|
Uveitis Associated With Childhood Rheumatic Diseases: The Pediatric Rheumatology Perspective
Alan M. Rosenberg* and Carol B.
Lindsley**
Departments of Pediatrics,
Universities of
Authors:
Alan M. Rosenberg
Professor, Department of Pediatrics
Carol B. Lindsley MD
Professor, Department of Pediatrics
Key Words: iridocyclitis, juvenile arthritis,
juvenile rheumatoid arthritis, juvenile idiopathic arthritis, uveitis
Corresponding Author:
Dr. Alan M. Rosenberg
Department of Pediatrics
Telephone: 306.966.8112
Fax: 306.966.8640
Email: rosenberg@sask.usask.ca
Abstract
Uveitis is an important and
potentially debilitating extraarticular manifestation of a variety of childhood
rheumatic diseases. The association of
chronic uveitis with oligoarticular juvenile arthritis (JIA) and antinuclear
antibodies is a particularly distinctive pediatric clinical entity. This review will highlight the importance of
uveitis as a pediatric rheumatology clinical care concern, consider the
pediatric rheumatologist’s role in the diagnosis and management of the child with uveitis, review the
biological basis and classification of eye inflammation relevant to childhood
rheumatic diseases, consider approaches for evaluating and monitoring the child
with uveitis, and review current uveitis management strategies.
INTRODUCTION
Eye disease is a prominent, potentially
debilitating extra-articular manifestation associated with a variety of
childhood rheumatic diseases. The
association of juvenile arthritis and uveitis represents a particularly
distinctive pediatric clinical entity. While the coexistence of uveitis and
articular disease is well recognized, reasons for this curious association
remain unknown.
In the general population, the
estimated prevalence and annual incidence of chronic uveitis associated with
juvenile arthritis is as high as 11 per 100,000 and 1.5 per 100,000
respectively (1). Chronic uveitis
associated with childhood arthritis can have debilitating ocular consequences;
approximately one-third of eyes develop substantial visual impairment and
one-tenth become blind (1). Despite
suggestions that both the frequency and severity of uveitis associated with
juvenile arthritis might be diminishing, the condition nevertheless remains an
important clinical concern (2;3).
Features associated with a predisposition to
developing chronic uveitis in juvenile idiopathic arthritis (JIA) (young onset
age, female sex, oligoarthritis and antinuclear antibody positivity) are
apparent but characteristics that help predict uveitis severity and prognosis
are not as obvious. Predicting uveitis
severity could aid in refining currently available monitoring guidelines and,
by identifying those patients at risk for visual impairment, could help justify
earlier introduction of more aggressive therapy. Conditions most consistently predictive of
poor visual prognosis of chronic uveitis associated with JIA include a short
duration between the onset of arthritis and uveitis, uveitis onset prior to
arthritis onset and the severity of uveitis at first detection of ocular
disease (4-8). Other proposed predictors
of uveitis severity include the histocompatibility antigen B15/w62, antibodies
to retinal S-antigen and elevated alpha-2 globulin (8-10) .
Uveitis as a Model
A better understanding of uveitis is itself
important, but it is also enticing to contemplate the prospect that rheumatic
disease-related uveitis could serve as a valuable model for the study of other
childhood rheumatic diseases. Exploring
uveitis associated with JIA, for example, has the potential to provide insights
into the origins of rheumatic diseases that begin at a young age; the
mechanisms that account for linkages between inflammatory joint disease and
associated extra-articular organ involvement; gender disparity in childhood
rheumatic diseases; and, the basis for the relationship between inflammatory
arthropathies and antinuclear antibody positivity.
The
Role of the Pediatric Rheumatologist
Collaboration between the pediatric
rheumatologist and ophthalmologist is essential to provide optimal care for the
affected uveitic child. The pediatric
rheumatologist’s role is to ensure prompt detection of uveitis, evaluate for
possible etiologic factors and for associated extra-ocular disease, consider
indications for introducing advanced immunomodulatory therapies and monitor the
efficacy and safety of such treatments.
