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Ocular Findings in Hypercalcemia*
856
NOTES, CASES, INSTRUMENTS
The corrected retinoscopic findings were:
O.D, O.S.,
At Macula -2.2SD. -l.OOD.
In Area At Decreased Disc Pigmentation -4.S0D. - 8.2SD. -4.S0D. -10.00D.
Subjectively the patient accepted —2.5D. sph. for the right eye and — 1.5D. sph. for the left eye with a resultant corrected visual acuity of 20/30, O.U. Field studies revealed:
With the one-meter tangent screen and two-mm. and three-mm. white test objects there was a definite bitemporal field defect similar to that found by Rucker*· 5 in his cases. The isopters passed over the midline. without alteration of their course. The out line of the tangent screen defect rather closely resembled the pattern of the less pigmented area of each eye. 76 South Fitzhugh
Street.
REFERENCES
1. Mann, I.: Developmental Abnormalities of the Eye. London, Cambridge Univ. Press, 1937, p. 123. 2. Ibid. 3. Walsh, F. B.: Clinical Neuro-ophthalmology. Baltimore, Williams & Wilkins, 1947, p. 417. 4. Rucker, C. W.: The interpretation of visual fields. Tr. Am. Acad. Ophth., 1948, p. 38. 5. Rucker, C. W.: Bitemporal defects in visual fields resulting from developmental anomalies of the optic disks. Arch. Ophth., 35 :S46-5S4, 1946. 6. Fuchs, E.: Beitrag zu den angeborenen Anomalien des Sehnerven. Arch. f. Ophth., 28:139, 1882. 7. von Szily, A.: Der Konus nach unten. Zentralbl. f. prak. Augenh., 7:3S8, 1883. 8. Duke-Elder, W. S.: Textbook of Ophthalmology, St. Louis, Mosby, 1938, v. 2, p. 134S. 9. Fuchs, A.: Myopia inversa. Arch. Ophth., 37:722-739, 1947.
OCULAR FINDINGS IN HYPERCALCEMIA* A CLINICAL AND HISTOLOGIC STUDY VICTOR GOODSIDE,
M.D.
Bronx, New York That ocular lesions exist in conditions as sociated with hypercalcemia has been ade quately recorded by many authors includ ing Cogan, Albright, and Barter, 1 Walsh and Howard, 2 and Walsh and Murray. 3 The mechanisms by which hypercalcemia is pro duced in hyperparathyroidism, Boeck's sarcoidosis, vitamin-D poisoning, chronic nephritis, and excessive calcium and alkali intake, are described at length in the monu mental work of Albright and Reifenstein.4 It would not seem worthwhile at this time to discuss them except to say that the ocular findings when noted in these conditions are a result of the hypercalcemia. Justification for making the present report * From the Ophthalmologic Service of the Leba non Hospital.
rests on the fact that (1) the globe was obtained for histologic study and (2) the interesting funduscopic picture was perhaps related to the other ocular conditions noted. The ocular findings repeatedly observed by many writers consist of conjunctival and corneal lesions—the former being minute glasslike nodules containing whitish flecks thought to be calcium phosphate; the latter taking the form of a band-shaped keratitis with the heaviest opacity at the limbus and shading off axialward. Howard and Meyer5 noted in a number of cases that the conjuctival lesions receded with improvement but that the keratopathy did not. Fleischner and Shalek6 were able to demonstrate calcific deposition on X-ray examination of the orbit in areas consistent with the clinical findings. Histologic studies described in the litera ture are meager and are confined to two biopsies of the nodular conjunctival lesions, and histologic examination of one globe from an individual who had taken milk and alkali in excess for many years for duodenal ucler. The globe had been removed because of an entirely incidental painful glaucoma.
NOTES, CASES, INSTRUMENTS
Fig. 1 (Goodside). Calcareous plaque in the sclera.
Walsh 2 in his examination of the nodular conjunctival lesions noted the presence of amorphous purple-staining material in the superficial connective tissue which he took to be calcium phosphate. Cogan's findings, al though the eye he examined histologically was the site of an old penetrating injury and had come to enucleation as the result of pain ful glaucoma having nothing to do with systemic hypercalcemia, are very much like those of the case to be presented except as to the extent of calcific deposition in the sclera. CASE REPORT
A young white woman, aged 25 years, was hospitalized from February 24, 1947, until March 19, 1947, with symptoms of weight loss, nervousness, and tachycardia. A note was made at that time of complaint of ocular pain and redness but no ocular consultation was obtained. The diagnoses of hypertensive disease or of possible thyroid toxicosis were considered. A small mass in the right side of the neck suggested the diagnosis of thy roid adenoma. The patient was discharged somewhat improved. The second and final admission to the hos pital was on November 16, 1952, at which time the history was that there had been no complaints until three months before ad-
857
Fig. 2 (Goodside). Section at the limbus, showing calcific deposition in the subconjunctiva in a straight line continuous with the calcified Bowman's mem brane.
