- Email: [email protected]
Chorioretinitis And Hydrocephalus
so
RALPH D. ANDERSON AND DALE A. TEAGUE
6. Quereau, J. V. D., and Souder, P. F. : Teflon implant to elevate the eye in depressed fractures of the orbit. AM A Arch. Ophth., 55:685,1956. 7. Browning, C. W., and Walker, R. V.: Reconstruction of posttraumatic orbital fractures with poly ethylene. Am. J. Ophth., 52:672-677, 1961.
CHORIORETINITIS AND HYDROCEPHALUS* CONRAD L. GILES,
M.D.
Detroit, Michigan AND ALLEN S. LEWIS,
M.D.
Ann Arbor, Michigan The association of chorioretinitis, central nervous system disturbances and cerebral calcification in infancy has recently attracted considerable attention from clinical investi gators. Because this triad of signs points toward a diagnosis of toxoplasmosis, a study was undertaken to determine the incidence of chorioretinitis in hydrocephalus at the Coldwater (Michigan) State Home and Training School. A total of 31 idiopathic hydrocéphalie patients were examined at the institution. Five of this group exhibited concomitant chorioretinitis and form the basis of this report. Beginning with the discovery by Wolf and co-workers of toxoplasmosis in man in 1938,1 and followed in 10 years by the toxoplasmin skin test,2 and the Sabin-Feldman toxoplasmosis dye test,8 hundreds of papers have been published on the ocular and neurologic aspects of the disease. Chorio retinitis is, of course, one of the most con sistent features of congenital toxoplasmosis and is reported in an incidence as high as 99 percent of cases.4 Feldman and Miller reported an incidence of 94 percent of chorioretinal lesions in 150 cases of toxo plasmosis.5 Hydrocephalus has been reported to occur in 22 percent of 147 cases of toxo plasmosis.5 Cytomegalic inclusion disease is another entity that deserves consideration in the pres* From the Department of Ophthalmic Surgery, University of Michigan Medical Center.
ence of hydrocephalus and chorioretinitis with or without cerebral calcification. A viral disease which may affect many organ sys tems, the cytomegalic virus has been impli cated as a cause of chorioretinitis in several reports in the ophthalmic literature. The first reported cases of generalized cytomegalic inclusion disease with clinical chorioretinitis was published in 1957 by Weller, et. al.T Christensen8 reported a case of cytomegalic disease with detailed studies of the ocular pathology and concluded that the "retinopathy of cytomegalic inclusion dis ease is nondescript and may be of little diagnostic value." A third case of chorio retinitis is cytomegalic disease was reported by Guyton.* Theobald13 reported the eye pathology findings in a still-born infant with viral in clusion disease and noted cataract and necro sis of the retina, with very large mononuclear cells in the retina, containing cytoplasmic nuclear inclusions. Weiler and Henshaw 12 analyzed a series of 17 patients with nonfatal cytomegalic in clusion disease and found chorioretinitis in five of them. These five patients presented with mental retardation and spasticity. Three of the five were noted to have cerebral cal cifications ; in one no data was available and in one no cerebral calcification was found. For a complete review of this disease the reader is referred to this excellent article. Burns 6 reported an additional case of an terior and posterior uveitis where an agent
CHORIORETINITIS AND HYDROCEPHALUS
51
TABLE 1 CLINICAL AND LABORATORY MANIFESTATIONS
Etiology Clinical Features a. Central nervous system
Cytomegalic Inclusion Disease
Congenital Toxoplasmosis
Cytomegalovirus
Toxoplasma gondii
Microcephalus (commonly) Hydrocephalus (rarely) Psychomotor retardation Convulsions
Microcephalus (rarely) Hydrocephalus (frequently) Psychomotor retardation Convulsions
b. Visceral
Hepatomegaly Splenomegaly Jaundice Enteritis
Hepatomegaly Splenomegaly Jaundice Enteritis
c. Ocular
Chorioretinitis (often diffuse, peripheral with macular sparing)
Chorioretinitis (often with marked de struction and usually with macular involvement) Anterior uveitis (relatively rare) Optic nerve atrophy Cataracts (rarely)
Anterior uveitis Optic nerve atrophy Membranous conjunctivitis d. Cutaneous
Petechiae
Petechiae Maculo-papular eruption
e. Associated findings
Fever Pneumonitis
Fever Pneumonitis
Periventricular calcification
Intracerebral calcification
Urine Liver biopsy material
Blood Cerebrospinal fluid Lymph node
b. Serologie
Viral neutralization test (of questionable significance) Complement fixation (may give false nega tive results and is therefore unreliable)
Complement fixation Hemagglutination Fluorescence inhibition Méthylène blue dye test All of these serological tests are reliaable.
c. Skin test
Material not available
Sensitivity present 4-6 weeks after on set of disease
d. Hematology
Anemia, thrombocytopenia
Anemia, (?) thrombocytopenia
X-ray Findings Laboratory Features a. Culture
isolated from the anterior chamber produced inclusions in tissue culture similar to those primarily isolated from the urine. Table 1 lists the clinical and laboratory manifestations of congenital toxoplasmosis and cytomegalic inclusion disease. METHOD OF STUDY
The Coldwater State Home and Training School is a state-operated institution estab lished for the care of mentally defective in dividuals. This study encompassed the ex amination of all hydrocéphalies between the ages of six months and five years in the
institution in November, 1958. A complete external ophthalmologic ex amination was performed. The infants' eyes were then dilated with Cyclogyl (one per cent) and Neosynephrine (10 percent). A routine ophthalmoscopic examination was performed on each child. Slitlamp examina tions were not performed. After surveying the entire infant hydrocephalic population, all cases with chorio retinitis received a uveitis evaluation consist ing of the following tests: 1. Skin testing to histoplasmosis, coccidioidomycosis, blastomycosis, lymphogranuloma
52
CONRAD L. GILES AND ALLEN S. LEWIS
venereum (Frei test), toxoplasmosis skin test and control (Lilly) and old tuberculin. 2. Chest X-ray 3. Serologie test for syphilis 4. Skull X-ray films 5. Complete urinalysis and hemogram 6. Toxoplasmosis dye test (Sabin-Feldman) 7. Stool cultures In some of the cases all of these tests were not obtained following the discovery of an ocular lesion but had been obtained prior to the ocular survey. All hydrocéphalie patients were skin tested with the set of antigens used. As mentioned in the introduction to this report, 31 hydrocéphalies were examined and five (16 percent) exhibited chorioretinitis. Following are the reports of these five cases : CASE REPORTS CASE 1
