An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

Aim: In this retrospective cohort study we investigated the long-term course and visual outcomes of intermediate uveitis (IU). Methods: We performed an institutional study of patients with IU with a follow-up of at least 10 years, followed at a tertiary referral centre. Results: We studied 29 patients with unilateral or bilateral IU. The average age at onset of IU was 31 (range 8–64) years. At onset, three patients (10%) had associated systemic disease (two with sarcoidosis and one with multiple sclerosis) and one patient had granuloma annulare. During the follow-up period, one additional patient was diagnosed with sarcoidosis and one with multiple sclerosis. The percentage of eyes with legal blindness and visual impairment gradually increased over time (from 9/53 (17%) at onset to 15/53 (28%) at 10-year follow-up), with macular oedema, cataract and vitreous opacities being the most common causes of vision loss. The presence of associated anterior uveitis was more frequently noted in patients younger than 20 years at onset. Remissions of intraocular inflammation of at least 1 year were noted in 10/29 (34%) of patients. The mean time-to-remission was 8.6 years; patients who had remissions were younger at the onset of IU than those with ongoing active IU (p = 0.036). Remissions of IU showed borderline association with the absence of systemic disease (p = 0.046). Conclusions: One-third of IU patients achieved a remission of their intraocular inflammation for longer than 1 year and had a mean time-to-remission of 8.6 years. Patients who were younger at onset of IU were more likely to achieve remission than those who were older at onset.

To study the intraocular and serum cytokine and chemokine profile in patients with intermediate uveitis (IU) at various stages of inflammatory activity. Institutional, prospective association study. Paired aqueous humor (AqH) and serum samples were collected from 36 consecutive IU patients and 10 controls. The concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF)-α, CC - chemokine ligand 5/regulated upon activation normal T-cell expressed, and secreted (CCL5/RANTES), CC - chemokine ligand 3/macrophage inflammatory protein 1alpha (CCL3/MIP-1α), CCL4/MIP-1β, and CC - chemokine ligand 2/monocyte chemotactic protein - 1 (CCL2/MCP-1) were measured in both AqH and serum by multiplex immunoassay. Main outcome measures were serum and intraocular levels of the analyzed cyto- and chemokines. Patients with IU had higher serum levels of TNF-α than non-uveitic controls (p<0.0001), whereas their AqH TNF-α levels did not show a difference (p=0.323). IU patients had higher intraocular levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70 and CCL2/MCP-1 than the controls (p=0.020, 0.001, <0.0001, 0.005, 0.003, and 0.003, respectively). Active stages of IU were characterized by higher levels of IL-6, IL-8, CCL5/RANTES and CCL2/MCP-1 (p=0.003, <0.0001, 0.033, and 0.033, respectively). Higher levels of IL-6 and IL-8 were found in IU patients with cystoid macular edema (CME) compared to non-CME IU patients (p=0.026 and 0.012, respectively). Significant positive correlations between various observed mediators were present in the AqH of IU patients only. Significantly elevated concentrations of multiple intraocular cytokines were found in IU patients, especially IL-6 and IL-8 in those with CME and active disease. In serum elevated TNF-α levels were observed in IU patients. Our findings improve the understanding of the pathogenesis of IU and contribute to the identification of factors which may contribute to the activity of IU.

Purpose: To report on six patients who developed vitreous hemorrhage (VH) in the course of intermediate uveitis (IU) associated with multiple sclerosis (MS). Methods: Observational case series. Results: Six out of 25 patients (24%) with IU and MS seen at two tertiary centers developed VH. Average age at onset of MS was 26 years and average age at the onset of IU was 25 years. IU developed before the onset of MS in four of the six patients (67%). All patients had IU associated with peripheral phlebitis. The average interval between the onset of IU and the occurrence of VH was five years (range: 0–11 years; VH was the initial sign of uveitis in 2 patients). VH cleared spontaneously in all cases; however, subsequent retinal detachment developed in two eyes. All six patients had ischemic retinal areas and four had subretinal neovascularizations. Optimal visual acuity five years after VH varied from no light perception to full visual acuity. The causes of diminished acuity included optic neuritis, cystoid macular edema (CME), and retinal detachment. Conclusion: The possibility of MS-associated uveitis should be considered in patients with IU and VH.

Aim. Functional and morphological macular study after cataract surgery in a group of diabetics without diabetic retinopathy compared to nondiabetics to evaluate the effect of surgical oxidative stress on diabetic retina.Methods. Prospective, comparative study. Preoperative eye exam, best corrected visual acuity (BCVA) measured by ETDRS letters, and optical coherence tomography (OCT) were followed by standard cataract surgery. The follow-up visits at 1, 3, and 6 months postoperatively included BCVA, OCT, and microperimetry, to analyze changes within and between the groups.Results. The BCVA improved significantly in diabetics and controls: 64.2 to 81.0 and 61.9 to 82.1 ETDRS at 6 months, respectively. The central macula at OCT significantly thickened in both groups, while the central 5 fields, corresponding to the microperimetry area, subclinically thickened from 284.20 to 291.18 μm at 6 months only in diabetics (p=0.026). A matching slight decrease in the microperimetry sensitivity from 1 to 6 months was found also only in diabetics, with mean average difference −0.75 dB (p=0.04).Conclusion. Underlying diabetes does not influence the surgical outcome in diabetics without diabetic retinopathy. However, slight thickening of wider macula and corresponding decrease in retinal sensitivity observed in diabetics 6 months postoperatively might influence visual function on long term.