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Serum Lysozyme in Sarcoid Uveitis
SERUM LYSOZYME IN SARCOID UVEITIS R O B E R T S. W E I N B E R G , M.D.,
AND H O W A R D H. T E S S L E R ,
M.D.
Chicago, Illinois March 1975. Serum, obtained after centrifugation of whole blood, was stored at 4°C until analyzed, within two weeks of venipuncture.
While sarcoidosis may produce lesions in almost all tissues of the globe and ocular adnexae, uveitis is the most com mon ophthalmologic presentation. 1 - 4 However, because the ocular findings are not pathognomonic and systemic evi dence of disease may not be present, a diagnostic approach involving the serum lysozyme test may be useful in diagnos ing sarcoidosis.
RESULTS
M A T E R I A L AND M E T H O D S
We determined serum lysozyme levels spectrophotometrically according to the method of Litwack. 5 We used the Lyso zyme Assay Kit (Worthington Biochemi cal Corp.) in all measurements, with 10 mg/100 ml of the substrate Micrococcus lysodeikticus in 0.06M sodium phosphate buffer, p H 6.2. Reactions were run at 25°C with optical density readings taken at 30-second intervals for three minutes at 550 nm. A commercially available egg white lysozyme preparation containing 40 μg of lysozyme per milliliter was used to prepare a standard curve. Lysozyme values were then determined by plotting change in optical density during the three-minute test period for the test serum and comparing the result to the standard curve. A minimum of 0.2 ml of serum is required for the test. Normal range for serum lysozyme with this technique is 0 to 10 μg/ml ) with a mean of 6.4 μg/ml. 6 Ten milliliters of whole blood was ob tained by venipuncture from 100 patients with uveitis at initial evaluation by the Uveitis Service between May 1974 and From the Uveitis Service, Department of Ophthal mology, University of Illinois Eye and Ear Infirma ry, Chicago, Illinois. Reprint requests to Howard H. Tessler, M.D., University of Illinois Eye and Ear Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
Thirteen patients had sarcoidosis, diag nosed either by peripheral lymph node biopsy or by the presence of bilateral hilar adenopathy and uveitis. 7 Nine of the 13 had active uveitis. The mean serum lysozyme level for this group was mark edly elevated, with no values within the normal range (Table 1). None was taking systemic corticosteroids at the time of the lysozyme determination. The four pa tients with sarcoidosis and inactive ocular disease showed evidence of previous in flammation by the presence of posterior synechiae and they were receiving large doses of prednisone at the time of examination. The mean serum lysozyme TABLE 1 SERUM LYSOZYME LEVELS m PATIENTS W I T H UVEITIS
Diagnosis Active systemic sarcoidosis and active uveitis Inactive system ic sarcoidosis and inactive uveitis on sys temic corticosteroid therapy Presumptive systemic sar coidosis and active uveitis Chronic recur rent idiopathic iridocyclitis Acute idiopathic iritis
105
No. of Mean, Patients μg/ml± S.D.
Range, μg/mI
9
24.2±11.1
12.0-50.0
4
6.3+0.7
5.4-7.0
15
17.1±4.1
9.3-28.0
24
10.0±4.0
6.1-26.0
23
9.7±4.4
5.2-25.8
106
AMERICAN JOURNAL OF OPHTHALMOLOGY
level for these four was within the normal range (Table 1). Fifteen patients had an ophthalmologic picture compatible with sarcoidosis, with an anterior chamber reaction and two or more findings of ocular sarcoidosis (Table 2) but no radiologie, immunologie, bio chemical, or other clinical evidence of sarcoidosis. Diagnosis was presumptive sarcoidosis in these patients. The mean serum lysozyme level for this group was elevated (Table 1) and was not statistical ly different by the Student's t-test from the mean level of the group with sarcoid osis. One of the 15 patients had a serum lysozyme level within the normal range. Twenty-four patients had chronic re current iridocyclitis of unknown cause. The mean serum lysozyme level for this group was within the normal range (Table 1), with approximately 25% of patients with serum lysozyme levels greater than 10 μ β /ιη1. The mean lysozyme level in the 23 patients with acute