Clinical manifestation of Fuchs uveitis syndrome in childhood.

PURPOSE: The aim of this study was to describe clinical signs and complications of Fuchs uveitis syndrome (FUS) with onset in childhood. METHODS: Ophthalmologic findings and complications in patients with FUS becoming manifest before the age of 16 years were analyzed in a retrospective study at a tertiary referral uveitis center. Inclusion criteria were the presence of pathognomonic FUS findings at any time point and exclusion of any systemic immune-mediated or infectious disease. RESULTS: A total of 23 patients (male = 16, female = 7) with juvenile FUS (unilateral n = 20, bilateral n = 3 patients) were included in the study. Mean ages at uveitis and FUS diagnosis were 12.0 ± 4.2 and 22.7 ± 10.7 years, respectively. In six patients, inflammation was noted at age ≤ 7 years. The following inflammatory signs were observed in a total of 26 eyes: ≤ 1+ anterior chamber cell grade (n = 26), vitreous cells (n = 24), fine keratic precipitates (KPs; n = 23), stellate KPs (n = 11), mutton-fat KPs (n = 23), diffuse (n = 24) or inferior (n = 8) distribution of KPs, Koeppe nodules (n = 10), and iris heterochromia (n = 14). A representative subgroup of patients (n = 5) is shown who presented with non-specific clinical signs in the beginning and in whom typical FUS signs became manifest only at a later stage. Secondary complications such as cataract (n = 19), ocular hypertension (n = 3), or glaucomatous disc damage (n = 2) were found after a mean uveitis duration of 11.6, 19.5, and 20.3 years, respectively. CONCLUSION: FUS may begin in early childhood, and the characteristic findings may not be present at onset of disease. The diagnosis is often delayed for years, occasionally with the consequence of overtreatment with anti-inflammatory drugs.

Everolimus for the treatment of uveitis refractory to cyclosporine A: a pilot study.

BACKGROUND: This study investigated the efficacy of everolimus, a potent inhibitor of T lymphocyte proliferation, for treating noninfectious uveitis. The study design was an open-label prospective trial. METHODS: Twelve patients with severe chronic uveitis (anterior and intermediate n = 9, panuveitis n = 3) refractive to cyclosporine A (CsA) received additional everolimus. MAIN OUTCOME MEASURE: the primary outcome measure was uveitis inactivity at 3 months. Secondary outcome measures were uveitis recurrence, visual acuity (BCVA), laser flare photometry values, cystoid macular edema, and tapering of concomitant corticosteroids and/or immunosuppressive drugs in 12 months with the addition of everolimus and after withdrawing everolimus. Percentages of peripheral blood CD3(+)CD4(+)CD25(+)Foxp3(+) cells were studied. RESULTS: At month 3 with everolimus, uveitis was inactive in all patients. By 12 months, uveitis had recurred in four patients after tapering (n = 2) or withdrawing (n = 2) CsA. BCVA remained stable in all patients, mean foveal thickness (OCT) was slightly reduced from 308 µm at baseline to 255 µm (p = 0.1), and mean flare values were slightly reduced from 27.8 to 19.3 photons/msec (p = 0.1). It was possible to achieve a 50 % dose reduction of systemic prednisone (n = 8) or CsA (n = 8). After withdrawing everolimus, uveitis recurred in 50 % within 1 month; by 6 months, BCVA dropped ≥2 lines in five patients, and prednisone use increased ≥50 % in four patients. The percentage of peripheral blood CD3(+)CD4(+)CD25(+)FoxP3(+) T cells increased during the everolimus treatment, and dropped after withdrawal. CONCLUSIONS: Uveitis inactivity was achieved with the addition of everolimus in patients with chronic, CsA-refractive anterior and intermediate uveitis, or panuveitis.

Influence of corneal thickness changes during active uveitis on Goldmann applanation and dynamic contour tonometry.

