The Impact and Implication of Peripheral Vascular Leakage on Ultra-Widefield Fluorescein Angiography in Uveitis

Purpose: To study if peripheral vascular leakage (PVL) on ultra-widefield fluorescein angiography (UWFFA) prognosticates complications of uveitis or necessitates treatment augmentation.

Methods: Retrospective cohort study of uveitis patients imaged with UWFFA and ≥1 yr of follow-up.

Results: We included 73 eyes of 42 patients with uveitis. There was no difference in baseline, intermediate, final visual acuity (p = 0.47–0.95) or rates of cystoid macular edema (CME) (p = 0.37–0.87) in eyes with PVL vs. those without. Eyes with PVL receiving baseline treatment augmentation were more likely to have baseline CME but were not more likely to have impaired visual acuity at final follow-up. PVL was independently associated with treatment augmentation on generalized estimating equation analysis with multivariable linear regression (OR: 4.39, p = 0.015).

Conclusions: PVL did not confer an increased risk of impaired VA or CME at ≥1 yr follow-up but was possibly an independent driver of treatment augmentation.     

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.     

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.     

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.     

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 Profile,Ultra-Wide-Field Fluorescence Angiography Findings,and Long-Term Prognosis of Uveitis in Tubulointerstitial Nephritis and Uveitis Syndrome at One Tertiary Medical Institute in China

Purpose: To analyze the clinical features and long-term prognosis of uveitis in tubulointerstitial nephritis and uveitis (TINU) syndrome in a cohort of Chinese patients.

Methods: A total of 32 patients with TINU syndrome between 2000 - 2016 were analyzed retrospectively.

Results: Mild anterior inflammation was observed in all cases. Ultra-wide-field fluorescence angiography (UWFA) was conducted on 13 patients, and peripheral vascular leakage was observed in 22/26 eyes (84.62%) compared with active anterior chamber inflammation in 13/26 eyes (50%). Three patients received increased corticosteroid dosage therapy on their first episode of uveitis guided by UWFA had stopped steroids without recurrence.

Conclusion: The uveitis in TINU syndrome was mild. Corticosteroids were efficient in most cases, but a slower tapering and long-term treatment were required. UWFA is sensitive in detecting the activity of uveitis and might be useful in monitoring disease progression. Complete withdrawal of medication was difficult to achieve in some cases.     

Glaucoma Secondary to Uveitis in Children in a Tertiary Care Referral Center

Purpose: To study outcome of secondary glaucoma in pediatric uveitis patients.

Methods: Retrospective analysis of records of uveitis patients ≤16 years.

Results: Of 182 pediatric uveitis patients, secondary glaucoma was seen in 48 patients (75 eyes, 26.23%) with female preponderance (F:M-29:19) . JIA was the most common etiology (35.71%). BCVA of ≥20/40 was seen in 22 eyes at presentation and in 38 eyes at final follow up (p<0.001). Twenty eight children (66.67%) received systemic antiglaucoma therapy while 17 children (21 eyes) required surgery (60.71%). Logistic regression showed pseudophakia could predict the higher use of oral antiglaucoma medication (p=0.03) while anatomical site of involvement was predictive of higher chances of surgery (p=0.003). Overall success was seen in 82.10% and 71.64% using IOP limit of 21 and 18 mmHg respectively at mean follow-up of 3.9 years.

Conclusion: Pediatric uveitic glaucoma though require multitude of therapies, can be managed effectively with appropriate therapy.     

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.     

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.     

The Role of IFN-alpha in Experimental and Clinical Uveitis

Purpose: IFN-α is the only treatment capable of inducing long-term remission in some patients with ocular Behçet’s disease. In this review, we focus on immune mechanisms of IFN-α in animal models and patients and compare the outcome of different clinical studies.

Methods: Review of literature using PubMed and Google and original data from rat models with monophasic/chronic or relapsing experimental autoimmune uveitis treated with IFN-α.

Results: The role of IFN-α and its effect on various cell types were investigated, in some cases with contradictory results. Some patients respond very well to IFN-α treatment, while others are non-responders, which was reflected in the uveitis rat models: relapsing uveitis was ameliorated, the monophasic/chronic disease even aggravated.