iritis of unknown cause (Table 1) was similar to that of the group with chronic recurrent iridocycli tis, and a similar percentage of patients had elevated serum lysozyme levels. Mean levels for these two groups were similar and statistically different from the group with presumptive sarcoidosis. The following patients had normal mean values: four patients with toxoplasmosis, diagnosed clinically and serologically; five patients with pars planitis, di agnosed by the clinical picture of an exudative membrane over the pars plana; two patients with sympathetic ophthalTABLE 2 I N T R A O C U L A R F I N D I N G S IN S A R C O I D O S I S 1 " 4
Mutton-fat keratitic precipitates Iris stromal (Busacca) nodules Vitreous "snowball" opacities Chorioretinal nodules Retinal periphlebitis (candle-wax drippings) Optic nerve head nodules
JULY, 1976
TABLE 3 M E A N SERUM LYSOZYME L E V E L S IN P A T I E N T S W I T H UVEITIS
Diagnosis Toxoplasmosis Pars planitis Sympathetic ophthalmia Syphilitic iritis Active tuberculosis Inactive tuberculosis
No. of Patients
Mean, u.g/ml
4 5 2 3 3 3
8.8 8.7 7.3 8.4 17.6 8.8
mia, diagnosed histopathologically after enucleation; and three patients with syphilitic iritis, diagnosed on the basis of a reactive FTA-ABS and granulomatous inflammation of the fundus of the eye (Table 3). Three patients with ocular tu berculosis, whose diagnoses were based on a markedly positive first-strength puri fied protein derivative with granuloma tous choroiditis and improvement of ocular inflammation on a regimen of isoniazid, had elevated serum lysozyme lev els (Table 3). Three patients with inactive tuberculosis (old scarring on chest x-ray film) and a history of previous systemic antituberculous therapy and inactive ocu lar disease had normal serum lysozyme levels (Table 3). Individual patients with Reiter's disease and systemic lupus erythematosus had elevated serum lyso zyme levels. An individual patient with Vogt-Koyanagi-Harada disease and two patients with presumed ocular histoplasmosis had normal serum lysozyme levels. DISCUSSION
One customarily diagnoses sarcoidosis by using laboratory and possibly biopsy confirmation. Many of the traditional bio chemical tests used in the evaluation of a patient with suspected sarcoidosis are of little diagnostic value. Hypercalcemia may be found in less than 10% of patients with sarcoidosis. 8 An abnormal protein electrophoresis may be seen in 34%, with abnormal immunoglobulin levels in
VOL. 82, NO. 1
SARCOID UVEITIS
49%. 9 Recently the Kveim test, positive in 75% of patients with sarcoidosis and sup posedly specific for the disease, has been positive in other granulomatous condi tions. 10 The need for a biopsy has been questioned. Winterbauer, Belie, and Moores 7 suggested that a biopsy is not necessary, and that in patients with an otherwise normal physical examination, bilateral hilar adenopathy associated with erythema nodosum or uveitis is a priori evidence of sarcoidosis. Pascual, Gee, and Finch during 1973 11 reported the lysozyme test, a laboratory test used in the evaluation of patients with sarcoidosis. They studied 45 pa tients with biopsy-proved sarcoidosis and found a strong correlation between serum lysozyme levels, activity, and extent of the systemic disease. They also found lowered serum lysozyme levels in pa tients treated with systemic corticosteroids. The sources of serum lysozyme are monocytes, polymorphonuclear leuko cytes, and their precursors. 1 1 However, Pascual, Gee, and Finch 1 1 found no cor relation in sarcoidosis between monocytosis and lysozyme levels, and postulated that increased serum lysozyme levels re flect macrophage and giant cell activity in granulomas. Elevated serum lysozyme levels, which are not specific for sarcoidosis, have been correlated with the extent of disease activ ity in tuberculosis, 1 2 and may be found in uremia, 6 megaloblastic anemia, 1 3 monomyelocytic leukemia, 1 4 and Crohn's dis ease. 15 Serum lysozyme levels have also been elevated occasionally in both rheu matoid arthritis and osteoarthritis. 16 Of the 25% of our patients with chronic recurrent idiopathic iridocyclitis or acute idiopathic iritis who had elevated serum lysozyme levels, approximately half were being treated for osteoarthritis. When evaluating a case of uveitis, we are often unable to determine the cause or
