-
International Ophthalmology May 2020To review the multimodal imaging patterns of posterior syphilitic uveitis.
PURPOSE
To review the multimodal imaging patterns of posterior syphilitic uveitis.
METHODS
A systematic review.
RESULTS
The percentage of syphilis has started to increase again: The World Health Organization has reported 12 million new cases of syphilis each year. In addition, syphilis was responsible for 0.3% of deaths globally in 2002. Eye manifestations happen prevalently in secondary and tertiary stages of syphilis, even though ocular involvement can occur in all stages. Syphilis has the nickname: "the great imitator" since it has no unique clinical presentation, even though posterior uveitis is considered the most common form. Syphilis is known as "the great imitator," making its diagnosis in the presence of posterior uveitis particularly challenging as it presents similarly to other ocular conditions such as acute retinal necrosis. However, with the advent of multimodal imaging some particular patterns of pre-retinal, retinal, retinochoroidal and optic nerve involvement from syphilis can be identified to guide the diagnosis and the laboratory workup.
CONCLUSION
This review highlights the various patterns of pre-retinal precipitates, multifocal retinitis, retinochoroiditis (confluent and placoid) and optic neuritis caused by syphilis, the appropriate laboratory work to be obtained and the treatment to be initiated.
Topics: Anti-Bacterial Agents; Eye Infections, Bacterial; Humans; Multimodal Imaging; Prognosis; Syphilis; Uvea; Uveitis, Posterior; Visual Acuity
PubMed: 31927680
DOI: 10.1007/s10792-020-01285-9 -
Genetics in Medicine : Official Journal... Mar 2022This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases. (Review)
Review
PURPOSE
This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases.
METHODS
This review was prospectively registered (CRD42021229812). A comprehensive literature search was performed in Ovid MEDLINE, Ovid Embase, Cochrane Central, and clinical trial registries (February 2021). Clinical studies describing DNA-based gene therapy treatments for monogenic posterior ocular diseases were eligible for inclusion. Risk of bias evaluation was performed. Data synthesis was undertaken applying Synthesis Without Meta-analysis guidelines.
RESULTS
This study identified 47 full-text publications, 50 conference abstracts, and 54 clinical trial registry entries describing DNA-based ocular gene therapy treatments for 16 different genetic variants. Study summaries and visual representations of safety and efficacy outcomes are presented for 20 unique full-text publications in RPE65-mediated retinal dystrophies, choroideremia, Leber hereditary optic neuropathy, rod-cone dystrophy, achromatopsia, and X-linked retinoschisis. The most common adverse events were related to lid/ocular surface/cornea abnormalities in subretinal gene therapy trials and anterior uveitis in intravitreal gene therapy trials.
CONCLUSION
There is a high degree of variability in ocular monogenic gene therapy trials with respect to study design, statistical methodology, and reporting of safety and efficacy outcomes. This review improves the accessibility and transparency in interpreting gene therapy trials to date.
Topics: Color Vision Defects; Genetic Therapy; Humans; Optic Nerve Diseases; Retina; Retinal Dystrophies
PubMed: 34906485
DOI: 10.1016/j.gim.2021.10.013 -
Ocular Immunology and Inflammation Apr 2023The present study aimed to estimate the global prevalence of ocular toxoplasmosis in the general population and patients with uveitis.
PURPOSE
The present study aimed to estimate the global prevalence of ocular toxoplasmosis in the general population and patients with uveitis.
METHODS
Four electronic databases were searched and 130 studies for evaluating the prevalence of OT among the general population and uveitis patients were included.
RESULTS
The pooled prevalence of OT among the general population was estimated at 2% (95% CI, 2-3%; 762/486 051). The highest prevalence rate was observed in America 6% (95% CI, 1-11%). In uveitis patients, a prevalence rate of 9% (95% CI, 8-10%; 5668/88 006) was reported. The countries with a lower middle income had higher prevalence rates. The prevalence of OT in posterior uveitis 33% (95%CI, 24-42%) was substantially higher than in panuveitis 7% (95% CI, 5-8%).
