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.     

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.     

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.     

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.     

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.     

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.     

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%).     

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.     

Interferon Alpha-2a for the Treatment of Post-Infectious Uveitis Secondary to Presumed Intraocular Tuberculosis

Purpose: To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB).

Methods: Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months.

Results: Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months (p = 0.03). Mean CRT decreased from 372 ± 132.2 μm to 274.66 ± 34.9 μm at six months (p = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded.

Conclusions: IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB.     

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.     

Cataract Surgery in HIV Seropositive Patients: Long-Term Follow-Up

Purpose: To study epidemiology and clinical findings of cataract in HIV+ patients.

Methods: A total of 32 HIV+ patients, 11 with uveitis/retinitis before surgery and 21 without, mean follow-up 44.9 ± 36.6 months, and 114 HIV- patients, 57 with uveitis/retinitis before surgery and 57 without, were retrospectively compared.

Results: Visual acuity improved in all HIV+ patients (p < 0.001), who were younger (p = 0.01) and more frequently males (p = 0.027). HIV+ patients with uveitis prior surgery improved less (p = 0.046) than HIV- (p < 0.001); their anterior chamber inflammation was similar to baseline. Male sex (p = 0.005), younger age (p < 0.001), dyslipidaemia (p = 0.058), HBV+ (p = 0.037), and unilateral cataract (p = 0.001) were more frequent in HIV+ patients with senile cataract, but they showed the same postoperative course as HIV- patients.

Conclusion: Cataract surgery in HIV+ patients is safe and effective. Uveitis prior to surgery did not significantly affect the postoperative course. Systemic comorbidities are more frequent in HIV+ patients with senile cataract than in HIV- subjects.     

Long-Term Efficacy of Pegylated Interferon Alpha-2b in Behçet’s Uveitis: A Small Case Series

Purpose: To assess the long-term efficacy and safety of pegylated interferon alpha-2b (peg-IFN-α-2b) for severe uveitis associated with Behçet’s disease.

Methods: Peg-IFN-α-2b was administrated at an initial dosage of 0,5–1,5 µg/kg/week. If any complications were observed, the dosage was tapered. Ocular examinations, systemic findings, and treatment compliance of the patients were evaluated.

Results: Control of ocular inflammation was achieved in all patients (n = 4). The average increase in visual acuity after drug administration of 0,425 ± 0,125 logMAR was not statistically significant (Wilcoxon Test, p = 0,066) due to small number of cases. Any side-effects with laboratory abnormalities returned to baseline levels with reduction of the doses. Due to less frequent injections, increased satisfaction of the patients was noted.

Conclusions: This series highlights the peg-IFN-α-2b administration in Behçet’s uveitis. Peg-IFN-α-2b has a potential long-term therapeutic effect for the treatment of severe uveitis. Efficacy with a reduced number of injections improved the quality of Behçet patients’ lives.     

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.     

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.     

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.     

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.     

Twenty-Four Months Follow-Up of Intravitreal Bevacizumab Injection Versus Intravitreal Triamcinolone Acetonide Injection for the Management of Persistent Non-Infectious Uveitic Cystoid Macular Edema

Purpose: To report the efficacy of intravitreal bevacizumab (IVB) injection versus intravitreal triamcinolone acetonide (IVT) for persistent non-infectious uveitic cystoid macular edema (CME).

Methods: Interventional retrospective comparative case series evaluated 37 consecutive patients (44 eyes) with completely controlled uveitis and recalcitrant CME. Patients received repeated injections of 1.25 mg of IVB or 4 mg of IVT.

Results: Best-corrected visual acuity (BCVA) at baseline and 24 months was logMAR 1 and 0.8 respectively, in the IVB group (p = 0.002) and; logMAR of 1.1 and 0.6, in the IVT group (p = 0.001). Central macular thickness at baseline and 24 months was 399.2 µm and 333.7 µm (p < 0.0009), respectively, for the IVB group and; 464.4 µm and 316.5 µm in the IVT group (p = 0.044). Postoperatively, IOP increased in the IVT group.

Conclusions: Repeated injections with IVT improve BCVA as effectively as repeated injections with IVB in the long-term management of persistent uveitic CME.     

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.     

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.