Petrushkin H, Thomas D, Vaughan R, Kondeatis E, Stanford MR, Edelsten C, Wallace GR. Possession of the HLA-DRB1*1501 Allele and Visual Outcome in Idiopathic Intermediate Uveitis. JAMA Ophthalmol. 2015;133(4):482-483. doi:10.1001/jamaophthalmol.2014.5868
Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disease characterized by breakdown of the blood-retina barrier with consequent leukocytic infiltration of the vitreous and retina. Poor visual outcome has been associated with cystoid macular edema, poor vision at presentation, and male sex.1 The human leukocyte antigen (HLA) allele DRB1*1501 has long been associated with multiple sclerosis (MS). Tang et al2 prospectively analyzed 18 patients and found that HLA-DRB1*1501 conferred increased risk of developing IIU associated with MS in some patients.
The purposes of this study were to prospectively evaluate the association between the HLA-DRB1*1501 allele and IIU in patients and to determine whether HLA-DRB1*1501 might be a separate independent risk factor for visual loss.
Participants included 85 patients with IIU and 300 healthy, demographically matched controls. Idiopathic intermediate uveitis was classified on the basis of ophthalmological examination and fluorescein angiography findings. Patients with systemic inflammatory, neoplastic, or infectious diseases were excluded, as were patients with a history of optic neuritis. Written informed consent for HLA typing was obtained from all individuals. This study received approval from the St Thomas’ Ethical Committee and adheres to the Declaration of Helsinki.
Patients were reviewed at 3 months, 5 years, and 10 years (where possible) between 2000 and 2014. Additional appointments were given as required to adequately maintain control of intraocular inflammation.
Visual acuity (VA) of 6/12 or better was defined as a good outcome. Genomic DNA was extracted and genotyped for the HLA class II allele HLA-DRB1*1501 using polymerase chain reaction amplification with sequence-specific primers.3 Polymerase chain reaction products were electrophoresed and read using ethidium bromide and UV illumination.
The Table shows VA and demographic data. Thirty-eight cases (45%) were HLA-DRB1*1501 positive compared with 90 controls (30%) (15% difference; χ2 = 6.45; P = .007; odds ratio = 1.89; 95% CI, 1.15-3.09).
We found no association between VA and possession of the HLA-DRB1*1501 allele. Twelve HLA-DRB1*1501–positive patients (31%) had a VA less than 6/12 at the end of the study, compared with 8 HLA-DRB1*1501–negative patients (17%) (14% difference; P = .15; relative risk = 1.52; 95% CI, 0.94-2.47). There was no identifiable difference in sex between HLA-DRB1*1501–positive and HLA-DRB1*1501–negative patients (2.5% difference; P = .65; odds ratio = 0.77; 95% CI, 0.31-1.91). The mean (SD) age at presentation was 62.09 (11.6) years for the HLA-DRB1*1501–positive patients and 59.72 (16.04) years for the HLA-DRB1*1501–negative patients (P = .46).
Our findings are in agreement with the previously reported association between IIU and HLA-DRB1*1501. However, we were unable to identify any association between possession of the HLA-DRB1*1501 allele and sex or age at presentation, as has been found in MS. We also did not find an association between HLA-DRB1*1501 and final VA.4
Our exclusion criteria, prospective design, and extended follow-up distinguish this study from those previously reported. The patient population was comparable to those in other studies in terms of race, sex, and age.2,5,6
The results reflect the relatively benign nature of IIU in that 76% of our patients had good vision at 10 years. Similarly, Raja et al5 reported a VA higher than 6/12 in 82% of their patients after 4 years.
The prediction of visual outcome from haplotype analysis has not been supported by this study. However, our findings cannot rule out the possibility that IIU is made up of a number of separate disease processes, of which some affect all age groups and others (HLA-DRB1*1501 related) represent a forme fruste of MS. It is possible that patients in this study developed an associated systemic disease after their second review at 5 years but were not seen again at 10 years.
Finally, our data suggest that VA at 3 months reliably predicts vision at 5 and 10 years. This is important for future clinical studies as a shorter follow-up time can be used to determine clinical efficacy.
Corresponding Author: Graham R. Wallace, PhD, Centre for Translational Inflammation Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, England (firstname.lastname@example.org).
Published Online: January 29, 2015. doi:10.1001/jamaophthalmol.2014.5868.
Author Contributions: Dr Wallace had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Stanford, Wallace.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Petrushkin, Thomas, Stanford, Wallace.
Critical revision of the manuscript for important intellectual content: Petrushkin, Vaughan, Kondeatis, Stanford, Edelsten, Wallace.
Statistical analysis: Petrushkin, Thomas.
Administrative, technical, or material support: Petrushkin, Kondeatis.
Study supervision: Vaughan, Stanford, Edelsten, Wallace.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.