mission when the patient became weak and tired. Elevated blood pressure was noted and she complained of pain in both eyes and photophobia. A small nodule thought to be in the thyroid gland was again noted. A review of the skull film taken in 1947 suggested the possibility of hyperparathyroid disease, and this was borne out by blood calcium and phosphorus studies and by further X-ray studies of the skull and long bones. Blood calcium ranged between 16 and 17.7 mg. per 100 cc.; blood phosphorus about 2.9 mg. per 100 cc.; and alkaline phosphatase at 24.1 to 25.7 Bodansky units. Ocular examination was made under some difficulty because of the considerable photo phobia. Slitlamp examination was not per formed since the patient was confined to bed and, perhaps for this reason, the frequently described conjunctival nodules were not noted at this time. There was chemosis and injection of the bulbar conjunctiva of both eyes, the involve ment being most marked in the interpalpebral fissure. Here the injection extended to the limbus and was continuous with a chalkwhite line extending for four mm. along the limbus.
858
NOTES, CASES, INSTRUMENTS
Central from this chalk-white line and also in the interpalpebral fissure was a fainter superficial corneal opacity likewise vertically oriented and separated from the calcium line by what seemed to be a clear interval. The calcium line and the fainter opacity were noted both at the nasal and temporal limbus in each eye. The fundi were somewhat distorted as a result of a high degree of astigmatism. Discs were pale and vertically oval. The retinal vessels were rather attenuated. Scattered throughout the central areas were very numerous pale-pink, poorly defined lesions of many shapes lying underneath the retinal vessels. In many areas they were coalescent and in the macula they became larger, reach ing the size of 0.25 disc diameters. Between these patches there appeared an increase in retinal pigmentation in many areas. Inferior to the left disc the retina seemed edematous. The nature of the patches was uncertain. A biopsy of a submaxillary nodule was carried out. That night the patient died evi dently in acute parathyroid poisoning. Post-mortem examination revealed adeno ma of the right inferior parathyroid gland, hyperparathyroidism with extensive skeletal demineralization, and generalized calcinosis. Histologie examination of the globe showed plaques of calcium and bone forma tion in the sclera in the ciliary region, the region of the ora serrata, and behind the equator. One plaque involved the suprachoroid. There was a mild chronic inflamma tory reaction in the uveal tissue. Amorph
ous calcium deposition was noted in the subconjunctiva' at the limbus. One deposit formed a straight line which was continu ous with Bowman's membrane, and Bow man's membrane was itself calcified for a short distance at the limbus. The calcification of Bowman's membrane was seen to become increasingly less definite axialward. CONCLUSIONS
A woman who died of acute parathyroid poisoning with generalized calcinosis was found to have calcium deposition in the sclera, conjunctiva, and cornea. Her ocular fundi showed poorly defined pale-pink lesions deep to the retinal vessels and pos sibly related to the scleral calcium plaques either through transmitted pressure or as the result of local inflammatory response per haps in the choroid. The patient's recurrent arterial hypertension was mirrored by the attenuation of the retinal arterioles. The only other note in the literature made of positive funduscopic findings in hypercalcemia is by. Walsh, 3 who noted moderate hypertension and choroidal sclerosis of unusual severity in one of his cases. The patient's complaint of photophobia and redness of the eyes is undoubtedly related to irritation from exposed calcium deposits at the limbus or in the subconjunctiva. 1777 Grand Concourse (53). Acknowledgement is made of the assistance of Mrs. H. C. Wilder of the Armed Forces Institute of Pathology and of Dr. Samuel Gartner of Montefiore Hospital, New York, in the histologic interpre tation of the globe.
REFERENCES
1. Cogan, D., Albright, F., and Barter, F. C.: Hypercalcemia and band kerotopathy. Arch. Ophth., 40:624, 1948. 2. Walsh, F. B., and Howard, J. E.: Conjunctival and corneal lesions in hypercalcemia. J. Clin. Endocrinol., 7:644, 1947. 3. Walsh, F. B., and Murray, R. G.: Ocular manifestations of disturbances in calcium metabolism. Am. J. Ophth., 36:16S7 (Dec.) 19S3. 4. Albright, F., and Reifenstein, E.: The Parathyroid Glands and Metabolic Bone Disease. Baltimore, Williams & Wilkins, 1948. 5. Howard, J. E., and Meyer, R. J.: Intoxication with vitamin D. J. Clin. Endocrinol., 8:895, 1948. 6. Fleischner, F. G., and Shalek, S R.: Conjunctival and corneal calcification in hypercalcemia. New England J. Med., 241:863, 1949.
