Histocompatibility Leukocyte Antigen-A29-Associated Retinal Vasculitis without Choroidal Lesions: A Report of 4 Cases.

This study describes a cohort of patients presenting with histocompatibility leukocyte antigen (HLA)-A29-associated retinal vasculitis without choroidal lesions that may share clinical features with birdshot retinochoroiditis. The methods include a retrospective chart review of patients presenting with HLA-A29-associated retinal vasculitis without choroidal lesions. The data on the patients were entered retrospectively into a new database and analyzed. Four patients who had HLA-A29-associated retinal vasculitis without choroidal lesions were identified. The median age at presentation was 40 years (range: 14-71); 75% were female. At presentation, all four patients had a visual acuity of 20/50 or better in both eyes. All the eyes had mild vitritis, three eyes (37.5%) had cystoid macular edema, and two eyes (25%) had optic disc edema. All the patients required treatment with systemic steroids and immunosuppressive therapy. HLA-A29-associated retinal vasculitis without choroidal lesions appears to share many clinical features with birdshot chorioretinitis, including the need for systemic immunosuppressive therapy. Whether this entity represents an early form of birdshot retinochoroiditis or a more localized variant of the disease is a topic for additional studies.

Characteristics, Upon Presentation, of a Cohort of Hispanic Patients with Birdshot Retinochoroidopathy.

OBJECTIVE: To describe the characteristics, upon presentation, of a cohort of Hispanic patients with birdshot retinochoroidopathy. METHODS: A retrospective chart review of Hispanic patients with birdshot retinochoroidopathy of was performed. The demographic and clinical characteristics were analyzed. RESULTS: Nine patients who met the research criteria for a diagnosis of birdshot retinochoroidopathy were identified and included in the analysis, all of whom were HLA-A29 positive. The median age of the cohort upon presentation was 52 years; 89% of the patients were female, and all were Hispanics. Ninety-four percent of the eyes had an initial visual acuity of 20/50 or better, while 72% had measured 20/25 or better. Sixty-one percent of the eyes had retinal vasculitis, which was bilateral in 83% of the cases. Thirty-three percent of the patients had, upon presentation, evidence of cystoid macular edema, which was always bilateral. All the eyes had the typical birdshot lesions, at presentation. CONCLUSION: Birdshot retinochoroidopathy can be found in Hispanic patients. Our study suggests that the characteristics upon presentation in Hispanics may be similar to those of Caucasian cohorts.

Long-term outcomes of systemic corticosteroid-sparing immunomodulatory therapy for Birdshot Retinochoroidopathy.

PURPOSE: To report the visual prognosis, electroretinography (ERG) and perimetry outcomes of systemic corticosteroid-sparing immunomodulatory treatment (IMT) for birdshot retinochoroidopathy (BSRC). METHODS: Retrospective non-comparative case series of 132 patients (264 eyes) with BSRC treated with IMT from Massachusetts Eye Research and Surgery Institution. RESULTS: The average follow-up time was 60.1 months. After one year on IMT, 39.4% showed no clinically active inflammation. After 5 years of IMT, 78.0% had no signs of clinical inflammation. No significant differences were observed on best-corrected visual acuity (BCVA), ERG parameters, and perimetry parameters between baseline and subsequent visits on IMT. CONCLUSION: Long-term systemic corticosteroid-sparing IMT was associated with a low rate of BSRC disease exacerbation. While differences were seen on testing parameters, they were not consistent trends and difference were attributed to variability of testing or fluctuation of inflammation that may be expected in the course of the disease.

Outcomes of "Early" Withdrawal of Corticosteroid Sparing Immunomodulatory Therapy for Birdshot Retinochoroidopathy.

Purpose: To review early withdrawal of immunomodulatory therapy (IMT) for birdshot retinochoroidopathy (BSRC). Design: Retrospective case-series of sixteen patients with Human-leukocyte-antigen-A29-positive BSRC treated with IMT ≥ 1 year and discontinued prior to achieving durable remission, observed ≥ 6 months off IMT. Results: Mean duration on IMT was 42.4 months. At discontinuation, quiescence was achieved in 75.0% of eyes. Subjects off IMT for 6 months, 1 year, and 3 years showed quiescence in 75.0%, 77.8%, and 80.0% of eyes. No significantly decreased vision was found 6 or 12 months after discontinuation. One eye experienced significantly decreased vision following 3 years without IMT. Significantly decreased amplitude on electroretinography and worse deviation parameters in perimetry were found in patients 3 years after withdrawal that experienced early discontinuation when compared with those achieving durable remission on IMT > 2 years (p < 0.05). Conclusion: The possibility of electroretinography and perimetry results worsening after early IMT discontinuation remained if the patients couldn't achieve remission.

Rituximab as a monotherapy or in combination therapy for the treatment of non-paraneoplastic autoimmune retinopathy.

