Grand Rounds Conference Eric Downing MD Sclerod...malacia Perforans University of Louisville Department of Ophthalmology and Visual Sciences

Subjective CC/HPI: 68F referred by outside ophthalmologist for eval. Pt has been having irritation and light sensitivity OD for 7 years, but has gotten worse recently Ptosis – progressive over several years, OD > OS. Holds lids up to see.

History POH: none PMH: Rheumatoid Arthritis(~30 years), HLD, HTN Eye Meds: Art tears, Restasis OU BID Meds: Prednisone 5mg PO daily, MTX 25mg weekly, Enbrel 50mg weekly FOH: Glaucoma FH: Cancer, stroke

Objective OD OS VA: 20/300 20/25 Pupils: 4→3 4→3, no rAPD IOP: 20 13 EOM: full OU Levator function > 10 mm is excellent; < 5 is poor

Objective PLE: E/L/L WNL OU C/S Superior scleral thinning OD K few SPEs OU AC no cell or flare OU I/L PCIOL/1+NS Vit WNL DFE: ON/M/V/P: all WNL

Clinical photos

Assessment 68F with Rheumatoid Arthritis and scleral thinning OD without inflammation Dx: Scleromalacia Plan: referral back to rheumatologist, monitor for progression and development of glaucoma

Scleromalacia Perforans AKA necrotizing scleritis without inflammation Distinct from other forms of scleritis, which are characterized by redness, edema, and pain are not apparent here Typically associated with RA, but has also been reported with Granulomatosis with Polyangitis, SLE, JRA, Relapsing Polychondritis, TB, Gout, Syphilis, HSV, and HZV

Anterior Scleritis Three forms Diffuse: non-granulomatous reaction with anterior scleral edema with episcleral venous dilation Nodular: one or more nodules, usually tender to palpation Necrotizing: granulomatous reaction with a central area of fibrinoid necrosis With inflammation Without inflammation—Scleromalacia perforans

Pathophyisiology Inflammatory process thought to be caused by a type III hypersensitivity (immune complex) and possibly subsequent type IV reaction Causes immune complex vessel disposition in episcleral and scleral vasculature with thinning of the adjacent tissue

Epidemiology More common in women (3:2) Most common in fourth to sixth decades 1/3 of diffuse/nodular scleritis and 2/3 of patients with necrotizing scleritis is associated with connective tissue or autoimmune disease ½ of cases are bilateral at some point

Medical Treatment Diffuse/Nodular: Severe nodular/necrotizing disease: Oral NSAIDs Topical steroids Subconjunctival steroids Severe nodular/necrotizing disease: Oral steroids MTX Infliximab Cyclosporine Cyclophosphamide Sjogren and Hashimoto thyroiditis; HIV

Surgical Treatment For extreme corneal/scleral thinning or perforation, donor sclera or fascia lata, or periosteum can be used

Literature review of 30 manuscripts No RTC, on retrospective reviews, case reports, and case series All cases were scleritis refractory to immunosuppressive therapy Infliximab/adalimumab is more effective than etanercept Also effective at treating PUK Rituximab Good option for necrotizing scleritis and vasculitis-associated scleritis 60% of patients were able to d/c treatment after only one cycle 500mg better than1000mg dose

Actemra, IL-6 receptor antagonist Retrospective review of 17 patients who had failed treatment with other immunosuppresive and biological therapies 50% of scleritis patients achieved quiescence ¾ achieved remained quiet through 32 months ¼ stopped due to side effects, such as neutropenia, nausea, edema, +/- GI upset Tocilizumab is moderately effective

References BCSC Section 8: External Disease and Cornea, pp 204-212. Akpek, EK. Necrotising Scleritis: Diagnosis and Therapy, PDF. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol 1976; 60:163-191 Sales AF, Vieira LA, Freitas D. Biologic therapy for refractory scleritis: a new treatment perspective. Int Ophthal Dec 2015; 35:6 pp903-912.