- Email: [email protected]
THE IMPORTANCE OF BEING SHORT-SIGHTED
732 Our own observations 4 of a positive correlation between measles and rubella virus antibody titres and autoantibodies in chronic active hepatitis suggest that continued studies of the paramyxoviruses in relation to a number of diseases of unknown aetiology may be of interest, but where differences between patients and control groups are marginal careful selection of the controls will be essential. Professorial Medical Unit, Royal South Hants Hospital, Fanshawe Street, Southampton SO9 4PE.
RALPH WRIGHT D. R. TRIGER.
1. Lancet, Feb. 16, 1974, p. 247. 2. Triger, D. R., Kurtz, J. B., MacCallum, F. O., Wright, R. ibid. 1972, i, 665. 3. Lucas, C. J., Brouwer, R., Feltkamp, T. E. W., Ten Veen, J. H., Van Loghem, J. J. ibid. p. 115. 4. Triger, D. R., Kurtz, J. B., Wright, R. Gut (in the press).
DEVELOPMENT OF THE CORNEA
SIR,-An unexpected developmental pattern of the be hypothesised from findings in affected males and in females heterozygous for Fabry’s disease. Lyon1 and Mintz2 suggested that the distribution of a striped coat-pattern in female mice heterozygous for an X-linked coat-colouring character, and in some chimseric mice, is an indication of the clonal growth of melanoblasts. These cells originate from the neural crest, and their transverse dorsoventral migration is seen as striping or patches in the cornea can
adult mice. Likewise, Mintz and Sanyal3 noted a radial pattern in the distribution of photoreceptors in chimseric mice produced by fusion of normal embryos and embryos carrying a gene for retinal degeneration. They took this distribution as indicative of centrifugal clonal growth of these cells. Although it is at present disputed that the maximum number of stripes in the coat4 corresponds to the clonal number of melanoblasts, the stripes, when present, are thought to indicate the route of clonal growth,5 and the irregular borders between the stripes to indicate cell
by localised duplication and ridges in the basal membrane of the epithelium.7 Subepithelial ridges are presumably caused by abnormal metabolism in the adjacent corneal epithelial cells, and the spiral pattern of the opacities can then be perceived as a reflection of the migration of these cells during the development of the anterior part of the cornea.
It would be reasonable to assume that the growth of the corneal epithelium follows the same pattern as that of the corneal stroma. The latter would thus also seem to develop
spirally. The opacities
are always densest and closest together in the centre of the cornea and taper out in the periphery. This could indicate that the entire cornea develops in a spiral centrifugal direction and not, as hitherto supposed, by invasion from the periphery of a specialised mesenchymal tissue into the loose mesodermal tissue originally present in front of the optic invagination. The opacities in individuals carrying the gene for Fabry’s disease are not always spiral-shaped but may be fan-shaped; some heterozygotes have opacities only in a restricted area of the cornea. This may be due to differences in selectional value or repair of the precursor cells. The radiating pattern, however, is evident in all cases. This hypothesis of the development of the cornea can explain the occurrence of microcornea and megalocornea as a result of an abnormal clonal-growth rate of the corneal progenitor cells.
Copenhagen Eye Clinic for the Mentally Retarded, Sognevej 40, Gentofte, Copenhagen, Denmark. 2820
1. 2. 3. 4. 5. 6. 7.
METTE WARBURG.
Lyon, M. Biol. Rev. 1972, 47, 1. Mintz, B. Symp. Soc. exp. Biol. 1971, 25 (suppl.), 435. Mintz, B., Sanyal, S. Genetics, 1970, 64 (suppl.), 43. Wolpert, L., Gingell, D. J. theoret. Biol. 1970, 29, 147. McLaren, A., Gauld, I. K., Bowman, P. Nature, 1973, 241, 180. Lewis, J. J. theoret. Biol. 1973, 39, 47. Weingeist, I. A., Blodi, F. C. Archs Ophthal. 1971, 85, 169.
