-
International Ophthalmology Clinics Jul 2022Immune checkpoint inhibitors and targeted therapies are two classes of pharmacologic therapies used to treat metastatic malignancy by amplifying the immune system...
Immune checkpoint inhibitors and targeted therapies are two classes of pharmacologic therapies used to treat metastatic malignancy by amplifying the immune system activity against cancerous cells. However, these drugs can consequently cause immune-related adverse events (irAEs). Albeit rare, cases of ocular IRAEs occurring among patients taking these drugs have been documented in literature, including a spectrum of uveitis findings. The classes of immune checkpoint inhibitors explored here include anti-CTLA4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab) and anti-PDL-1 (atezolizumab, avelumab, durvalumab). Targeted therapies include the MEK inhibitors (trametinib) and BRAF enzyme inhibitors (dabrafenib, vemurafenib), both of which are involved in the MAPK/ERK signaling pathway responsible for cell proliferation. Reported cases of ocular irAEs caused by these drugs include anterior uveitis, posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada (VKH)-like syndrome. Treatment can be determined on a case-by-case basis and depending on the severity of the irAE, may include temporary cessation of the offending drug, local corticosteroids, or systemic corticosteroids. Although the mechanism by which these ocular toxicities occur is not clearly elucidated, it is hypothesized that they are secondary to increased activity of auto-reactive T-cells. Further investigation into mechanisms underlying these inflammatory findings are relevant for cancer targeting, as well as insights into ocular autoimmune diseases.
Topics: Autoimmunity; Humans; Immunotherapy; Neoplasms; Uveitis
PubMed: 35752885
DOI: 10.1097/IIO.0000000000000434 -
Pediatric Rheumatology Online Journal Apr 2021The early detection of uveitis associated with systemic inflammatory disease in children is important for proper treatment and prognosis. However, the diagnosis may be... (Observational Study)
Observational Study
BACKGROUND
The early detection of uveitis associated with systemic inflammatory disease in children is important for proper treatment and prognosis. However, the diagnosis may be delayed because of difficulties in childhood examinations and early minor systemic symptoms. The objective of our study was to identify the pattern of childhood uveitis and investigate the frequency and clinical features of rheumatic diseases in pediatric patients with uveitis.
METHODS
This retrospective observational study reviewed the medical records of children (age ≤ 18 years) with uveitis at a Korean tertiary hospital between January 2005 and December 2018. Data collected included the age at onset of uveitis, sex, anatomic location of ocular inflammation, comorbid disease (including systemic inflammatory disease), ocular complications, relevant laboratory data, and treatment. Fisher's exact test was used to compare categorical variables and the Mann-Whitney U test was used to compare continuous variables. A p-value of < 0.05 was considered statistically significant.
RESULTS
A total of 155 pediatric patients with uveitis were included in this study. The median age at diagnosis was 13.0 years (interquartile range, 9.5-16.0 years). The male-to-female ratio was 1.09. The process was unilateral in 51.6% of children. Anterior uveitis, panuveitis, intermediate uveitis, and posterior uveitis represented 51.6, 26.5, 6.5, and 1.9% of the cases, respectively. Idiopathic uveitis (65.2%) was the most frequent type of uveitis. Systemic rheumatic disease associations were responsible for 28.4% of the cases, among which juvenile idiopathic arthritis (JIA) was the most frequent cause (14.8%). Human leukocyte antigen (HLA)-B27 and antinuclear antibody (ANA) positive rates were significantly higher in patients with JIA than in those with idiopathic uveitis (p = 0.006 and p = 0.007, respectively).
CONCLUSIONS
Approximately one-third of children with uveitis in Korea have a systemic rheumatic disease, of which JIA accounts for the majority of cases. HLA-B27 and ANA can serve as risk factors for JIA-associated uveitis.
Topics: Adolescent; Child; Female; Humans; Male; Retrospective Studies; Rheumatic Diseases; Uveitis
PubMed: 33794945
DOI: 10.1186/s12969-021-00516-2 -
Eye (London, England) Apr 2023To examine risk factors for development of glaucoma in a large cohort of subjects with uveitis and scleritis.
BACKGROUND
To examine risk factors for development of glaucoma in a large cohort of subjects with uveitis and scleritis.
