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Ocular Involvement in Chronic Sarcoidosis
AMERICAN
JOURNAL
VOLUME 102
OF
OPHTHALMOLOGY® SEPTEMBER,1986
NUMBER 3
Ocular Involvement in Chronic Sarcoidosis Douglas A. Jabs, M.D., and Carol J. Johns, M.D.
Although spontaneous remissions often occur in sarcoidosis, chronic persistent disabling disease is also observed. Of a series of 183 patients with chronic sarcoidosis, 47 (26%) had ophthalmic involvement. In this series, chronic sarcoid was defined as disease for a minimum of five years. Patients were followed primarily for their systemic disease for a mean of 13 years. Uveitis developed in 35 patients (19%) and was an early manifestation in 32 (91 %). The course of the ocular disease did not necessarily parallel that of the systemic disease. Despite the chronic nature of the underlying disease, the anterior uveitis did not pursue a chronic course in 15 of 33 patients (45%) and was generally characterized by a single episode at the onset of disease. Chronic uveitis and secondary glaucoma were poor prognostic signs, as eight of 11 patients with uveitis and glaucoma suffered severe visual loss. SARCOIDOSIS is a multisystem granulomatous disorder of unknown origin that most often includes intrathoracic involvement, particularly bilateral hilar lymphadenopathy with or without pulmonary infiltration. Ocular inAccepted for publication June 18, 1986. From the Wilmer Ophthalmological Institute, Departments of Ophthalmology (Dr. Jabs) and Medicine (Dr. Johns), Johns Hopkins University School of Medicine, Baltimore, Maryland. This study was supported in part by grant EY 01765 from the National Institutes of Health. This study was presented in part at the meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, April 29, 1986. Reprint requests to Douglas A. Jabs, M. D., Uveitis and Clinical Immunology Service, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, 600 N. Wolfe si.. Baltimore, MD 21205.
©AMERICAN JOURNAL OF OPHTHALMOLOGY
102:297-301,
volvement is common and occurs in 22% of patients worldwide." The natural course of sarcoidosis is variable. Spontaneous remissions of pulmonary disease occur, 2-5 but chronic persistent disabling disease is also observed.t" Although "chronic" sarcoidosis is often described as a disease of two or more years in duration, we selectively studied that subgroup of patients in whom clinical evidence of persistent sarcoidosis extended five years or more.
SUbjects and Methods We conducted a retrospective review of the medical records of 183 patients with chronic sarcoidosis. For the purposes of this study we defined chronic sarcoidosis as persistent disease requiring management of five or more years in duration. Patients were followed up at the Johns Hopkins Medical Institutions, primarily the Johns Hopkins Hospital Sarcoid Clinic and Consultation Services; a few patients were seen at Sinai Hospital of Baltimore. All patients had a clinical pattern compatible with sarcoidosis and histologic support for this diagnosis from either a tissue biopsy specimen or a Kveim test. Details of the first 101 patients in this series have been reported previously. 7 Of the 183 patients, 143 were black and 40 were white; 126 were female and 57 were male. A total of 172 (94%) were treated with systemic corticosteroids (prednisone). Treatment was usually initiated with 40 mg of prednisone a day, decreasing every two weeks by 5 mg/day until a dosage of 15 mg/day was reached. Only 40 (22%) received corticosteroids for less than SEPTEMBER,
1986
297
298
AMERICAN JOURNAL OF OPHTHALMOLOGY
two years and 115 (63%) required more than five years of treatment. The mean duration of corticosteroid therapy was 8.3 years. Twentysix patients (14%) were treated with chloroquine or hydroxychloroquine. Treatment with chloroquine started at 500 mg a day for 14 days and was then reduced to 250 mg a day for a period of not more than six months. The mean duration of follow-up for these patients was 14 years. Further details concerning the entire patient population, systemic treatment, and pulmonary outcome appear elsewhere." Forty-seven patients with ophthalmic involvement (26%) were identified, and their charts reviewed by one of us (D.A.J.). The ophthalmic manifestations were tabulated, the clinical course for each patient was reviewed, and the visual outcome noted. The mean duration of follow-up for patients with ocular involvement was 13 years; the median duration was 12 years. For the purposes of this study, we defined acute anterior uveitis as an episode of iridocyclitis less than six months in duration and chronic anterior uveitis as iridocyclitis of more than six months in duration. Severe visual loss was defined as a visual acuity of 20/200 or worse or visual field loss with 10 degrees or less of central visual field remaining. We compared the ophthalmic series and the overall series by means of the X2 test. Comparisons within the ophthalmic series of factors relating to visual outcome were done with Fisher's exact test.
