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Systematic Reviews Jul 2021Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and corticosteroids lower the risk of permanent visual loss by controlling infection and inflammation. However, there remains disagreement regarding optimal antibiotic therapy for OT. Therefore, this systematic review and meta-analysis were performed to determine the effects and safety of existing antibiotic treatment regimens for OT.
METHODS
MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, LILACS, WHO International Clinical Trials Registry Platform portal, ClinicalTrials.gov, and Gray Literature in Europe ("OpenGrey") were searched for relevant studies; manual searches of reference lists were performed for studies identified by other methods. All published and unpublished randomized controlled trials that compared antibiotic schemes known to be effective in OT at any dosage, duration, and administration route were included. Studies comparing antibiotics with placebo were excluded. This review followed standard methodological procedures recommended by the Cochrane group.
RESULTS
Ten studies were included in the narrative summary, of which four were included for quantitative synthesis (meta-analysis). Interventions were organized into three groups: intravitreal clindamycin versus pyrimethamine + sulfadiazine, trimethoprim + sulfamethoxazole versus other antibiotics, and other interventions. The first comparison favored intravitreal clindamycin (Mean difference (MD) = 0.10 logMAR; 95% confidence interval = 0.01 to 0.22). However, this finding lacks clinical relevance. Other outcomes showed no statistically significant differences between the treatment groups. In general, the risk of performance bias was high in evaluated studies, and the quality of the evidence found was low to very low.
CONCLUSIONS
No antibiotic scheme was superior to others, and the selection of a treatment regimen depends on multiple factors; therefore, treatment should be chosen based on safety, sulfa allergies, and availability.
Topics: Anti-Bacterial Agents; Clindamycin; Europe; Humans; Toxoplasmosis, Ocular
PubMed: 34275483
DOI: 10.1186/s13643-021-01758-7 -
Journal of Ophthalmology 2021Corticosteroids are used in a variety of ophthalmological diseases. One challenge faced by ophthalmologists is to deliver corticosteroids to the posterior segment of the... (Review)
Review
Corticosteroids are used in a variety of ophthalmological diseases. One challenge faced by ophthalmologists is to deliver corticosteroids to the posterior segment of the eye with efficacy and safety. Sustained-release corticosteroid implants may be the answer to this problem. The 0.19 mg fluocinolone acetonide (FAc) implant (Iluvien®) releases FAc for 36 months, and it is approved for the treatment of diabetic macular edema (DME) and noninfectious uveitis. We decided to do a systematic review to acknowledge in which other diseases FAc implant is being used off-label. A literature search was performed in the following three electronic databases: PubMed, Scopus, and Web of Science (from January 1, 2000, to September 20, 2020), using the following query: ("Fluocinolone Acetonide" OR Iluvien®) AND ("eye" OR "ocular" OR "intravitreal)." A total of 11 papers were included, and the use of FAc implant was analyzed in the following diseases: radiation-induced maculopathy (RM); paraneoplastic visual syndromes (melanoma-associated retinopathy (MAR) and cancer-associated retinopathy (CAR)); Sjogren's syndrome-related keratopathy; retinal vein occlusion (RVO); cystoid macular edema (CME); diabetic retinal neurodegeneration (DRN); and retinitis pigmentosa (RP). FAc implant may be a potential treatment for these diseases; however, the level of scientific evidence of the included studies in this review is limited. Further studies with larger cohorts and longer follow-ups are needed to validate this data.
PubMed: 34055398
DOI: 10.1155/2021/6678364 -
Journal of Ophthalmic & Vision Research 2021Uveitis is the third leading cause of blindness worldwide. This study aimed to summarize the pattern of uveitis in Iran through a systematic review.
PURPOSE
Uveitis is the third leading cause of blindness worldwide. This study aimed to summarize the pattern of uveitis in Iran through a systematic review.
METHODS
This review was conducted according to the guidelines for systematic reviews in the following four steps: literature search, study selection and assessment, inclusion and exclusion criteria, and statistical analysis.
RESULTS
One hundred and fifteen articles were identified by an encyclopedic literature search, and three independent investigators examined them according to the defined inclusion and exclusion criteria. Eventually, 109 manuscripts were retrieved and six cross-sectional studies covering 3,567 patients were included and reviewed. According to the results, the mean age of patients was 40 years, and sex was not a statistically significant predisposing factor. The most common anatomical pattern of involvement was anterior uveitis, and the prevalence of the other three types of uveitis, including middle, posterior, and pan-uveitis, were almost equal. Overall, the most common etiologies of uveitis in the Iranian population were idiopathic uveitis, toxoplasmosis, Behcet's syndrome, and Fuchs heterochromic iridocyclitis.
