French recommendations for the management of non-infectious chronic uveitis.

This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.

[Ocular toxicity of targeted therapies with MEK inhibitors and BRAF inhibitors in the treatment of metastatic cutaneous melanoma]. / Toxicité oculaire des thérapies ciblées anti-MEK et anti-BRAF dans le traitement des mélanomes cutanés métastatiques.

INTRODUCTION: Cutaneous melanoma is a malignant tumor, which develops from dermal melanocytes. Targeted therapies have changed the therapeutic management of metastatic melanoma and improved the survival rate. Among the various targeted therapies, MEK inhibitors and BRAF inhibitors have demonstrated efficacy, but they may lead to ocular toxicity. The goal of this study was to assess the incidence of ocular complications caused by the use of MEK inhibitors and BRAF inhibitors and to report their clinical features and therapeutic management. MATERIAL AND METHODS: This retrospective, observational, descriptive, single center study was conducted between May 2015 and December 2019 and included all patients with metastatic cutaneous melanomas treated with MEK inhibitors and BRAF inhibitors in whom ophthalmic toxicity was suspected. The data collected were demographic data (age, sex), the type of MEK inhibitors and BRAF inhibitors used, the length of time from melanoma diagnosis, mean duration of ophthalmological follow-up, time differential between starting therapy and the emergence of ocular complications, initial and final logMAR visual acuity, biomicroscopic examination of the anterior segment, dilatated fundus examination, and treatment administered. RESULTS: Fifty-four eyes of 27 patients with a mean age of 61.3±14.3 were included. The mean time delay between melanoma diagnosis and initiation of treatment was 23.2±8 months. Twenty patients (74%) were treated with a combination of MEK inhibitors and BRAF inhibitors (trametinib/dabrafenib), 5 patients (19%) were treated with MEK inhibitor monotherapy (cobimetinib), and 2 patients (7%) were treated with BRAF inhibitor monotherapy (vemurafenib). The mean duration of ophthalmological follow-up was 77.8±29 days, and the delay between the start of therapy and the emergence of symptoms was 87.2±78 days. The mean initial visual acuity was 0.075±0.13 logMAR, and the final visual acuity was 0.01±0.03 logMAR. Twelve patients (44%) developed ocular complications due to the targeted therapy. In the patients who received combination trametinib/dabrafenib, 5 patients (18.5%) developed clinical signs of uveitis, from acute anterior uveietis to panuveitis, and 2 patients (7.4%) developed bilateral central serous chorioretinopathy; in the patients who received cobimetinib, 4 patients (14.8%) developed bilateral central serous chorioretinopathy; and one patient (3.7%) who received vemurafenib developed acute anterior uveitis. For these 12 patients with ophthalmic side effects, temporary discontinuation of therapy was chosen for six patients (22.2%), three patients (11.1%) received half the initial dose, and for three patients (11.1%), normal dosing was continued. CONCLUSION: The two main side effects of targeted therapies are uveitis for BRAF inhibitors and central serous chorioretinopathy for MEK inhibitors. A multidisciplinary approach including ophthalmologists, dermatologists and oncologists is essential in order to adapt treatment in the advent of these ocular complications.

[Ocular syphilis, the rise of a forgotten disease: Retrospective study of 18 cases diagnosed at Amiens University Hospital]. / La syphilis oculaire, retour d'une maladie oubliée : étude rétrospective de 18 cas diagnostiqués au CHU d'Amiens.

OBJECTIVES: A disturbing resurgence of syphilis has been observed in the past few years. Ocular involvement of syphilis is infrequent. The goal of our study was to analyze the demographic data and clinical features and to analyze visual outcomes in cases of ocular syphilis at Amiens UH between January 1, 2015 and December 31, 2019. MATERIAL AND METHODS: This descriptive, observational, single-center study included a retrospective cohort of patients who were diagnosed with ocular syphilis. The data collected were demographic data (age, sex and sexual orientation), history of risky sexual behavior, HIV status and potential co-infections, stage of syphilis, chief complaint, initial and final logMAR visual acuity, biomicroscopic examination of the anterior segment, dilatated fundus examination, extraocular clinical manifestations and treatment initiated. RESULTS: Twenty-four eyes of eighteen patients (17 men and 1 woman) with a mean age of 48±12 were included in the study. 9 patients were homosexual, and 9 were heterosexual. A history of risky sexual behavior was noted in 6 patients (33.3%), and 4 patients (22%) were HIV positive. 2 patients (11.1%) had primary syphilis, 14 patients (77.7%) had secondary syphilis and 2 patients (11.1%) had tertiary syphilis. All patients were symptomatic, and vision loss was the main ophthalmologic symptom. The mean initial visual acuity was -0.55±0.56 logMAR, and the final visual acuity was 0.04±0.07 logMAR. Posterior uveitis was the predominant type of involvement (42%), and 9 patients presented with neurosyphilis. 11 patients (61.1%) showed extraocular clinical manifestations. 9 patients (50%) received subcutaneous ceftriaxone 2g, 6 patients (33.3%) received daily intravenous benzylpenicillin G, 2.4 million IU, and 3 patients (16.6%) were treated with oral doxycycline 200mg. CONCLUSION: Ocular syphilis remains a diagnostic and therapeutic challenge because of the various ocular manifestations it provokes. Since this pathology can result in severe damage, every clinician who diagnoses uveitis should consider the possibility of syphilis so as to avoid any delay in treatment. Even though ocular syphilis remains a rare clinical entity, it is a potentially devastating infection.