THE
BIOLOGICAL BASIS OF UVEITIS
Anatomy
of the Eye
The uveal tract is a densely pigmented, vascular
coat interposed between the scleral-corneal shell externally and the retinal
layer internally (Figure 1) (11). The tract is a continuous layer
formed by the choroid, the ciliary body, and the iris. After removal of the sclera, the similarity in
appearance of the underlying structure to the glistening, veined surface of a
peeled purple grape prompted the derivation of the word uvea from the Greek
word uva, meaning grape.
Relative to its size, the eye contains a larger, avascular mass of tissue than any other organ. As an essentially vascular structure, the uvea’s primary function is to provide nutrition to the retina through the choriocapillaris vessels and to the avascular lens, cornea, and vitreous, via the aqueous. Additional uveal tract functions include control of pupil size by the musculature of the iris and alterations in accommodation of the lens via a series of suspensory fibers, the zonula, that arise from the ciliary body and insert onto the lens capsule.
The eye encloses three
chambers. The large vitreous cavity
posteriorly is bounded by the lens and zonula anteriorly and the retina
posteriorly. The tiny intermediate
chamber is limited in front by the posterior surface of the iris and by the
lens and zonula behind. The anterior
chamber is limited anteriorly by the cornea and posteriorly by the anterior
surface of the iris.
The choroid (a term derived from the resemblance of this structure to the fetal chorion), which nourishes the outer segment of the retina, extends from the optic nerve posteriorly to the ora serrata, an irregular margin at a point where the retina terminates. The brownish pigmentation of the choroid renders it impermeable to light and thus prevents internal reflections.
The
ciliary body begins beyond the ora serrata, encircling the eye at the plane of
the lens and in sagittal section has a triangular shape, the base of which
abuts against the sclera, and the apex lies free. The term is derived from the Latin word cilia, a hair. The ciliary body, while considered a single
structure, is actually derived from both ectodermal (retinal) and mesodermal
(uveal) primordia.
The iris, a term derived from the Greek word
meaning rainbow, represents the most anterior portion of the uveal tract. Peripherally, it is continuous with the
anterior portion of the ciliary body. Parts of the sclera and ciliary body
reside in the anterior chamber of the eye.
Physiology
of the Eye
Normally there is little transfer of immunoglobulins, cells or presumably, therapeutic drugs, into the aqueous or vitreous humors as a result of tight junctions between the retina's endothelial cells and the surrounding tissue. However, during inflammation, intercellular separation occurs allowing egress of materials into the aqueous and vitreous.
Immunology
of the Eye
The tendency for antigens to persist
in the vitreous is due partly to the relative stagnation of the vitreous and to
the stable complexes such antigens form with hyaluronic acid and collagen. Augmentation and prolongation of the immune
response to antigens deposited in the vitreous might be a result of this depot
effect.
Although antigen is processed
extraocularly, primed immune cells return to the eye and antibody production,
in response to intraocular antigens, occurs in the eye, especially in the
vascularized uvea. Thus, the production
of antibody occurs locally (12) and memory lymphocytes remain in the uveal
tract (13).
THE CLASSIFICATION OF UVEITIS
Anatomical Classification
Uveal tract inflammation is categorized according
to the location of the inflammatory process as anterior, intermediate, or
posterior uveitis or, when all chambers are affected, as panuveitis (Table 1) (14).
Of all uveitis seen in children,
approximately 30-40%
will be anterior uveitis, 40-50% posterior uveitis, 10-20%
intermediate uveitis and 5-10% panuveitis (15).
Almost half of children presenting with uveitis will have associated
extra-ocular sites of involvement.
Etiologic/Pathologic Classification
Frequently, children with unexplained uveitis are
referred to the pediatric rheumatologist to exclude an associated rheumatic
disease and, during this process, to evaluate the child for other possible
underlying diagnostic considerations.
Therefore, the pediatric rheumatologist should be familiar with possible
causes of uveitis including those not necessarily associated with rheumatic
diseases. Table 2 outlines conditions
associated with uveitis. Frequently, the
cause for isolated uveitis in a child cannot be established and the condition
remains idiopathic.
