Amblyopia and yellow spectacles

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LETTERS to the

EDITOR

Binge-eating and polycystic ovaries SiR,—Patients with bulimia nervosa binge-eat, especially carbohydrates, and usually describe a menstrual disturbance despite being at normal weight.’ The mechanisms underlying the irregular menstruation and amenorrhoea are poorly understood. In women with polycystic ovary syndrome we suggested an association between abnormal ovarian morphology and binge-eating.2 We have investigated ovarian ultrasound in women with bulimia nervosa. 34 patients fulfilling D SM-IIIR criteria for bulimia nervosa had real-time pelvic ultrasound done in the early follicular phase of their cycle if menstruating or randomly if amenorrhoeic. Ovarian appearance was classified as normal, multifollicular, or polycystic according to the criteria of Adams et al. Polaroid pictures were taken that allowed independent classification by a third investigator. Disparities led to rescanning by the two investigators together. All patients were asked about their current menstrual cycle, which was defined as irregular when cycle length varied by more than seven days, and amenorrhoeic if menstruation was absent for greater than three times their previous cycle length. Body mass index was calculated. 19

patients (56%) reported a menstrual disturbance, 5 being amenorrhoeic. The patients were of normal body weight for height and age (102% mean-matched population weight [MMPW]).4 Of the 34 patients, only 4 (12%) had normal ovarian morphology and ultrasound. 30 patients (88%) had either polycystic (76%) or multifollicular (12%) ovaries. Those patients with multifollicular ovaries were lighter (92% MMPW, range 83%-110%) than those with normal or polycystic ovaries (102%, 98%-107%), although this did not reach statistical significance. No significant difference was found in reported menstrual cycles between the groups classified according to diagnosis. Our study showed that it was rare for bulimia nervosa patients to have normal ovarian morphology on ultrasound. Our previous work in patients with polycystic ovary syndrome attending an infertility clinic showed that one-third binge-ate in a way similar to bulimia nervosa patients.2 Together, these results support an association between binge-eating and the presence of polycystic ovaries. We believe that polycystic ovaries and menstrual who maintain a normal starvation and binge-eating. We suggest that insulin-resistance as a result of gross fluctuations in calorie ingestion/,5 especially carbohydrates, may aid the expression of an underlying tendency to polycystic ovaries. Our ultrasound results differ from the findings of Treasure who reported multifollicular ovaries in bulimic patients. This disparity may be accounted for by the difference in body weight of the two groups of patients. The mean body mass index of Treasure’s patients was 188, akin to some anorectic patients, compared with a mean body mass index of 23-3 in our group. The 20 patients reported by Treasure were all amenorrhoeic compared with 15 % of our population. Of interest is the low mean body mass index of our 4 women who had multifollicular ovaries. Mutifollicular ovaries are associated with nocturnal pulses of luteinising hormone before the onset of regular menstrual cycles, a situation seen at menarche and

irregularity

are

characteristic of

weight yet

eat

chaotically, fluctuating between

women

anorectics.7 A different ovarian reaction described It remains to be seen if correction of chaotic eating patterns in women with bulimia nervosa is associated with a return of normal ovarian morphology. in

recovering

above, may operate in those women who binge-eat.

Department of Psychiatry, University of Newcastle

S. E. MCCLUSKEY

Division of General Psychiatry, and Department of Gynaecology and Obstetrics, St George’s Hospital, London SW17 0RE, UK

J. H. LACEY J. M. PEARCE

CDH, Lacey JH, Pearce JM. Menstrual and ovulatory BMJ 1988; 287: 836-37. 2. McCluskey SE, Evans CDH, Lacey JH, Pearce JM, Jacobs HS Polycystic ovaries and abnormal eating behaviour: a comparative study of women attending an infertility clinic. Fertil Steril 1991; 55: 287-91. 3. Adams J, Franks S, Poison DW, et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 1985; ii:

1. Cantopher T,

Evans

disturbance in bulimia.

1375-79. 4. 5. 6.

