DIAGNOSING, TREATING, AND MANAGING SCLERITIS IN 2020 AN EXPERT PANEL RECOMMENDATION PANEL MEMBERS MELISSA TOYOS, MD STEPHEN D. ANESI, MD, FACS n Partner and Director of Research n Massachusetts Eye Research & Surgery Institution n Toyos Clinic n Waltham, MA n Nashville, TN DAVID S. CHU, MD n Medical Director, Metropolitan Eye Research THOMAS A. ALBINI, MD & Surgery Institute n Professor of Clinical Ophthalmology n Associate Professor of Clinical Ophthalmology n University of Miami Health n Rutgers University n Bascom Palmer Eye Institute n Newark, NJ n Miami, FL ROBERT C. WANG, MD n Texas Retina Associates n Dallas, TX Corresponding Author: Melissa Toyos, MD; Toyos Clinic, Nashville, TN; [email protected]. This work was supported by an unrestricted medical writing grant from Mallinckrodt Pharmaceuticals and is based on a virtual roundtable discussion hosted by Evolve Medical Education LLC. Although uncommon, scleritis is a dangerous immune-me- DIAGNOSING SCLERITIS diated disease that can potentially threaten the structural Melissa Toyos, MD: What percentage of patients in integrity of the eye and may be indicative of potentially your practice have scleritis? life-threatening systemic vasculitis.1,2 Data on the genetic factors of scleritis is lacking, but it is thought that genes affect- Stephen D. Anesi, MD, FACS: Scleritis accounts for 10% ing systemic autoimmune diseases impact scleritis as well.2 to 15% of the patients I see in my practice. Differentiating between episcleritis and scleritis and posterior and anterior scleritis can be challenging for physicians. An David S. Chu, MD: I agree; 10% to 15% sounds right to accurate diagnosis is critical to properly treat the disease and me as well. prevent vision loss. In the following summary of a roundtable discussion, experts comment on the complexity in diagnos- Thomas A. Albini, MD: It is a small number. I see more ing scleritis, compare the efficacy of therapeutics based on posterior segment inflammatory disease, but scleritis patient presentation, and review treatment plans for patients makes up about 5% of my uveitis patients. The cases are who are refractory or nonresponders. often among the most painful cases and the most chal- lenging to treat. FEBRUARY 2020 1 DIAGNOSING, TREATING, AND MANAGING SCLERITIS IN 2019 Robert C. Wang, MD: I’d say about 50% of my practice is Posterior scleritis, which is a risk factor for decreased vision, treating uveitis and 5% is treating scleritis. is difficult to diagnose because there is no redness when the anterior sclera is not involved, pain is more variable, and Dr. Toyos: The literature tells us that most scleritis examination may show elevation of the adjacent retina and patients are between ages 30 and 50, and that women are choroid. Up to 12% of scleritis is posterior.12 affected by scleritis twice as much as men.3 Its prevalence is Distinguishing between scleritis and episcleritis is not estimated to be about six cases per 100,000 people, but it is straightforward either, but there are some differences. higher in patients with rheumatoid arthritis or granuloma- Patients with scleritis, which is typically bilateral, can expe- tosis with polyangiitis (formerly known as Wegener granulo- rience extreme pain, have symptoms for years, and have a matosis).3 How do scleritis patients typically present in your violaceous vessel color. Patients usually describe a dull, achy office? What symptoms do you normally see? pain with a slow onset that typically increases over several days. Patients with episcleritis, however, present with min- Dr. Chu: Most of my scleritis patients are referred to me imal pain, have symptoms for days or months, and have a from optometrists and other ophthalmologists, and they light pink vessel color. Further, episcleritis is almost always typically present with chronic scleritis that isn’t improving, unilateral and acute; onset may occur overnight. The sig- despite months of treatment or scleritis that’s recurred. nature clinical feature of episcleritis is sectorial injection in They typically have a painful eye that’s tender to palpation the nasal or temporal quadrant. Cells are not usually in the and redness.4 It’s important to note that not every scleritis anterior chamber.2,4 patient has pain. If the patient appears to have scleritis but I was trained to examine the patient under normal lights, doesn’t have pain, it could still be scleritis. This is especially not under slit lamps, because you can miss that deep purple true in children; their scleritis could be painless.5 hue indicative of scleritis. If I’m not sure, I’ll use the phenyl- ephrine blanching technique, which is blanching congested Dr. Anesi: Many of my patients are referred to me for conjunctival and superficial episcleral blood vessels with pink eye or uveitis, and they actually have scleritis. I’ve either the 2.5% or the 10% concentration.9,13 If the deep epis- actually had patients with uveitis who later develop scleri- cleral plexus does not blanch, it’s scleritis; if the redness disap- tis