mingling.6 In affected males and in females
heterozygous for
Fabry’s disease, the cornea presents a curvilinear fanshaped pattern in which opaque stripes meet in the centre and widen as they radiate to the periphery (see figure). The lack of difference in the pattern seen in hemizygous and heterozygous individuals shows that the feature cannot be directly explained by Lyon’s hypothesis of random inactivation of the X chromosome. The corneal haze seen in affected males is due to epithelial storage of glycolipids, but the whorls are produced
THE IMPORTANCE OF BEING SHORT-SIGHTED
SiR,—Your leader under this heading, if judged by its contents, would have been better entitled " The unimportance of being short-sighted ". Not only, as your correspondent Mr Dinning points out, do the complications of myopia blind a considerable number of people, but even more suffer visual incapacity to a greater or lesser degree. Very many more still are anxious about their " weak " eyesight. We are in ignorance of its cause, of what determines its progress, why progress ceases when it does, of how its complications arise and of any convincing preventive measures.
It seems a more satisfactory concept that a process which has such devastating effects in youth and the prime of life is a disease, rather than merely the simple opposite biological optical dimension to hypermetropia which has no such disastrous complications. If myopia is a disease, whether in whole or in part, then it should be approached with all the resources which are employed in the investigation and treatment of many more
Cornea from patient with Fabry’s disease.
(Photograph:
Dr H. W.
Larsen.)
minor ocular complaints. This department is at present investigating some of the aspects of difference between myopes and hypermetropes touched on in your leader. Particularly you mention in your concluding remarks that critical checking of the conventional picture of a hypermetrope as " idle, slightly unprincipled, good at games and girls " is desirable. For a start we have discovered that there are hyper-
733
metropic girls and
it will
surprise
us
if
they share
these
attributes. Guy’s Hospital, London SE1.
P. A.
GARDINER,
Research Fellow in Ophthalmology.
PRACTOLOL IN THE CONTROL OF INTRAOCULAR TENSION SiR,—There have been several reports of the oculartension-lowering effect of p-adrenergic-blocking agents in glaucoma. These included the peroral, intravenous, and Vale local application as eye-drops of 1% propanolol. and Phillips recently demonstrated the tension-lowering effect of practolol, a cardioselective p-adrenergic-receptorblocking drug, on a group of open-angle-glaucoma patients.1 Treatment with 10% practolol eye-drops was followed up for 2t-3t months in some patients. We report our experience with practolol in an open-angle-glaucoma patient who was followed up for more than a year. On Dec. 11, 1969, a man of 56 was referred to us with glaucoma. Since June, 1968, he had been treated for a nonbacterial allergic or vasomotoric conjunctivitis with dexamethasone, which was stopped when an increase in bilateral ocular tension was discovered. Despite administration of pilocarpine and phospholine iodine, ocular tension remained high (38 mm. Hg). On admission to hospital we found normal discs, normal visual fields, wide open angles of the anterior chambers, and no pigment or synechiae. Tension could be controlled by eye-drops of 2% pilocarpine 3 times daily and adrenaline (’Epirest’) 2 times daily. Tension was 21-25 mm. Hg in the right eye and 18-22 mm. Hg in the left (first admission December, 1969). Afterwards tension rose again and a Scheie operation was performed on the right eye (second admission June, 1970). After a third admission to the hospital (April, 1971) the tension was again 24 mm. Hg in the right eye and 30 mm. Hg in the left, with eye-drops of 4% pilocarpine 4 times daily and adrenaline twice daily. Because of a cardiac attack in November, 1971, the patient was treated with 100 mg. practolol 3 times daily in anothet hospital. At follow-up (January, 1972) we were puzzled by the bilateral drop in tension to 15 mm. (right eye) and 16 mm. (lefi eye). This could only be attributed to the administration oj
(’ Eppy ’)
practolol. With once-daily 2% pilocarpine in both
eyes and twice-daily eppy in the left eye, tension remained low (15 mm. Hg righ1 eye and 17 mm. Hg left eye) until March, 1973. After the dose
Ocular tension
during
of practolol had been reduced to 100 mg. once daily, ocular tension again rose to 21 mm. Hg in the right eye and 23 mm. Hg in the left eye (April 4, 1973). An asthma attack followed and practolol treatment was stopped completely. 1 week later tension was 27 mm. Hg in the right eye and 31 mm. Hg in the left eye, and more intense local treatment became necessary. Ocular tension during these 4 years is given in the accompanying figure. Tonographic findings with 300 mg. practolol and 2% pilocarpine eye-drops once daily in both eyes and eppy in the left twice daily were: coefficient of facility of outflow (c.) right eye=0-14, c. left eye==0-12. Tonographic findings without practolol but with 4% pilocarpine 4 times daily and eppy eye-drops twice daily in both eyes were: c. right eye=0-03, c. left eye=0-06. A trial with 10% practolol eye-drops was done in the left eye (October, 1973). Without treatment, tension went up sharply. Thereafter practolol was discontinued and 4% pilocarpine was given 4 times a day and eppy was given twice a day.