D. S. was born on March 5, 1957. She was the product of a 33-week gestation and weighed six pounds, 12 ounces at birth. The labor and de livery was uneventful and the infant was "vigorous and lively" at birth. At eight weeks of age, the mother first noted abnormal head enlargement and, in June, 1957, the patient was first seen at the University of Michigan Medical Center. Her head size at that time was 19.25 inches. The fontanelles were open and tense and good transillumination of the skull was present. A right esotropia and right macular chorioretinitis were noted. Examination of the left eye was within normal limits. Laboratory studies performed included a toxoplasmosis dye test drawn on August 30, 1957, performed in Chamblee, Georgia, which was reported negative, both for the patient and her mother. Skull X-ray films taken on July 1, 1957, revealed pronounced hydrocephalus of indeterminate type and etiology with no evi dence of intracranial calcification. A negative ex amination of the chest was obtained. A urinalysis, including an examination for cytomegalic inclusion bodies, and peripheral blood smear were within nor mal limits. Lumbar puncture examination showed 25 cells and a protein of 51 mg. percent. The cerebrospinal fluid sugar was 31 mg. percent. Com plement fixation studies for the deep fungus dis eases were all reported as negative. The serum Kahn was negative. On July 24, 1958, a Holter valve was placed but this did not result in any change in the pro gression of the head enlargement, which progressed to 24 inches at the time of the last examination in
November, 1958. Ophthalmoscopic examination in November, 1958, confirmed the findings found at the University of Michigan Medical Center in June, 1957. Optic nerve atrophy in each eye was also noted at this time. Skin tests performed for the chronic granulomatous diseases on December 12, 1958 were all negative. The Brucella agglutina tion report was also negative. CASE 2
D. A. was born on March 4, 1954. Nitrous oxide and oxygen anesthesia were administered at the time of the uneventful delivery. The baby was active and normal appearing at birth, and it was not until three weeks of age that the parents noted abnormal enlargement of the child's head. The pa tient was referred to the University of Michigan Medical Center on August 10, 1954, where a diag nosis of hydrocephalus coupled with physical and mental retardation was made. At that time the head circumference was 20.5 inches. Lumbar puncture performed revealed an elevated opening and closing pressure, a spinal fluid sugar of 50 mg. percent, and spinal fluid protein of 55 mg. percent. Culture of the cerebrospinal fluid was negative. Chest films and the serum Kahn were negative and skull films demon strated moderately advanced hydrocephalus with no evidence of intracranial calcification. Consultation with the Department of Ophthalmology revealed bilateral extensive peripheral chorioretinitis without involvement of the macula in each eye. The re mainder of the ophthalmologic examination was within normal limits. Ventriculograms were per formed by the Department of Neurosurgery, but were unsatisfactory. They doubted the necessity
Fig. 1 (Giles and Lewis). Profile view of patient in Case 2, with moderately advanced hydrocephalus.
CHORIORETINITIS AND HYDROCEPHALUS
S3
for a shunt procedure because of the advanced hydrocephalus. A toxoplasmosis dye test was drawn and was reported negative, both for the child and her mother. At the time of the ophthalmologic examination at the Coldwater State Home and Training School, the head had enlarged to 25 inches. Bilateral, pe ripheral inactive chorioretinitis was again noted. Skin tests for the chronic granulomatous diseases were performed and were all negative, as were the complement fixation studies for the deep fungus in fections. The child has continued to maintain slow skull enlargement and remains functioning at the idiot level (fig. 1). CASE 3
R. C. was born on April 28, 1958, after eight and one-half months gestation, at an uneventful delivery. Crying was immediate and a strong suck reflex noted. During the pregnancy, the mother had some form of meningitis with increased cells and protein in her spinal fluid, had a negative culture at five months' gestation, and responded well to penicillin and sulfa. Because of an enlarging head the baby was seen at the University of Michigan Medical Center on May 13, 1958. Examination at that time revealed a two-week old baby, weighing six pounds, six ounces, with a head circumference of 14.5 inches. There was a wide separation of the coronal, sagittal and 1amboidal sutures and the fontanelles were tense and did not pulsate. While the child was in the hos pital over a two-week period the head increased to 15.75 inches. Laboratory studies at the time of that admission included a normal urinalysis, including studies for inclusion bodies, a normal hemogram, and a nega tive serum Kahn. Cerebrospinal fluid protein was 130 mg. percent and no cells were found in the cerebrospinal fluid. X-ray films taken at that time revealed apparent enlargement and thickening of the bones of the cranial vault. No intracranial calcifi cation was noted. The chest film showed a slight pneumonitis, but was otherwise normal. Toxo plasmosis dye studies at that time were negative for both the mother and the child. The child was examined at the Coldwater State Home and Training School on December 12, 1958, at which time extensive chorioretinitis was noted in each eye, involving the macular area and the periphery, bilaterally. The child had a pendular nystagmus in each eye. Optic nerve atrophy was not present. Prior to the examination by one of us (C. L. G.) on September 15, 1958, an attempt at placing a Holter valve was made, but this failed. Chronic granulomatous skin tests and complement fixation for deep fungus infections were all nega tive. The child developed acute pneumonitis early in November, 1960, and died on November 25, 1960. The eyes were enucleated and the pathoanatomic diagnosis stated "both eyes exhibited an old, non-
Fig. 2 (Giles and Lewis). Marked retinal de struction with areas of total atrophy and de struction seen in the posterior segment in Case 3. granulomatous uveitis which was still active. The long-standing choroiditis has resulted in virtually complete destruction of the retina. Schiff's stain was negative" (fig. 2). Cultures of the eyes were made and were reported as negative for viral and bactériologie etiologic agents by the Francis I. Proctor Laboratories at the University of Cali fornia. CASE 4
C. S. was born on September 15, 1954, the prod uct of a full-term cesarean section, weighing seven pounds, 12 ounces. Because of a slowly enlarging head, she was taken to the University of Michigan Medical Center at one month of age on October 18, 1954. Examination revealed a head circum ference of 17 inches with bossing of both parietal areas and dilatation of the superficial scalp veins. Both fontanelles were enlarged. Ophthalmoscopic examination performed by the Pédiatrie Service was reported as negative except for pale optic nerve heads. Bilateral ventricular taps were performed and it was found that less than two to three mm. of cortex remained. Be cause of the small degree of cortex encountered, it was the feeling of the Neurosurgery Service that a neurosurgical approach was not warranted. Xray examination of the skull showed an abnormally large skull with no intracranial calcification pres ent. Laboratory examination revealed a normal urinalysis and hemogram at the time of discharge on November 7, 1954; her head size was 18.25 inches.
