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The Enigma of Pars Planitis
AMERICAN JOURNAL FRANK
W.
NEWELL,
OF O P H T H A L M O L O G Y ® Publisher and Editor-in-Chief
Tribune Tower, Suite 1415, 435 North Michigan Ave., Chicago, Illinois 60611
EDITORIAL BOARD Thomas M. Aaberg, Miltvaukee Mathea R. Allansmith, Boston Douglas R. Anderson, Miami Jules Baum, Boston William M. Bourne, Rochester Ronald M. Burde, St. Louis Fred Ederer, Bethesda Frederick T. Fraunfelder, Portland Eugene Helveston, Indianapolis Frederick A. Jakobiec, New York Michael A. Kass, St. Louis Herbert E. Kaufman, New Orleans Kenneth R. Kenyon, Boston
Steven G. Kramer, San Francisco Irving H. Leopold, Irvine Robert Machemer, Durham A. Edward Maumenee, Baltimore Irene H. Maumenee, Baltimore Nancy M. Newman, San Francisco Don H. Nicholson, Miami Edward W. D. Norton, Miami Arnall Patz, Baltimore Deborah Pavan-Langston, Boston Thomas H. Pettit, Los Angeles Allen M. Putterman, Chicago
Dennis Robertson, Rochester Merlyn M. Rodrigues, Bethesda Stephen J. Ryan, Los Angeles Jerry A. Shields, Philadelphia M. Bruce Shields, Durham David Shoch, Chicago Ronald E. Smith, Los Angeles Bruce E. Spivey, San Francisco Bradley R. Straatsma, Los Angeles H. Stanley Thompson, Iowa City E. Michael Van Buskirk, Portland Gunter K. von Noorden, Houston George O. Waring, Atlanta
Published monthly by the OPHTHALMIC PUBLISHING COMPANY Tribune Tower, Suite 1415, 435 North Michigan Avenue, Chicago, Illinois 60611 Directors A. Edward Maumenee, President David Shoch, Vice President Frank W. Newell, Secretary and Treasurer
Edward W. D. Norton Bruce E. Spivey Bradley R. Straatsma
EDITORIAL The Enigma of Pars Planitis Thomas M. Aaberg (30%) have indolent disease for a decade or more with intermittent severe exacerbations. 7 ' 8 The severity may differ between the two eyes in bilateral cases 9 (bilaterality approaches 80% with long-term follow-up10). The perplexity of an unknown cause and nonspecific treatment is compounded by the frequency of the condition. Schlaegel11 found that peripheral uveitis was the third most common type of uveitis. In more absolute terms, reported prevalences in referral uveitis practices have been in the range of 8%.8 Although the exact prevalence depends upon the local referral patterns, peripheral uveitis represents a significant segment of the uveitis population. The insidious course of the early disease process in more than half of the afflicted patients makes it impossible to determine an accurate incidence. The data on prevalence are confounded by the long-term duration of the disease in most patients. Some authors have noted
Since the first mention of peripheral uveitis as a distinct entity 40 years ago, 1 there have been few significant advances in the understanding of this frustrating disease. Elaboration of the clinical characteristics of peripheral uveitis2"4 or pars planitis 5 emphasized the wide spectrum of severity from minor symptoms to relentless progression with devastating complications. 6 With rare exception, the condition becomes symptomatic within the first three decades of life in otherwise healthy individuals. The age of onset correlates inversely with the severity of expression: when symptomatic within the first decade of life the severity of inflammation, the resulting vitreous opacification, and the resistance to therapy are significantly greater than when the onset occurs in the second to fourth decades. Early onset is not common (in about 10% of affected patients); about 60% have a mild or moderately severe prolonged course. 7 The remaining patients
828
Vol. 103, No. 6
resolution within a decade of onset 10 ; however, most rarely encounter a patient in whom the uveitis becomes quiescent even after two decades.11,12 Thus, although it is comforting to counsel patients that the process will eventually "burn out" (as indicated by the occasional patient with evidence of old pars plana membranes but no active disease), in reality ophthalmologists rarely observe permanent spontaneous resolution of the inflammation. None of the names by which this process is known are totally satisfactory. The initial name, peripheral uveitis, 1-4 does not acknowledge the role (possibly primary) of the retinal vasculature. Peripheral uveoretinitis 10 ' 13 hedges the contributions of retinal and uveal tissue. Pars planitis 6 connotes a localized geographic area of involvement despite the original descriptions. These included gelatinous exudates in the anterior chamber angle with subsequent synechiae, 2 anterior chamber flare and rare cells sometimes resulting in fine or moderate keratic precipitates, 2 ' 6,11 and posterior uveoretinal involvement in rare cases with posterior vasculopathy and underlying pigment epithelial atrophy. One of the curiosities of this disease is the invariable localization of aggregated exudate