Explore the vast range of titles available.

The term ocular microbiota refers to all types of commensal and pathogenic microorganisms present on or in the eye. The ocular surface is continuously exposed to the environment and harbors various commensals. Commensal microbes have been demonstrated to regulate host metabolism, development of immune system, and host defense against pathogen invasion. An unbalanced microbiota could lead to pathogenic microbial overgrowth and cause local or systemic inflammation. The specific antigens that irritate the deleterious immune responses in various inflammatory eye diseases remain obscure, while recent evidence implies a microbial etiology of these illnesses. The purpose of this review is to provide an overview of the literature on ocular microbiota and the role of commensal microbes in several eye diseases. In addition, this review will also discuss the interaction between microbial pathogens and host factors involved in intraocular inflammation, and evaluate therapeutic potential of targeting ocular microbiota to treat intraocular inflammation.

To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD). A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up. A total of 190 eyes were included. Patients received a mean of 34.2±23 anti-VEGF injections over 182.41±128 weeks prior to switching to faricimab. Patients then received a mean of 6.99±2.3 faricimab injections with an average 34.88±8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33±0.32 logMAR ≈20/43 to 0.27±0.32 logMAR ≈20/37 ( =0.0022). The central subfield thickness (CST) improved from 312±87μm to 287±71μm ( <0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64±6.2 weeks) was significantly longer than that for ranibizumab (5.16±2.0 weeks, <0.001) or aflibercept (5.57±3.6 weeks, <0.001). No patients developed idiopathic intraocular inflammation. Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.

Purpose To investigate the epidemiology of uveitis in Japan and assess its changes over time. Study design Retrospective multicenter study Methods Sixty-six hospitals in Japan with uveitis specialty clinics participated in this retrospective nationwide survey. A questionnaire was sent to each hospital to survey the total number of patients who made a first visit to the outpatient uveitis clinic of each hospital between 1 April 2016 and 31 March 2017. The diagnosis of uveitis was based on guidelines when available or on commonly used diagnostic criteria. Results In 2016, new patients with uveitis accounted for 3.2% of the total number of new patients with ophthalmic diseases. A total of 5378 patients were enrolled in the survey; 3408 cases could be classified with a specific uveitis entity, and 1970 cases were described as unclassified intraocular inflammation. Among the classified cases, the most frequent disease was sarcoidosis (10.6%), followed by Vogt–Koyanagi–Harada disease (8.1%), herpetic iritis (6.5%), acute anterior uveitis (5.5%), sclerouveitis (4.4%), Behçet’s disease (4.2%), malignant disease (2.6%), acute retinal necrosis (1.7%), Posner–Schlossman syndrome (1.7%), and diabetic iritis (1.4%). The rates of sarcoidosis, Vogt–Koyanagi–Harada disease, and Behçet’s disease were similar; however, the rate of herpes iritis increased (4.2–6.5%) when compared with the 2009 survey. Conclusions Some changes were observed between the previous nationwide surveys (2002 and 2009) and the present survey. It must be valuable to continue such nationwide epidemiologic surveys at regular intervals.

BackgroundUveitis appears to be less prevalent in the UK compared with other parts of the world and studies characterising the disease in the UK are lacking. The objectives of this retrospective study were to describe acute and recurrent cases presenting for management of uveitis in a referral hospital on the North West of England and compare the signalment of horses presenting with uveitis with the equine hospital population during the same period.MethodsMedical records of horses presented to the referral Equine Hospital, University of Liverpool with signs of uveitis between 2008 and 2018 were reviewed and clinical details extracted.ResultsSeventy horses presented with uveitis; 33 were classified as acute and 37 as recurrent cases. Sixteen of the horses were affected bilaterally. More bilateral cases were classified as recurrent than acute (P=0.04). No differences in age or sex were noted between acute and recurrent cases, or between cases and the general hospital population. Warmbloods and Appaloosas were over-represented when compared with the general hospital population (P<0.001). Twenty-one horses (30 per cent, 95 per cent CI 20.5 to 41.4) underwent surgery for the control of the uveitis. Fourteen of the 70 horses (20.0 per cent, 95 per cent CI 12.3 to 30.8) underwent enucleation.ConclusionWhile relatively uncommon in the UK, uveitis can affect horses from a relatively young age. The disease appears to have a relatively higher frequency than expected in Warmbloods and Appaloosas. It is more likely that a recurrent case will have both eyes affected.

Molecular or antigenic mimicry is a term for the similarity of different antigens, which can be confused by the immune system. Antigen recognition by antibodies and T cell receptors is specific, but not restricted to a single antigen. Both types of receptors specifically recognize antigens and are expressed with a very high but still restricted variability compared to the number of different antigens they potentially could bind. T cell receptors only can bind to antigen peptides presented on certain self-MHC-molecules by screening only some amino acid side chains on both the presented peptides and the MHC molecule. The other amino acids of the peptide are not directly perceived by the T cell, offering the opportunity for a single T cell to recognize a variety of different antigens with the same receptor, which significantly increases the immune repertoire. The immune system is usually tolerant to autoantigens, especially to those of immune privileged sites, like the eye. Therefore, autoimmune diseases targeting these organs were hard to explain, unless a T cell is activated by an environmental peptide (e.g. pathogen) that is similar, but not necessarily identical with an autoantigen. Here we describe antigenic mimicry of retinal autoantigens with a variety of non-ocular antigens resulting in the induction of intraocular inflammation. T cells that are activated by mimotopes outside of the eye can pass the blood-retina barrier and enter ocular tissues. When reactivated in the eye by crossreaction with autoantigens they induce uveitis by recruiting inflammatory cells.

PurposeTo describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO).MethodsThis was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on IOI following anti-VEGF therapy was also conducted.ResultsAmong 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received ≥ 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event.ConclusionsIOI may precede RV or RO in some patients treated with brolucizumab.

