Characterization of autoimmune eye disease in association with Down's syndrome.

BACKGROUND: Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. RESULTS: We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. DISCUSSION: A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

Bilateral Acute Iris Transillumination Associated with Moxifloxacin Antibiotic Use.

PURPOSE: To describe the clinical and demographic characteristics and associated factors leading to bilateral acute iris transillumination (BAIT) syndrome. METHODS: A retrospective review of patients with BAIT syndrome was performed. RESULTS: Thirty-five patients with a diagnosis of BAIT were identified. The median age at presentation was 53 years; 80% of the patients were female. Twenty-six patients (74%) had recent histories of systemic antibiotic treatment. Of those with such a history, 24 patients (92%) had been receiving moxifloxacin. Two patients within our cohort were prescribed moxifloxacin prophylactically prior to a systemic surgical procedure and had no evidence of systemic illness or recent viral illness. CONCLUSIONS: Our data support the notion that moxifloxacin might be associated with the onset of BAIT syndrome. Notably, within our cohort, two patients received moxifloxacin as surgical prophylaxis and subsequently developed BAIT syndrome. This could suggest a potential association between moxifloxacin and the onset of BAIT, though further studies are needed to confirm this finding.

Characterization of autoimmune eye disease in association with Down's Syndrome.

Background Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down Syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In 3 consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. Subjects/Methods: This was a multicentered, retrospective case series. De-identified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. Results We characterized 8 subjects (mean age 29 [range, 19-37] years). The mean age of uveitis onset was 23.5 [range, 11-33] years. All 8 subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in 6 and 5 subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. Discussion A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in 3 subjects in our series supports a causal association between DS and autoimmune eye disease.

The impact of polymerase chain reaction (PCR) on diagnosis and management of infectious uveitis at a tertiary care facility.

BACKGROUND: Polymerase Chain Reaction (PCR) is a well-accepted adjunct in the management of infectious uveitis. In turn, few reports in the literature have evaluated how PCR then impacts patient care. This study aims to evaluate the impact of PCR sampling on diagnosis and treatment of infectious uveitidies at a large tertiary care facility. MAIN BODY: This is a retrospective, observational study of patients with aqueous and vitreous PCR samples obtained from 2014 to 2019. The study was undertaken at a single institution. At least one follow up visit following results of PCR testing was required for inclusion. If a patient had multiple PCR samples taken, only the first sample was included. The patients were divided into three categories based on pre-sampling diagnosis. A chi-square test was used to analyze the data. 108 cases were available for analysis. PCR did not change diagnosis or management in any of the cases where pre-sampling diagnosis carried a high clinical suspicion for negative PCR. Overall, the results of PCR testing had a more significant impact on diagnosis in those cases where pre-sampling diagnosis was unknown versus those where it was confirmatory in nature, thus presumed to be related to an infectious entity tested by PCR (74% vs. 29%, p = 0.00006). The rate of treatment change based on PCR was similar between those cases where there was a high clinical suspicion for positive PCR and those where pre-sampling diagnosis was unknown (32% vs. 33%, p = 0.95). Further analyzing specimens separately depending on source of sample, this pattern persisted for aqueous samples, with PCR showing a more significant impact on diagnosis in those cases where the diagnosis was unknown versus those where sampling was confirmatory (86% vs. 31%, p = 0.00004). The rate of change in treatment between the two groups was similar (35% vs. 31%, p = 0.79). Vitreous samples followed a similar pattern with a higher rate of diagnosis change for those cases where pre-sampling diagnosis was unknown and a similar rate in treatment change between the two groups, however this did not reach statistical signifigance (44% vs. 25%, p = 0.28; 27% vs. 33%, p = 0.74). CONCLUSION: There is no well-defined algorithm as to when to employ PCR testing in uveitis. As expected, in our experience, it has the largest impact on diagnosis when the diagnosis is unknown, however even when confirmatory in nature, it continues to impact patient management.

Management Strategies of Acute Retinal Necrosis: Current Perspectives.

Acute retinal necrosis is a rare yet devastating disease, with significant ocular morbidity. Over the past several decades, initial treatment regimens have shifted from intravenous antivirals requiring hospital admission to the routine use of oral antivirals with intravitreal antivirals for immediate local control. Given the rarity of this disease process and a lack of large-scale research trials, debate continues over recommended practice guidelines. In this paper, we review current diagnostic criteria and recommend a treatment algorithm based on available evidence.

OCT Angiography and En Face OCT Reflectance Aid in Monitoring Subclinical Inflammation in Serpiginous Choroidopathy.

Introduction. We present a case of serpiginous choroidopathy (SC) with novel OCTA and en face OCT reflectance findings which help identify subclinical disease progression. Case Presentation. En face OCT reflectance images demonstrated outer retinal tubules (ORT) at the serpiginous lesion margins of affected and unaffected retina on multimodal imaging. OCTA findings demonstrate variable dropout of choriocapillaris in "normal" retina beyond lesion borders which was not visible on standard imaging and which demonstrated a clear transition zone beyond the ORT. Discussion. This is the first report of choriocapillaris atrophy identified on OCTA not identified on traditional multimodal imaging in serpiginous choroidopathy. Damage to vasculature only visible with OCTA may help characterize the distribution of inflammation, aiding in monitoring of suppression not illustrated by traditional imaging and which may threaten the central macula. ORT in SC suggest death and reorganization of outer segments from dysfunction of the choriocapillaris and RPE, as well as serve to demarcate the area of chronic or old inflammation, supporting the hypothesis that the choriocapillaris is the primary site of inflammation in SC. Based on these findings, we recommend OCTA on all patients with serpiginous choroidopathy to monitor underlying state of inflammation and help determine immunosuppressive threshold.