Knight I. Office of Population Censuses and Surveys: the heights and weights of adults in Britain. London: HM Stationery Office, 1981. Schweiger U, Pollinger J, Lassle R, Wolfram S, Fichter HM, Pirke K. Altered insulin response to a balanced test meal in bulimia patients. Int J Eating Disord 1987; 6: 551. Treasure J. The ultra-sonographic features in anorexia nervosa and bulimia nervosa: a simplified method of monitoring hormonal status during weight gain. J Psychosom Res

1988; 32: 623-34. JL, Wheeler M, King EA, Gordon PAL, Russell GFM. Weight

7 Treasure

functions: ultrasonographic and endocrine features in Clin Endocrinol 1988; 29: 607-16.

reproductive nervosa.

gain and anorexia

Amblyopia and yellow spectacles SIR,-We were intrigued by Mrs Fowler and colleagues’ reports (refs 1, 2 and May 16, p 1230) that yellow filters improve vision in children with bilateral amblyopia. They described often instantaneous and striking improvement in visual acuity in bilaterally amblyopic children with yellow-tinted spectacle lenses of negligible dioptric power. Such findings could well be regarded as a "miracle cure". Our concern starts with the definition of amblyopia. This condition usually affects only one eye. Bilateral amblyopia may result from opacities of the ocular media such as a cataract, or from a bilateral refractive error which prevents either eye receiving a focused retinal image. This latter condition, in the absence of an opacity, is almost always due to hypermetropia, and is called isoametropic amblyopia.3 The data in the original article’ were too few for analysis and even in an expanded version’ Fowler et al state that cycloplegic refraction was done if judged necessary. We are not told how many of the cohort of 20 fell into this categpry, or how Fowler et al found that "no child had a refractive error greater than +05 dioptres". Cycloplegia and concomitant pupillary dilatation are both mandatory for accurate refraction and detailed ophthalmoscopy, respectively. This is standard clinical practice and their omission is a fundamental error that could have resulted in the failure to quantify accurately refractive state or to identify a subtle ophthalmoscopic abnormality. A key issue is that any child with unexplained visual loss should be fully examined before the diagnoses of amblyopia or hysterical visual loss can be entertained.

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Possibly Fowler et al adopt the term amblyopia in its classical sense (blunt sight, from the Greek) but if this is so it is confusing. With respect to the reported magnitude of the visual deficit that constituted amblyopia, Fowler et al correctly say that acuity in many children exceeds the standard normal value of 6/6. This is merely a statement that normal acuity is best represented by a range rather than a single value. However, for this cohort 6/6 was regarded as abnormal and to require treatment, although in this respect amblyopia and reading difficulties (the presumed basis for a substantial proportion of the referrals) need to be differentiated. The situation is further complicated by the knowledge that, as these investigators recognise, yellow filters may improve the vision of individuals with normal and abnormal visual function. Fowler and colleagues’ reports are confusing: some children of this cohort have been fully examined, others have not; some have what would generally be considered normal acuity. All children in this study, which did not include controls, have been treated by a method already shown to enhance normal vision. The idea is good, but until each child has been meticulously evaluated and compared with a control population, we do not know whether bilateral amblyopia without refractive error or media opacity really exists. Indeed if it does, perhaps a term other than amblyopia should be found since the use of this word is not in accord with current clinical practice and is causing confusion. Department of Ophthalmology, University of Birmingham Medical School, Birmingham and Midland Eye Hospital, Birmingham B3 2NS, UK

ALISTAIR FIELDER GARY MISSON MERRICK MOSELEY

1. Fowler MS, Mason AJ S, Richardson A, Stein JF. Yellow spectacles to improve vision in children with binocular amblyopia Lancet 1991; 338: 1109-10. 2. Mason AJS, Fowler MS, Stein JF. Yellow glasses improve the vision of children with binocular amblyopia. Invest Ophthalmol Vis Sci 1992; 33 (suppl): 1337. 3. Day S Normal and abnormal visual development. In: Taylor D, ed. Pediatric

ophthalmology. Oxford. Blackwell Scientific, 1990: 7-20. 4. Fowler MS, Richardson A, Mason AJS, Stem JF. Bilateral amblyopia in children can be improved by yellow filters. Br Orthopt J 1992; 49: 7-11.

