Managing Ocular Disorders in Inflammatory Joint Disease: An Interdisciplinary Approach

With a dearth of large-scale randomized controlled trials investigating treatments for corneal and scleral disorders related to inflammatory joint disease, physicians presently rely on smaller reports and clinical experience to guide clinical decision making. This is difficult, however, given the limits of rheumatologists’ ophthalmologic expertise and the limits of ophthalmologists’ rheumatology experience. Experts say that the situation calls for close collaboration — in the same physical location if possible — between the 2 specialties.¹

Prevalence data for inflammatory ocular disorders are scarce. In a study of 196 patients with rheumatoid arthritis (RA), 39% had ocular manifestations;² the most common was dry eye, which affected 28% of this patient population. Scleritis, inflammation of the sclera that signals a medical emergency and has a poor prognosis, affected only 4 patients (2%) in this analysis.² A previous study found a similar prevalence of ocular disease in RA.³

“The vast majority of rheumatic diseases can affect the eye. Examples include [RA], lupus, ankylosing spondylitis, juvenile idiopathic arthritis, Sjogren syndrome, and giant cell arteritis,” James T. Rosenbaum, MD, professor of ophthalmology, medicine, and cell biology and head of the division of arthritis and rheumatic diseases at Oregon Health & Science University in Portland, told Rheumatology Advisor.

In some cases, he said, ocular symptoms are the dominant clinical manifestation of rheumatic disease. “A knowledge of these relationships and their implications can improve the care of both the eye and the joint disease.”

In a recent paper, a research team led by Gaelle Clavel, MD, PhD, of the Fondation Ophtalmologique Adolphe de Rothschild in Paris, France, wrote that ocular involvement creates difficulty for rheumatologists in determining which structure is affected and thus establishing an accurate diagnosis.¹ While ophthalmologists can assess the ocular abnormality in detail, the investigators stated, most are unfamiliar with managing the extra-ocular manifestations of chronic inflammatory rheumatic diseases (cIRD). “The rheumatologist and ophthalmologist must therefore work in partnership to ensure that the many facets of disease in each patient receive appropriate attention,” wrote Clavel, et al.

Dr Rosenbaum noted that, “the ideal collaboration is an interdisciplinary clinic in which the ophthalmologist and rheumatologist are physically in the same space. This optimizes communication, since most rheumatologists do not fully understand the eye disease and its importance. And conversely, most ophthalmologists don’t have the same knowledge of immunosuppression when compared to a rheumatologist.” Phone calls and letters can also be effective communication tools, he said, but they usually incur delays and provide less opportunity to understand the full implications of a finding.

According to Dr Clavel and colleagues, rheumatologists should consider scleritis as similar in severity to neurologic involvement, skin ulcers, and rheumatoid vasculitis.¹ Moreover, they added, the somber association of scleritis with poor prognosis suggests that scleritis, as well as peripheral ulcerative keratitis, should be viewed as a manifestation of subclinical vasculitis that warrants increasing systemic treatment of RA, even in the absence of joint findings indicating active disease or structural progression.

“The development of scleral inflammation requires the coordinated intervention of an ophthalmologist and a rheumatologist or internist,” wrote Clavel, et al. The objectives of this dialogue include:

● Determining optimal treatment of the acute episode (based largely on the severity of the ocular condition)

● Choosing the tests needed to establish the diagnosis in patients with isolated ocular manifestations and no previous diagnosis of systemic inflammatory disease (a task which falls mainly to the rheumatologist after the ophthalmologist rules out infectious causes such as herpes virus)

● Setting the optimal long-term treatment strategy in patients with known cIRD

The presence or absence of a known underlying systemic disease strongly influences scleritis treatment. A retrospective study of 119 patients with scleritis revealed that 76.5% had no evidence of autoimmune disease when diagnosed with scleritis.⁴

If scleritis develops before a diagnosis of systemic disease, said Clavel, et al, close collaboration between the ophthalmologist and rheumatologist assumes particular importance because the etiologic diagnosis can only be provided by the investigations done initially or during follow-up. The interdisciplinary team must evaluate patients for systemic diseases even with no signs that provide diagnostic orientation, the researchers added, and physicians must repeat the investigations over time if needed.

“In patients receiving follow-up for cIRD,” wrote Clavel and colleagues, “the role of the ophthalmologist is to differentiate scleritis from episcleritis, to identify the clinical disease pattern, and to assess severity.” The rheumatologist and ophthalmologist can then cooperate to determine the best initial treatment and decide whether changes in disease-modifying antirheumatic drug (DMARD) therapy are needed, they added.

Patients with idiopathic nodular or diffuse scleritis who do not respond to topical glucocorticoid therapy, and possibly subconjunctival triamcinolone injection, should be considered for nonsteroidal anti-inflammatory drug or oral glucocorticoid therapy.¹ “However,” wrote Dr Clavel and colleagues, “except in the mildest forms, an immunomodulating drug must be given, if only to decrease the glucocorticoid requirements.” DMARDs that have been used in this scenario, with varying efficacy, include methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, and chlorambucil. A 9250-patient cohort study failed to establish that any of these outperforms the others for the treatment of particular ocular diseases.⁵

Depending on the clinical situation, said Dr Rosenbaum, ophthalmologists can also help to assess whether vision loss is due to active inflammation as opposed to structural damage. “Rheumatologists can help an ophthalmologist diagnose a systemic illness such an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in a patient with scleritis. Rheumatologists can help choose the optimal therapy for a patient with sight-threatening uveitis. And a rheumatologist is sometimes needed to monitor the safety of that therapy,” he said.

Real-world obstacles to such close collaboration include time and money. Dr Rosenbaum said, “The clinic needs to be structured so that it is an efficient use of time for both the ophthalmologist and the rheumatologist. And most physicians are understandably reluctant to provide consultation without compensation.”

An article on collaborative management of uveitis in which Dr Rosenbaum was a co-investigator elaborates further, recognizing the challenges of clinicians familiarizing themselves with diseases that cannot be fully assessed with the tools available in a conventional rheumatology clinic.⁶ “We empathize with the time requirements that impair optimal management of the patient whose illness requires 2 or more subspecialists to confer,” the investigators wrote. “Mechanisms that facilitate communication with an ophthalmologist include interdisciplinary clinics and case conferences to discuss patients whose illness lies in the interstices between these 2 disciplines.”

References

1. Clavel G, Gabison E, Semerrano L.  Corneal and scleral involvement in inflammatory joint disease: rheumatologists and ophthalmologists exchanging views [published online January 31, 2019]. Joint Bone Spine. doi:10.1016/j.jbspin.2019.01.014

2. Vignesh AP, Srinivasan R.  Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies. Clin Ophthalmol. 2015;9:393-397.

3. Smith JR, Mackensen F, Rosenbaum JT. Therapy insight: scleritis and its relationship to systemic autoimmune disease. Nat Clin Pract Rheumatol. 2007;3:219-226.

4. Lin P, Bhullar SS, Tessler HH, Goldstein DA.  Immunologic markers as potential predictors of systemic autoimmune disease in patients with idiopathic scleritis. Am J Ophthalmol. 2008;145:463-471.

5. Kempen JH, Daniel E, Gangaputra S, et al. Methods for identifying long-term adverse effects of treatment in patients with eye diseases: the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Ophthalmic Epidemiol. 2008;15:47-55.

6. Rosenbaum JT, Dick AD. The eyes have it: a rheumatologist’s view of uveitis. Arthritis Rheumatol. 2018;70(10):1533-1543.