[Ocular tuberculosis]. / Tuberculose oculaire.

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.

[Therapeutic strategy for the treatment of non-infectious uveitis proposed by an expert panel]. / Avis d'experts pour le traitement des uvéites non infectieuses.

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

[Eales' disease]. / La maladie de Eales.

The syndrome of recurrent vitreous hemorrhages in young men was described for the first time by Henry Eales in 1880. The association with a clinical manifestation of ocular inflammation was reported 5years later. Eales disease affects young adults who present with ischemic retinal vasculitis, with the peripheral retina most commonly affected. Most cases have been reported in South Asia. Although the etiology of this abnormality is unknown, it may be related to an immune sensitivity to Mycobacterium tuberculosis antigens. Its pathogenesis is related to extensive ischemia that affects the retina, secondary to an obliterative retinal vasculopathy with release of angiogenic factors of the VEGF type. Involvement of the retina is the hallmark of the disease, which manifests as follows: periphlebitis, retinal capillary ischemia most often affecting the periphery with secondary proliferative retinopathy and retinal and/or papillary neovascularization, recurrent vitreous hemorrhages and tractional retinal detachment. These complications are potentially blinding. The natural history of Eales disease varies, with temporary or permanent remission in some cases and continuous progression in others. Progression is often bilateral, which necessitates regular follow-up. The treatment of Eales disease depends on the stage of the disease and is not well defined. Observation only, pars plana vitrectomy surgery and/or intravitreal injections of anti-VEGF are recommended in cases of vitreous hemorrhage, associated with corticosteroids when retinal vasculitis is present. Laser pan-retinal photocoagulation is necessary when neovascularization is present.

Correlation between aqueous flare and chorioretinal neovascularization in age-related macular degeneration following intravitreal bevacizumab injections.

PURPOSE: Prospective evaluation of aqueous flare following intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization due to age-related macular degeneration. PATIENTS AND METHODS: Sixteen eyes of eight patients were recruited. Aqueous humor flare was determined by laser flare meter every month after one intravitreal injection of 1.25mg of bevacizumab at baseline followed by a second injection at month3 (day 100±21days). Four patients received an injection at month6 (±10days), and one patient received an injection at month7. RESULTS: Two months after the first intravitreal bevacizumab injection, flare values decreased from 10±5.57 (mean±standard deviation) to 5.2±1.69photon count/ms (P=0.0207) and from 8.3±3.59 to 5.4±0photon counts/ms, 2months after the second injection (P=0.02). CONCLUSION: Significantly decreased aqueous humor flare levels were noted after repeated injections of bevacizumab.

[A rare case of cystoid maculopathy]. / Un cas rare de maculopathie cystoïde.

We describe the case of a healthy 67-year-old Caucasian female who developed a rare, reversible case of cystoid maculopathy without late leak on fluorescein angiogram. She presented initially with a 5-year history of bilateral, variable central scotomata. The visual acuities were 6/6, while foveal reflexes were abnormal. Fluorescein angiogram showed no leakage; however, optical coherence tomography (OCT) revealed cystic spaces in the fovea of both eyes. The patient had been taking niacin supplements averaging 100mg daily for 30 years. Niacin was discontinued, and 7 months later, her symptoms and OCT results improved. Although niacin-induced maculopathy is uncommon, the clinician should enquire about possible niacin supplementation in any patient with cystoid macular edema in the absence of late leakage on fluorescein angiography. We describe a new reason for niacin maculopathy due to chronic low dose niacin supplementation and a slower pattern of visual recovery than that previously suggested in the literature.

[Unusual retinal abnormality: retinal hemorrhages related to scurvy]. / Une cause inhabituelle d'anomalies rétiniennes, hémorragies rétiniennes révélatrices de scorbut.

A diet restricted to rice and boiled fruit and vegetables leads to vitamin C deficiency. We describe the third case, to our knowledge, of retinal hemorrhages related to scurvy. Reduced bilateral visual acuity in a 50-year-old patient was associated with macrocytic anemia, denutrition, and cutaneous ecchymoses. Oral vitamin C treatment provided subjective clinical improvement and regression of the retinal hemorrhages on fundus examination, with no side effects. Vitamin C plays an important role in collagen stability in vascular and bone walls.

