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JCI Insight Jan 2022BackgroundMore than 1500 variants in the ATP-binding cassette, sub-family A, member 4 (ABCA4), locus underlie a heterogeneous spectrum of retinal disorders ranging from...
BackgroundMore than 1500 variants in the ATP-binding cassette, sub-family A, member 4 (ABCA4), locus underlie a heterogeneous spectrum of retinal disorders ranging from aggressive childhood-onset chorioretinopathy to milder late-onset macular disease. Genotype-phenotype correlation studies have been limited in clinical applicability as patient cohorts are typically small and seldom capture the full natural history of individual genotypes. To overcome these limitations, we constructed a genotype-phenotype correlation matrix that provides quantifiable probabilities of long-term disease outcomes associated with specific ABCA4 genotypes from a large, age-restricted patient cohort.MethodsThe study included 112 unrelated patients at least 50 years of age in whom 2 pathogenic variants were identified after sequencing of the ABCA4 locus. Clinical characterization was performed using the results of best corrected visual acuity, retinal imaging, and full-field electroretinogram testing.ResultsFour distinct prognostic groups were defined according to the spatial severity of disease features across the fundus. Recurring genotypes were observed in milder prognoses, including a newly defined class of rare hypomorphic alleles. PVS1 (predicted null) variants were enriched in the most severe prognoses; however, missense variants were present in a larger-than-expected fraction of these patients. Analysis of allele combinations and their respective prognostic severity showed that certain variants, such as p.(Gly1961Glu), and both rare and frequent hypomorphic alleles, were "clinically dominant" with respect to patient phenotypes irrespective of the allele in trans.ConclusionThese results provide much-needed structure to the complex genetic and clinical landscape of ABCA4 disease and add a tool to the clinical repertoire to quantitatively assess individual genotype-specific prognoses in patients.FUNDINGNational Eye Institute, NIH, grants R01 EY028203, R01 EY028954, R01 EY029315, P30 19007 (Core Grant for Vision Research); the Foundation Fighting Blindness USA, grant no. PPA-1218-0751-COLU; and Research to Prevent Blindness.
Topics: ATP-Binding Cassette Transporters; Age of Onset; Chorioretinitis; Electroretinography; Female; Fundus Oculi; Gene Frequency; Genetic Association Studies; Genetic Variation; Humans; Macular Degeneration; Male; Middle Aged; Prognosis; Sequence Analysis, Protein; Tomography, Optical Coherence; United States; Visual Acuity
PubMed: 34874912
DOI: 10.1172/jci.insight.156154 -
Eye (London, England) Jan 2022Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. This review aimed to provide a novel perspective of the disease. We took into account... (Review)
Review
Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. This review aimed to provide a novel perspective of the disease. We took into account recent developments in the understanding of the disease and crucial progress in investigational modalities of the choroid, which has led to new, simpler diagnostic criteria. We analysed recent novel notions in the literature and new diagnostic tools for VKH. We identified the following updates for VKH disease: (1) A crucial differentiation between the acute initial-onset and the chronic forms of the disease; (2) the integration of new, precise imaging methods to assess choroidal inflammation; (3) the promotion of simplified, more reliable diagnostic criteria for acute initial-onset of the disease, based on the sine qua non presence of diffuse choroiditis, detected with indocyanine green angiography (ICGA) and/or Enhanced Depth Imaging OCT (EDI-OCT); and (4) treatment optimisation through early, vigorous, sustained corticosteroid and nonsteroidal immunosuppression, as the first line of treatment for initial-onset VKH disease, and monitoring subclinical choroidal inflammation during follow-ups. Several studies have shown that most patients could discontinue treatment without an inflammation relapse. ICGA and EDI-OCT represented the methods of choice for precisely monitoring disease evolution. Simplified, precise, new diagnostic criteria allow early diagnosis of VKH. In VKH disease, inflammation exclusively originates in the choroidal stroma. Therefore, in many cases, early, sustained treatment, with dual corticosteroid and nonsteroidal immunosuppressive therapy can result in full "healing", which obviates chronic, uncontrolled, subclinical choroidal inflammation.