107
to discover an associated illness. When a patient with uveitis has ocular signs com patible with sarcoidosis (Table 2) with no evidence of systemic disease by chest x-ray films or routine laboratory tests, the serum lysozyme test appears to be valua ble. There is a marked similarity between the lysozyme values in patients with sys temic sarcoidosis and uveitis and those in patients with the ocular findings of sar coidosis alone (Table 1). In laboratory animals with experimen tally induced uveitis, an inflammatory focus localized to the eye may not affect the serum lysozyme level. 17 Thus, the elevation of serum lysozyme levels in the group of patients with presumptive sar coidosis may have been related to system ic granulomatous disease that could not be detected clinically. Since the Kveim test is not always available or accurate, the serum lysozyme test, with an ophthalmologically compati ble picture, may be an important clue in diagnosing sarcoidosis. SUMMARY
In a study of 100 patients, the mean serum lysozyme value for patients with sarcoidosis and active uveitis was elevat ed, while the mean value for patients with inactive sarcoidosis and inactive uveitis was within the normal range. The mean value for patients with a clinical picture of sarcoid uveitis, but without an estab lished diagnosis of sarcoidosis, was high. In patients with ophthalmologic findings compatible with sarcoidosis, but without radiologie, immunologie, or other clinical evidence of the disease, an elevated serum lysozyme level may be indicative of systemic disease. REFERENCES
1. Crick, R. R., Hoyle, C , and Smellie, H.: The eyes in sarcoidosis. Br. J. Ophthalmol. 45:461,1961. 2. James, D. G., Anderson, R., Langley, D., and Ainslie, D.: Ocular sarcoidosis. Br. J. Ophthalmol. 48:461, 1964.
108
AMERICAN JOURNAL O F OPHTHALMOLOGY
3. Geeraets, W. J., McNeer, K. W., Maxey, E. F., and Guerry, D.: Retinopathy in sarcoidosis. Acta Ophthalmol. 40:492, 1962. 4. Chumbley, L. C., and Kearns, T. P.: Retinopa thy of sarcoidosis. Trans. Am. Ophthalmol. Soc. 69:307, 1972. 5. Litwack, G.: Photometric determination of ly sozyme activity. Proc. Soc. Exp. Biol. Med. 89:401, 1955. 6. Prockop, D. J., and Davidson, W. D.: A study of urinary and serum lysozyme in patients with renal disease. N. Engl. J. Med. 270:269, 1964. 7. Winterbauer, R. H., Belie, N., and Moores, K. D.: A clinical interpretation of bilateral hilar adenopathy. Ann. Intern. Med. 78:65, 1973. 8. Israel, H. L.: Present status of laboratory diag nosis of sarcoidosis. Ann. Clin. Lab. Sei. 3:73,1973. 9. James, D. G.: Sarcoidosis. D M : l - 4 3 , Feb. 1970. 10. Hurley, T. H., Sullivan, J. R., and Hurley, J. V.: Reaction to Kveim test material in sarcoidosis and other diseases. Lancet 1:494, 1975. 11. Pascual, R. S., Gee, B. L., and Finch, S. C :
JULY, 1976
Serum lysozyme analysis in diagnosis and evalua tion of sarcoidosis. N. Engl. J. Med. 289:1074,1973. 12. Perillie, P. E., Khan, K., and Finch, S. C : Serum lysozyme in pulmonary tuberculosis. Am. J. Med. Sei. 265:297, 1973. 13. Perillie, P. F., Kaplan, S. S., and Finch, S. C : Significance of changes in serum muramidase activ ity in megaloblastic anemia. N. Engl. J. Med. 277: 10, 1961. 14. Osserman, E. F., and Lawlor, D. D.: Serum and urinary lysozyme (muramidase) in monocytic and monomyelocytic leukemia. J. Exp. Med. 124: 921, 1966. 15. Falchuk, K. R., Perotto, J. L., and Isselbacher, K. J.: Serum lysozyme in Crohn's disease and ulcerative colitis. N. Engl. J. Med. 292:395, 1975. 16. Pruzanski, W., Ogryzlo, M. A., and Katz, A.: Lysozyme production and abnormalities in rheu matic diseases. In Osserman, E. F., Canfield, R. E., and Beychok, S. (eds.): Lysozyme. New York, Aca demic Press, 1974, p. 409. 17. Tessler, H. H., and Weinberg, R. S.: Aqueous and serum lysozyme values in experimental uveitis in rabbits. Invest. Ophthalmol. 14:953, 1975.
