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What Makes Some Children

Short-sighted?

THE LANCET

MANY children become short-sighted, or near-sighted, to use the even more lucid American term,and grow up into short-sighted adults. How many,and are there proportionally more than there used tobe? Getting a fair sample of any population is verydifficult. Military conscription presents a specialopportunity to study a well-selected populationsample; in Britain, Sorsby and his colleagues took itand found an 11 % prevalence in young British menbut recognised that the true value might have beenhigher if they had made too little allowance for themen rejected for service.’ A more recent Americaninvestigation using a complex sampling design tocompensate for the lack of any similar opportunity,calculated that 25% of individuals in the UnitedStates between the ages of 12 and 54 are myopic, abouthalf only mildly so (under 2 dioptres). But the

sampling difficulties make it impossible to tellwhether the prevalence anywhere is rising or not.When we reflected on the characteristics of short-

sighted people in a 1974 editorial3 we noted theirtendency to an introverted ability at intellectual

pursuits, and wondered whether they got that way inearly life because of their short-sightedness. It wasknown that babies in general started off hyper-metropic ; the hypermetropia diminishes as they growolder, and if short-sightedness develops, it usuallydoes so around the time of starting school. Whyshould it befall some and not others? There had been

suggestions that too much reading did it; others reliedon twin studies which indicated a hereditary origin formyopia;S or was it perhaps a bookish pre-myopicpersonality that was the real inheritance, and readingthen brought on the myopia? Thirteen years ago therewas no useful animal model that could be used to testtheories of myopia’s origin and causes, and to suggestanswers to questions which cannot be directlyattacked, such as: "If we keep one identical twin gluedto the books during his first year at school, and pushthe other out into the playground all the time, willboth be equally likely to become short-sighted?"1. Sorsby A, Sheridan M, Leary GA, Benjamin B. Vision, visual acuity and ocular

refraction of young men. Br Med J 1960; i 1394-98.2. Sperduto RD, Seigel D, Roberts J, Rowland M. Prevalence of myopia in the United

States Arch Ophthalmol 1983; 101: 405-073. Editorial. The importance of being short-sighted. Lancet 1974; i: 393-94.4 Sorsby A, Leary GA. A longitudinal study 6f refraction and its components during

growth. Medical Research Council Special Report Senes, no 309. London: HMStationery Office, 1970.

5. Sorsby A, Sheridan M, Leary GA. Refraction and its components in twins. MedicalResearch Council Special Report Series, no 303 London: HM Stationery Office,1962.

Not much later the first model materialised-

serendipitously-while Hubel and Wiesel were

conducting their Nobel-prize-winning work on thefunction and development of the visual nervous

system. Some of the work involved keeping the eyelidsof very young monkeys closed. The results provedvery instructive about, for instance, the damage tohuman vision that results from squint.6 But Wieselnoticed with surprise that the covered eyes becamemyopic and much longer from front to rear thannormal eyes, like most short-sighted human eyes. Hestarted with Raviola to explore the underlyingmechanisms.

It was not darkness that initiated the myopia, nor (inrhesus monkeys) the muscular effort of accommoda-tion ; it was diffuse unpattemed light, which entersthrough the closed eyelids.8 Eyelids are remarkablytranslucent: try detecting with closed eyes when aweak light bulb is switched on or off across the room.In the same way, children’s eyes with disorders thatallow only diffuse light to reach the retina becomemyopic too.9 -

In the work on monkeys and in the observations onchildren, often one eye could serve as control for theother. Studying young chickens, Wallman and hiscolleagues have even been able to use part of one eye ascontrol for the rest, by providing translucentoccluders that block the entry of patterned light intoonly half the retina. There are peculiar difficulties indiscovering without error whether small animal eyesare short-sighted or otherwise, largely because theophthalmoscope beam is reflected from the interfacebetween vitreous and retina, not from the actual conesand rods. The distance between them is small in ahuman eye and makes little difference to themeasurement of refraction, it is about the same inmicrometres in a small eye, but there it does make adifference. 10 Overcoming this problem, Wallman andhis colleagues showed that the half eye where theretina had met only unpattemed light had becomemyopic and indeed measurably longer than the otherhalf, coming to bulge asymmetrically at the back."

So these eyes are evidently long-sighted at hatching,as human eyes generally are in infancy, and then growtowards short-sightedness,12 being arrested at thecorrect length if patterned light reaches the retina, andgrowing too large from front to rear if it does not. Themechanism is conjectural. The rods and cones

themselves, the photoreceptive part nearest to thegrowing coat of the eyeball, do not "know" whetherlight is patterned or not; this is information availableonly as analysis proceeds in the inner layers of the6. Wiesel TN. Postnatal development of the visual cortex and the influence of

environment. Nature 1982; 299: 583-917. Kolata G. What causes near-sightedness? Science 1985; 229: 1249-50.8. Raviola E, Wiesel TN An animal model of myopia. N Engl J Med 1985; 312: 1609-15.9. Rabin J, van Sluyters RC, Malach R. Emmetropisation a vision-dependent

phenomenon. Invest Ophthalmol Vis Sci 1981; 20: 561-64.10. Glickstein M, Millodot M. Retinoscopy and eye size. Science 1970, 168: 605-06.11 Wallman J, Gottlieb MD, Rajaram V, Fugate-Wentzek L Local retinal regions

control local eye growth and myopia Science 1987; 237: 73-77.12. Wallman J, Adams JI, Trachtman JN. The eyes of young chickens grow towards

emmetropia Invest Ophthalmol Vis Sci 1981, 20: 557-61

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retina and subsequently in the brain. So any molecularmessage travelling direct from inner retina outwardsmust diffuse a long way and somehow avoid beingwashed away by the choroidal blood circulation in itspath. On the other hand, if the message travels in thegeneral bloodstream, how does the target half of theeye know from which side of the retina (or perhapsfrom which half of the brain) the message originated?

