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International Ophthalmology Feb 2022To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the... (Review)
Review
PURPOSE
To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs.
METHODS
A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors' departments were examined.
RESULTS
Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin's lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to "bull's eye" maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment.
CONCLUSION
The level of evidence for most of the drug reactions described herein is restricted to the "likely" or "possible" rather than to the "certain" category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Glaucoma, Open-Angle; Humans; Iatrogenic Disease; Rituximab
PubMed: 34802085
DOI: 10.1007/s10792-021-02058-8 -
The Journal of Rheumatology Jan 2021Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review.
METHODS
A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis.
RESULTS
There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively.
CONCLUSION
Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.
Topics: Arthritis, Rheumatoid; Connective Tissue Diseases; Granulomatosis with Polyangiitis; Humans; Lupus Erythematosus, Systemic; Rheumatic Diseases
PubMed: 32358156
DOI: 10.3899/jrheum.190768 -
BMJ Open Ophthalmology Jun 2023This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of...
OBJECTIVE
This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of autoimmune uveitis.
METHODS
A systematic search was conducted across PubMed, Scopus, Web of Science and Google Scholar from 2014 until February 2022. The search included the following keywords "Adalimumab", "Infliximab", "Autoimmune", "Anterior", "Intermediate", "Posterior", "Panuveitis", "Refractory" and "Uveitis". Primary studies comparing both ADA and IFX in a population of autoimmune uveitis patients were considered. Outcomes of interest were measures of response to treatment and incidence of adverse events.
RESULTS
The preliminary literature search generated 7156 references. Six studies fulfilled the eligibility criteria and were included in the final analysis; all were non-randomised, retrospective or observational. The included studies found similar effectiveness and side effect profiles for both ADA and IFX in the management of autoimmune uveitis, however, one did not report effectiveness for each separately, and three were limited to Behcet's disease.
CONCLUSION
ADA and IFX seem to display comparable effectiveness and safety profiles. However, the available evidence remains scarce, of low quality and at high risk of bias. A direct comparison between ADA and IFX through large randomised controlled trials is needed to provide more substantial evidence of equivalence or superiority in uveitis.
Topics: Humans; Adalimumab; Infliximab; Retrospective Studies; Treatment Outcome; Uveitis; Tumor Necrosis Factor-alpha; Behcet Syndrome
PubMed: 37493653
DOI: 10.1136/bmjophth-2023-001303 -
Nephrology, Dialysis, Transplantation :... Apr 2022Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic...
BACKGROUND
Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic diseases. The most comprehensive review on this condition was published in 2001.
METHODS
We conducted a systematic review of the literature for cases of TINU syndrome. MEDLINE and Embase databases were screened. Full-length articles or letters reporting cases with both TIN and uveitis were selected. We investigated differences between males and females and paediatric and adult cases. Multivariate analysis was performed to identify potential risk factors for chronic kidney disease (CKD) development.
RESULTS
A total of 233 articles reporting 592 TINU cases were retained for the analysis. The median age of the included subjects was 17 years (interquartile range 13-46) with a female predominance (65%). Uveitis most frequently (52%) followed renal disease and was mostly anterior (65%) and bilateral (88%). Children tended to have more ocular relapses, while they were slightly less likely than adults to suffer from acute kidney injury and to develop CKD. Adult age as well as posterior or panuveitis were associated with an increased risk of developing CKD.
CONCLUSIONS
TINU affects both children and adults, with some differences between these two categories. Adult age and the presence of a posterior uveitis or panuveitis appear to be associated with the development of CKD.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Nephritis, Interstitial; Panuveitis; Renal Insufficiency, Chronic; Uveitis
PubMed: 33561271
DOI: 10.1093/ndt/gfab030 -
Seminars in Arthritis and Rheumatism Feb 2011To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic... (Review)
Review
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.
Topics: Antibodies, Monoclonal; Arthritis, Juvenile; Autoimmune Diseases; Humans; Immunosuppressive Agents; Macular Edema; Treatment Outcome; Uveitis, Anterior; Uveitis, Posterior
PubMed: 20656330
DOI: 10.1016/j.semarthrit.2010.05.008 -
Health Technology Assessment... Nov 2017Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs.
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis.
DATA SOURCES
Electronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization's International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016.
REVIEW METHODS
Review methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken.
RESULTS
Of the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70; < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84; = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20; = 0.010) but not the VISUAL II trial (mean difference 2.12; = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero ( < 0.014), the mean best corrected visual acuity improvement ( ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score ( < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness.
LIMITATIONS
The clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base.
CONCLUSIONS
Two RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016041799.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Cost-Benefit Analysis; Dexamethasone; Humans; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Uveitis, Intermediate; Uveitis, Posterior
PubMed: 29183563
DOI: 10.3310/hta21680 -
Seminars in Arthritis and Rheumatism Dec 2020Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management.
Efficacy and safety of immunomodulatory drugs in patients with non-infectious intermediate and posterior uveitis, panuveitis and macular edema: A systematic literature review.
BACKGROUND
Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management.
OBJECTIVES
To evaluate the published evidence regarding the use of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME).
