Anterior and Intermediate Uveitis Following Yellow Fever Vaccination with Fractional Dose: Case Reports

Purpose: To describe two cases of anterior and intermediate uveitis following yellow fever vaccination with fractional dose.

Methods: Case report.

Results: Case 1: A 35 year-old healthy woman presented with unilateral anterior uveitis 10 days after the yellow fever vaccination. Testing excluded infectious and rheumatic diseases and the episode was fully recovered after a short course of topical treatment. Case 2: A 21 year-old previously healthy woman presented with blurred vision in the left eye (OS) 14 days after the yellow fever vaccination. The ophthalmic examination of the OS revealed intermediated uveitis. Testing excluded infectious and neurological diseases. After six weeks of treatment with oral prednisone, the ocular inflammation had resolved.

Conclusion: Physicians should be aware of the possibility of eye inflammation following the yellow fever vaccination.     

Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis Associated Uveitis

Purpose: To identify the clinical features and prognostic factors of uveitis associated with ankylosing spondylitis (AS).

Methods: This retrospective, interventional case series study reviewed the medical records of 91 AS patients with uveitis.

Results: The characteristics of AS-associated uveitis included male preponderance (70%), average onset in the fourth decade, unilateral manifestation (87.9%), and vitreous involvement or retinal vascular leakage (36.3%). All patients had acute anterior uveitis. The best corrected visual acuity in logMAR improved from 0.8 ± 0.3 to 0.1 ± 0.2. The use of biologic agents was the only significant factor in the multivariate analysis. Patients with vitreous involvement/retinal vascular leakage were more likely to use systemic/peribulbar steroids for inflammation control, and achieved equally favorable visual outcome as in those without vitreous involvement/retinal vascular leakage.

Conclusion: The clinical characteristics and profile of visual prognostic factors suggest an association between the severity of ocular inflammation and systemic disease.     

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-Positive and HIV-Negative Patients in South Africa

Purpose: To use polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) calculation to diagnose infectious uveitis.

Methods: Prospective cross-sectional study.

Results: Twenty-seven of 106 patients had positive PCR and/or GWC results on aqueous humor (AH) sampling and 15 of 27 (55.6%) were HIV-positive. Patients with non-anterior uveitis (NAU) were more likely to be HIV+ (p = 0.005). More than 1 possible pathogen was identified in 9 of 27 patients of whom 7 were HIV+. The final clinical diagnosis was discordant with AH findings in 9 of 27 cases. A positive EBV PCR result was associated with a discordant diagnosis (p = 0.001). All cases of herpetic anterior uveitis (42.9% HIV+) tested PCR-/GWC+ while all cases of herpetic NAU tested PCR+/GWC- (83.3% HIV+). All rubella virus cases were PCR+/GWC+.

Conclusion: PCR is useful to diagnose herpetic NAU in HIV+ patients while GWC is useful to diagnose herpetic anterior uveitis.     

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.     

Rapid and Sustained Efficacy of Golimumab in the Treatment of Multirefractory Uveitis Associated with Behçet’s Disease

Purpose: To evaluate golimumab (GOL) efficacy in the management of Behçet’s disease (BD)-related uveitis.

Methods: We retrospectively collected data from 5 patients (8 eyes) with at least two recent relapses of uveitis, treated with GOL at the standard dose of 50 mg every 4 weeks.

Results: A complete control of intraocular inflammation was observed in 7/8 eyes (87.5%) at 12-month follow-up. The number of relapses 12 months before and after GOL initiation was 11 and 1, respectively. At baseline, four eyes had active retinal vasculitis (RV). At 3-month follow-up evaluation RV resolved in all eyes. Mean Best Corrected Visual Acuity was 6.93 ± 4.34 at baseline and 7.32 ± 3.87 at 12-months follow-up.

Conclusion: We confirm GOL efficacy in reducing intraocular inflammation in BD, both in term of reduction in the number of uveitis relapses and in achieving a prompt resolution of active RV.     

Certification of Vision Impairment in Patients with Uveitis Attending a Specialist Clinic

Purpose: To identify the causes of severe visual loss in a UK uveitis clinic, to suggest means of reducing incidence, and to propose improvement in data collection of vision impairment.

Patients and methods: Retrospective case series.

Results: Over 128 months, 76 (3.5–4% of patients referred) were certified as vision-impaired or severely vision-impaired. The mean age at registration was 48.4 years, 76% were of working age, and 7% were children. The diagnosis leading most often to registration was sympathetic ophthalmia and the most frequent uveitis complications were secondary cataract (whether or not operated upon) in 62%, chronic cystoid macular edema in 43%, and secondary glaucoma in 28%. Visual loss was often multifactorial.