Department of Ophthalmology, Hospital of the Vrije University,
Academic
De Boelelaan 1117,
Amsterdam, The Netherlands.
A. HAGEDOORN S. T. TJOA.
Vale, J., Phillips, C. I. Br. J. Ophthal. 1973, 57,
1.
210.
PRIMARY ENURESIS AND AFFECTIVE ILLNESS
SIR,-Dr Sacks (March 23, p. 508) has suggested that there is a familial relationship between childhood enuresis In our family study of bipolar and adult depression. (manic-depressive) and unipolar (depressive) illness, primary enuresis was the most frequently reported child-1 hood disturbance among the offspring of our patients. More specifically, we found this condition only in sons of bipolar probands. Among our 204 affectively ill probands, however, only 1 (a bipolar) reported enuresis in his childhood. Whether enuresis is an early symptom of affective illness or rather a reaction to a parent’s illness cannot be determined from these data. Department of Medical Genetics, New York State Psychiatric Institute, New York 10032, and Columbia University, U.S.A. 1.
JULIEN MENDLEWICZ JUDITH KLOTZ.
Mendlewicz, J., Klotz, J. in Psychiatric Problems of Childhood (edited by S. Sankar). Hicksville, New York (in the press).
4 years of treatment with various drugs.
RALPH WRIGHT D. R. TRIGER.
1. Lancet, Feb. 16, 1974, p. 247. 2. Triger, D. R., Kurtz, J. B., MacCallum, F. O., Wright, R. ibid. 1972, i, 665. 3. Lucas, C. J., Brouwer, R., Feltkamp, T. E. W., Ten Veen, J. H., Van Loghem, J. J. ibid. p. 115. 4. Triger, D. R., Kurtz, J. B., Wright, R. Gut (in the press).
DEVELOPMENT OF THE CORNEA
SIR,-An unexpected developmental pattern of the be hypothesised from findings in affected males and in females heterozygous for Fabry’s disease. Lyon1 and Mintz2 suggested that the distribution of a striped coat-pattern in female mice heterozygous for an X-linked coat-colouring character, and in some chimseric mice, is an indication of the clonal growth of melanoblasts. These cells originate from the neural crest, and their transverse dorsoventral migration is seen as striping or patches in the cornea can
adult mice. Likewise, Mintz and Sanyal3 noted a radial pattern in the distribution of photoreceptors in chimseric mice produced by fusion of normal embryos and embryos carrying a gene for retinal degeneration. They took this distribution as indicative of centrifugal clonal growth of these cells. Although it is at present disputed that the maximum number of stripes in the coat4 corresponds to the clonal number of melanoblasts, the stripes, when present, are thought to indicate the route of clonal growth,5 and the irregular borders between the stripes to indicate cell
by localised duplication and ridges in the basal membrane of the epithelium.7 Subepithelial ridges are presumably caused by abnormal metabolism in the adjacent corneal epithelial cells, and the spiral pattern of the opacities can then be perceived as a reflection of the migration of these cells during the development of the anterior part of the cornea.