54
CONRAD L. GILES AND ALLEN S. LEWIS
Fig. 3 (Giles and Lewis). The patient in Case 5, at the age of two and one-half years. Marked hydrocephalus is readily apparent in this profile photograph. In December, 1958, she was first examined by the ophthalmologist at the Coldwater State Home and Training School, at which time the head size was 33 inches and extensive bilateral central and pe ripheral inactive chorioretinitis with bilateral optic nerve atrophy were noted. Toxoplasmosis dye tests drawn at the time of the University of Michigan Hospital admission on the child and mother were negative. Skin tests and complement fixation studies to the deep fungal diseases were all negative. While in the Coldwater State Home and Train ing School, the patient became completely spastic in all four extremities and has continued to do poorly throughout her stay at that institution.
spinal fluid protein was recorded as 36 and showed two cells, but was otherwise negative. When examined by one of us (C. L. G.) on December 12, 1958, extensive bilateral chorio retinitis, both central and peripheral, was present in both eyes, the left eye being further advanced than the right (fig. 3). Moderate optic nerve atrophy was present in both eyes. A corneal ulcer was pres ent in the right eye which responded slowly to neosporin drops over a three-week period. The patient developed measles with severe pneumonitis in May 1960; death occurred on May 11, 1960. The autopsy revealed marked hydrocephalus and bilateral lower lobe pneumonitis. Sections of the brain failed to reveal an etiologic agent. Pathologic examination of the retina showed excessive scarring and degeneration, with virtually no normal appearing retina remaining. The pig ment epithelium showed large areas of total atrophy and destruction with some areas of slight pigment proliferation. Broad areas of choroidal retinal ad hesions and diffuse perivascular lymphocytic infil tration were present. Some plasma cells were seen in the choroid. The optic nerve was cut quite short but appeared atrophie. Schiff stains for fungi were negative (fig. 4). Dr. J. R. Wolter stated that "both eyes exhibit an old, nongranulomatous uveitis which is still ac tive. The long-standing choroiditis has resulted in virtually complete destruction of the retina." Bactériologie cultures and mice inoculations were both reported as negative by the Francis I. Proctor Foundation for Research in Ophthalmology at the University of California. DISCUSSION
Previous reports 4 ' 5 ' 8 · 9 · 1 2 ' 1 4 ' 1 5 have empha sized the not uncommon association of cho rioretinitis and cerebral damage. This report deals with one manifestation of cerebral
CASE 5
P. G. was born on May 29, 1957, a product of a nine-month gestation, weighed six pounds, seven ounces, with a good cry and suck reflex at the time of birth. Maternal complications included varicose veins and anemia, but no history of gestational ex posure to communicable diseases was elicited. The child was admitted to the Coldwater State Home and Training School in July, 1958, after continued enlargement of the head had resulted in a diagnosis of congenital hydrocephalus. The Kahn test and chest films were both nega tive. Skull films at that time revealed a thin bony vault with sellar erosion. No intracranial calcifica tion was seen. Complete blood studies and urinalysis were negative on three occasions in 1958. Toxoplas mosis dye test drawn in December, 1958, was re corded as negative, as were the complement fixa tion studies to the deep fungus diseases. On August 10, 1958, a Holter valve was placed. Cerebro-
Fig. 4 (Giles and Lewis). Extensive retinal de struction with scarring and atrophy. This photo micrograph also illustrates destruction of the pig ment epithelium, with resulting direct contact be tween choroid and retina in Case 5. A few lympho cytes can be recognized in the choroid in the area of the chorioretinal adhesion.
55
CHORIORETINITIS AND HYDROCEPHALUS TABLE 2 ANALYSIS OF PATIENTS
Case No.
Age and Time of Examina tion
Toxoplasmosis Dye Titers
1. D. S.
20 mo.
Patient Neg.
2. D. A.
4§ yr.
Urine Exami- Intranation for cranial Cytomegalic CalcifiInclusion cation Bodies
Comments
Mother Neg.
Negative
None
Complete uveitis workup unrevealing. Unilateral macular chorioretinitis
Neg.
Neg.
Negative
None
Complete uveitis workup negative. Bilateral, severe, peripheral chorio retinitis with macular sparing
3. R. C.
7 mo.
Neg.
Neg.
Negative
None
Bilateral macular and peripheral chorioretinitis; workup negative
4. C. S.
4 yr.
Neg.
Neg.
Negative
None
Bilateral macular and peripheral chorioretinitis; workup negative
5. P. G.
18 mo.
Neg.
Not drawn
Negative
None
Bilateral macular and peripheral chorioretinitis; workup negative
damage, hydrocephalus, and its association with chorioretinal inflammatory disease and is presented to emphasize two points. The first of these is the high incidence of these two signs in an unselected group of institutionalized hydrocéphalie patients. Six teen percent of these patients exhibited ad vanced idiopathic hydrocephalus and con comitant marked chorioretinitis. The second point of importance pertains to the etiology of the disease entities. An extensive diag nostic uveitis evaluation did not yield a single clue as to a specific agent involved in the disease. This work-up included skull films, the toxoplasmosis dye study (SabinFeldman) and urine examination for inclu sion bodies in an attempt to rule in or out the commonly associated disease entities in this symptom complex. Those two cases on which autopsies were performed, and the eyes subjected to microscopic and bactério logie examination, failed to implicate any specific etiologic agent. This lends support to the study of Sabin and Feldman10 who, in 1949, reported a series of 19 cases of chorioretinopathy and cerebral damage and found no laboratory evi dence to implicate Toxoplasma gondii as an etiologic agent in their group of patients. In
their group, four patients presented with hydrocephalus and 13 with microcephalus. They felt that "chorioretinopathy associated with other evidence of ocular and cerebral damage or defects and not due to toxo plasmosis is not infrequently encountered in infancy and early childhood." Three out of the five patients in this series showed extensive bilateral macular chorio retinitis often associated with smaller pe ripheral lesions. One patient had unilateral central chorioretinitis and one had bilateral marked peripheral chorioretinitis with macu lar sparing. Thus three of the infants pre sented the ocular picture believed most com monly associated with toxoplasmosis. Fair 14 · 15 has examined a great number of children in state schools for the blind and institutions for the mentally retarded. He states that he sees "more infant children with hydrocephalus, convulsions, intracerebral calcifications, mental and physical retarda tion and chorioretinitis not due to congenital toxoplasmosis than similar cases in which a diagnosis of congenital toxoplasmosis can be made, the only difference being in the results of the sérologie tests." This report re-emphasizes this finding since investigation of this group of five
56
CONRAD L. GILES AND ALLEN S. LEWIS
severely retarded hydrocéphalie infants failed to reveal positive sérologie proof of toxoplasmosis. It is further interesting to note that none of the 25 hydrocéphalies without chorio retinitis exhibited positive skin tests to toxoplasmin. It has been previously found that 22 percent of toxoplasmosis patients ex hibited hydrocephalus. I t seems apparent, however, that Toxoplasma gondii cannot be implicated as the causative agent in the majority of congenital hydrocéphalies. On the basis of Sabin and Feldman's re port and the work of Fair, one would not be surprised to find sérologie evidence for toxo plasmosis lacking in some of these hydro céphalies with chorioretinitis. Additionally, the lack of urine or autopsy confirmation of cytomegalic inclusion disease is not com pletely surprising. W h a t is a little disconcert ing is the fact that none of these infants demonstrated any positive sérologie or labo ratory findings for any of the known causes of chorioretinitis. None will dispute the fact that the elucidation of toxoplasmosis and cytomegalic inclusion disease as causative agents in the production of infant chorio retinitis is a major contribution t o our knowledge of uveal inflammation. This re port serves to re-emphasize the fact that these entities, although important, are prob ably only two of many, as yet unknown, etio-
logic factors in the production of posterior uveitis in infancy. SUMMARY AND CONCLUSIONS
1. A group of 31 cases of advanced idiopathic hydrocephalus institutionalized at the Coldwater State Home and Training School were examined to determine the incidence of associated chorioretinitis. Five, or 16 percent, of the patients demonstrated extensive chori oretinitis. 2. An extensive uveitis survey failed to implicate a specific etiology as a cause of this combination of clinical signs. 3. Pathologic and bactériologie examina tions of the eyes in two of the patients were unrevealing. 4. The absence of any associated labora tory or pathologic implication of toxoplas mosis or cytomegalic inclusion disease, as well as the high incidence of chorioretinitis in a group of hydrocéphalies is emphasized. Northland Professional Building. University Hospital. ACKNOWLEDGMENT
We wish to thank Dr. E. J. Rennell and his staff at the Coldwater (Michigan) State Home and Training School for their wonderful coopera tion in all aspects of this investigation. Dr. J. Reimer Wolter prepared, reviewed and photographed the pathologic material. His help in this matter is grate fully acknowledged.