Conclusions: Severe and permanent visual loss in uveitis affects people predominantly of working age. It is probably underreported and a restructuring of the certificate of vision impairment may improve data collection. Early referral to a tertiary center may reduce the incidence of vision impairment.     

An Intraocular Inflammatory Profile of Rubella Associated Uveitis

Purpose: To analyze intraocular cytokine levels and cell profiles in patients with rubella virus-associated uveitis (RVU).

Methods: We collected intraocular fluid samples from patients with RVU (n = 10), uveitis of other causes (n = 27), and cataract (n = 22). Levels of 15 cytokines (IL-1β, IL-1ra, IL-2, IL-6, IL-6rα, IL-7, IL-8, IL-10, IL-17A, IL-23, TARC, MCP-1, TNF-α, PlGF, and VEGF) were measured using multiplex assay, and intraocular cell populations were determined by multiparameter flowcytometry. Clinical characteristics of RVU patients were collected and compared to laboratory outcomes.

Results: RVU patients exhibited high intraocular levels of MCP-1, IL-6rα, and TARC, whilst patients with noninfectious uveitis were characterized by high levels of PlGF. Cataract patients showed high levels of IL-2 and IL-23. Intraocular cell population of RVU patients disclosed mainly T-cells and monocytes/macrophages and B-cells were scarcely detected.

Conclusion: RVU patients exhibit a cytokine profile distinct from noninfectious uveitis and cataract.     

Multiple Evanescent White Dot Syndrome Following Intradermal Influenza Vaccination

Purpose: To present a case report of MEWDS following an intradermal influenza vaccination.

Methods: Review of the clinical, laboratory, photographic, and angiographic records of a patient with MEWDS.

Results: 27-year-old female that presented to our clinic with photopsias OD. These symptoms began 2 weeks following an influenza intradermal vaccination.

Fundus examination and diagnostic testing were consistent with MEWDS.

Conclusion: While rare, MEWDS can occur following influenza vaccination.     

Effect of Adalimumab on Peripheral Blood Mononuclear Cells in Non-Infectious Uveitis

Purpose: This study analyzed the effect of adalimumab on peripheral blood mononuclear cells (PBMCs) in uveitis.

Methods: PBMCs and serum S100A12 levels from 14 uveitis patients and 28 healthy controls were analyzed. Patient samples were taken before (w0), and 6 (w6) and 12 (w12) weeks after initiation of adalimumab therapy.

Results: Monocytes expressing CD124, CD86, CD39, CD115, and MHCII were decreased in patients. Adalimumab induced CD86+ and CD39+ monocytes, and further decreased the frequency of MHCII- and CD124-positive cells. Patients (w0) had increased percentages of Th1-, Th17-, and Th2 cells and T cell subsets showed a pro-inflammatory polarization (p = 0.02 ratio Th17/Treg patients w0 vs controls), which was reduced upon adalimumab treatment (p = 0.05 w0 vs w6). S100A12 levels were increased in patients (p = 0.02) and reduced under treatment (p = 0.02 for w6/w12).

Conclusions: The phenotype of PBMCs from uveitis patients is modified upon adalimumab treatment. Serum S100A12 levels reflect the systemic immune response.     

The Challenge of Pediatric Uveitis: Tertiary Referral Center Experience in the United States

Purpose: To describe the distribution, clinical findings, visual outcomes, treatment, and complications of children with uveitis at a tertiary referral ophthalmic center.

Methods: Retrospective cohort study. We reviewed the medical records of all patients ≤16 years with uveitis referred to Massachusetts Eye Research and Surgery Institution from March 2005 to July 2016.

Results: Of 286 included children, 62.24% were female. Mean age of onset was 8.4 years. The uveitis was mainly anterior (61.9%), recurrent (68.53%), bilateral (81.82%), and noninfectious (96.5%). Idiopathic cases accounted for 51.4%. The most frequent systemic association was juvenile idiopathic arthritis (34.96%). The majority of patients (78.32%) experienced complications. All patients, except one, needed systemic therapy.

Conclusion: Pediatric uveitis is challenging to diagnose and manage, with frequent and potentially severe complications. Most cases were bilateral, recurrent, and idiopathic. Prompt referral to uveitis-specialized centers and an appropriate systemic therapy are mandatory for good visual outcomes.     

