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Ocular Immunology and Inflammation 2020: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.: A survey was distributed... (Review)
Review
: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.: A survey was distributed to uveitis specialists to identify patients who developed uveitis while receiving either PD-1 inhibitors pembrolizumab and nivolumab; PD-L1 inhibitors atezolizumab, avelumab, and durvalumab; or the CTLA-4 inhibitor ipilimumab.: Fifteen patients from seven institutions were identified. The most common cancer diagnosis (13/15) was malignant melanoma. Fourteen patients had a new uveitis diagnosis following checkpoint blockade administration (six anterior uveitis, six panuveitis, one posterior uveitis, one anterior/intermediate combined); one patient developed optic neuritis. Uveitis was diagnosed within 6 months after drug initiation for 11/12 patients (median 63 days). Corticosteroid treatment was effective for most patients, although two patients had permanent loss of vision.: Patients on checkpoint inhibitor therapy should be educated to seek care if they develop ocular symptoms, and prompt referral to specialists should be incorporated into oncology protocols.
Topics: Antineoplastic Agents, Immunological; CTLA-4 Antigen; Humans; Programmed Cell Death 1 Receptor; Uveitis
PubMed: 30821569
DOI: 10.1080/09273948.2019.1577978 -
Progress in Retinal and Eye Research Mar 2020A diagnostic sign refers to a quantifiable biological parameter that is measured and evaluated as an indicator of normal biological, pathogenic, or pharmacologic... (Review)
Review
A diagnostic sign refers to a quantifiable biological parameter that is measured and evaluated as an indicator of normal biological, pathogenic, or pharmacologic responses to a therapeutic intervention. When used in translational research discussions, the term itself often alludes to a sign used to accelerate or aid in diagnosis or monitoring and provide insight into "personalized" medicine. Many new diagnostic signs are being developed that involve imaging technology. Optical coherence tomography is an imaging technique that provides in vivo quasi-histological images of the ocular tissues and as such it's able to capture the structural and functional modifications that accompany inflammation and infection of the posterior part of the eye. From the hyperreflective inflammatory cells and deposits in the vitreous and on the hyaloid, to the swollen photoreceptors bodies in multiple evanescent white dots syndrome, and from optical differences in the subretinal fluid compartments in Vogt-Koyanagi-Harada disease to the hyporeflective granulomas in the choroid, these tomographical signs can be validated to reach the status of biomarkers. Such non-invasive imaging diagnostic signs of inflammation can be very useful to clinicians seeking to make a diagnosis and can represent a dataset for machine learning to offer a more empirical approach to the detection of posterior uveitis.
Topics: Choroid; Humans; Tomography, Optical Coherence; Uveitis, Posterior; Visual Acuity
PubMed: 31513851
DOI: 10.1016/j.preteyeres.2019.100797 -
Cells Feb 2021Retinal vascular diseases have distinct, complex and multifactorial pathogeneses yet share several key pathophysiological aspects including inflammation, vascular... (Review)
Review
Retinal vascular diseases have distinct, complex and multifactorial pathogeneses yet share several key pathophysiological aspects including inflammation, vascular permeability and neovascularisation. In non-infectious posterior uveitis (NIU), retinal vasculitis involves vessel leakage leading to retinal enlargement, exudation, and macular oedema. Neovascularisation is not a common feature in NIU, however, detection of the major angiogenic factor-vascular endothelial growth factor A (VEGF-A)-in intraocular fluids in animal models of uveitis may be an indication for a role for this cytokine in a highly inflammatory condition. Suppression of VEGF-A by directly targeting the leukotriene B4 (LTB4) receptor (BLT1) pathway indicates a connection between leukotrienes (LTs), which have prominent roles in initiating and propagating inflammatory responses, and VEGF-A in retinal inflammatory diseases. Further research is needed to understand how LTs interact with intraocular cytokines in retinal inflammatory diseases to guide the development of novel therapeutic approaches targeting both inflammatory mediator pathways.
Topics: Animals; Disease Models, Animal; Humans; Inflammation; Receptors, Leukotriene B4; Retinal Vasculitis; Uveitis; Vascular Endothelial Growth Factor A
PubMed: 33671954
DOI: 10.3390/cells10020396 -
European Journal of Ophthalmology May 2023To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year.
PURPOSE
To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year.
METHODS
Retrospective observational case reports.