NOTES, CASES, INSTRUMENTS
The corrected retinoscopic findings were:
O.D, O.S.,
At Macula -2.2SD. -l.OOD.
In Area At Decreased Disc Pigmentation -4.S0D. - 8.2SD. -4.S0D. -10.00D.
Subjectively the patient accepted —2.5D. sph. for the right eye and — 1.5D. sph. for the left eye with a resultant corrected visual acuity of 20/30, O.U. Field studies revealed:
With the one-meter tangent screen and two-mm. and three-mm. white test objects there was a definite bitemporal field defect similar to that found by Rucker*· 5 in his cases. The isopters passed over the midline. without alteration of their course. The out line of the tangent screen defect rather closely resembled the pattern of the less pigmented area of each eye. 76 South Fitzhugh
Street.
REFERENCES
1. Mann, I.: Developmental Abnormalities of the Eye. London, Cambridge Univ. Press, 1937, p. 123. 2. Ibid. 3. Walsh, F. B.: Clinical Neuro-ophthalmology. Baltimore, Williams & Wilkins, 1947, p. 417. 4. Rucker, C. W.: The interpretation of visual fields. Tr. Am. Acad. Ophth., 1948, p. 38. 5. Rucker, C. W.: Bitemporal defects in visual fields resulting from developmental anomalies of the optic disks. Arch. Ophth., 35 :S46-5S4, 1946. 6. Fuchs, E.: Beitrag zu den angeborenen Anomalien des Sehnerven. Arch. f. Ophth., 28:139, 1882. 7. von Szily, A.: Der Konus nach unten. Zentralbl. f. prak. Augenh., 7:3S8, 1883. 8. Duke-Elder, W. S.: Textbook of Ophthalmology, St. Louis, Mosby, 1938, v. 2, p. 134S. 9. Fuchs, A.: Myopia inversa. Arch. Ophth., 37:722-739, 1947.
OCULAR FINDINGS IN HYPERCALCEMIA* A CLINICAL AND HISTOLOGIC STUDY VICTOR GOODSIDE,
M.D.
Bronx, New York That ocular lesions exist in conditions as sociated with hypercalcemia has been ade quately recorded by many authors includ ing Cogan, Albright, and Barter, 1 Walsh and Howard, 2 and Walsh and Murray. 3 The mechanisms by which hypercalcemia is pro duced in hyperparathyroidism, Boeck's sarcoidosis, vitamin-D poisoning, chronic nephritis, and excessive calcium and alkali intake, are described at length in the monu mental work of Albright and Reifenstein.4 It would not seem worthwhile at this time to discuss them except to say that the ocular findings when noted in these conditions are a result of the hypercalcemia. Justification for making the present report * From the Ophthalmologic Service of the Leba non Hospital.
rests on the fact that (1) the globe was obtained for histologic study and (2) the interesting funduscopic picture was perhaps related to the other ocular conditions noted. The ocular findings repeatedly observed by many writers consist of conjunctival and corneal lesions—the former being minute glasslike nodules containing whitish flecks thought to be calcium phosphate; the latter taking the form of a band-shaped keratitis with the heaviest opacity at the limbus and shading off axialward. Howard and Meyer5 noted in a number of cases that the conjuctival lesions receded with improvement but that the keratopathy did not. Fleischner and Shalek6 were able to demonstrate calcific deposition on X-ray examination of the orbit in areas consistent with the clinical findings. Histologic studies described in the litera ture are meager and are confined to two biopsies of the nodular conjunctival lesions, and histologic examination of one globe from an individual who had taken milk and alkali in excess for many years for duodenal ucler. The globe had been removed because of an entirely incidental painful glaucoma.
NOTES, CASES, INSTRUMENTS
Fig. 1 (Goodside). Calcareous plaque in the sclera.
Walsh 2 in his examination of the nodular conjunctival lesions noted the presence of amorphous purple-staining material in the superficial connective tissue which he took to be calcium phosphate. Cogan's findings, al though the eye he examined histologically was the site of an old penetrating injury and had come to enucleation as the result of pain ful glaucoma having nothing to do with systemic hypercalcemia, are very much like those of the case to be presented except as to the extent of calcific deposition in the sclera. CASE REPORT
A young white woman, aged 25 years, was hospitalized from February 24, 1947, until March 19, 1947, with symptoms of weight loss, nervousness, and tachycardia. A note was made at that time of complaint of ocular pain and redness but no ocular consultation was obtained. The diagnoses of hypertensive disease or of possible thyroid toxicosis were considered. A small mass in the right side of the neck suggested the diagnosis of thy roid adenoma. The patient was discharged somewhat improved. The second and final admission to the hos pital was on November 16, 1952, at which time the history was that there had been no complaints until three months before ad-
857
Fig. 2 (Goodside). Section at the limbus, showing calcific deposition in the subconjunctiva in a straight line continuous with the calcified Bowman's mem brane.