METHODS
Retrospective review of subjects diagnosed with uveitis or scleritis between 2006 and 2019 at Auckland District Health Board. Subjects were excluded if they had glaucoma due to another cause. Main outcome measure was development of glaucoma. Data for local steroid use was not available.
RESULTS
3462 eyes of 2414 subjects were included in the study. Mean follow-up was 5.7 years (total follow-up time 19,897 eye years). Median age was 44.3 years and 1189 (49.3%) were female. Glaucoma developed in 222 eyes (6.3%) during the follow-up. Five-year cumulative risk of glaucoma was 6.2% (CI 5.0-7.5%) for anterior uveitis, 5.4% (CI 3.2-9.0%) for intermediate uveitis, 1.6% (CI 0.4-6.7%) for posterior uveitis, 8.7% (CI 6.5-11.7%) for panuveitis, and 3.2% (CI 1.0-9.5%) for scleritis. Five-year cumulative risk of glaucoma was lowest in HLA-B27 uveitis at 0.9% (CI 0.4-2.1%) and highest in viral uveitis 15.1% (CI 10.1-22.3%), sarcoidosis 9.9% (CI 6.1-15.9%) and tuberculosis 9.7% (CI 5.4-17.0%). On multivariate analysis, risk factors for development of glaucoma were older age at presentation, higher presenting intraocular pressure, chronic inflammation, and cystoid macular oedema.
CONCLUSIONS
Glaucoma is a common complication of uveitis and scleritis and was more frequent in older subjects, high presenting IOP, chronic inflammation and those with cystoid macular oedema. Local steroid therapy contributes to this, but is not quantifiable in this study. Targeted screening is required to avoid irreversible progression of glaucomatous optic neuropathy.
Topics: Humans; Female; Aged; Adult; Male; Scleritis; Macular Edema; Intraocular Pressure; Glaucoma; Uveitis; Uveitis, Anterior; Retrospective Studies; Inflammation; Steroids
PubMed: 35610358
DOI: 10.1038/s41433-022-02101-7 -
Medicina (Kaunas, Lithuania) Jan 2022Primary inflammatory choriocapillaropathies (PICCPs) belong to a group of intraocular inflammatory diseases with the common characteristic of inflammatory... (Review)
Review
PURPOSE
Primary inflammatory choriocapillaropathies (PICCPs) belong to a group of intraocular inflammatory diseases with the common characteristic of inflammatory choriocapillaris hypo- or non-perfusion as the main clinicopathological mechanism. The purpose of our article is to describe clinical characteristics and multimodal imaging, that can help the diagnosis and treatment of PICCPs.
METHODS
Narrative review with multimodal imaging analysis.
RESULTS
Choriocapillaris non-perfusion can affect the end-choriocappilaries, at the benign end of the PICCP spectrum (MEWDS), to larger choriocapillaris vessels or precapillary vessels at the origin of more severe forms such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), idiopathic multifocal choroiditis (MFC) and Serpiginous Choroiditis (SC). Diagnosis is mostly based on multimodal imaging and especially on indocyanine green angiography (ICGA), fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT)/OCT-angiography (OCT-A). ICGA shows the typical pattern of patchy lobular hypofluorescence reflecting hypo- or non-perfusion of the choriocapillaris that can also take the aspect of geographic areas in the more severe forms. Treatment depends on the severity of the disease and goes from observation in MEWDS and some mild cases of APMPPE, to oral corticosteroid and/or immunomodulator agents in the more severe conditions of APMPPE and MFC and SC cases. Close multimodal monitoring is crucial in order to introduce or adjust treatment.
CONCLUSION
PICCPs are resulting from one common clinicopathological mechanism, inflammatory choriocapillaris hypo- or non-perfusion. ICGA findings are essential for the diagnosis and follow-up of PICCPs, but non-invasive methods such as FAF and SD-OCT/OCT-A also have their role especially in follow-up of the diseases. Treatment should be individualized according to the pathology and the evolution of lesions.
Topics: Choroid; Choroiditis; Fluorescein Angiography; Humans; Multifocal Choroiditis; Tomography, Optical Coherence
PubMed: 35208488
DOI: 10.3390/medicina58020165 -
Redox Biology Nov 2023Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is...
Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.