RESULTS
Two patients (one female and one male) under follow-up for posterior uveitis having stable course with absence of ocular inflammation for more than a year presented with recurrence of choroiditis lesions 2-6 weeks following anti-SARS-CoV-2 vaccination. Both the patients were managed with intravitreal dexamethasone implant (Ozurdex®, Allergan, Inc., Irvine, CA, USA) and showed resolution of choroiditis lesions upon follow-up.
CONCLUSIONS
Acute onset recurrence of inflammation, in absence of any change in health status or treatment suggests the potential role of vaccination being the trigger of this reactivation. Given large-scale vaccination against novel coronavirus- SARS-CoV-2, careful vigilance is warranted to pick up the disease recurrence in patients with posterior uveitis.
Topics: Humans; Male; Female; Retrospective Studies; COVID-19; SARS-CoV-2; Choroiditis; Dexamethasone; Uveitis, Posterior; Inflammation
PubMed: 35306917
DOI: 10.1177/11206721221088439 -
Medical Hypothesis, Discovery &... 2018Treatment of infectious posterior uveitis represents a therapeutic challenge for ophthalmologists. The eye is a privileged site, maintained by blood ocular barriers,... (Review)
Review
Treatment of infectious posterior uveitis represents a therapeutic challenge for ophthalmologists. The eye is a privileged site, maintained by blood ocular barriers, which limits penetration of systemic antimicrobials into the posterior segment. In addition, topical and subconjunctival therapies are incapable of producing sufficient drug concentrations, intraocularly. Posterior infectious uveitis can be caused by bacteria, virus, fungi, or protozoa. Mode of treatment varies greatly based on the infectious etiology. Certain drugs have advantages over others in the treatment of infectious uveitis. Topical and systemic therapies are often employed in the treatment of ocular infection, yet the route of treatment can have limitations based on penetration, concentration, and duration. The introduction of intravitreal antimicrobial therapy has advanced the management of intraocular infections. Being able to bypass blood-ocular barriers allows high drug concentrations to be delivered directly to the posterior segment with minimal systemic absorption. However, because the difference between the therapeutic and the toxic doses of some antimicrobial drugs falls within a narrow concentration range, intravitreal therapy could be associated with ocular toxicity risks. In many cases of infectious uveitis, combination of intravitreal and systemic therapies are necessary. In this comprehensive review, the authors aimed at reviewing clinically relevant data regarding intraocular and systemic antimicrobial therapy for posterior segment infectious uveitis. The review also discussed the evolving trends in intraocular treatment, and elaborated on antibiotic pharmacokinetics and pharmacodynamics, efficacy, and adverse effects.
PubMed: 30505865
DOI: No ID Found -
Clinical Ophthalmology (Auckland, N.Z.) 2015The purpose of this study was to identify the causes, clinical features, and outcomes of intermediate uveitis, posterior uveitis, and panuveitis in patients managed in a...
BACKGROUND
The purpose of this study was to identify the causes, clinical features, and outcomes of intermediate uveitis, posterior uveitis, and panuveitis in patients managed in a mid-Atlantic tertiary care center.
METHODS
This was a retrospective observational study of intermediate uveitis, posterior uveitis, and panuveitis patients seen at the University of Virginia from 1984 to 2014.
RESULTS
One hundred and fifty-nine intermediate uveitis, posterior uveitis, and panuveitis patients (237 eyes) were identified. The patient population was 54.72% female; 67.30% of patients were Caucasian, and 22.01% were African-American. Mean age at diagnosis was 45.5 years. Mean duration of follow-up was 3.95 years. Mean number of visits to the clinic was 10.35. Of 491 uveitis patients, 26 (5.30%) had intermediate uveitis, 62 (12.60%) had posterior uveitis, and 71 (14.50%) had panuveitis. The leading diagnoses in the intermediate uveitis group were pars planitis (73.08%) and sarcoidosis (11.54%); toxoplasma uveitis (17.74%), multifocal choroiditis (14.52%), undifferentiated posterior uveitis (14.52%), and birdshot chorioretinitis (11.29%) in the posterior uveitis group; and undifferentiated panuveitis (29.58%), post-surgical panuveitis (18.31%), sarcoidosis (12.68%), acute retinal necrosis (12.68%), and toxoplasma uveitis (4.23%) in the panuveitis group. The most common treatment modalities included local steroids (57.23%) and systemic steroids (42.14%). Ocular hypertension was found in 38 patients (23.90%). Glaucoma surgery was performed in 18.24% of patients and cataract surgery in 21.38%. Mean best-corrected visual acuity was 0.66 logMAR at baseline across all anatomical locations and 0.57 logMAR at final follow-up. Best-corrected visual acuity improved or remained stable during follow-up in all groups.