AND H O W A R D H. T E S S L E R ,
M.D.
Chicago, Illinois March 1975. Serum, obtained after centrifugation of whole blood, was stored at 4°C until analyzed, within two weeks of venipuncture.
While sarcoidosis may produce lesions in almost all tissues of the globe and ocular adnexae, uveitis is the most com mon ophthalmologic presentation. 1 - 4 However, because the ocular findings are not pathognomonic and systemic evi dence of disease may not be present, a diagnostic approach involving the serum lysozyme test may be useful in diagnos ing sarcoidosis.
RESULTS
M A T E R I A L AND M E T H O D S
We determined serum lysozyme levels spectrophotometrically according to the method of Litwack. 5 We used the Lyso zyme Assay Kit (Worthington Biochemi cal Corp.) in all measurements, with 10 mg/100 ml of the substrate Micrococcus lysodeikticus in 0.06M sodium phosphate buffer, p H 6.2. Reactions were run at 25°C with optical density readings taken at 30-second intervals for three minutes at 550 nm. A commercially available egg white lysozyme preparation containing 40 μg of lysozyme per milliliter was used to prepare a standard curve. Lysozyme values were then determined by plotting change in optical density during the three-minute test period for the test serum and comparing the result to the standard curve. A minimum of 0.2 ml of serum is required for the test. Normal range for serum lysozyme with this technique is 0 to 10 μg/ml ) with a mean of 6.4 μg/ml. 6 Ten milliliters of whole blood was ob tained by venipuncture from 100 patients with uveitis at initial evaluation by the Uveitis Service between May 1974 and From the Uveitis Service, Department of Ophthal mology, University of Illinois Eye and Ear Infirma ry, Chicago, Illinois. Reprint requests to Howard H. Tessler, M.D., University of Illinois Eye and Ear Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
Thirteen patients had sarcoidosis, diag nosed either by peripheral lymph node biopsy or by the presence of bilateral hilar adenopathy and uveitis. 7 Nine of the 13 had active uveitis. The mean serum lysozyme level for this group was mark edly elevated, with no values within the normal range (Table 1). None was taking systemic corticosteroids at the time of the lysozyme determination. The four pa tients with sarcoidosis and inactive ocular disease showed evidence of previous in flammation by the presence of posterior synechiae and they were receiving large doses of prednisone at the time of examination. The mean serum lysozyme TABLE 1 SERUM LYSOZYME LEVELS m PATIENTS W I T H UVEITIS
Diagnosis Active systemic sarcoidosis and active uveitis Inactive system ic sarcoidosis and inactive uveitis on sys temic corticosteroid therapy Presumptive systemic sar coidosis and active uveitis Chronic recur rent idiopathic iridocyclitis Acute idiopathic iritis
105
No. of Mean, Patients μg/ml± S.D.
Range, μg/mI
9
24.2±11.1
12.0-50.0
4
6.3+0.7
5.4-7.0
15
17.1±4.1
9.3-28.0
24
10.0±4.0
6.1-26.0
23
9.7±4.4
5.2-25.8
106
AMERICAN JOURNAL OF OPHTHALMOLOGY
level for these four was within the normal range (Table 1). Fifteen patients had an ophthalmologic picture compatible with sarcoidosis, with an anterior chamber reaction and two or more findings of ocular sarcoidosis (Table 2) but no radiologie, immunologie, bio chemical, or other clinical evidence of sarcoidosis. Diagnosis was presumptive sarcoidosis in these patients. The mean serum lysozyme level for this group was elevated (Table 1) and was not statistical ly different by the Student's t-test from the mean level of the group with sarcoid osis. One of the 15 patients had a serum lysozyme level within the normal range. Twenty-four patients had chronic re current iridocyclitis of unknown cause. The mean serum lysozyme level for this group was within the normal range (Table 1), with approximately 25% of patients with serum lysozyme levels greater than 10 μ β /ιη1. The mean lysozyme level in the 23 patients with acute iritis of unknown cause (Table 1) was similar to that of the group with chronic recurrent iridocycli tis, and a similar percentage of patients had elevated serum lysozyme levels. Mean levels for these two groups were similar and statistically different from the group with presumptive sarcoidosis. The following patients had normal mean values: four patients with toxoplasmosis, diagnosed clinically and serologically; five patients with pars planitis, di agnosed by the clinical picture of an exudative membrane over the pars plana; two patients with sympathetic ophthalTABLE 2 I N T R A O C U L A R F I N D I N G S IN S A R C O I D O S I S 1 " 4
