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1.
Ocul Immunol Inflamm ; 28(2): 217-227, 2020.
Article in English | MEDLINE | ID: mdl-30821569

ABSTRACT

Purpose: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.Methods: 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.Results: 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.Conclusions: 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.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , CTLA-4 Antigen/antagonists & inhibitors , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Uveitis/drug therapy , Humans , Uveitis/immunology , Uveitis/metabolism
2.
Hum Immunol ; 69(6): 349-53, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18571006

ABSTRACT

Vogt-Koyanagi-Harada (VKH) disease is a putative autoimmune ocular inflammatory disease and is known to be associated with HLA-DR4 and -DR1 in Mestizos. We examined the genes encoding KIR receptors and human leukocyte antigen (HLA) class I ligands in patients with VKH disease and compared to published controls. We found trends toward more group B KIR haplogroups (p=0.059), with more activating KIR genes, in patients compared to controls. All putative activating KIR-HLA combinations were more common in patients, and some inhibitory KIR-HLA combinations were more common in controls, although the differences were not statistically significant. The trends observed in this study are consistent with those reported for other autoimmune diseases.


Subject(s)
HLA-DR Antigens/genetics , Indians, North American , Receptors, KIR/genetics , Uveomeningoencephalitic Syndrome/genetics , California/ethnology , Female , Gene Frequency , Genetic Predisposition to Disease , HLA-DR Antigens/analysis , Haplotypes , Humans , Male , Protein Interaction Domains and Motifs/genetics , Protein Interaction Domains and Motifs/immunology , Uveomeningoencephalitic Syndrome/ethnology
3.
Ocul Immunol Inflamm ; 26(8): 1228-1236, 2018.
Article in English | MEDLINE | ID: mdl-28914568

ABSTRACT

PURPOSE: We investigated the effect of exogenously administered human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) in experimental autoimmune uveitis (EAU) in B10.RIII mice, a murine model of severe uveitis. METHODS: B10.RIII mice were immunized with an uveitogenic peptide, and intraperitoneal injections of 5 million hESC-MSCs per animal were given on the same day. Behavioral light sensitivity assays, histological evaluation, cytokine production, and regulatory T cells were analyzed at the peak of the disease. RESULTS: Histological and behavioral evidence demonstrated that early systemic treatment with hESC-MSCs decreases the development of severe EAU in B10.RIII mice. hESC-MSCs suppress Th17 and upregulate Th1 and Th2 responses as well as IL-2 and GM-CSF in splenocytes from hESC-MSC-treated mice. CONCLUSIONS: MSCs that originate from hESC decrease the development of severe EAU in B10.RIII mice, likely through systemic immune modulation. Further investigation is needed to determine any potential effect on active EAU.


Subject(s)
Autoimmune Diseases/prevention & control , Human Embryonic Stem Cells/cytology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Stromal Cells/physiology , Uveitis/prevention & control , Animals , Autoimmune Diseases/immunology , Cytokines/metabolism , Disease Models, Animal , Female , Flow Cytometry , Humans , Mice , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Uveitis/immunology
4.
Am J Ophthalmol ; 144(6): 829-837, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17937923

ABSTRACT

PURPOSE: To describe visual field parameters at baseline examination of 80 participants in a longitudinal cohort study of birdshot chorioretinopathy and to identify relationships between these parameters and visual acuity, symptoms, clinical findings, and results of laboratory tests. DESIGN: Single-center cross-sectional study. METHODS: Standardized Fastpac, full-threshold Humphrey 30-2 (Carl Zeiss Meditec, Dublin, California, USA) visual field studies were performed for both eyes of all patients. A standardized protocol identified foveal threshold and mean deviation, specified categories of total deviation, and assigned visual field pattern descriptors. These parameters were compared with best-corrected visual acuity (BCVA), symptoms, color confusion score (CCS), cataract, vitreous inflammatory reactions, retinal vasculitis, birdshot lesion characteristics, and ocular coherence tomography (OCT) and fluorescein angiography parameters. RESULTS: Each visual field parameter was closely related to the others, although mean deviation could be abnormal in the presence of a near normal foveal threshold. Mean deviation was related to BCVA, but the correlation was moderate (the Spearman correlation, -0.55; P < .001). It was also related to CCS and the symptoms of blurry vision, poor contrast sensitivity, and nyctalopia. The most common visual field patterns were multiple foci and arcuate defects. Among clinical and laboratory findings, visual field parameters were most closely related to absence of the third highly reflective band on OCT (P < .001). CONCLUSIONS: Patients with birdshot chorioretinopathy may have a variety of visual field abnormalities, even with normal BCVA. Abnormalities seem to be associated with retinal damage. Automated visual field testing may provide objective measures for monitoring disease activity.