in the lower one half of the eye in the region of the vitreous base. Although some have thought the process to be a diffuse vasculitis (phlebitis 14 ) and that possibly the dependent accumulation is a gravitational phenomenon, the original description of the clinical picture 3 diagrammed the early perivasculitis and diapedesis to be in the inferior peripheral quadrants. As the process continues, the inflammatory accumulation spreads superiorly in a circumferential pattern, the original inferior areas often developing a condensed quiescent appearance. This seems to belie a gravitational facet to the exudative accumulation. A recent article in THE AMERICAN JOURNAL OF by Henderly and associates 9 attempts to correlate the presence or absence of aggregated peripheral exudate with severity and subsequent complications of the disease process. While these authors conclude the presence of aggregated exudate connotes a worse prognosis as compared to diffuse vitreous cells without aggregation, they do not mention the peripheral vascular abnormalities that result from the chronic inflammation and contribute to the intractable nature of the disease. Neovascularization that extends across the ora serrata and forms a racemose network OPHTHALMOLOGY
Editorial
829
within the vitreous base is a common finding in chronic cases.10,13,15"17 The presence of vitreous opacities, aggregated peripheral exudate, and the anterior location of these vessels make recognition difficult. A histopathologic report by Pederson and associates 16 of the light and electron microscopic findings of eyes with pars planitis found prominent lymphocytic cuffing and mural infiltration of peripheral terminal veins that spared the arteries. Within the vitreous base a loose fibrovascular membrane lay internal to hyperplastic nonpigmented epithelium of the pars plana in direct continuity with similar peripheral epiretinal fibroglial membranes. From their findings, these authors hypothesized that the fibroglial "snowbank" may be a direct extension of a common inflammatory process involving both peripheral retina and vitreous base. The presence of these vascular anomalies, particularly peripheral neovascularization, is correlated with intractable disease and a progressively refractory response to corticosteroid therapy (which remains the mainstay of therapy). These observations form the basis for employing ablative procedures (that is, diathermy 17 and cryotherapy10,13,15) to eliminate the neovascularization and the diseased, possibly ischemic, tissue. Elimination of the permeable neovascular tissue seems to reduce exudative accumulation and thus break the vicious cycle that adds to the perpetuation of disease (even though it does not address the primary inflammatory process). The final surgical therapy for eyes with pars planitis is vitrectomy, which does not address the inflammatory nature of the process but assists in the management of the resulting complications (retinal detachment, cataract, nonresolving vitreous opacification, and pupillary membranes). The goal of treatment must be the elimination of the inflammatory process; however, this rarely is achieved. More realistically, the ophthalmologist must strive to reduce the severity of the inflammatory process. A therapeutic compromise of low grade inflammation with occasional exacerbations controlled by periodic short-term corticosteroid therapy must often be accepted. A more satisfying therapeutic end point awaits definite delineation of etiologic agents or processes of this enigmatic disease.
Reprint requests to Thomas M. Aaberg, M.D., Medical College of Wisconsin, 8700 W. Wisconsin Ave., Milwaukee, WI 53226.
830
AMERICAN JOURNAL OF OPHTHALMOLOGY
References 1. Schepens, C. L.: A new ophthalmoscope demonstration. Trans. Am. Acad. Ophthalmol. Otolaryngol. 51:298, 1947. 2. Brockhurst, R. J., Schepens, C. L., and Okamura, I. D.: Uveitis. I. Gonioscopy. Am. J. Ophthalmol. 42:545, 1956. 3. Brockhurst, R. J., Schepens, C. L., and Okamura, I. D.: Uveitis. II. Peripheral uveitis. Clinical description, and differential diagnosis. Am. J. Ophthalmol. 49:1257, 1960. 4. Brockhurst, R. J., Schepens, C. L., and Okamura, I. D.: Uveitis. III. Peripheral uveitis. Pathogenesis, etiology and treatment. Am. J. Ophthalmol. 51:19, 1961. 5. Welch, R. B., Maumenee, A. E., and Wahlen, H. E.: Peripheral posterior segment inflammation, vitreous opacities, and edema of the posterior pole. Arch. Ophthalmol. 64:540, 1960. 6. Brockhurst, R. J., and Schepens, C. C : Uveitis. IV. Peripheral uveitis. The complications of retinal detachment. Arch. Ophthalmol. 80:747, 1968. 7. Aaberg, T. M.: Pars planitis. In Fraunfelder, F. T., and Roy, F. H. (eds.): Current Ocular Therapy. Philadelphia, W. B. Saunders, 1980, p. 481. 8. Smith, R. E., Godfrey, S. A., and Kimura, S. J.: Chronic cyclitis. I. Course and visual prognosis.