BACKGROUND: To compare the influence of central corneal thickness (CCT) during active anterior uveitis and after resolution on intraocular pressure (IOP) measurements by Goldmann applanation tonometry (GAT) and by dynamic contour tonometry (DCT). DESIGN: Prospective, single-center study including 30 consecutive patients with active unilateral uveitis. MAIN OUTCOME MEASURE: CCT influence on GAT and DCT in active uveitis. RESULTS: Average age of included patients (total n = 30; 16 women) was 46.5 years (range: 22.3-75.4). During activity, the cornea was thicker than on the unaffected side (645 vs. 585 µm, p = 0.0001). At the follow-up visit (inactive time point), the corneal thickness of the affected eye fell to a CCT of 581 µm (p < 0.0001). IOP measured by DCT was always higher than that measured by GAT. IOP was significantly lower during the active phase (GAT = 14.3 ± 5.8 mm Hg, DCT = 16.3 ± 5.9 mm Hg) than when disease was inactive (GAT = 17 ± 6.2 mm Hg, p = 0.016; DCT = 19.6 ± 6.9 mm Hg, p = 0.0006). The two techniques showed a high concordance, with a correlation coefficient of 0.76 (p < 0.001) in the affected eye at the active time point and when inactive 0.95 (p < 0.001). In addition, no systematic difference between these two techniques was observed according to the Bland-Altman method of comparison. No correlation between ΔIOP (GAT - DCT) and CCT could be detected at either time point. CONCLUSIONS: CCT increases during active phases of anterior uveitis. The edematous corneas lead to an additional decrease in IOP measurements by GAT and DCT. Both techniques were in good concordance in the patients, and the difference between GAT and DCT IOP readings was not influenced by CCT.

Smoking complicates the course of non-infectious uveitis.

BACKGROUND: Data concerning the association of smoking and uveitis are limited. The aim of this study was to evaluate the effect of tobacco smoking on uveitis activity and complications of noninfections uveitis and the need for immunosuppressive therapy. METHODS: We conducted an observational cross-sectional study in 350 patients with noninfectious uveitis. All patients completed a questionnaire concerning smoking habits. Primary outcome measure was uveitis activity in smokers as compared to nonsmokers; secondary outcome measures were need for immunosuppression and uveitis complications. RESULTS: In all 115 patients (32.9%) were smokers. Smokers had an increased risk for active uveitis (OR 1.8; 95% CI, 1.2-2.9; p = 0.007). Smokers with anterior uveitis had anterior chamber cells more often than nonsmokers (p = 0.008) and required significantly more topical steroid eyedrops (p = 0.002). Uveitis developed at a younger age in smokers than in nonsmokers (p = 0.027). The number of smokers who needed any second-line immunosuppression (p = 0.642) and the number of immunosuppressive agents required (p = 0.794) did not differ from that for nonsmokers. The number of pack-years significantly increased the risk of macular edema (p = 0.020) und cataract (p = 0.022). CONCLUSIONS: Smoking is associated with uveitis activity, leading to increased need for steroid eyedrops and increased incidence of cataract and macular edema. The results highlight the need to encourage uveitis patients to stop or at least to reduce their smoking.

Comparison of orbital floor triamcinolone acetonide and oral prednisolone for cataract surgery management in patients with non-infectious uveitis.

PURPOSE: To compare orbital floor triamcinolone acetonide and oral prednisolone in cataract surgery in patients with chronic non-infectious uveitis with regard to visual outcome, postoperative inflammation and macular edema. METHODS: Monocentric prospective randomized clinical trial with 40 eyes included. Patients underwent phacoemulsification with intraocular acrylic foldable lens (IOL) implantation. Patients were randomized either to intraoperative orbital floor triamcinolone acetonide (TA) (1 ml = 40 mg) (group 1, n = 20), or to 4-week postoperative oral prednisolone (group 2, n = 20). Laser flare photometry (LFM), cells in the anterior chamber (AC), best-corrected visual acuity (BCVA), IOL cell deposits, cystoid macular edema (CME) by means of fluorescein angiography, and central foveal thickness (OCT), posterior capsule opacification (PCO), and intraocular pressure (IOP) were analysed during a 6-months period. RESULTS: Mean BCVA postoperatively improved (p < 0.01) from logMAR 0.74 and 0.86 to 0.23 and 0.35 in groups 1 and 2 respectively.The number of AC cells, LFM and IOL cell deposits did not differ. Macular edema stayed unchanged in most cases in both groups, and mean foveal thickness (OCT) initially increased postoperatively, but after 6 months it nearly returned to baseline thickness. Differences between the groups were not significant. Up to 12% in group 1 and 28% of group 2 developed IOP elevation over 21 mmHg. CONCLUSIONS: A single intraoperative orbital floor injection of triamcinolone acetonide is as effective on postoperative inflammation, macular edema, and visual outcome as a 4-week course of postoperative oral prednisolone in cataract surgery with IOL implantation in uveitis patients.

Fundus autofluorescence and spectral domain optical coherence tomography in uveitic macular edema.

