S100A12 and S100A8/9 proteins are biomarkers of articular disease activity in Blau syndrome.

OBJECTIVE: To identify biomarkers of articular and ocular disease activity in patients with Blau syndrome (BS). METHODS: Multiplex plasma protein arrays were performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year follow-up in all patients from a prospective multicentre cohort study. CRP was measured using Meso Scale Discovery immunoassay. Active joint counts, standardization uveitis nomenclature for anterior uveitis cells and vitreous haze by Nussenblatt scale were the clinical parameters. RESULTS: Multiplex Luminex arrays identified S100A12 as the most significantly elevated protein in five selected BS vs eight NHVs and this was confirmed by ELISA on additional samples from the same five BS patients. In the patient cohort, S100A12 (n = 39) and S100A8/9 (n = 33) were significantly higher compared with NHVs (n = 44 for S100A12, n = 40 for S100A8/9) (P = 0.0000004 and P = 0.0003, respectively). Positive correlations between active joint counts and S100 levels were significant for S100A12 (P = 0.0008) and S100A8/9 (P = 0.015). CRP levels did not correlate with active joint count. Subgroup analysis showed significant association of S100 proteins with active arthritis (S100A12 P = 0.01, S100A8/9 P = 0.008). Active uveitis was not associated with increased S100 levels. CONCLUSION: S100 proteins are biomarkers of articular disease activity in BS and potential outcome measures in future clinical trials. As secreted neutrophil and macrophage products, S100 proteins may reflect the burden of granulomatous tissue in BS.

In Vivo Laser Confocal Microscopy Using the HRT-Rostock Cornea Module: Diversity and Diagnostic Implications in Patients with Uveitis.

PURPOSE: Keratic precipitates (KP) are a common feature of uveitis. We prospectively examined KP with the Heidelberg Retinal Tomograph II confocal laser scanning microscope and Rostock Corneal Module (HRT-RCM) to explore their diagnostic implications. METHODS: Prospective, observational, multicenter study. HRT-RCM images were classified by two masked observers. RESULTS: 120 scans on 120 eyes from 110 subjects were included. The majority (N = 93) had non-infectious uveitis. Sixty eyes had active disease at scanning. Eight KP morphologies were defined. Agreement between the two masked graders was high (Kappa value across all categories = 0.81). Cluster and nodular KP were associated with active infectious uveitis (p < 0.01): patients with cluster KP (odds ratio [OR] = 3.03, 95% confidence interval [CI]: 1.43, 6.45) and nodular KP (OR = 3.89, 95% CI: 1.42, 10.65) were more likely to have infectious uveitis than those without. CONCLUSIONS: Laser confocal microscopy of KP may have a role in determining between infectious and non-infectious uveitis.

Blau Syndrome-Associated Uveitis: Preliminary Results From an International Prospective Interventional Case Series.

PURPOSE: Provide baseline and preliminary follow-up results in a 5-year longitudinal study of Blau syndrome. DESIGN: Multicenter, prospective interventional case series. METHODS: Baseline data from 50 patients from 25 centers worldwide, and follow-up data for patients followed 1, 2, or 3 years at the end of study enrollment. Ophthalmic data were collected at baseline and yearly visits by means of a standardized collection form. RESULTS: Median age at onset of eye disease was 60 months and duration of eye disease at baseline 145 months. At baseline 38 patients (78%) had uveitis, which was bilateral in 37 (97%). Eight patients (21%) had moderate to severe visual impairment. Panuveitis was found in 38 eyes (51%), with characteristic multifocal choroidal infiltrates in 29 eyes (39%). Optic disc pallor in 9 eyes (12%) and peripapillary nodules in 9 eyes (12%) were the commonest signs of optic nerve involvement. Active anterior chamber inflammation was noted in 30 eyes (40%) at baseline and in 16 (34%), 17 (57%), and 11 (61%) eyes at 1, 2, and 3 years, respectively. Panuveitis was associated with longer disease duration. At baseline, 56 eyes (75%) were on topical corticosteroids. Twenty-six patients (68%) received a combination of systemic corticosteroids and immunomodulatory therapy. CONCLUSIONS: Blau uveitis is characterized by progressive panuveitis with multifocal choroiditis, resulting in severe ocular morbidity despite continuous systemic and local immunomodulatory therapy. The frequency and severity of Blau uveitis highlight the need for close ophthalmologic surveillance as well as a search for more effective therapies.

Enteric-coated mycophenolate sodium in the treatment of non-infectious intermediate uveitis: results of a prospective, controlled, randomised, open-label, early terminated multicentre trial.

