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Cerebrospinal fluid in 25 cases of optic neuritis
228
Surv Ophthalmol
20 (3) November-December,
1975
over the age of sixty who died with senile dementia (Schwartz, Tram NY Acad Sci 27:393, 1965). Amyloid has been implicated as the cause of lattice degeneration of the cornea and other primary hereditary cornea1 degenerations, and it is present in the ciliary bodies of many aged individuals including those with pseudoexfoliation syndrome. Indeed at one time we felt (Henkind and Friedman, unpublished data) that the pseudoexfoliative
CURRENT
OPHTHALMOLOGY
material might contain amyloid. In retrospect, we were probably detecting a fairly common (“normal?“) aging change. Cohen (N Engl J Med 277.522-530, 574-583, 628-638, 1967) provides an excellent review of this
very complicated subject. I expect that we will hear much more about amyloid in the eye within the next few years. PAUL HENKIND
Development of Cornea1 Transparency in Embryonic Chick: Influence of Exogenous Thyroxine and Thiouracil on Structure, Water and Electrolyte Content, by E Masterson, HF Edelhauser and DL van Horn. Dev Biol 43:233-239, 1975 Thyroxine (T,) and thiouracil were injected into the extra-embryonic circulation of chick embryos at various developmental stages to determine their effects on cornea1 cellularity, dehydration and structure. Corneas were removed 2-9 days after treatment for analysis of (Na+) and (K+) concentration, water content and histological structure. In normal chick corneas, water content and (Na+) concentration decreased with advancing embryonic age, whereas (K+) increased up to stage 42 and then rapidly declined. Corneas from embryos injected with 10 pg thiouracil at stage 36 had significantly reduced (K+) at stages 40 and 42. Corneas at stages 40,42 and 45 had a significantly elevated water content as compared to controls. Injection of 15 rg of T, prior to stage 36 or at stage 40 or later did not produce significant changes in water and ionic content as compared to control cornea1 levels. In contrast, injection of 15 Fg of T, during the period of rapid cell proliferation (stages 36-40) produced a significant increase in cornea1 (K+) levels. Histological analysis revealed a total increase in cornea1 thickness following thiouracil
Cerebrospinal
treatment and a decrease in cornea1 thickness following T, treatment. Epithelial growth was reduced in thiouracil treatment while T, had little effect. Comment It is well known that the water content of the cornea is high in the early embryo, but decreases as development proceeds. Concomitant with this dehydration, the cornea achieves transparency. It has been demonstrated that cornea1 hydration is influenced by thyroid hormone (Coulombre and Coulombre, Exp Eye Res 3: 105, 1964). This paper extends these earlier observations by treating chick embryos with excess thyroxine and thiouracil, an inhibitor of thyroid function and then measuring cornea1 thickness, water and ion content. They suggest that thiouracil treatment decreases cell division in the cornea and orevents the formation of the epithelial barrier whereas thyroxine accelerates these processes. 1
JOE G HOLLYFIELD
Fluid in 25 Cases of Optic Neuritis, by M Sandberg and H Bynke.
Acta New-01 &and 49:443-452,
1973
Occurrence of cerebrospinal fluid changes (CSF) in monosymptomatic optic neuritis patients have been thought to serve as a possible indicator of future development of multiple sclerosis. Such changes include mononuclear pleocytosis, increase in total protein and relative immunoglobin G (IgG) concentration, varying numbers of discrete IgG bonds in the gamma globulin fraction on agar gel electrophoresis and a possible abnormal dis-
tribution of kappa and lambda antigenic determinants in immunodiffusion and on immunoelectrophoresis. Twenty-five patients with acute monosymptomatic optic neuritis were studied for changes in the CSF as a possible indicator of future development of multiple sclerosis. After ocular and neurological examinations, the patients were subjected to cytological examinations, determinations
229
of total protein and IgG concentrations, and agar gel electrophoreses. CSF changes included mononuclear leucocytosis, 60%, elevated protein concentration, 24% and elevated relative IgG concentration, 16%. Electrophoresis bands in the gamma globulin region, on agar gel, were found in 24%. Since CSF changes were infrequent in the monosymptomatic optic neuritis patients, the case for optic neuritis’ being a manifestation of multiple sclerosis is significantly weakened. Comment The authors found that the most common CSF abnormality in their 2.5 patients was mononuclei leucocytosis, which occurred in 60%. Other abnormalities were infrequent. The total protein concentration was elevated in six of the 25. The relative IgG concentration was elevated in four cases. Electrophoretic bands in the gamma globulin region were found in six cases. Three patients of the 25
developed multiple sclerosis. The cell count in the cerebrospinal fluid is the most sensitive indicator of the first attack. This fact is indicated in this series and also in the series of Link and Muller (Arch Neurol 25:326, 1971) and Schwartz et al. (Europ Neurol 4.267, 1970). The results of the CSF investigation of these patients differ greatly from those reported in multiple sclerosis patients. It is apparent from the results of this paper that in acute optic neuritis changes are found infrequently in the CSF, and when found, they are not very pronounced. It is probable that the CSF changes are related to the amount of nervous tissue that is damaged. Since relatively little nervous tissue is damaged in an initial attack of monosymptomatic optic neuritis, we should expect little or no change in the CSF. It is obvious, at this point, that early CSF changes in optic neuritis cannot be used as a prognostic indicator for the future development of multiple sclerosis. ROBERT JAMPEL