METHODS
We performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale.
RESULTS
Nineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis.
CONCLUSION
Several IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes.
Topics: Adult; Humans; Macular Edema; Panuveitis; Pharmaceutical Preparations; Treatment Outcome; Uveitis; Uveitis, Posterior
PubMed: 33065425
DOI: 10.1016/j.semarthrit.2020.08.010 -
Survey of Ophthalmology 2022Uveitis is among the leading causes of visual loss in the working age population. In noninfectious uveitis, corticosteroids are the first line therapy. We sought to... (Review)
Review
Uveitis is among the leading causes of visual loss in the working age population. In noninfectious uveitis, corticosteroids are the first line therapy. We sought to review systematically the evidence regarding the regional corticosteroid delivery modalities in the treatment of noninfectious uveitis. A 5-database search (Pubmed, ISI Web of Science, Cochrane, ClinicalTrials.gov, and Scopus) was performed from inception to February, 2021. Nineteen studies with a total of 1,935 eyes of 1,753 patients were selected from 8,922 abstracts retrieved by the initial search. The most frequently compared regimens were intravitreal triamcinolone acetonide injection and orbital floor triamcinolone acetonide injection (2 studies), intravitreal triamcinolone acetonide injection and posterior sub-Tenon triamcinolone acetonide injection (2 studies), and posterior sub-Tenon triamcinolone acetonide injection with the intravitreal dexamethasone implant (2 studies). Our results show that the intravitreal injection of corticosteroids is more effective, but is associated with more adverse events, than periocular injection. Some evidence supports the use of subconjunctival triamcinolone acetonide over intravitreal/periocular triamcinolone acetonide. Moreover, the overall results of 0.59 mg dosage of the intravitreal fluocinolone acetonide implant were superior to those from the 2.1 mg dose. The evidence, however, is not robust, and further studies with standardized outcomes are warranted.
Topics: Adrenal Cortex Hormones; Glucocorticoids; Humans; Injections, Intraocular; Intravitreal Injections; Treatment Outcome; Triamcinolone Acetonide; Uveitis; Visual Acuity
PubMed: 34896190
DOI: 10.1016/j.survophthal.2021.12.002 -
American Journal of Ophthalmology Oct 2014To critically assess the evidence base regarding outcomes following cataract surgery in uveitic cases. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To critically assess the evidence base regarding outcomes following cataract surgery in uveitic cases.
DESIGN
Systematic evidence-based review and meta-analysis.
METHODS
A comprehensive search query was performed on MEDLINE, EMBASE, CINHAL, and CENTRAL databases. Relevant publications were identified by reviewing query results and reference list searches.
RESULTS
A total of 89 articles met eligibility criteria. Among uveitic eyes with quiet or mostly quiet uveitis before cataract surgery, 20/40 visual acuity or better (≥20/40) was achieved in 68% following phacoemulsification, 72% following extracapsular cataract extraction, and 40% following pars plana lensectomy. More eyes undergoing cataract surgery with intraocular lens (IOL) implantation than eyes left aphakic achieved ≥20/40 postoperatively (71% vs 52%). Eyes receiving acrylic IOLs or heparin-surface-modified (HSM) polymethylmethacrylate had better visual outcomes than those receiving non-HSM polymethylmethacrylate or silicone IOLs. Active uveitis at the time of cataract surgery was associated with worse visual outcomes. Compared with other uveitis cases, the proportion achieving 20/40 or better post cataract surgery was better for Fuchs heterochromic cyclitis cases and worse for uveitis related to Behçet disease, Vogt-Koyanagi-Harada disease, or sympathetic ophthalmia, and also posterior uveitis in general.
CONCLUSION
Cataract surgery in eyes with uveitis resulted in normal range levels of visual acuity in most cases. The review suggests that preoperative control of uveitis, use of an acrylic or HSM IOL, and a diagnosis of Fuchs heterochromic cyclitis were associated with better outcomes. Posterior-involving uveitides tended to do worse, likely because of vision-limiting complications of uveitis. Average results may not be applicable to specific clinical scenarios.
Topics: Cataract; Cataract Extraction; Databases, Factual; Humans; Lens Implantation, Intraocular; Refraction, Ocular; Treatment Outcome; Uveitis; Visual Acuity
PubMed: 24983790
DOI: 10.1016/j.ajo.2014.06.018 -
BMJ Clinical Evidence Apr 2010Anterior uveitis is rare, with an annual incidence of 12/100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of... (Review)
Review
INTRODUCTION
Anterior uveitis is rare, with an annual incidence of 12/100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors, such as high frequency of HLA-B27 in the population. It is often self-limiting, but can, in some cases, lead to complications such as posterior synechiae, cataract, glaucoma, and chronic uveitis.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of anti-inflammatory eye drops on acute anterior uveitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found six systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, mydriatics, and non-steroidal anti-inflammatory drug eye drops.
Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Evidence-Based Medicine; Humans; Incidence; Mydriatics; Ophthalmic Solutions; Uveitis, Anterior
PubMed: 21736765
DOI: No ID Found