Results Of the 47 patients with ophthalmic involvement, 44 were black and three were white; 32 were women and 15 were men. The prevalence of ophthalmic involvement was signficantly greater in black patients with chronic sarcoidosis (44 of 143,31 %) than in white patients (three of 40, 8%) with chronic sarcoidosis (X2 = 8.87; P<.003). The sex distribution of patients with ophthalmic involvement (32 of 47 or 68% female) did not differ significantly from that in the overall series of patients (126 of 183 or 69% female). The ophthalmic manifestations of patients with chronic sarcoidosis are shown in Table 1. Table 2 compares the total number of patients with a given ophthalmic lesion and the number of patients who had the lesion at the time of diagnosis. We found that 53 of 63 lesions (84%)
September, 1986
were present at the time sarcoidosis was diagnosed. Uveitis occurred in 35 patients (19% of the overall series), and was present at the diagnosis of sarcoidosis in 32 of the 35 patients (91%). Thirty-three of the 35 patients had anterior uveitis. In 15 of these patients the uveitis was classified as acute and was generally manifested by a single episode of iridocyclitis at the time of diagnosis with no further recurrence. Eighteen patients developed chronic anterior uveitis. Patients with chronic uveitis did not appear to have more severe systemic disease than those with acute uveitis. The prevalences of the extraocular manifestations of sarcoid (cutaneous disease, pulmonary disease, visceral disease) and the pulmonary outcome (final forced vital capacity) were no different in the two groups. Posterior uveitis occurred in 13 patients (7% of the overall series and 28% of patients with ophthalmic involvement); this was manifested by periphlebitis in eight patients, by vitritis in seven patients, by choroiditis or a choroidal nodule in two patients, and by exudative retinal detachments in two patients. In both patients with exudative retinal detachments other posterior segment manifestations of sarcoidosis were also present (periphlebitis in one and vitritis and a choroidal nodule in the other). In only two patients was posterior segment involvement noted without coexisting anterior uveitis; one had choroidal involvement and the second had periphlebitis and posterior vitreous cells without anterior segment inflammation. One additional patient had optic nerve involvement by sarcoid. Glaucoma was present in 12 of the 47 patients in this series. In 11 it was thought to be secondary to the uveitis with posterior synechiae and iris bornbe in two, increased intraocular pressure with active disease (not caused by corticosteroids) in one, and angle damage with peripheral anterior synechiae in the rest. One patient with conjunctival, lacrimal, and cutaneous sarcoid but without uveitis also had glaucoma. Eight of the 11 patients with secondary glaucoma ultimately suffered severe visual loss (12 of 19 involved eyes). The responses to glaucoma medications and glaucoma surgery (five patients) were typically poor. Cataracts were present in eight patients, seven of whom had uveitis. Lacrimal gland involvement was noted in 13 patients (7% of the overall series and 28% of patients with ophthalmic involvement). In
Vol. 102, No.3
Ocular Involvement in Sarcoidosis
299
TABLE 1 OCULAR INVOLVEMENT IN CHRONIC SARCOIDOSIS
NO. OF MANIFESTATION
PATIENTS
Uveitis Anterior Posterior Iris nodules Secondary glaucoma Cataracts Lacrimal gland involvement Conjunctival involvement Eyelid nodules Band keratopathy Scleralplaque Optic nerve involvement
35 33 13
% OF THOSE WITH
% OF THOSE WITH
OCULAR SARCOID
CHRONIC SARCOID
(NO.
(NO.