Mutton-fat keratitic precipitates Iris stromal (Busacca) nodules Vitreous "snowball" opacities Chorioretinal nodules Retinal periphlebitis (candle-wax drippings) Optic nerve head nodules
JULY, 1976
TABLE 3 M E A N SERUM LYSOZYME L E V E L S IN P A T I E N T S W I T H UVEITIS
Diagnosis Toxoplasmosis Pars planitis Sympathetic ophthalmia Syphilitic iritis Active tuberculosis Inactive tuberculosis
No. of Patients
Mean, u.g/ml
4 5 2 3 3 3
8.8 8.7 7.3 8.4 17.6 8.8
mia, diagnosed histopathologically after enucleation; and three patients with syphilitic iritis, diagnosed on the basis of a reactive FTA-ABS and granulomatous inflammation of the fundus of the eye (Table 3). Three patients with ocular tu berculosis, whose diagnoses were based on a markedly positive first-strength puri fied protein derivative with granuloma tous choroiditis and improvement of ocular inflammation on a regimen of isoniazid, had elevated serum lysozyme lev els (Table 3). Three patients with inactive tuberculosis (old scarring on chest x-ray film) and a history of previous systemic antituberculous therapy and inactive ocu lar disease had normal serum lysozyme levels (Table 3). Individual patients with Reiter's disease and systemic lupus erythematosus had elevated serum lyso zyme levels. An individual patient with Vogt-Koyanagi-Harada disease and two patients with presumed ocular histoplasmosis had normal serum lysozyme levels. DISCUSSION
One customarily diagnoses sarcoidosis by using laboratory and possibly biopsy confirmation. Many of the traditional bio chemical tests used in the evaluation of a patient with suspected sarcoidosis are of little diagnostic value. Hypercalcemia may be found in less than 10% of patients with sarcoidosis. 8 An abnormal protein electrophoresis may be seen in 34%, with abnormal immunoglobulin levels in
VOL. 82, NO. 1
SARCOID UVEITIS
49%. 9 Recently the Kveim test, positive in 75% of patients with sarcoidosis and sup posedly specific for the disease, has been positive in other granulomatous condi tions. 10 The need for a biopsy has been questioned. Winterbauer, Belie, and Moores 7 suggested that a biopsy is not necessary, and that in patients with an otherwise normal physical examination, bilateral hilar adenopathy associated with erythema nodosum or uveitis is a priori evidence of sarcoidosis. Pascual, Gee, and Finch during 1973 11 reported the lysozyme test, a laboratory test used in the evaluation of patients with sarcoidosis. They studied 45 pa tients with biopsy-proved sarcoidosis and found a strong correlation between serum lysozyme levels, activity, and extent of the systemic disease. They also found lowered serum lysozyme levels in pa tients treated with systemic corticosteroids. The sources of serum lysozyme are monocytes, polymorphonuclear leuko cytes, and their precursors. 1 1 However, Pascual, Gee, and Finch 1 1 found no cor relation in sarcoidosis between monocytosis and lysozyme levels, and postulated that increased serum lysozyme levels re flect macrophage and giant cell activity in granulomas. Elevated serum lysozyme levels, which are not specific for sarcoidosis, have been correlated with the extent of disease activ ity in tuberculosis, 1 2 and may be found in uremia, 6 megaloblastic anemia, 1 3 monomyelocytic leukemia, 1 4 and Crohn's dis ease. 15 Serum lysozyme levels have also been elevated occasionally in both rheu matoid arthritis and osteoarthritis. 16 Of the 25% of our patients with chronic recurrent idiopathic iridocyclitis or acute idiopathic iritis who had elevated serum lysozyme levels, approximately half were being treated for osteoarthritis. When evaluating a case of uveitis, we are often unable to determine the cause or