BACKGROUND/AIMS: To evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis (IU). METHODS: Open-label, prospective, controlled, randomised multicentre trial. Patients were randomised in a 1:1 ratio to either the treatment group (prednisolone plus EC-MPS) or control group (prednisolone monotherapy). Patients in the control group who relapsed within 6 months changed to the crossover group (prednisolone plus EC-MPS). Maximum treatment duration was 15 months. The primary endpoint was the time to first relapse in the treatment group and control group. RESULTS: Forty-one patients at eight sites were analysed. Twenty-two patients were allocated to the treatment group, with 19 patients in the control group. A first relapse occurred in 9 patients (40.9%) in the treatment group and 15 patients (78.9%) in the control group (p=0.03). The median time to the first relapse was >15 months for the treatment group and 2.8 months for the control group (p=0.07). The probability of relapse-free survival at month 15 was estimated to be 52.9% in the treatment group and 19.7% in the control group (p=0.01). 15 patients changed to the crossover group. Of these, only four patients developed a second relapse. No safety concerns arose during the trial. Only one patient had to discontinue EC-MPS due to increased liver enzymes. CONCLUSION: EC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU. TRIAL REGISTRATION NUMBER: EUDRACT number: 2009-009998-10, Results.

Randomized Controlled Study to Evaluate the Efficacy of Adalimumab in Patients with Different Forms of Refractory Uveitis.

PURPOSE: TNF alpha inhibitors have revolutionized the care of vision-threatening uveitis. This study evaluated the efficacy of adalimumab (ADA) for the treatment of refractory noninfectious uveitis. DESIGN: Randomized, prospective, controlled, two-center clinical trial Methods: Patients with active uveitis despite combined oral low-dose prednisolone and immunosuppression were randomized for additional ADA with corticosteroids in a fixed tapering regime, or corticosteroids only. Primary outcome measure at three months was improved best-corrected visual acuity (BCVA; >2 lines). In case of treatment failure, switch to the other arm was possible. RESULTS: Twenty-five patients (10 ADA, 15 controls) were included. BCVA increased with ADA by > 2 lines in 6/10 patients (60%; mean increase of 0.23 logMAR), but in only 2/15 from controls (13%, mean increase of 0.04 logMAR, Fisher´s exact test p = 0.00221). CONCLUSIONS: The results show superiority of ADA over controls in severe ocular inflammation including anterior uveitis.

Evidence for Tocilizumab as a Treatment Option in Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

OBJECTIVE: To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. RESULTS: A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. CONCLUSION: TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.

In vivo confocal microscopy of inflammatory cells in the corneal subbasal nerve plexus in patients with different subtypes of anterior uveitis.

PURPOSE: Previously we could show increased numbers and densities of dendritic-like cells (DLCs) in the subbasal nerve plexus of the central cornea in patients with herpetic anterior uveitis (HAU). Now we aimed to explore these and other inflammatory cells seen in this layer in different subtypes of anterior uveitis using in vivo confocal microscopy. METHODS: Consecutive eyes of patients with different types of anterior uveitis, HAU, Fuchs' uveitis syndrome (FUS), juvenile idiopathic arthritis (JIA) and human leucocyte antigen (HLA)-B27-related anterior uveitis were examined in vivo with the combination of Heidelberg Retina Tomograph II/III and Rostock Cornea Module. The contralateral eye was used as control. Inflammatory cells were defined on the basis of their morphology: type 1 (DLCs) and type 2 (cell bodies lacking dendrites). Frequencies were evaluated statistically in each group. RESULTS: The difference between means of type 1 cells density of affected eyes in all four groups was significant (one-way analysis of variance (ANOVA) p=0.039). The difference between means of type 1 cell densities of affected eyes in patients with HAU (96.8±44.2 cells/mm2, n=10) and that of patients with FUS (46.4±38.7 cells/mm2, n=17) was significant (Tukey's post hoc p=0.025), whereas the difference between patients with HAU and JIA (53.3±34.5 cells/mm2, n=7) and patients with HAU and HLA-B27 (63.1±59.2 cells/mm2, n=10) was not significant (Tukey's post hoc p=0.181 and 0.300). In contrast, the following means resulted from the evaluation of type 2 cells: the difference between means of affected eyes in all four groups was not significant (one-way ANOVA p=0.185). Density means difference of patients with HAU (44.9±22.6 cells/mm2, n=5) and that of FUS (20.0±11.0 cells/mm2, n=2) and that of patients with JIA (56.0±18.3 cells/mm2, n=2) and that of HLA-B27 (36.1±24.1 cells/mm2, n=5) was not significant (Tukey's post hoc p=0.302, 0.877 and 0.739). The contralateral eye of all patient groups showed also an inflammatory cell infiltrate of lesser extent. CONCLUSIONS: The high density and morphology of DLCs in the central cornea of patients with HAU assessed by confocal microscopy supports the clinical diagnosis of HAU especially when compared with patients with FUS but not when compared with patients with JIA or HLA-B27. CLINICAL RELEVANCE: This study suggests that the non-invasive confocal microscopy of the cornea is capable of supporting a clinical diagnosis in patients with uveitis.

