy people people in the United States. 1989 1989 practically Board, recommendations of the Food and Nutrition Board, National Academy of Sciences, Washington DC. 20 Lawrence RA, Burk RF. Glutathione peroxidase activity in Biochem Biophys Biophys Res Res Commun selenium-deficient rat liver. liver. Biochem selenium-deficient 1976; 71: 952-8. 1976; 21 Agergaard N, Jensen PT. Procedure for blood glutathione peroxidase determination in cattle and swine. Acta Vet Scand 1982; 23: 23: 515-27. 515-27. 1982; 22 Rogers KM, Augusteyn RC. Glutathione reductase in normal Eye Res 1978; 1978; 27: 719719and cataractous human lenses. Exp Eye 21. 21. 23 Marklund S, S, Marklund G. G. Involvement Involvement of of the the superoxide superoxide anion radical in the autoxidation of pyrogallol pyrogallol and aa convenconvenE ur] Biochem 1974; 1974; 47: ient assay for superoxide dismutase. 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Ophthalmoll993; Ophthalmol 1993; 111: Downloaded from bjo.bmj.com on March 19, 2013 - Published by group.bmj.com Cohen, Olin, Feuer, Hjelmeland, Keen, Morse 794 28 Tsang NCK, Penfold PL, Snitch PJ, Billson F. Serum levels of antioxidants and age-related macular degeneration. Doc Ophthalmol 1992; 81: 387-400. 29 Straatsma BR, Lightfoot DO, Barke RM, Horwitz J. Lens Ophcapsule and epithelium in age-related cataract. Am J Ophthalmoll991; thalmol 1991; 112: 283-96. 30 El-Hazmi EI-Hazmi MA, Warsy AS. Glutathione reductase in the southwestern province of Saudi Arabia -- genetic variation vs. acquired deficiency. Haematologica 1989; 22: 37-42. 31 Bates CJ. Human riboflavin requirements and metabolic consequences of deficiency in man and animals. World Rev N ulr Diet 1987; SO: 50: 215-65. Nutr ophthalmology History of ofophthalmology Eyesight and the public services Around the 1880s, eminent British ophthalmologists became concerned with matters which they sincerely believed would save hundreds of lives. This was no technical innovation, but merely the institution of proper sight testing for those who piloted boats, trains, and planes. At that time, the official requirements were lax -ships required only a 'percentage of seamen' to have 'approximately normal' vision and officialdom seemed completely oblivious of the dangers of defective sight. Ophthalmologists thus felt duty bound to instruct the government and regulatory bodies, and those arriving by horsedrawn cab for the meeting of the Ophthalmic Society on 9 March 1882 would have been party to the following debate: W A Brailey, dressed in the customary top hat and frock coat, opened with the stateof vision at sea' drawn up by ment that the 'Tests ofvision the International Medical Congress in 1881 were somewhat inadequate, yet had been opposed on the grounds that 'defects of vision have no practical interest'. Presumably, murmurs of dissent were heard in the gas-lit room. To refute this, Dr Fitzgerald recounted a case whereby a seaman was promoted to captain and on his maiden voyage ran into and sank another vessel while coming into port. He was reprimanded and demoted for 6 months, then reinstated. Steering into port on his second voyage he ran down a steamer lying at anchor, and at the subsequent tribunal, he was dismissed in disgrace and obtained a post on a smaller vessel. By interviewing the man and his colleagues, Fitzgerald ascertained that his vision was so impaired that he had 'long been .unable to recognise street names and the numbers on omnibuses' . omnibuses'. It was agreed that testing of both colour and acuity should be done, preferably by someone medically qualified, on all sailors involved in signalling and lookout. Although it was noted that a member of parliament had promised to raise the matter in the House during the current session, feelings were still running high 3 years later at the meeting of January 1895. Then, Mr Bickerstaff reported the case of the Iron Duke which, sailing in convoy, altered its course to avoid a ship seen ahead by one of the five watchmen. This caused it to collide with the . Vanguard, and a quarter of a million pounds' worth of equipment sank to the bottom. During the inquiry, the First Sea Lord heard with fury that the only lookout man to see this 'phantom ship' had defective vision, VISIon, having twice been treated for blindness. Parliament rose up in wrath at this, as did the ophthalmologists who sent an urgent deputation, via the British Medical Association, to the Board of Trade. Seventy years later, in 1953, the great increase in commercial air travel led the next generation of eminent ophthalmologists to consider the question of pilots' vision, the Civil Aeronautics Administration having announced (unsurprisingly) that candidates with normal vision were more likely to succeed at flight training. However, it was concluded that candidates with defective vision managed quite well if they lived to become suitably experienced. Therefore, the CAA decided to accept future trainees with defective vision, providing that their performance on landing was scrutinised before awarding them a licence! The ophthalmologists had no quarrel with this, but considered that possibly central and peripheral vision should be tested separately, as diseases such as retinitis pigmentosa could affect the latter only. (It was commented that this affliction afffiction made approach shots at golf rather difficult.) However, one ophthalmologist knew an Imperial Airways pilot with retinitis pigmentosa who asserted that the worst moments of his day were crossing Victoria station in the mornings and evenings. The company concluded that high visual acuity may not, in fact, be paramount in flying. (NB For those who feel worried, the CAA now insists on 6/9, 6/9 with satisfactory colour and peripheral vision.) With regard to trains, the Snellen test was employed to yield a standard of vision allowing a driver to see the rails up to the next curve, and for those who drove electric trains in a closed cabin, spectacles could be worn. This was felt to be satisfactory. With visual standard for motor drivers, mortality statistics (15 fatalities a day) raised cries of 'something must be done' done',, until it was stated that more accidents occurred in the home. 'To be logical, therefore, we should not stay at home, but should seek the relative safety of our motor cars,' stated the President, and having apparently exhausted their ire on ships and planes, the company turned to other matters. FFROMAN ROMAN Brailey WA. Tests of vision at sea. Trans Ophthalmol Soc UK 1882; OphthalmolSoc 1882; 2: 184-97. Mackay G. Eyesight and the public services. Trans Ophthalmol Soc UK 1895; 1895; 15: 199-205. Visual requirements in relation to modern travel. Trans OphthalOphthalmol Soc UK 1953; 73: 334-45. Downloaded from bjo.bmj.com on March 19, 2013 - Published by group.bmj.com Low glutathione reductase and peroxidase activity in age-related macular degeneration. S M Cohen, K L Olin, W J Feuer, et al. Br J Ophthalmol 1994 78: 791-794 doi: 10.1136/bjo.78.10.791 Updated information and services can be found at: http://bjo.bmj.com/content/78/10/791 These include: References Article cited in: http://bjo.bmj.com/content/78/10/791#related-urls Email alerting service Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article. Notes To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/