APPROACH
TO EVALUATING THE CHILD WITH UVEITIS
Making the Diagnosis of Uveitis
The definitive diagnosis of uveitis requires
slit-lamp biomicroscopic examination. Slit-lamp signs indicative of active
inflammation include the presence of inflammatory cells, protein flare and
keratic precipitates (Figure 2). Increased vascular permeability secondary to
inflammation permits extravasations of protein and inflammatory cells into the
anterior chamber. The deposition of
inflammatory cells on the posterior surface of the cornea, the anterior chamber
angle and the pupillary border of the iris can result in fibrous adhesions
(posterior synechiae) between the pupillary margins of the iris and the
underlying lens. Anterior synechiae
(adhesions between the anterior surface of the iris and the posterior surface
of the cornea) may also occur. Keratic
precipitates represent the deposition of lymphocytes and plasma cells on the
corneal endothelium.
Complications of uveitis, such as band
keratopathy, cataracts, and synechiae can eventually be evident on routine
ophthalmoscopic examination.
Monitoring
for Development of Chronic Asymptomatic Uveitis
Because chronic uveitis
associated with juvenile arthritis is ordinarily asymptomatic, judicious
monitoring of children is required.
Guidelines for ophthalmologic examinations in children with juvenile
rheumatoid arthritis have been proposed
(Table
3)
(16). Uveitis associated with other childhood rheumatic diseases, including the
spondyloarthropathies, is ordinarily associated with symptoms that can prompt
assessments and early detection.
Vigilant surveillance is also required to assess the child who is too
young to complain of ocular symptoms such as might occur in association with
Kawasaki’s disease or neonatal onset multisystem inflammatory disease (17;18).
Approach to Establishing a Diagnosis of Uveitis
Establishing a diagnosis of uveitis
requires consideration of the intraocular location of the inflammatory process
(anterior, intermediate, posterior), the course of the disease (acute, chronic
or recurrent), characteristics of the inflammatory process including the type
and distribution of inflammatory cells, the demographic characteristics of the
patient, and the results of microbiologic studies. A thorough history and
physical examination, judicious laboratory testing and interdisciplinary
collaboration can facilitate establishing a cause for uveitis. When indicated, considering and excluding
even rare causes of uveitis are important to ensure appropriate and safe
treatment. Table
4 summarizes representative characteristics that can be diagnostically
helpful.
APPROACH TO MANAGING THE CHILD WITH UVEITIS
An approach to monitoring and managing children
with JIA and associated chronic uveitis is illustrated in Figure 3.
Similar approaches could be applied to other forms of childhood uveitis.
Pharmacologic
Therapy
Optimal pharmacologic management of
uveitis associated with childhood rheumatic diseases requires close
collaboration between the ophthalmologist and rheumatologist, and awareness of
the potential efficacy of new therapeutic options for uveitis. The rheumatologist’s communication with the
ophthalmologist is essential to ensure that alterations in management for
extra-ocular disease do not adversely influence management of uveitis.
Neither conventional nor novel treatments for
childhood uveitis have been developed on the basis of substantive
evidence. Consequently, treatment
protocols can be inconsistent, imprecise and of equivocal effectiveness. Even the preferred protocols for
corticosteroid therapy, the foundation of uveitis management, have not been
established. The relative practicality,
effectiveness and safety of administering corticosteroids at various
frequencies and doses and by different routes
(topically, intra-ocularly or systemically), have not been reliably
evaluated. Multi-centered, multi-disciplinary, randomized, controlled,
prospective studies will be necessary to determine the most effective and
safest treatment protocols for both corticosteroid and emerging new
therapies.
Experiences in management of adults
with uveitis can help, at times, guide the treatment of children, especially
when uncommon conditions are considered.
However, the prominence and peculiarities of certain uveitic conditions
in the pediatric population, the requirements for age-related drug dosing, and
the potential adverse effects of certain therapies in children demands that
appropriate treatment studies be undertaken specifically in the pediatric
population.