Purpose: To assess the morphological and functional outcomes within the first year of treatment with intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 21 eyes from 19 patients with refractory nAMD followed for 12 months. All patients were switched to brolucizumab after treatment with at least two other anti-vascular endothelial growth factors (VEGF). All eyes received 3x brolucizumab 6 mg/0.05 ml intravitreal injections (IVI) monthly as an upload phase. Then eyes received an IVI every 8 weeks with interval adjustment to every 12 weeks if disease activity was not present. Main outcome measures: best corrected visual acuity (BCVA), central macular thickness (CMT) and retinal fluid distribution. In addition, we reported the adverse event rate. Results: The number of previous anti-VEGF IVIs/eye was 36 ± 22 before switching to brolucizumab. BCVA (ETDRS) was 51 ± 16 before treatment and 50 ± 19 at week 52 ( p = 0.6). CMT was 374 ± 158 μm before treatment and 298 ± 92 μm at week 52 ( p = 0.01). The number of IVIs/eye decreased from 9.6 ± 1.9 IVIs in the last year before switching to 6.4 ± 0.9 IVIs in the first year after switching to brolucizumab ( p < 0.001). The rate of eyes with subretinal fluid and pigment epithelial detachment decreased at week 52. Finally, two cases of intraocular inflammation were observed as adverse events. Conclusion: In the first year of treatment, intravitreal brolucizumab was able to stabilize visual acuity with significantly less IVIs in patients with refractory nAMD. It also improved anatomic outcomes in these patients, particularly reducing subretinal fluid and pigment epithelial detachment and subsequently central macular thickness. However, two cases of intraocular inflammation were observed as adverse events.

Brolucizumab (Beovu®) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns.ImportanceBrolucizumab (Beovu®) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns.We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world.ObjectiveWe evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world.This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020.Design Setting and ParticipantsThis was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020.Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events.Main Outcomes and MeasuresChanges in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events.The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001).ResultsThe majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001).Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER.Conclusions and RelevanceBrolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER.

PurposeTo provide a comprehensive review of rituximab use for the treatment of non-infectious uveitis and scleritis.MethodsReview of literature through December 2020.ResultsIndividual data was available for 229 patients with refractory non-infectious uveitis (n = 108) or scleritis (n = 121) who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (uveitis: 67/90, 74.4%; scleritis: 90/96, 93.8%) at a mean of 33.5 months following the diagnosis of uveitis (range = 0 to 168.0 months; median = 24.0 months) and 39.4 months after diagnosis of scleritis (range = 1.0 to 168.0 months; median = 21.0 months). Patients with non-infectious uveitis and scleritis either received prior treatment with corticosteroids only (uveitis: 18/90, 20%; scleritis: 4/94, 4.3%), or with one (uveitis: 19/90, 21.1%; scleritis: 30/94, 31.9%), two (uveitis: 11/90, 12.2%; scleritis 27/94, 28.7%), or three or more (uveitis: 37/90, 41.1%; scleritis: 31/94, 33.0%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (uveitis: 45/87, 51.7%; scleritis: 87/114, 76.3%), followed by the Foster protocol (eight weekly infusions of 375 mg/m2 RTX; uveitis: 18/87, 20.7%; scleritis: 10/114, 8.8%), and the oncologic protocol (four weekly infusions of 375 mg/m2 RTX; uveitis: 5/87, 5.7%; scleritis: 6/114, 5.3%). Various other off-label regimens were used infrequently (uveitis: 19/87, 21.8%; scleritis 11/114, 9.6%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with non-infectious uveitis (81/97, 83.5%). Commonly treated uveitic diagnoses included non-paraneoplastic autoimmune retinopathy (30/107, 28.0%), juvenile idiopathic arthritis (21/107, 19.6%), Vogt-Koyanagi-Harada disease (12/107, 11.2%), and Behçet disease (11/107, 10.3%). Cases of non-infectious scleritis were most commonly attributed to granulomatosis with polyangiitis (75/121, 62.0%) and rheumatoid arthritis (15/121, 12.4%), and showed an even greater rate of positive therapeutic response (112/120, 93.3%) following RTX treatment. No side effects were reported in 76.3% (74/97) of uveitis and 85.5% (71/83) scleritis cases. Of those cases associated with RTX-induced adverse events, the most common were infusion reactions of various severity (11/35, 31.4%).ConclusionsOverall, RTX appeared to be both effective and well-tolerated as second or third-line therapy for patients with non-infectious uveitis and scleritis.

Ocular alkali burn (OAB) is a sight-threatening disease with refractory ocular inflammation causing various blinding complications. Th17 lymphocytes account for the pathogeneses of the autoimmune disease and chronic inflammation, but their role in prolonged anterior intraocular inflammation after OAB is still unknown. A rat OAB model was established for this purpose. Anterior intraocular inflammation was observed in both the acute and late phases of OAB, and histological examination confirmed the presence of inflammatory cell infiltration and fibrin exudation in the anterior segment. Luminex xMAP technology and qPCR were used to evaluate the intraocular levels of cytokines. The levels of IL-1β, IL-6, and TNF-α were significantly elevated during the acute phase. The expression of IL-17A gradually increased from day 7 onwards and remained at a relatively high level. Immunofluorescence was performed to identify Th17 cells. CD4 and IL-17A double positive cells were detected in the anterior chamber from days 7 to 28. Flow cytometry showed that the frequency of Th17 cells increased in both lymph nodes and spleen, while the frequency of Treg cells remained unchanged, resulting in an elevated Th17/Treg ratio. The present study suggests that Th17 activation and Th17/Treg imbalance account for prolonged anterior intraocular inflammation after OAB.