S2k guideline: Rosacea.

This updated and upgraded S2k guideline deals with the diagnosis and treatment of rosacea, which is a common, chronic inflammatory skin disease mostly affecting the face. Initially, rosacea is characterized by recurrent erythema, telangiectasia and flushing. Later, the inflammatory component predominates, with persistent erythema with follicular papules, papulopustules and pustules. The development of phyma, which usually occurs on the acral localizations, is the most severe manifestation. For the treatment of rosacea, the interdisciplinary guideline committee, with representatives of the German Dermatological Society (DDG), the Professional Association of German Dermatologists (BVDD), the German Opthalmological Society (DOG), the Society for Dermopharmacy (GD), the Swiss Society for Dermatology and Venereology (SGDV) and the German Rosacea Aid e. V., recommends the avoidance of trigger factors and topical applications of metronidazole, azelaic acid or ivermectin. For symptomatic treatment of persistent centrofacial erythema, the topical vasoconstrictors brimonidine or oxymetazoline can also be used. Systemic therapy is recommended for therapy-resistant and severe forms of rosacea papulopustulosa. The drug of choice is low-dose doxycycline. Alternatively, low-dose isotretinoin can be recommended. Ocular rosacea should be treated with lid margin hygiene. For topical treatment, ciclosporin eye drops, azithromycin, ivermectin or metronidazole are suggested.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

[Evolving Consensus of International Uveitis Study Group, Intraocular Inflammation Society, and Foster Ocular Inflammation Society with Uveitis in the Time of COVID-19 Infection]. / Konsenserfahrung von International Uveitis Study Group, Intraocular Inflammation Society und Foster Ocular Inflammation Society zur Uveitis in der Zeit der COVID-19-Infektion.

This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS) and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic.

Graft versus self (GvS) against T-cell autoantigens is a mechanism of graft-host interaction.

Graft-versus-host disease (GVHD) represents the major nonrelapse complication of allogeneic hematopoietic cell transplantation. Although rare, the CNS and the eye can be affected. In this study, manifestation in the retina as part of the CNS and T-cell epitopes recognized by the allogeneic T cells were evaluated. In 2 of 6 patients with posttransplantation retina diseases and 6 of 22 patients without ocular symptoms, antigen-specific T-cell responses against retina-specific epitopes were observed. No genetic differences between donor and recipient could be identified indicating T-cell activation against self-antigens (graft versus self). Transplantation of a preexisting immunity and cross-reactivity with ubiquitous epitopes was excluded in family donors and healthy individuals. In summary, an immunological reaction against retina cells represents a mechanism of graft-versus-host interaction following hematopoietic cell transplantation.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates.

Vitreoretinal diffuse large B-cell lymphoma is a rare disorder, occurring as primary ocular disease or as secondary involvement by primary central nervous system lymphoma. It is usually diagnosed by cytologic, immunocytochemical, and molecular examination of vitreous aspirates. However, distinguishing vitreoretinal diffuse large B-cell lymphoma from uveitis remains difficult, and clonality analysis may be either unsuccessful or misleading. Diffuse large B-cell lymphoma arising in immune-privileged sites (eg, the central nervous system) shows a high frequency of MYD88 mutations. Therefore, we retrospectively assessed the frequency of MYD88 mutations in vitreoretinal lymphoma (VRL) and their diagnostic potential in 75 vitrectomy samples of 69 patients, and validated our results in a separate cohort (n = 21). MYD88 mutations were identified in 20 of 29 (69%) clinically, histologically, and molecularly confirmed VRL, including 6 cases of the test cohort initially diagnosed as reactive (3/6) or suspicious (3/6) for lymphoma. MYD88 mutations, especially L265P, are very frequent in VRL and their detection significantly improves the diagnostic yield of vitrectomy specimens.

Ophthalmic Rosacea: Case Report in a Child and Treatment Recommendations.