Subject(s)
Choroid Diseases/physiopathology , Retinal Diseases/physiopathology , Vision Disorders/physiopathology , Visual Fields/physiology , Adult , Aged , Choroid Diseases/diagnosis , Color Vision Defects/physiopathology , Cross-Sectional Studies , Female , Fluorescein Angiography , Humans , Longitudinal Studies , Male , Middle Aged , Retinal Diseases/diagnosis , Tomography, Optical Coherence , Visual Acuity/physiology , Visual Field Tests
5.
Am J Ophthalmol ; 144(6): 818-828, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17949671

ABSTRACT

PURPOSE: To describe optical coherence tomography (OCT) and fluorescein angiography (FA) parameters at baseline examination of 80 subjects (160 eyes) in a longitudinal cohort study of birdshot chorioretinopathy and to compare these parameters with measures of visual function and clinical findings. DESIGN: Single-center cross-sectional study. METHODS: Comparisons were made between OCT and FA parameters. The existence of relationships was examined between three OCT parameters (macular thickness, status of the third highly reflective band [HRB], epiretinal membrane) and the following factors: best-corrected visual acuity (BCVA), symptoms, color confusion score (CCS), vitreous haze, retinal vasculitis, and birdshot lesion characteristics. Grade of vascular leakage by FA was compared with the same factors. RESULTS: There was not good agreement between macular edema identified by OCT vs FA (kappa, 0.37). On multivariate analyses, decreased BCVA was related to abnormal macular thickness (P < .001), loss of the third HRB (P < .001), and vascular leakage (P = .034). When compared with macular parameters, symptoms were related most closely to loss of the third HRB. There were no strong relationships between birdshot lesion characteristics and macular parameters. CONCLUSIONS: Macular changes are reflected in reduced BCVA and may provide insight into mechanisms of some visual symptoms. Loss of the third HRB was the parameter most commonly related to other disease factors. Birdshot chorioretinopathy can result in macular thinning with central vision loss. FA and OCT each may be useful tests for the evaluation of the macula in patients with birdshot chorioretinopathy.


Subject(s)
Choroid Diseases/diagnosis , Fluorescein Angiography , Macula Lutea/pathology , Retinal Diseases/diagnosis , Tomography, Optical Coherence , Adult , Aged , Color Vision Defects/diagnosis , Contrast Sensitivity , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Macular Edema/diagnosis , Male , Middle Aged , Visual Acuity
6.
Invest Ophthalmol Vis Sci ; 58(10): 4015-4025, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28800648

