Paul A. Kurz

The NOD2 defect in Blau syndrome does not result in excess interleukin 1 activity

OBJECTIVE Blau syndrome is a rare, autosomal-dominant, autoinflammatory disorder characterized by granulomatous arthritis, uveitis, and dermatitis. Genetics studies have shown that the disease is caused by single nonsynonymous substitutions in NOD-2, a member of the NOD-like receptor or NACHT-leucine-rich repeat (NLR) family of intracellular proteins. Several NLRs function in the innate immune system as sensors of pathogen components and participate in immune-mediated cellular responses via the caspase 1 inflammasome. Mutations in a gene related to NOD-2, NLRP3, are responsible for excess caspase 1-dependent interleukin-1beta (IL-1beta) in cryopyrinopathies such as Muckle-Wells syndrome. Furthermore, functional studies demonstrate that caspase 1-mediated release of IL-1beta also involves NOD-2. The aim of this study was to test the hypothesis that IL-1beta may mediate the inflammation seen in patients with Blau syndrome. METHODS IL-1beta release was measured in peripheral blood mononuclear cells cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15) mutation. RESULTS We observed no evidence for increased IL-1beta production in cells obtained from subjects with Blau syndrome compared with healthy control subjects. Furthermore, we presented 2 cases of Blau syndrome in which recombinant human IL-1 receptor antagonist (anakinra) was ineffective treatment. CONCLUSION Taken together, these data suggest that in contrast to related IL-1beta-dependent autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL-1beta or other IL-1 activity.

Adalimumab therapy for refractory uveitis: results of a multicentre, open-label, prospective trial

Objective Tumour necrosis factor (TNF) blockers have been demonstrated to be effective in the treatment of systemic and ocular inflammatory diseases. We conducted a prospective, multicentre, open-label Phase II clinical trial to assess the effectiveness and safety of adalimumab, a fully human anti-TNF monoclonal antibody, in treating refractory uveitis. Methods Subjects with non-infectious uveitis refractory to corticosteroids and at least one other immunosuppressive medication were enrolled. Treatment outcome was ascertained by a composite endpoint comprised of visual acuity, intraocular inflammation, ability to taper immunosuppressives, and posterior segment imaging. Clinical response was defined by improvement in at least one parameter, worsening in none, and well controlled intraocular inflammation. Week 10 responders were permitted to continue receiving adalimumab for the study duration of 50 weeks. Results Twenty-one of 31 patients (68%) were characterised as clinical responders at 10 weeks, of whom 12 patients (39%) exhibited durable response after 50 weeks. The most common reason for study termination was primary or secondary inefficacy. No patients experienced treatment-limiting toxicity clearly related to study therapy. Conclusions Adalimumab was safe and effective in 68% of refractory uveitis patients 10 weeks after study enrolment, and maintained in 39% after 1 year. Ongoing study is required to determine the place of adalimumab and other TNF blockers in the treatment of uveitis.

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.

Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis in a Patient With Antiphospholipid Syndrome

genetic evaluation in any child with suspected genetically controlled retinal pathology. In the updated classification system for CXLRS inclusive of OCT findings, all 4 subtypes demonstrate foveal cystic schisis. Although this patient has multiple features of CXLRS, his lack of this critical finding places him outside this previously described classification system. It has been observed that children with CXLRS may not have clinical foveal changes at birth, but they usually manifest by age 8 years in our experience. The clinical picture of this case is somewhat of an outlier. This case may represent a fifth type of CXLRS with peripheral schisis and no associated macular lamellar schisis or foveal cystic schisis.

Effects of twice-daily topical difluprednate 0.05% emulsion in a child with pars planitis.

Purpose: To report the effects of twice-daily difluprednate in a child with pars planitis (PP). Design/methods: Case report. Results: PP was controlled with topical difluprednate for 1 year. Then an atypical pattern of steroid response—delayed, relatively sudden onset of recalcitrant ocular hypertension (OHT)—and posterior subcapsular cataract (PSC) formation necessitated alternative treatment. Conclusion: Although not a standard treatment, in select cases of PP topical difluprednate therapy could be a useful short-term treatment option while alternative treatments are considered or immunosuppressive agents build to therapeutic levels. Ophthalmologists must be aware of the potential for delayed onset of serious complications when using difluprednate.

Endogenous Endophthalmitis With Brain Abscesses Caused by Streptococcus constellatus

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Macular hole closure and visual improvement with topical nonsteroidal treatment.

technique were not explained. Liquid nitrogen cryotherapy has been proven to be safe and effective for conjunctival malignant neoplasms, and it also appears to be efficacious in the treatment of other ocular conditions, including benign conjunctival vascular tumors, advancing wavelike epitheliopathy, superior limbic keratoconjunctivitis, pterygia, and conjunctival amyloidosis. Based on this case series, liquid nitrogen cryotherapy could be considered an effective surgical alternative in the treatment of conjunctival lymphangiectasia. Repeat cryotherapy may be indicated should recurrent lymphangiectasia occur.

Injectable intraocular corticosteroids

■ Although risks are present, intravitreal corticosteroid injection is a relatively safe and effective treatment in a variety of conditions.