Epidemiologic Characteristics of Presumed Ocular Ganley. Acta Ophthalmol Suppl 119: l-63. 1973 A case-control
study
of the association of and disciform scars of presumed _ ocular histoplasmosis is described. Cases were obtained from a group ophthalmic practice in Hagerstown, Washington County, Maryland. Three groups of controls were used: a group of individuals with fundus scars other than the cases; a random sample of patients from the ophthalmic practice; and a random sample from the 1963 Washington County census. Cases and controls were selected from individuals aged 30-69 years and living in Washington County at the time of the examination, Data were gathered from a self-administered questionnaire, a complete ocular examination, serologic studies, and delayed skin tests administered independently and read without knowledge of the individual’s ocular status. Nineteen cases of disciform scars and 15 cases of peripheral scars of presumed ocular histoplasmosis were identified. All disciform cases had a positive histoplasmin skin test (defined as 5 mm or more diameter of induration) compared with 60.0% of those with peripheral scars, and 60.7% of controls. On repeat histoplasmin skin test, 93.3% of individuals with peripheral scars were positive compared with 69.5% of the controls. People with disciform scars had larger mean induration size to histoplasmin, greater frequency of positive reactions to the yeast complement fixing antibody test, Histoplasma capsdatum
Histoplasmosis,
by
JP
and greater likelihood of having calcification on pulmonary x-ray, attesting to the strong association in the past with H. capsulatum. Disciform cases tended to live in wood frame houses, to smoke cigarettes more heavily, to have more frequent exposure to dust, birds, bats and guano, to have a positive tuberculin skin test, and to be lower on the socioeconomic scale. These same risk factors for people with only peripheral scars were more similar in value to those of the controls. Peripheral lesions seem most likely to occur at the time of first exposure to and infection with H. capsdatum, whereas the disciform process probably occurs IO-30 years later. People who have disciform scars generally have a heightened cellular and serologic immune response to histoplasmin, possibly resulting either from reexposure to the organism or from innate allergic hypersensitivity. It is postulated that for the disciform process to occur, there must be prior sensitization of the choroid by H. capsdatum organisms, the presence of an altered choroidal vascular permeability, and a primed cellular immune system. (Abstract reprinted from the original article) Comment This long doctoral thesis is recommended for those interested in ocular histoplasmosis. The data
Surv Ophthalmol
20 (3) November-December,
1975
over the age of sixty who died with senile dementia (Schwartz, Tram NY Acad Sci 27:393, 1965). Amyloid has been implicated as the cause of lattice degeneration of the cornea and other primary hereditary cornea1 degenerations, and it is present in the ciliary bodies of many aged individuals including those with pseudoexfoliation syndrome. Indeed at one time we felt (Henkind and Friedman, unpublished data) that the pseudoexfoliative
CURRENT
OPHTHALMOLOGY
material might contain amyloid. In retrospect, we were probably detecting a fairly common (“normal?“) aging change. Cohen (N Engl J Med 277.522-530, 574-583, 628-638, 1967) provides an excellent review of this
very complicated subject. I expect that we will hear much more about amyloid in the eye within the next few years. PAUL HENKIND
Development of Cornea1 Transparency in Embryonic Chick: Influence of Exogenous Thyroxine and Thiouracil on Structure, Water and Electrolyte Content, by E Masterson, HF Edelhauser and DL van Horn. Dev Biol 43:233-239, 1975 Thyroxine (T,) and thiouracil were injected into the extra-embryonic circulation of chick embryos at various developmental stages to determine their effects on cornea1 cellularity, dehydration and structure. Corneas were removed 2-9 days after treatment for analysis of (Na+) and (K+) concentration, water content and histological structure. In normal chick corneas, water content and (Na+) concentration decreased with advancing embryonic age, whereas (K+) increased up to stage 42 and then rapidly declined. Corneas from embryos injected with 10 pg thiouracil at stage 36 had significantly reduced (K+) at stages 40 and 42. Corneas at stages 40,42 and 45 had a significantly elevated water content as compared to controls. Injection of 15 rg of T, prior to stage 36 or at stage 40 or later did not produce significant changes in water and ionic content as compared to control cornea1 levels. In contrast, injection of 15 Fg of T, during the period of rapid cell proliferation (stages 36-40) produced a significant increase in cornea1 (K+) levels. Histological analysis revealed a total increase in cornea1 thickness following thiouracil
Cerebrospinal
treatment and a decrease in cornea1 thickness following T, treatment. Epithelial growth was reduced in thiouracil treatment while T, had little effect. Comment It is well known that the water content of the cornea is high in the early embryo, but decreases as development proceeds. Concomitant with this dehydration, the cornea achieves transparency. It has been demonstrated that cornea1 hydration is influenced by thyroid hormone (Coulombre and Coulombre, Exp Eye Res 3: 105, 1964). This paper extends these earlier observations by treating chick embryos with excess thyroxine and thiouracil, an inhibitor of thyroid function and then measuring cornea1 thickness, water and ion content. They suggest that thiouracil treatment decreases cell division in the cornea and orevents the formation of the epithelial barrier whereas thyroxine accelerates these processes. 1
JOE G HOLLYFIELD
Fluid in 25 Cases of Optic Neuritis, by M Sandberg and H Bynke.