independently. Scleritis can crop up later, especially in pears, it’s episcleritis. patients with autoimmune disease. Symptoms that help to differentiate scleritis from other types of eye redness Dr. Toyos: What is your approach to diagnosing these are exquisite tenderness, pain with eye movement or pain patients? that awakens patients from sleep. The association between scleritis and systemic disease has been reported in up to Dr. Chu: We have patients complete an intake question- 50% of cases,6 the most common being rheumatoid arthri- naire, which helps us save time when reviewing the symp- tis, followed by granulomatosis with polyangiitis, inflam- toms and the systems. The intake form is comprehensive, matory bowel disease, and systemic lupus erythematosus, but if a patient comes in with scleritis, we concentrate on the among others.7-10 patient’s history of autoimmune disease, osteoarthritis, and rheumatoid arthritis.14 It’s also important to assess for other Dr. Albini: My patients often complain of focal or pin- collagen-vascular diseases, and focus on that in the physical point tenderness in the involved area. I typically ask patients examination, blood test, and rheumatology consult. We want to lightly close their eyes and gently touch their eyes to know what else may be hiding in their immune system. through the eyelids. If they have scleritis, you will see signs of pain readily. Eye pain is the most consistent symptom. In Dr. Albini: I ask for history of rheumatoid arthritis or systemic the setting of pain, enlargement of the deep scleral vessels vasculitis and order some basic laboratory screening. Recognizing makes the diagnosis. associated systemic conditions is critical to the patient’s overall care, but usually does not change the treatment of scleritis. The Dr. Wang: The most distinctive symptom of scleritis most difficult problem is identifying infectious cases, so I look is orbital pain, which is found in about 60% of patients.11 for corneal changes or intraocular inflammation to tip me off. Many of my scleritis patients present with deep, achy ocu- Continued observation as more aggressive therapies, like oral ste- lar pain that they have a difficult time verbalizing. I agree roids, are initiated is critical because patients who do not respond that not everyone will complain of classic scleritis pain to high-dose steroids are at risk for infectious causes. symptoms, which makes the examination so important. Differentiating between the different types of scleritis and Dr. Toyos: How do you differentiate between viral and between scleritis and episcleritis can be challenging. infectious scleritis? 2 FEBRUARY 2020 DIAGNOSING, TREATING, AND MANAGING SCLERITIS IN 2019 Dr. Chu: Most scleritis cases are noninfectious. The patient’s history is key to diagnosing infectious scleritis, as the majority of cases have an identifiable factor that triggered the symptoms.15 The most common include prior ocular surgery such as pterygium excision, cataract extraction, and scleral buckle.16-18 If the patient has a prior history of ocular surgery, then I am automatically suspicious of infection and (Photo courtesy of David S. Chu, MD.) am quick to take a scleral biopsy to identify the organism. These patients can present with infectious scleritis years after surgery. If the scleritis is unilateral and not responding to therapy, you should suspect a herpetic etiology. It’s estimated that herpes viruses account for 7% of all scleritis cases.19 Dr. Anesi: Scleritis and uveitis have similar symptoms Figure 1. A patient with anterior scleritis. Note the enlargement of the deep at presentation: redness and pain. However, with scleritis, scleral vessels. there’s almost always a distinct lack of light sensitivity, pho- tophobia, or visual changes. Uveitis is extremely symptomat- Dr. Albini: As I mentioned, response to treatment is criti- ic, poses a threat to vision, and typically occurs in older peo- cal. Almost all cases of noninfectious scleritis should improve ple. Bright light tends to exasperate symptoms. Uveitis is typ- on 1 mg/kg of oral prednisone. If the scleritis does not ically unilateral and patients present with increased vascular improve, it may be time for a diagnostic procedure to see if dilation over the ciliary body. If you have someone with just an infectious etiology can be cultured. redness in their eye and the deep scleral vessels are involved, you can often tell that from the examination. However, if the Dr. Wang: When diagnosing scleritis, I look for the five patient has posterior scleritis, it becomes more challenging most common underlying causes: rheumatoid arthritis, to diagnose because you don’t know if it’s the eyeball or the lupus, polyarteritis nodosa, granulomatosis with polyangiitis, part of the orbit. It’s all very closely associated. and relapsing polychondritis. The challenge is there is not When it comes to working up the patient, unilateral a single blood test available to diagnose these conditions, versus bilateral symptoms make a big difference to me.