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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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%).     

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.     

Choroidal Thickness in Patients Diagnosed with Human Immunodeficiency Virus Infection: Results from Two Populations of Different Ethnicities

Purpose: To measure the choroidal thickness among subjects with human immunodeficiency virus (HIV) infection from two diverse ethnic populations and to compare it with healthy controls.

Methods: Subjects with HIV infection and healthy controls were enrolled in two referring centers in Italy and India. Clinical data were collected. All subjects underwent enhanced-depth imaging optical coherence tomography and measurement of choroidal thickness.

Results: A total of 68 eyes from 68 patients with HIV (44 Caucasian, 24 Indians) and 60 eyes from 60 healthy volunteers (36 Caucasian, 24 Indians) were included. Mean choroidal thickness was significantly higher in HIV patients compared to controls (312.91 ± 65 µm vs. 266.57 ± 47 µm; p < 0.001). Choroidal thickness was higher among subjects with HIV-related retinopathy compared to HIV without retinopathy (285 ± 30 µm vs. 352 ± 17 µm; p < 0.01).

Conclusions: Patients with HIV infection, especially with HIV microangiopathy, have thicker choroid compared to age- and gender-matched healthy control subjects. These changes may be related to HIV-associated choroidal vascular dysfunction.     

Color Doppler imaging of orbital vasculature before and after orbital decompression in thyroid eye disease

Purpose: To measure alterations in orbital blood flow parameters using color Doppler imaging (CDI) before and after orbital decompression in patients with moderate to severe thyroid eye disease (TED).

Methods: Resistance index (RI) and maximum and minimum velocity of ophthalmic artery (OA), superior ophthalmic vein (SOV), and central retinal artery (CRA) of 24 eyes (14 patients) with TED were measured before and at least 3 months after cosmetic orbital decompression procedure (single or double walls) using CDI. Complete eye examination was performed to define the severity (EUGOGO classification) and activity (clinical activity score) of TED.

Results: Median OA (p = 0.003) and CRA (p = 0.001) resistance indices were significantly reduced postoperatively. Significant differences were found in maximum (p = 0.001) and minimum (p = 0.014) velocity of SOV before and after surgery. While a significant decrease in exophthalmometry was observed after the orbital decompression (p = 0.031), intraocular pressure changes were not significant (p = 0.182).

Conclusion: Orbital decompression procedure led to a significant reduction of RI in both CRA and OA in patients with TED.     

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.     

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.     

Interventions and Outcomes in Patients with Infectious Pseudomonas scleritis: A 10-Year Perspective

Purpose: To identify interventional factors associated with improved visual results and faster time to resolution for patients with Pseudomonas scleritis.

Methods: Retrospective study analyzing inciting factors, therapeutic modalities, and outcomes of patients with Pseudomonas scleritis.

Results: A total of 24 patients were analyzed; 22 were treated as outpatients. All had resolution of infection and 58% (n = 14) maintained ≥20/200 vision. Medical therapy included topical and oral antibiotics; seven received additional subconjunctival injections; two were admitted for IV antibiotics. Patients presenting with ≥20/200 vision were more likely to maintain this level of vision (n = 8, 80%) compared to those presenting with severe vision loss (n = 5, 36%) (p = 0.04). A similar proportion of patients who received (n = 8, 61%) and did not receive (n = 5, 39%) oral steroids achieved 20/200 vision or better once infection resolved, p = 1.0.

Conclusions: Pseudomonas scleritis can be successfully managed in the outpatient setting. Oral steroids do not appear harmful in the treatment of this disease.     

Assessment of Tear Functions in Patients with Acne Rosacea without Meibomian Gland Dysfunction

Purpose: To evaluate the results of tear functions in acne rosacea.

Methods: This prospective study includes 64 eyes of 32 acne rosacea patients without blepharitis and meibomian gland dysfunction and 90 eyes of 45 patients as control group. Tear functions of all were evaluated with ocular surface disease index (OSDI) questionnaire, and measurements of tear osmolarity were performed by using TearLab, Schirmer I tests without anesthesia and fluorescein tear break-up time (TBUT).

Results: The mean Schirmer test result was 12.53 ± 6.54 in study group and 16.21 + 7.52 mm/5 min in control group (p = 0.28). The mean TBUT in study group was 8.21 ± 4.01 and in control group was 18.03 ± 6.45 s (p = 0.02). Mean tear osmolarity in study group was 304.77 ± 15.59and in control group was 275.23 + 28.52 mOsms/L (p = 0.03). Mean OSDI score in study group was 27.51 ± 16.73 and was 18.15 ± 7.05 in control group (p = 0.38).

Conclusions: Our study demonstrated lower dry eye tests before the appearance of clinical signs of meibomian gland disease in acne rosacea.     

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.     

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.     

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.