UVEITIS OPHTHALMIC PEARLS Ocular Involvement in Rheumatoid Arthritis heumatoid arthritis (RA) is of RA. The ocular conditions associated 1 an autoimmune disease that with RA have pathological features in Rclassically presents with sym- common with vasculitis, which may metrical inflammatory polyarthritis, include vascular occlusion, infiltration, joint stiffness, fever, weight loss, and and fibrinoid necrosis. Processes at play malaise. There may also be periartic- include immune complex deposition, ular bony erosions, joint deformities, secretion of collagenases (e.g., matrix and nodules, with classic sparing of the metalloproteinases) by macrophages distal interphalangeal joints. Females and neutrophils, cytokine production, are more commonly affected, and there complement activation, and formation is an association with human leukocyte of autoantibodies.1 antigen (HLA)-DR4 and increased cytokine Th17. RA has diverse extra- Dry Eye Syndrome ANTERIOR SCLERITIS. Slit-lamp photo articular manifestations, including in Dry eye syndrome, also known as kera- displays dilation of the episcleral vessels the cardiac, pulmonary, nervous, renal, toconjunctivitis sicca, is the most com- in a patient with underlying RA. skeletal, circulatory, and ocular systems. mon ocular manifestation of RA. It can occur as a result of meibomian gland, ally, the prevalence of positive anti-Ro Diagnosis lacrimal gland, accessory lacrimal antibodies and anti-La antibodies is Diagnosis of RA is based on joint involve- gland, or goblet cell dysfunction. low in patients with RA, found in one ment, symptom duration, and serum Characteristics. Symptoms of dry study to be 12.2% and 11.3%, respec- studies, including rheumatoid factor eye syndrome include foreign body tively.3 and anti­­–cyclic citrullinated protein sensation, burning, decreased visual Other considerations. The normal (the most specific marker). Evaluation acuity, photophobia, and pruritus. tear film has antimicrobial properties may also include joint radiographs and Diagnostic signs include less than and contains immunomodulatory complete blood count with differential, 5 mm of tear extension on Schirmer’s factors such as collagenase inhibitors C-reactive protein level, and erythro- test, tear break-up time of 5 seconds or (e.g., alpha-2 macroglobulin). Patients cyte sedimentation rate. Uric acid level less, decreased lacrimal lake, and stain- with dry eye syndrome are deficient in and liver and kidney function tests can ing with fluorescein, rose bengal, or these protective mechanisms and have help exclude other etiologies or guide lissamine green.1 Up to 25% of patients increased proteolytic enzymes such as medication dosing. with RA meet criteria for secondary plasminogen activator in the tear film.4 Sjögren syndrome, which is less com- Consequentially, dry eye syndrome can Pathophysiology monly associated with xerostomia than lead to superficial punctate keratitis, Like the joints, the sclera and cornea is primary Sjögren syndrome. Notably, filamentary keratitis, corneal ulcer, and contain proteoglycans and collagen. different HLA genes are associated with ultimately, corneal melt.1 Accordingly, This histologic similarity likely accounts primary Sjögren syndrome and Sjögren RA is a relative contraindication against for many of the ocular manifestations syndrome secondary to RA.2 Addition- refractive surgery, especially LASIK, due to its potential to exacerbate dry eye syndrome.4 (See also “Surgical Consid- BY TAYLER M. SCHWARTZ, SCB, ROBERT T. KEENAN, MD, MPH, AND erations in RA Ocular Disease.”) MELISSA B. DALUVOY, MD. EDITED BY SHARON FEKRAT, MD, AND INGRID Treatment. Therapeutic modalities Robert T. Keenan, MD, MPH MD, Keenan, T. Robert U. SCOTT, MD, MPH. include lubricating drops and oint- EYENET MAGAZINE • 37 ments, topical cyclosporine, and oral Other considerations. The pres- 2 pilocarpine. The recent approval of ence of scleritis in patients with RA is lifitegrast has added a new medication associated with increased mortality.1 to our armamentarium of topical treat- Posterior scleritis can cause serous ret- ments. In-office procedures include inal detachment or chorioretinal folds. punctal occlusion, use of amniotic Other sequelae associated with scleritis membrane, and tarsorrhaphy. include uveitis, cataracts, glaucoma, posterior segment damage, and periph- Episcleritis eral ulcerative keratitis. Episcleritis is inflammation of the epis- Treatment. Topical medications are clera, which lies just beneath Tenon’s generally not effective in the treatment capsule. Although the disorder is usu- of scleritis. Therapy should focus on ally idiopathic, it can also be associated SCLEROMALACIA PERFORANS. Slit- managing the underlying RA, with with RA and other systemic diseases. It