CONCLUSION
The most common diagnoses in our series by anatomical location were pars planitis (intermediate uveitis), toxoplasmosis (posterior uveitis), and undifferentiated uveitis (panuveitis). Panuveitis had significantly worse visual outcomes and higher rates of complications than did intermediate or posterior uveitis, a finding that confirms earlier reports. In this series, unilateral disease, regardless of anatomical location, was associated with poorer visual outcome, in contrast with the findings of other reports.
PubMed: 26345421
DOI: 10.2147/OPTH.S89428 -
Survey of Ophthalmology 2023An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for... (Review)
Review
An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a 'multimodal' approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.
Topics: Humans; Multimodal Imaging; Uveitis, Posterior; Uveitis; Fluorescein Angiography; Fundus Oculi; Tomography, Optical Coherence; Choroid
PubMed: 36724831
DOI: 10.1016/j.survophthal.2023.01.006 -
Journal of Clinical Medicine Aug 2022Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disorder typically characterized by sudden-onset non-granulomatous anterior uveitis associated with...
BACKGROUND
Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disorder typically characterized by sudden-onset non-granulomatous anterior uveitis associated with tubulointerstitial nephritis (TIN). However, the prevalence and clinical features of TINU are still a matter of debate. To add information about TINU, we describe here the clinical features of a series of patients affected by TINU in a retrospective study.
METHODS
A total of 9358 clinical records of both adult and pediatric patients up to 21 years of age, referred to the Uveitis Center of the Sapienza University of Rome, were examined. The medical records covered a period from 1990 to 2020. Various demographic and clinical features were analyzed in patients who met the criteria for TINU.
RESULTS
Twenty-one patients with TINU were identified. TINU was classified as definite, possible, or probable by the currently recognized international criteria. The median age at diagnosis was 14 years (interquartile range 12-35). Females were predominant (15/21, 71.4%). In most cases (14/21, 66.6%), patients developed ocular disease concurrently with renal disease. The most frequent type of ocular involvement was bilateral anterior uveitis (9/21, 42.8%). In two cases, patients presented with bilateral intermediate uveitis; in three cases, they presented with bilateral or unilateral alternating posterior uveitis; and in four cases, they presented with bilateral panuveitis. In one case, the uveitis was anterior in the right eye (OD) and posterior in the left eye (OS), and two cases presented with bilateral asynchronous or unilateral alternating anterior uveitis. All patients received treatment with systemic corticosteroids and topical ocular therapy. At the end of the follow-up, a significant improvement in ocular signs and symptoms with a return to normal visual acuity was generally observed. In all patients, acute kidney injury (AKI) reverted completely and none progressed to chronic kidney disease (CKD).
CONCLUSIONS
Patients with TINU may often present with atypical uveitis. We suggest that patients with sudden-onset uveitis, even if not bilateral anterior, should be referred to a nephologist for an assessment of the possible presence of renal disease.
PubMed: 36078924
DOI: 10.3390/jcm11174995 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU).
PURPOSE
To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU).
DESIGN
Machine learning of cases with MFCPU and 8 other posterior uveitides.
METHODS
Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on 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 posterior uveitides. The resulting criteria were evaluated on the validation set.
RESULTS
One thousand sixty-eight cases of posterior uveitides, including 138 cases of MFCPU, were evaluated by machine learning. Key criteria for MFCPU included (1) multifocal choroiditis with the predominant lesions size >125 µm in diameter; (2) lesions outside the posterior pole (with or without posterior involvement); and either (3) punched-out atrophic chorioretinal scars or (4) more than minimal mild anterior chamber and/or vitreous inflammation. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for MFCPU were 15% in the training set and 0% in the validation set.
CONCLUSIONS
The criteria for MFCPU had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Adult; Anterior Chamber; Female; Humans; Machine Learning; Male; Middle Aged; Multifocal Choroiditis; Visual Acuity
PubMed: 33845016
DOI: 10.1016/j.ajo.2021.03.043 -
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