PURPOSE: To examine the efficacy of rituximab as a monotherapy or in combination therapy for the treatment of patients with non-paraneoplastic autoimmune retinopathy. METHODS: Twelve eyes of six patients with non-paraneoplastic autoimmune retinopathy who were treated with rituximab and had at least 6 months of follow-up were included. Demographic data, clinical data, visual field parameters, electroretinography parameters, and anti-retinal and anti-optic nerve autoantibody bands were collected from the Massachusetts Eye Research and Surgery Institution database between September 2010 and January 2015. Changes in visual acuity, visual field parameters, electroretinography parameters, and anti-retinal and anti-optic nerve autoantibody bands from the initial visit to the most recent visit were examined. RESULTS: From the initial visit to the last visit, visual acuity was stable in eight (66.7%) eyes. Visual field was stable in six (50%) eyes and improved in two (16.7%) eyes. Electroretinography was stable or improved in eight (66.7%) eyes. The average number of anti-retinal and anti-optic nerve antibody bands was reduced. CONCLUSION: Stabilization and/or improvement of visual acuity, visual field parameters, and electroretinography parameters were observed in a high number of patients (75%) on rituximab, as a monotherapy (one patient) or in combination therapy.

Efficacy of Anti-IL6-Receptor Tocilizumab in Refractory Cystoid Macular Edema of Birdshot Retinochoroidopathy Report of Two Cases and Literature Review.

PURPOSE: To evaluate tocilizumab (TCZ) efficacy in severe and refractory birdshot chorioretinopathy (BSCR). METHODS: Assessment of BSCR patients refractory to conventional immunosuppressive and anti-TNF-α drugs who underwent TCZ therapy. RESULTS: Two HLA-A29 positive patients (man/37 years and woman/38 years; four affected eyes) with BSCR were studied. They had a chronic bilateral posterior uveitis. Patient 1 had been treated with intraocular and oral corticosteroids, cyclosporine A, and infliximab whereas Patient 2 received intravenous methylprednisolone pulses, cyclosporine A, azathioprine, and adalimumab. At TCZ onset they had macular edema (four eyes); visual acuity (VA) impairment (four eyes); vitritis (one eye); and diffuse angiographic signs of vasculitis (periphlebitis) (two eyes). Improvement of VA and OCT was observed following TCZ therapy in both patients. After a follow-up of 18 months (Patient 1) and 10 months (Patient 2), respectively, a corticosteroid sparing effect without any adverse effects was achieved in both cases. CONCLUSIONS: TCZ was effective in two patients with BSCR refractory to anti-TNF-α agents.

Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.

PURPOSE: To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. METHODS: This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. RESULTS: A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3%) who had >0.5+ cells in the anterior chamber. CONCLUSIONS: Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.

[Birdshot retinochoroidopathy: Key messages]. / Rétinochoroïdopathie de type Birdshot : les éléments clés.

Birdshot retinochoroidopathy (BRC) is a potentially blinding posterior autoimmune uveitis that affects Caucasian patients in their fifties. Strongly associated with the HLA A 29 phenotype, BRC is characterized by the presence of suggestive choroidal lesions on the fundus, but their apparition can be delayed. Visual acuity is not a good descriptive factor of visual function. Ancillary tests can therefore help establish the diagnosis and allow proper follow-up of BRC patients: optical coherence tomography can reveal either oedema or atrophy of the macula. Fluorescein and infracyanine green angiograms can show signs of inflammatory activity and give further diagnostic clues. Electroretinograms and visual fields can be useful for the diagnosis and follow-up. BCR patients should be examined periodically and undergo exhaustive clinical and paraclinical tests to insure the best prognosis. Corticosteroids should be associated with immunosuppressive treatments as early as possible in the presence of factors that are predictive of the worse prognoses.

Dexamethasone intravitreal implant for treatment of persistent macular oedema in Birdshot retinochoroidopathy.

CLINICAL CASE: The case is reported of a 32 year-old man with a bilateral cystoid macular oedema and serous macular detachment due to birdshot retinochoroidopathy. An intravitreal implant of 0.7 mg dexamethasone (Ozurdex®, Allergan) was performed on both eyes, after a partial response of the macular oedema to oral and subtenon corticosteroids. Anatomical and visual improvements were observed and maintained after six months of follow up. DISCUSSION: Intravitreal dexamethasone implant may be a good therapeutic option in patients with macular oedema due to Birdshot retinochoroidopathy, and who were refractory or had intolerance to previous therapies.

Molecular Genetic Advances in Uveitis.

Uveitis is usually considered as an intraocular inflammation characterized by variety of clinical features. Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU), and birdshot chorioretinopathy (BCR) are examples of noninfectious forms of uveitis. Although the precise pathogenesis remains unclear, accumulating evidence shows that complex genetic backgrounds coupled with an aberrant immune response may be implicated in the development of uveitis. The complement and pattern recognition systems are both important factors of the innate immune system and are involved in the pathogenesis of uveitis. Copy number variants (CNVs) of complement component 4 have been found to be associated with BD and VKH syndrome, but not with AAU. Several CNVs and gene polymorphisms of toll-like receptors were found to be associated with BD. Leukocytes are an important part of the adaptive immune system and various molecules on these cells play an important role in the development of uveitis. Genes encoding for human leukocyte antigens (HLAs) have been shown to be associated with certain uveitis entities, including BD (HLA-B51), VKH syndrome (HLA-DR4, DRB1/DQA1), AAU (HLA-B27), and BCR (HLA-A29). Genome wide association studies showed that the IL-23R locus was a shared risk factor for multiple uveitis entities including BD, AAU, and VKH syndrome. In addition, various other non-HLA genes are also associated with BD or VKH syndrome, such as IL-10, STAT4, STAT3, and UBAC2. These studies support the hypothesis that genetic factors play a key role in the pathogenesis of uveitis.