BACKGROUND: Cystoid macular edema (CME) is a common vision-limiting complication of uveitis. This study correlated fundus autofluorescence (FAF) and optical coherence tomography (OCT) with visual acuity (VA). PATIENTS AND METHODS: Prospective, observational, cross-sectional study with 31 patients (53 eyes) with endogenous uveitis and fluorescein angiographically (FA) confirmed CME. Foveal thickness, epiretinal membrane formation, and altered (increased or decreased) foveal FAF were analyzed with a combined spectral domain OCT/FA device (Spectralis/HRA Heidelberg Retina Angiograph 2). Primary outcome measures were an association between central FAF with foveal thickness and VA (t-test, each). Secondary outcome measures included the association of FAF and epiretinal membrane formation, the presence of cystoid spaces in the outer plexiform and inner nuclear layers, and integrity of the third highly reflective band as detected by OCT (Fisher s exact test, each). RESULTS: Of the 24 eyes (59%) with altered FAF in the central 500 microm, all had increased foveal FAF, and 10% also had increased perifoveal petaloid FAF. In eyes with altered FAF, the VA was frequently worse (p = 0.019) and foveal thickness increased (p = 0.015). Foveal thickness (mean 369.4 mum) correlated with VA (p < 0.01). FAF alterations correlated with the presence of cystoid spaces in the outer plexiform and inner nuclear layer in OCT (p < 0.001). Epiretinal membrane formation (70%) was associated with increased foveal thickness (p = 0.003) and poor VA (p = 0.08). Irregularity or loss of the third HRB (51%) correlated with poor VA (p < 0.01) and altered central FAF (p = 0.031). CONCLUSIONS: FAF and OCT are useful diagnostic tools for the evaluation of uveitic CME. Increased central FAF, presence of cystoid retinal changes and disrupted third highly reflective band in OCT, and epiretinal membrane formation are associated with poor vision.

Intravitreal and orbital floor triamcinolone acetonide injections in noninfectious uveitis: a comparative study.

PURPOSE: To compare the effect of orbital floor (OFTA) or intravitreal (IVTA) administration of triamcinolone acetonide on visual acuity and chronic cystoid macular edema (CME) in patients with uveitis. METHODS: Retrospective study of patients suffering from chronic noninfectious uveitis in whom CME (n = 97) did not respond to systemic corticosteroids and/or immunosuppression combined with acetazolamide. Patients received a single injection of either IVTA (n = 48, group 1) or OFTA (n = 49, group 2). Best-corrected visual acuity, macular edema (fluorescein angiography), uveitis activity, ocular hypertension, and cataract formation were analyzed over the course of 1 year. RESULTS: Improvement in visual acuity (> or = 2 lines, LogMAR) was noted in 50% (IVTA) and 34% (OFTA) after 3 months (p = 0.23), and in 18% (IVTA) and 20% (OFTA) after 12 months. CME improved in 100% (IVTA) and 76% (OFTA) of the eyes within the first month postoperatively (p = 0.36). Macular edema was reduced in 100% (group 1) and 20% (group 2) after 3 months (p < 0.01). At 1 year, cataract progression was noted in 68% (IVTA) and 27% (OFTA) (p < 0.01). Increased intraocular pressure (>21 mm Hg) was detected in 21% (IVTA) and 0% (OFTA) at 4 weeks (p < 0.01) after injection. CONCLUSION: Uveitic CME and visual acuity not responding to systemic immunosuppression and acetazolamide may improve after an IVTA and OFTA injection. The effect is mostly transient. While the IVTA injections were more effective for improving CME, ocular hypertension and cataracts developed more often.

Uveal and capsular biocompatibility of two foldable acrylic intraocular lenses in patients with endogenous uveitis--a prospective randomized study.

BACKGROUND: To compare a hydrophobic and a hydrophilic acrylic single-piece intraocular lens (IOL) in uveitis patients with respect to biocompatibility and visual outcome. METHODS: Prospective, randomized study in patients with noninfectious uveitis after phacoemulsification and implantation of either a hydrophobic AcrySof (group 1, n = 30) or a hydrophilic Akreos adapt (group 2, n = 30), sharp-edged acrylic IOL. The primary outcome was uveal biocompatibility, detected by giant-cell deposition, anterior chamber cell count and laserflare photometry over a 6-month follow-up period. Secondary outcome measures were capsular biocompatibility, as detected by posterior capsule opacification (PCO), lens epithelial cell outgrowth and Nd:YAG capsulotomies, and visual outcome. RESULTS: The groups did not differ with respect to anatomic type of uveitis, immunosuppressive treatment, associated systemic disease, and intraoperative manipulation. The number of giant cells on the anterior IOL surface was higher in group 1 than in group 2 (p = 0.03). The number of anterior chamber cells, laser flare photometry levels, and uveitis reactivations after surgery did not differ between the groups. After 6 months, the number of patients with PCO development (p = 1.0) and Nd:YAG capsulotomies (p = 0.21), lens epithelial cell outgrowth, visual outcome and uveitis complications were comparable in both groups. CONCLUSIONS: Both of the acrylic IOLs used had good uveal and capsular biocompatibility, leading to significant improvement in BCVA in patients with noninfectious uveitis. No obvious differences were detected at 6 months with respect to uveal and capsular biocompatibility and visual outcome.

