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Purpose: To investigate clinical and biological factors influencing recurrences of severe toxoplasmic retinochoroiditis (TRC) confirmed by aqueous humor analysis., Design: Retrospective case series., Methods: Retrospective analysis of 87 subjects with severe TRC, proven by positive Goldmann-Witmer coefficient (GWC), Toxoplasma gondii (T. gondii) immunoblot, or T. gondii-specific polymerase chain reaction (PCR) in aqueous humor. Cases with immunosuppression or retinal scars without previous recorded episode were excluded. Time-dependent, clinical, treatment-related, and biological factors were explored by univariate and multivariate shared frailty survival analyses., Results: Among 44 included subjects (age, 40.4 ± 17.6 years; follow-up, 8.3 ± 2.7 years), 22 presented recurrences. There was 0.11 recurrence/patient/year and mean disease-free interval was 5.0 ± 2.9 years. The risk of recurrence was higher immediately after an episode (P < .0001). Among recurrent cases, the risk of multiple recurrences was higher when the first recurrence occurred after longer disease-free intervals (P = .046). In univariate analysis, the recurrence risk declined with higher number of intense bands on aqueous T. gondii immunoblot (P = .006), and increased when venous vasculitis was present initially (P = .019). Multivariate analysis confirmed that eyes with more intense bands on immunoblot had fewer recurrences (P = .041). There was a near-significant risk elevation after pyrimethamine/azithromycin treatment (P = .078 and P = .054, univariate and multivariate). Intravenous corticosteroid administration, oral corticosteroid administration, aqueous GWC, and T. gondii PCR did not influence recurrences (P = .12, P = .10, P = .39, and P = .96, respectively)., Conclusions: Recurrences of severe TRC are not random and may be influenced by clinical and biological factors possibly related to blood-retinal barrier alterations. These results may contribute to identifying biomarkers for TRC reactivation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine the prognostic factors of long-term visual outcome in birdshot retinochoroidopathy (BRC)., Methods: Design: Retrospective case series. Study Population: Successive HLA-A29+ BRC patients whose latest visit was between May and August 2013 at a single tertiary center (Pitié-Salpétrière Hospital, Paris)., Observation Procedure: Endpoint visual status (remission or deterioration) was determined for each patient based on clinical and ancillary data from the latest visit including optical coherence tomography (OCT), automated visual field (AVF), and angiograms. Main Outcome Measure: Epidemiologic, clinical, OCT, AVF, angiographic, and electrophysiological data at baseline were correlated to final visual status., Results: Fifty-five patients were included. Mean observation period was 8 years (range: 0.6-23 years). Mean disease duration was 9.8 years (range: 1.2-32.7 years). Female-to-male sex ratio was 1.6:1. Factors of good visual prognosis (remission vs deterioration) included at baseline: late age of disease onset (49.5 vs 45 years, P = .05), presence of vitreous inflammatory reactions >2+ (35.9% vs 6.2%, P = .04), vascular leakage on fluorescein angiograms (FA) (44.4% vs 12.5%, P = .03), absence of macular pigment epithelium atrophy on FA (88.9% vs 62.5%, P = .05), and presence of macular edema on OCT (33.3% vs 6.2%, P = .04). Preserved electrooculography light peak and Arden ratio (P = .06) and presence of choroidal spots on infracyanine green angiograms (80.0% vs 53.3%, P = .08) seemed associated with the best prognoses., Conclusion: This study suggests a series of prognostic factors of long-term visual outcome in BRC. Keeping in mind the insidious evolution of the disease, knowledge of such prognostic factors should help tailor the treatment and monitoring of birdshot patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

More than a century after the identification of Toxoplasma gondii, major issues need to be addressed for the optimal management of ocular disease. Toxoplasmic retinochoroiditis is the main cause of posterior uveitis in several geographical areas. The parasite establishes a love-hate relationship with the eye, manipulating the immune response and inducing variable initial lesions and further relapses. It is now well established that most cases are acquired after birth and not congenital. The severity of the disease is mainly due to the parasite genotype and the host immune status. Diagnosis is based on clinical features, but may be confirmed by biological tools applied to ocular fluids. Combining several techniques improves the diagnostic yield in equivocal cases. Therapeutic management is the most important challenge. Even though evidence-based data on the efficacy of anti-parasitic drugs are still missing, new strategies with a good safety profile are available and may be proposed earlier during the course of the disease, but also in selected cases, to reduce sight-threatening relapses. Revisiting the therapeutic options and indications may be an important step towards long-term maintenance of the visual function and avoidance of major complications.

