vitamin-d complex in progressive myopia*
TRANSCRIPT
VITAMIN-D COMPLEX IN PROGRESSIVE MYOPIA*
ETIOLOGY, PATHOLOGY, AND TREATMENT PRELIMINARY STUDY
ARTHUR ALEXANDER KNAPP, M.D. New York
The etiology of progressive myopia of progressive myopia examined by Flem-has always been a problem. The theories that have been advanced may be divided into groups characterizing the etiology as mechanical, hereditary, and acquired. Under the acquired causes vitamin deficiency has been mentioned without being emphasized. From experimental work which Blackberg and I have done on dogs in the Department of Pharmacology, Columbia University,1 and from clinical application of these laboratory findings, it seems that vitamin deficiency deserves greater stress in considering the etiology of progressive myopia. The improvement that has been shown in myopia treated from this standpoint has been so encouraging that we may hope that the cause of this visual defect is nearer solution. It is with this thought in mind that this brief report is made. Further, it is hoped this paper may act as a stimulus to other observers to check our results.
Rohmer and BezsnofP have said "The clinical recognition of vitamin deficiency states is no longer confined to the diagnosis of the classical picture. Knowledge must be extended to the recognition of the 'Forme Frustes' by a greater appreciation of how the specific vitamin functions in maintaining nutritional balance under normal and pathologic conditions." Strebel3 has shown that the normal sclera is rich in calcium. Buffington,4 in a discussion of myopia, states "Calcium deficiency is often present in progressive myopia." Fourteen out of 15 cases
* Presented before the Association for Research in Ophthalmology in Saint Louis, May 16, 1939.
ing5 showed a low blood calcium. Wood6
has found calcium deficiency in rapidly advancing myopia. Walker7 and Sorsby et al,8 too, are of the opinion that myopia is scleral rickets.
The production of axial myopia in the experimental animal presents intrinsic difficulties, but it seems that it is not an entirely impossible task. Tron9 has shown that the anteroposterior diameter of the eyeball cannot be used as a criterion, for emmetropic, hyperopic, and axial myopic eyes show wide individual variations. The fact is, the myopic eye may have an even smaller anteroposterior diameter than the hyperopic. Nor does retinoscopy in the presence of ectasia of the cornea offer any aid in the laboratory animal. Hence, we must content ourselves with indirect evidence of the presence of induced myopia in the animal.
Prominence of the eyes, wide palpebral fissures, and deep anterior chamber are very frequently associated with axial myopia in the human. Keratoconus and complicated cataract are unusual findings. All of our animals, fed a deficient vitamin-D-low-calcium diet, developed these eye changes. They may be interpreted as suggestive of the presence of myopia. Ectasia of the cornea, alone, may be sufficient to cause myopia. True axial myopia, the type usually seen in man, is particularly characterized by stretching of the sclera. Sir Arthur Keith10 remarks, "If the sclerotic fibro-blasts lay sound material and lay it rightly, then all is well, whatever be the usage we give our eyes. But, if the ma-
1329
1330 ARTHUR ALEXANDER KNAPP
terial is unsound and laid wrongly, then it is possible that forces which leave the normal eye unaffected may damage the abnormal eye."
Clinically, our rachitic dogs manifested primary ectasia of the cornea. Histologic examination of the membrane showed definite pathology which grew progressively worse with the advancement of the deficiency. Edema of the substantia pro-pria and irregularity of the lamellae were the principal changes. The sclera showed a similarly altered structure (figs. 1 and 2). These abnormal findings are an expression of the weakened fibrous tunic. Wood11 has said "When the cornea gives way, the sclera does also." Argafiaraz12
regards axial myopia as having the same origin as primary ectasia of the cornea. In a recent study of 18 human eyes13 I have shown that the vitamin-D complex is to be considered in the etiology of keratoconus.
A careful consideration of the clinical and pathologic findings in our animals leads to the conclusion that myopia probably has been induced in them by feeding a deficient vitamin-D-low-calcium diet.
Assuming a disorder of the vitamin-D-complex metabolism to be a basic factor in the etiology of myopia, certain facts readily are explained: The rarity of myopia in the American Indian; the fact that the rural inhabitant is freer from this complaint than is his city brother; that fewer myopic eyes are found in high altitudes; the prevalence of myopia in China. As for monocular myopia, it is Wiener's belief14 that it cannot be considered as an entity separate from the binocular variety. It may be that our greater food-consciousness, especially in relation to vitamin supply, explains why we are seeing fewer cases of progressive myopia today.
From thousands of cases at the New York Eye and Ear Infirmary, and from
some in my private practice, I have selected S3 patients for this study. Their periods of observation varied from 5 to 28 months. All of them were chosen because it was believed that their myopia would progress. Their age and past and present refractive errors were considered. The ages were from 3 to 20 years. Their myopia ranged from —0.25D. to —41.D. Vitamin D, in the form of Viosterol, and calcium, in the form of Mineral Mixture Tablets were prescribed.15 Dosage of the latter varied with the milk intake. If a patient drank one quart of milk daily, one tablet was prescribed. For each glass less than this, two tablets were added. During the first three months the majority had been taking their medication three times a day, after meals. After that time, the tablets were prescribed before breakfast, all in one dose, and the Viosterol, 60 drops, after the meal. This changed routine was adopted because it has been found that calcium is best absorbed in an acid medium. Otherwise, the patients' diet and regimen were unchanged.