11 8
13 8 5 3 1 1
= 183)
19 18
74
70 28 11 23 17 28 17 11
5
eight of these patients lacrimal gland enlargement was evident on clinical examination; in the remaining five, dry eyes were noted in the absence of clinically evident lacrimal gland enlargement. Severe visual loss developed in nine patients. All had uveitis and eight had glaucoma. One patient had a visual acuity of R.E.: 20170 and L.E.: 20150 and visual fields of less than 10 degrees. The other eight had visual acuities of 20/200 or less. The cause of the visual loss was often multifactorial and included glaucomatous optic nerve damage (five cases), media opacities (five cases), macular edema (two cases), and phthisis (one case). It was often difficult to determine the exact causes of visual loss. Because fluorescein angiography was often not performed, the prevalence of macular edema is probably higher and may also have been present in those patients with media opacities. When we analyzed the factors contributing to a poor visual outcome, we found that eight of the 11 patients with uveitis and secondary glaucoma suffered severe visual loss (Fisher's exact test, P<.OOOI). Posterior uveitis was also associated with a poor visual outcome; six of thirteen patients with posterior uveitis suffered severe visual loss (Fisher's exact test, P = .05). The posterior segment manifestations in these six patients included periphlebitis (three cases), vitritis (four cases), choroidal nodule (one case), and exudative retinal detachments (two cases). However, the six patients with posterior uveitis who suffered severe visual loss also had secondary glaucoma.
= 47)
7 3 6 4 7 4 3 2
6 2 2
0.5 0.5
Discussion Several studies have documented the common occurrence of ocular involvement in sarcoidosis and the ophthalmic manifestations of sarcoidosis.P:" Estimates of the prevalence of ophthalmic involvement in sarcoidosis have ranged as high as 50%9but are generally closer to 25% .1,10,11 In a study of manifestations of sarcoidosis worldwide, Siltzbach and associates' noted an overall 22% prevalence of ophthalmic involvement. Obenauf and associates" noted a 38% prevalence of ophthalmic involvement. These differences are related to the patient population studied, definitions of ophthalmic involvement, and the nature of the evaluations conducted. Indeed, the highest prevalence rate was noted by Crick, Hoyle, and Smellie," who classified keratoconjunctivitis
TABLE 2 EARLY OCULAR LESIONS PRESENT AT DIAGNOSIS LESIONS
NO.
NO.
%
Uveitis Lacrimal gland Conjunctiva Eyelid nodules Optic nerve
35 13 8
32 11
6
3 1
91 85 75 50 100
1
6
300
September, 1986
AMERICAN JOURNAL OF OPHTHALMOLOGY
sicca as evidence of lacrimal gland involvement in sarcoidosis. Several aspects of our data must be interpreted with caution. First, our patient population clearly represented a selected group of patients. Not only was the study population chosen for the chronic nature of the disease, but it also represented patients seen at a referral center; thus, this was not a population-based study. Second, the study was a retrospective one of patients followed primarily for systemic disease. As such, all prevalence data can be regarded only as an estimate. The lack of a defined ophthalmic protocol, variability of follow-up, and referral of symptomatic patients would all lead to an underreporting of ocular disease and a bias toward more severe ocular disease. Finally, as with all retrospective studies, the data base is incomplete, and arbitrary decisions concerning interpretation of data were made. These problems were particularly true for the data on lacrimal gland involvement, where lacrimal gland enlargement was often based on the clinical judgment of the observer and not on predetermined criteria. Finally, the frequent and long-term use of systemic corticosteroids may have altered the natural course of the ocular disease. However, despite these limitations, this study had a follow-up period (mean, 13 years) difficult to achieve in a prospective fashion. Our estimate of ophthalmic involvement in 47 of 183 patients (26%) with chronic sarcoid was similar to prevalence estimates in all sarcoid derived from other series.I,IO,1l One striking finding was the racial difference in patients with ophthalmic disease. Of the 143 black patients with chronic sarcoid, 44 developed ocular disease (31 %), whereas only three of 40 of white patients (8%) developed ocular lesions. There were no sex differences between the overall series and patients with ocular involvement. Previous studies-! in the southeastern United States also noted an increased number of blacks among patients with ocular sarcoidosis, but our study suggested that blacks with chronic sarcoid may be more likely to develop ocular lesions. Both acute and chronic iridocyclitis have been described in patients with sarcoidosis.P:" Although all patients in this series had chronic sarcoidosis, not all patients had chronic ocular disease. In 15 of 33 patients with anterior uveitis (45%), the disease pursued an acute and occasionally recurrent course that generally did not lead to visual impairment. Most often this
was a single episode of iridocyclitis at the onset of disease. Conversely, patients with chronic uveitis did poorly. The major prognostic factor in a poor visual outcome appeared to be the presence of secondary glaucoma. Of the 11 patients who developed secondary glaucoma, eight suffered severe visual loss. Additionally, in two other patients with secondary glaucoma, moderate visual impairment was noted with visual acuities ranging from 20/40 to 20/50 in the three involved eyes. A similar association between uveitis with secondary glaucoma and a poor visual result has been found in patients with juvenile chronic arthritis and chronic iridocyclitiS.