Topics: Adrenal Cortex Hormones; Choroid; Choroiditis; Fluorescein Angiography; Humans; Inflammation; Uveomeningoencephalitic Syndrome
PubMed: 34145419
DOI: 10.1038/s41433-021-01573-3 -
Clinical Rheumatology Apr 2023
Topics: Humans; Ulcer; Intestinal Diseases; Behcet Syndrome; Intestines
PubMed: 36564555
DOI: 10.1007/s10067-022-06489-1 -
American Journal of Ophthalmology Oct 2020This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases.
PURPOSE
This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases.
DESIGN
Retrospective cohort study.
METHODS
Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4 US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors.
RESULTS
A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR] = 109), undifferentiated choroiditis (OR = 9.18), sympathetic ophthalmia (OR = 8.43), primary or secondary panuveitis (OR = 7.09), multifocal choroiditis with panuveitis (OR = 4.51), and "other" forms of posterior uveitis (OR = 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate = 0.47% [0.40%-0.56%/eye-year]). VKH (HR = 13.2), sympathetic ophthalmia (HR = 5.82), undifferentiated choroiditis (HR = 6.03), primary or secondary panuveitis (HR = 4.21), and rheumatoid arthritis (HR = 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD.
CONCLUSIONS
Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.
Topics: Adult; Choroiditis; Exudates and Transudates; Female; Fluorescein Angiography; Humans; Incidence; Inflammation; Male; Middle Aged; Ophthalmia, Sympathetic; Prevalence; Retinal Detachment; Retrospective Studies; Risk Assessment; Risk Factors; Uveitis, Posterior; Uveomeningoencephalitic Syndrome; Visual Acuity
PubMed: 32621891
DOI: 10.1016/j.ajo.2020.06.019 -
Medecine Et Sante Tropicales Feb 2017The aim of the current study was to describe the epidemiological and clinical features of Behçet disease in western Algeria. This observational retrospective study... (Observational Study)
Observational Study
The aim of the current study was to describe the epidemiological and clinical features of Behçet disease in western Algeria. This observational retrospective study examined records for patients with Behçet disease seen in our department from 1990 to 2015. Of the 61 patients included in the study, 80.3% were men, for a sex ratio of 4.08. The mean age at onset was 27.2±7 years, and the mean interval between the onset of symptoms and diagnosis was 4.8±6.3 years. Dermatologic manifestations were the most common finding. Oral ulcers were seen in all patients, genital ulcers in 60%, pseudofolliculitis in 56.4%, and erythema nodosum in 13.5%. A pathergy test was positive in 20% of the patients. The frequencies of the remaining manifestations were as follows: joint involvement 50%, ocular involvement 71.2%, vascular complications 29.6%, neurological involvement 19%, and gastrointestinal complications 7.5%. Besides dermatological manifestations, ocular and vascular complications were the most common features observed in our patients.
Topics: Adult; Algeria; Behcet Syndrome; Female; Humans; Male; Retrospective Studies
PubMed: 28406402
DOI: 10.1684/mst.2017.0656 -
PloS One 2023To confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis.
PURPOSE
To confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis.
METHOD
We retrospectively studied patients who had been diagnosed with uveitis and had undergone W-OCT. All patients had visited at Osaka Metropolitan University between January 2019 and January 2022. On W-OCT, vitreous opacity ("W-OCT VO") and the presence of vitreous cells ("W-OCT Cells") were identified by three specialists. We compared findings from ophthalmoscopy ("Ophthalmoscopic findings") and fluorescein angiography ("FAG findings") with those from W-OCT.