Defining the desired treatment end
point is required to judge the efficacy of uveitis therapy. In JIA, for example, gradation of uveitis
severity is determined by the presence of varying degrees of protein and cells
in the anterior chamber. Absence of
either protein or cells is the indicator of inactivity. Inactive uveitis from
all medications is the ultimate goal of therapy (19).
Topical corticosteroid therapy remains
the mainstay of treatment for non-infectious uveitis in children. However, because long-term corticosteroid
therapy is associated with adverse effects in most patients and inadequate
response in some, the search continues for more effective and safer therapeutic
options. An adjunctive therapeutic role
for non-steroidal anti-inflammatory drugs (NSAIDS) in managing uveitis has been
suggested (19-21) Immunomodulatory
therapies are often considered for patients who display inadequate
responsiveness to corticosteroid therapy or in whom toxicity occurs (22). Even if the severity
of uveitis could be reliably predicted to guide the aggressiveness of therapy,
advanced treatment options currently available for consideration are not of
certain efficacy in uveitis. Furthermore, the use of such agents cannot
currently be based on a strong rationale because of limited insight into the underlying
pathogenesis of uveitis, imprecise knowledge about modes of pharmacologic
action of certain advanced drug therapies, and insufficient information about
the distribution in the eye of drugs delivered systemically. Immunomodulatory treatments that have been
employed, with variable success, in the treatment of uveitis include
chlorambucil (23;24) , methotrexate (22), cyclosporine (25), tumor necrosis
factor alpha (TNF-)
(26) and others (27). There are
indications that immunosuppression might induce or aggravate uveitis. The use of TNF- inhibitor agents, for
example, while showing promise in controlling uveitis in JIA patients, has been
associated with the first appearance of uveitis in both experimental animals
and human subjects. This suggests that the inhibition of TNF-alpha might induce
or exacerbate uveitis in certain circumstances (28;29). However, despite these
concerns, judicious use of new immunosuppressive and biologically based
therapies have the potential to improve the management of uveitis. Intraocular delivery of immunomodulatory
therapies using intravitreal implants could contribute to improved uveitis
management in the future (30).
PROGNOSIS
The prognosis of childhood uveitis
varies in accordance with the extent, severity and duration of uveitis, the
underlying disease, the promptness with which therapy is initiated, and the
rapidity and completeness of treatment responses. Outcomes of uveitis associated with
oligoarticular JIA have been most thoroughly studied while information concerning
prognosis of other childhood uveitic conditions associated with rheumatic
diseases is meagre.
Outcomes of uveitis associated with
JIA appear to be improving, although adequate, long-term prospective
surveillance studies have not be undertaken to unequivocally support this
impression(2;31). Purported improvements in outcomes could be accounted for
partly by more judicious uveitis screening resulting in the recognition of
milder disease which, in the past, may
not have been detected or
referred to the advanced care centers from which the earlier outcome reports
had originated. However, a real
improvement in prognosis may have occurred as a consequence of earlier
detection and therapeutic intervention, more conscientious monitoring, and more
effective pharmacologic and surgical treatments. The reduced frequency of visual impairment (<
20/200) or blindness reflects improvement in prognosis. Representative uveitis studies during the
past three decades have documented visual outcomes in 1228 eyes of which 98
(8.0%) were blind (3;5;7;32-43). Among
the 558 eyes studied in the first 20 years of the survey period, 74 (13.3%)
were blind. In contrast, 24 of 670 eyes (3.6%) reported in the most recent decade
were blind. Despite this apparent reduction
in visual loss, the potential for visual impairment as a consequence of uveitis
remains.
Long-term
surveillance into adulthood of childhood arthritis associated uveitis is
limited. However, because onset of
uveitis complications during adulthood does occur, lifelong surveillance of
high-risk patients has been recommended (43;44).
There is minimal information concerning the
prognosis of other forms of rheumatic disease-related uveitic syndromes in
children. In contrast to the adult
population, uveitis associated with psoriatic arthritis does not commonly
present with acute symptoms. Rather, the
ocular manifestations associated with childhood psoriatic arthritis tends to
mimic those characterizing oligoarticular JIA including chronicity, lack of
symptoms and association with antinuclear antibodies (45;46). The suggestion that uveitis associated with
psoriatic arthritis in children might be less responsive to topical
corticosteroid therapy, if substantiated, could result in a relatively poorer prognosis
if introduction of advanced immunomodulatory therapy is delayed (33).