It would be reasonable to assume that the growth of the corneal epithelium follows the same pattern as that of the corneal stroma. The latter would thus also seem to develop
spirally. The opacities
are always densest and closest together in the centre of the cornea and taper out in the periphery. This could indicate that the entire cornea develops in a spiral centrifugal direction and not, as hitherto supposed, by invasion from the periphery of a specialised mesenchymal tissue into the loose mesodermal tissue originally present in front of the optic invagination. The opacities in individuals carrying the gene for Fabry’s disease are not always spiral-shaped but may be fan-shaped; some heterozygotes have opacities only in a restricted area of the cornea. This may be due to differences in selectional value or repair of the precursor cells. The radiating pattern, however, is evident in all cases. This hypothesis of the development of the cornea can explain the occurrence of microcornea and megalocornea as a result of an abnormal clonal-growth rate of the corneal progenitor cells.
Copenhagen Eye Clinic for the Mentally Retarded, Sognevej 40, Gentofte, Copenhagen, Denmark. 2820
1. 2. 3. 4. 5. 6. 7.
METTE WARBURG.
Lyon, M. Biol. Rev. 1972, 47, 1. Mintz, B. Symp. Soc. exp. Biol. 1971, 25 (suppl.), 435. Mintz, B., Sanyal, S. Genetics, 1970, 64 (suppl.), 43. Wolpert, L., Gingell, D. J. theoret. Biol. 1970, 29, 147. McLaren, A., Gauld, I. K., Bowman, P. Nature, 1973, 241, 180. Lewis, J. J. theoret. Biol. 1973, 39, 47. Weingeist, I. A., Blodi, F. C. Archs Ophthal. 1971, 85, 169.
mingling.6 In affected males and in females
heterozygous for
Fabry’s disease, the cornea presents a curvilinear fanshaped pattern in which opaque stripes meet in the centre and widen as they radiate to the periphery (see figure). The lack of difference in the pattern seen in hemizygous and heterozygous individuals shows that the feature cannot be directly explained by Lyon’s hypothesis of random inactivation of the X chromosome. The corneal haze seen in affected males is due to epithelial storage of glycolipids, but the whorls are produced
THE IMPORTANCE OF BEING SHORT-SIGHTED
SiR,—Your leader under this heading, if judged by its contents, would have been better entitled " The unimportance of being short-sighted ". Not only, as your correspondent Mr Dinning points out, do the complications of myopia blind a considerable number of people, but even more suffer visual incapacity to a greater or lesser degree. Very many more still are anxious about their " weak " eyesight. We are in ignorance of its cause, of what determines its progress, why progress ceases when it does, of how its complications arise and of any convincing preventive measures.
It seems a more satisfactory concept that a process which has such devastating effects in youth and the prime of life is a disease, rather than merely the simple opposite biological optical dimension to hypermetropia which has no such disastrous complications. If myopia is a disease, whether in whole or in part, then it should be approached with all the resources which are employed in the investigation and treatment of many more
Cornea from patient with Fabry’s disease.
(Photograph:
Dr H. W.
Larsen.)
minor ocular complaints. This department is at present investigating some of the aspects of difference between myopes and hypermetropes touched on in your leader. Particularly you mention in your concluding remarks that critical checking of the conventional picture of a hypermetrope as " idle, slightly unprincipled, good at games and girls " is desirable. For a start we have discovered that there are hyper-
733
metropic girls and
it will
surprise
us
if
they share
these
attributes. Guy’s Hospital, London SE1.
P. A.
GARDINER,
Research Fellow in Ophthalmology.