mission when the patient became weak and tired. Elevated blood pressure was noted and she complained of pain in both eyes and photophobia. A small nodule thought to be in the thyroid gland was again noted. A review of the skull film taken in 1947 suggested the possibility of hyperparathyroid disease, and this was borne out by blood calcium and phosphorus studies and by further X-ray studies of the skull and long bones. Blood calcium ranged between 16 and 17.7 mg. per 100 cc.; blood phosphorus about 2.9 mg. per 100 cc.; and alkaline phosphatase at 24.1 to 25.7 Bodansky units. Ocular examination was made under some difficulty because of the considerable photo phobia. Slitlamp examination was not per formed since the patient was confined to bed and, perhaps for this reason, the frequently described conjunctival nodules were not noted at this time. There was chemosis and injection of the bulbar conjunctiva of both eyes, the involve ment being most marked in the interpalpebral fissure. Here the injection extended to the limbus and was continuous with a chalkwhite line extending for four mm. along the limbus.
858
NOTES, CASES, INSTRUMENTS
Central from this chalk-white line and also in the interpalpebral fissure was a fainter superficial corneal opacity likewise vertically oriented and separated from the calcium line by what seemed to be a clear interval. The calcium line and the fainter opacity were noted both at the nasal and temporal limbus in each eye. The fundi were somewhat distorted as a result of a high degree of astigmatism. Discs were pale and vertically oval. The retinal vessels were rather attenuated. Scattered throughout the central areas were very numerous pale-pink, poorly defined lesions of many shapes lying underneath the retinal vessels. In many areas they were coalescent and in the macula they became larger, reach ing the size of 0.25 disc diameters. Between these patches there appeared an increase in retinal pigmentation in many areas. Inferior to the left disc the retina seemed edematous. The nature of the patches was uncertain. A biopsy of a submaxillary nodule was carried out. That night the patient died evi dently in acute parathyroid poisoning. Post-mortem examination revealed adeno ma of the right inferior parathyroid gland, hyperparathyroidism with extensive skeletal demineralization, and generalized calcinosis. Histologie examination of the globe showed plaques of calcium and bone forma tion in the sclera in the ciliary region, the region of the ora serrata, and behind the equator. One plaque involved the suprachoroid. There was a mild chronic inflamma tory reaction in the uveal tissue. Amorph
ous calcium deposition was noted in the subconjunctiva' at the limbus. One deposit formed a straight line which was continu ous with Bowman's membrane, and Bow man's membrane was itself calcified for a short distance at the limbus. The calcification of Bowman's membrane was seen to become increasingly less definite axialward. CONCLUSIONS
A woman who died of acute parathyroid poisoning with generalized calcinosis was found to have calcium deposition in the sclera, conjunctiva, and cornea. Her ocular fundi showed poorly defined pale-pink lesions deep to the retinal vessels and pos sibly related to the scleral calcium plaques either through transmitted pressure or as the result of local inflammatory response per haps in the choroid. The patient's recurrent arterial hypertension was mirrored by the attenuation of the retinal arterioles. The only other note in the literature made of positive funduscopic findings in hypercalcemia is by. Walsh, 3 who noted moderate hypertension and choroidal sclerosis of unusual severity in one of his cases. The patient's complaint of photophobia and redness of the eyes is undoubtedly related to irritation from exposed calcium deposits at the limbus or in the subconjunctiva. 1777 Grand Concourse (53). Acknowledgement is made of the assistance of Mrs. H. C. Wilder of the Armed Forces Institute of Pathology and of Dr. Samuel Gartner of Montefiore Hospital, New York, in the histologic interpre tation of the globe.
REFERENCES
1. Cogan, D., Albright, F., and Barter, F. C.: Hypercalcemia and band kerotopathy. Arch. Ophth., 40:624, 1948. 2. Walsh, F. B., and Howard, J. E.: Conjunctival and corneal lesions in hypercalcemia. J. Clin. Endocrinol., 7:644, 1947. 3. Walsh, F. B., and Murray, R. G.: Ocular manifestations of disturbances in calcium metabolism. Am. J. Ophth., 36:16S7 (Dec.) 19S3. 4. Albright, F., and Reifenstein, E.: The Parathyroid Glands and Metabolic Bone Disease. Baltimore, Williams & Wilkins, 1948. 5. Howard, J. E., and Meyer, R. J.: Intoxication with vitamin D. J. Clin. Endocrinol., 8:895, 1948. 6. Fleischner, F. G., and Shalek, S R.: Conjunctival and corneal calcification in hypercalcemia. New England J. Med., 241:863, 1949.