June, 1987
Trans. Am. Acad. Ophthalmol. Otolaryngol. 77:760, 1973. 9. Henderly, D. E., Haymond, R. S., Rao, N. A., and Smith, R. E.: The significance of the pars plana exudate in pars planitis. Am. J. Ophthalmol. 103:669, 1987. 10. Aaberg, T. M., Cesarz, T. J., and Fleckinger, R. R., Jr.: Treatment of pars planitis. I. Cryotherapy. Surv. Ophthalmol. 22:120, 1977. 11. Schlaegel, T. F., Jr.: Ocular Toxoplasmosis and Pars Planitis. New York, Grune and Stratton, 1978, p. 263. 12. Hogan, M. J., Kimura, S. J., and O'Connor, G. R.: Peripheral retinitis and chronic cyclitis in children. Trans. Ophthalmol. Soc. U.K. 85:39, 1965. 13. Aaberg, T. M., Cesarz, T. J., and Flickinger, R. R.: Treatment of peripheral uveoretinitis by cryotherapy. Am. J. Ophthalmol. 75:685, 1973. 14. Pruett, R. C , Brockhurst, R. J., and Letts, N.: Fluorescein angiography of peripheral uveitis. Am. J. Ophthalmol. 77:448, 1974. 15. Felder, K. S., and Brockhurst, R. J.: Neovascular fundus abnormalities in peripheral uveitis. Arch. Ophthalmol. 100:750, 1982. 16. Pederson, J. E., Kenyon, K. R., Green, W. R., and Maumenee, A. E.: Pathology of pars planitis. Am. J. Ophthalmol. 86:762, 1978. 17. Gills, J. P.: Combined medical and surgical therapy for complicated cases of peripheral uveitis. Arch. Ophthalmol. 79:723, 1968.
W.
NEWELL,
OF O P H T H A L M O L O G Y ® Publisher and Editor-in-Chief
Tribune Tower, Suite 1415, 435 North Michigan Ave., Chicago, Illinois 60611
EDITORIAL BOARD Thomas M. Aaberg, Miltvaukee Mathea R. Allansmith, Boston Douglas R. Anderson, Miami Jules Baum, Boston William M. Bourne, Rochester Ronald M. Burde, St. Louis Fred Ederer, Bethesda Frederick T. Fraunfelder, Portland Eugene Helveston, Indianapolis Frederick A. Jakobiec, New York Michael A. Kass, St. Louis Herbert E. Kaufman, New Orleans Kenneth R. Kenyon, Boston
Steven G. Kramer, San Francisco Irving H. Leopold, Irvine Robert Machemer, Durham A. Edward Maumenee, Baltimore Irene H. Maumenee, Baltimore Nancy M. Newman, San Francisco Don H. Nicholson, Miami Edward W. D. Norton, Miami Arnall Patz, Baltimore Deborah Pavan-Langston, Boston Thomas H. Pettit, Los Angeles Allen M. Putterman, Chicago
Dennis Robertson, Rochester Merlyn M. Rodrigues, Bethesda Stephen J. Ryan, Los Angeles Jerry A. Shields, Philadelphia M. Bruce Shields, Durham David Shoch, Chicago Ronald E. Smith, Los Angeles Bruce E. Spivey, San Francisco Bradley R. Straatsma, Los Angeles H. Stanley Thompson, Iowa City E. Michael Van Buskirk, Portland Gunter K. von Noorden, Houston George O. Waring, Atlanta
Published monthly by the OPHTHALMIC PUBLISHING COMPANY Tribune Tower, Suite 1415, 435 North Michigan Avenue, Chicago, Illinois 60611 Directors A. Edward Maumenee, President David Shoch, Vice President Frank W. Newell, Secretary and Treasurer
Edward W. D. Norton Bruce E. Spivey Bradley R. Straatsma
EDITORIAL The Enigma of Pars Planitis Thomas M. Aaberg (30%) have indolent disease for a decade or more with intermittent severe exacerbations. 7 ' 8 The severity may differ between the two eyes in bilateral cases 9 (bilaterality approaches 80% with long-term follow-up10). The perplexity of an unknown cause and nonspecific treatment is compounded by the frequency of the condition. Schlaegel11 found that peripheral uveitis was the third most common type of uveitis. In more absolute terms, reported prevalences in referral uveitis practices have been in the range of 8%.8 Although the exact prevalence depends upon the local referral patterns, peripheral uveitis represents a significant segment of the uveitis population. The insidious course of the early disease process in more than half of the afflicted patients makes it impossible to determine an accurate incidence. The data on prevalence are confounded by the long-term duration of the disease in most patients. Some authors have noted
Since the first mention of peripheral uveitis as a distinct entity 40 years ago, 1 there have been few significant advances in the understanding of this frustrating disease. Elaboration of the clinical characteristics of peripheral uveitis2"4 or pars planitis 5 emphasized the wide spectrum of severity from minor symptoms to relentless progression with devastating complications. 6 With rare exception, the condition becomes symptomatic within the first three decades of life in otherwise healthy individuals. The age of onset correlates inversely with the severity of expression: when symptomatic within the first decade of life the severity of inflammation, the resulting vitreous opacification, and the resistance to therapy are significantly greater than when the onset occurs in the second to fourth decades. Early onset is not common (in about 10% of affected patients); about 60% have a mild or moderately severe prolonged course. 7 The remaining patients
828
Vol. 103, No. 6