Approximately one-quarter of children with
ankylosing spondylitis develop acute anterior uveitis, but chronic progressive
ocular inflammation tends not to occur.
Episodes of symptomatic uveitis are generally responsive to topical
treatment and consequently, permanent visual impairment is rare (47-49)
Uveitis is a prominent manifestation
in childhood sarcoidosis, especially when onset occurs at a young age
(50;51). As symptoms of uveitis can be
absent in children with sarcoidosis, judicious screening is required. Sequelae of childhood sarcoid uveitis
including synechiae, band keratopathy, and cataracts can result in visual
impairment.
Although rare in children, Behçet’s
syndrome represents a potentially blinding condition. Uveitis, though less frequent in children
than in adults with Behçet’s syndrome, is associated with a poor prognosis,
especially in boys (52). Prompt,
aggressive immunomodulatory therapy of Behçet’s syndrome may substantially
improve the prognosis for the disease in general and ocular morbidity in
particular (53-56).
SUMMARY
Uveitides associated with
childhood rheumatic diseases represent distinctive clinical entities and
important causes of visual impairment in children. Although clinical characteristics associated
with uveitis have been reasonably well defined, etiologies remain unknown, the
pathophysiology is still poorly understood, and therapeutic strategies are
predominantly empirical and not sufficiently effective. Future studies of uveitis associated with
childhood rheumatic diseases, undertaken by multidisciplinary collaborative
research teams, should aid in providing better care for children afflicted with
this potentially debilitating disorder.
REFERENCES
1.
2. Sherry D, Mellins ED, Wedgwood RJ. Decreasing
severity of chronic uveitis in children with pauciarticular arthritis. Am J Dis
Child 1991; 145:1026-1028.
3. Kotaniemi
K, Kautiainen H, Karma A, Aho K. Occurrence of uveitis in recently diagnosed
juvenile chronic arthritis: A
prospective study. Ophthalmology 2001; 108:2071-2075.
4. Dana MR, Merayo-Lloves J, Schaumberg DA,
Foster CS. Visual outcomes prognosticators in juvenile arthritis-associated
uveitis. Ophthalmology 1997; 104:236-244.
5. Edelsten C, Lee V, Bentley CR, Kanski JJ,
Graham EM. An evaluation of baseline risk factors predcitng severity in
juvenile idiopathic arthritis associated uveitis and other chronic atnerior
uveitis in early childhood. Br J Ophthalmol 2002; 86:51-56.
6. Kanski.
Juvenile arthritis and uveitis. Surv Ophthalmol 1990; 34:253-267.
7. Wolf MD, Lichter PR, Ragsdale CG. Prognostic
factors in the uveitis of juvenile rheumatoid arthrits. Ophthalmology 1987;
94:1242-1248.
8. Zulian F, Martini G, Falcini F, Gerloni V,
Zannin ME, Pinello L et al. Early predictors of severe course of uveitis in
oligoarticular juvenile idiopathic arthritis. J Rheumatol 2002;
29(11):2446-2453.
9. Leak AM, Ansell BM, Burman SJ. Antinculear
antibody studies in juvenile chronic arthritis. Arch Dis Childh 1986;
61:168-172.
10. Uusitalo RJ, Stjernschantz J, Mahlberg K,
Gregerson DS, Uusitalo H, Tallberg T et al. Serum antibody level to S-antigen
in children with chronic uveitis. Br J Ophthalmol 1985; 69:212-216.
11.
12. Rahi AHS, Garner A. Immunopathology of the
Eye.
13. Pribnow JF, Hall JM. Studies on intravitreal
initiation of the immune response. Invest Ophthalmol Vis Sci 2003; 9:639-646.
14. Bloch-Michel E, Nussenblatt RB. International
uveitis study group recommendations for the evaluation of intraocular
inflammatory disease. Am J Ophthalmol 1987; 103:234-235.