REFERENCES
1. Wolf, A., Cowan, D., and Paige, B. H.: Human toxoplasmosis: Occurrence in infants as encephalomyelitis ; verification by transmission to animals. Science, 89:226-227 (Mar.) 1939. 2. Frenkel, J. K.: Dermal hypersensitivity to toxoplasma antigens. Proc. Soc. Exper. Biol. & Med., 68:634-639 (Dec. 10) 1948. 3. Sabin, A. B., and Feldman, H. A.: Dyes as microchemical indications of a new immunity phenome non affecting a protozoon parasite (Toxoplasma). Science, 108:660-663, 1948. 4. Feldman, H. A.: Congenital toxoplasmosis: A study of 103 cases. AM A J. Dis. Child., 86:487-488 (Oct.) 1953. 5. Feldman, H. A., and Miller, L. T.: Congenital human toxoplasmosis. Ann. N. Y. Acad. Sei., 64: 180-184 (July 5) 1956. 6. Burns, R. P.: Cytomegalic inclusion disease uveitis: Report of case with isolation from aqueous humor of virus in tissue culture. AMA Arch. Ophth., 61:376-387, 1959. 7. Weiler, T. H., Macauley, I. G, Craig, J. M., and Wirth, P.: Isolation of intraocular inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease. Proc. Soc. Exper. Biol. & Med., 94:4-12 (Jan.) 1957. 8. Christensen, L., Beeman, H. W., and Allen, A. : Cytomegalic inclusion disease. AMA Arch. Ophth., 57:90-99 (Jan.) 1957.
CHORIORETINITIS AND HYDROCEPHALUS
57
9. Guyton, T. B.: New observations in generalized cytomegalic inclusion disease of the newborn: Report of a case with chorioretinitis. New Eng. J. Med., 257:803-807 (Oct.) 1957. 10. Sabin, A. B., and Feldman, H. A.: Chorioretinopathy associated with other evidence of cerebral damage in childhood. J. Pediat, 35:296-309, 1949. 11. Weiler, T. H., and Henshaw, J. B.: Virologie and clinical observation on cytomegalic inclusion disease. New Eng. J. Med., 266:1233-1244 (June) 1962. 12. Fair, J. R.: Clinical eye findings in congenital toxoplasmosis. Survey Ophth., 6:923-935 (Dec.) 1961. 13. Theobald, G. D.: Cytomegalic inclusion disease: Report of a case. Am. J. Ophth., 47:52-56 (May, Pt. II) 1959. 14. Fair, J. R.: Congenital toxoplasmosis: III. Ocular signs of the disease in state schools for the blind. Am. J. Ophth, 48:165-172 (Aug.) 1959. 15. : Congenital toxoplasmosis: IV. Case finding using the skin test and ophthalmoscope in state schools for mentally retarded children. Am. J. Ophth, 48:813-819 (Dec.) 1959. T H E EFFECT O F A CONTACT LENS ON T H E CONTENT CARBON DIOXIDE IN T H E AQUEOUS HUMOR* CLEMENT
MCCULLOCH,
M.D.,
AND INGRID FIELDING,
OF
M.T.
Toronto, Ontario T h e influence of a contact lens on the meta bolic processes in the eye has been investi gated by several workers. Smelser and Ozanics 1 showed the importance of atmos pheric oxygen for the maintenance of the op tical properties of the cornea. Smelser 2 also found that deficiency of oxygen results in corneal edema. McCulloch and Morley 3 showed an increase of lactic acid in the cor nea under a contact lens. McCulloch 4 reported that bubbles appear under a contact lens when the wearer goes to low atmospheric pressure. T h e content of these bubbles is not known, but one of the important gases present may be carbon di oxide. If there is significant loss of carbon di oxide from the eye through the cornea, this would be decreased on wearing a contact lens and a rise in carbon dioxide content of the aqueous would occur. These experiments were carried out to de termine the C 0 2 content in the aqueous of rabbit eyes with or without contact lenses in place. * From the Department of Ophthalmology, Fac ulty of Medicine, University of Toronto. This study was supported by a Public Health Grant, No. 605-7-151. This paper was originally printed in The Journal, 55:718 (April) 1963, but due to a printing mishap the text was not in proper sequence. It is reprinted here with apologies to the authors.
METHOD
Six groups of adult albino rabbits weigh ing approximately 1.6 to 2.1 kg. were used. T h e contact lenses, fitted from five stock sizes and averaging 11.6 mm. in diameter, were put over the right eyes; the left eyes were used as controls. T h e animals in the five groups wore the contact lenses as follows: Group A, 30 minutes ; group B, one hour ; group C, two hours ; group D, three hours ; group E , five hours and group F , 24 hours. A t the end of the wearing time aqueous was withdrawn from either eye and carbon di oxide estimations were made by the methods of Scholander and co-workers 5 and the Natelson micromanometric method. 8 RESULTS
T h e carbon-dioxide content in the anterior TABLE 1 C 0 2 CONTENT IN RABBIT AQUEOUS EXPRESSED IN MILLIMOLS GAS PER LITER
(contact lens wearing time 24 hours)
Under contact lens Control
No.