Clinical Features and Prognosis of Uveitis in a Turkish Patient Population with Ankylosing Spondylitis: Incidence and Management of Ocular Complications

Purpose: To investigate clinical features, visual prognosis, and ocular complications in patients with ankylosing spondylitis (AS)-associated anterior uveitis (AU).

Methods: Data of 211 eyes of 145 patients with AU associated with AS were reviewed retrospectively.

Results: Mean follow-up time was 6.31 ± 6.33 years. Men were younger than women at AS diagnosis (p = 0.035). The mean number of uveitis flares was highest during the first quarter of the year and lowest during the third quarter (p = 0.017). Immunosuppressive agent use was higher in women than men (p = 0.052). Ocular complications developed in 120 eyes (56.9%), and the complication rate was 0.146/eye year. Males developed cystoid macular edema more frequently than females (p = 0.05). Glaucoma was observed more often in early-onset disease (age at AS onset <45 years) than late-onset disease (p = 0.028).

Conclusions: Visual prognosis of AU in patients with AS was good, although more than half of the eyes developed ocular complications (56.9%).     

Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine the Role of Epstein-Barr Virus in Uveitis

Purpose: To use polymerase chain reaction (PCR) and Goldmann-Witmer Coefficient (GWC) calculation to search for evidence that Epstein-Barr virus (EBV) causes uveitis.

Methods: A prospective cross-sectional study where participants with positive multiplex EBV PCR results were further investigated by: 1) real-time PCR for EBV viral loads (VL) and 2) EBV GWC.

Results: Eleven of 106 consecutive uveitis patients (10.4%) had positive multiplex PCR for EBV on aqueous humor sampling and 7/11 (63.6%) were HIV-positive. Only 4/10 (40%) cases had detectable intraocular EBV VLs which were always lower than the blood or plasma VL. EBV GWC was negative in all 10 cases tested. In 9/11 (81.8%) of these cases an alternative, more plausible cause of uveitis was identified.

Conclusion: We found no evidence of active intraocular replication or antibody production to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified.     

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

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.     

Ocular Manifestations and Visual Outcomes of Behçet’s Uveitis in a Thai population

Purpose: To report on ocular manifestations and visual outcomes of Thai patients with Behçet’s Uveitis (BU).

Methods: We reviewed medical records of 50 BU patients (31 males and 19 females). Ocular manifestations, treatment modalities, complications, and visual outcomes were registered.

Results: Ocular involvement was bilateral in 76% of patients, resulting in 89 affected eyes. Panuveitis and posterior uveitis were the most common types. Retinal vasculitis was noted in majority of affected eyes and specifically arteritis was noticed in 32/57(56%). Most patients received combination therapy of systemic corticosteroids and immunosuppressive agents (azathioprine 72%). At final visit, VA ≤20/200 was observed in 25 affected eyes (28%). Risk factors for poor visual outcome were poor visual acuity at presentation (p < 0.001) and development of optic atrophy (p = 0.01).

Conclusions: Typical ocular manifestations of Thai patients with BU consisted of bilateral uveitis affecting posterior eye segment with high rate of complications and frequent visual loss.     

Long-Term Efficacy and Safety of Interferon Alpha-2a in the Treatment of Chinese Patients with Behçet’s Uveitis Not Responding to Conventional Therapy

Purpose: To investigate the long-term efficacy and safety of interferon alpha-2a (IFNα-2a) in Chinese patients with Behçet’s uveitis (BU) refractory to conventional therapy.

Methods: In a prospective observational cohort study, 127 patients were treated with an initial dosage of 3 million units per day in the first three months, followed by gradual tapering of the dose.

Results: After 3 months of treatment, IFNα-2a was shown to be effective in 115 cases (91%). At the end of the 1-year follow-up, the frequency of ocular relapses decreased to 1.59 ± 1.68 per year (ranging 0–6) (p < 0.001), as compared to 5.09 ± 2.51 per year (ranging 3–15). Moreover, the frequency of oral ulcer relapses also decreased to 2.49 ± 1.84 per year (ranging 0–6) (p < 0.001), as compared to 8.20 ± 3.72 per year (ranging 2–10). Visual improvement or stability was observed in 32 patients (59%) in these 54 patients. During a mean follow-up of 11 months (range 3–33), the mean final VA (logMAR) had progressed from 1.0 logMAR to 0.8 logMAR in all treated patients.

Conclusions: Long-term low dose of IFNα-2a is useful in treating Chinese BU patients who do not respond adequately to conventional therapy.     