15. Cunnigham ET. Uveitis in children. Ocul
Imunol Immunopath 2000; 8:251-261.
16.
17. Burns J, Joffe L, Sargent R, Glode M.
Anterior uveitis associated with Kawasaki syndrome. Pediatr Infect Dis 1985;
4(3):258-261.
18. Dollfus H, Hafner R, Hofmann HM, Russo RA,
Denda L, Gonzales LD et al. Chronic infantile neurological cutaneous and
articular/neonatal onset multisystem inflammatory disease syndrome: ocular
manifestations in a recently recognized chronic inflammatory disease of
childhood. Arch Ophthalmol 2000; 118(10):1386-1392.
19. Nguyen QD, Foster S. Saving the vision of
children with juvenile rheumatoid arthritis-associated uveitis. JAMA 1998;
280:1133-1134.
20. Olson NY, Lindsley CB, Godfrey WA.
Nonsteroidal anti-inflammatory drug therapy in chronic childhood iridocyclitis.
Am J Dis Child 1988; 142:1289-1292.
21. Pepmueller PH, Daud U, Lee DH,
22. Jabs DA, Rosenbaum JT, Foster CS, Holland GN,
Jaffe GJ, Louie JS et al. Guidelines for the use of immunosuppresssive drugs in
patients with ocular inflammatory disorders:
Recommendations of an expert panel. Am J Ophthalmol 2000; 130:492-513.
23. Mehra R, Moore TL, Catalano D, Neucks SH,
Zuckner J. Chlorambucil in the treatment of iridocyclitis in juvenile
rheumatoid arthritis. J Rheumatol 1981; 8:141-144.
24. Miserocchi E, Baltatzis S, Baltatzis S, Ekong
A, et al. Efficacy and safety of chlorambucil in intraractable non-infectious
uveitis. Ophthalmology 2002; 109:137-142.
25. Gerloni V, Cimaz R, Gattinara M, Arnoldi C,
Pontikaki I, Fantini F. Efficacy and safety profile of cyclosporine A in the
treatment of juvenile chornic (idiopathic) arthritis. Results of a 10-year
prospective study. Rheumatology 2001; 40:907-913.
26. Reiff A, Takei S, Sadeghi S, Stout A, Shaham
B, Bernstein B et al. Etanercept therapy in children with treatment-resistant
uveitis. Arthritis Rheum 2001; 44:1411-1415.
27. Smith JR, Rosenbaum JT. Management of
Uveitis: A rheumatologic perspective.
Arthritis Rheum 2002; 46:309-318.
28. Kasner L, Chan C-C, Whitcup SM, Gery I. The
paradoxical effect of tumor necrosis factor alpha (TNF-a) in endotoxin-induced
uveitis. Invest Ophthalmol Vis Sci 1993; 34:2911-2917.
29. Smith JR,
30. Jaffe GJ, Ben Nun J, Guo H, Dunn JP, Ashton
P. Fluocinolone acetonide sustained drug delivery device to treat severe
uveitis. Ophthalmology 2000; 107:2024-2033.
31. Kotaniemi K, Savolainen A, Karma A, Aho K.
Recent advances in uveitis of juvenile idiopathic arthritis. Surv Ophthalmol
2003; 48:489-502.
32. Berk AT, Kocak N, Unsal E. Uveitis in
juvenile arthritis. Ocul Imunol Immunopath 2003; 9:243-251.
33. Cabral DA, Petty RE, Malleson PN, Ensworth S,
McCormick AQ, Schroeder ML. Visual prognosis in children with chronic anterior
uveitis and arthritis. J Rheumatol 1994; 21:2370-2375.
34. Calabro JJ, Parrino GR, Atchoo PD, Marchesano
JM, Goldberg LS. Chronic iridocyclitis in juvenile rheumatoid arthritis.
Arthritis Rheum 1970; 13:406-413.
35. Cassidy JT, Sullivan DB, Petty RE. Clinical
patterns of chronic iridocyclitis in children with juvenile rheumatoid
arthritis. Arthritis Rheum 1977; 20:224-226.