lamp photo of the left eye shows severe a multi disciplinary team approach is bilateral 40% of the time, and man- superotemporal scleral thinning with involving the patient’s primary care ifests with salmon-pink eyes and mild visible choroid bulging anteriorly, but physician and rheumatologist. Oral pain. It can occur sectorally in a radial with minimal inflammation. NSAIDs are most effective in mild cases distribution; in a diffuse pattern; and, and for nodular anterior scleritis. less commonly, in a nodular form. In of the time and is classified as anterior For more severe disease, the treat- contrast to scleritis, eye redness resolves or posterior based on its position rela- ment of choice is oral corticosteroids with topical phenylephrine. tive to the ora serrata. (1 mg/kg/day of prednisone equiva- Treatment. Episcleritis is usually Types of scleritis. Anterior scleritis lents), with an optional bolus of methyl- self-limiting. Topical corticosteroids can be nodular, diffuse, or necrotizing. prednisolone 1 g daily for 3 days. or oral nonsteroidal anti-inflammatory It usually presents with intense pain Depending on response and severity drugs (NSAIDs) can be used for symp- amplified by eye movements, blurry vi- of scleritis at presentation, additional tomatic relief. sion, photophobia, and tearing (Fig. 1). systemic medications include metho- Scleromalacia perforans describes trexate, azathioprine, mycophenolate Scleritis anterior necrotizing scleritis without mofetil, cyclosporine, and biologic RA is the most common cause of scleri- inflammation (Fig. 2). This condition agents such as infliximab, adalimumab, tis, which is an inflammation of the often presents without pain, despite its rituximab, and anakinra.Immunologic sclera characterized by vasodilation of ability to lead to visual loss, astigma- agents, most commonly intravenous or the superficial and deep episcleral ves- tism, and globe perforation. oral cyclophosphamide, can be added sels. Occasionally, scleritis may present Posterior scleritis is characterized by for necrotizing disease and refractory before the onset of joint symptoms in the “T” sign on B-scan. This classic sign cases.1 the RA patient. It may also occur as a is produced by hyporeflectivity from For necrotizing scleritis, exploration manifestation of systemic vasculitis. both the optic nerve and fluid under and debridement with tectonic patch Scleritis occurs bilaterally 40% to 50% Tenon’s capsule. grafting may be necessary for severe thinning or perforation.4 Peripheral Ulcerative Keratitis Surgical Considerations in RA Ocular Disease Peripheral ulcerative keratitis (PUK) is a type of corneal melt that occurs Surgical trauma can initiate macrophage and neutrophil infiltration, resulting when immune complexes infiltrate the in a progressive immunologic response and the deposition of immune com- vascular arcades in the 0.5-mm corneal plexes. When deposited in the cornea, these immune complexes contribute to periphery. RA is the most common a keratolytic response. During the initial inflammatory process, fibroblasts are etiology, accounting for 34% of cases; recruited and activated, producing complement component C1 and contribut- however, it can also be caused by other ing to the activation of the classical complement cascade. The surgical trauma auto immune, infectious, neurologic, itself may compromise ocular immune privilege and incite immune responses and dermatologic conditions.5 In the due to molecular mimicry. setting of severe RA, PUK is usually Additionally, the risk of postsurgical sterile corneal melt is higher in the accompanied by other ocular manifes- setting of RA and coexisting dry eye syndrome, so treatment of the RA and tations, and it can occur secondary to surface disease should be optimized prior to any ocular surgery. Perioperative scleritis, especially necrotizing scleritis.1,5 oral prednisone should be considered in patients with known RA. If necrotiz- Characteristics. PUK presents with ing scleritis occurs after ocular surgery without known underlying RA or other stromal thinning and a secondary systemic collagen vascular diseases, these entities should be suspected.1 overlying epithelial defect and is char- 1 Perez VL et al. Semin Ophthalmol. 2002;17(3-4):124-130. acterized by neovascularization of the MD B. Daluvoy, Melissa 38 • NOVEMBER 2016 leflunomide, infliximab, adalimumab, 3 or rituximab. Oral cyclosporine can be used if there is no underlying systemic vasculitis. Oral cyclophosphamide can be used in cases unresponsive to treat- ment, while etanercept is less effective. Ocular support. Additional mea- sures to help protect the cornea include topical medroxyprogesterone and Stay acetylcysteine, which act as collagenase inhibitors, and oral tetracycline,