Interventions for the treatment of uveitic macular edema: a systematic | OPTH
Noninfectious uveitis results in vision loss and ocular complications without In other studies, macular edema has been estimated to be present in 85% of cases of covariates based on a literature review and were defined using International .. biologics for uveitis; however, those results are difficult to compare with those . unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient. Keywords: uveitic macular edema, uveitis. Uveitis and Macular Edema: A Complex Relationship. dations for the treatment of noninfectious uveitis in the era of biologics. glaucoma, macular edema, and cataract.1e14 Recurring flares may lead to cumulative eye in relation to cycles of treatment in-class before moving to a new treatment Answers were developed based on the literature searches and.
The rate of continuing remission without relapse was Patients who relapsed typically did so when the infusion interval was lengthened; when this occurred, they were returned to a shorter interval. For instance, those who had previously taken mycophenolate or azathioprine had among the highest incidence rates of remission.
Incidence of relapse was highest among patients with prior use of methotrexate and daclizumab. The researchers noted that while their results require confirmation by a large multicenter study, continued follow-up of their patient cohort is also necessary to fully determine the long-term effects of infliximab.
They found that RD is common after open-globe trauma—although often not appearing until days or weeks after the initial traumatic event. For this case-control study, the researchers reviewed the charts of patients with open-globe injuries.
From these injuries, eyes 29 percent were ultimately diagnosed with RD. The remaining served as controls. Of the eyes that developed RD, 69 27 percent detached within 24 hours of primary open-globe repair, 47 percent detached within the first week, and 72 percent detached within the first month.
Fourteen eyes 5 percent experienced RD more than one year after the open-globe injury. Compared with controls, patients who developed RD were more likely to have a zone III injury defined as involving the sclera more than 5 mm posterior to the limbus. Using these and other clinical factors, the researchers created a multivariable logit model they call the Retinal Detachment after Open Globe Injury score.
The score awards points based on three factors: On this scale, a patient with one point would have a 3 percent probability of developing an RD, while a patient with 7. For this prospective, longitudinal study, the researchers evaluated eyes of 90 glaucoma patients and 72 eyes of 40 individuals who did not have the disease.
More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used.
Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents.
When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient. The full terms of this license are available at https: To date, none of the biologics discussed herein have been approved in the US for the treatment of uveitis, but they have been used off-label to treat uveitis or ocular inflammation.
The clinical data have appeared primarily in case reports and series, and less frequently from clinical trials. Table 2 summarizes examples of biologics used in ophthalmology, dosage, route of administration, and their potential side effects. Table 2 Characteristics, route of administration, dosage, and potential side effects for selected biologic agents Notes: Adapted with permission from Retina Today.
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Biologic therapy for posterior uveitis and panuveitis. One of the most successful biological approaches to disease is the inhibition of vascular endothelial growth factor VEGF within the eye since VEGF is strongly implicated in ocular neovascularization. Since the rationale is to treat a complication of the uveitis rather than the uveitis itself, we have elected to omit a discussion of this important class of biologics from this review.
Infliximab has been described to be a rapid and very effective therapy for the treatment of BD-related panuveitis, 9 — 11 and retinal vasculitis. Infliximab has been reported to effectively treat serpiginous choroidopathy SC in two refractory cases; 4647 however, one patient died due to disseminated tuberculosis despite previously negative purified protein-derivative skin test.
Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis
Our study was too small to draw definitive conclusions, but we speculate that the combination of very high drug levels resulting from intravenous infusion and a minimal elevation in serum TNF in patients with just localized eye inflammation resulted in the inordinate number of adverse effects.
The route of administration is subcutaneous injection. Initial clinical studies have shown its potential for juvenile uveitis mainly JIAand more recent data have also demonstrated promising results in adults. Favorable outcomes of etanercept therapy for uveitis have been previously reported.