Topics: Animals; Mice; Humans; Toxoplasmosis, Ocular; Ferroptosis; Toxoplasma; Chorioretinitis; Retina; Iron
PubMed: 37738924
DOI: 10.1016/j.redox.2023.102890 -
Journal of Ophthalmic Inflammation and... Sep 2022Uveitis is one of the common causes of visual impairment in Malaysia. It remains a challenging entity to diagnose and manage due to variation in its clinical...
INTRODUCTION
Uveitis is one of the common causes of visual impairment in Malaysia. It remains a challenging entity to diagnose and manage due to variation in its clinical presentation. This study aims to observe the demographic and clinical pattern of cases from the participating ophthalmology units in Malaysia.
METHODS
This study involved prospective and multicentered data collection for patients newly diagnosed with uveitis from 1 January 2018 to 31 December 2018. Variables collected and analyzed included age, gender, ethnicity, nationality, state of origin, laterality, granulomatous or non-granulomatous uveitis, and etiology of uveitis.
RESULTS
A total of 1199 newly diagnosed uveitis patients were analyzed within the study period. There was a significant association between the anatomical location of uveitis with age at presentation. The percentage of patients with anterior uveitis was higher in the '40 to 60' years and 'above 60' years age groups at 52.1% (n = 210) and 61.3% (n = 114) respectively. In contrast the percentage of patients with posterior and panuveitis was higher in the 1 to 20 and 20 to 40 years age groups at 51.4% (n = 54) and 48.7% (n = 246) respectively. Sixty three percent of the patients presented with unilateral uveitis (n = 760, p < 0.001) vs bilateral. Non-granulomatous uveitis comprised 84.5% of all patients (n = 1013, p < 0.001) compared to granulomatous uveitis. Non-infectious etiology contributed to 65.7% of all patients (n = 788, p < 0.001) with the majority being unclassifiable uveitis (n = 686, 57.2%,). Specific inflammatory entities contributed to only 8.5% (n = 102) of the non-infectious causes with Vogt-Koyanagi-Harada (VKH) syndrome being the most common (n = 25, 2.1%,). Infectious uveitis comprised 34.3% (n = 411) with tubercular (TB) uveitis (n = 105, 8.8%) and viral uveitis (n = 107, 8.9%) contributing the most followed by ocular Toxoplasmosis (n = 93,7.8%).] CONCLUSION: This study has highlighted the demographic data and common causes of uveitis in Malaysia.
PubMed: 36048269
DOI: 10.1186/s12348-022-00306-1 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for pars planitis.
PURPOSE
To determine classification criteria for pars planitis.
DESIGN
Machine learning of cases with pars planitis and 4 other intermediate uveitides.
METHODS
Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set.
RESULTS
Five hundred eighty-nine cases of intermediate uveitides, including 226 cases of pars planitis, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for pars planitis included unilateral or bilateral intermediate uveitis with either 1) snowballs in the vitreous or 2) snowbanks on the pars plana. Key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0% in the training set and 1.7% in the validation set, respectively.
CONCLUSIONS
The criteria for pars planitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.
Topics: Adolescent; Adult; Child; Female; Humans; Machine Learning; Male; Pars Planitis; Visual Acuity; Young Adult
PubMed: 33845006
DOI: 10.1016/j.ajo.2021.03.045 -
American Journal of Ophthalmology Jan 2021To elucidate molecular risk factors for posterior segment uveitis using a functional genomics approach.
OBJECTIVE
To elucidate molecular risk factors for posterior segment uveitis using a functional genomics approach.
DESIGN
Genetic association cohort study.
METHODS
Setting: Single-center study at an academic referral center.
STUDY POPULATION
164 patients with clinically diagnosed uveitis of the posterior segment.
MAIN OUTCOME MEASURES
Exome sequencing was used to detect variants identified in 164 patients with posterior segment uveitis. A phenotype-driven analysis, protein structural modeling, and in silico calculations were then used to rank and predict the functional consequences of key variants.