We report a rare case of rosacea with ocular involvement in a child that remitted with prolonged anti-inflammatory oral tetracycline therapy and provide general expert recommendations. A 14-year-old girl presented with discrete papules and pustules on both cheeks with blepharitis and conjunctivitis. Ophthalmologic examination confirmed bilateral severe blepharitis, as well as a corneal infiltrate in the right eye with additional neovascularization. The diagnosis of rosacea with ocular involvement was made. In addition to the existing antibiotic and anti-inflammatory topical eye therapy, systemic treatment with minocycline 50 mg twice a day was started. After marked improvement, the dose was reduced to 50 mg once a day. After further amelioration, treatment was switched to maintenance therapy with 40 mg of prolonged-release doxycycline. Three years after a 12-month course of anti-inflammatory therapy, the patient remained recurrence free.

Diagnostic relevance of direct immunofluorescence in ocular mucous membrane pemphigoid.

BACKGROUND AND OBJECTIVES: The objective was to determine the diagnostic value of direct immunofluorescence (DIF) in ocular mucous membrane pemphigoid (ocular MMP), taking into account immunofluorescence patterns and biopsy sites. PATIENTS AND METHODS: DIF results and medical records of 54 patients with a suspected diagnosis of ocular MMP were reviewed. RESULTS: There was an overall prevalence of ocular MMP in 70.4 % of cases. Linear deposition of IgA, IgG, or C3 showed a high positive predictive value (84-100 %). Sensitivity and negative predictive value of IgG, IgM, IgG, and C3 in DIF were higher in cutaneous samples than in conjunctival biopsies, thus yielding a higher diagnostic accuracy. The sensitivity of DIF in ocular MMP seems to be lower than in bullous pemphigoid. CONCLUSIONS: The diagnostic value of DIF in the workup of ocular MMP was confirmed. However, biopsies taken from non-conjunctival, cutaneous tissue appear to yield more accurate results.

Is cyclophotocoagulation an option in the management of glaucoma secondary to Fuchs' uveitis syndrome?

BACKGROUND: Glaucoma is one of the sight-threatening complications of Fuchs' uveitis syndrome (FUS) and the most difficult to manage. The goal of this study was to assess the efficacy and safety of cyclophotocoagulation (CPC) in the management of glaucoma secondary to FUS. METHODS: In a retrospective analysis, the charts of all patients with FUS referred to our clinic from January 2002 to December 2012 were reviewed. In patients with glaucoma or ocular hypertension, controlled eye pressure was defined using two alternative upper limits of 6 ≤ IOP ≤ 21 mmHg and 6 ≤ IOP ≤ 18 mmHg at 1 year follow-up. RESULTS: One hundred and seventy-six patients with FUS were included in this study. Of those, 28 had ocular hypertension (OHT) or glaucoma. Mean maximal intraocular pressure (IOP) of patients with glaucoma/OHT was 40.8 mmHg. Twenty-three patients (82.1 %) had maximal IOP levels of 35 mmHg or higher. Sixteen patients with glaucoma/OHT underwent CPC alone (ten patients) or in combination with other surgical procedures (six patients). After 1 year, control of IOP for both upper limits (6 ≤ IOP ≤ 18 mmHg) and (6 ≤ IOP ≤ 21 mmHg) was achieved in six of ten patients (60 %) who received CPC alone, and in five of six patients (83.3 %) who required additional surgery after CPC. The mean number of cycloablative procedures was 1.3 (range 1-2) in the CPC alone group and 1.2 (range 1-2) in patients for whom CPC was used as adjunct therapy. There was no exacerbation of intraocular inflammation, no postoperative hypotony and no phthisis bulbi in the 16 patients who underwent CPC. CONCLUSIONS: CPC is a safe and effective procedure that should be considered if medical treatment has failed to control glaucoma in FUS.

Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials.

PURPOSE: To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis. DESIGN: Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE. PARTICIPANTS: A total of 118 patients with Behçet's uveitis (SHIELD study); 31 patients with active, noninfectious, non-Behçet's uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non-Behçet's uveitis (ENDURE study) were enrolled. METHODS: After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study. MAIN OUTCOME MEASURES: Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes. RESULTS: After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies. CONCLUSIONS: The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM.

Experts Opinion: OCTA vs. FFA/ICG in Uveitis - Which Will Survive?

