[Observational study of QuantiFERON® management for ocular tuberculosis diagnosis: Analysis of 244 consecutive tests]. / Étude observationnelle de l'usage du QuantiFERON® pour le diagnostic de tuberculose oculaire, basée sur 244 tests consécutifs.

INTRODUCTION: Ocular tuberculosis (TB) diagnosisremains difficult and quantiferon (QFT) contribution needs still yet to be specified, despite its generalization in France. The purpose of this observational study is to assess in which ocular inflammation (OI) presentation QFT is prescribed and to evaluate the added value of new QuantiFERON®-TB Gold Plus (QFT-Plus) test for diagnosis ocular TB diagnosis. PATIENTS AND METHODS: Monocentric, observational study, carried out in an ophthalmology department over a period of 5 months. Inclusion criteria were defined as an existence of an OI for which a QFT-Plus test was part of the etiological investigations. Of the 316 consecutive files, 72 were excluded (indeterminate test, prescription before anti-TNFα or immunosuppressant initiation, missing data, wrong indication) and 244 were selected and divided into two groups: group one (anterior uveitis/episcleritis, n=129) and group two (intermediate/posterior uveitis/optic neuritis/ocular myositis, n=115). All positive QFT patients underwent an etiological investigation including thoracic imaging. RESULTS: Forty-five patients, aged 52±12 years, had positive QFT (18.5%), including 18 patients for group 1 and 27 for group 2. Living in TB-endemic area, TB exposure and chest imaging abnormalities were identified in 70%, 27% and 22% of cases, respectively. OI was chronic in 36% of cases (group one, 4/18; group two, 12/27). None of the 18 patients, in group 1, received anti-tuberculosis treatment (ATT) or experienced a relapse during one-year follow-up. Four QFT+ patients, from group 2 (15%) had another associated disease explaining their uveitis. Among the 23 other patients without identified etiology, 13 had at least one relevant ophthalmological signs predictive of TB uveitis (posterior synechiae, retinal vasculitis and/or choroidal granuloma) (59%). Eleven patients received a 6-month ATT trial. Radiological abnormalities and granulomas at angiography were significantly more frequent among treated patients (p=0.03 and 0.001, respectively). A full OI recovery was observed for 8 patients (73%), considered ex-post as ocular TB. Nine patients in group 2 received rifampicin/isoniazid dual therapy for 3 months, but no conclusion could be drawn as to the benefit of such prescription on OI. QFT rate comparison, according to CD4 stimulation by ESAT-6/CFP-10 peptides or by CD4/CD8 co-stimulation, was comparable and found only 4 cases of discrepancy (1.6%). None of these 4 cases had ocular TB diagnosis. CONCLUSION: Positive QFT frequency among patients consulting for posterior OI remains high. In this study, radiological abnormalities and granulomas at angiography seemed to be more closely related to clinician decision for starting ATT trial in QFT+ patients, which was effective in 73% of cases. QFT-Plus does not seem more relevant than QFT-TB in exploring an OI. Prospective studies are necessary to codify QFT management in the etiological assessment of OI and clearly define ATT trial indications as well as their modalities.

INFLIXIMAB and ADALIMUMAB in Uveitic Macular Edema.

PURPOSE: To compare the efficacy of infliximab and adalimumab in patients with refractory uveitis-related macular edema (ME). METHODS: A retrospective study was conducted in all patients with refractory uveitis-related ME treated with infliximab or adalimumab in Pitié-Salpêtrière hospital between January 1, 2006 and January 1, 2016. All patients underwent a complete ophthalmologic examination, OCT and retinal angiography at baseline, and 6 (M6) and 24 months (M24) after treatment initiation. Main outcome was a decrease in central foveal thickness (CFT) on OCT. RESULTS: Twenty-five patients were included: 12 treated with adalimumab and 13 treated with infliximab. The median baseline CFT was 381 µm (Q1 = 254; Q3 = 470) in the adalimumab group and 469 µm (307; 539) in the infliximab group. At M6, 6/12 adalimumab-treated patients (50%) and 8/13 infliximab-treated patients (61%) were responders. The median CFT decrease from baseline was 61 µm (17-136) and 66 µm (-59-119) respectively at M6 and M24 in the adalimumab group versus 92 µm (9-165) and 52 µm (33-130) respectively at M6 and M24 in the infliximab group (all p > 0.05). CONCLUSION: No significant difference in efficacy was observed between infliximab and adalimumab at M6 and M24.