resolution within a decade of onset 10 ; however, most rarely encounter a patient in whom the uveitis becomes quiescent even after two decades.11,12 Thus, although it is comforting to counsel patients that the process will eventually "burn out" (as indicated by the occasional patient with evidence of old pars plana membranes but no active disease), in reality ophthalmologists rarely observe permanent spontaneous resolution of the inflammation. None of the names by which this process is known are totally satisfactory. The initial name, peripheral uveitis, 1-4 does not acknowledge the role (possibly primary) of the retinal vasculature. Peripheral uveoretinitis 10 ' 13 hedges the contributions of retinal and uveal tissue. Pars planitis 6 connotes a localized geographic area of involvement despite the original descriptions. These included gelatinous exudates in the anterior chamber angle with subsequent synechiae, 2 anterior chamber flare and rare cells sometimes resulting in fine or moderate keratic precipitates, 2 ' 6,11 and posterior uveoretinal involvement in rare cases with posterior vasculopathy and underlying pigment epithelial atrophy. One of the curiosities of this disease is the invariable localization of aggregated exudate in the lower one half of the eye in the region of the vitreous base. Although some have thought the process to be a diffuse vasculitis (phlebitis 14 ) and that possibly the dependent accumulation is a gravitational phenomenon, the original description of the clinical picture 3 diagrammed the early perivasculitis and diapedesis to be in the inferior peripheral quadrants. As the process continues, the inflammatory accumulation spreads superiorly in a circumferential pattern, the original inferior areas often developing a condensed quiescent appearance. This seems to belie a gravitational facet to the exudative accumulation. A recent article in THE AMERICAN JOURNAL OF by Henderly and associates 9 attempts to correlate the presence or absence of aggregated peripheral exudate with severity and subsequent complications of the disease process. While these authors conclude the presence of aggregated exudate connotes a worse prognosis as compared to diffuse vitreous cells without aggregation, they do not mention the peripheral vascular abnormalities that result from the chronic inflammation and contribute to the intractable nature of the disease. Neovascularization that extends across the ora serrata and forms a racemose network OPHTHALMOLOGY
Editorial
829
within the vitreous base is a common finding in chronic cases.10,13,15"17 The presence of vitreous opacities, aggregated peripheral exudate, and the anterior location of these vessels make recognition difficult. A histopathologic report by Pederson and associates 16 of the light and electron microscopic findings of eyes with pars planitis found prominent lymphocytic cuffing and mural infiltration of peripheral terminal veins that spared the arteries. Within the vitreous base a loose fibrovascular membrane lay internal to hyperplastic nonpigmented epithelium of the pars plana in direct continuity with similar peripheral epiretinal fibroglial membranes. From their findings, these authors hypothesized that the fibroglial "snowbank" may be a direct extension of a common inflammatory process involving both peripheral retina and vitreous base. The presence of these vascular anomalies, particularly peripheral neovascularization, is correlated with intractable disease and a progressively refractory response to corticosteroid therapy (which remains the mainstay of therapy). These observations form the basis for employing ablative procedures (that is, diathermy 17 and cryotherapy10,13,15) to eliminate the neovascularization and the diseased, possibly ischemic, tissue. Elimination of the permeable neovascular tissue seems to reduce exudative accumulation and thus break the vicious cycle that adds to the perpetuation of disease (even though it does not address the primary inflammatory process). The final surgical therapy for eyes with pars planitis is vitrectomy, which does not address the inflammatory nature of the process but assists in the management of the resulting complications (retinal detachment, cataract, nonresolving vitreous opacification, and pupillary membranes). The goal of treatment must be the elimination of the inflammatory process; however, this rarely is achieved. More realistically, the ophthalmologist must strive to reduce the severity of the inflammatory process. A therapeutic compromise of low grade inflammation with occasional exacerbations controlled by periodic short-term corticosteroid therapy must often be accepted. A more satisfying therapeutic end point awaits definite delineation of etiologic agents or processes of this enigmatic disease.