Acute Retinal Necrosis: Diagnostic and Treatment Strategies in Germany.

PURPOSE: To analyze the preferred practice respective diagnosis, treatment, and complications in patients with acute retinal necrosis in Germany. METHODS: The uveitis-section of the German Ophthalmologic Society developed a questionnaire with 12 questions concerning patients with acute retinal necrosis seen in the 5 years up to August 2009. RESULTS: In total, 35 eye hospitals answered the questionnaire and reported 213 patients with acute retinal necrosis. Diagnosis was made clinically in 86%. Anterior chamber tap, vitreous biopsy, diagnostic vitrectomy, and serology were performed for confirmation. Therapy was started with acyclovir in all institutions, and continued with ganciclovir, foscarnet and brivudine in some cases. Intravitreal injections were performed in 46%. Additional oral steroids were given in 80%. A following oral antiviral treatment was performed in 94%. CONCLUSIONS: Relevant variations were seen in diagnosis and treatment practices. The survey outlines the need for a unique diagnostic and therapeutic guideline.

Influence of drug therapy on the risk of recurrence of ocular toxoplasmosis.

BACKGROUND/AIMS: Retrospective, observational case series with follow-up examination to analyse the influence of drug therapy on ocular toxoplasmosis (OT) in terms of recurrence-risk. METHODS: In this one centre study an existing data set of 84 patients with active OT was used. Drug therapy for 255 active lesions was retrospectively reconstructed. Median recurrence-free survival time was calculated for the different treatment regimes using Kaplan-Meier estimates. RESULTS: 20 different regimens were used as treatment of OT in the catchment area of the Interdisciplinary Uveitis Center, University of Heidelberg, Germany. Median recurrence-free survival time was significantly lower after using systemic corticosteroid monotherapy (0.9 years; 95% CI 0.5 to 1.3 years) compared with Toxoplasma gondii-specific antibiotic treatment (3.0 years; 95% CI 2.2 to 3.9 years; p<0.001) or compared with no therapy (3.0 years; 95% CI 2.1 to 3.9 years; p=0.006). No difference could be detected when comparing median recurrence-free survival time after using T gondii-specific antibiotics compared with no therapy (p=0.679). CONCLUSIONS: Although our study shows that drug therapy seems to influence the risk of recurrence of OT, there is no consensus regarding the choice of antiparasitic agents for treatment regimens in the catchment area of the Interdisciplinary Uveitis Center, University of Heidelberg. Survey results provide useful information for treating physicians and for clinical investigators interested in therapy.

Ocular toxoplasmosis: background and evidence for an antibiotic prophylaxis.

PURPOSE OF REVIEW: The purpose of this review was to provide an overview of current data on antibiotic prophylaxis in ocular toxoplasmosis. RECENT FINDINGS: Studies showing the prophylactic effect of long-term antibiotics are discussed. Prophylaxis seems to be justified in patients with a high risk of recurrence because of antibiotic's potential side-effects. Therefore, predisposing factors leading to a higher risk of recurrence and the time period during which an antibiotic prophylaxis is most appropriate are reviewed. Finally, a patient-individualized treatment recommendation is summarized. SUMMARY: In the current literature, two prospective, randomized case-control studies exist, which show the protective effect of an antibiotic prophylaxis. Hematologic, gastrointestinal and dermatologic complications are potential side-effects. Especially during the first year after suffering a recurrence, an antibiotic prophylaxis seems to be justified. The risk of a recurrence is inter alia influenced by the duration of the disease, the immune status of the host and the patient's age. Therefore, an antibiotic prophylaxis should be considered for patients who have recently been infected with ocular toxoplasmosis, for middle-aged and elderly patients and patients with a compromised immune system. This should be discussed with each patient individually, especially if the lesion is close to the macula.

Abatacept in the treatment of severe, longstanding, and refractory uveitis associated with juvenile idiopathic arthritis.

OBJECTIVE: Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor-α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications. RESULTS: In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup. CONCLUSION: A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

Time patterns of recurrences and factors predisposing for a higher risk of recurrence of ocular toxoplasmosis.