Will optical coherence tomography angiography (OCTA) replace invasive imaging techniques like fundus fluorescein angiography (FFA) and indocyanine green (ICG) angiography entirely? While OCTA is being increasingly applied in the field of medical retina, will we see this change in the subspeciality of uveitis? In this article, five uveitis specialists with renowned imaging expertise answer to 10 specific questions to address this issue. The final verdict based on the comments of the experts suggests that FFA and ICG cannot be replaced by OCTA in uveitis, at least for now. While OCTA can offer new insights into the pathogenesis of certain inflammatory conditions and help in the diagnosis of complications like inflammatory choroidal neovascularisation, multimodal imaging is still the preferred approach in the assessment of patients with uveitis.

Identification of immunodominant epitopes of alpha-crystallins recognized by antibodies in sera of patients with uveitis.

BACKGROUND: A high incidence of autoantibodies to lens proteins has been found in sera of patients with uveitis. We showed previously that the anti-lens antibodies reacted predominantly with α-crystallins. The aim of the present study was to identify immunodominant epitopes within the protein chains of human αA- and αB-crystallin. METHODS: Epitope specificities of antibodies to αA- and αB-crystallin were examined by ELISA using synthetic overlapping peptides, spanning the entire length of both α-crystallins. The peptides consisted of 25 amino acid residues, with an overlap of at least eight amino acids each. The synthetic peptides were tested against sera of 110 patients with different uveitis forms, classified according to anatomical location of intraocular inflammation. RESULTS: Four immunodominant regions within the protein chains of αA- and αB-crystallin could be identified. These regions were recognized by antibodies in sera of 56% of uveitis patients. Anti-lens antibodies of IgG-type reacted preferentially with regions located at amino acid (aa) residues aa:69-93 and aa:137-161 of αA-crystallin as well as aa:69-110 and aa:137-161 of αB-crystallin. IgM antibodies recognized predominantly region aa:149-173 of αA-crystallin, and aa:69-110 and aa:151-175 of αB-crystallin. IgM antibodies directed to peptide aa:69-93 of αB-crystallin were found in sera of 30% of patients with intermediate uveitis. CONCLUSIONS: Four immunodominant B-cell epitopes within the protein chains of αA- and αB-crystallin have been identified; however, no clear correlation with the anatomically defined uveitis subtypes has been found except for intermediate uveitis. Whether there may be a correlation with uveitis forms with similar etiopathogenesis has to be evaluated in further studies.

Epidemiology of Viral Induced Anterior Uveitis.

PURPOSE: Viral agents are the most common cause of infectious anterior uveitis worldwide. The purpose of this review is to analyze the frequency, gender and racial differences of viral anterior uveitis (VAU) in various populations. METHODS: Systematized literature review of epidemiological reports of VAU cited in PubMed, EMBASE and the Cochrane Library database published until June 30th, 2020. RESULTS: A total of 12 clinical studies on epidemiology of definite VAU and 36 clinical studies of presumed VAU were identified. Members of Herpesviridae family represent the most common causes of VAU. Other less frequently reported causes, such as rubella and endemic viruses (HTLV-1, Chikungunya, Dengue, Ebola, Zika virus) were also analyzed. CONCLUSION: HSV, VZV are prevalent worldwide. CMV is more frequent in Asia, and rubella in the West. However, due to globalization and air travel, HTLV-1, Chikungunya, Dengue and Ebola may become important causes of VAU across the world.

Rosacea and Dry Eye Disease.

Ocular rosacea is a chronic potentially sight-threatening inflammatory condition, which can occur in approximately 20% of patients without skin involvement. However, an accurate diagnosis of ocular rosacea has not been defined yet due to its rather nonspecific symptoms and clinical findings. Therefore, this article updates the current recommendations for diagnosis and treatment of ocular rosacea and the previously published consensus recommendations from the ROSCO expert panel on the management of rosacea.

Mesalazine Suppresses Proinflammatory Cytokines in Patients with Acute Anterior Uveitis Independently of HLA-B27.

PURPOSE: The aim is to unravel the mechanism of mesalazine (5-ASA) on proinflammatory cytokines in PBMCs of patients with HLA-B27 +and HLA-B27 -acute anterior uveitis (AAU), and whether this may explain the different effects of 5-ASA in both disoders. METHODS: PBMCs from 12 HLA-B27+ and 4 HLA-B27- AAU patients were preincubated with 5-ASA and stimulated with LPS. As mesalazine (5-ASA) could be involved in ER stress, proinflammatory and ER stress-associated cytokines and markers were measured. RESULTS: Mesalazine (5-ASA) suppressed IL-6 mRNA in healthy donors and in HLA-B27+ and HLA-B27- patients but did not lead to induction and secretion of IL-1ß. In HLA-B27 + or - patients the ER stress-associated markers CHOP (DDIT3) and ATF6 were suppressed. CONCLUSIONS: Here we show that mesalazine (5-ASA) inhibits the transcription of proinflammatory and (ER) stress associated cytokines and markers, independently of the HLA-B27 status. Results show the similarities of both AAU types but do not decipher the mechanism why the HLA-B27 status determines the therapeutic response to mesalazine in AAU.