ABSTRACT

Purpose: The purpose of this study was to describe fundus autofluorescence (FAF) findings in eyes with birdshot chorioretinitis (BSCR) and to compare findings to demographic, medical, and clinical characteristics. Methods: In this multicenter, prospective, cross-sectional study, 172 eyes (86 patients) with BSCR were investigated. Participants underwent a standardized evaluation including collection of demographic data, ophthalmic and treatment history, and ophthalmologic examination. Using a standardized protocol, hypo- and hyperautofluorescence in macular and extramacular regions and specific patterns of abnormal FAF could be scored for 167 eyes. Images were scored by two independent, masked graders. Measures of visual function included best-corrected visual acuity (BCVA), contrast sensitivity (CS), color vision, and Humphrey visual field mean deviation (HVF-MD). Results: Any abnormal FAF finding was observed in 132 eyes (79.0%); macular abnormalities were observed in 84 eyes (49.1%). The most common findings were peripapillary confluent hypoautofluorescence (122 eyes [73.1%]); extramacular granular hypoautofluorescence (100 eyes [59.9%]); and macular granular hypoautofluorescence (67 eyes [40.1%]). Confluent hypoautofluorescence was related to longer median disease duration (8.7 years) than granular hypoautofluorescence (7.9 years) or hyperautofluorescence (5.6 years). Macular confluent hypoautofluorescence was associated with BCVA ≤20/25 (odds ratio [OR] = 7.83, P = 0.007), BCVA ≤20/50 (OR = 4.94, P = 0.002), and abnormal CS (OR = 4.56, P = 0.009). Presence of macular or extramacular hypoautofluorescence was related to HVF-MD ≤-3 dB (OR = 2.43, P = 0.01 and OR = 2.89, P = 0.003, respectively). Conclusions: In this large cohort, various FAF abnormalities were found, indicating that disorders of the retinal pigment epithelium are features of BSCR. Abnormal FAF is a marker of visual dysfunction in the disease.


Subject(s)
Chorioretinitis/diagnosis , Optical Imaging , Retinal Pigment Epithelium/pathology , Birdshot Chorioretinopathy , Chorioretinitis/physiopathology , Color Vision/physiology , Cross-Sectional Studies , Female , Fluorescein Angiography , Fundus Oculi , Humans , Male , Middle Aged , Prospective Studies , Retinal Pigment Epithelium/physiopathology , Tomography, Optical Coherence , Visual Acuity/physiology , Visual Field Tests , Visual Fields/physiology
7.
Am J Ophthalmol ; 141(1): 185-7, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16386995

ABSTRACT

PURPOSE: To present and evaluate research criteria for the diagnosis of birdshot chorioretinopathy. DESIGN: Consensus statement. METHODS: Investigators who attended an international conference on birdshot chorioretinopathy drafted diagnostic criteria, which were refined after comment by conference attendees. Sensitivity and specificity of the criteria were evaluated by review of 82 previously diagnosed cases and evaluation of 80 consecutive patients with other forms of uveitis. RESULTS: Criteria, including presence of "birdshot lesions" and mild intraocular inflammation in both eyes, are based on clinical findings in the absence of systemic disease; HLA-A29 is supportive of diagnosis, but not required. Diagnostic criteria were found to be 100% specific and 97.5% sensitive. Positive predictive value was 100%; negative predictive value was 97.6%. CONCLUSIONS: Standardized criteria for the diagnosis of birdshot chorioretinopathy will facilitate clinical research and the comparison of results from studies performed at different institutions by ensuring a homogeneous population of study patients.


Subject(s)
Choroid Diseases/diagnosis , Retinal Diseases/diagnosis , Uveitis, Posterior/diagnosis , Biomedical Research , Diagnostic Techniques, Ophthalmological/standards , False Positive Reactions , HLA-A Antigens/analysis , Humans , Predictive Value of Tests , Sensitivity and Specificity
8.
Am J Ophthalmol ; 141(1): 135-42, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16386987

ABSTRACT

PURPOSE: To describe baseline clinical characteristics of a cohort of 80 patients with birdshot chorioretinopathy in anticipation of a longitudinal study, and to identify relationships between visual acuity, symptoms, and ophthalmic findings. DESIGN: Single-center cross-sectional study. METHODS: A standardized examination was performed in the same order on a single day for each patient. A grading system for birdshot lesions was established prospectively to evaluate the following lesion characteristics: quantity, distribution, morphology, and pigmentation. Relationships between clinical features of disease were sought in multivariate analyses that adjusted for age, duration of uveitis, and treatment. RESULTS: Mean age at baseline examination was 55.6 years. Median best-corrected visual acuity (BCVA) was 0.8 (range, counting fingers to 1.2). There were no relationships between BCVA and any birdshot lesion characteristic. The most common cause of BCVA < or =0.4 was macular edema. Visual symptoms were present in 78 patients (97.5%), including 17 (94.4%) of 18 patients with BCVA > or =1.0 in both eyes. Blurred vision was associated with decreased BCVA (P = .02) and macular edema (P = .022). Increased lesion pigmentation was associated with complaints of blurred vision (P = .030), vibrating vision (P = .011), and nyctalopia (P = .056). CONCLUSIONS: Symptoms are common in patients with birdshot chorioretinopathy, even among those with good BCVA. Lesion pigmentation may be a marker of decreased visual function that is not reflected in central visual acuity. These findings highlight the limitation of using visual acuity measurements for monitoring patients with birdshot chorioretinopathy and as an outcome measure for studies of this disease.


