Wendy M. Smith

Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

PURPOSE To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. DESIGN Modified Delphi process. METHODS A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. RESULTS There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. CONCLUSIONS Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Lack of Consensus in the Diagnosis and Treatment for Ocular Tuberculosis among Uveitis Specialists

Abstract Purpose: To assess the approach of specialists to ocular tuberculosis (TB). Methods: The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Results: Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1–75%) or that a patient with a risk factor for TB had ocular TB (range 0–90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Conclusions: Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

Gender and Spondyloarthropathy-Associated Uveitis

Spondyloarthropathies encompass a group of inflammatory diseases with arthritis and other features such as enthesitis and dermatologic and gastrointestinal involvement. Up to 37% of spondyloarthropathy patients may develop uveitis which is typically bilateral asynchronous acute anterior uveitis. Spondyloarthropathies with and without uveitis are more prevalent among males; the reasons for gender imbalance are unclear. This review will focus on gender differences in the prevalence, incidence, clinical manifestations, and prognosis of uveitis associated with spondyloarthropathies.

Orbital and external ocular manifestations of Mycobacterium tuberculosis: A review of the literature

Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis that most commonly affects the lungs. However, extrapulmonary manifestations of TB can affect the eye and surrounding orbital tissues. TB can affect nearly any tissue in the eye, and a high index of suspicion is required for accurate diagnosis. Systemic anti-tuberculosis treatment is required in cases of ocular TB, and steroids are sometimes necessary to prevent tissue damage secondary to inflammation. Delays in diagnosis are common and can result in morbidities such as loss of an affected eye. It is important for ophthalmologists and infectious disease specialists to work together to accurately diagnose and treat ocular TB in order to prevent vision loss. This article reports the various known presentations of orbital and external ocular TB and reviews important elements of diagnosis and treatment.

Clinical characteristics of inflammatory ocular disease in anti-neutrophil cytoplasmic antibody associated vasculitis: a retrospective cohort study

Objective To characterize the clinical correlates and outcome of inflammatory ocular disease (IOD) among patients with ANCA-associated vasculitides (AAV). Methods Medical records of potential cases of AAV seen at Mayo Clinic from 2003 to 2013, inclusive, were reviewed to identify confirmed cases meeting the diagnosis of AAV using the Chapel Hill Consensus Conference 2012 descriptors. Records of confirmed cases of AAV were then further reviewed for IOD, and clinical characteristics, treatment and outcomes abstracted. Results A total of 1171 confirmed cases of AAV were identified of which 183 patients (mean age 49.0 years; 51% female; 95% Caucasian) had IOD. The most common manifestation of IOD was injection of the eye (57%) followed by eye pain (46%) and visual acuity loss (18%). Scleritis was the most common type of IOD (22%) followed by episcleritis (21%), orbital inflammation (18%), lacrimal duct stenosis (10%) and uveitis (9%). Oral glucocorticoids were used to treat IOD in the majority of patients (96%). CYC and rituximab were the most frequently used immunosuppressive agents (54 and 36%, respectively). Of those with orbital inflammation, 52% underwent therapeutic surgical intervention. Clinical remission of IOD was achieved in 91% of patients but relapses were seen in 23%. Significant visual acuity loss was observed in only six patients. Conclusion IOD is a common manifestation of AAV and seen in about 16% of patients with AAV. Scleritis, episcleritis and orbital inflammation are the most common subtypes. Most patients respond well to glucocorticoids and immunosuppression, but relapse of IOD is common.

Intraocular manifestations of mycobacterium tuberculosis: A review of the literature

Mycobacterium tuberculosis: is most commonly associated with pulmonary infection. However, tuberculosis (TB) can also affect the eye. TB can affect nearly any tissue in the eye, and a high index of suspicion is required for accurate diagnosis, as many of the intraocular manifestations of TB can mimic other, more common diseases. Correct diagnosis is critical because systemic anti-tuberculosis treatment may be required, and vision loss or even loss of the affected eye can occur without proper treatment. Thus, it is important for ophthalmologists and infectious disease specialists to work together to accurately diagnose and treat intraocular TB. This article reports the various known presentations of intraocular TB and reviews important elements of diagnosis and treatment.

