Massimo Accorinti

Infliximab Treatment for Ocular and Extraocular Manifestations of Behçet's Disease

PurposeTo assess the efficacy and safety of infliximab in the treatment of sight-threatening uveitis and extraocular manifestations in patients with Behçets disease.MethodsTwelve patients with Behçets disease and uveitis were treated with infliximab after unsuccessful therapy with other immunosuppressive drugs. The main outcome measures were as follows: the number of uveitis relapses, the number of Behçets disease-related extraocular lesions, and the amount of corticosteroids administered during the treatment as well as during an equal prior period of time while the patients were on other immunosuppressive agents. Visual acuity was recorded at the beginning of infliximab therapy and at the end of follow-up, and was defined as stable if it did not change from baseline, increased if it showed at least one line of improvement from baseline, and decreased if it showed at least a one line decrease from baseline.ResultsDuring an average follow-up of 16.67 ± 7.63 months (median, 15 months), 11 patients (91.6%) showed a reduction in the number of ocular relapses (relapse/month, from 0.35 ± 0.17 to 0.12 ± 0.17, P < 0.001). All of the patients (n = 11) who were taking corticosteroids before infliximab were able to reduce the amount of corticosteroids taken daily during infliximab treatment (from 24.33 ± 10.84 mg/prednisone per day to 8.97 ± 6.81 mg/prednisone per day, P < 0.001), and all presented with a reduced onset of extraocular manifestations of Behçets disease (mean total number, from 2.83 ± 3.61 to 1.51 ± 2.35, P = 0.039). One patient, who had to stop treatment 2 months after starting because of the onset of pulmonary tuberculosis, showed the same number of relapses during infliximab treatment but was able to reduce the mean daily corticosteroid dose. Visual acuity increased by one or more lines in three eyes (12.5%) and remained unchanged in 87.5% of the eyes. Infliximab-related side effects appeared in four patients (33.3%).ConclusionsInfliximab was effective in the treatment of uveitis in these Behçets disease patients, significantly reducing the number of ocular relapses and making possible a significant reduction in the daily dose of corticosteroids administered. Extraocular manifestations of Behçets disease were also controlled by infliximab. Nevertheless, side effects were not uncommon, and an extensive study of systemic conditions before infliximab administration had to be carried out to exclude systemic infection, particularly prior tuberculosis. Jpn J Ophthalmol 2007;51:191–196

Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease

PURPOSE To determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis. DESIGN Comparative case series. PARTICIPANTS We included 1147 patients. METHODS All patients with bilateral ocular inflammatory disease presenting to any of 10 uveitis centers in the 3-month period between January 1 and March 31, 2006 (inclusive), were asked to participate. The clinical and historical features of disease were obtained from the participants via direct interview and chart review. Patients were stratified based on whether they were diagnosed with VKH disease or non-VKH uveitis for statistical analysis. MAIN OUTCOME MEASURES Presence or absence of various clinical features in the 2 populations. RESULTS Of 1147 patients, 180 were diagnosed with VKH disease and 967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed with VKH than non-VKH disease compared with other ethnicities. In acute disease, the finding of exudative retinal detachment was most likely to be found in VKH disease with a positive predictive value (PPV) of 100 and negative predictive value (NPV) of 88.4, whereas in chronic disease, sunset glow fundus was most likely to be found, with a PPV of 94.5 and NPV of 89.2. CONCLUSIONS Numerous clinical findings have been described in the past as important in the diagnosis of VKH. The current study reveals that of these, 2 are highly specific to this entity in an ethnically and geographically diverse group of patients with nontraumatic bilateral uveitis. These clinical findings are exudative retinal detachment during acute disease and sunset glow fundus during the chronic phase of the disease.

CARDIAC INVOLVEMENT IN BEHCET'S DISEASE

To assess the prevalence and the extent of cardiac involvement in patients with Behçets disease and to investigate the possible causes that may predispose to this involvement, 30 patients affected by Behçets disease and 30 normal control subjects were submitted to M-mode, two-dimensional, and Doppler echocardiographic evaluation. Moreover, antinuclear and anticardiolipin autoantibodies were determined in the sera of both patients and control subjects. Finally, HLA-B51 positivity was assessed in the patients and in a historical control group. Mitral valve prolapse was observed in 50% and proximal aorta dilatation in 30% of the patients. There was a significant difference in the rate of these abnormalities in comparison with the control group. Left ventricular function parameters were similar between the two groups. The positivity rate of antinuclear and anticardiolipin autoantibodies was very low (7%), without differences between the groups. HLA-B51 was detected in 82.7% of the patients versus 21.7% in the control group (p < 0.00001). In conclusion, this study demonstrates a high rate of cardiac abnormalities in patients with Behçets disease.