RESULTS
A total of 203 single nucleotide variants, in 23 genes across 164 patients, were included in this study. Both known and novel variants were identified in genes previously implicated in specific types of syndromic uveitis-such as NOD2 (Blau syndrome) and CAPN5 NIV (neovascular inflammatory vitreoretinopathy)-as well as variants in genes not previously linked to posterior segment uveitis. Based on a ranked list and protein-protein-interaction network, missense variants in NOD-like receptor family genes (NOD2, NLRC4, NLRP3, and NLRP1), CAPN5, and TYK2 were characterized via structural modeling and in silico calculations to predict how specific variants might alter protein structure and function. The majority of analyzed variants were notably different from wild type.
CONCLUSIONS
This study implicates new pathways and immune signaling proteins that may be associated with posterior segment uveitis susceptibility. A larger cohort and functional studies will help validate the pathogenicity of the mutations identified. In specific cases, whole-exome sequencing can help diagnose nonsyndromic uveitis in patients harboring known variants for syndromic inflammatory diseases.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calpain; Child; Child, Preschool; Female; Genetic Association Studies; Humans; Inflammasomes; Male; Middle Aged; Mutation, Missense; NLR Proteins; Proteomics; TYK2 Kinase; Uveitis, Posterior; Exome Sequencing
PubMed: 32707200
DOI: 10.1016/j.ajo.2020.07.021 -
Journal of Vitreoretinal Diseases 2022This work presents a case of syphilitic outer retinopathy with findings similar to those of acute zonal occult outer retinopathy (AZOOR). We also discuss the clinical... (Review)
Review
PURPOSE
This work presents a case of syphilitic outer retinopathy with findings similar to those of acute zonal occult outer retinopathy (AZOOR). We also discuss the clinical characteristics, treatment, and prognosis of this entity.
METHODS
A case report and systematic literature review are presented.
RESULTS
A 56-year-old woman presented with acute vision loss, localized photopsia, a central scotoma, and retinal findings that were all consistent with AZOOR. A further workup led to a diagnosis of syphilis. Oral prednisone and intravenous penicillin resulted in the resolution of the posterior uveitis and the restoration of visual acuity. However, the central scotoma remained at the 3-year follow-up visit.
CONCLUSIONS
Syphilitic outer retinopathy is a distinct entity characterized by the disruption of the ellipsoid zone visible on optical coherence tomography and a corresponding increase in fundus hyperautofluorescence in the affected areas. Although some patients may present with a demarcation line, as is seen with AZOOR, the fundus is oftentimes unremarkable or may show only subtle retinal pigment epithelium changes. Uveitis resolution and visual acuity restoration may be expected following treatment; however, visual field disturbances may persist.
PubMed: 37007722
DOI: 10.1177/24741264211018300 -
Journal of Ophthalmic & Vision Research 2022To investigate the pattern of ocular involvement in Behcet's disease (BD) with predictors of patients' final state of vision.
PURPOSE
To investigate the pattern of ocular involvement in Behcet's disease (BD) with predictors of patients' final state of vision.
METHODS
This historical cohort encompassed the clinical records of 200 patients diagnosed according to the International Criteria for BD (ICBD), over a period of 17 years between 2004 and 2021.
RESULTS
The prevalence of Behcet's uveitis (BU) was more common in females and patients in the fourth decade of life. Ninety-five patients (47.5%) had evidence of ocular involvement in the initial ophthalmologic evaluation, and 171 patients (85.5%) manifested evidence of BU during the follow-up visits of which bilateral non-granulomatous panuveitis was the most common anatomical pattern of involvement (32.9%) followed by posterior (27.6%), anterior (26.5%), and intermediate (13.8%) uveitis. The prevalent accompanying signs were oral aphthous (67%), skin lesions (29%), and genital ulcers (19.5%). Cystoid macular edema (CME) was the most frequent ocular complication (62%), followed by cataract (57.5%) and epiretinal membranes (ERM) (36.5%). Univariate analysis showed the following determinants: male gender, younger age at onset, panuveitis, posterior uveitis, retinal vasculitis, and longer duration of uveitis as poorer visual prognostic factors of the disease. Multivariate analysis demonstrated a higher chance of poor visual prognosis of BD in patients with panuveitis, posterior uveitis, retinal vasculitis, and longer duration of uveitis.
CONCLUSION
This cohort study demonstrated an overview on epidemiological patterns of BU along with the visual prognostic factors in Iranian patients.
PubMed: 35765637
DOI: 10.18502/jovr.v17i2.10796