107
to discover an associated illness. When a patient with uveitis has ocular signs com patible with sarcoidosis (Table 2) with no evidence of systemic disease by chest x-ray films or routine laboratory tests, the serum lysozyme test appears to be valua ble. There is a marked similarity between the lysozyme values in patients with sys temic sarcoidosis and uveitis and those in patients with the ocular findings of sar coidosis alone (Table 1). In laboratory animals with experimen tally induced uveitis, an inflammatory focus localized to the eye may not affect the serum lysozyme level. 17 Thus, the elevation of serum lysozyme levels in the group of patients with presumptive sar coidosis may have been related to system ic granulomatous disease that could not be detected clinically. Since the Kveim test is not always available or accurate, the serum lysozyme test, with an ophthalmologically compati ble picture, may be an important clue in diagnosing sarcoidosis. SUMMARY
In a study of 100 patients, the mean serum lysozyme value for patients with sarcoidosis and active uveitis was elevat ed, while the mean value for patients with inactive sarcoidosis and inactive uveitis was within the normal range. The mean value for patients with a clinical picture of sarcoid uveitis, but without an estab lished diagnosis of sarcoidosis, was high. In patients with ophthalmologic findings compatible with sarcoidosis, but without radiologie, immunologie, or other clinical evidence of the disease, an elevated serum lysozyme level may be indicative of systemic disease. REFERENCES
1. Crick, R. R., Hoyle, C , and Smellie, H.: The eyes in sarcoidosis. Br. J. Ophthalmol. 45:461,1961. 2. James, D. G., Anderson, R., Langley, D., and Ainslie, D.: Ocular sarcoidosis. Br. J. Ophthalmol. 48:461, 1964.
108
AMERICAN JOURNAL O F OPHTHALMOLOGY
3. Geeraets, W. J., McNeer, K. W., Maxey, E. F., and Guerry, D.: Retinopathy in sarcoidosis. Acta Ophthalmol. 40:492, 1962. 4. Chumbley, L. C., and Kearns, T. P.: Retinopa thy of sarcoidosis. Trans. Am. Ophthalmol. Soc. 69:307, 1972. 5. Litwack, G.: Photometric determination of ly sozyme activity. Proc. Soc. Exp. Biol. Med. 89:401, 1955. 6. Prockop, D. J., and Davidson, W. D.: A study of urinary and serum lysozyme in patients with renal disease. N. Engl. J. Med. 270:269, 1964. 7. Winterbauer, R. H., Belie, N., and Moores, K. D.: A clinical interpretation of bilateral hilar adenopathy. Ann. Intern. Med. 78:65, 1973. 8. Israel, H. L.: Present status of laboratory diag nosis of sarcoidosis. Ann. Clin. Lab. Sei. 3:73,1973. 9. James, D. G.: Sarcoidosis. D M : l - 4 3 , Feb. 1970. 10. Hurley, T. H., Sullivan, J. R., and Hurley, J. V.: Reaction to Kveim test material in sarcoidosis and other diseases. Lancet 1:494, 1975. 11. Pascual, R. S., Gee, B. L., and Finch, S. C :
JULY, 1976
Serum lysozyme analysis in diagnosis and evalua tion of sarcoidosis. N. Engl. J. Med. 289:1074,1973. 12. Perillie, P. E., Khan, K., and Finch, S. C : Serum lysozyme in pulmonary tuberculosis. Am. J. Med. Sei. 265:297, 1973. 13. Perillie, P. F., Kaplan, S. S., and Finch, S. C : Significance of changes in serum muramidase activ ity in megaloblastic anemia. N. Engl. J. Med. 277: 10, 1961. 14. Osserman, E. F., and Lawlor, D. D.: Serum and urinary lysozyme (muramidase) in monocytic and monomyelocytic leukemia. J. Exp. Med. 124: 921, 1966. 15. Falchuk, K. R., Perotto, J. L., and Isselbacher, K. J.: Serum lysozyme in Crohn's disease and ulcerative colitis. N. Engl. J. Med. 292:395, 1975. 16. Pruzanski, W., Ogryzlo, M. A., and Katz, A.: Lysozyme production and abnormalities in rheu matic diseases. In Osserman, E. F., Canfield, R. E., and Beychok, S. (eds.): Lysozyme. New York, Aca demic Press, 1974, p. 409. 17. Tessler, H. H., and Weinberg, R. S.: Aqueous and serum lysozyme values in experimental uveitis in rabbits. Invest. Ophthalmol. 14:953, 1975.