Association of Low Vitamin D Levels with Noninfectious Uveitis and Scleritis.

Purpose: To determine whether an association between Vitamin D and noninfectious ocular inflammation exists. Methods: Retrospective case-control study with 765 patients (333 uveitis cases, 103 scleritis cases, 329 controls). Logistic regression models examined the relationship between hypovitaminosis D and ocular inflammation. Results: The odds of having uveitis were 1.92 times higher for patients with hypovitaminosis D compared to patients with normal Vitamin D levels in the multivariate analysis [odds ratio (OR) = 1.92, 95% Confidence Interval (CI) = 1.36-2.72, p = 2.32 × 10-4]. A secondary analysis demonstrated that the odds of developing uveitis or scleritis were 5% lower and 4% lower, respectively, for every unit increase in Vitamin D level (uveitis: OR = 0.95, 95% CI = 0.94-0.97, p = 9.87 × 10-6; scleritis: OR = 0.96, 95% CI = 0.93-0.99, p = 0.009). Conclusion: Hypovitaminosis D was associated with increased risk of ocular inflammation in this retrospective study.

Intravitreal rituximab for the treatment of a secondary intraocular relapse of a large B-cell lymphoma.

PURPOSE: To report a rare case of secondary intraocular lymphoma treated with intravitreal rituximab, following pars plana vitrectomy. OBSERVATIONS: A 74-year-old female with history of parotid gland large B-cell lymphoma presented bilateral intraocular recurrence 10 years after the onset of the primary malignancy. Systemic work-up including PET/CT Scan, bone marrow biopsy, brain MRI and CSF analysis were unremarkable, and the patient declined to undergo systemic chemotherapy. Vision loss in her left eye was severe due to significant sub-retinal pigment epithelium (RPE) infiltration involving the macula; this eye was treated with external beam radiation therapy. On the right eye, the relapse manifested with vitreous involvement and fovea-sparing multifocal, sub-RPE infiltration for which the patient received monthly intravitreal rituximab injections, following pars plana vitrectomy. Through the course of therapy, the patient achieved good local control and maintained 20/20 visual acuity on her right eye. Brain magnetic resonance imaging (MRI) surveillance, every 3 months, was performed and revealed a cerebellar recurrence 24 months into the course of therapy. CONCLUSIONS AND IMPORTANCE: Our case illustrates how intravitreal immunotherapy with rituximab may provide local control of CD-20 positive secondary intraocular lymphoma; particularly in cases where systemic therapy is not amenable. In our case, a prior vitrectomy, did not appear to interfere with the therapeutic effect of intravitreal rituximab. Close quarterly surveillance with Brain MRI may help disclose central nervous system recurrences in such cases.

Cataract Surgery Complications in Uveitis Patients: A Review Article.

Uveitis is a leading causes of blindness worldwide, and the development of cataracts is common due to both the presence of intraocular inflammation and the most commonly employed treatment with corticosteroids. The management of these cataracts can be very challenging and often requires additional procedures that can compromise surgical results. The underlying disease affects a relatively young population at higher risk of complications. Preoperative control of inflammation/quiescent disease for at least three months is generally accepted as the minimum amount of time prior to surgical intervention. Phacoemulsification with intraocular lens is the preferred method for surgery, with some studies showing improvement in visual acuity in over 90% of patients. The most common postoperative complications include macular edema, posterior capsule opacification, recurrent or persistent inflammation, glaucoma, epiretinal membrane and IOL deposits, or dislocation. Despite the potential complications, cataract surgery in uveitis patients is considered a safe and successful procedure.

SPONTANEOUS CLOSURE OF A FULL-THICKNESS MACULAR HOLE SECONDARY TO IRVINE-GASS SYNDROME.

PURPOSE: To report a case of spontaneous closure of a full-thickness macular hole after a posterior subtenon injection of triamcinolone in a patient with Irvine-Gass syndrome. METHODS: Case report and literature review. RESULTS: A 70-year-old man presented to the retina clinic with visual disturbance in his right eye after an uneventful cataract surgery. Patient was found to have macular edema associated with a full-thickness macular hole, treated with a posterior subtenon injection of triamcinolone with subsequent spontaneous closure of the hole and excellent visual acuity. CONCLUSION: This case demonstrates possible resolution of a condition which traditionally requires surgical intervention, with a nonsurgical approach.

Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia.

BACKGROUND: Most patients with migraine report photophobia associated with headache; a subset report interictal photophobia. These patients are light sensitive even during headache-free periods. The objective of this case-control study was to assess the prevalence of symptoms of anxiety and depression in migraine patients with and without interictal photophobia. METHODS: We recruited 16 subjects with migraine and interictal photophobia, 16 age- and gender-matched migraine subjects without interictal photophobia, and 16 age- and gender- matched controls. Migraine subjects met International Headache Society classification criteria. Participants completed a photophobia questionnaire, Beck Depression Inventory (BDI-II), and Beck Anxiety Inventory (BAI). Chi-square analyses and two-tailed Wilcoxon rank sum tests were used for the analyses. RESULTS: Subjects with interictal photophobia had significantly higher scores on the photophobia questionnaire compared to subjects without interictal photophobia. Subjects with interictal photophobia had significantly higher scores on the BDI-II and BAI compared to subjects without interictal photophobia. CONCLUSIONS: Migraine patients with interictal photophobia are more likely to manifest symptoms of depression and anxiety compared to migraine patients without interictal photophobia. Care providers should be aware of increased prevalence of these symptoms in this population and consider appropriate referrals. Future research could assess whether treatment of photophobia leads to improvements in symptoms of depression and anxiety in migraine patients.