Subject(s)
Choroid Diseases/diagnosis , Retinal Diseases/diagnosis , Uveitis, Posterior/diagnosis , Vision Disorders/diagnosis , Adult , Aged , Choroid Diseases/complications , Chronic Disease , Cohort Studies , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Retinal Diseases/complications , Uveitis, Posterior/complications , Vision Disorders/etiology , Visual Acuity
9.
Am J Ophthalmol ; 142(6): 1013-8, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17157585

ABSTRACT

PURPOSE: To describe color vision at the baseline examination of 80 participants in a longitudinal cohort study of birdshot chorioretinopathy and to identify relationships between color vision and visual acuity, symptoms, and ophthalmic signs. DESIGN: Single center cross-sectional study. METHODS: Color vision was evaluated with the desaturated Lanthony 15-Hue test. Relationships were sought between the square root of the color confusion scores (CCS) and the following factors: best-corrected visual acuity (BCVA), symptoms, cataract, vitreous inflammatory reactions, retinal vasculitis, cystoid macular edema (CME), and birdshot lesion characteristics. RESULTS: When compared with published, age-matched normal control subjects, 49 patients (61.3%; 76 eyes [47.5%]) had abnormal CCS values. Abnormal CCS values were found in nine of 51 phakic eyes (18%) with normal BCVA (>or=1.0) and without cataract. Although most eyes did not have classifiable defects, 30 eyes (18.8%) had tritan (blue-yellow) defects (88% of eyes with classifiable defects). With the use of multivariate analyses, there were significant associations between increased CCS values and the symptoms of altered color vision (P = .005) and altered contrast sensitivity (P = .015). There was a significant, but weak, relationship between CCS values and birdshot lesion morphologic condition (P = .049), but no relationships were found with other lesion characteristics or with vitreous inflammatory reactions, retinal vasculitis, or CME. CONCLUSION: The Lanthony 15-Hue test provides an objective technique to assess complaints of altered color vision in people with birdshot chorioretinopathy. Color vision can be abnormal in eyes with normal visual acuity; therefore, this parameter may be useful as an additional measure for monitoring the disease.


Subject(s)
Choroid Diseases/diagnosis , Color Vision Defects/diagnosis , Retinal Diseases/diagnosis , Adult , Aged , Cataract/complications , Color Perception Tests , Contrast Sensitivity , Cross-Sectional Studies , Eye Diseases/complications , Female , Humans , Longitudinal Studies , Male , Middle Aged , Visual Acuity , Vitreous Body/pathology
10.
Ocul Immunol Inflamm ; 14(6): 325-32, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17162602

ABSTRACT

PURPOSE: To adapt a standardized technique for assessment of visual fields to the study of patients with birdshot chorioretinopathy and to describe visual field patterns and changes over time for affected individuals. METHODS: A retrospective chart review was performed of patients with a diagnosis of birdshot chorioretinopathy who had undergone at least two automated visual field studies. A masked evaluation of each visual field was performed using standardized criteria. Subjective symptoms and visual acuity measurements were compared to visual field data from the same examination dates. Serial visual field studies were evaluated for changes in the findings over time. RESULTS: Six patients met inclusion criteria. A total of 104 visual field studies (ranging from 2-19 studies per eye) were evaluated. Visual field abnormalities occurred in all tested eyes and were observed even in eyes with a Snellen visual acuity of 20/15. Discordant patterns were observed in the two eyes of some individual patients. On serial testing, multiple patterns of visual field abnormality were observed in the same eye over time. CONCLUSIONS: A standardized protocol for systematic evaluation of visual field measurements can be used to characterize disturbances of vision in patients with birdshot chorioretinopathy. Abnormalities of visual fields may occur even when central visual acuity is preserved.