Clinical Characteristics of Ocular Sarcoidosis: A Population-Based Study 1976–2013

ABSTRACT Purpose: To characterize the epidemiology and clinical characteristics of ocular involvement in patients with systemic sarcoidosis. Methods: An inception cohort of patients with systemic sarcoidosis in 1976–2013 in Olmsted County, Minnesota, was identified based on comprehensive individual medical record review. Medical records of those patients were then reviewed for ocular involvement. Results: A total of 345 incident cases of systemic sarcoidosis were identified. Ocular involvement occurred in 23 patients (7%). The most common ocular disease was uveitis (61%) followed by dry eye disease, conjunctival nodule, episcleritis, anterior scleritis, and conjunctivitis. Anterior uveitis was the most common type of uveitis (71%). The visual outcome of uveitis was favorable with only one patient lost three or more lines of VA during follow-up and had VA of less than 20/200 at last visit. Conclusion: Ocular involvement occurred in 7% of sarcoidosis patients. Uveitis was the most common type of ocular disease.

A case of bilateral human herpes virus 6 panuveitis with genomic viral DNA integration.

BackgroundWe report a rare case of bilateral panuveitis from human herpes virus 6 (HHV-6) with genomic viral DNA integration in an immunocompromised man.FindingsA 59-year-old man with history of multiple myeloma presented with altered mental status, bilateral eye redness, and blurry vision. Examination revealed bilateral diffuse keratic precipitates, 4+ anterior chamber cell, hypopyon, vitritis, and intraretinal hemorrhages. Intraocular fluid testing by polymerase chain reaction (PCR) was positive for HHV-6. The patient was successfully treated with intravitreal foscarnet and intravenous ganciclovir and foscarnet. Despite clinical improvement, his serum HHV-6 levels remained high, and it was concluded that he had HHV-6 chromosomal integration.ConclusionsHHV-6 should be considered in the differential for infectious uveitis in immunocompromised hosts who may otherwise have a negative work-up. HHV-6 DNA integration may lead to difficulties in disease diagnosis and determining disease resolution.

Clinical Correlates, Outcomes, and Predictors of Inflammatory Ocular Disease Associated with Rheumatoid Arthritis in the Biologic Era

Objective. Inflammatory ocular disease (IOD) is a rare but severe extraarticular manifestation of rheumatoid arthritis (ExRA) with high mortality. The aim of our study was to examine clinical characteristics of IOD in rheumatoid arthritis (RA) and their effect on disease severity and outcomes in recent years. Methods. A retrospective cohort of RA patients with IOD evaluated between 1996 and 2013 was assembled and compared to RA comparators without IOD and matched for age, sex, and disease duration. Results. We identified 92 patients (69% female; mean age 62 yrs) with IOD: 33 scleritis, 23 episcleritis, 21 peripheral ulcerative keratitis (PUK), 14 uveitis, and 1 with orbital inflammation. The majority of patients with scleritis, episcleritis, and PUK was seropositive versus uveitis (> 80% vs 62%, p = 0.048). PUK and scleritis were more symptomatic compared to episcleritis and uveitis, and often required systemic therapy. Time to resolution was longer in scleritis than episcleritis (p = 0.01). PUK, scleritis, and uveitis had severe ocular sequelae. Prevalence of severe ExRA (18% vs 4%, p = 0.004) and dry eye syndrome (42% vs 26%, p = 0.024) was higher among patients with IOD than comparators. The incidence of new ExRA over 5-year followup was also higher among cases (29% vs 11%, p = 0.022). Ten-year survival was similar among RA patients with and without IOD (66% vs 64%, p = 0.56), with no differences noted among IOD subtypes. Conclusion. This large single-center study highlights the variable presentation and outcomes of IOD in RA. Although ocular complications are associated with significant morbidity, it is reassuring that survival among those with IOD is now similar to those without ocular disease.

Imaging in Uveitis: Spectral Domain and Enhanced Depth Imaging Ocular Coherence Tomography

Ocular coherence tomography (OCT) is one of the most ubiquitous technologies utilized to analyze the posterior segment. It is a non-contact, real-time, imaging technology that generates cross-sectional images of the retina and choroid. OCT is particularly well suited to diagnose and manage posterior uveitides as demonstrated in this chapter by case examples of punctate inner choroidopathy, serpiginous choroiditis, multifocal choroiditis, Vogt-Koyanagi-Harada syndrome, and multiple evanescent white dot syndrome.