Mean
6 6
30.9 29.5
Difference Stand from ard Mean Deviation + 1.7 ±2.6
1.94 2.82
RALPH D. ANDERSON AND DALE A. TEAGUE
6. Quereau, J. V. D., and Souder, P. F. : Teflon implant to elevate the eye in depressed fractures of the orbit. AM A Arch. Ophth., 55:685,1956. 7. Browning, C. W., and Walker, R. V.: Reconstruction of posttraumatic orbital fractures with poly ethylene. Am. J. Ophth., 52:672-677, 1961.
CHORIORETINITIS AND HYDROCEPHALUS* CONRAD L. GILES,
M.D.
Detroit, Michigan AND ALLEN S. LEWIS,
M.D.
Ann Arbor, Michigan The association of chorioretinitis, central nervous system disturbances and cerebral calcification in infancy has recently attracted considerable attention from clinical investi gators. Because this triad of signs points toward a diagnosis of toxoplasmosis, a study was undertaken to determine the incidence of chorioretinitis in hydrocephalus at the Coldwater (Michigan) State Home and Training School. A total of 31 idiopathic hydrocéphalie patients were examined at the institution. Five of this group exhibited concomitant chorioretinitis and form the basis of this report. Beginning with the discovery by Wolf and co-workers of toxoplasmosis in man in 1938,1 and followed in 10 years by the toxoplasmin skin test,2 and the Sabin-Feldman toxoplasmosis dye test,8 hundreds of papers have been published on the ocular and neurologic aspects of the disease. Chorio retinitis is, of course, one of the most con sistent features of congenital toxoplasmosis and is reported in an incidence as high as 99 percent of cases.4 Feldman and Miller reported an incidence of 94 percent of chorioretinal lesions in 150 cases of toxo plasmosis.5 Hydrocephalus has been reported to occur in 22 percent of 147 cases of toxo plasmosis.5 Cytomegalic inclusion disease is another entity that deserves consideration in the pres* From the Department of Ophthalmic Surgery, University of Michigan Medical Center.
ence of hydrocephalus and chorioretinitis with or without cerebral calcification. A viral disease which may affect many organ sys tems, the cytomegalic virus has been impli cated as a cause of chorioretinitis in several reports in the ophthalmic literature. The first reported cases of generalized cytomegalic inclusion disease with clinical chorioretinitis was published in 1957 by Weller, et. al.T Christensen8 reported a case of cytomegalic disease with detailed studies of the ocular pathology and concluded that the "retinopathy of cytomegalic inclusion dis ease is nondescript and may be of little diagnostic value." A third case of chorio retinitis is cytomegalic disease was reported by Guyton.* Theobald13 reported the eye pathology findings in a still-born infant with viral in clusion disease and noted cataract and necro sis of the retina, with very large mononuclear cells in the retina, containing cytoplasmic nuclear inclusions. Weiler and Henshaw 12 analyzed a series of 17 patients with nonfatal cytomegalic in clusion disease and found chorioretinitis in five of them. These five patients presented with mental retardation and spasticity. Three of the five were noted to have cerebral cal cifications ; in one no data was available and in one no cerebral calcification was found. For a complete review of this disease the reader is referred to this excellent article. Burns 6 reported an additional case of an terior and posterior uveitis where an agent
CHORIORETINITIS AND HYDROCEPHALUS
51
TABLE 1 CLINICAL AND LABORATORY MANIFESTATIONS
Etiology Clinical Features a. Central nervous system
Cytomegalic Inclusion Disease
Congenital Toxoplasmosis
Cytomegalovirus
Toxoplasma gondii
Microcephalus (commonly) Hydrocephalus (rarely) Psychomotor retardation Convulsions
Microcephalus (rarely) Hydrocephalus (frequently) Psychomotor retardation Convulsions
b. Visceral
Hepatomegaly Splenomegaly Jaundice Enteritis
Hepatomegaly Splenomegaly Jaundice Enteritis
c. Ocular
Chorioretinitis (often diffuse, peripheral with macular sparing)
Chorioretinitis (often with marked de struction and usually with macular involvement) Anterior uveitis (relatively rare) Optic nerve atrophy Cataracts (rarely)
Anterior uveitis Optic nerve atrophy Membranous conjunctivitis d. Cutaneous
Petechiae
Petechiae Maculo-papular eruption
e. Associated findings
Fever Pneumonitis
Fever Pneumonitis
Periventricular calcification
Intracerebral calcification
Urine Liver biopsy material
Blood Cerebrospinal fluid Lymph node
b. Serologie
Viral neutralization test (of questionable significance) Complement fixation (may give false nega tive results and is therefore unreliable)
Complement fixation Hemagglutination Fluorescence inhibition Méthylène blue dye test All of these serological tests are reliaable.
c. Skin test
Material not available
Sensitivity present 4-6 weeks after on set of disease
d. Hematology
Anemia, thrombocytopenia
Anemia, (?) thrombocytopenia
X-ray Findings Laboratory Features a. Culture
isolated from the anterior chamber produced inclusions in tissue culture similar to those primarily isolated from the urine. Table 1 lists the clinical and laboratory manifestations of congenital toxoplasmosis and cytomegalic inclusion disease. METHOD OF STUDY
The Coldwater State Home and Training School is a state-operated institution estab lished for the care of mentally defective in dividuals. This study encompassed the ex amination of all hydrocéphalies between the ages of six months and five years in the
institution in November, 1958. A complete external ophthalmologic ex amination was performed. The infants' eyes were then dilated with Cyclogyl (one per cent) and Neosynephrine (10 percent). A routine ophthalmoscopic examination was performed on each child. Slitlamp examina tions were not performed. After surveying the entire infant hydrocephalic population, all cases with chorio retinitis received a uveitis evaluation consist ing of the following tests: 1. Skin testing to histoplasmosis, coccidioidomycosis, blastomycosis, lymphogranuloma
52
CONRAD L. GILES AND ALLEN S. LEWIS
venereum (Frei test), toxoplasmosis skin test and control (Lilly) and old tuberculin. 2. Chest X-ray 3. Serologie test for syphilis 4. Skull X-ray films 5. Complete urinalysis and hemogram 6. Toxoplasmosis dye test (Sabin-Feldman) 7. Stool cultures In some of the cases all of these tests were not obtained following the discovery of an ocular lesion but had been obtained prior to the ocular survey. All hydrocéphalie patients were skin tested with the set of antigens used. As mentioned in the introduction to this report, 31 hydrocéphalies were examined and five (16 percent) exhibited chorioretinitis. Following are the reports of these five cases : CASE REPORTS CASE 1