Risk Factors for Development of Rhegmatogenous Retinal Detachment in Patients with Uveitis

Purpose: To describe risk factors for development of rhegmatogenous retinal detachment (RRD) in patients with uveitis.

Methods: We performed a retrospective review of 411 consecutive human immunodeficiency virus-negative patients with uveitis (571 affected eyes) and report on prevalence, risk factors and visual outcomes of patients with RRD.

Results: Prevalence of RRD was 7% of all patients with uveitis. Multivariate analysis revealed that posterior uveitis and panuveitis were associated with RRD (P = 0.001). Strong association between RRD development and infectious uveitis was also observed (P = 0.009). Acute retinal necrosis (ARN) was firmly associated with RRD development (P = 0.016). Although anatomical success was obtained, functional outcome was poor. Poor visual outcomes at 6-month and 1-year follow-up were associated with initial VA < counting fingers (P = 0.05, P = 0.044).

Conclusions: Prevalence of RRD in uveitis was 7% and development of RRD was encountered in posterior and panuveitis. Infectious uveitis (specifically ARN) formed a high risk for RRD.     

Difluprednate 0.05% versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: Pooled Efficacy Analysis of Two Phase 3 Studies

Purpose: To analyse pooled data from 2 similar phase 3 noninferiority studies comparing difluprednate 0.05% versus prednisolone acetate 1% in patients with endogenous anterior uveitis.

Methods: Patients received difluprednate alternating with vehicle or prednisolone acetate for 14 days (8 drops/day in both groups), followed by tapering from day 14 to 28. All patients were observed until day 42.

Results: More patients on difluprednate than on prednisolone acetate were cleared of anterior chamber cells on day twenty one (71.3% vs 54.7%; p = 0.02); results were similar at the other time points. Treatment withdrawals were higher with prednisolone acetate than difluprednate (19.8% vs 7.4%; log-rank p = 0.02). Study discontinuation due to lack of efficacy was also higher with prednisolone acetate than difluprednate (14.0% vs 0%; p = 0.0002 [pre-specified exploratory analysis]).

Conclusions: More difluprednate-treated eyes were quiet following 21 days of treatment, and difluprednate-treated patients were much less likely to be withdrawn from the study because of treatment failure.     

Ten-Year Retention Rate of Infliximab in Patients with Behçet’s Disease-Related Uveitis

Purpose: To evaluate the 10-year drug retention rate of infliximab (IFX) in Behçet’s disease (BD)-related uveitis, the effect of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on drug survival and differences according to the lines of biologic treatment.

Methods: Cumulative survival rates were studied using the Kaplan-Meier plot, while the Log-rank (Mantel-Cox) test was used to compare survival curves.

Results: Forty patients (70 eyes) were eligible for analysis. The drug retention rates at 12-, 24-, 60- and 120-month follow-up were 89.03%, 86.16%, 75.66% and 47.11% respectively. No differences were identified according to the use of concomitant DMARDs (p = 0.20), while a statistically significant difference was observed in relation to the different lines of IFX treatment (p = 0.014). Visual acuity improved from baseline to the last follow-up visit (p = 0.047) and a corticosteroid-sparing effect was observed (p < 0.0001).

Conclusions: IFX retention rate in BD-uveitis is excellent and is not affected by concomitant DMARDs.     

Ultra-Wide Field Imaging Characteristics of Primary Retinal Vasculitis: Risk Factors for Retinal Neovascularization

Aim: To evaluate patterns of retinal vasculitis with ultra-wide field imaging (UWF) and ascertain the risk factors for retinal neovascularization.

Methods: Consecutive patients of retinal vasculitis were included prospectively. Patients with retinal vasculitis secondary to uveitis were excluded. UWF was done for all the patients. Retinal involvement was classified into three zones and area of capillary non-perfusion was stratified into clock hours.

Results: Two hundred patients were included, 85% (n = 170) were male. Mean age was 28.99 ± 10.56 years. Clinical examination revealed 65% cases (n = 130) to be bilateral, while UWF angiography detected 72.5% (n = 145) to have bilateral involvement. Retinal neovascularization was present in 47% (n = 188).Presence of posterior disease had very high odds ratio for development of retinal neovascularization as compared to cases restricted to retinal periphery (OR = 45.03, CI = 6.10–332.30, p = < 0.001).

Conclusion: UWF imaging is useful in detecting retinal vasculitis, which is otherwise obscure to clinical examination and assessing risk factors for retinal neovascularization.