CONCLUSION
This study depicted the pattern of uveitis in the Iranian society; this can help physicians in the diagnostic approach, management, and treatment of patients.
PubMed: 33520132
DOI: 10.18502/jovr.v16i1.8255 -
Journal of Ophthalmic Inflammation and... Jan 2020This study aims to determine if the intravitreal dexamethasone implant (DEX implant, Ozurdex; Allergan, Inc., Irvine, California) is effective for treating intermediate,...
BACKGROUND
This study aims to determine if the intravitreal dexamethasone implant (DEX implant, Ozurdex; Allergan, Inc., Irvine, California) is effective for treating intermediate, posterior, and panuveitis as a monotherapy or adjunctive treatment to systemic immunomodulatory therapies.
METHODS
A systematic review using MEDLINE, EMBASE, and PubMed database searches was conducted with the Oxford Centre for Evidence-based Medicine Levels of Evidence criteria to select publications. Available background information and patient data from each study was tabulated. Outcomes studied were central retinal thickness (CRT), best corrected visual acuity, intraocular inflammation (anterior chamber cells, vitreous haze), number of patients with prior and concomitant immunomodulatory treatments, intraocular pressure (IOP) elevation (≥ 25 mmHg), and other adverse effects associated with the implant.
RESULTS
One hundred ninety-five (61.51%) patients had previous immunomodulatory treatment while 232 (64.8%) were treated with concomitant immunomodulatory therapy with the DEX implant. CRT decreased by an average of 198.65 μm (42.74%). Visual acuity improved to an average of 0.451 (logMAR) or 20/57 (Snellen) which is a 43.11% improvement from baseline. One hundred seventy-three (59%) of eyes were quiescent at the end of the trials, of which 40 (13.7%) previously inflamed eyes became quiescent. Elevated IOP occurred in 91 (20.6%). The most common adverse events were cataract/posterior subcapsular opacities in 47 (11.03%) patients and conjunctival hemorrhage in 24 (5.44%) patients.
CONCLUSIONS
The DEX implant is an effective medication for the treatment of posterior segment uveitis, uveitic macular edema, and results in improved visual acuity. Development of elevated IOP and cataract should be closely monitored as they are tangible risks associated with the DEX implant. This study was not able to determine whether the DEX implant was more effective as a monotherapy or as an adjunctive therapy to systemic immunomodulatory treatment.
PubMed: 31925591
DOI: 10.1186/s12348-019-0189-4 -
Acta Ophthalmologica May 2019To explore the effectiveness and safety of vitrectomy for congenital cataract surgery. (Meta-Analysis)
Meta-Analysis
PURPOSE
To explore the effectiveness and safety of vitrectomy for congenital cataract surgery.
METHODS
We searched PubMed, Science Direct, The Cochrane Library, China National Knowledge Infrastructure and the Wanfang Database. Two researchers extracted data and assessed paper quality independently. Posterior capsule opacification (PCO) or visual axis opacification (VAO), reoperation rate, visual acuity, intraocular lenses (IOL) deposit, synechias, uveitis, secondary glaucoma, low-contrast sensitivity and IOL decentration were compared.
RESULTS
We included 11 randomized controlled trials (RCTs) with 634 congenital cataract eyes. Cases of posterior capsule opacification in vitrectomy group were significantly less than that of control group, with risk ratio (RR) of 0.15 [95% confidence interval (CI): 0.09, 0.26], and there was no heterogeneity (I = 0%, p = 0.94). Reoperation rate in vitrectomy group was lower than that of control group either (RR = 0.40, 95%CI: 0.17, 0.94), and there was no heterogeneity (I = 0%, p = 0.85). Best-corrected visual acuity (BCVA) measured in LogMAR unit of vitrectomy group was smaller, with a mean difference (MD) of -0.17 (95%CI: -0.28, -0.05), and I was only 22%, indicating of a small heterogeneity. No statistical difference was found between two groups on IOL deposit (RR = 1.23, 95%CI: 0.70, 2.17), and the heterogeneity was small (I = 16%, p = 0.31). No statistical difference was found between two groups on synechias (RR = 1.08, 95%CI: 0.60, 1.94), with a quite small heterogeneity (I = 3%, p = 0.38). No statistical difference was found between two groups on uveitis (RR = 0.55, 95%CI: 0.15, 2.01), and there was no heterogeneity (I = 0%, p = 0.94). There was no statistical difference on IOP either, with a MD of 0.25 (95%CI: -1.56, 2.07), and there was no heterogeneity (I = 0%). Egger's test showed that there was no publication bias for all assessed outcomes. Low-contrast sensitivity was better in the vitrectomy group. And no evidence indicated vitrectomy could lead to a higher risk on secondary glaucoma or IOL decentration.