Epidemiology of Behçet Disease

Behçet disease (BD) is a multisystem inflammatory disorder that is an important cause of morbidity worldwide. BD is most common along the ancient “Silk Road” route in the Far East and Mediterranean basin. The eye is the most commonly involved organ in BD patients.The prototypical form of involvement is a relapsing remitting panuveitis and retinal vasculitis. Less commonly, BD may present in the form of conjunctivitis, conjunctival ulcers, keratitis, episcleritis, scleritis, and extraocular muscle paralysis. Uveitis in BD carries significant implications for the patient, because it is a chronic recurrent disease characterized by explosive attacks of severe inflammation that may cause significant, cumulative damage to the intraocular structures. This review summarizes the epidemiology of systemic and ocular clinical features of BD with particular focus on risk factors, clinical characteristics, complications, and prognosis of BD-associated uveitis.

Optical Coherence Tomography for Classification and Clinical Evaluation of Macular Edema in Patients with Uveitis

Purpose: To study use of optical coherence tomography (OCT) for macular edema in uveitis. Methods: In total, 44 patients with uveitis and macular edema underwent OCT. Data obtained were correlated with anatomic type, duration of uveitis, and visual acuity (VA). Results: Both cystoid macular edema (CME) and diffuse macular edema (DME) correlate negatively with VA, although statistically CME showed stronger correlation (p = .02). Also CME had higher mean foveal thickness than DME (p < .01). Negative correlation between foveal thickness and VA (p < .05) was observed. CME correlates with uveitis duration (p < .01). Conclusions: CME and macular thickening correlate with VA reduction and uveitis duration.

Indocyanine green angiographic findings in Behçet disease.

Background The authors studied indocyanine green (ICG) angiographic features in proven cases of ocular Behçet disease. Methods Twenty-six patients (18 male, 8 female; mean age 39.9 ± 8.9 years) with Behçet disease underwent simultaneous ICG and fluorescein angiography (FA) according to a uveitis angiographic standard protocol. Patients were divided into three groups based on their ocular disease duration: Group A (9 patients), less than 3-year duration; Group B (8 patients), 4- to 10-year duration; Group C (9 patients), more than 10-year duration. The relation between ICG angiographic findings and ocular disease duration and FA signs was delimited. Results Three findings were disclosed by ICG angiography: 1) poorly defined areas of intermediate and late hyperfluorescence (50% of eyes); 2) well-defined hypofluorescent areas becoming isofluorescent in the late phase (26.92% of eyes); and 3) large, poorly defined hypofluorescent areas visible up to the late phase (30.77% of eyes). The presence of ICG hypofluorescent areas up to the late phase was related to disease duration (P = 0.01), whereas ICG hypofluorescent areas becoming isofluorescent in the late phase were predominant in patients in early stages of ocular disease (P = 0.02). The presence or absence of FA signs did not indicate any significant correlation with the presence or absence of signs revealed by ICG angiography. Conclusion Indocyanine green angiography enabled the identification of different choroidal abnormalities related to the ocular disease duration. The presence of some ICG findings undetectable with FA suggests that ICG and FA are complementary means to diagnose and monitor ocular vascular involvement in patients with Behçet disease.

Vogt-Koyanagi-Harada Disease and HLA Type in Italian Patients

PURPOSE To study the frequencies of human leukocyte antigen (HLA) specificities in Italian patients with Vogt-Koyanagi-Harada disease and to correlate the presence of each specificity to the clinical features. METHODS Human leukocyte antigen specificities were determined by standard microlymphocytotoxicity assay in 16 patients with Vogt-Koyanagi-Harada disease and compared with HLA specificities of 116 healthy controls. RESULTS HLA-DR4 was statistically related to Vogt-Koyanagi-Harada disease (P = .0063), whereas only a trend toward a significant association between the disease and HLA-B41 was found (P = .06). HLA-DQ1 was detected in a disproportionate number of controls (68.9%) compared with patients (37.5%). CONCLUSIONS HLA-DR4 was significantly related to Vogt-Koyanagi-Harada disease in Caucasian European patients, specifically in Italian patients, as it was described in other racial groups. No clear relation was found between the ophthalmologic and systemic manifestations of Vogt-Koyanagi-Harada disease and the presence of HLA specificities.