Reprint requests to Thomas M. Aaberg, M.D., Medical College of Wisconsin, 8700 W. Wisconsin Ave., Milwaukee, WI 53226.
830
AMERICAN JOURNAL OF OPHTHALMOLOGY
References 1. Schepens, C. L.: A new ophthalmoscope demonstration. Trans. Am. Acad. Ophthalmol. Otolaryngol. 51:298, 1947. 2. Brockhurst, R. J., Schepens, C. L., and Okamura, I. D.: Uveitis. I. Gonioscopy. Am. J. Ophthalmol. 42:545, 1956. 3. Brockhurst, R. J., Schepens, C. L., and Okamura, I. D.: Uveitis. II. Peripheral uveitis. Clinical description, and differential diagnosis. Am. J. Ophthalmol. 49:1257, 1960. 4. Brockhurst, R. J., Schepens, C. L., and Okamura, I. D.: Uveitis. III. Peripheral uveitis. Pathogenesis, etiology and treatment. Am. J. Ophthalmol. 51:19, 1961. 5. Welch, R. B., Maumenee, A. E., and Wahlen, H. E.: Peripheral posterior segment inflammation, vitreous opacities, and edema of the posterior pole. Arch. Ophthalmol. 64:540, 1960. 6. Brockhurst, R. J., and Schepens, C. C : Uveitis. IV. Peripheral uveitis. The complications of retinal detachment. Arch. Ophthalmol. 80:747, 1968. 7. Aaberg, T. M.: Pars planitis. In Fraunfelder, F. T., and Roy, F. H. (eds.): Current Ocular Therapy. Philadelphia, W. B. Saunders, 1980, p. 481. 8. Smith, R. E., Godfrey, S. A., and Kimura, S. J.: Chronic cyclitis. I. Course and visual prognosis.
June, 1987
Trans. Am. Acad. Ophthalmol. Otolaryngol. 77:760, 1973. 9. Henderly, D. E., Haymond, R. S., Rao, N. A., and Smith, R. E.: The significance of the pars plana exudate in pars planitis. Am. J. Ophthalmol. 103:669, 1987. 10. Aaberg, T. M., Cesarz, T. J., and Fleckinger, R. R., Jr.: Treatment of pars planitis. I. Cryotherapy. Surv. Ophthalmol. 22:120, 1977. 11. Schlaegel, T. F., Jr.: Ocular Toxoplasmosis and Pars Planitis. New York, Grune and Stratton, 1978, p. 263. 12. Hogan, M. J., Kimura, S. J., and O'Connor, G. R.: Peripheral retinitis and chronic cyclitis in children. Trans. Ophthalmol. Soc. U.K. 85:39, 1965. 13. Aaberg, T. M., Cesarz, T. J., and Flickinger, R. R.: Treatment of peripheral uveoretinitis by cryotherapy. Am. J. Ophthalmol. 75:685, 1973. 14. Pruett, R. C , Brockhurst, R. J., and Letts, N.: Fluorescein angiography of peripheral uveitis. Am. J. Ophthalmol. 77:448, 1974. 15. Felder, K. S., and Brockhurst, R. J.: Neovascular fundus abnormalities in peripheral uveitis. Arch. Ophthalmol. 100:750, 1982. 16. Pederson, J. E., Kenyon, K. R., Green, W. R., and Maumenee, A. E.: Pathology of pars planitis. Am. J. Ophthalmol. 86:762, 1978. 17. Gills, J. P.: Combined medical and surgical therapy for complicated cases of peripheral uveitis. Arch. Ophthalmol. 79:723, 1968.