Purpose: To report familial cases of birdshot chorioretinopathy (BSCR)., Design: Retrospective, observational case series., Methods: Five families with 2 members in each (10 patients) with BSCR were included in this case series from a cohort of 225 patients followed up for BSCR. A review of medical and angiographic records of familial cases of BSCR was performed. We described and compared in each family the histocompatibility leukocyte antigen (HLA) typing, age at onset, ethnic group, clinical features, fluorescein and indocyanine green angiography results, evolution of disease, and treatment used with efficiency., Results: HLA-A29 and HLA-B44 results were positive in 100% of patients tested. Mean age at onset was 46.5 years. All patients were White. Corticosteroids were required in 7 patients, and 3 patients had no treatment because of mild or moderate lesions. Cyclosporine A was administered in 2 patients from the same family. Period of follow-up ranged from 1 to 32 years (median, 7 years)., Conclusions: Familial forms of BSCR remain rare and do not justify systematic examination in relatives of patients with BSCR.

Introduction: To assess the diagnostic and therapeutic management of extensive toxoplasmic retinochoroiditis., Patients and Methods: The files of all patients referred between December 1999 and December 2001 for the management of a severe, potentially sight-threatening toxoplasmic retinochoroiditis were retrospectively analyzed. The therapeutic strategy and the progression of intraocular inflammation are reported., Results: Thirteen eyes of seven patients were finally included in the study. The sex ratio (F/M) and the mean age were respectively 4/3 and 44.5 years. Most of the patients were immunocompromised. Both eyes were initially affected in five cases. The diagnosis was confirmed by polymerase chain reaction (PCR) after anterior chamber paracentesis in six cases. Retinal detachment was observed in three cases, initially or during follow-up. All patients were treated with a combination of sulfadiazine and pyrimethamine, but azithromycin was necessary in two cases. Clindamycin was used in two cases of allergy to sulfadiazine. Corticosteroids were associated in five cases. For all patients, infection and inflammation were finally controlled. The visual acuity improved more than two lines in four eyes and remained stable in seven other eyes., Discussion: Clinical diagnosis is still a challenge in severe cases of extensive toxoplasmic retinochoroiditis. PCR is helpful in identifying Toxoplasma gondii DNA. A systemic immunosuppression is frequently associated with a positive PCR. Treatment is based on a standard antiparasitic association and steroids must be discussed for each case according to the intensity of inflammation and the degree of immunosuppression., Conclusion: Extensive ocular toxoplasmosis is a serious condition. The final prognosis depends on the location of the necrotic lesions, rapid diagnosis, and efficient treatment.

Purpose: To determine the value of aqueous humor analysis for confirming the diagnosis of ocular toxoplasmosis in patients who present with atypical clinical features and to relate the results of local antibody production and polymerase chain reaction (PCR) with the extent of active retinitis and the immune status of the patient., Design: Retrospective case series., Methods: Sixty-seven consecutive patients with retinitis or retinochoroiditis that was clinically consistent with atypical ocular toxoplasmosis underwent diagnostic anterior chamber paracentesis and serological studies. The aqueous humor was analyzed both by PCR to detect Toxoplasma gondii B1 gene and by the Goldman-Witmer coefficient to determine levels of local anti-T. gondii antibody production., Results: In nine of the 67 cases, PCR was positive for T. gondii; seven of these were negative for local antibody production. All nine patients had illnesses associated with immunosuppression or advanced old age and all had active retinitis with a mean area of 11.5 disk areas (DA). Twenty-five of the remaining 58 cases were positive for local antibody production. These 25 had a mean area of active retinitis measuring 2.6 DA, and 24 of these patients were immunocompetent. All 34 cases with laboratory evidence of ocular toxoplasmosis diagnosed by either method responded to anti-T. gondii agents. The remaining 33 were negative for T. gondii infection by these two methods; some had laboratory evidence of other infections., Conclusions: Although in the present study, the sensitivity and specificity of the aqueous humor PCR and Goldman-Witmer coefficient could not be ascertained in the laboratory diagnosis of toxoplasmic retinochoroiditis, the PCR method appears to confirm the diagnosis in immunocompromised individuals with large atypical foci of retinitis. Conversely, determination of local antibody production may be appropriate for proper diagnosis in immunocompetent individuals presenting with small foci of retinitis.

Aim: To evaluate the efficacy of intravenous immunoglobulin (IVIg) in the treatment of Birdshot retinochoroiditis., Patients and Methods: Eighteen patients were followed-up prospectively in a total number of 37 patients recorded. Inclusion criteria were birdshot retinochoroiditis (BRC) according to the criteria defined by Ryan et al., and a decrease in visual acuity (VA). Efficacy was assessed by measurements of visual acuity and a decrease in inflammation and macular edema on fluorescein angiograms., Results: Sex ratio=1, mean age was 51 (range 29 to 72 years), HLA A29 was positive in 100% of the patients. VA at baseline was 0.6+/-2.4 (range 0.25 to 0.9). Angiography showed retinal vasculitis in 32 patients (86.48%) and cystoid macular edema in 16 patients (43.24%). IVIg was administered at a dosage of 0.4g/kg/d for 4 days then 0.6g/kg/d for 2 days every 4 weeks. Follow-up lasted a mean of 2.7+/-2.0 years (range, 4 months to 5.6 years). Visual acuity of 35 out of 66 eyes (53%) increased by 2.6+/-1.5 (range 1 to 5). In 19 eyes out of 66 (29%), VA remained stable and in 12 eyes out of 66 (18%), VA decreased by -1.8+/-0.8 (ranges-4 to -1). Inflammation on fluorescein angiography improved in 17 patients (81%) and cystoid macular edema decreased in 65% of the cases. Side effects were rare. Treatment was discontinued for side effects in only 3 patients., Discussion: BRC is a chronique disease threatening vision. Treatments including systemic corticosteroids and cyclosporin A may result in severe long-term side effects. IVIg is well tolerated and may be therapeutic alternative for the treatment of BRC.