Favourable outcome after cataract surgery with IOL implantation in uveitis associated with juvenile idiopathic arthritis.

PURPOSE: Management of uveitic cataract in patients with juvenile idiopathic arthritis (JIA) is challenging, and intraocular lens (IOL) implantation is controversial. This study investigated the outcome after minimally invasive surgery with IOL implantation. METHODS: Retrospective analysis after phacoemulsification with in-the-bag IOL implantation was performed in 16 patients (17 operations) with ANA-positive JIA-associated chronic uveitis. In these patients, 25 G capsulectomy and anterior vitrectomy was performed and they received an intravitreal triamcinolone (TA) injection. RESULTS: Mean age at uveitis onset was 5 ± 2 years, and surgery was performed at a mean age of 11 ± 2.2 years. Preoperatively, uveitis was inactive in all patients, and visual acuity was logMAR 0.8 ± 0.44; additional uveitis complications were present in all patients, and 15 patients were receiving systemic immunosuppression/biologicals. After surgery (mean follow-up 26.5 ± 11.7 months), presence of cystoid macular oedema, papilloedema, ocular hypertension/glaucoma and hypotony did not increase compared with baseline. There was no significant worsening of AC inflammation (by cell numbers and laser flare values). IOL deposits persisted in four patients, and synechiae developed in eight. The visual acuity was improved (≥2 lines) in all patients (mean logMAR 0.3 ± 0.24). Retrolental membrane formation was not noted. Secondary capsular opacification was observed in seven patients, requiring Nd:YAG capsulotomy in five of them. CONCLUSIONS: Phacoemulsification and in-the-bag IOL implantation may improve visual outcome in JIA-associated uveitis with minimally invasive surgical technique and intravitreal TA injection. Well-controlled uveitis with appropriate use of topical steroids and systemic immunosuppression or biologicals appears as a perioperative requirement.

Elevated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis.

PURPOSE: To evaluate the prognostic value of anterior chamber (AC) laser flare (LF) in uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Monocentre, retrospective study of 150 JIA children (girls n = 107, 71.3%) with unilateral or bilateral chronic anterior uveitis (statistical analysis of one eye per patient). LF values (KOWA FM-500), visual acuity, intraocular pressure, glaucoma treatment and uveitis complications were investigated longitudinally. RESULTS: Patients were followed up for a mean of 8.7 months (range 1-36). High LF values correlated with poor visual acuity (p < 0.0001). Patients with low LF values (LF ≤ 20 photon units per millisecond) less often required glaucoma medication (p = 0.0005) or surgery (p = 0.01) and showed a lower prevalence of cataract, band keratopathy, posterior synechiae, epiretinal membrane, optic disc oedema and glaucoma/ocular hypertension (p < 0.05, each). Baseline LF > 20 photon units per millisecond was a better prognosticator for the development of subsequent complications than baseline AC cells (p = 0.04). CONCLUSIONS: High LF values in patients with JIA uveitis are associated with poor vision and a higher prevalence of uveitis complications.

Oral voclosporin: novel calcineurin inhibitor for treatment of noninfectious uveitis.

Voclosporin, a novel immunomodulatory drug inhibiting the calcineurin enzyme, was developed to prevent organ graft rejection and to treat autoimmune diseases. The chemical structure of voclosporin is similar to that of cyclosporine A, with a difference in one amino acid, leading to superior calcineurin inhibition and less variability in plasma concentration. Compared with placebo, voclosporin may significantly reduce inflammation and prevent recurrences of inflammation in patients with noninfectious uveitis. Future studies have to show if these advantages are accompanied by greater clinical efficacy and fewer side effects compared with the classic calcineurin inhibitors.

Comparison of retinal thickness and fundus-related microperimetry with visual acuity in uveitic macular oedema.