Acta New-01 &and 49:443-452,
1973
Occurrence of cerebrospinal fluid changes (CSF) in monosymptomatic optic neuritis patients have been thought to serve as a possible indicator of future development of multiple sclerosis. Such changes include mononuclear pleocytosis, increase in total protein and relative immunoglobin G (IgG) concentration, varying numbers of discrete IgG bonds in the gamma globulin fraction on agar gel electrophoresis and a possible abnormal dis-
tribution of kappa and lambda antigenic determinants in immunodiffusion and on immunoelectrophoresis. Twenty-five patients with acute monosymptomatic optic neuritis were studied for changes in the CSF as a possible indicator of future development of multiple sclerosis. After ocular and neurological examinations, the patients were subjected to cytological examinations, determinations
229
of total protein and IgG concentrations, and agar gel electrophoreses. CSF changes included mononuclear leucocytosis, 60%, elevated protein concentration, 24% and elevated relative IgG concentration, 16%. Electrophoresis bands in the gamma globulin region, on agar gel, were found in 24%. Since CSF changes were infrequent in the monosymptomatic optic neuritis patients, the case for optic neuritis’ being a manifestation of multiple sclerosis is significantly weakened. Comment The authors found that the most common CSF abnormality in their 2.5 patients was mononuclei leucocytosis, which occurred in 60%. Other abnormalities were infrequent. The total protein concentration was elevated in six of the 25. The relative IgG concentration was elevated in four cases. Electrophoretic bands in the gamma globulin region were found in six cases. Three patients of the 25
developed multiple sclerosis. The cell count in the cerebrospinal fluid is the most sensitive indicator of the first attack. This fact is indicated in this series and also in the series of Link and Muller (Arch Neurol 25:326, 1971) and Schwartz et al. (Europ Neurol 4.267, 1970). The results of the CSF investigation of these patients differ greatly from those reported in multiple sclerosis patients. It is apparent from the results of this paper that in acute optic neuritis changes are found infrequently in the CSF, and when found, they are not very pronounced. It is probable that the CSF changes are related to the amount of nervous tissue that is damaged. Since relatively little nervous tissue is damaged in an initial attack of monosymptomatic optic neuritis, we should expect little or no change in the CSF. It is obvious, at this point, that early CSF changes in optic neuritis cannot be used as a prognostic indicator for the future development of multiple sclerosis. ROBERT JAMPEL
Epidemiologic Characteristics of Presumed Ocular Ganley. Acta Ophthalmol Suppl 119: l-63. 1973 A case-control
study
of the association of and disciform scars of presumed _ ocular histoplasmosis is described. Cases were obtained from a group ophthalmic practice in Hagerstown, Washington County, Maryland. Three groups of controls were used: a group of individuals with fundus scars other than the cases; a random sample of patients from the ophthalmic practice; and a random sample from the 1963 Washington County census. Cases and controls were selected from individuals aged 30-69 years and living in Washington County at the time of the examination, Data were gathered from a self-administered questionnaire, a complete ocular examination, serologic studies, and delayed skin tests administered independently and read without knowledge of the individual’s ocular status. Nineteen cases of disciform scars and 15 cases of peripheral scars of presumed ocular histoplasmosis were identified. All disciform cases had a positive histoplasmin skin test (defined as 5 mm or more diameter of induration) compared with 60.0% of those with peripheral scars, and 60.7% of controls. On repeat histoplasmin skin test, 93.3% of individuals with peripheral scars were positive compared with 69.5% of the controls. People with disciform scars had larger mean induration size to histoplasmin, greater frequency of positive reactions to the yeast complement fixing antibody test, Histoplasma capsdatum
Histoplasmosis,
by
JP
and greater likelihood of having calcification on pulmonary x-ray, attesting to the strong association in the past with H. capsulatum. Disciform cases tended to live in wood frame houses, to smoke cigarettes more heavily, to have more frequent exposure to dust, birds, bats and guano, to have a positive tuberculin skin test, and to be lower on the socioeconomic scale. These same risk factors for people with only peripheral scars were more similar in value to those of the controls. Peripheral lesions seem most likely to occur at the time of first exposure to and infection with H. capsdatum, whereas the disciform process probably occurs IO-30 years later. People who have disciform scars generally have a heightened cellular and serologic immune response to histoplasmin, possibly resulting either from reexposure to the organism or from innate allergic hypersensitivity. It is postulated that for the disciform process to occur, there must be prior sensitization of the choroid by H. capsdatum organisms, the presence of an altered choroidal vascular permeability, and a primed cellular immune system. (Abstract reprinted from the original article) Comment This long doctoral thesis is recommended for those interested in ocular histoplasmosis. The data