D. S. was born on March 5, 1957. She was the product of a 33-week gestation and weighed six pounds, 12 ounces at birth. The labor and de livery was uneventful and the infant was "vigorous and lively" at birth. At eight weeks of age, the mother first noted abnormal head enlargement and, in June, 1957, the patient was first seen at the University of Michigan Medical Center. Her head size at that time was 19.25 inches. The fontanelles were open and tense and good transillumination of the skull was present. A right esotropia and right macular chorioretinitis were noted. Examination of the left eye was within normal limits. Laboratory studies performed included a toxoplasmosis dye test drawn on August 30, 1957, performed in Chamblee, Georgia, which was reported negative, both for the patient and her mother. Skull X-ray films taken on July 1, 1957, revealed pronounced hydrocephalus of indeterminate type and etiology with no evi dence of intracranial calcification. A negative ex amination of the chest was obtained. A urinalysis, including an examination for cytomegalic inclusion bodies, and peripheral blood smear were within nor mal limits. Lumbar puncture examination showed 25 cells and a protein of 51 mg. percent. The cerebrospinal fluid sugar was 31 mg. percent. Com plement fixation studies for the deep fungus dis eases were all reported as negative. The serum Kahn was negative. On July 24, 1958, a Holter valve was placed but this did not result in any change in the pro gression of the head enlargement, which progressed to 24 inches at the time of the last examination in
November, 1958. Ophthalmoscopic examination in November, 1958, confirmed the findings found at the University of Michigan Medical Center in June, 1957. Optic nerve atrophy in each eye was also noted at this time. Skin tests performed for the chronic granulomatous diseases on December 12, 1958 were all negative. The Brucella agglutina tion report was also negative. CASE 2
D. A. was born on March 4, 1954. Nitrous oxide and oxygen anesthesia were administered at the time of the uneventful delivery. The baby was active and normal appearing at birth, and it was not until three weeks of age that the parents noted abnormal enlargement of the child's head. The pa tient was referred to the University of Michigan Medical Center on August 10, 1954, where a diag nosis of hydrocephalus coupled with physical and mental retardation was made. At that time the head circumference was 20.5 inches. Lumbar puncture performed revealed an elevated opening and closing pressure, a spinal fluid sugar of 50 mg. percent, and spinal fluid protein of 55 mg. percent. Culture of the cerebrospinal fluid was negative. Chest films and the serum Kahn were negative and skull films demon strated moderately advanced hydrocephalus with no evidence of intracranial calcification. Consultation with the Department of Ophthalmology revealed bilateral extensive peripheral chorioretinitis without involvement of the macula in each eye. The re mainder of the ophthalmologic examination was within normal limits. Ventriculograms were per formed by the Department of Neurosurgery, but were unsatisfactory. They doubted the necessity
Fig. 1 (Giles and Lewis). Profile view of patient in Case 2, with moderately advanced hydrocephalus.
CHORIORETINITIS AND HYDROCEPHALUS
S3
for a shunt procedure because of the advanced hydrocephalus. A toxoplasmosis dye test was drawn and was reported negative, both for the child and her mother. At the time of the ophthalmologic examination at the Coldwater State Home and Training School, the head had enlarged to 25 inches. Bilateral, pe ripheral inactive chorioretinitis was again noted. Skin tests for the chronic granulomatous diseases were performed and were all negative, as were the complement fixation studies for the deep fungus in fections. The child has continued to maintain slow skull enlargement and remains functioning at the idiot level (fig. 1). CASE 3
R. C. was born on April 28, 1958, after eight and one-half months gestation, at an uneventful delivery. Crying was immediate and a strong suck reflex noted. During the pregnancy, the mother had some form of meningitis with increased cells and protein in her spinal fluid, had a negative culture at five months' gestation, and responded well to penicillin and sulfa. Because of an enlarging head the baby was seen at the University of Michigan Medical Center on May 13, 1958. Examination at that time revealed a two-week old baby, weighing six pounds, six ounces, with a head circumference of 14.5 inches. There was a wide separation of the coronal, sagittal and 1amboidal sutures and the fontanelles were tense and did not pulsate. While the child was in the hos pital over a two-week period the head increased to 15.75 inches. Laboratory studies at the time of that admission included a normal urinalysis, including studies for inclusion bodies, a normal hemogram, and a nega tive serum Kahn. Cerebrospinal fluid protein was 130 mg. percent and no cells were found in the cerebrospinal fluid. X-ray films taken at that time revealed apparent enlargement and thickening of the bones of the cranial vault. No intracranial calcifi cation was noted. The chest film showed a slight pneumonitis, but was otherwise normal. Toxo plasmosis dye studies at that time were negative for both the mother and the child. The child was examined at the Coldwater State Home and Training School on December 12, 1958, at which time extensive chorioretinitis was noted in each eye, involving the macular area and the periphery, bilaterally. The child had a pendular nystagmus in each eye. Optic nerve atrophy was not present. Prior to the examination by one of us (C. L. G.) on September 15, 1958, an attempt at placing a Holter valve was made, but this failed. Chronic granulomatous skin tests and complement fixation for deep fungus infections were all nega tive. The child developed acute pneumonitis early in November, 1960, and died on November 25, 1960. The eyes were enucleated and the pathoanatomic diagnosis stated "both eyes exhibited an old, non-
Fig. 2 (Giles and Lewis). Marked retinal de struction with areas of total atrophy and de struction seen in the posterior segment in Case 3. granulomatous uveitis which was still active. The long-standing choroiditis has resulted in virtually complete destruction of the retina. Schiff's stain was negative" (fig. 2). Cultures of the eyes were made and were reported as negative for viral and bactériologie etiologic agents by the Francis I. Proctor Laboratories at the University of Cali fornia. CASE 4
C. S. was born on September 15, 1954, the prod uct of a full-term cesarean section, weighing seven pounds, 12 ounces. Because of a slowly enlarging head, she was taken to the University of Michigan Medical Center at one month of age on October 18, 1954. Examination revealed a head circum ference of 17 inches with bossing of both parietal areas and dilatation of the superficial scalp veins. Both fontanelles were enlarged. Ophthalmoscopic examination performed by the Pédiatrie Service was reported as negative except for pale optic nerve heads. Bilateral ventricular taps were performed and it was found that less than two to three mm. of cortex remained. Be cause of the small degree of cortex encountered, it was the feeling of the Neurosurgery Service that a neurosurgical approach was not warranted. Xray examination of the skull showed an abnormally large skull with no intracranial calcification pres ent. Laboratory examination revealed a normal urinalysis and hemogram at the time of discharge on November 7, 1954; her head size was 18.25 inches.