Subject(s)
Chorioretinitis/physiopathology , Visual Field Tests/standards , Visual Fields/physiology , Chorioretinitis/diagnosis , Disease Progression , Follow-Up Studies , Humans , Middle Aged , Severity of Illness Index
11.
PLoS One ; 11(8): e0160392, 2016.
Article in English | MEDLINE | ID: mdl-27490240

ABSTRACT

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral-infection that may trigger VKH pathogenesis in genetically susceptible individuals, such as HLA-DR4 carriers.


Subject(s)
Genetic Predisposition to Disease , HLA-DR4 Antigen , Immunity, Cellular/genetics , Killer Cells, Natural/immunology , Receptors, KIR , Uveomeningoencephalitic Syndrome , Asian People , Chromosomes, Human , Female , Genome-Wide Association Study , HLA-DR4 Antigen/genetics , HLA-DR4 Antigen/immunology , Humans , Japan , Male , Receptors, KIR/genetics , Receptors, KIR/immunology , Uveomeningoencephalitic Syndrome/genetics , Uveomeningoencephalitic Syndrome/immunology
12.
Invest Ophthalmol Vis Sci ; 57(9): OCT591-9, 2016 07 01.
Article in English | MEDLINE | ID: mdl-27599125

ABSTRACT

PURPOSE: The purposes of this study were to describe choroidal findings observed using optical coherence tomography with enhanced depth imaging (EDI-OCT) in eyes with birdshot chorioretinitis (BSCR) and to test the hypothesis that these findings are related to participant demographics, clinical characteristics, and treatment. METHODS: In a multicenter, cross-sectional study, 172 eyes of 86 individuals with BSCR underwent a standardized clinical evaluation, including defined protocols for EDI-OCT imaging, with macular and peripapillary volume scans. Choroidal findings were compared to demographic information, ophthalmic examination findings, and treatment history, using logistic regression models. EDI-OCT images were evaluated by two independent, masked graders. RESULTS: Median age was 56 years old; 54 participants (62.8%) were female. One or more choroidal lesions (a predefined hyporeflective zone) were identified in 105 eyes (63.6%). Median choroidal thickness was 293 µm. Choroidal lesions were associated with longer disease durations (odds ratio [OR]: 1.08; P = 0.03), increased vitreous haze (>0.5+; OR: 4.43; P = 0.02), presence of macular edema (OR: 3.00; P = 0.02), and thick choroids (OR: 3.89; P = 0.001). Use of immunomodulatory therapy was associated with lower risk of thin choroids (lower 25th percentile, OR: 0.17; P = 0.001) or thick choroids (upper 25th percentile, OR: 0.22; P = 0.002). At least some choroidal lesions did not have corresponding, clinically apparent "birdshot lesions" on fundus examination. CONCLUSIONS: Choroidal abnormalities identified by EDI-OCT imaging are common in the macular and peripapillary regions of eyes with BSCR. Choroidal lesions were associated with clinical signs of inflammation, suggesting that they represent foci of disease activity. EDI-OCT may provide useful information about disease mechanisms and response to treatment in future, longitudinal studies of BSCR.