Just as TNF inhibitors may paradoxically trigger psoriasis or sarcoidosis, uveitis has been reported as a consequence of anti-TNF therapy. Several case reports and series demonstrated successful control of recalcitrant uveitis associated with JIA, 68 — 70 BD, 71 idiopathic retinal vasculitis, 68 spondyloarthropathies, 72 and HLA-B27 positivity. Ocular and joint inflammation were successfully controlled after switching to golimumab with concurrent use of methotrexate. In this series, a year-old male with AS and bilateral anterior uveitis was satisfactorily treated with at least 30 months of follow-up.
Golimumab may further assist the control of systemic conditions in those with inactive uveitis, as reported in a 7-year-old girl with uncontrolled joint inflammation PsAwhile her panuveitis was quiescent under mycophenolate mofetil therapy. The conditions were inadequately controlled with cyclosporine, infliximab, and prednisone. Golimumab therapy resulted in complete resolution of vitritis and macular edema 5 weeks after switching from infliximab to golimumab. Uveitis remained quiescent after cyclosporine and prednisone tapering up to 6 months of follow-up.
As a relatively new medication, golimumab was used as a primary biologic agent in none of the above reported cases. An open-label, Phase IV study, investigating the incidence of uveitis attacks in participants with AS before and after treatment with golimumab is underway.
A single case report demonstrated its efficacy for the treatment of recalcitrant RA and scleritis in a patient who was intolerant to infliximab and rituximab therapy. It was used for the prophylaxis of organ transplant rejection. Some patients were transitioned to subcutaneous daclizumab therapy after 4 years of intravenous infusions, with most patients maintaining good response.
It is given by intravenous infusions in various doses depending on the diagnosis.
Pediatric Intermediate Uveitis - American Academy of Ophthalmology
Case reports and series demonstrated benefits for scleritis and orbital inflammatory diseases. Some evidence suggests that rituximab may be effective for the treatment of BD-related conditions, in spite of the fact that it is conceptualized predominantly as a T-cell-driven disease.
Sadreddini et al reported that one course of two rituximab infusions 1, mg, 2-week interval was effective to control BD-related uveitis and retinal vasculitis, and control of inflammation was sustained at 18 months of follow-up. The subjects were randomized into two groups: The results showed that the rituximab group had more substantial improvement of the Total Adjusted Disease Activity Index, while ocular inflammation was significantly improved in both groups.
The fusion protein binds to an antigen presenting cell and blocks the activity of what is called an accessory molecule that activates the T-cell. It is given by monthly intravenous infusions after initial loading at 0, 2, and 4 weeks in children with JIA, but may be used as weekly subcutaneous injections after a single intravenous loading in adults with RA.
Several reports demonstrated its efficacy to control or improve refractory JIA-uveitis in children and young adults range, 8—23 years old with intravenous infusions.
To date, Zulian et al reported the largest series of seven patients. The results showed that uveitis was improved in all patients, but only one patient had complete remission over the 7—month follow-up period. One patient discontinued treatment due to oral mycosis and arthritic flare.
Preliminary results showed that abatacept was effective, at least partially, to control refractory uveitis in the first three patients enrolled thus far. It is approved for the prophylaxis of acute renal transplant rejection. A randomized controlled pilot study of its use for high-risk penetrating keratoplasty showed that it has inferior efficacy in preventing graft reactions compared with cyclosporine.
There are no reports on the use for uveitis at present. It is approved for the treatment of RA and cryopyrin-associated periodic syndromes.
The recommended dose for RA is mg daily by subcutaneous injection, and dose adjustment is needed for renal insufficiency. An animal study showed that it may suppress experimental immune-mediated uveitis in mice.
It is generally administered by subcutaneous injection every 4—8 weeks, but can also be given intravenously. Ugurlu et al described a case of a year-old female with severe bilateral panuveitis with hypopyon and retinal vasculitis associated with BD.
The patient was intolerant to IFN therapy and refractory to conventional immunosuppressive and several biologic agents, including infliximab, adalimumab, and anakinra. The inflammation resolved with improved visual acuity, which was sustained for at least 8 weeks after a single infusion of mg canakinumab.