13
Posterior segment involvement in sarcoidosis is well documented. 9-12,14-23 These lesions include vitreous inflammation (snowballs, string of pearls), retinal periphlebitis, choroidal granulomata, retinal neovascularization, and optic nerve disease. In our series of patients with chronic sarcoidosis, posterior uveitis occurred in 13 (7% of the overall series and 28% of those with ophthalmic sarcoid). Posterior involvement was most often present at the onset of systemic disease. Two patients had exudative retinal detachments, an unusual finding that to the best of our knowledge has been described in only two other patients with sarcoidosis.P Both patients had anterior uveitis and other manifestations of posterior segment inflammation simultaneously. Posterior uveitis was associated with a poor visual outcome as well. Although the course of ophthalmic involvement did not necessarily parallel that of the systemic disease, the ocular manifestations in most patients with chronic sarcoidosis declared themselves early in the course of the disease. Table 2 demonstrates that most patients with ocular involvement had lesions at the time of the initial diagnosis. This finding was in keeping with the other manifestations of sarcoidosis, where the major manifestations of sarcoidosis are generally present at the time of diagnosis."
References 1. Siltzbach, 1. E., James, D. G., Neville, E., Turia, F. J., Battesti, J. P., Sharma, O. M. P., Hosada, Y., Mikami, R., and Odaka, M.: Course and prognosis of sarcoidosis around the world. Am. J. Med. 57:847, 1985.
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Ocular Involvement in Sarcoidosis
2. Longcope, W. T., and Freiman, D. G.: Study of sarcoidosis based on combined investigation of 160 cases including 30 autopsies from Johns Hopkins Hospital and Massachusetts General Hospital. Medicine 31:1, 1952. 3. Mayock, R. L., Bertrand, T., Morrison, C. E., and Scott, J. H.: Manifestations of sarcoidosis. Analysis of 145 patients with a review of nine series selected from the literature. Am. J. Med. 35:67, 1963. 4. Smellie, H., and Hoyle, c.: The natural history of pulmonary sarcoidosis. Q. J. Med. 29:539, 1960. 5. Wurm, K., and Rosner, R.: Prognosis of chronic sarcoidosis. Ann. N.Y. Acad. Sci. 278:732, 1976. 6. Johns, C. J., Zachary, J. B., and Ball, W. c.. Jr.: A ten-year study of corticosteroid treatment in pulmonary sarcoidosis. Johns Hopkins Med. J. 134:251, 1974. 7. Johns, C. J., Zachary, J. B., MacGregor, M. I., Curtis, J. L., Scott, P. P., and Terry, P. B.: The longitudinal study of chronic sarcoidosis. Trans. Am. Clin. Climatol. Assoc. 94:173, 1982. 8. Johns, C. J., Schonfeld, S. A., Scott, P. P., Zachary, J. B., and MacGregor, M. I.: Longitudinal study of chronic sarcoidosis with low dose maintenence corticosteroid therapy. Outcome and complications. Ann. N.Y. Acad. Sci. 265:702, 1986. 9. Crick, R. P., Hoyle, c., and Smellie, H.: The eyes in sarcoidosis. Br. J. Ophthalmol. 45:461, 1961. 10. James, D. G., Anderson, R., Langley, D., and Ainslie, D.: Ocular sarcoidosis. Br. J. Ophthalmol. 48:461, 1964. 11. James, D. G., Neville, E., and Langley, D. A.: Ocular sarcoidosis. Trans. Ophthalmol. Soc. U.K. 96:133, 1976. 12. Obenauf, C. D., Shaw, H. E., Sydnor, C. F., and Klintworth, G. K.: Sarcoidosis and its ophthal-
301