**This letter has been shown to Mrs Fowler and colleagues, whose reply follows.-ED. L. SIR,-Professor Fielder and colleagues criticise our reports that some children with poor vision in both eyes can be helped by wearing yellow-tinted lenses. They seem to suggest that the binocular amblyopia of the children we described may have been the result of refractive errors that we failed to detect by not using cycloplegics for all our refractions. Although we agree with Fielder et al that the most accurate refractions do need the use of cycloplegics, we cannot agree that undetected refractive errors could have been the cause of these children’s visual problems. As stated in our original Lancet article and the other articles Fielder et al cite, the initial orthoptic examination of these children included testing acuity with 1 mm pinholes. This should improve acuity if optical correction is warranted. In no case did doing this, or using trial lenses, improve vision. However, yellow filters, which have no effect on the refractive state of the eye, did. Every child was seen by at least one ophthalmologist, and 7 children were assessed more than once. The ophthalmologists who did the refractions were all highly experienced. In the 10 younger children cycloplegics were used for the refraction, but in the 10 older children the ophthalmologists felt they were able to relax the accommodation simply by using fogging techniques; this consists of adding a positive (convex) lens, so that the eye obtains the clearest image only when accommodation is fully relaxed. Under these conditions none of the children had refractions greater than + 05D, which excludes important myopia. This examination might miss hyperopia, but hyperopia does not compromise visual acuity for charts at 6 m. Fielder et al also criticise our use of the term binocular amblyopia, especially in the 6 children whose visual acuity would usually be regarded as normal (6/6). By itself, we agree that this would be stretching the accepted use of this term. However, visual acuity is a rather limited measure of visual performance; the contrast sensitivity function is more comprehensive. As we reported, all these children (including those with visual acuity of 6/6) had much

poorer contrast sensitivity than is normal. We therefore felt that this fmding, in addition to their reduced accommodative range and poor stereoacuity, justified including these 6 with the other 14 with more

severely reduced acuity. We believe that we have found a means of improving the visual responses of a group of children in whom the cause of visual problems is unclear. Since yellow filters seem to lead to real benefits for these children, which cannot be achieved by other means, we are investigating the reasons for the visual defect in such children. Royal Berkshire Hospital, Reading

University Laboratory of Physiology, Oxford OX1 3PT, UK

M. S. FOWLER A. J. S. MASON A. J. RICHARDSON R. A. WELHAM J. F. STEIN

Carcinogenicity of 1,3-butadiene SiR,—The usefulness of rodent studies for identifying human carcinogens has long been debated. One recent opinion1 is that species differences in the metabolism of 1,3-butadiene raise doubts about the relevance of mouse experiments for human cancer risk assessment. We contend that carcinogenicity studies in laboratory animals remain a valuable means for predicting potential human risk, especially since several agents (eg, vinyl chloride) were shown in animals before similar evidence was obtained in Butadiene is another example of carcinogenicity first observed in animals.2 We have been investigating butadiene since the early 1980s, when epidemiological studies of the synthetic rubber industry began to focus attention on the potential carcinogenic effects of this chemical, and summarise here data on the metabolism and carcinogenicity of butadiene that provide a clearer picture of the potential risk to man. Butadiene is well recognised as a potent carcinogen in laboratory animals. In long-term studies it caused cancer at several sites in mice and rats. Because there were no exposure levels of butadiene at which a carcinogenic response was not induced, it is likely that exposure to concentrations below 6-25 parts per million (ppm) would also cause cancer. Induction of lung tumours at 6 25 ppm3 is noteworthy since that concentration is 160 times less than the current US permissible workplace exposure limit of 1000 ppm. Tumour induction on B6C3F mice exposed to butadiene was suggested to be affected by an endogenous leukaemia virus.’ However, although these mice do carry two ecotropic leukaemia viruses the spontaneous incidence of leukaemia/lymphoma is very low, and these cannot account for the carcinogenicity of 1,3butadience, especially since NIH Swiss mice, which lack this class of virus, still have a significant incidence of thymic lymphoma.’ Furthermore, as with human lung adenocarcinomas, butadieneinduced lung tumours in B6C3F mice frequently contained activated K-ras proto-oncogenes. Likewise, inactivating mutations in the p53 tumour suppressor gene, analogous to those observed in a wide variety of human cancers, have been characterised in butadiene-induced tumours in mice.s Butadiene metabolism in mammalian species is not different enough to account for the varied target sites or dose-response carcinogenic effects of this chemical. Butadiene is metabolised to mutagenic and carcinogenic epoxides in liver tissue from all species studied, including man. Although epoxide metabolites have been found in different amounts in the blood of mice, rats, and monkeys exposed to butadiene, the methods were inadequate for quantitative comparison.6 Species differences may arise through differences in body weight and breathing rates, and most risk assessment models take these factors into account. Butadiene is metabolised via the enzyme that is responsible for the oxidation of other low-molecular-weight hydrocarbons such as vinyl chloride and acrylonitrile to carcinogenic epoxidesActivity of this enzyme in the liver is highly variable in man and many individuals may produce carcinogenic epoxides at rates at least as high as those observed in laboratory rodents. Butadiene epoxides are mainly detoxified by epoxide hydrolase or glutathione S-transferase dependent metabolism. Hydrolysis predominates in man, glutathione conjugation in mice. to cause cancer man.