Uveitic macular edema.

Macular edema (ME) may complicate anterior, intermediate, and posterior uveitis, which may be because of various infectious, neoplastic or autoimmune etiologies. BRB breakdown is involved in the pathogenesis of Uveitic ME (UME). Optical coherence tomography has become a standard tool to confirm the diagnosis of macular thickening, due to its non-invasive, reproducible, and sensitive features. Retinal fluorescein and indocyanine green angiography is helpful to study the macula and screen for associated vasculitis, detect ischemic areas and preretinal, prepapillary or choroidal neovascular complications, and it may provide information about the etiology and be needed to assess the therapeutic response. UME due to an infection or neoplastic infiltration may require a specific treatment. If it remains persistent or occurs in other etiologies, immunomodulatory treatments may be needed. Intravitreal, subconjunctival, or subtenon corticosteroids are widely used. Their local use is contraindicated in glaucoma patients and limited by their short-lasting action. In case of bilateral sight-threatening chronic posterior uveitis, systemic treatments are usually needed, and corticosteroids are used as the standard first-line therapy. In order to reduce the daily steroid dose, immunosuppressive or immunomodulatory agents may be added, some of them being now available intravitreally. Ongoing prospective studies are assessing biotherapies and immunomodulators to determine their safety and efficacy in this indication.

[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.

[Comparison of early management of central retinal vein occlusion with ranibizumab versus hemodilution]. / Comparaison de la prise en charge précoce des occlusions de la veine centrale de la rétine par ranibizumab et/ou hémodilution.

PURPOSE: This study was designed to evaluate and compare the efficacy of early treatment of CRVO with either hemodilution by erythrocytopheresis or intravitreal (IVT) ranibizumab, or both. MATERIAL AND METHODS: A multicentric prospective randomized study including patients with CRVO for less than 1 month was designed. Patients were randomized into 3 treatment groups: hemodilution (HD group), 3 monthly intravitreal injections of ranibizumab followed by PRN treatment (IVT group), or combined treatment (IVT+HD group). A monthly evaluation during a 6-month follow-up included best-corrected visual acuity (BCVA) and macular thickness measurements with OCT. Fluorescein angiography was performed at baseline, month 2 and month 6. Local and systemic tolerability of the different treatments were also compared. RESULTS: Forty-four CRVO patients were included between February 2010 and June 2013: 20 in the IVT group, 13 in the HD group and 11 in the HD+IVT group. The mean duration of CRVO at baseline was 10 days and 16 days at the time of treatment without any significant difference between groups. Retinal ischemia was present at baseline in 40% of eyes in each group. After a 6-month follow-up, no difference between the 3 groups was observed in BCVA (10.5 ETDRS letters, 14.6 and 14.1 in the IVT group, HD group and IVT+HD group respectively, P=0.726) or in macular thickness (398 µ, 440 µ and 379 µ respectively, P=0.465). The time until treatment from CRVO onset, ranging from 1 to 35 days, was not correlated to final outcomes. No significant difference in the mean number of IVT (3.2 in the IVT+HD group vs 3.7 in the IVT group) was observed at 6 months. CONCLUSION: No difference in BCVA nor in macular thickness was seen at M6 between the study groups. The duration of CRVO at the time of the initiation of the treatment was not correlated to better visual outcomes. Therefore, etiologic treatment with HD can still be proposed as a first-line treatment in young patients, which allows delaying or avoiding the IVT treatment and its potential side effects. Anti-VEGF IVT still remains an effective option in every case and can be started one month after the beginning of the CRVO.

[Uveitic macular edema]. / Œdème maculaire au cours des uvéites.