mic manifestations. Am. J. Ophthalmol. 86:648, 1978. 13. Kanski, J. J., and Shun-Shin, G. A.: Systemic uveitis syndromes in childhood. An analysis of 340 cases. Ophthalmology 91:1247, 1984. 14. Gould, H., and Kaufman, H. E.: Sarcoid of the fundus. Arch. Ophthalmol. 65:453, 1961. '15. Algvere, P.: Fluorescein studies of retinal vasculitis in sarcoidosis. Report of a case. Acta Ophthalmol. 48:1129, 1970. 16. Chumbley, L. c.. and Kearns, T. P.: Retinopathy of sarcoidosis. Am. J. Ophthalmol. 73:123, 1972. 17. Letocha, C. E., Shields, J. A., and Goldberg, R. E.: Retinal changes in sarcoidosis. Can. J. Ophthalmol. 10:184, 1975. 18. Asdourian, G. K., Goldberg, M. F., and Busse, B. J.: Peripheral retinal neovascularization in sarcoidosis. Arch. Ophthalmol. 93:787, 1975. 19. Sanders, M. D., and Shilling, J. s.: Retinal, choroidal, and optic disc involvement in sarcoidosis. Trans. Ophthalmol. Soc. U.K. 96:140, 1976. 20. Gass, J. D. M., and Olson, C. L.: Sarcoidosis of optic nerve and retinal involvement. Arch. Ophthalmol. 94:945, 1976. 21. Doxanas, M. T., Kelley, J. 5., and Prout, T. E.: Sarcoidosis with neovascularization of the optic nerve head. Am. J. Ophthalmol. 90:347, 1980. 22. Spalton, D. J., and Sanders, M. D.: Fundus changes in histologically confirmed sarcoidosis. Br. J. Ophthalmol. 65:348, 1981. 23. Campo, R. V., and Aaberg, T. M.: Choroidal granuloma in sarcoidosis. Am. J. Ophthalmol. 97:419, 1984. 24. Marcus, D. F., Bovino, J. A., and Burton, T. c.: Sarcoid granuloma of the choroid. Ophthalmology 89:1326, 1982.
JOURNAL
VOLUME 102
OF
OPHTHALMOLOGY® SEPTEMBER,1986
NUMBER 3
Ocular Involvement in Chronic Sarcoidosis Douglas A. Jabs, M.D., and Carol J. Johns, M.D.
Although spontaneous remissions often occur in sarcoidosis, chronic persistent disabling disease is also observed. Of a series of 183 patients with chronic sarcoidosis, 47 (26%) had ophthalmic involvement. In this series, chronic sarcoid was defined as disease for a minimum of five years. Patients were followed primarily for their systemic disease for a mean of 13 years. Uveitis developed in 35 patients (19%) and was an early manifestation in 32 (91 %). The course of the ocular disease did not necessarily parallel that of the systemic disease. Despite the chronic nature of the underlying disease, the anterior uveitis did not pursue a chronic course in 15 of 33 patients (45%) and was generally characterized by a single episode at the onset of disease. Chronic uveitis and secondary glaucoma were poor prognostic signs, as eight of 11 patients with uveitis and glaucoma suffered severe visual loss. SARCOIDOSIS is a multisystem granulomatous disorder of unknown origin that most often includes intrathoracic involvement, particularly bilateral hilar lymphadenopathy with or without pulmonary infiltration. Ocular inAccepted for publication June 18, 1986. From the Wilmer Ophthalmological Institute, Departments of Ophthalmology (Dr. Jabs) and Medicine (Dr. Johns), Johns Hopkins University School of Medicine, Baltimore, Maryland. This study was supported in part by grant EY 01765 from the National Institutes of Health. This study was presented in part at the meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, April 29, 1986. Reprint requests to Douglas A. Jabs, M. D., Uveitis and Clinical Immunology Service, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, 600 N. Wolfe si.. Baltimore, MD 21205.