PURPOSE: To ascertain time patterns of recurrences and factors predisposing for a higher risk of recurrence of ocular toxoplasmosis. METHODS: Retrospective observational case series with follow-up examination. Database of 4,381 patients with uveitis was used. Data of 84 patients with ocular toxoplasmosis (sample group) could be included. RESULTS: Two hundred and eighty active lesions in the first affected eye were detected. The mean number of recurrences per year was 0.29 (standard deviation, 0.24). Median recurrence-free survival time was 2.52 years (95% confidence interval, 2.03-3.02 years). Risk of recurrence was highest in the first year after the most recent episode (26%) implying a decrease with increasing recurrence-free interval. The risk of recurrence decreased with the duration of disease (P < 0.001). Treatment of the first active lesion influenced the risk of recurrence (P = 0.048). Furthermore, the risk of recurrence was influenced by patient age at the time of the first active lesion (P = 0.021) and the most recent episode (P = 0.002). CONCLUSION: A secondary antibiotic prophylaxis could be discussed 1) during the first year after an active lesion has occurred, especially in case of the first active lesion of ocular toxoplasmosis, and 2) in older patients, especially if primarily infected with Toxoplasma gondii at an older age.

Characterisation of uveitis in association with multiple sclerosis.

PURPOSE: To characterise uveitis in association with multiple sclerosis (MS). METHODS: We conducted a retrospective chart review of patients with uveitis and MS at two uveitis centres (Portland, Oregon, USA and Heidelberg, Germany). Baseline characteristics and ophthalmic data were collected at the patient's first and last visits. Additionally, neurological records were obtained when possible. RESULTS: We identified 113 patients (196 eyes) with uveitis and MS. Of these, 53 had a diagnosis of MS confirmed by review of neurological records, 50 additional patients fulfilled the Poser criteria for MS and 10 with MS were referred by an outside neurologist. Among them, 83 (73%) were women and the mean age of presentation was 40.6 years (range 13-64 years). The average visual acuity in affected eyes at presentation was 20/39. There were 90 patients (80%) who presented with intermediate uveitis and 24 patients (15%) with anterior uveitis. Posterior and pan-uveitis were found in four patients (3%) and two patients (2%), respectively. During a median follow-up of 3.2 years (range 0.04-21 years), visual acuity improved -0.09 logMar/year. Compared with our location-matched controls with idiopathic intermediate uveitis (n=16), patients with MS and intermediate uveitis were significantly older when diagnosed with uveitis (p=0.027) and more likely to be female (p=0.01). There was no statistical difference in visual acuity or rate of vision change between our cases and controls (p=0.58 and p=0.36, respectively). CONCLUSIONS: Uveitis with MS generally presents as intermediate uveitis with a minority presenting with anterior uveitis. Patients are significantly older and more likely to be women than patients with idiopathic intermediate uveitis. The visual prognosis is generally favourable.

Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes.

OBJECTIVE: To report baseline articular, functional and ocular findings of the first international prospective cohort study of Blau syndrome (BS). METHODS: Three-year, multicentre, observational study on articular, functional (HAQ, Childhood HAQ and VAS global and pain), ophthalmological, therapeutic and radiological data in BS patients. RESULTS: Baseline data on the first 31 recruited patients (12 females and 19 males) from 18 centres in 11 countries are presented. Of the 31 patients, 11 carried the p.R334W NOD2 mutation, 9 the p.R334Q and 11 various other NOD2 missense mutations; 20 patients were sporadic and 11 from five BS pedigrees. Median disease duration was 12.8 years (1.1-57). Arthritis, documented in all but one patient, was oligoarticular in 7, polyarticular in 23. The median active joint count was 21. Functional capacity was normal in 41%, mildly impaired in 31% and moderate-severe in 28% of patients. The most frequently involved joints at presentation were wrists, ankles, knees and PIPs. On radiographs, a symmetrical non-erosive arthropathy was shown. Previously unknown dysplastic bony changes were found in two-thirds of patients. Ocular disease was documented in 25 of 31 patients, with vitreous inflammation in 64% and moderate-severe visual loss in 33%. Expanded manifestations (visceral, vascular) beyond the classic clinical triad were seen in 52%. CONCLUSION: BS is associated with severe ocular and articular morbidity. Visceral involvement is common and may be life-threatening. Bone dysplastic changes may show diagnostic value and suggest a previously unknown role of NOD2 in bone morphogenesis. BS is resistant to current drugs, suggesting the need for novel targeted therapies.

Risk of Recurrence of Preexisting Ocular Toxoplasmosis during Pregnancy.