Herpes simplex virus vaccine in recurrent herpetic ocular infection.

PurposeTo facilitate increased use of keratolimbal allograft transplantation (KLAL) for severe ocular surface disease (OSD) by informing clinicians and eye banks of differences in tissue requirements and preparation for the procedure and to describe the surgical technique of KLAL transplantation.MetPURPOSE To evaluate the efficacy of an antiherpetic vaccine in recurrent herpetic ocular infections. METHODS Twenty patients with herpes simplex virus 1-related recurrent keratitis/keratouveitis were prospectively enrolled and randomly assigned to receive either a specific vaccination with heat shock-inactivated herpes simplex virus type 1 (10 patients) or to be observed as controls (10 patients). The number, duration, and anatomic localization of relapses were recorded in all the patients for 12 months before inclusion in the study and for a similar period after the assignment of each subject to vaccine or control group. RESULTS In the vaccine group, we observed a reduction both in the number (p = 0.016) and average duration (p = 0.050) of recurrences, whereas in the control group, no significant change was found comparing a 12-month period before and after inclusion in the study. The comparison between the two groups highlighted a significant reduction in the number (p = 0.013) and average duration (p = 0.051) of relapses in treated subjects, who did not show any significant vaccine-induced side effects. CONCLUSION The use of a vaccination with heat shock-inactivated herpes simplex virus 1 seems to be able to reduce the number and duration of relapses in herpes simplex virus 1-related keratitis/keratouveitis.

Clinical Features and Prognosis of HLA B27-associated Acute Anterior Uveitis in an Italian Patient Population

Purpose: To report clinical features and prognosis of HLA B27 acute anterior uveitis. Methods: 165 patients with recurrent acute anterior uveitis were divided into two groups: HLA B27-positive (group 1, 60 patients) and HLA B27-negative (group 2, 105 patients). A comparison between the two groups was performed. Results: Unilateral involvement was higher in group 1 (p = .046), and more simultaneous bilateral cases occurred in group 2 (p = .004). Group 1 was more correlated to systemic diseases than group 2 (50 versus 17.1%, p < .001), particularly to ankylosing spondylitis (35 versus 3.8%, p < .001). Uveitis was diagnosed before spondylitis in 57% of patients. In groups 1 and 2 an immunosuppressive therapy was administered to 20 and 9.5% of patients but was exclusively given to control uveitis in 1.6 and in 2.8% of cases, respectively. Conclusions: A strong association between HLA B27 uveitis and ankylosing spondylitis was confirmed and usually uveitis preceded rheumatological involvement.

Spectral-Domain Optical Coherence Tomography in Uveitic Macular Edema: Morphological Features and Prognostic Factors

Aim: To assess the morphological characteristics of uveitic macular edema studied with Spectralis optical coherence tomography (OCT) and to investigate the correlation between the tomographic features and visual acuity. Methods: 71 eyes of 55 patients underwent examination with Spectralis OCT (Heidelberg Engineering, Germany). Data was correlated with logMAR best-corrected visual acuity (BCVA). Results: Two morphological patterns were observed: cystoid macular edema (CME) in 69% and diffuse macular edema in 31% of eyes. BCVA was 0.2 in CME, 0.1 in diffuse edema (p = 0.008). Foveal thickness was 413.4 ± 212 µm in CME, 311.27 ± 53 µm in diffuse edema (p = 0.03). BVCA was 0.3 in eyes with serous retinal detachment (SRD), 0.2 in eyes without SRD (p = 0.02). BCVA was 0.4 in eyes with inner segment/outer segment (IS/OS) disruption, 0.1 in eyes with integrity of the IS/OS junction (p = 0.01). Conclusions: BCVA is negatively correlated with cystoid pattern, foveal thickening and SRD. Disruption of the IS/OS junction is associated with poor vision in uveitic macular edema.