CONCLUSION
Our results provide a new perspective on the prevalence of OT. Knowledge of international and regional patterns of disease is essential for the establishment of precise diagnostic protocols and control programs.
PubMed: 37043543
DOI: 10.1080/09273948.2023.2190801 -
Ocular Immunology and Inflammation Nov 2023Choroidal neovascularization (CNV) affects 64-75% of eyes with punctate inner choroidopathy (PIC). Although anti-VEGF agents are considered first-line therapy, there is...
Choroidal neovascularization (CNV) affects 64-75% of eyes with punctate inner choroidopathy (PIC). Although anti-VEGF agents are considered first-line therapy, there is controversy regarding other modalities, such as immunosuppression. We performed a systematic review of individual participant data (IPD) and generated a dataset of 278 eyes with PIC-related CNV from 45 studies. Forty-two percent presented with moderate visual loss (MVL) or worse. Four different treatment modalities (anti-VEGF, photodynamic therapy, local immunosuppression, and systemic immunosuppression) and most combinations among them were represented. Anti-VEGF injections decreased the likelihood of MVL (Odds Ratio 0.3, p = .027), an effect moderated by presenting visual acuity and patient age. Eyes receiving more than 3 injections were more likely to receive additional therapeutic modalities. Increasing number of modalities was associated with longer follow-up time and did not improve vision. The beneficial effect of anti-VEGF injections persisted when controlling for presenting visual acuity and follow-up time.
Topics: Humans; Choroidal Neovascularization; White Dot Syndromes; Eye; Fluorescein Angiography; Angiogenesis Inhibitors; Retrospective Studies
PubMed: 36179037
DOI: 10.1080/09273948.2022.2124176 -
The British Journal of Ophthalmology Aug 2020Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD...
BACKGROUND
Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD manifestations.
OBJECTIVE
To review the evidence base for biologics in the treatment of ocular BD.
METHODS
Systematic literature search was made using exploded key words-Behçet's, ocular, biologics in MEDLINE, Cochrane library, Database of Abstracts Reviews and Effects, Clinical Trials.gov, Science Direct and Google Scholar. There was no limitation on region, language or date (Search updated 16th October 2018). Literature retrieval was restricted to randomised controlled trials (RCTs) of biologics.
RESULTS
Of 237 papers retrieved, eight met the inclusion criteria. RCTs on interferon alpha 2a (INF-α 2a), adalimumab, secukinumab, gevokizumab, rituximab and daclizumab were retrieved (two for adalimumab and gevokizumab). The outcome measures were not met for secukinumab, daclizumab and gevokizumab. Rituximab and INF-α 2a showed promising preliminary results but sufficiently powered RCTs are needed to provide adequate evidence of efficacy. The RCTs on adalimumab did not evaluate efficacy for BD uveitis specifically, hence are of limited value for this review.
CONCLUSION
Some biologics show promise in treating BD uveitis, but more RCTs are needed for firm conclusions about efficacy. A phase IV study or, registry of adalimumab could provide data on its efficacy in BD uveitis compared to other forms.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Behcet Syndrome; Biological Factors; Biological Therapy; Daclizumab; Humans; Interferon-alpha; Rituximab; Uveitis
PubMed: 31676596
DOI: 10.1136/bjophthalmol-2019-314154 -
Survey of Ophthalmology 2021To identify clinical presentations, main causes, and prognosis of ophthalmic involvement in chronic lymphocytic leukemia (CLL), we performed a systematic review of... (Review)
Review
To identify clinical presentations, main causes, and prognosis of ophthalmic involvement in chronic lymphocytic leukemia (CLL), we performed a systematic review of articles describing CLL ophthalmic involvement in January 2019, using the PubMed database. We found 86 articles describing 123 cases of patients with ophthalmic involvement associated with CLL. Ophthalmic symptoms were CLL's first manifestation in 25.6% of patients and revealed Richter transformation in 11.0%. There were three main causes of ophthalmic features: CLL-infiltration (52.0%), lymphoma (26.0%), and infection (15.4%), with specific clinical and radiological characteristics. CLL-infiltration was mostly bilateral, whereas lymphoma was usually unilateral (P = 0.02). Optic neuropathy was always secondary to CLL-infiltration, and in those cases, cerebrospinal fluid immunophenotyping was a potential alternative to invasive biopsy as it confirmed the diagnosis in 4 patients (36.4%). On the contrary, lymphoma usually presented as adnexal involvement (P = 0.04), particularly as an orbital mass (P = 0.004). Infections concerned mostly patients previously treated for CLL (P < 0.0001), and main presentations included posterior uveitis (P = 0.0002) and retinal infiltrates (P < 0.0001). Overall, the prognosis was poor, as 29.3% of the patients died within 36 months of follow-up, and 26.1% had a partial or total visual loss. Eye infections were associated with the poorest prognosis as 47% of patients died, with a 6-month-median survival.
Topics: Biopsy; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Prognosis
PubMed: 32407752
DOI: 10.1016/j.survophthal.2020.05.001 -
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 -
Frontiers in Genetics 2022Th17 and regulatory T cells (Tregs) play crucial roles in the pathogenesis of autoimmune diseases. Th17/Treg homeostasis is critically involved in maintaining the immune...
Th17 and regulatory T cells (Tregs) play crucial roles in the pathogenesis of autoimmune diseases. Th17/Treg homeostasis is critically involved in maintaining the immune balance. Disturbed Th17/Treg homeostasis contributes to the progression of autoimmune diseases. MicroRNAs (miRNAs) have emerged as a new vital factor in the regulation of disturbed Th17/Treg homeostasis. To better understand the epigenetic mechanisms of miRNAs in regulating Treg/Th17 homeostasis, we included and evaluated 97 articles about autoimmune diseases and found that miRNAs were involved in the regulation of Treg/Th17 homeostasis from several aspects positively or negatively, including Treg differentiation and development, Treg induction, Treg stability, Th17 differentiation, and Treg function. Uveitis is one of the ocular autoimmune diseases, which is also characterized with Th17/Treg imbalance. However, our understanding of the miRNAs in the pathogenesis of uveitis is elusive and not well-studied. In this review, we further summarized miRNAs found to be involved in autoimmune uveitis and their potential role in the regulation of Th17/Treg homeostasis.
PubMed: 36186459
DOI: 10.3389/fgene.2022.848985 -
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 -
Revista Da Sociedade Brasileira de... 2023Ocular toxoplasmosis is the leading cause of infectious posterior uveitis worldwide, accounting for 30-50% of all cases in immunocompetent patients. Conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ocular toxoplasmosis is the leading cause of infectious posterior uveitis worldwide, accounting for 30-50% of all cases in immunocompetent patients. Conventional treatment is associated with adverse effects and does not prevent recurrence. Intravitreal drug administration can improve disease outcomes and reduce side effects. Herein, we conducted a systematic review and meta-analysis on the efficacy of intravitreal injections for treating ocular toxoplasmosis.
METHODS
The systematic search was conducted using PubMed, SciELO, and Google Scholar with the descriptors "ocular toxoplasmosis" AND "intravitreal". We analyzed studies that met the inclusion criteria, i.e., experimental cases in patients treated intravitreally for ocular toxoplasmosis. Considering the systematic review, we focused on the number of intravitreal injections, the therapeutic drug class, and the presence of preexisting conditions. To assess the efficacy of intravitreal injections, a meta-analysis was performed using visual acuity, side effects, disease recurrence, and inflammatory responses as variables.
RESULTS
Intravitreal injection-induced side effects were rarely observed (0.49% [0.00, 1.51%] ). The use of antiparasitic and anti-inflammatory drugs afforded improved visual acuity (99.81% [98.60, 100.00%]) and marked effectiveness in treating ocular toxoplasmosis.
CONCLUSIONS
Intravitreal injections may facilitate the successful treatment of ocular toxoplasmosis. However, clinicians should carefully evaluate the presence of preexisting conditions for ocular toxoplasmosis or previous diseases, as these can impact the decision to administer intravitreal injections.
Topics: Humans; Drug-Related Side Effects and Adverse Reactions; Eye Infections; Toxoplasmosis
PubMed: 37222350
DOI: 10.1590/0037-8682-0552-2022