[Intermediate and Posterior Uveitis - Disease entities]. / Intermediäre und posteriore Uveitis ­ Teil 2.

Intermediate and posterior uveitis can have multiple infectious and noninfectious causes, and posterior uveitis in particular is clinically multifaceted. Some entities require prompt initiation of therapy to ensure visual prognosis. This article presents typical characteristics of intermediate and posterior uveitides and explains special features of their treatment.

Infectious Posterior Uveitis - Toxoplasmosis, Treponema, Tuberculosis (TTT). / Infektiöse posteriore Uveitis ­ Toxoplasmose, Treponema, Tuberkulose (TTT).

Toxoplasma gondii, Treponema pallidum and Mycobacterium tuberculosis are the most important infectious causes of posterior uveitis. The epidemiology, clinical picture, diagnostic and treatment strategies of these diseases are presented.

Multimodal imaging in infectious and noninfectious intermediate, posterior and panuveitis.

PURPOSE OF REVIEW: Given the heterogeneity of uveitis, markers of inflammation vary from patient to patient. Multimodal imaging has proven itself to be critical for accurate evaluation for disease activity and treatment response in uveitis. RECENT FINDINGS: Ultra-widefield (UWF) fluorescein angiography and autofluorescence (AF) as well as optical coherence tomography angiography (OCTA) have provided insights into disease pathogenesis and monitoring not previously appreciated. In addition to structural retinal imaging, OCT can be used to assess the choroid, the posterior cortical vitreous and the retinal vasculature in eyes with uveitis. SUMMARY: Multimodal ocular imaging in eyes with uveitis is critical for disease diagnosis and assessing response to treatment. UWF fluorescein angiography can detect retinal vasculitis even in the absence of overt vascular sheathing. UWF AF can help detect more chorioretinal lesions than clinically visible. OCT can be used to assess the posterior cortical vitreous, retina, large retinal vessels and choroid in uveitis. The use of multimodal imaging will likely be needed to determine clinical trial endpoints in studies evaluating therapeutics for uveitis.

Development of a Core Outcome Set for Clinical Trials in Non-infectious Uveitis of the Posterior Segment.

PURPOSE: To develop an agreed upon set of outcomes known as a "core outcome set" (COS) for noninfectious uveitis of the posterior segment (NIU-PS) clinical trials. DESIGN: Mixed-methods study design comprising a systematic review and qualitative study followed by a 2-round Delphi exercise and face-to-face consensus meeting. PARTICIPANTS: Key stakeholders including patients diagnosed with NIU-PS, their caregivers, and healthcare professionals involved in decision-making for patients with NIU-PS, including ophthalmologists, nurse practitioners, and policymakers/commissioners. METHODS: A long list of outcomes was developed based on the results of (1) a systematic review of clinical trials of NIU-PS and (2) a qualitative study of key stakeholders including focus groups and interviews. The long list was used to generate a 2-round Delphi exercise of stakeholders rating the importance of outcomes on a 9-point Likert scale. The proportion of respondents rating each item was calculated, leading to recommendations of "include," "exclude," or "for discussion" that were taken to a face-to-face consensus meeting of key stakeholders at which they agreed on the final COS. MAIN OUTCOME MEASURE: Items recommended for inclusion in the COS for NIU-PS. RESULTS: A total of 57 outcomes grouped in 11 outcome domains were presented for evaluation in the Delphi exercise, resulting in 9 outcomes directly qualifying for inclusion and 15 outcomes being carried forward to the consensus meeting, of which 7 of 15 were agreed on for inclusion. The final COS contained 16 outcomes organized into 4 outcome domains comprising visual function, health-related quality of life, treatment side effects, and disease control. CONCLUSIONS: This study builds on international work across the clinical trials community and our qualitative research to construct the world's first COS for NIU-PS. The COS provides a list of outcomes that represent the priorities of key stakeholders and provides a minimum set of outcomes for use in all future NIU-PS clinical trials. Adoption of this COS can improve the value of future uveitis clinical trials and reduce noninformative research. Some of the outcomes identified do not yet have internationally agreed upon methods for measurement and should be the subject of future international consensus development.

Role of Ocular Imaging in Diagnosis and Determining Response to Therapeutic Interventions in Posterior and Panuveitis.

ABSTRACT: This review provides a comprehensive description and careful interpretation of various ocular imaging techniques to visualize the different ocular structures in posterior and panuveitis. This can help in the diagnosis, follow-up, and monitoring the response to treatment in patients with different posterior and panuveitic entities.