CONCLUSION
Vitrectomy helps lower the PCO risk and reoperation risk after congenital cataract surgery, and also, vitrectomy helps patients gain a better BCVA and achieve a better low-contrast sensitivity, with no trade-off on IOP control, IOL deposit, synechias, uveitis and secondary glaucoma. We recommend performing vitrectomy during congenital cataract surgery.
Topics: Cataract; Cataract Extraction; Humans; Lenses, Intraocular; Randomized Controlled Trials as Topic; Visual Acuity; Vitrectomy
PubMed: 30565873
DOI: 10.1111/aos.13974 -
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 -
The Cochrane Database of Systematic... May 2016Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce the risk of permanent visual loss, recurrent retinochoroiditis, and the severity and duration of acute symptoms. There is uncertainty about the effectiveness of antibiotic treatment.
OBJECTIVES
To compare the effects of antibiotic treatment versus placebo or no treatment for toxoplasma retinochoroiditis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2016, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2016), EMBASE (January 1980 to February 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 February 2016. We searched the reference lists of identified articles and contacted pharmaceutical companies for unpublished trials.
SELECTION CRITERIA
We included randomised controlled trials that compared any antibiotic treatment against placebo or no treatment. We excluded trials that included immunocompromised participants. We considered any antibiotic treatment known to be active against Toxoplasma gondii. Antibiotic treatment could be given in any dose orally, by intramuscular injection, by intravenous infusion, or by intravitreal injection.
DATA COLLECTION AND ANALYSIS
The primary outcomes for this review were visual acuity at least three months after treatment and risk of recurrent retinochoroiditis. Secondary outcomes were improvement in symptoms and signs of intraocular inflammation, size of lesion, and adverse events. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Four trials that randomised a total of 268 participants met the inclusion criteria. In all four studies antibiotic was administered orally.One study conducted in Brazil in both adults and children compared trimethoprim-sulfamexacocol over 20 months to no treatment and was judged to be at high risk of performance, detection, and attrition bias. The other three studies compared antibiotic treatment to placebo. We judged these three studies to be at a mixture of low or unclear risk of bias due to poor reporting. One study conducted in the US in adults studied pyrimethamine-trisulfapyrimidine for eight weeks; one study conducted in the UK in children and adults evaluated pyrimethamine for four weeks; and one study conducted in Brazil in adults investigated trimethoprim-sulfamethoxazole for 12 months. In the last study, all participants had active retinochoroiditis and were treated with antibiotics for 45 days prior to randomisation to trimethoprim-sulfamethoxazole versus placebo.Only the study in Brazil of trimethoprim-sulfamethoxazole over 12 months, in participants with healed lesions, reported the effect of treatment on visual acuity. People treated with antibiotics may have a similar change in visual acuity compared with people treated with placebo at one year (mean difference -1.00 letters, 95% confidence interval (CI) -7.93 to 5.93 letters; 93 participants; low-quality evidence).Treatment with antibiotics probably reduces the risk of recurrent retinochoroiditis compared with placebo (risk ratio (RR) 0.26, 95% CI 0.11 to 0.63; 227 participants; 3 studies; I(2) = 0%; moderate-quality evidence); similar results were seen for acute and chronic retinochoroiditis.The UK study of pyrimethamine for four weeks reported an improvement in intraocular inflammation in treated compared with control participants (RR 1.76, 95% CI 0.98 to 3.19; 29 participants; low-quality evidence). The study in Brazil of trimethoprim-sulfamethoxazole for 12 months stated that the severity of inflammation was higher in the comparator group when compared to the antibiotic-treated group but did not provide further details. In the US study of pyrimethamine-trisulfapyrimidine for eight weeks intraocular inflammation had almost completely resolved by eight weeks in all participants, however in this study all participants received steroid treatment.Two studies (UK and US studies) reported an increased risk of adverse events in treated participants. These were a fall in haemoglobin, leucocyte, and platelet count, nausea, loss of appetite, rash, and arthralgia.
AUTHORS' CONCLUSIONS
Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. Further trials of people with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effects of antibiotic treatment on visual outcomes.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Child; Chorioretinitis; Drug Combinations; Humans; Pyrimethamine; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Sulfadiazine; Sulfamerazine; Sulfamethazine; Toxoplasmosis, Ocular; Trimethoprim, Sulfamethoxazole Drug Combination; Visual Acuity; Watchful Waiting
PubMed: 27198629
DOI: 10.1002/14651858.CD002218.pub2 -
The Cochrane Database of Systematic... Feb 2016Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary body, choroid). Uveitis is the fifth most common cause of vision loss in high-income countries, accounting for 5% to 20% of legal blindness, with the highest incidence of disease in the working-age population.Corticosteroids are the mainstay of acute treatment for all anatomical subtypes of non-infectious uveitis and can be administered orally, topically with drops or ointments, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.