Subject(s)
Chorioretinitis/diagnosis , Choroid/pathology , Image Enhancement/methods , Tomography, Optical Coherence/methods , Birdshot Chorioretinopathy , Choroid/blood supply , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Severity of Illness Index
13.
Surv Ophthalmol ; 50(6): 519-41, 2005.
Article in English | MEDLINE | ID: mdl-16263368

ABSTRACT

Birdshot chorioretinopathy is a well-known, yet poorly understood, form of posterior uveitis, characterized by multiple, distinctive, hypopigmented choroidal lesions, and strongly associated with human leukocyte antigen (HLA)-A29. We reviewed all English language publications regarding birdshot chorioretinopathy and performed analyses of combined patient data taken from these articles. The mean age at presentation was 53 years, with a slight female predominance (54.1%). At least 95.7% of reported patients have been HLA-A29-positive. Blurring of vision and floaters are the most prevalent presenting complaints, even in patients with visual acuity of 20/20 or better in both eyes. Birdshot chorioretinopathy is a slowly progressive disease with profound dysfunction of vision that may not be reflected in Snellen visual acuity. Two or more lines of Snellen visual acuity were lost in approximately 20% of eyes over a median follow-up of 3.5 years; macular edema was the most common cause of reduced visual acuity. Overall, patients had a slow decline in visual acuity, despite the fact that nearly all were treated with anti-inflammatory therapies. Final visual acuity in the better eye was 20/40 or better in 75.1% of patients and 20/200 or worse in 9.8% of patients. Oral corticosteroids and cyclosporine were the most commonly used medications. Using a regression model, patients in the literature that have been treated with cyclosporine alone had better final visual acuity than patients treated with oral corticosteroids alone. Further study is needed to determine the optimal methods for treating and monitoring patients with birdshot chorioretinopathy.


Subject(s)
Chorioretinitis , Chorioretinitis/diagnosis , Chorioretinitis/epidemiology , Chorioretinitis/immunology , Diagnosis, Differential , Fluorescein Angiography , Fundus Oculi , HLA-A Antigens/immunology , Humans , Prevalence , Visual Acuity
14.
Invest Ophthalmol Vis Sci ; 44(2): 653-7, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12556395

ABSTRACT

PURPOSE: To identify genetic markers for the tubulointerstitial nephritis and uveitis (TINU) syndrome by using human leukocyte antigen (HLA) genotyping. METHODS: Eighteen patients who had TINU syndrome were evaluated at three institutions. Typing of class I and II genes was performed by using DNA-based techniques. RESULTS: Significant associations were found with HLA-B14 (6/18 patients, 33.3%; control subjects, 5.5%; P = 0.0003; relative risk [RR] = 8.5), HLA-DQA1*01 (17/18 patients, 94.4%; control subjects, 46.6%, P = 0.0001; RR = 19.5), HLA-DQA1*0101 (14/18 patients, 77.8%; control subjects 22.2%; P < 0.0001; RR = 12.2), HLA-DQB1*05 (14/18 patients, 77.8%; control subjects 17.7%; P < 0.0001; RR = 16.3), HLA-DQB1*0501 (13/18 patients, 72.2%; control subjects 12.9%; P < 0.0001; RR = 17.6), HLA-DRB1*01 (14/18 patients, 77.8%; control subjects, 12.1%; P < 0.0001; RR = 25.5), and HLA-DRB1*0102 (13/18 patients, 72.2%; control subjects, 1.6%; P < 0.0001, RR = 167.1). The HLA haplotype most frequently identified in the study patients was HLA-DQA1*01/DQB1*05/DRB1*01 (13/18 patients, 72.2%). CONCLUSIONS: TINU syndrome is strongly associated with HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01. The association with HLA-DRB1*0102 is one of the highest reported for any disease. Because these genes are in linkage disequilibrium, the role of the individual alleles is difficult to assess. Based on the results of the present study and on previously reported HLA associations in patients with TINU syndrome, the alphabeta dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease.