[Treatment of noninfectious intermediate uveitis, posterior uveitis, or panuveitis]. / Traitement des uvéites intermédiaires, postérieures et panuvéites non infectieuses.

Controlling long-term inflammation during non-infectious intermediate, posterior or panuveitis while limiting side effects remains challenging. There is no standardized pre-therapeutic evaluation providing diagnostic certainty, but some simple tests allow us to identifiy the main etiologies. The ophthalmologist identifies the type of uveitis, and the internist completes the investigations according to the ophthalmologist's findings. Fundus photographs, optical coherence tomography, and fluorescein and indocyanine green angiography should be considered during diagnosis and follow-up. Ocular complications of uveitis are numerous. They require close monitoring and specific medical and sometimes surgical management. The growing number of available drugs makes it possible to optimize the management of these conditions with varied etiologies and presentations. Currently, systemic corticosteroids remain the mainstay of therapy, and other alternatives are considered in the case of poor tolerance, steroid resistance or dependence. The choice of a systemic, periocular or intravitreal treatment depends on several factors: chronicity or recurrence of uveitis, duration, bilaterality, association with a systemic inflammatory disease, the presence of contraindications to certain treatments, and also socioeconomic constraints. It is of the utmost importance to find the best compromise allowing tight control of ocular inflammation by means of adapted systemic and/or local treatment while avoiding the main complications.

[Diagnostic Strategy and Therapeutic Dilemma in Acute Posterior and Panuveitis]. / Diagnostische Strategie und therapeutisches Dilemma bei akuter posteriorer und Panuveitis.

Acute posterior and panuveitis mostly affect younger patients and affect both eyes in more than half of cases. Because of the severe consequences in the clinical course, rapid and broad differential diagnosis are critical steps. Permanent loss of vision after a delay in starting therapy and the initiation of ineffective treatment are both serious risks. The initial diagnostic classification is based on clinical presentation (anatomical localisation and type of inflammation) and clinical course and, secondarily, on the response to acute therapy. The aetiology is acute in as many as one third of cases. The most frequent acute posterior uveitis in immunocompetent persons is acute viral retinal necrosis. It is difficult to distinguish this clinically from Behçet uveitis, as long as there are no systemic manifestations. In patients with disease threatening the macula, high dose steroid therapy must be started no later than 24 hours after the start of antiviral and anti-parasitic acute therapy. Thus, misdiagnosis has therapeutic consequences. Moreover, the prognosis is favourably affected by aggressive treatment of acute posterior uveitis. Any delay in starting therapy increases infectious and inflammatory tissue damage, and increases the risk of involvement of the other eye and of other organs. On the other hand, the use of high doses of steroids, immunosuppressives and biological agents can lead to uncontrolled proliferation of the pathogen and relapses.

Need for Quantitative Measurement Methods for Posterior Uveitis: Comparison of Dual FA/ICGA Angiography, EDI-OCT Choroidal Thickness and SUN Vitreous Haze Evaluation in Stromal Choroiditis.

BACKGROUND/PURPOSE: Quantitative methods for posterior uveitis are necessary for precise appraisal and follow-up of inflammation in practice and in clinical trials. The aim of this study was to assess fluorescein angiography (FA), indocanine green angiography (ICGA), and enhanced depth imaging optical coherence tomography choroidal thickness (EDI-OCT CT) in two stromal choroiditis entities, birdshot retinochoroiditis (BRC), and Vogt-Koyanagi-Harada disease (VKH), as well as to determine (1) disease patterns, (2) respective response to therapy, and (3) their potential utility in clinical trials in comparison to vitreous haze, the present standard outcome used in clinical trials. METHODS: This retrospective study included newly diagnosed patients with BRC and VKH, seen at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiographic signs were quantified using an established dual FA/ICGA scoring system for uveitis at presentation and on follow-up. FA/ICGA score ratios were compared between diseases to determine disease patterns. EDI-OCT CT was determined using a spectral domain instrument. Vitreous haze was determined using the SUN (Standardization of Uveitis Nomenclature) method. RESULTS: Among 1872 uveitis patients seen from 1995 to 2016, 8 newly diagnosed BRC patients (16 eyes) and 6 newly diagnosed VKH patients (12 eyes) had sufficient data for study inclusion. Patients with BRC and VKH at initial onset had mean FA scores of 16.1 ± 7.0 vs. 4.6 ± 2.1 (p < 0.0001), respectively, while mean ICGA scores were similarly high in the two diseases, 18.9 ± 3.6 (BRC) vs. 20.8 ± 7.5 (VKH). After therapy, FA and ICGA scores decreased significantly for both entities (- 60% of FA score and 55% of ICGA score in BRC vs. - 72% of FA score and - 87% for ICGA score in VKH). EDI-OCT CT decreased significantly in the two entities. Vitreous haze was almost absent in VKH and low in BRC. CONCLUSION: Dual FA/ICGA scoring showed the diverse disease patterns of BRC and VKH; both the retina and choroid were involved at onset in BRC, whereas VKH was a pure choroidal disease with later spillover into the retina. Dual FA/ICGA allowed for the precise measurement of inflammation at onset and upon follow-up. EDI-OCT CT responded to therapy in both diseases but was found to be of limited use in this early/subacute disease phase because it lacked sensitivity to detect subclinical recurrences and was therefore only useful for long-term follow-up. Vitreous haze was low in both entities and thus useless as an inflammatory parameter.