54
CONRAD L. GILES AND ALLEN S. LEWIS
Fig. 3 (Giles and Lewis). The patient in Case 5, at the age of two and one-half years. Marked hydrocephalus is readily apparent in this profile photograph. In December, 1958, she was first examined by the ophthalmologist at the Coldwater State Home and Training School, at which time the head size was 33 inches and extensive bilateral central and pe ripheral inactive chorioretinitis with bilateral optic nerve atrophy were noted. Toxoplasmosis dye tests drawn at the time of the University of Michigan Hospital admission on the child and mother were negative. Skin tests and complement fixation studies to the deep fungal diseases were all negative. While in the Coldwater State Home and Train ing School, the patient became completely spastic in all four extremities and has continued to do poorly throughout her stay at that institution.
spinal fluid protein was recorded as 36 and showed two cells, but was otherwise negative. When examined by one of us (C. L. G.) on December 12, 1958, extensive bilateral chorio retinitis, both central and peripheral, was present in both eyes, the left eye being further advanced than the right (fig. 3). Moderate optic nerve atrophy was present in both eyes. A corneal ulcer was pres ent in the right eye which responded slowly to neosporin drops over a three-week period. The patient developed measles with severe pneumonitis in May 1960; death occurred on May 11, 1960. The autopsy revealed marked hydrocephalus and bilateral lower lobe pneumonitis. Sections of the brain failed to reveal an etiologic agent. Pathologic examination of the retina showed excessive scarring and degeneration, with virtually no normal appearing retina remaining. The pig ment epithelium showed large areas of total atrophy and destruction with some areas of slight pigment proliferation. Broad areas of choroidal retinal ad hesions and diffuse perivascular lymphocytic infil tration were present. Some plasma cells were seen in the choroid. The optic nerve was cut quite short but appeared atrophie. Schiff stains for fungi were negative (fig. 4). Dr. J. R. Wolter stated that "both eyes exhibit an old, nongranulomatous uveitis which is still ac tive. The long-standing choroiditis has resulted in virtually complete destruction of the retina." Bactériologie cultures and mice inoculations were both reported as negative by the Francis I. Proctor Foundation for Research in Ophthalmology at the University of California. DISCUSSION
Previous reports 4 ' 5 ' 8 · 9 · 1 2 ' 1 4 ' 1 5 have empha sized the not uncommon association of cho rioretinitis and cerebral damage. This report deals with one manifestation of cerebral
CASE 5
P. G. was born on May 29, 1957, a product of a nine-month gestation, weighed six pounds, seven ounces, with a good cry and suck reflex at the time of birth. Maternal complications included varicose veins and anemia, but no history of gestational ex posure to communicable diseases was elicited. The child was admitted to the Coldwater State Home and Training School in July, 1958, after continued enlargement of the head had resulted in a diagnosis of congenital hydrocephalus. The Kahn test and chest films were both nega tive. Skull films at that time revealed a thin bony vault with sellar erosion. No intracranial calcifica tion was seen. Complete blood studies and urinalysis were negative on three occasions in 1958. Toxoplas mosis dye test drawn in December, 1958, was re corded as negative, as were the complement fixa tion studies to the deep fungus diseases. On August 10, 1958, a Holter valve was placed. Cerebro-
Fig. 4 (Giles and Lewis). Extensive retinal de struction with scarring and atrophy. This photo micrograph also illustrates destruction of the pig ment epithelium, with resulting direct contact be tween choroid and retina in Case 5. A few lympho cytes can be recognized in the choroid in the area of the chorioretinal adhesion.
55
CHORIORETINITIS AND HYDROCEPHALUS TABLE 2 ANALYSIS OF PATIENTS
Case No.
Age and Time of Examina tion
Toxoplasmosis Dye Titers
1. D. S.
20 mo.
Patient Neg.
2. D. A.
4§ yr.
Urine Exami- Intranation for cranial Cytomegalic CalcifiInclusion cation Bodies
Comments
Mother Neg.
Negative
None
Complete uveitis workup unrevealing. Unilateral macular chorioretinitis
Neg.
Neg.
Negative
None
Complete uveitis workup negative. Bilateral, severe, peripheral chorio retinitis with macular sparing
3. R. C.
7 mo.
Neg.
Neg.
Negative
None
Bilateral macular and peripheral chorioretinitis; workup negative
4. C. S.
4 yr.
Neg.
Neg.
Negative
None
Bilateral macular and peripheral chorioretinitis; workup negative
5. P. G.
18 mo.
Neg.
Not drawn
Negative
None
Bilateral macular and peripheral chorioretinitis; workup negative
damage, hydrocephalus, and its association with chorioretinal inflammatory disease and is presented to emphasize two points. The first of these is the high incidence of these two signs in an unselected group of institutionalized hydrocéphalie patients. Six teen percent of these patients exhibited ad vanced idiopathic hydrocephalus and con comitant marked chorioretinitis. The second point of importance pertains to the etiology of the disease entities. An extensive diag nostic uveitis evaluation did not yield a single clue as to a specific agent involved in the disease. This work-up included skull films, the toxoplasmosis dye study (SabinFeldman) and urine examination for inclu sion bodies in an attempt to rule in or out the commonly associated disease entities in this symptom complex. Those two cases on which autopsies were performed, and the eyes subjected to microscopic and bactério logie examination, failed to implicate any specific etiologic agent. This lends support to the study of Sabin and Feldman10 who, in 1949, reported a series of 19 cases of chorioretinopathy and cerebral damage and found no laboratory evi dence to implicate Toxoplasma gondii as an etiologic agent in their group of patients. In
their group, four patients presented with hydrocephalus and 13 with microcephalus. They felt that "chorioretinopathy associated with other evidence of ocular and cerebral damage or defects and not due to toxo plasmosis is not infrequently encountered in infancy and early childhood." Three out of the five patients in this series showed extensive bilateral macular chorio retinitis often associated with smaller pe ripheral lesions. One patient had unilateral central chorioretinitis and one had bilateral marked peripheral chorioretinitis with macu lar sparing. Thus three of the infants pre sented the ocular picture believed most com monly associated with toxoplasmosis. Fair 14 · 15 has examined a great number of children in state schools for the blind and institutions for the mentally retarded. He states that he sees "more infant children with hydrocephalus, convulsions, intracerebral calcifications, mental and physical retarda tion and chorioretinitis not due to congenital toxoplasmosis than similar cases in which a diagnosis of congenital toxoplasmosis can be made, the only difference being in the results of the sérologie tests." This report re-emphasizes this finding since investigation of this group of five
56
CONRAD L. GILES AND ALLEN S. LEWIS
severely retarded hydrocéphalie infants failed to reveal positive sérologie proof of toxoplasmosis. It is further interesting to note that none of the 25 hydrocéphalies without chorio retinitis exhibited positive skin tests to toxoplasmin. It has been previously found that 22 percent of toxoplasmosis patients ex hibited hydrocephalus. I t seems apparent, however, that Toxoplasma gondii cannot be implicated as the causative agent in the majority of congenital hydrocéphalies. On the basis of Sabin and Feldman's re port and the work of Fair, one would not be surprised to find sérologie evidence for toxo plasmosis lacking in some of these hydro céphalies with chorioretinitis. Additionally, the lack of urine or autopsy confirmation of cytomegalic inclusion disease is not com pletely surprising. W h a t is a little disconcert ing is the fact that none of these infants demonstrated any positive sérologie or labo ratory findings for any of the known causes of chorioretinitis. None will dispute the fact that the elucidation of toxoplasmosis and cytomegalic inclusion disease as causative agents in the production of infant chorio retinitis is a major contribution t o our knowledge of uveal inflammation. This re port serves to re-emphasize the fact that these entities, although important, are prob ably only two of many, as yet unknown, etio-
logic factors in the production of posterior uveitis in infancy. SUMMARY AND CONCLUSIONS
1. A group of 31 cases of advanced idiopathic hydrocephalus institutionalized at the Coldwater State Home and Training School were examined to determine the incidence of associated chorioretinitis. Five, or 16 percent, of the patients demonstrated extensive chori oretinitis. 2. An extensive uveitis survey failed to implicate a specific etiology as a cause of this combination of clinical signs. 3. Pathologic and bactériologie examina tions of the eyes in two of the patients were unrevealing. 4. The absence of any associated labora tory or pathologic implication of toxoplas mosis or cytomegalic inclusion disease, as well as the high incidence of chorioretinitis in a group of hydrocéphalies is emphasized. Northland Professional Building. University Hospital. ACKNOWLEDGMENT
We wish to thank Dr. E. J. Rennell and his staff at the Coldwater (Michigan) State Home and Training School for their wonderful coopera tion in all aspects of this investigation. Dr. J. Reimer Wolter prepared, reviewed and photographed the pathologic material. His help in this matter is grate fully acknowledged.