The cycloplegic employed for the refractions previous to my supervision, in most cases, was not known. The atro-pine tests were made after the patients had had one drop of 1-percent atropine three times daily for three days, and a tenth drop on the morning of examination. Blood-serum calcium and phosphorus investigations were made in a few patients, but in too few to permit any conclusion to be drawn. Because of the laboratory limitations, more calcium and phosphorus studies were not obtained. It would be of value to carry on further research in myopia along these lines, to determine the blood-serum calcium and phosphorus, the amount of diffusible and nondiffusible calcium, and also the ioniz-able fraction. In addition, calcium-balance studies would be interesting, with a check of the urinary and fecal output.
VITAMIN-D COMPLEX IN PROGRESSIVE MYOPIA 1331
Fig. 1 (Knapp). Normal sclera of the dog. Fig. 2 (Knapp). Corresponding area of sclera of dog after it had been on vitamin-D deficient,
low-calcium diet for seven months, showing edema and irregularity of fibers.
RESULTS Of the 53 cases, insufficient data were
obtained on 7. In the remaining 46, only 12 patients took their medication regularly. Six of these 12 showed a reduction in their myopia; 2 remained stationary, 4 progressed. Considering the 46 patients, without regard to the regularity of medication, we find that 16, or 34.72 percent, had a reduction in their myopia ; 7 of them, or 15.19 percent, remained stationary; 21, or 45.57 percent, progressed ; and 2, or 4.34 percent, displayed a decrease of myopia in the left eye and a progression in the right. In other words, 66.67 percent of the patients who regularly took their medication either manifest a reduction in their myopia, or remained stationary. Taking into consideration the entire series, 50 percent revealed either a reduced myopia or were unchanged on reexamination.
To check further the influence of the administration of the vitamin-D complex on the human fibrous tunic, measurements of the cornea and the exposed scleral segment were made from plaster-of-Paris casts of the eyes with anterior-
curvature myopia before and after treatment with vitamin D and calcium. These figures were computed by Professors Carlos de Zafra and Louis Granath of the engineering and physics departments, respectively, of New York University. Very accurately they have shown that the cornea and the sclera, too, actually may shrink following this therapy. Scleral shrinkage also was found in both eyes of a patient with progressive myopia of 20.0 D., who, after the treatment period of eight months showed a reduction of 2.0 D. Clinically, this fact is well illustrated by two of the patients, who, without loss of weight or evident pathology of the levator palpebralis, developed a ptosis following the medication.
One of our patients, case 16, had been taking the Viosterol and Mineral Mixture Tablets for eight months. Atropine retinoscopy then showed less myopia in both eyes. After the patient had been without the prescribed therapy for eight months, atropine retinoscopy indicated an increase. Following another eight months of persistent taking of the medication, the condition again revealed
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No.
37
38
39
40
41
42
43
44
45
46
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PREV
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1336 ARTHUR ALEXANDER KNAPP a reduction. Another patient, case 46, only occasionally took his Viosterol and calcium for a period of 11 months. Atropine refraction brought out an increase in the myopia. Subsequent to 7 ^ months of regular medication there was a definite decrease.
As a result of this treatment, the majority of the patients noticed increased visual acuity for distance and near. Objectively, some showed better vision. They were not so dependent upon their glasses as formerly. Fo r distinct near vision without lenses, they found that reading matter could be held at a greater distance from the eyes. Characteristic poor muscle tonus improved. In none of this series have I noticed irritative conjunctivitis symptomatic of vitamin-D toxicity. The only toxic symptoms observed were anorexia in three patients, nausea and vomiting in two, and a mild skin eruption in two.
CONCLUSIONS
From this study, it appears that a disturbance in the vitamin-D-calcium-phos-phorus metabolism is concerned in the
etiology of myopia. In the presence of a calcium imbalance, there may be a weakening of the fibrous tunic, which may give rise to myopia. Once a condition of progressive myopia has been established, treatment with the vitamin-D complex is indicated. The myopic eyes that respond to this therapy may undergo an actual shrinkage of the globe.
For the prevention of the onset of myopia, the vitamin-D complex probably has another field of usefulness. Given a patient showing a diminishing degree of hyperopia, and one who is approaching the axial myopia side, it would be well to fortify his diet with vitamin D and calcium.
Assistance was given by Miss Diana Shrage of the social service department of the New York Eye and Ear Infirmary. My thanks are due the surgeons of the New York Eye and Ea r Infirmary for permission to present these patients. To the Mead Johnson Company of Evans-ville, Indiana, I wish to express my thanks for their generosity in financing this work.