COVID-19 Vaccination and Uveitis: Epidemiology, Clinical Features and Visual Prognosis.

PURPOSE: To study the epidemiological and clinical features of uveitis post-COVID-19 vaccination. PATIENTS AND METHODS: Retrospective chart review of patients presenting with uveitis after COVID-19 vaccination in tertiary uveitis services. RESULTS: In total, 25 patients, 76% females, mean age 43.2 years, were included. Uveitis occurred after Pfizer, Moderna, Astra-Zeneca and Covaxin vaccination. Anterior uveitis was the most frequent type of uveitis (56%). History of uveitis was found in 19 cases (76%), among whom 90.9% of the tested patients developed anti-Sars-CoV-2 spike antibodies after vaccination. In a mean follow-up of 5 months, one-line decrease in visual acuity was found in 12% of patients. During post-vaccine uveitis, 15.8% of cases needed an increase in their systemic therapy. According to Naranjo score, new-onset uveitis had a higher probability of being associated with vaccination (p < .01). CONCLUSION: COVID-19 vaccination can cause uveitis but has no significant impact on the visual prognosis after resolution.

Tuberculous Scleritis and Multidrug Resistance.

PURPOSE: To present a case of necrotizing sclerokeratitis in a patient with multidrug-resistant tuberculosis and study the challenges in diagnosis and management of anterior tuberculous scleritis. METHODS: Retrospective observational case report and review of anterior tuberculous scleritis. RESULTS: A 28-year-old woman, previously diagnosed as presumed tubercular panuveitis, presented with necrotizing sclerokeratitis and progressed to develop panophthalmitis. Laboratory investigations revealed multidrug-resistant Mycobacterium tuberculosis as the etiological agent. We reviewed cases of anterior tuberculous scleritis published in the literature, with regards to clinical features, microbiological investigations, treatment, and outcomes. Treatment includes standard antitubercular therapy, with or without systemic corticosteroids. Poor response to treatment is seen either due to delayed diagnosis or drug resistance, and the significance of the same is highlighted in our case. CONCLUSION: Diagnosis of tuberculous scleritis is a challenge. Therapeutic failure must alert the clinician for drug resistance which is diagnosed early, can prevent the devastating outcomes.

Drug-induced Sarcoid Uveitis with Biologics.

PURPOSE/OBJECTIVES: to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features. MATERIALS AND METHODS: This is a multicenter, retrospective case series. Patients under biologic therapy were included if they developed uveitis for the first time or experienced intraocular inflammation which was different in location or laterality to previous inflammation. RESULTS: Sixteen patients were identified. The underlying disorders included ankylosing spondylitis, juvenile idiopathic arthritis, rheumatoid arthritis, and Behçet's Disease. The biologic agents associated with a first episode of uveitis (n = 11) or with a new recurrence of uveitis (n = 5) were etanercept, adalimumab, abatacept, infliximab, and golimumab. Sarcoidosis based on bihilar lymphadenopathy, other computer tomography-findings, or biopsy was diagnosed in five patients under therapy with etanercep, adalimumab, and abatacept. Additionally, seven patients developed clinical changes in their uveitis pattern, suggesting sarcoid uveitis. CONCLUSIONS: Biologic treatment-induced uveitis often presents as granulomatous disease.

Long-term remission after cessation of interferon-α treatment in patients with severe uveitis due to Behçet's disease.

OBJECTIVE: To retrospectively assess the development of visual acuity and the frequency and duration of relapse-free periods in patients who were treated with interferon-α (IFNα) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of ≥2 years. METHODS: IFN alfa-2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission. RESULTS: Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0-12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long-term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered. CONCLUSION: Our findings indicate that IFNα induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis.