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American Journal of Ophthalmology Case... Dec 2023To report panuveitis with exudative retinal detachments in a healthy 27-year-old woman with biallelic mutations in the RPE65 gene, who underwent bilateral sequential...
PURPOSE
To report panuveitis with exudative retinal detachments in a healthy 27-year-old woman with biallelic mutations in the RPE65 gene, who underwent bilateral sequential gene therapy with subretinal administration of voretigene neparvovec-rzyl.
OBSERVATIONS
Visual acuity improved for 30 days after surgery as oral corticosteroids were tapered. At postoperative week 6, vision declined due to sudden onset uveitis and exudative retinal detachments in both eyes. HLA Class II typing revealed the haplotype associated with sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH). The inflammation improved after corticosteroid, mycophenolate mofetil, and adalimumab therapy while vision remained poor.
CONCLUSIONS AND IMPORTANCE
Surgically-induced sympathetic ophthalmia is a plausible explanation for the clinical findings; surgery of both eyes within one week would conceal the inciting eye. VKH or inflammation related to the gene therapy are other possible etiologies but severe bilateral panuveitis has not been reported with voretigene neparvovec-rzyl. Informed consent for gene therapy surgery should include a discussion of the rare complication of sympathetic ophthalmia following vitrectomy surgery.
PubMed: 37521805
DOI: 10.1016/j.ajoc.2023.101879 -
International Journal of Ophthalmology 2024To determine the common causes and visual outcome after treatment among uveitis and scleritis patients.
AIM
To determine the common causes and visual outcome after treatment among uveitis and scleritis patients.
METHODS
This is a retrospective cohort observational study. All consecutive clinical records of patients with newly diagnosed uveitis and scleritis over a 4-year period, from Jan. 1, 2017 to Dec. 31, 2020, were analysed. Data was collected at the presentation and included a follow-up period of one year.
RESULTS
A total of 288 patients were recruited during the study period. Anterior uveitis was the most common anatomical diagnosis (50.0%) followed by panuveitis (25.0%), scleritis (13.5%), posterior uveitis (6.9%), and intermediate uveitis (4.5%). Viral Herpes was the most common cause of infectious cases, while Vogt-Koyanagi-Harada (VKH) disease and human leucocyte antigen (HLA) B27 spondyloarthropathy were the leading causes of identifiable non-infectious cases. Majority of patients presented with unilateral, non-granulomatous uveitis with an absence of hypopyon. Anatomical locations like posterior uveitis and panuveitis, and visual acuity worse than 3/60 at presentation were the factors associated with poor visual outcomes (<0.05). About 60% of patients had an identifiable cause for the uveitis and scleritis, with nearly equal distribution of infectious (=85, 29.5%) and non-infectious causes (=84, 29.2%). About 14.5% of patients were clinically blind at 1y of follow-up. The most common complication in our uveitis patients was glaucoma (47.5%), followed by cystoid macula oedema (18.9%) and cataract (13.9%).
CONCLUSION
Uveitis and scleritis are important causes of ocular morbidity. They are potentially blinding diseases which can have a good outcome if diagnosed and treated early.
PubMed: 38721518
DOI: 10.18240/ijo.2024.03.14 -
Research Square Aug 2023Studies on uveitis in Sierra Leone were conducted prior to the Ebola Virus Disease epidemic of 2013-16, which was associated with uveitis in 20% of survivors. They did...
BACKGROUND/OBJECTIVES
Studies on uveitis in Sierra Leone were conducted prior to the Ebola Virus Disease epidemic of 2013-16, which was associated with uveitis in 20% of survivors. They did not include imaging or investigation of tuberculosis and used laboratory services outside the country. We performed a cross-sectional study on patients presenting with uveitis to establish their clinical characteristics and identify the impact of in-country laboratory diagnoses.
METHODS
We invited uveitis cases presenting to Eye Clinics in Sierra Leone from March to September 2022 to participate in the study. They underwent a diagnostic work-up, including fundus and ocular coherence tomography imaging. Active uveitis cases underwent further investigations including serology and immunological tests for syphilis, tuberculosis and herpetic viruses and HIV, and chest radiographs.
RESULTS
We recruited 128 patients. The mean age was 36 ± 14 years and there was an equal gender split. Panuveitis was the predominant anatomical uveitis type (n=51, 40%), followed by posterior uveitis (n=36, 28%). Bilateral disease affected 40 patients (31%). Active uveitis was identified in 75 (59%) cases. ICD 11 definition of blindness with VA<3/60 occurred in 55 (33%) uveitis eyes. Aetiology of uveitis from clinical and laboratory assessment demonstrated that most cases were of undifferentiated aetiology (n=66, 52%), followed by toxoplasmosis (n=46, 36%). Trauma contributed to eight (6%) cases, syphilis to 5 (4%) cases and Ebola to 2 (2%).
CONCLUSIONS
Uveitis was associated with high levels of visual impairment. Posterior and panuveitis contributed to the highest proportion of uveitis cases. Laboratory studies helped differentiate syphilis as a significant aetiology of uveitis.
PubMed: 37609303
DOI: 10.21203/rs.3.rs-3222203/v1 -
International Journal of Ophthalmology 2023To ascertain the pattern of investigations at first contact in uveitic patients and evaluate compliance to treatment.
AIM
To ascertain the pattern of investigations at first contact in uveitic patients and evaluate compliance to treatment.
METHODS
An observational study comprised of 201 uveitic patients presenting for the first time to our centre from January 2019 to June 2020. Detailed information regarding systemic investigations undertaken by specialists at the time of first contact and the cost of these investigations were reviewed on the first visit to our centre. Compliance with the treatment was determined and reasons behind non-compliance were evaluated on the first follow-up in patients who had no improvement in clinical signs and symptoms.
RESULTS
The mean age of the study group was 35.35±14.1y and gender composition was 59.7% males and 40.3% females. Anterior uveitis was observed in 45.3% of patients, intermediate uveitis in 31.8% of patients, posterior uveitis in 14.9% of patients and panuveitis in 8.0% of patients. Association with a systemic disease was evident in 17.9% of patients. When compared with standard guidelines and uveitis patterns, systemic investigations were identified to be relevant only in 38.3% of patients. Non-compliance to treatment was documented in 22.4% of patients. Common reasons for non-compliance were inadequate counselling by the treating physician about treatment in 26.7% of patients and a busy schedule at work/school in 22.2% of patients.
CONCLUSION
Significant number of investigations performed at first contact is found to be contrary to standard guidelines and are not contributory to the care. About a quarter of patients in this study are found to be non-compliant with the treatment. Compliance is more challenging to achieve in school-going children and working adults. The availability of comprehensive, periodically updated, evidence-based guidelines on the role of investigations and the use of trained counsellors may help to channelize proper evaluation and improve compliance to treatment, respectively, in patients with uveitis.
PubMed: 38028517
DOI: 10.18240/ijo.2023.11.13 -
Clinical and Experimental Rheumatology Oct 2023To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in IL17 genes and BD susceptibility.
METHODS
We searched the Medline, Embase, and Cochrane databases for relevant articles. We performed a meta-analysis of serum/plasma IL-17 levels in BD patients and controls and evaluated the associations between IL17A rs4711998, rs8193036, and rs2275913 and IL17F rs763780 and rs2397084 polymorphisms and the risk of BD.
RESULTS
Twelve studies, involving 901 patients with BD and 1,131 controls, were included. Our meta-analysis revealed that circulating IL-17 levels were significantly higher in the BD group than in the control group (SMD = 1.422, 95% confidence interval [CI] = 0.689-2.155, p<0.001). Subgroup analysis by data type indicated higher IL-17 levels in the BD group in both the original and calculated data populations. Stratification by publication year revealed significantly lower vitamin D levels in the SSc group in both recent and older publication years. No significant differences in IL-17 levels were observed between the active and inactive disease groups. We found no evidence of associations between BD and IL17A rs2275913, L17F rs763780, or rs2397084 polymorphisms. However, a significant association was found between BD and IL17A rs4711998 and rs8193036 polymorphisms in the pooled cohort of affected individuals compared to that in pooled controls (odds ratio [OR] = 1.347, 95% CI = 1.043-1.741, p<0.001; OR = 0.691, 95% CI = 0.542-0.880, p=0.003).
CONCLUSIONS
This meta-analysis revealed significantly higher circulating IL-17 levels in BD patients and showed evidence of associations between IL17A rs4711998 and rs8193036 polymorphisms and BD.