Macular edema may complicate anterior, intermediate, and posterior uveitis, which may be due to various infectious, tumoral, or autoimmune etiologies. Breakdown of the internal or external blood-retinal barrier is involved in the pathogenesis of inflammatory macular edema. Optical coherence tomography has become standard in confirming the diagnosis of macular thickening, due to its non-invasive, reproducible and sensitivity characteristics. Fluorescein and indocyanine green angiography allows for, in addition to study of the macula, screening for associated vasculitis, detection of ischemic areas, easy diagnosis of preretinal, prepaillary or choroidal neovascular complications, and it can provide etiological information and may be required to evaluate the therapeutic response. Treatment of inflammatory macular edema requires specific treatment in cases of infectious or tumoral etiologies. If it remains persistent, or occurs in other etiologies, anti-inflammatory treatments are needed. Steroid treatment, available in intravitreal, subconjunctival and sub-Tenon's routes, are widely used. Limitations of local use include induced cataract and glaucoma, and their short-lasting action. Such products may reveal retinal infection. Thus, bilateral chronic sight-threatening posterior uveitis often requires systemic treatment, and steroids represent the classic first-line therapy. In order to reduce the daily steroid dose, immunosuppressant or immunomodulatory drugs may be added. Certain of these compounds are now available intravitreally.

Choroidal and adnexal extranodal marginal zone B-cell lymphoma: presentation, imaging findings, and therapeutic management in a series of nine cases.

PURPOSE: To describe the clinical and imaging presentation, pitfalls in the diagnosis of choroidal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), as well as the therapeutic management and prognosis. METHODS: A retrospective case review of nine choroidal MALT lymphomas was performed. Initial clinical presentation and imaging findings of these histologically confirmed cases of lymphoma were analyzed. Treatment methods, time to diagnosis, systemic work-up, and treatment prognosis were assessed. RESULTS: Initial presentation was essentially blurred vision. The features described on examination were: anterior and posterior scleritis, iridocyclitis, choroidal infiltration, and exudative retinal detachment. Fluorescein and indocyanine green angiography as well as ultrasonography and optic coherence tomography provided arguments in favor of the diagnosis. Biopsy sites included conjunctiva, Tenon's capsule, deep scleral tissue, episclera, lacrimal gland, and choroid. Treatment mostly consisted of a combination of chemotherapy and radiotherapy. The mean time to diagnosis was 12 months. CONCLUSIONS: Owing to the insidious onset of these tumors and their ability to simulate other conditions, the diagnosis is commonly delayed. The prognosis is generally good and treatment is effective in the case of localized lymphoma.

[Maculopathy and dengue fever]. / Maculopathie et fièvre dengue.

The authors report a case of a 20 year old female who presented a bilateral decrease in vision. Detailed history revealed that 15 days before the onset of symptoms, the patient presented a dengue fever during her stay in Martinique. On initial examination, the fundus exam revealed a bilateral loss of foveal reflection. The optical coherence tomography demonstrated the macular edema and the dengue serology was postive. The patient received an interferon2a-based therapy. The macular edema disappeared and we noticed a partial but fast improvement of visual acuity 12 days after the treatment initiation.

Toxoplasmosis: new challenges for an old disease.

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.

[Critical review of the new recommendations on screening for hydroxychloroquine retinopathy]. / Lecture critique des nouvelles recommandations américaines sur le suivi ophtalmologique des patients traités par hydroxychloroquine (Plaquénil®).

New recommendations for screening of hydroxychloroquine retinopathy, updating those of 2002, have been recently published by the American Academy of Ophthalmology. These recommendations have been necessary because of new knowledge about the prevalence of toxicity and because of improved screening tools. Amsler grid testing, color vision testing, fluorescein angiography, full-field electroretinogram, and electro-oculogram are no longer recommended. It is now recommended to perform fundus examinations with 10-2 automated fields, and whenever possible, at least one objective test including multifocal electroretinogram, fundus autofluorescence or spectral domain optical coherence tomography (SD-OCT). A baseline examination is advised as a reference and then, annual screening should be initiated no later than 5 years after starting hydroxychloroquine therapy.

[Chronic postoperative endophthalmitis]. / Endophtalmies chroniques postopératoires.