PRACTOLOL IN THE CONTROL OF INTRAOCULAR TENSION SiR,—There have been several reports of the oculartension-lowering effect of p-adrenergic-blocking agents in glaucoma. These included the peroral, intravenous, and Vale local application as eye-drops of 1% propanolol. and Phillips recently demonstrated the tension-lowering effect of practolol, a cardioselective p-adrenergic-receptorblocking drug, on a group of open-angle-glaucoma patients.1 Treatment with 10% practolol eye-drops was followed up for 2t-3t months in some patients. We report our experience with practolol in an open-angle-glaucoma patient who was followed up for more than a year. On Dec. 11, 1969, a man of 56 was referred to us with glaucoma. Since June, 1968, he had been treated for a nonbacterial allergic or vasomotoric conjunctivitis with dexamethasone, which was stopped when an increase in bilateral ocular tension was discovered. Despite administration of pilocarpine and phospholine iodine, ocular tension remained high (38 mm. Hg). On admission to hospital we found normal discs, normal visual fields, wide open angles of the anterior chambers, and no pigment or synechiae. Tension could be controlled by eye-drops of 2% pilocarpine 3 times daily and adrenaline (’Epirest’) 2 times daily. Tension was 21-25 mm. Hg in the right eye and 18-22 mm. Hg in the left (first admission December, 1969). Afterwards tension rose again and a Scheie operation was performed on the right eye (second admission June, 1970). After a third admission to the hospital (April, 1971) the tension was again 24 mm. Hg in the right eye and 30 mm. Hg in the left, with eye-drops of 4% pilocarpine 4 times daily and adrenaline twice daily. Because of a cardiac attack in November, 1971, the patient was treated with 100 mg. practolol 3 times daily in anothet hospital. At follow-up (January, 1972) we were puzzled by the bilateral drop in tension to 15 mm. (right eye) and 16 mm. (lefi eye). This could only be attributed to the administration oj
(’ Eppy ’)
practolol. With once-daily 2% pilocarpine in both
eyes and twice-daily eppy in the left eye, tension remained low (15 mm. Hg righ1 eye and 17 mm. Hg left eye) until March, 1973. After the dose
Ocular tension
during
of practolol had been reduced to 100 mg. once daily, ocular tension again rose to 21 mm. Hg in the right eye and 23 mm. Hg in the left eye (April 4, 1973). An asthma attack followed and practolol treatment was stopped completely. 1 week later tension was 27 mm. Hg in the right eye and 31 mm. Hg in the left eye, and more intense local treatment became necessary. Ocular tension during these 4 years is given in the accompanying figure. Tonographic findings with 300 mg. practolol and 2% pilocarpine eye-drops once daily in both eyes and eppy in the left twice daily were: coefficient of facility of outflow (c.) right eye=0-14, c. left eye==0-12. Tonographic findings without practolol but with 4% pilocarpine 4 times daily and eppy eye-drops twice daily in both eyes were: c. right eye=0-03, c. left eye=0-06. A trial with 10% practolol eye-drops was done in the left eye (October, 1973). Without treatment, tension went up sharply. Thereafter practolol was discontinued and 4% pilocarpine was given 4 times a day and eppy was given twice a day.
Department of Ophthalmology, Hospital of the Vrije University,
Academic
De Boelelaan 1117,
Amsterdam, The Netherlands.
A. HAGEDOORN S. T. TJOA.
Vale, J., Phillips, C. I. Br. J. Ophthal. 1973, 57,
1.
210.
PRIMARY ENURESIS AND AFFECTIVE ILLNESS
SIR,-Dr Sacks (March 23, p. 508) has suggested that there is a familial relationship between childhood enuresis In our family study of bipolar and adult depression. (manic-depressive) and unipolar (depressive) illness, primary enuresis was the most frequently reported child-1 hood disturbance among the offspring of our patients. More specifically, we found this condition only in sons of bipolar probands. Among our 204 affectively ill probands, however, only 1 (a bipolar) reported enuresis in his childhood. Whether enuresis is an early symptom of affective illness or rather a reaction to a parent’s illness cannot be determined from these data. Department of Medical Genetics, New York State Psychiatric Institute, New York 10032, and Columbia University, U.S.A. 1.
JULIEN MENDLEWICZ JUDITH KLOTZ.
Mendlewicz, J., Klotz, J. in Psychiatric Problems of Childhood (edited by S. Sankar). Hicksville, New York (in the press).
4 years of treatment with various drugs.