©AMERICAN JOURNAL OF OPHTHALMOLOGY
102:297-301,
volvement is common and occurs in 22% of patients worldwide." The natural course of sarcoidosis is variable. Spontaneous remissions of pulmonary disease occur, 2-5 but chronic persistent disabling disease is also observed.t" Although "chronic" sarcoidosis is often described as a disease of two or more years in duration, we selectively studied that subgroup of patients in whom clinical evidence of persistent sarcoidosis extended five years or more.
SUbjects and Methods We conducted a retrospective review of the medical records of 183 patients with chronic sarcoidosis. For the purposes of this study we defined chronic sarcoidosis as persistent disease requiring management of five or more years in duration. Patients were followed up at the Johns Hopkins Medical Institutions, primarily the Johns Hopkins Hospital Sarcoid Clinic and Consultation Services; a few patients were seen at Sinai Hospital of Baltimore. All patients had a clinical pattern compatible with sarcoidosis and histologic support for this diagnosis from either a tissue biopsy specimen or a Kveim test. Details of the first 101 patients in this series have been reported previously. 7 Of the 183 patients, 143 were black and 40 were white; 126 were female and 57 were male. A total of 172 (94%) were treated with systemic corticosteroids (prednisone). Treatment was usually initiated with 40 mg of prednisone a day, decreasing every two weeks by 5 mg/day until a dosage of 15 mg/day was reached. Only 40 (22%) received corticosteroids for less than SEPTEMBER,
1986
297
298
AMERICAN JOURNAL OF OPHTHALMOLOGY
two years and 115 (63%) required more than five years of treatment. The mean duration of corticosteroid therapy was 8.3 years. Twentysix patients (14%) were treated with chloroquine or hydroxychloroquine. Treatment with chloroquine started at 500 mg a day for 14 days and was then reduced to 250 mg a day for a period of not more than six months. The mean duration of follow-up for these patients was 14 years. Further details concerning the entire patient population, systemic treatment, and pulmonary outcome appear elsewhere." Forty-seven patients with ophthalmic involvement (26%) were identified, and their charts reviewed by one of us (D.A.J.). The ophthalmic manifestations were tabulated, the clinical course for each patient was reviewed, and the visual outcome noted. The mean duration of follow-up for patients with ocular involvement was 13 years; the median duration was 12 years. For the purposes of this study, we defined acute anterior uveitis as an episode of iridocyclitis less than six months in duration and chronic anterior uveitis as iridocyclitis of more than six months in duration. Severe visual loss was defined as a visual acuity of 20/200 or worse or visual field loss with 10 degrees or less of central visual field remaining. We compared the ophthalmic series and the overall series by means of the X2 test. Comparisons within the ophthalmic series of factors relating to visual outcome were done with Fisher's exact test.
Results Of the 47 patients with ophthalmic involvement, 44 were black and three were white; 32 were women and 15 were men. The prevalence of ophthalmic involvement was signficantly greater in black patients with chronic sarcoidosis (44 of 143,31 %) than in white patients (three of 40, 8%) with chronic sarcoidosis (X2 = 8.87; P<.003). The sex distribution of patients with ophthalmic involvement (32 of 47 or 68% female) did not differ significantly from that in the overall series of patients (126 of 183 or 69% female). The ophthalmic manifestations of patients with chronic sarcoidosis are shown in Table 1. Table 2 compares the total number of patients with a given ophthalmic lesion and the number of patients who had the lesion at the time of diagnosis. We found that 53 of 63 lesions (84%)
September, 1986
were present at the time sarcoidosis was diagnosed. Uveitis occurred in 35 patients (19% of the overall series), and was present at the diagnosis of sarcoidosis in 32 of the 35 patients (91%). Thirty-three of the 35 patients had anterior uveitis. In 15 of these patients the uveitis was classified as acute and was generally manifested by a single episode of iridocyclitis at the time of diagnosis with no further recurrence. Eighteen patients developed chronic anterior uveitis. Patients with chronic uveitis did not appear to have more severe systemic disease than those with acute uveitis. The prevalences of the extraocular manifestations of sarcoid (cutaneous disease, pulmonary disease, visceral disease) and the