Subject(s)
HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Nephritis, Interstitial/genetics , Uveitis/genetics , Adolescent , Adult , Child , DNA/analysis , Female , Gene Frequency , Genetic Linkage , Genotype , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Male , Middle Aged , Syndrome
15.
Hum Immunol ; 65(12): 1477-82, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15603876

ABSTRACT

We evaluated human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles as genetic markers for Vogt-Koyanagi-Harada (VKH) disease in Mestizo patients in Southern California. Mestizo individuals with VKH disease (n = 29) at two institutions were evaluated. Typing of HLA-DRB1 and DQB1 genes was performed using DNA-based techniques. Gene frequencies were compared to Mestizo individuals living in Southern California. All patients had HLA-DRB1*01, DRB1*04, DQB1*03 or DQB1*05, or a combination of these genes. The gene frequency of combined HLA-DR4 alleles was increased when compared to controls. The frequencies of HLA-DRB1*0404 and DRB1*0407 were increased compared to controls, but were not significant after Bonferroni correction. Three patients had the HLA-DRB1*0410 allele; this allele was not found in controls. All HLA-DRB1*01 positive patients had the DRB1*0102 subtype. No HLA-DQB1 allele was significantly increased compared to controls. This study is the first to identify a possible association between HLA-DRB1*0404 and VKH disease, as well as to find DRB1*0102 and DRB1*0410 in Mestizo patients.


Subject(s)
HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Uveomeningoencephalitic Syndrome/genetics , Uveomeningoencephalitic Syndrome/immunology , Alleles , California , Case-Control Studies , Gene Frequency , HLA-DQ beta-Chains , HLA-DRB1 Chains , Hispanic or Latino/genetics , Humans
16.
Am J Ophthalmol ; 138(4): 631-4, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15488792

ABSTRACT

PURPOSE: To determine whether birdshot retinochoroidopathy is associated with subtypes of the human leukocyte antigen (HLA)-A29 other than HLA-A*2902. DESIGN: Experimental study. METHODS: High-resolution DNA typing of HLA-A29 subtypes was performed on blood from 20 subjects with birdshot retinochoroidopathy using polymerase chain reaction-based typing methods. Results were compared with published controls. RESULTS: Four of 20 subjects (20%) had the HLA-A*2901 allele; two were homozygous for HLA-A*29, and both had the HLA-A*2901 and HLA-A*2902 alleles. Among 18 subjects with only one HLA-A*29 allele, the HLA-A*2902 allele was found in 16 (89%) and the HLA-A*2901 allele was found in two (11%). No subject was found to have HLA-A*2903, HLA-A*2904, HLA-A*2905, or HLA-A*2906. CONCLUSIONS: Both HLA-A*2901 and HLA-A*2902 are associated with birdshot retinochoroidopathy. Our data do not support the previous suggestion that the HLA-A29.1 serotype may be protective against development of birdshot retinochoroidopathy. Additional studies will be required to determine whether the other, less common subtypes are associated with the disease. HLA-A29 subtype testing is not required for the clinical evaluation of HLA-A29-positive patients with birdshot retinochoroidopathy.


Subject(s)
Chorioretinitis/genetics , HLA-A Antigens/genetics , DNA/analysis , DNA Fingerprinting , Gene Frequency , Humans , Polymerase Chain Reaction
17.
J Cataract Refract Surg ; 28(4): 662-9, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11955908

ABSTRACT

PURPOSE: To compare the changes in visual acuity and the development of posterior capsule opacification (PCO) with AcrySof acrylic intraocular lenses (IOLs) (Alcon Laboratories) and second-generation PhacoFlex silicone IOLs (Allergan ). SETTING: Eye Associates of New Mexico and Southwest Colorado, Albuquerque, New Mexico, USA. METHODS: Medical charts of patients having cataract extraction with implantation of an AcrySof MA30BA or MA60BM (MA30/60) or PhacoFlex SI-30NB or SI-40NB (SI-30/40) IOL between January 1995 and June 1997 were abstracted. Analyzed were the changes in visual acuity and development of PCO 1 month postoperatively and at the last available ophthalmologist visit or the visit before neodymium:YAG (Nd:YAG) capsulotomy. RESULTS: Patients with MA30/60 acrylic IOLs were significantly older, had a worse preoperative best corrected visual acuity (BCVA), and had more concomitant ocular diseases than those with SI-30/40 silicone IOLs. The change in BCVA from preoperatively to 1 month postoperatively was equivalent in the 2 lens groups. The BCVA declined from 1 month postoperatively to the last recorded or pre-Nd:YAG visit. This decline was greater in eyes with SI-30/40 silicone IOLs than in those with MA30/60 acrylic IOLs. Although the decrease in BCVA between IOL types was not significantly different, eyes with a SI-30/40 silicone IOL were significantly more likely to develop PCO and have Nd:YAG capsulotomy. Eyes developing PCO had a statistically significant decline in BCVA from 1 month postoperatively to the last/pre-Nd:YAG visit. CONCLUSIONS: The MA30/60 acrylic lenses were associated with lower PCO and Nd:YAG capsulotomy rates than second-generation SI-30/40 silicone IOLs. Patients with MA30/60 IOLs also tended to have less of a decrease in visual acuity than patients with SI-30/40 silicone lenses, probably as a result of the difference in PCO rates between groups.