36. Chalom EC, Goldsmith DP, Koehler MA, Bittar
B, Rose CD, Ostrov BE et al. Prevalence and outcome of uveitis in regional
cohort of patients with juvenile rheumatoid arthritis. J Rheumatol 1997;
24:2031-2034.
37. Kanski JJ. Anterior uveitis in juvenile
rheumatoid arthritis. Arch Ophthalmol 1977; 95:1794-1797.
38. Oren B, Sehgal A, Simon JW, et al. The
prevalence of uveitis in juvenile rheumatoid arthritis. J AAPOS 2001; 5:2-4.
39.
40. Schaller J, Kupfer C, Wedgewood RJ.
Iridocyclitis in juvenile rheumatoid arthritis. Pediatrics 1969; 44:92-100.
41. Smiley WK. The visual prognosis of Still's
disease with eye invovlement. Proc R Soc Lond 1960; 53:196.
42. Spalter HF. The visual prognosis in juvenile
rheumatoid arthritis. Trans Am Ophthalmol Soc 1975; 73:554-570.
43. Zak M, Fledelius H, Pedersen FK. Ocular
complications and visual outcome in juvenile chornic arthritis: a 25-year
follow-up study. Acta Ophthalmol Scand 2003; 81(211):215.
44. Foster CS, Havrlikova K, Baltatzis S,
Christen WG, Meyayo-Lloves J. Secondary glaucoma in patients with juvenoe
rheumatoid arthritis-associated iridocyclitis. Acta Ophthalmol Scand 2000;
78:576-579.
45. Paiva ES,
46. Southwood TR, Petty RE, Maellson PN, Delgado
EA, Hunt DW, Wood B et al. Psoriatic arthritis in children. Arthritis Rheum
1989; 32(1007):1013.
47. Calabro JJ. The spondyloarthropathies: an
overview. Scan J Rheum 1980;
48. Calabro JJ. Clinical aspects of jvuenile
ankylosing spondylitis. Br J Rheum 1983; 22:104-109.
49. Scharf J, Scharf Y, Haim T. Relation between
HLA-B27 and clinical features in patients with acute anterior uveitis. Ann
Ophthalmol 1982; 14:488-499.
50.
51.
52. Kone-Paut I, Yurdakul S, Bahabri SA, Shafae
N, Ozen S, Ozdogan H et al. Clinical features of Behcet's disease in children:
an international collaborative study of 86 cases. J Pediatr 1998; 132:721-725.
53. Joseph A, Raj D, Dua HS, Powell PT, Lanyon
PC, Powell RJ. Infliximab in the treatment of refractory posterior uveitis.
Ophthalmology 2003; 110:1449-1453.
54. Kotter I, Ziehut M, Eckstein AK, Vonthein R,
Ness T, Gunaydin I et al. Human recombinant interferon alfa-2a for the
treatment of Behcet'ss disease with sight threatening posterior or panuveitis.
Br J Ophthalmol 2003; 87:423-431.
55. Nussenblatt RB. Bench to bedside: new approaches to the immunotherapy of
uveitic disease. Int Rev Immunol 2002; 21:273-289.
56. Ozdal PC, Ortac S, Taskintuna I, Firat E.
Long-term therapy with low dose cyclosporin A in ocular Behcet's disease. Doc
Oophthalmol 2002; 105:301-312.
FIGURE
LEGENDS
Figure 1. Sagittal diagram of the eye. The uveal tract
is comprised
of the iris, ciliary
body, and choroid. The terms uveitis,
iritis and iridocyclitis are ordinarily used synonymously to indicate an
inflammatory process involving the uveal tract
Figure 2. A
slit-lamp light beam passing through the anterior chamber of a uveitic
eye demonstrating the appearance of cells, keratic precipitates and protein
flare.
Figure 3. A proposed scheme for managing chronic uveitis in children with juvenile arthritis. It should be noted that there are no adequately controlled studies to support this protocol. The idea that mild uveitis need not necessarily be treated immediately (*) has not been evaluated