pulmonary outcome (final forced vital capacity) were no different in the two groups. Posterior uveitis occurred in 13 patients (7% of the overall series and 28% of patients with ophthalmic involvement); this was manifested by periphlebitis in eight patients, by vitritis in seven patients, by choroiditis or a choroidal nodule in two patients, and by exudative retinal detachments in two patients. In both patients with exudative retinal detachments other posterior segment manifestations of sarcoidosis were also present (periphlebitis in one and vitritis and a choroidal nodule in the other). In only two patients was posterior segment involvement noted without coexisting anterior uveitis; one had choroidal involvement and the second had periphlebitis and posterior vitreous cells without anterior segment inflammation. One additional patient had optic nerve involvement by sarcoid. Glaucoma was present in 12 of the 47 patients in this series. In 11 it was thought to be secondary to the uveitis with posterior synechiae and iris bornbe in two, increased intraocular pressure with active disease (not caused by corticosteroids) in one, and angle damage with peripheral anterior synechiae in the rest. One patient with conjunctival, lacrimal, and cutaneous sarcoid but without uveitis also had glaucoma. Eight of the 11 patients with secondary glaucoma ultimately suffered severe visual loss (12 of 19 involved eyes). The responses to glaucoma medications and glaucoma surgery (five patients) were typically poor. Cataracts were present in eight patients, seven of whom had uveitis. Lacrimal gland involvement was noted in 13 patients (7% of the overall series and 28% of patients with ophthalmic involvement). In
Vol. 102, No.3
Ocular Involvement in Sarcoidosis
299
TABLE 1 OCULAR INVOLVEMENT IN CHRONIC SARCOIDOSIS
NO. OF MANIFESTATION
PATIENTS
Uveitis Anterior Posterior Iris nodules Secondary glaucoma Cataracts Lacrimal gland involvement Conjunctival involvement Eyelid nodules Band keratopathy Scleralplaque Optic nerve involvement
35 33 13
% OF THOSE WITH
% OF THOSE WITH
OCULAR SARCOID
CHRONIC SARCOID
(NO.
(NO.
11 8
13 8 5 3 1 1
= 183)
19 18
74
70 28 11 23 17 28 17 11
5
eight of these patients lacrimal gland enlargement was evident on clinical examination; in the remaining five, dry eyes were noted in the absence of clinically evident lacrimal gland enlargement. Severe visual loss developed in nine patients. All had uveitis and eight had glaucoma. One patient had a visual acuity of R.E.: 20170 and L.E.: 20150 and visual fields of less than 10 degrees. The other eight had visual acuities of 20/200 or less. The cause of the visual loss was often multifactorial and included glaucomatous optic nerve damage (five cases), media opacities (five cases), macular edema (two cases), and phthisis (one case). It was often difficult to determine the exact causes of visual loss. Because fluorescein angiography was often not performed, the prevalence of macular edema is probably higher and may also have been present in those patients with media opacities. When we analyzed the factors contributing to a poor visual outcome, we found that eight of the 11 patients with uveitis and secondary glaucoma suffered severe visual loss (Fisher's exact test, P<.OOOI). Posterior uveitis was also associated with a poor visual outcome; six of thirteen patients with posterior uveitis suffered severe visual loss (Fisher's exact test, P = .05). The posterior segment manifestations in these six patients included periphlebitis (three cases), vitritis (four cases), choroidal nodule (one case), and exudative retinal detachments (two cases). However, the six patients with posterior uveitis who suffered severe visual loss also had secondary glaucoma.
= 47)
7 3 6 4 7 4 3 2
6 2 2
0.5 0.5
Discussion Several studies have documented the common occurrence of ocular involvement in sarcoidosis and the ophthalmic manifestations of sarcoidosis.P:" Estimates of the prevalence of ophthalmic involvement in sarcoidosis have ranged as high as 50%9but are generally closer to 25% .1,10,11 In a study of manifestations of sarcoidosis worldwide, Siltzbach and associates' noted an overall 22% prevalence of ophthalmic involvement. Obenauf and associates" noted a 38% prevalence of ophthalmic involvement. These differences are related to the patient population studied, definitions of ophthalmic involvement, and the nature of the evaluations conducted. Indeed, the highest prevalence rate was noted by Crick, Hoyle, and Smellie," who classified keratoconjunctivitis
TABLE 2 EARLY OCULAR LESIONS PRESENT AT DIAGNOSIS LESIONS
NO.