35 East Sixty-fourth Street.
BIBLIOGRAPHY 1 Blackberg, S. N. and Knapp, A. A. Ocular changes accompanying disturbances of calcium-
phosphorus metabolism. Arch, of Ophth., 1934, v. 11, April, pp. 665-669; The influence of vitamin-D-calcium-phosphorus complex in the production of ocular pathology. 1. A histologi-cal study of the changes in the fibrous tunic. Amer. Jour. Ophth., 1937, v. 20, April, p. 405.
2Rohmer, P. and Bezsnoff, N. Investigations into the pathogenesis of scorbutic dystrophy. Arch. Dis. Child., 1935, v. 10, Aug., pp. 319-326.
* Strebel, J. Qualitative inorganic analyses of the sclera in normal human eyes. Schweiz. Med. Woch., 1931, v. 61, Nov. 14, p. 1102.
' Buffington, W. R. Discussion of Dr. L. Bothman's paper in Arch, of Ophth., 1933, v. 9, Feb., p. 306.
5 Fleming, N. Discussion of F. W. Law's paper, Calcium and parathyroid therapy in progressive myopia. Trans. Ophth. Soc. U. Kingdom, 1934, v. 44, pp. 281-290.
6 Wood, D. J. Calcium deficiency in the blood with reference to spring catarrh and malignant myopia. Brit. Jour. Ophth., 1927, v. 11, May, pp. 224-230.
'Walker, J. P. Progressive myopia. Brit. Jour. Ophth., 1932, v. 16, Aug., pp. 485-488. 8 Sorsby, A., Wilcox, K., and Ham, D. The calcium content of the sclerotic and its variation
with age. Brit. Jour. Ophth., 1935, v. 19, June, pp. 327-337. 9 Tron, E. Variationstatistische Untersuchungen fiber Refraktion. Arch. f. Ophth., 1929, v. 122,
May, p. 1. 10 Keith, A. Near sight and civilization. Brit. Jour. Physiol. Optics, 1925, v. 1, Sept., p. 3. " See ref. 6. 12 Arganaraz, R. Myopias progresivas y perturbaciones endocrinas: Contribucion a su estudio
etipatogenico. Semana med., 1922, v. 20, p. 1161.
VISUAL LOSS IN NEUROLOGICAL DISEASE 1337
"Knapp, A. A. Vitamin-D complex in keratoconus. Jour. Amer. Med. Assoc, 1938, v. 110, June 11, pp. 1993-1994.
" Wiener, Meyer. Discussion of Dr. Jonas S. Friedenwald's paper at the meeting of the Amer. Acad. of Ophth. and Oto-Laryn., in Montreal, Can., Sept., 1932.
15 Viosterol and Mineral Mixture tablets kindly supplied by the Mead Johnson Company of Evans-ville, Ind. The Mineral Mixture tablet contains the following in milligrams: Calcium, 140; Phosphorus, 83; Iron, 1; Copper, 0.05; Magnesium, 2.8; Sodium, 5; Potassium, 5.
DISCUSSION
D R . A L L E N GREENWOOD (Boston,
Mass.) : I would like to ask Dr. Knapp, in regard to his first patient, whether careful slitlamp examinations were made of the lens from time to time ? H e speaks of the lenses as being cataractous. I was wondering whether he kept careful slit-
lamp records from time to time of those lens changes, if there were any.
D R . A R T H U R ALEXANDER K N A P P : I
will publish that case history as a separate entity. It was exceedingly interesting. The eyes were frequently examined with the aid of the slitlamp and a record kept.
U N I L A T E R A L L O S S O F V I S I O N I N N E U R O L O G I C A L D I S E A S E *
P . J. LEINFELDER, M.D. Iowa City, Iowa
Gradual loss of vision in one eye is always an alarming symptom to the patient, and etiologic diagnosis is frequently difficult. Especially is this t rue in those cases in which external and oph-thalmoscopic evidence of ocular or general disease is absent. Usually a diagnosis can be made in such cases only after careful general and neurologic examination, ophthalmoscopic study, estimation of the visual fields, and roentgenographic observation of the orbits, optic canals, and skull. In the roentgenograms, the pituitary fossa and the sphenoidal ridges are of special interest, for in this region pathology most frequently occurs. Repeated observations of the ocular and general condition must be made to determine new signs that would lead to a diagnosis of the underlying etiology. The visual acuity may remain stationary, and all efforts toward localization may fail, but when
* From the Department of Ophthalmology, College of Medicine, State University of Iowa, Iowa City, Iowa.
vision progressively decreases in the interval between examinations, every effort must be made to determine the pathologic process. Although, on an anatomic basis, unilateral loss of vision can occur only as a result of pathology in a rather limited area at the base of the brain, a relatively large number of conditions can produce the symptom. Thoroughness and repeated observations will aid in obtaining an early diagnosis that will not only point out the causative pathologic condition, but also favor preservation or restitution of vision.
Adenoma of the Pituitary Body. Because, as was pointed out by Cushing,1
the field of vision in pituitary tumors is frequently diminished first in one eye, unilateral loss of vision is often an early complaint. Headache may be an accompanying symptom, but the visual loss is usually more distressing to the patient. Since prominent, clinical signs of pituitary disease are absent in most cases, the necessity for close study of the visual