. The origins of myopia in man may be quitedifferent from those in monkeys and chickens; indeed,rhesus monkeys responded differently from stump-tailed monkeys.8 The animal models of myopia all usevery young growing eyes; the results apply only towhether unpatterned light contributes to myopia inyoung children. Adults and adult animals do not getmyopic in the absence of patterned vision, and earlyremoval of adult cataracts, to prevent elongation of theeyeball, is not required. But early removal of

children’s cataracts may help to interrupt furthermyopic change.What about reading? Much reading, or early

reading, cannot be the sole cause of myopia, since itoccurs in quite unschooled peoples. But Wallman andhis colleagues are aware that the characters on aprinted page are small; no one wants to waste paper,and so printers make the majority of them about assmall as will get by. They are pattern only to fovealneurons in the retina, which are the sole retinalneurons that can "read" them. The rest of the retinacannot extract pattern except from much grosserstimuli: while the young child is reading, perhaps witheyes very close to the page, could most of his tworetinae outside the foveae be bored stiff and besomehow making him or her short-sighted ? Any effectof this kind would be enhanced by big pages with bigmargins, and by absence of pictures and colour.Further, darkness did not seem to produce myopia inthe monkey experiments, but unpattemed lightentering through the eyelids did. Until recent years, itwas hardly feasible for a child to be sleeping at nightunder bright light. Nowadays, if a child seems to

prefer it, bedroom light at night is easily provided,perhaps to seep unseen (because it has then no pattern)through the sleeping child’s eyelids, and to contributesomething to myopia.These are interesting speculations, but hard to test

on children. And as explanations of human myopia asit usually appears, they have to struggle for plausibilityagainst evidence like Sorsby’s study of twins5-78pairs of uniovular twins showed close agreement innine measurements of eye size and refraction, whereas40 pairs of binovular twins showed little more

agreement than control pairs of children. Could thepairs of binovular twins, but not the pairs of identicaltwins, have grown up with materially differingexperience of light and of reading? Unless they could,it seems that in children reading may not ordinarilymake much difference, and experience of patternedlight must be grossly deficient from very early in life toplay a part in generating myopia. There is no case yetto shut up all sleeping children in pitch darkness.

Hyperprolactinaemia: When is aProlactinoma not a Prolactinoma?

HYPERPROLACTINAEMIA is a blood test result, nota diagnosis. It may indicate the presence of a pituitaryprolactinoma, although there are other reasons for theserum prolactin being high-natural (trauma,pregnancy), pharmacological (methyldopa, pheno-thiazines, metoclopramide), and artefactual

(laboratory factors).1-3 But even if these confoundingcauses can be excluded, the clinician must stillremember that hyperprolactinaemia is not a disease inits own right, but an immunoassay result whichrequires interpretation.

In patients with large pituitary tumours and

hyperprolactinaemia, it is not always clear whether thehyperprolactinaemia occurs because the tumour is aprolactinoma (a prolactin-secreting adenoma), or

because compression of the pituitary stalk by a

non-functioning tumour prevents access of the

hypothalamic prolactin inhibitory factor, dopamine,with increased secretion of prolactin by the

lactotrophs of the remaining normal gland. To allintents and purposes, however, this question nowseems resolved. On the basis of extensive clinical

experience, Nabarr04 suggested that a serum prolactinconcentration less than 2500 mU/1 (approximately100-125 ng/ml) was usually the result of stalk

compression in patients with large tumours, andBevan and colleagues5 have lately come to a similarconclusion. Bevan et al correlated preoperative serumprolactin concentration with the immunostainingcharacteristics of pituitary tissue in 128 patientscoming to pituitary surgery (ie, a selected population,favouring those with large tumours). They found thatpatients with a serum prolactin less than 3000 mU/1were likely to have a non-functioning tumour,whereas those with concentrations greater than 8000

mU/1 were almost certain to have a prolactinoma.Between these two limits either diagnosis was

possible. These simple criteria should now be

adopted, but they have one limitation-they applyonly to large tumours. The diagnostic difficulties ofmicroprolactinomas are far more complex.The symptoms and signs of a microprolactinoma

are non-specific--oligomenorrhoea or amenorrhoeain women, impotence in men, and loss of libido andinfertility in both. Even the symptom (or sign) ofgalactorrhoea is of little help,6,7 and the primarydiagnosis rests almost entirely on the prolactin assay

1. Jeffcoate SL. Diagnosis of hyperprolactinaemia. Lancet 1978; ii: 1245-47.2. Franks S, Jacobs HS. Hyperprolactinaemia. Clin Endocrinol Metab 1983; 12: 641-68.3. Editorial. Hyperprolactinaemia: pituitary tumour or not? Lancet 1980; i: 515-19.4. NabarroJDN. Pituitary prolactinomas. Clin Endicronol 1982; 17: 129-55.5. Bevan JS, Burke CW, Esiri MM, Adams CBT. Misinterpretation of prolactin levels

leading to management errors in patients with sella enlargement. Am J Med1987; 82: 29-32.

6. Franks S, Nabarro JDN, Jacobs HS. Prevalence and presentation of

hyperprolactinaemia in patients with "functionless" pituitary tumours.

Lancet 1977; i: 778-80.7. Kleinberg DL, Noel GL, Frantz AG. Galactorrhoea: a study of 235 cases, including

48 with pituitary tumours. N Engl J Med 1977; 296: 589-60.