Birdshot retinochoriodopathy is a bilateral posterior uveitis seen in adults over 45 years of age. The uveitis is associated with moderate vitreal inflammation, vasculides of large vessels, chronic papillitis and the yellow birdshot spots typical of the disease. The disease shows tight linkages with HLA A29 carried by more than 90% of the patients. The visual prognosis depends on the development of complications of the chronic ocular inflammation, particularly crystoid macular edema. These complications lead to lowered visual acuity which becomes a major handicap. Long-term local or general corticosteroid therapy is required and leads to cortico-dependence. An immunosuppressor (cyclosporinA) may be associated. As these treatments cause major morbidity, intravenous immunoglobulins offer a less toxic therapeutic approach. Intravenous immunoglobulins can reduce inflammatory phenomena, providing an interesting alternative for the treatment of birdshot retinochoroidopathy.

Purpose: To describe and analyse relationship between chorioretinal toxoplasmosis and retinal detachment., Patients and Methods: Seven immunocompetent patients examined and treated between November 1992 and March 1996, with ocular toxoplasmic retinochoroiditis and retinal detachment., Results: Of the 7 patients examined, 5 had active retinochoroiditis and 2 had typical inactive scars. Of the patients with active focus 3 had giant retinal tears, one had a posterior retinal tear and one had a retinal tear located at the edge of an atrophic scar. Of the patients with inactive lesions, one had tractional retinal detachment and the other presented with a complete retinal detachment, multiples tears and PVR. Five patients were treated by corticosteroid without antitoxoplasmic drug before they were referred. The seven patients underwent endo-ocular surgery with silicon oil or long actic gas tamponade. Three patients developed PVR and redetachment of the retina and two patients underwent further surgery. Good anatomical result was obtained in 6 patients., Conclusion: Retinal detachment associated with toxoplasmic retinochoroiditis is rare. However it represents a serious complication. Steroid administrated to salvage vision may then worsen the clinical course, these may be justified to reduce hypersensitivity to toxoplasma antigen, but they should be combined with an antimicrobial agent.

Birdshot retinochoroidopathy is strongly associated with HLA-A29. This antigen can be divided into two subtypes, A29.1 and A29.2, using an immunoprecipitation method succeeded by one-dimensional electrofocusing gel electrophoresis. We reviewed the HLA typings of 58 white French patients who had birdshot retinochoroidopathy. Of these 58 subjects, 54 (93.1%) had HLA-A29 with a relative risk of 157.30. We further analyzed the HLA-A29 subtypings of 33 patients with birdshot retinochoroidopathy. Evaluation of the results showed that HLA-A29.2 subtype was present in all patients (100%). We concluded that the absence of HLA-A29.1 subtype is statistically significant (P less than .01) in this study of HLA-A29 subtyping.

The Birdshot choroidoretinopathy (BSCR) is an ocular disease strongly associated with HLA-A29. The HLA-A29 specificity can be split using immunoelectrofocusing in two subtypes A29.1 and A29.2. BSCR susceptibility is exclusively linked to the HLA-A29.2 molecule. The sequence of HLA-A29.2 was established (EMBL X60108 and found to be identical between patients and healthy individuals. A single difference was found (H----D) 102) in the extra cellular domains between HLA-A29.2 and HLA-A29.1. The HLA-A29 sub-types shares the consensus HLA class I sequence (D102). The mutation exhibited by HLA-A29.1 (H102) is unique to that molecule. The ancestral type is thus HLA-A29.2 that confers the susceptibility to BSCR whereas HLA-A29.1 has arisen from a more recent mutation conferring resistance to BSCR. Another single amino-acid difference between HLA-A29.1 and HLA-A29.2 was found in the intracytoplasmic part of the molecule, HLA-A29.2 exhibiting the HLA-A consensus sequence whereas A29.1 shares with AW33.1 the mutation S----F321. In addition, the A29 specificity was assigned to L and Q amino-acids at position 62-63, which can interact with peptides into the binding groove. No specific T or B epitope of susceptibility could be considered involving the region of the mutation discriminating HLA-A29.2 from HLA-A29.1. The HLA-A29.1 mutation is unable to interact with the T cell receptor and did not seem to induce significant structural changes in the peptide-binding groove. Conversely, its position suggests that the A29.1 mutation might interfere with the binding of an accessory molecule, the CD8 molecule being the most likely candidate for that role.