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Ocular inflammatory disease comprises of a diverse group of clinical entities that may result from autoimmune processes, infections, or both. While many individual ocular inflammatory diseases are quite rare, ocular inflammation is one of the more common causes of visual disability, including blindness, in the developed world. Better understanding of ocular inflammatory disease is an important step in designing more sophisticated therapies that may help prevent loss of visual function for these patients.

Objective Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects ∼40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation—AAU—of a multisystem, inflammatory, genetically complex disease, AS. Methods Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA–B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. Results As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA–B). Strong linkage was seen at a region on chromosome 9p21–9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23–1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. Conclusion This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21–9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

Objective To evaluate the clinical usefulness of tumor necrosis factor (TNF) inhibitors in patients with inflammatory eye disease that is resistant to conventional immunosuppressive therapies. Methods Sixteen patients (4 males and 12 females aged 7 to 78 years) who received etanercept (n = 14) or infliximab (n = 2) for either inflammatory eye disease or associated joint disease were studied retrospectively to determine the effect of these medications on their ocular inflammation. Results Nine cases of uveitis and 7 cases of scleritis were treated. Systemic diagnoses included rheumatoid arthritis (n = 8), juvenile rheumatoid arthritis (n = 3), ankylosing spondylitis (n = 1), and psoriatic spondylarthropathy (n = 1). Three patients had uveitis without associated systemic disease. Although 12 of 12 patients with active articular inflammation (100%) experienced improvement in joint disease, only 6 of 16 with ocular inflammation (38%) experienced improvement in eye disease. Five patients developed inflammatory eye disease for the first time while taking a TNF inhibitor. No patient discontinued treatment because of adverse drug effects. Conclusion TNF inhibitors are well tolerated immunosuppressive medications that may benefit certain subgroups of patients with inflammatory eye disease, but they appear to be more effective in controlling associated inflammatory arthritis.

e recently reported that 73.8%of subjects diagnosed withVogt–Koyanaga–Harada (VKH) dis-ease experienced recurrences (Erreraet al. 2011). Based on our experience,we believed that finding an exudativeretinal detachment (ERD) thatresponded to corticosteroids or othermedical treatment more than 1 yearafter onset is low. To better evaluatelate posterior recurrences, we reviewedthe records of a large series of 45patients with VKH disease from fourtertiary centres. The median follow-upduration was 34 months since initialpresentation.Late posterior segment relapses weredefined as posterior segment manifes-tations of inflammation occurring laterthan 52 weeks after first presentationof VKH (Garcia-Valenzuela et al.2000; Sachdev et al. 2008; Dolz-Marcoet al. 2011). The study adhered to thetenets of the Declaration of Helsinki.Relapsing ERDs were noted within10 months after presentation in 16(84%) of 19 subjects who experiencedsuch reactivation, with only four expe-riencing late ERDs, one of whom alsohad early relapses. Report of foursubjects with late ERDs relapses at amedian of 19 months (16–25 months).By examination and optical coher-ence tomography (OCT), subretinalfluid was limited localized areas ofsubmacular ERDs in all late posteriorsegment relapses (Fig. 1).Intravenous pulse therapy was usedwithin the first month for three of thefour subjects who experienced a lateposterior reactivation. In the fourthsubject, the diagnosis of VKH diseasewas made 3 months after the firstinflammatory signs, which caused adelay in the initiation of the correcttreatment. This latter subject had treat-ment with corticosteroids for only1 month, while the other three subjectsreceived an initial duration of systemiccorticosteroids for at least 6 months.In all four subjects, immunosuppres-sive therapy (infliximab, cyclosporin orinterferon) was initiated after the firstrelapse because response to therapywith corticosteroid at acceptable long-term doses was insufficient.All four subjects had been on immu-nomodulatory agents (cyclophospha-mide, infliximab and azathioprine),but these agents had been stopped 5to 13 months prior to the relapse.In one subject, the relapse occurredwhile he was taking 25 mg/day ofprednisone. He had responded to rein-troduction of high-dose corticotherapyfor an episode 6 months previously,and he was on tapering of therapy. Thesecond subject was receiving bothprednisone and cyclophosphamide.The third was on infliximab and low-dose oral corticosteroids at the time ofrelapse.In the experience at our institutionsthere were 4 late relapses (ERDs) of 45subjects with an incidence rate of 12cases per 1000 VKH affected person-years. Late relapses as ERDs occurredin patients receiving early intravenouspulse corticosteroids, and all four hadbeen on other corticosteroid-sparingimmunomodulatory therapy at somepoint. One possible explanation is thatthe need for more aggressive treatmentin our patients with late relapses ofVKH may be a marker of more severedisease. Early corticosteroid-sparingimmunomodulatory therapy might beuseful as first-line therapy to reduce thedevelopment of complications (AbuEl-Asrar et al. 2013). Although it is

Purpose Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare form of uveitis but there is reason to believe that this syndrome is underdiagnosed and renal manifestation may not be treated. Gold standard for diagnosisng TINU is invasive renal biopsy. Here, we show that performing beta-2 microglobulin analysis in urine and HLA typing is helpful to find otherwise undiagnosed TINU cases with subclinical forms of nephritis. Methods Beginning January 2006 we prospectively obtained Ub2MG levels in all children with AU attending our pediatric uveitis clinic for the first time. Mandeville criteria were used to grade certainty of diagnosis. We compared with a healthy control group of children. HLA typing on patients with AU but no nephritis (n =28) by a Luminex-based PCR-SSO typing method was performed in another study. We compared frequencies to normal published controls and a published TINU cohort (n=20). Results The simple screening method of determining urinary Beta-2-Mikroglobulin showed in up to 2/3 of children with new-onset AU subclinical renal manifestation. HLA Typing showed the TINU associated HLA DRB1*0102 in 12.5% of patients with AU with normal renal function opposed to 0.6% in healthy controls (p