Birdshot Chorioretinopathy : Prospective Follow-up and Immunogenetic Studies(CO-BIRD) (CO-BIRD)

October 28, 2022 updated by: Assistance Publique - Hôpitaux de Paris

Longitudinal Cohort Study of Patients With Birdshot Chorioretinopathy.

The purpose of this study is twofold:

  1. To analyze the clinical features of a cohort of patients with birdshot chorioretinopathy (BCR), an inflammatory bilateral ocular disease, affecting the choroid and the retina.

    Various imaging techniques will be used to assess the effect of the disease on the retina and the choroid.

    A standardized assessment of the visual function will be performed with visual acuity, visual field and color vision testing. The quality of life of the patients will be evaluated with the VFQ-25 questionnaire.

    These analyses will help delineating different forms of the disease among its heterogeneous presentations.

  2. To identify predisposing factors for the disease. The condition is unique from the immunogenetic standpoint by its association with the HLA-A29 allele, which is the strongest link between an HLA class I antigen and a disease. To date, however, the mechanisms leading to birdshot chorioretinopathy remain unknown. GWAS (Genome Wide association Study) based on DNA of the cohort patients will be performed with the aim to identify other susceptibility genes associated with BCR.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Birdshot chorioretinopathy is a bilateral chronic posterior uveitis that has been named in 1980. The "birdshot lesions" are the hallmark of the disease. In their most typical aspect these lesions are ovoid shaped hypopigmented spots at the level of the choroid.

One of the main difficulties of the diagnosis lies in the spectrum of presentations of the disease. The typical birdshot lesions are ovoid with their main axis oriented toward the optic disc. However, some are round and the can be clearly seen on fundus examination while others can be limited to subtle depigmentations. Typical lesions are one-quarter to one-half disc diameters, but confluent lesions may yield larger areas of depigmentation that are difficult to recognize. Although the typical lesions are depigmented, their presentation may change over time and pigment or atrophy may replace the initial cream-colored spots. The typical location, or the most easily seen location of the spots, is nasal to the optic disc. However, involvement of the posterior pole inside the temporal arcade is also possible. The spots usually predominate in the mid-periphery, but may also extend to the equator. A standardized classification of the birdshot lesions according to their size, their number, their pigmentation and their localization has been suggested to help in the categorization of the various disease presentations and for the longitudinal follow-up of affected patients. Spots clearly visible at the time of the diagnosis may disappear later. Hence, if the diagnosis of the birdshot chorioretinopathy is not made when spots are clearly visible, later presentations may not meet the definition commonly used for the disease. The disappearance of birdshot spots after treatment has been documented, but the effect of treatment on spots has not yet been assessed in large cohorts of patients. Indocyanine green angiography has been suggested as a reliable method to detect spots. However, it remains to be validated by a randomized assessment comparing indocyanine green angiography to color photographs for the detection of birdshot lesions.

Fluorescein angiography is useful in patients with birdshot chorioretinopathy to assess disease activity. In active disease, angiographic findings include leakage of the retinal veins, macular edema and optic disk hyperfluorescence. These findings are not disease specific, but they require a careful examination of the fundus seeking subtle spots when birdshot lesions are not obvious.

Given the above, the first goal of our prospective cohort study is to assess the heterogeneity of the disease, its spectrum of presentation and its evolution over time.

One of the characteristics of birdshot chorioretinopathy is its association with the HLA-A29 allele, which constitutes the strongest link between a disease and class I HLA allele. The mechanism by which HLA-A29 confers a risk for birdshot chorioretinopathy is a key question that remains unanswered. As with other associations between HLA class I antigens and diseases (HLA-B27 with spondylarthropathies and HLA B51 with Behçet's disease), the physiopathogeny of these links have not been elucidated.

Other factors playing a role in the physiopathogeny of the disease and not linked to the major histocompatibility complex are researched. A few families of patients with birdshot chorioretinopathy have been reported, which could point to additional genetic factors for disease susceptibility but does not rule out an environmental effect.

Hence, the complex physiopathology of birdshot chorioretinopathy could involve the HLA-A29 allele, other unknown genetic factors, as well as environmental factors.

Given the above, we are planning a GWAS (Genome Wide association Study) based on DNA of the cohort patients, which will be performed with the aim to identify other susceptibility genes associated with BCR.