Subject(s)
Acrylic Resins , Cataract/physiopathology , Lens Capsule, Crystalline/physiopathology , Lenses, Intraocular , Silicone Elastomers , Visual Acuity/physiology , Adult , Aged , Aged, 80 and over , Biocompatible Materials , Cataract Extraction , Female , Humans , Lens Implantation, Intraocular , Male , Middle Aged , Outcome Assessment, Health Care
18.
Ophthalmol Clin North Am ; 15(3): 343-50, vii, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12434483

ABSTRACT

Birdshot retinochoroidopathy (BSR) is a bilateral posterior uveitis. A putative organ-specific autoimmune disease, it is strongly associated with the HLA-A29 allele, and understanding the immunopathogenesis of BSR is of great interest. The clinical features include minimal anterior uveitis, vitritis, retinal vasculitis, cystoid macular edema, and distinctive hypopigmented choroidal lesions. Findings on electrophysiology studies and angiography have implications for understanding the pathophysiology of the disease, and may be useful for following the course of BSR and the response to therapy in individual patients. The decision to initiate therapy can be difficult, but corticosteroids and immunosuppressive agents are often used.


Subject(s)
Autoimmune Diseases/immunology , Chorioretinitis/etiology , Chorioretinitis/immunology , HLA-A Antigens/immunology , Uveitis, Posterior/immunology , Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Autoimmune Diseases/etiology , Chorioretinitis/diagnosis , Chorioretinitis/drug therapy , Humans , Uveitis, Posterior/diagnosis , Uveitis, Posterior/drug therapy , Uveitis, Posterior/etiology
19.
Ocul Immunol Inflamm ; 10(2): 133-9, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12778349

ABSTRACT

BACKGROUND: A significant increase in the number of episodes of acute anterior uveitis was found in December for two consecutive years at a community-based ophthalmology practice. PURPOSE: To evaluate the monthly variation in episodes of acute anterior uveitis (AAU). METHODS: The charts of all patients with AAU in a practice within a community-based multispecialty ophthalmology group in Albuquerque, New Mexico, were reviewed. Seventy-seven patients with acute, self limited, nontraumatic, unilateral, nongranulomatous anterior uveitis over a two-year period were identified. RESULTS: Ninety-four episodes of AAU occurred in 77 patients (42 men, 35 women). The median number of episodes of AAU was three episodes per month (range: 0-14 episodes/month). An increased number of episodes was found in December of both years (11 in December 1996 [p < 0.01] and 14 in December 1997 [p < 0.003]). Smaller clusters of AAU were seen in other months, but did not reach statistical significance. CONCLUSIONS: The presence of a seasonal variation in the number of episodes of AAU suggests that environmental factors are important. A search for such factors that increase the risk of AAU during selected periods may be useful for a better understanding of disease pathogenesis.


Subject(s)
Seasons , Uveitis, Anterior/epidemiology , Acute Disease , Community Health Services , Female , HLA-B27 Antigen/genetics , Humans , Male , New Mexico/epidemiology , Ophthalmology , Retrospective Studies , Risk Factors , Uveitis, Anterior/genetics
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