Successful multi-modality approach in management of human leukocyte antigen-B27 associated fulminant panuveitis - rare presentation.

Objective: To report a multimodality approach in the management of human leukocyte antigen B27 (HLA-B27) associated fulminant posterior uveitis, an uncommon presentation, with good visual and anatomical recovery. Methods: A 33-year-old young male presented with HLA-B27 associated severe posterior uveitis, which is a relatively uncommon presentation. The patient had severe vitritis with papillitis, which was sequentially and stepwise managed with oral steroids, pars plana vitrectomy, immunosuppressive agents and sustained release intravitreal steroid implant. Results: The patient had a good recovery of vision with complete resolution of inflammation and without any long-term complication. Conclusion: HLAB27 positivity can be associated with an uncommon presentation of fulminant posterior uveitis that requires a judicious and stepwise multimodality approach in its management, and can have a good visual and anatomical outcome as demonstrated in our case.

COSUMO: study protocol for the development of a core outcome set for efficacy and effectiveness trials in posterior segment-involving uveitis.

BACKGROUND: Uveitis, a group of disorders characterised by intraocular inflammation, causes 10-15% of total blindness in the developed world. The most sight-threatening uveitis affects the posterior segment of the eye (posterior-segment involving uveitis (PSIU)). Numerous different outcomes have been used in clinical trials evaluating alternative treatments for uveitis, limiting inter-trial comparison and aggregation of data. We aim to develop a core outcome set (COS) that would provide a standardised set of outcomes to be measured and reported in all effectiveness trials for PSIU. METHODS: A three-phase design will be used informed by recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Phase 1: a comprehensive list of outcomes will be identified through both a systematic review of effectiveness trials of PSIU and qualitative research with stakeholders. The qualitative study will comprise focus groups with patients and their carers in parallel with one-to-one telephone interviews with health professionals and policy-makers. In the focus groups, patients will be grouped according to whether or not their uveitis is complicated by the sight-threatening condition uveitic macular oedema (UMO) since it is hypothesised that the presence of UMO may significantly impact on patient experience of PSIU. Phase 2: Delphi methodology will be used to reduce the range of potential outcomes for the core set. Up to three Delphi rounds will be used through an online survey. Participants will be asked to rate the importance of each outcome on a 9-point Likert scale where 9 is most important. Phase 3: a consensus meeting will be held with key stakeholders to discuss the Delphi results and ratify the final outcomes to be included in the COS. DISCUSSION: The development of an agreed COS for PSIU would help ensure that outcomes which matter to key stakeholders are captured and reported in a consistent way. A COS for PSIU would allow greater comparison and aggregation of data across trials for the better evaluation of established and emerging therapies through evidence synthesis and meta-analysis to inform clinical guidelines and health policy. TRIAL REGISTRATION: COMET. http://comet-initiative.org/studies/details/640 . August 2015.

COMBINED VITRECTOMY AND INTRAVITREAL DEXAMETHASONE (OZURDEX) SUSTAINED-RELEASE IMPLANT.

PURPOSE: To evaluate the safety and efficacy of combining intravitreal dexamethasone implantation (Ozurdex) with pars plana vitrectomy (PPV). METHODS: A retrospective review was conducted on cases where Ozurdex injection was performed in the operating room in conjunction with pars plana vitrectomy. Our primary outcome measure was the presence of surgical complications in the perioperative and 3-month postoperative window. We also measured visual acuity, intraocular pressure (IOP), and macular edema at baseline, one, and 3 months after surgery. RESULTS: Fifteen eyes in 14 cases were reviewed. There were no complications intraoperatively or at 1-month postoperatively. Two patients (2 eyes) with prior retinal detachment developed proliferative vitreoretinopathy and redetachment at 3 months. Visual acuity improved in 7 of 15 eyes, and an average improvement of 2 lines was achieved for the entire cohort. There was no overall change in intraocular pressure although 1 patient developed an increase in intraocular pressure >5 mmHg. Five of 9 patients with baseline macular edema experienced improvement or resolution at 3 months. CONCLUSION: Intraoperative Ozurdex in combination with PPV may be safe and effective in treating macular edema caused by many different underlying diseases.