Study Type

Observational

Enrollment (Anticipated)

600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
    • Île-de-France
      • Paris, Île-de-France, France, 75014
        • Recruiting
        • Ophtalmopôle, Hôpital Cochin
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients followed in the Department of Ophthalmology in a Paris University Hospital. Tertiary center for rare inflammatory ocular disorders.

Description

Inclusion Criteria:

  1. Bilateral disease
  2. Presence of at least three peripapillary "birdshot lesions" inferior or nasal to the optic disk in one eye
  3. Low-grade anterior segment intraocular inflammation (defined as ≤ 1+cells in the anterior chamber)
  4. Low grade vitreous inflammatory reaction (defined as ≤ 2+ vitreous haze‡) Supportive findings

1. HLA-A29 positivity 2. Retinal vasculitis 3. Cystoid macular edema

Exclusion Criteria:

  1. Keratic precipitates
  2. Posterior synechiae
  3. Presence of infectious, neoplastic, or other inflammatory diseases that can cause multifocal choroidal lesions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Birdshot chorioretinopathy
Patients with a diagnosis of birdshot chorioretinopathy, with confirmed HLA-A29 positivity.
Other: Observational study
The goal of the study is purely observational. Treatment decisions will be made by physicians according to the grading of the intraocular inflammation related to birdshot chorioretinopathy and to their consequences on visual function. These treatment decisions will be independent from the observational study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Corrected Visual Acuity (BCVA)
Time Frame: Through study completion, an average of 1 year
Standard decimal clarity for distance visual acuity. It is expressed from 0 which is minimum & worse value, corresponding to no light perception; to 1.0 (20/20) which is maximum & best value
Through study completion, an average of 1 year
Visual field testing
Time Frame: Through study completion, an average of 1 year
Humphrey 30-2 automated threshold perimetry with foveal sensitivity. It is expressed in Mean Deviation from -25 decibels or unachievable which is minimum & worse value, to 0 decibel, which is maximum & best value.
Through study completion, an average of 1 year
Color vision
Time Frame: Through study completion, an average of 1 year
Assessed with Desaturated Lanthony 15-Hue Test: an objective technic evaluating sensitivity to color & colour vision deficiency. Test result is categorized as Abnormal for minimum & worse evaluation; and Normal for maximum & best evaluation.
Through study completion, an average of 1 year
National Eye Institute 25-Item Visual Function Questionnaire
Time Frame: Through study completion, an average of 1 year
Using a scale from 0 for minimum & worse, to 100 for maximum & best result; this questionnaire measures influence of visual impairment on various dimensions of quality of life such as emotional well-being and social functioning
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of birdshot spot size
Time Frame: Through study completion, an average of 1 year
It describes appearance of the birdshot spots as small for minimum or large for maximum.
Through study completion, an average of 1 year
Assessment of birdshot spot number
Time Frame: Through study completion, an average of 1 year
Spots are counted and categorized as <10 for minimum value & >50 for maximum
Through study completion, an average of 1 year
Assessment of birdshot spot localization
Time Frame: Through study completion, an average of 1 year
Spots are categorized as Juxtapapillary, Equator & Diffuse.
Through study completion, an average of 1 year
Assessment of birdshot spot pigmentation
Time Frame: Through study completion, an average of 1 year
Spot pigmentation is analysed and categorized as No pigmentation for minimum & Sever for maximum.
Through study completion, an average of 1 year
Assessment of edema
Time Frame: Through study completion, an average of 1 year
Papillary & macular edema are analysed by Optical Coherence Tomography, using a scale from 0 to 4 respectively for minimum & best, to maximum & worse value.
Through study completion, an average of 1 year
Assessment of retinal vasculitis
Time Frame: Through study completion, an average of 1 year
Arterial & venous vasculitis are analysed by Fluorescein Angiography, using a scale from 0 to 4 respectively for minimum & best, to maximum & worse value.
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Antoine BREZIN, PhD & MD, Université de Paris, Ophtalmopôle, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 2, 2004

Primary Completion (Anticipated)

December 31, 2030

Study Completion (Anticipated)

December 31, 2030

Study Registration Dates

First Submitted

January 12, 2021

First Submitted That Met QC Criteria

December 9, 2021

First Posted (Actual)

December 10, 2021

Study Record Updates

Last Update Posted (Actual)

October 31, 2022

Last Update Submitted That Met QC Criteria

October 28, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NI16002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Sharing of anonymized clinical data with other investigators experienced in the care of patients with birdshot chorioretinopathy.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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