PURPOSE: Comparison between the risk of recurrence during pregnancy with nonpregnant periods in patients with ocular toxoplasmosis (OT). METHODS: Records of 40 women were retrospectively reviewed. The women were subdivided into either a pregnant group or a control group formed by nonpregnant women during follow-up. Comparable cases from the literature were added. Mean number of recurrences per year was compared. RESULTS: Eleven women with pregnancies could be included. Six cases from the literature were added (total n = 17). Mean number of recurrences per year during versus not during pregnancy was 0.16 (SD 0.39) versus 0.32 (SD 0.30; p = 0.088), respectively. In the control group (n = 29) the mean number of recurrences per year (0.31; SD 0.27) was significantly higher when compared to cases during pregnant periods (p = 0.002). CONCLUSION: Adding to published series, the presented data do not provide evidence for a relevant impact of pregnancy on recurrence behavior in OT.

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

Ocular changes during pregnancy.

BACKGROUND: Most ocular changes in pregnancy are harmless. For example, 14% of pregnant women need a new eyeglass prescription. Some changes, however, are serious, such as retinal effects of hypertension, which can be a sign of pre-eclampsia. Ocular changes may give rise to uncertainty about the administration of ophthalmological drugs or the optimal method of childbirth. METHOD: This review is based on pertinent literature retrieved by a selective search in Medline and on guidelines from Germany and abroad. Recommendations about drugs were taken from the Embryotox and Reprotox databases, the German Red List, and the United States Food and Drug Administration (FDA). RESULTS: 40% to 100% of pregnant women with high blood pressure have retinal changes whose severity is correlated with the severity of pre-eclampsia or eclampsia. Diabetic women should undergo ocular examination before and during pregnancy. Pre-existing retinal changes worsen during pregnancy in 55% of cases. Most ocular diseases can be treated with the usual drugs in pregnant women and nursing mothers, although the evidence for drug safety is derived from case series and the treatment is usually provided off label. Ocular conditions that are present before pregnancy are irrelevant to the choice of a method of childbirth. CONCLUSION: Pregnant women and nursing mothers can undergo most types of ophthalmological examination and treatment. Recommendations about drug treatment should be checked against current information that can be found on the embryotox.de and reprotox.de websites.

Experiences with rituximab for the treatment of autoimmune diseases with ocular involvement.

OBJECTIVE: To report the efficacy of rituximab (RTX) in the treatment of ocular or orbital inflammation accompanying autoimmune diseases refractory to previous standard immunosuppressive therapy. METHODS: We reviewed medical records of 9 consecutive patients with noninfectious ocular or orbital inflammation treated with RTX. RESULTS: Over a mean followup of 42 months, 7 patients were in clinical remission, 1 had partial response to treatment, and 1 did not respond. Best corrected visual acuity improved ≥ 1 line in 4 patients, was stable in another 4 patients, and worsened in 1. Concomitant immunosuppressive therapy was tapered in 6 cases. Systemic corticosteroids were tapered or kept below 7.5 mg a day in 5 patients 1 year after the first RTX cycle. CONCLUSION: RTX therapy, in patients who are refractory to standard immunosuppressive therapy, was effective and showed a beneficial response to treatment including induction of clinical remission of inflammation in most patients.

Use of intravitreal rituximab for treatment of vitreoretinal lymphoma.

AIM: Vitreoretinal lymphoma is a diffuse large B cell non-Hodgkin lymphoma. Targeting malignant cells with rituximab is being used increasingly as local chemotherapy, but information on this treatment is scant. We aimed to describe current therapeutic approaches, as well as responses to and complications of, intravitreal rituximab in patients with vitreoretinal lymphoma. METHODS: Clinical data were collected in a standardised manner retrospectively on patients with vitreoretinal lymphoma treated with intravitreal rituximab. RESULTS: 48 eyes (34 patients) with vitreoretinal lymphoma were treated with a median of 3.5 intravitreal injections of rituximab (1 mg/0.1 mL) for new diagnosis (68.8%), progressive disease (29.9%) and maintenance therapy (2.1%). Intravitreal rituximab±methotrexate was the sole treatment in 19 eyes (39.6%). 31 eyes (64.6%) eyes achieved complete remission, after a median of 3 injections; 7 of these eyes developed recurrent disease. 11 eyes (22.9%) achieved partial remission. Although rituximab may have contributed to complications reported in 12 eyes (25.0%), a 2-line loss of Snellen visual acuity occurred in only 2 of those eyes (4.2%). CONCLUSIONS: Approaches in rituximab-based intravitreal chemotherapy vary widely, but our findings suggest that this treatment may be safe and effective in inducing remission in a majority of eyes with vitreoretinal lymphoma.