Factors affecting therapeutic decisions in intermediate and posterior uveitis.

PURPOSE: To evaluate whether cost, insurance prior authorization, pregnancy considerations, and subspecialty practice lead to changes in therapeutic decisions among uveitis and retina specialists in the treatment of intermediate and posterior uveitis. DESIGN: Prospective cross-sectional study. METHODS: A total of 934 uveitis and retina specialists across the United States were surveyed via e-mail regarding their choice in long-term therapy for 3 hypothetical patients with uveitic conditions (Behçet disease, birdshot retinochoroiditis, and intermediate uveitis). Respondents were asked to select first- and second-choice therapies and then reselect first and second choices assuming cost of all options was equal to the patient and there would be no issues with insurance prior authorization. In 1 case, they were additionally asked for their treatment preferences if the patient desired a pregnancy. Outcomes of interest were differences in therapy choice based on cost/prior authorization, pregnancy, and subspecialty practice. RESULTS: One hundred and six respondents (11.3%) completed the survey; 44 were uveitis specialists and 62 retina specialists. Cost and prior authorization affected the therapy choices of uveitis specialists treating ocular Behçet disease (P = .008). Uveitis specialists and retina specialists differed in their first choice in therapy for each vignette when cost and prior authorization were equalized (P = .0018, P = .0049, and P = .0156). Both uveitis specialists and retina specialists changed their therapeutic choices for intermediate uveitis when pregnancy was a consideration (P = .00001 for uveitis specialists, P = .0044 for retina specialists). CONCLUSIONS: Physician decision making in intermediate and posterior uveitis is affected by cost and prior authorization concerns, pregnancy considerations, and subspecialty practice.

Use of Staurenghi lens angiography in the management of posterior uveitis.

PURPOSE: Retinal vasculitis is an important component of posterior uveitis. It may be difficult to detect either clinically or with conventional angiography. We assessed the role of Staurenghi lens angiography (SLA) in the diagnosis and management of patients with posterior uveitis. METHODS: A total of 26 patients attending the St Paul's Eye Unit uveitis clinic with posterior uveitis underwent wide-angle (150 degree) retinal angiography with the Heidelberg Retina Angiograph 2 Scanning Laser Ophthalmoscope using the Staurenghi SLO 230 contact lens. We determined the percentage of patients in whom this imaging modality assisted in diagnosing and quantifying the extent of vasculitis, planning treatment or monitoring disease activity. RESULTS: Staurenghi lens angiography assisted in diagnosing and quantifying the extent of vasculitis in 62% of patients, and in planning laser photocoagulation or immunosuppression titration in 62% of patients and enhanced disease monitoring in 35% of patients. In 31% of cases, SLA revealed vasculitis that was not evident clinically. CONCLUSION: Staurenghi lens angiography is a valuable tool in the management of patients with posterior uveitis and can be used for the diagnosis, treatment and follow-up of these patients.

Wide-field retinal imaging in the management of noninfectious posterior uveitis.

PURPOSE: To determine whether the use of ultra wide-field imaging changes the management or determination of disease activity in patients with noninfectious posterior uveitis. DESIGN: Prospective, observational case series. METHODS: setting: Divisions of Retina and Ocular Immunology at single academic medical center. patient population: Total of 43 patients with noninfectious posterior uveitis seen by 4 investigators at the Wilmer Eye Institute. procedures: Each patient underwent standard clinical examination, followed by ultra wide-field scanning laser ophthalmoscope (SLO) imaging and angiography. Investigators successively determined disease activity and management decisions based on clinical examination, examination plus simulated 30- or 60-degree fluorescein angiography (FA) (obtained by physically narrowing the field of view of the wide-field images), examination plus ultra wide-field SLO images, and examination plus wide-field FA. main outcome measures: The primary outcome was the percentage of patients whose management changed based on the availability of wide-field imaging, compared with standard examination and imaging. The secondary outcome was detection of disease activity with and without wide-angle imaging. RESULTS: Management was altered in 7 of 43 patients (16%) based on examination and limited FA, whereas 21 of 43 patients (48%) had management change with the use of the ultra wide-field imaging and angiography (P < .001). Disease activity was detected in 22 of 43 patients (51%) based on examination and simulated conventional imaging, and in 27 of 43 (63%) with wide-field imaging (P = .27). CONCLUSIONS: The index study, with several design limitations, has suggested that ultra wide-field imaging may alter management decisions compared to standard-of-care imaging and clinical examination. Additional studies, including longitudinal evaluations, are needed to determine whether these findings, or the subsequent management alterations, may improve patient outcomes.