REFERENCES
1. Wolf, A., Cowan, D., and Paige, B. H.: Human toxoplasmosis: Occurrence in infants as encephalomyelitis ; verification by transmission to animals. Science, 89:226-227 (Mar.) 1939. 2. Frenkel, J. K.: Dermal hypersensitivity to toxoplasma antigens. Proc. Soc. Exper. Biol. & Med., 68:634-639 (Dec. 10) 1948. 3. Sabin, A. B., and Feldman, H. A.: Dyes as microchemical indications of a new immunity phenome non affecting a protozoon parasite (Toxoplasma). Science, 108:660-663, 1948. 4. Feldman, H. A.: Congenital toxoplasmosis: A study of 103 cases. AM A J. Dis. Child., 86:487-488 (Oct.) 1953. 5. Feldman, H. A., and Miller, L. T.: Congenital human toxoplasmosis. Ann. N. Y. Acad. Sei., 64: 180-184 (July 5) 1956. 6. Burns, R. P.: Cytomegalic inclusion disease uveitis: Report of case with isolation from aqueous humor of virus in tissue culture. AMA Arch. Ophth., 61:376-387, 1959. 7. Weiler, T. H., Macauley, I. G, Craig, J. M., and Wirth, P.: Isolation of intraocular inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease. Proc. Soc. Exper. Biol. & Med., 94:4-12 (Jan.) 1957. 8. Christensen, L., Beeman, H. W., and Allen, A. : Cytomegalic inclusion disease. AMA Arch. Ophth., 57:90-99 (Jan.) 1957.
CHORIORETINITIS AND HYDROCEPHALUS
57
9. Guyton, T. B.: New observations in generalized cytomegalic inclusion disease of the newborn: Report of a case with chorioretinitis. New Eng. J. Med., 257:803-807 (Oct.) 1957. 10. Sabin, A. B., and Feldman, H. A.: Chorioretinopathy associated with other evidence of cerebral damage in childhood. J. Pediat, 35:296-309, 1949. 11. Weiler, T. H., and Henshaw, J. B.: Virologie and clinical observation on cytomegalic inclusion disease. New Eng. J. Med., 266:1233-1244 (June) 1962. 12. Fair, J. R.: Clinical eye findings in congenital toxoplasmosis. Survey Ophth., 6:923-935 (Dec.) 1961. 13. Theobald, G. D.: Cytomegalic inclusion disease: Report of a case. Am. J. Ophth., 47:52-56 (May, Pt. II) 1959. 14. Fair, J. R.: Congenital toxoplasmosis: III. Ocular signs of the disease in state schools for the blind. Am. J. Ophth, 48:165-172 (Aug.) 1959. 15. : Congenital toxoplasmosis: IV. Case finding using the skin test and ophthalmoscope in state schools for mentally retarded children. Am. J. Ophth, 48:813-819 (Dec.) 1959. T H E EFFECT O F A CONTACT LENS ON T H E CONTENT CARBON DIOXIDE IN T H E AQUEOUS HUMOR* CLEMENT
MCCULLOCH,
M.D.,
AND INGRID FIELDING,
OF
M.T.
Toronto, Ontario T h e influence of a contact lens on the meta bolic processes in the eye has been investi gated by several workers. Smelser and Ozanics 1 showed the importance of atmos pheric oxygen for the maintenance of the op tical properties of the cornea. Smelser 2 also found that deficiency of oxygen results in corneal edema. McCulloch and Morley 3 showed an increase of lactic acid in the cor nea under a contact lens. McCulloch 4 reported that bubbles appear under a contact lens when the wearer goes to low atmospheric pressure. T h e content of these bubbles is not known, but one of the important gases present may be carbon di oxide. If there is significant loss of carbon di oxide from the eye through the cornea, this would be decreased on wearing a contact lens and a rise in carbon dioxide content of the aqueous would occur. These experiments were carried out to de termine the C 0 2 content in the aqueous of rabbit eyes with or without contact lenses in place. * From the Department of Ophthalmology, Fac ulty of Medicine, University of Toronto. This study was supported by a Public Health Grant, No. 605-7-151. This paper was originally printed in The Journal, 55:718 (April) 1963, but due to a printing mishap the text was not in proper sequence. It is reprinted here with apologies to the authors.
METHOD
Six groups of adult albino rabbits weigh ing approximately 1.6 to 2.1 kg. were used. T h e contact lenses, fitted from five stock sizes and averaging 11.6 mm. in diameter, were put over the right eyes; the left eyes were used as controls. T h e animals in the five groups wore the contact lenses as follows: Group A, 30 minutes ; group B, one hour ; group C, two hours ; group D, three hours ; group E , five hours and group F , 24 hours. A t the end of the wearing time aqueous was withdrawn from either eye and carbon di oxide estimations were made by the methods of Scholander and co-workers 5 and the Natelson micromanometric method. 8 RESULTS
T h e carbon-dioxide content in the anterior TABLE 1 C 0 2 CONTENT IN RABBIT AQUEOUS EXPRESSED IN MILLIMOLS GAS PER LITER
(contact lens wearing time 24 hours)
Under contact lens Control
No.
Mean
6 6
30.9 29.5
Difference Stand from ard Mean Deviation + 1.7 ±2.6
1.94 2.82