RESULTS
This study investigated 132 eyes from 68 patients (34 males, 34 females; mean age, 53.97±22.71 years). Vitreous cells in posterior uveitis and panuveitis differed significantly between "W-OCT Cells" and "Ophthalmoscopic findings" for all cases (P = 0.00014). Vitreous opacities in posterior uveitis and panuveitis did not differ significantly between "W-OCT VO" and "Ophthalmoscopic findings" (P = 0.144) for all cases. Compared to "Ophthalmoscopic findings", "W-OCT Cells" offered 51.1% sensitivity and 66.7% specificity for all cases (p<0.01). Compared to "Ophthalmoscopic findings", "W-OCT VO" offered 78.6% sensitivity and 30% specificity for all cases (p = 0.19). In addition, "W-OCT Cells" did not differ significantly from "FAG findings" for all cases (P = 0.424).
CONCLUSION
W-OCT was shown to offer significantly greater sensitivity than ophthalmoscopy for detecting vitreous cells. The results of this study may add an option for the evaluation of uveitis.
Topics: Male; Female; Humans; Adult; Middle Aged; Aged; Retrospective Studies; Tomography, Optical Coherence; Uveitis, Posterior; Panuveitis; Uveitis; Inflammation; Ophthalmoscopy; Fluorescein Angiography; Vitreous Body
PubMed: 36763630
DOI: 10.1371/journal.pone.0281714 -
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 -
Orphanet Journal of Rare Diseases May 2016Birdshot chorioretinopathy (BCR) is a rare form of chronic, bilateral, posterior uveitis with a distinctive clinical phenotype, and a strong association with HLA-A29. It... (Review)
Review
Birdshot chorioretinopathy (BCR) is a rare form of chronic, bilateral, posterior uveitis with a distinctive clinical phenotype, and a strong association with HLA-A29. It predominantly affects people in middle age. Given its rarity, patients often encounter delays in diagnosis leading to delays in adequate treatment, and thus risking significant visual loss. Recent advances have helped increase our understanding of the underlying autoimmune mechanisms involved in disease pathogenesis, and new diagnostic approaches such as multimodality imaging have improved our ability to both diagnose and monitor disease activity. Whilst traditional immunosuppressants may be effective in BCR, increased understanding of immune pathways is enabling development of newer treatment modalities, offering the potential for targeted modulation of immune mediators. In this review, we will discuss current understanding of BCR and explore recent developments in diagnosis, monitoring and treatment of this disease. Synonyms for BCR: Birdshot chorioretinopathy, Birdshot retinochoroiditis, Birdshot retino-choroidopathy, Vitiliginous choroiditis. Orphanet number: ORPHA179 OMIM: 605808.
Topics: Birdshot Chorioretinopathy; Chorioretinitis; HLA-A Antigens; Humans; Immunomodulation; Th17 Cells
PubMed: 27175923
DOI: 10.1186/s13023-016-0429-8 -
Retinal Cases & Brief Reports 2016To report a case of panuveitis, retinal vasculitis, and optic disk granuloma due to sarcoidosis. (Review)
Review
PURPOSE
To report a case of panuveitis, retinal vasculitis, and optic disk granuloma due to sarcoidosis.
METHODS
Case report and literature review.
RESULTS
A 26-year-old previously healthy African American male presented with four months of gradual progressive visual decline in the right eye. Clinical examination revealed severe panuveitis, retinal vasculitis, and large optic nerve mass lesion. Diffuse supraclavicular lymphadenopathy was also present. Histopathologic examination of the lymph node biopsy revealed granulomatous inflammation with some areas of caseous necrosis consistent with sarcoidosis.
CONCLUSION
Sarcoidosis is a common cause of uveitis and retinal vasculitis. In rare cases, an optic disk granuloma may occur and can be treated with immunosuppressive therapy.
Topics: Adult; Granuloma; Humans; Male; Optic Nerve Diseases; Panuveitis; Retinal Vasculitis; Sarcoidosis
PubMed: 26650564
DOI: 10.1097/ICB.0000000000000254 -
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