Chronic postoperative endophthalmitis designates delayed-onset postoperative endophthalmitis appearing more than two weeks after surgery, revealed by chronic intraocular inflammation with phases of inflammatory recurrence, which, at the beginning of the disease course, is partially sensitive to local corticosteroid treatment. It differs therefore from acute endophthalmitis in the immediate postoperative phase, from acute differed endophthalmitis after filtrating surgery, which appears years after the surgery, and from endogenous endophthalmitis. The most frequent presentation is granulomatous uveitis, often hypertonic, in an eye operated for cataract, presenting phases of recurrence sensitive to corticosteroid therapy but which recurs as soon as treatment is interrupted. Whitish condensations in plaques on the posterior capsule suggest the diagnosis and over several months the vitreous becomes inflamed. Ocular samples allow cytological analysis of an infectious process and bacteriological analysis in culture and with PCR. Treatment includes lavage of the sac with vancomycin and can be associated with posterior capsulectomy and intravitreal injections of antibiotics possibly associated with systemic antibiotic therapy. Treatment is prolonged because of the slow replication of the microorganisms involved. In approximately one-third of cases, the implant, the capsule, and the sac must be removed over 360° to permanently halt the intraocular infection. The diagnosis and specific treatment should be as early as possible since the aggressiveness of the treatment required is correlated with the time to management of the infection.

Deep sclerectomy and trabeculectomy in uveitic glaucoma.

PURPOSE: To compare the results of deep sclerectomy (DS) and trabeculectomy (TRAB) in the management of uveitic glaucoma. METHODS: A retrospective chart review was carried out of 41 eyes (38 patients) operated on for uncontrolled uveitic glaucoma, 20 by DS with an implant and 21 by TRAB, with antiproliferative agents in both cases. Main outcome criteria were intraocular pressure (IOP), flare values, complications, and need for postoperative adjustments or re-operation. RESULTS: Mean follow-up lasted 21.1+/-11.3 months in the TRAB group and 18.9+/-10.7 months in the DS group (P=0.184). Mean IOP did not differ significantly in the two groups on the day before surgery, at postoperative days 1 and 7, or at months 1, 6, and 12. At postoperative month 12, IOP values in the TRAB and DS groups were 12.4+/-4.3 and 11.7+/-3.3 mm Hg (P=0.688), respectively. The cumulative probability of success at 12 months was 89% for TRAB and 88% for DS (P=0.306). After DS, more postoperative adjustments were necessary to lower IOP than after TRAB (85 vs 9.5%, P<0.001), but 7 days after surgery, intraocular inflammation was higher after TRAB (245.8 vs 38.5 ph/ms, P<0.001). CONCLUSIONS: DS and TRAB afforded equivalent IOP control in uveitic glaucoma. TRAB involved deeper invasion of the eye and resulted in more inflammation during the week after surgery, but successful DS required closer postoperative monitoring and more postoperative adjustments.

Uveitic macular oedema: correlation between optical coherence tomography patterns with visual acuity and fluorescein angiography.

AIMS: (1) To associate optical coherence tomography (OCT) patterns with particular fluorescein angiography (FA) findings in uveitis patients with macular oedema. (2) To investigate the correlation between tomographic features and visual acuity (VA). (3) To determine the impact of OCT patterns on visual improvement over time. METHODS: 129 eyes of 90 patients followed for uveitis with macular oedema and adequate media clarity were consecutively included from February to November 2004. We examined the relationship between VA, the fluorescein angiograms grading and central thickness. RESULTS: Mean retinal thickness at the central fovea was 357 (SD 128) microm. The mean VA was 0.5 (logMAR). There was agreement between OCT and FA in 112 eyes (86.8%). In eight eyes (6.2%), serous retinal detachment (SRD) was detected on OCT but not on FA. Nine eyes (7%) had perifoveal leakage on FA without macular thickening on OCT. There were three patterns of macular oedema on OCT: diffuse macular oedema (DMO), cystoid macular oedema (CMO) and SRD. CMO was detected in 61 eyes (50.8%), and in 18 of these eyes (15%), CMO was associated with SRD. DMO was detected in 45 eyes (37.5%), and in eight (6.7%) of these eyes, DMO was associated with SRD. SRD without retinal thickening was present in 14 eyes (11%). Epiretinal membrane was detected by OCT in 27 eyes (21%). Six eyes demonstrated vitreomacular traction (4.7%). There was a correlation between VA and central thickness on OCT (r = 0.407, p = 0.000001). Correlation between VA and central thickness is significant in the group with CMO (r = 0.401, p = 0.001) but not significant in the group with DMO. Furthermore, vision recovery was observed in patients with CMO but was limited in patients with DMO. SRD did not have a significant impact on visual recovery, but its presence reduced the correlation between vision and central thickness. CONCLUSION: OCT is effective in detection of macular oedema. It allows determination of the distribution of fluid and quantification of retinal thickness particularly in patients with CMO. In these patients, a potential for vision recovery was also identified. DMO was associated with a poor visual prognosis and a poor prognosis for vision recovery. SRD is associated with a high probability of vision recovery when observed alone or underlying CMO eyes. It should be substracted from the central thickness measurement when attempting to correlate central thickness with vision in patients with macular oedema in uveitis.