[25-Gauge transconjunctival vitrectomy in a case of bilateral epiretinal membrane associated with a Terson syndrome]. / Membrane épirétinienne bilatérale associée à un syndrome de Terson traitée par vitrectomie transconjonctivale sans suture à 25-gauges.

The formation of epiretinal membranes associated with proliferative vitreoretinopathy is known to be a complication of Terson syndrome. We report the first case of a 25-Gauge transconjunctival sutureless vitrectomy performed in one eye as treatment for an epiretinal membrane secondary to a case of Terson syndrome (most probably due to a history of subdural hematoma in childhood). Following a review of the current literature on the subject we report the physiopathologic mechanisms of Terson syndrome and the explanation for the proliferative vitreoretinopathy formation.

[Severe disseminated toxoplasmosis with atypical chorioretinitis. A case of primary infection]. / Toxoplasmose disséminée sévère avec choriorétinite atypique : à propos d'un cas de primo-infection.

The clinical diagnosis of ocular toxoplasmosis is based on clinical features and biological tests: polymerase chain reaction (PCR) and the determination of intraocular specific antibody secretion (Goldmann-Witmer coefficient) on aqueous humor. Older patients may have a higher prevalence of ocular involvement and more severe ocular disease during the acute phase of recently acquired systemic infection because of altered cell-mediated immunity. Moreover, the genotype of the infecting parasite (particularly involving neotropical Type I Toxoplasma gondii strain), appears to be an important determinant of disease severity.

Cerebral immunoglobulin light chain amyloid angiopathy-related hemorrhages.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage (ICH) particularly in elderly patients. In CAA-related hemorrhages, amyloid deposits in the brain vessel walls mainly contain amyloid beta-protein (A-beta). Rarely other forms of amyloid substances have been reported in sporadic CAA-related hemorrhages. METHODS: We report the case of a 44-year-old patient with recurrent ICH who had surgical evacuation of a large frontal hematoma. Following surgery, samples from the hematoma and adjacent cerebral cortex were obtained for histopathological examination. RESULTS: Within the recent hemorrhage, a few arteriolar walls were thickened with an amyloid deposit that was immunostained for immunoglobulin (Ig) M and light chain lambda. In the wall of some vessels, around the amyloid deposits, as well as in the adjacent cerebral cortex, there was an infiltration by monotypic lymphocytes and plasma cells expressing IgM and light chain lambda. No amyloid deposition was found outside the hemorrhage. There was no evidence of multiple myeloma, B-cell malignancy, or systemic amyloidosis. CONCLUSIONS: Recurrent ICH may be due to amyloid deposition of IgM lambda produced by monotypic proliferation of lymphocytes and plasma cells purely localized to the brain.

[Optical coherence tomography: a reliable tool for localisation of macular hemorrhage. Two case reports]. / Intérêt de la tomographie par cohérence optique pour localiser une hémorragie maculaire. A propos de deux cas.

Recent observations have found that premacular hemorrhage in Valsalva retinopathy is located under the internal limiting membrane. We confirm these findings in two case reports of Valsalva retinopathy. Visual acuity rehabilitation was obtained in the first case by conservative treatment and by draining the hemorrhage into the vitreous with Neodymium (Nd):Yag laser in the second case. We report the current therapeutic guidelines for Valsalva retinopathy, including the systematic search of autosomal dominant syndrome of retinal arterial tortuosity, a rare condition, often discovered after this type of benign macular hemorrhage.

[Usefulness of voriconazole in treatment of Phoma glomerata after penetrating injury]. / Endophtalmie à Phoma glomerata après plaie du globe et efficacité du traitement par voriconazole en intravitréen.

We report the first case of endophthalmitis caused by Phoma glomerata. A 32-year-old man who underwent retinal detachment surgery consecutive to a penetrating globe injury presented with endophthalmitis 7 days after surgery. Anterior chamber tap and intravitreal injection of antibiotics (ceftazidime and vancomycin) were performed systematically. Fungus was observed at microscopic examination of the aqueous humor and treatment with intravitreal injection of amphotericin B was decided. The patient failed to improve with intravitreal amphotericin B but responded clinically to intravitreal voriconazole. The fungus was identified after culture as Phoma glomerata. The MIC for amphotericin B was 1microg/ml, for caspofungin was 2microg/ml, and for itraconazole was 8microg/ml or more. The MIC for voriconazole was up to 8microg/ml. The clinical response after intravitreal injection may be related to the high concentrations reached in the vitreous. Because of severity and ominous prognosis of intraocular fungal infections and posttraumatic Phoma ocular infections, aggressive management is required by intravitreal voriconazole administration.