PURPOSE: Macular oedema is a common complication and vision-limiting factor in uveitis. The aim of this study was to compare retinal thickness as measured by optical coherence tomography and photoreceptor function as measured by fundus-related microperimetry with respect to their correlation with visual acuity. METHODS: Prospective observational monocentre study. Thirty-one patients (53 eyes) with endogenous uveitis and fluorescein angiographically confirmed macular oedema were evaluated. Foveal thickness was analysed using spectral-domain (Spectralis(TM) ; Heidelberg Engineering, Heidelberg, Germany) OCT and retinal sensitivity was assessed using fundus-related microperimetry (MP1; Nidek Technologies, Padova, Italy). All findings were correlated with best-corrected visual acuity (BCVA). RESULTS: Foveal thickness was correlated with BCVA [p = 0.005, r = 0.38, 95% confidence interval (CI) 0.12-0.59]. For microperimetry measurements, a negative correlation with logMAR visual acuity was found. Fixation abnormalities were not associated with poor visual acuity, increased foveal thickness or retinal sensitivity. In eyes with cystoid changes in the outer plexiform and inner nuclear layer, foveal thickness was increased (p < 0.0001). Epiretinal membrane formation was present in 70%. In these eyes, foveal thickness was significantly increased (p = 0.003) and visual acuity was worse (p = 0.08). CONCLUSION: Foveal thickness and fundus-related microperimetry were correlated with visual acuity. Cystoid changes in the outer plexiform and inner nuclear layer and the presence of epiretinal membrane were associated with poor visual acuity. Fixation abnormalities were not associated with poor visual acuity.

Risk factors for the development of macular edema in noninfectious uveitis.

PURPOSE: Macular edema (ME) is a vision-limiting complication of uveitis. The aim of the present study was to identify risk factors for the development of ME. METHODS: This was an observational, cross-sectional study including 350 patients with noninfectious uveitis. Data were acquired by using a questionnaire. Associations with ME were analyzed for age,alcohol consumption, coffee consumption, cardiovascular risk factors, and level of education. RESULTS: On univariate analysis, patients with ME were older (p<0.001, odds ratio [OR] 1.03) and had a longer history of uveitis (p=0.006, OR 1.03). Patients with university certificate or high school diploma had a significantly reduced risk (OR 0.25, p<0.001) to develop ME compared to patients with less education. For smoking, the number of pack-years was significantly but weakly associated with the presence of ME (p=0.02, OR 1.02). Smokers with a smoking history of more than 20 pack-years had a higher risk for ME (OR = 2.46, confidence interval 1.2-5.2). Daily coffee consumption predisposed to ME (p=0.02, OR 2.1). Arterial hypertension, body mass index, alcohol consumptions, and hypercholesterinemia were not associated with ME. Multivariate analysis confirmed age, coffee consumption,and low education to be risk factors for ME, whereas smoking was lost on multivariate analysis. CONCLUSIONS: Age, low level of education, daily coffee consumption, and possibly smoking are risk factors for ME in patients with noninfectious uveitis.

Comparison between intravitreal and orbital floor triamcinolone acetonide after phacoemulsification in patients with endogenous uveitis.

PURPOSE: To compare the effect of intravitreal and orbital floor triamcinolone acetonide (TA) on macular edema, visual outcome, and course of postoperative inflammation after cataract surgery in uveitis patients. DESIGN: Prospective, randomized clinical trial. METHODS: Monocenter study (40 patients) with chronic endogenous uveitis who underwent phacoemulsification with intraocular lens implantation with either 4 mg intravitreal TA (n = 20) or 40 mg orbital floor TA (n = 20). The primary outcome was influence on cystoid macular edema (CME). Secondary outcome measures were best-corrected visual acuity (BCVA), anterior chamber cell grade, laser flare photometry, giant cell deposition, posterior capsule opacification (PCO), and intraocular pressure. RESULTS: Mean central foveal thickness decreased in the intravitreal TA group and increased in the orbital floor TA group (P < .001 at one and three months). CME improved in 50% of patients after intravitreal TA, whereas it was unchanged after orbital floor TA (difference between the groups at three months, P = .049). Mean BCVA (logarithm of the minimal angle of resolution) improved postoperatively (P < .001) from 0.76 and 0.74 to 0.22 and 0.23 in the intravitreal TA and orbital floor TA group, respectively. Anterior chamber cell count at one month was lower in the intravitreal TA than in the orbital floor TA group (P = .02). Laser flare photometry values and giant cell numbers were slightly higher after orbital floor TA than after intravitreal TA. The groups did not differ with respect to PCO rate and ocular hypertension. CONCLUSIONS: The CME improvement and anti-inflammatory effect after intravitreal TA was better than after orbital floor TA injection in cataract surgery in uveitis patients.