[Interferon and retinal vasculitis]. / Interféron et vasculites rétiniennes.

The treatment of noninfectious posterior uveitis can lead to severe vision loss, and the first-line conventional treatment includes systemic steroids. When the prednisone doses necessary to control intraocular inflammation are above 0.3mg/day, a therapeutic association is proposed in order to lower the daily prednisone dose. The combined drugs are immunosuppressive or immunomodulative. The side effects of immunosuppressive drugs are oncogenic, infectious, and hematological, and can involve reproductive troubles, associated with specific toxic effects depending on the drug used. Recently adding polyclonal or monoclonal antibodies and the interferons to immunomodulative drugs has been suggested. Interferon alpha has been shown to be effective in Behçet's disease. The efficacy of interferon needs to be evaluated in other etiologies of retinal vasculitis through randomized studies.

[Acute posterior multifocal placoid pigment epitheliopathy, serpiginous and multifocal choroiditis: etiological and therapeutic management]. / Epithéliopathies en plaques, choroïdites serpigineuses et multifocales: analyse étiologique et prise en charge thérapeutique.

PURPOSE: To highlight the importance of an extensive medical work-up in serpiginous and multifocal choroiditis, and acute posterior multifocal placoid pigment epitheliopathy before therapeutic management. PATIENTS AND METHODS: Records of patients referred to our department, between January 2000 and January 2002, for the diagnostic and therapeutic management of choroiditis or acute posterior multifocal placoid pigment epitheliopathy were retrospectively reviewed. All patients had a complete ophthalmologic examination, fluorescein and infrared angiographies. An extensive work-up was performed in order to exclude an infectious etiology. RESULTS: Fourteen patients were included (six cases of serpiginous choroiditis, four cases of multifocal choroiditis, and four cases of APMPPE). The mean age was 42.1 years and the sex ratio was 9: 5. Six patients presented with a history of tuberculosis in the family or with a tuberculosis primary infection. Toxoplasmic retinochoroiditis was confirmed in one case by a positive PCR applied to the aqueous humor. In the serpiginous choroiditis group, two patients have been treated with antituberculous drugs, one of whom was initially resistant to immunosuppressive regimens. In the acute posterior multifocal placoid pigment epitheliopathy group, one patient was treated with antituberculous drugs and another received antibiotics. CONCLUSION: An infectious agent may be associated with this group of clinical presentations. All patients presenting with severe forms of ocular inflammation, who resist to corticosteroids or immunosuppressive regimens, must undergo an extensive infectious work-up in order to propose a specific treatment.

[Central serous chorioretinopathy and systemic diseases report of 2 cases associated with corticotherapy]. / Choriorétinopathie séreuse centrale et maladies systémiques: deux cas observés sous corticothérapie.

INTRODUCTION: Central serous chorioretinopathy is an uncommon retinal disease, whose pathogenesis is largely unknown. It is characterized by an accumulation of subretinal fluid at the posterior pole of the fundus, creating a circumscribed area of serous retinal detachment. It manifests generally as a visual loss or an abnormal colour vision. It is often idiopathic but may also be associated with numerous pathological situations, with frequent exposure to corticosteroids. EXEGESIS: We report on two patients with central serous chorioretinopathy. The first female patient had been treated with steroids for a systemic lupus erythematosus for fifteen years, and the second male patient had been treated with steroids for an idiopathic hypereosinophilic syndrome for a few months. Visual loss led to a diagnosis of central serous chorioretinopathy. Lowering of steroids doses was followed by a clinical improvement in both cases. CONCLUSION: Similarly to cataract or glaucoma, central serous chorioretinopathy belongs to the potential ocular side-effect of steroid treatment, and thus deserves to be known by internists.