Conclusions: Despite intensive investigations in patients and animal models, the immune mechanisms explaining the therapeutic effect of IFN-α in ocular Behçet’s disease are not yet fully understood and need further investigation.     

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.     

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.     

Conjunctival Flap with Biodegradable Collagen Matrix Implantation for the Treatment of Scleromalacia after Periocular Surgery

Purpose: To report a new surgical procedure using biodegradable collagen matrix (Ologen) implantation with conjunctival flap for reconstruction of scleromalacia after periocular surgery.

Methods: A total of 26 areas of 25 eyes in 25 patients were included. We divided all eyes according to the preoperative extent of calcified plaque or scleral defect as follows: small, large, and large and severe. Morphologic outcomes were graded from 0 to 7, with higher scores indicating worse cosmetic outcomes.

Results: Mean follow-up period was 8.3 ± 5.6 months. No eyes showed recurrence or specific complications related to Ologen such as implant extrusion or allergic reaction. Minor complications such as flap vessel engorgement and flap hypertrophy were easily treated. Mean morphologic outcome scores were 1.8, 2.4, and 5.3 in groups 1, 2, and 3, respectively.

Discussion: The combined surgery may be an effective and safe procedure for the treatment of scleromalacia after periocular surgeries.     

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.     

Systemic Moxifloxacin in Streptococcus viridans Endophthalmitis

Purpose: To evaluate the effectiveness of prophylactic systemic moxifloxacin in a rabbit model of Streptococcus viridans (S. viridans) endophthalmitis.

Methods: Animals (n=60) were divided into three groups. Intravenous moxifloxacin, vancomycin, normal saline was administered to 20 animals in each group and two hours later, 10⁴ colony-forming units (CFU) of S. salivarius were intravitreally injected into the left eye. Intravenous antibiotics injection was repeated on days 1, 2, and 3 after inoculation. The clinical features, bacterial culture from vitreous aspirates of 10 eyes from each group were evaluated on days 1, 3, 5, and 7. On day 7, eyes for clinical feature examination were enucleated for histopathologic examination.

Results: Clinical scores and log₁₀CFU/ml values were lower in moxifloxacin group on all examination days. Histopathologic examination showed less inflammation and relatively well-preserved retina in the moxifloxacin group.

Conclusions: Systemic moxifloxacin may have a prophyactic effect for S. viridans endophthalmitis after intraocular procedure.     

Enhanced Vitreous Imaging in Uveitis

Purpose: To study the structural visibility of the posterior vitreous cavity and vitreoretinal interface using Spectral Domain–Optical Coherence Tomography in patients with uveitis using conventional, Enhanced Depth Imaging (EDI), Combined Depth Imaging (CDI), and Enhanced Vitreous Imaging (EVI) techniques.

Methods: It was an observational cross-sectional study of 59 eyes of 33 patients between age group 12–72 years (Median 43) diagnosed as uveitis with posterior segment manifestations underwent OCT using conventional, EDI, CDI, and EVI techniques. The visibility of posterior vitreous was graded in all the techniques.

Results: A statistically significant difference was seen in posterior vitreous visibility on comparing all four techniques. EVI showed better visibility of posterior vitreous cavity compared to all other techniques (P < 0.001).

Conclusions: EVI technique provides better structural visibility of posterior vitreous compared to conventional, EDI, and CDI techniques.     

Induction of Vogt-Koyanagi-Harada Disease by Interferon-Alpha and Ribavirin Treatment in Patients with Hepatitis C: A Case Report and Review of the Literature

Purpose: To describe a case of Vogt-Koyanagi-Harada disease (VKH) presenting in a hepatitis C patient after interferon-alpha (IFN-α) and ribavirin treatment.

Methods: A retrospective review of our patient and a review of the published literature.

Results: A 59 year-old man developed VKH after the four months of IFN-α and ribavirin therapy for hepatitis C. The patient’s VKH was controlled by systemic corticosteroids. The relationship between VKH and IFN-α is discussed based on the published literature.

Conclusions: VKH is a rare autoimmune complication triggered by interferon-alpha therapy; the T-cell modulatory properties of IFN-α possibly contribute to this association. Early diagnosis of VKH and aggressive systemic corticosteroid intervention are essential for this type of IFN-α -related autoimmune complication.     

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.     

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.     

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.