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.

Smoking as a risk factor for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome.

PURPOSE: To investigate the relationship of smoking to choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). DESIGN: Retrospective, case-control study. PARTICIPANTS: A total of 568 patients 18 to 50 years of age, 142 of whom were diagnosed with CNV secondary to POHS in a private retina practice between July 1, 2000, and August 1, 2010. Four hundred twenty-six were controls selected from a private comprehensive ophthalmology practice at the same location. METHODS: A retrospective medical record review was performed for all participants. Age, gender, zip code, CNV diagnosis date, insurance status, and smoking status at CNV diagnosis date were collected first for the POHS patients. For each of these 142 patients, 3 randomly selected comprehensive clinic patients, whose visit date fell within 3 months of the corresponding POHS patient's CNV diagnosis date, served as controls. Age, gender, zip code, visit date, reason for visit, insurance type, and smoking status were recorded. Descriptive statistics were calculated for cases and controls. MAIN OUTCOME MEASURES: Logistic regression analyses were performed for both univariate and multivariate models, with CNV secondary to POHS as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, insurance type, median household income, and education level. RESULTS: The mean age of patients with CNV secondary to POHS was 39.0±7.1 years, whereas that of the control patients was 35.7±9.1 years. Of the patients with CNV secondary to POHS, 47.2% were current or former smokers (42.3% current, 4.9% former). Of the control patients, 22.5% were current or former smokers (21.8% current, 0.7% former). Age, insurance type, median income, educational attainment, and smoking status were significant in the univariate models. In the final adjusted logistic regression model, only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.07; P = 0.001), level of educational attainment by zip code (OR, 0.95; 95% CI, 0.92-0.98; P = 0.001) and smoking status (OR, 2.83; 95% CI, 1.86-4.31; P<0.0001) were significant. CONCLUSIONS: The odds of a smoker having CNV secondary to POHS are almost 3 times that of a nonsmoker. In this study, the odds of having CNV secondary to POHS increased with age and decreased with increasing level of educational attainment.

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.

A unique case of autoimmune retinopathy associated with anti-alpha-enolase antibodies.

Background. We report a case of autoimmune retinopathy associated with anti-alpha-enolase antibodies with unique manifestations. Methods. A case report. Results. A 30-year-old male experienced recurrent, primarily peripheral visual field disturbances and minimal photopsia, with interval symptom resolution. Fundus changes subsequently developed in areas corresponding to the previous visual field symptoms. Electroretinogram showed bilaterally symmetric abnormalities of light-adapted responses and suggested loss of photoreceptor function. Only anti-alpha-enolase antibodies were detected on Western blot. Our patient noted cutaneous symptoms at the time of both episodes of visual symptoms, but not in the interim. Biomicroscopy revealed subtle small reddish spots in areas of the peripheral retina corresponding to the areas of the patient's visual field where he noted symptoms. To our knowledge these reddish spots have not been reported in autoimmune retinopathy and may clinically support in vitro and in vivo evidence that anti-alpha-enolase antibodies may target photoreceptors. Conclusions. Our patient demonstrates some unique features adding to the known characteristics of autoimmune retinopathy associated with anti-alpha-enolase antibodies. As more cases are reported, further understanding of the features and pathophysiology of this rare condition will hopefully be elucidated.

Two patients with the von Szily reaction: herpetic keratitis and contralateral retinal necrosis.

PURPOSE: To present two patients with prior unilateral, herpetic keratitis who developed acute retinal necrosis (ARN) in the contralateral eye. These cases have noticeable similarities to the von Szily reaction. This describes the development of a contralateral retinitis subsequent to an anterior chamber injection of herpes simplex virus (HSV). DESIGN: Interventional case series. METHODS: Retrospective chart and literature review. RESULTS: The first patient had neonatally acquired herpetic keratitis and developed ARN at age 21. Polymerase chain reaction of a vitreous biopsy detected HSV type-2 (HSV-2). The second patient was clinically diagnosed with ARN contralateral to varicella zoster keratitis. A detailed literature search located seven prior case reports with a von Szily reaction. These resembled our two cases except none had HSV-2 or years of latency from keratitis to retinitis. CONCLUSIONS: Clinicians need to be cognizant of the von Szily reaction.