OBJECTIVES
To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 15 April 2013), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for studies. We last searched the electronic databases on 6 November 2015.We also searched reference lists of included study reports, citation databases, and abstracts and clinical study presentations from professional meetings.
SELECTION CRITERIA
We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone intravitreal implants with standard-of-care therapy with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed studies for inclusion. Two review authors independently extracted data and assessed the risk of bias for each study.
MAIN RESULTS
We included data from two studies (619 eyes of 401 participants) that compared FA implants with standard-of-care therapy. Both studies used similar standard-of-care therapy that included administration of prednisolone and, if needed, immunosuppressive agents. The studies included participants from Australia, France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, the United Kingdom, and the United States. We assessed both studies at high risk of performance and detection bias.Only one study reported our primary outcome, recurrence of uveitis at any point during the study through 24 months. The evidence, judged as moderate-quality, showed that a FA implant probably prevents recurrence of uveitis compared with standard-of-care therapy (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.14 to 0.59; 132 eyes). Both studies reported safety outcomes, and moderate-quality evidence showed increased risks of needing cataract surgery (RR 2.98, 95% CI 2.33 to 3.79; 371 eyes) and surgery to lower intraocular pressure (RR 7.48, 95% CI 3.94 to 14.19; 599 eyes) in the implant group compared with standard-of-care therapy through two years of follow-up. No studies compared dexamethasone implants with standard-of-care therapy.
AUTHORS' CONCLUSIONS
After considering both benefits and harms reported from two studies in which corticosteroids implants were compared with standard-of-care therapy, we are unable to conclude that the implants are superior to traditional systemic therapy for the treatment of non-infectious uveitis. These studies exhibited heterogeneity in design and outcomes that measured efficacy. Pooled findings regarding safety outcomes suggest increased risks of post-implant surgery for cataract and high intraocular pressure compared with standard-of-care therapy.
Topics: Adrenal Cortex Hormones; Adult; Chronic Disease; Drug Implants; Humans; Immunosuppressive Agents; Prednisolone; Randomized Controlled Trials as Topic; Recurrence; Standard of Care; Uveitis
PubMed: 26866343
DOI: 10.1002/14651858.CD010469.pub2 -
Orphanet Journal of Rare Diseases Aug 2015Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually... (Review)
Review
BACKGROUND
Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually rare, there has been an increasing tendency for clinical trials to group distinct uveitis syndromes together despite clear variations in phenotype which may reflect real aetiological and pathogenetic differences. Furthermore this grouping of distinct syndromes, and the range of manifestations within each uveitis syndrome, leads to a wide range of possible outcome measures. In this study we wished to review the degree of consensus or otherwise in the choice of primary outcome measures for registered clinical trials related to uveitis.
METHODS
Systematic review of data provided in clinical trial registries describing clinical trials dealing with medical treatment of intermediate, posterior, or panuveitis through 01 October 2013. We reviewed 15 on-line clinical trial registries approved by the International Committee of Medical Journal Editors. We identified all that met the following inclusion criteria: prospective, interventional design; target populations with intermediate, posterior or panuveitis; and one or more pre-specified outcome measures that were related to uveitis. Primary outcome measures were classified in terms of type (efficacy or safety or both; single, composite, or multiple); dimension (disease activity, disease damage, measured or patient-reported visual function); and domain (the specific study variable being measured).
RESULTS
Of 195 registered uveitis studies, we identified 104 clinical trials that met inclusion criteria. There were 14 different domains used as primary outcome measures. Among clinical trials that utilized primary outcome measures of treatment efficacy (n = 94), 70 (74 %) used a measure of disease activity (vitreous haze in 40/70 [57 %]; macular oedema in 19/70 [27 %]) and 49 (70 %) used a measure of visual function (visual acuity in all cases). Multiple primary outcome measures were used in 23 (22 %) of 104 clinical trials. With regard to quality, in 12 (12 %) of 104 clinical trials, outcome measures were poorly defined. No clinical trial utilized a patient-reported study variable as primary outcome measure.
CONCLUSIONS
This systematic review highlights the heterogeneity of outcome measures used in recent clinical trials for intermediate, posterior, and panuveitis. Current designs prioritize clinician-observed measures of disease activity and measurement of visual function as outcome measures. This apparent lack of consensus regarding outcome measures for the study of uveitis is a concern, as it prevents comparison of studies and meta-analyses, and weakens the evidence available to stake-holders, from patients to clinicians to regulators, regarding the efficacy and value of a given treatment.
Topics: Clinical Trials as Topic; Humans; Uveitis
PubMed: 26286265
DOI: 10.1186/s13023-015-0318-6