Topics: Humans; Interleukin-17; Behcet Syndrome; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Odds Ratio
PubMed: 37650348
DOI: 10.55563/clinexprheumatol/sh84va -
Clinical and Experimental Rheumatology Oct 2023The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the...
OBJECTIVES
The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm.
METHODS
In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study.
RESULTS
In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively).
CONCLUSIONS
Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.
Topics: Child; Humans; Behcet Syndrome; Oral Ulcer; Cross-Sectional Studies; Immunosuppressive Agents; Decision Trees
PubMed: 37902270
DOI: 10.55563/clinexprheumatol/5kr2b1 -
International Ophthalmology Nov 2023Behçet's uveitis (BU) is a debilitating manifestation of Behçet's disease, often requiring prompt and aggressive treatment to prevent vision loss. Glucocorticoids... (Review)
Review
Behçet's uveitis (BU) is a debilitating manifestation of Behçet's disease, often requiring prompt and aggressive treatment to prevent vision loss. Glucocorticoids (GCS) serve as a first-line therapy for BU; however, their long-term, high-dose use can result in significant adverse effects. This review summarizes the efficacy, adverse effects, and advances in combination therapy involving GCS for the management of BU. We discuss the benefits and drawbacks of various GCS administration routes, including periocular and intravitreal injections, intravitreal sustained-release devices, and systemic therapy, highlighting the role of fluocinolone acetonide and dexamethasone as primary sustained-release formulations. Moreover, we underscore the importance of combining GCS with immunosuppressive drugs and biological agents to minimize adverse reactions and optimize therapeutic outcomes. The review concludes that, while GCS remain a crucial component of BU treatment, careful consideration of their administration and combination with other therapies is essential to achieve long-term remission and improved visual outcomes for patients with BU.
Topics: Humans; Behcet Syndrome; Glucocorticoids; Delayed-Action Preparations; Uveitis; Immunosuppressive Agents
PubMed: 37420127
DOI: 10.1007/s10792-023-02808-w -
Ophthalmology May 2024Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary... (Meta-Analysis)
Meta-Analysis Review
TOPIC
Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial.
CLINICAL RELEVANCE
This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat.
METHODS
Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR).
RESULTS
Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%-0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%-0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%-0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal; 95% CI, -0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data.
DISCUSSION
Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Ophthalmia, Sympathetic; Retrospective Studies; Eye Enucleation; Eye Injuries; Eye Evisceration
PubMed: 38086434
DOI: 10.1016/j.ophtha.2023.12.006 -
Journal of Ophthalmic Inflammation and... Mar 2024Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such...
BACKGROUND
Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period.
MAIN FINDINGS
We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL).
SHORT CONCLUSION
CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).
PubMed: 38466527
DOI: 10.1186/s12348-023-00372-z -
Scientific Reports May 2024Previous research has linked serum metabolite levels to iridocyclitis, yet their causal relationship remains unexplored. This study investigated this potential causality...
Previous research has linked serum metabolite levels to iridocyclitis, yet their causal relationship remains unexplored. This study investigated this potential causality by analyzing pooled data from 7824 iridocyclitis patients in a Genome-Wide Association Study (GWAS) using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). Employing rigorous quality control and comprehensive statistical methods, including sensitivity analyses, we examined the influence of 486 serum metabolites on iridocyclitis. Our MR analysis identified 23 metabolites with significant causal effects on iridocyclitis, comprising 17 known and 6 unidentified metabolites. Further refinement using Cochran's Q test and MR-PRESSO indicated 16 metabolites significantly associated with iridocyclitis risk. LDSC highlighted the heritability of certain metabolites, underscoring genetic influences on their levels. Notably, tryptophan, proline, theobromine, and 7-methylxanthine emerged as risk factors, while 3,4-dihydroxybutyrate appeared protective. These findings enhance our understanding of the metabolic interactions in iridocyclitis, offering insights for diagnosis, unraveling pathophysiological mechanisms, and informing potential avenues for prevention and personalized treatment.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Iridocyclitis; Risk Factors; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Male; Female; Genetic Predisposition to Disease
PubMed: 38719907
DOI: 10.1038/s41598-024-61441-4