NO.
%
Uveitis Lacrimal gland Conjunctiva Eyelid nodules Optic nerve
35 13 8
32 11
6
3 1
91 85 75 50 100
1
6
300
September, 1986
AMERICAN JOURNAL OF OPHTHALMOLOGY
sicca as evidence of lacrimal gland involvement in sarcoidosis. Several aspects of our data must be interpreted with caution. First, our patient population clearly represented a selected group of patients. Not only was the study population chosen for the chronic nature of the disease, but it also represented patients seen at a referral center; thus, this was not a population-based study. Second, the study was a retrospective one of patients followed primarily for systemic disease. As such, all prevalence data can be regarded only as an estimate. The lack of a defined ophthalmic protocol, variability of follow-up, and referral of symptomatic patients would all lead to an underreporting of ocular disease and a bias toward more severe ocular disease. Finally, as with all retrospective studies, the data base is incomplete, and arbitrary decisions concerning interpretation of data were made. These problems were particularly true for the data on lacrimal gland involvement, where lacrimal gland enlargement was often based on the clinical judgment of the observer and not on predetermined criteria. Finally, the frequent and long-term use of systemic corticosteroids may have altered the natural course of the ocular disease. However, despite these limitations, this study had a follow-up period (mean, 13 years) difficult to achieve in a prospective fashion. Our estimate of ophthalmic involvement in 47 of 183 patients (26%) with chronic sarcoid was similar to prevalence estimates in all sarcoid derived from other series.I,IO,1l One striking finding was the racial difference in patients with ophthalmic disease. Of the 143 black patients with chronic sarcoid, 44 developed ocular disease (31 %), whereas only three of 40 of white patients (8%) developed ocular lesions. There were no sex differences between the overall series and patients with ocular involvement. Previous studies-! in the southeastern United States also noted an increased number of blacks among patients with ocular sarcoidosis, but our study suggested that blacks with chronic sarcoid may be more likely to develop ocular lesions. Both acute and chronic iridocyclitis have been described in patients with sarcoidosis.P:" Although all patients in this series had chronic sarcoidosis, not all patients had chronic ocular disease. In 15 of 33 patients with anterior uveitis (45%), the disease pursued an acute and occasionally recurrent course that generally did not lead to visual impairment. Most often this
was a single episode of iridocyclitis at the onset of disease. Conversely, patients with chronic uveitis did poorly. The major prognostic factor in a poor visual outcome appeared to be the presence of secondary glaucoma. Of the 11 patients who developed secondary glaucoma, eight suffered severe visual loss. Additionally, in two other patients with secondary glaucoma, moderate visual impairment was noted with visual acuities ranging from 20/40 to 20/50 in the three involved eyes. A similar association between uveitis with secondary glaucoma and a poor visual result has been found in patients with juvenile chronic arthritis and chronic iridocyclitiS.
13
Posterior segment involvement in sarcoidosis is well documented. 9-12,14-23 These lesions include vitreous inflammation (snowballs, string of pearls), retinal periphlebitis, choroidal granulomata, retinal neovascularization, and optic nerve disease. In our series of patients with chronic sarcoidosis, posterior uveitis occurred in 13 (7% of the overall series and 28% of those with ophthalmic sarcoid). Posterior involvement was most often present at the onset of systemic disease. Two patients had exudative retinal detachments, an unusual finding that to the best of our knowledge has been described in only two other patients with sarcoidosis.P Both patients had anterior uveitis and other manifestations of posterior segment inflammation simultaneously. Posterior uveitis was associated with a poor visual outcome as well. Although the course of ophthalmic involvement did not necessarily parallel that of the systemic disease, the ocular manifestations in most patients with chronic sarcoidosis declared themselves early in the course of the disease. Table 2 demonstrates that most patients with ocular involvement had lesions at the time of the initial diagnosis. This finding was in keeping with the other manifestations of sarcoidosis, where the major manifestations of sarcoidosis are generally present at the time of diagnosis."
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