Systematic review on the effectiveness of immunosuppressants and biological therapies in the treatment of autoimmune posterior uveitis.

OBJECTIVES: To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic arthritis, and macular edema. METHODS: Systematic review. We conducted a sensitive literature search in Medline (from 1961) and EMBASE (from 1980) until October 2007. Selection criteria were as follows: (1) population: autoimmune posterior uveitis, chronic anterior uveitis in juvenile idiopathic arthritis, and macular edema; (2) intervention: immunosuppressive and biologic therapies; (3) outcomes: visual acuity, Tyndall, vitreous haze, macular edema, pars planitis, and retinal vasculitis. There were no limitations regarding study design. The quality of each study was evaluated using the Jadad's scale and Oxford Levels of Evidence. RESULTS: Two hundred sixty-five articles were selected for detailed review of the 4235 found in the initial search: 128 records were on immunosuppressants, 105 on biological therapies, and 32 on macular edema. Overall, both the immunosuppressive and the biologic therapies appeared effective in the treatment of autoimmune posterior uveitis, except for daclizumab in uveitis related to Behçet's disease, and for etanercept in any uveitis. In the treatment of macular edema, the drugs tested were also effective. CONCLUSIONS: Based on the evidence collated, immunosuppressants and biological therapies (except for daclizumab in Behçet and etanercept) may be effective in autoimmune uveitis and macular edema. No superiority may be inferred from this review.

Necrotizing and nonnecrotizing variants of herpetic uveitis with posterior segment involvement.

OBJECTIVE: To describe the clinical characteristics and prognosis of diverse variants of herpetic uveitis with posterior segment involvement. METHODS/DESIGN: Retrospective observational study of clinical, imaging, and laboratory data. RESULTS: Twenty-five patients were classified as having typical acute retinal necrosis (ARN) and 13 patients as not having ARN (non-ARN). Age at symptom onset, sex, bilateral involvement, and prevalence of viral species were not significantly different between patients in the ARN and non-ARN groups. All patients in the ARN group had necrotic retinal lesions that progressed quickly, whereas only 4 of 13 patients (31%) in the non-ARN group (P < .001) had necrotic retinal lesions that progressed slowly. Necrotizing variants were noted in 29 of 38 patients (76%), including 4 patients with slowly progressing lesions. Nine remaining patients in the non-ARN group had non-necrotizing posterior uveitis without retinal lesions; their cases were characterized by vitritis, vasculitis, and/or papillitis, or as panuveitis without any distinct features (5 patients [38.5%]). At 6 months' follow-up, visual acuity of less than 0.1 developed in 13 of 25 patients (52%) in the ARN group and in 4 of 13 patients (31%) in the non-ARN group (P = .30). CONCLUSIONS: Herpes simplex and varicella zoster viruses can cause a wide spectrum of clinical manifestations ranging from severe ARN to slow-progressing necrotizing and non-necrotizing types of inflammation. The non-ARN variants are currently underdiagnosed. Patients with these variants could potentially benefit from earlier recognition and treatment.

[Clinical characteristics and treatment of syphilitic posterior uveitis].

OBJECTIVE: To study clinical characteristics, treatment and prognosis of syphilitic posterior uveitis. METHODS: A retrospective study was conducted in 26 patients with syphilitic posterior uveitis. The diagnosis was confirmed by clinical and laboratory tests. RESULTS: There were 26 patients, 16 males and 10 females, mean age was 40 years. Fourteen patients were bilateral. The symptoms included impaired vision and floaters. In 40 eyes, yellow-white lesions in the posterior pole were present in 8 eyes, 22 eyes showed mild congestion of optic discs and loss of reflex in the fovea, and 6 eyes showed significant congestion and swelling of the optic disc. Fluorescein angiography showed staining or hyperfluorescence of optic disc in 40 eyes, venous leakage in 26 eyes, retinal pigment epithelium damage with dye pooling in 6 eyes, and cystoid macular edema in 6 eyes. ICGA: squamous or disseminative hypofluorescence damage was present in all 40 eyes. After the treatment, 32 eyes had improved vision and fundus damage. CONCLUSIONS: Syphilitic posterior uveitis has typical symptoms and signs. This is a curable disease, early diagnosis and prompt treatment are important for the improvement of prognosis.