[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.

Optic disc morphology in preterm children. Influence of gestational age and birth weight.

PURPOSE: The characteristics of the optic disc and the development of the optic nerve can affect visual function in children. The purpose of our study was to assess optic disc morphology in preterm infants and to determine whether it is influenced by gestational age, birth weight and the presence of a retinopathy of prematurity. METHODS: In a retrospective study, RetCam fundus images of 109 premature newborns admitted to our tertiary-level neonatal intensive care unit were reviewed. We evaluated the cup to disc ratio (C/D), optic disc diameter, cup diameter, shape of the optic disc, adherence to the ISNT rule, and presence of a peripapillary atrophy. RESULTS: Of 218 photos, we found the following results: mean±SD gestational age 28.5±2.7 weeks, mean±SD birth weight 1122±394g, mean C/D 0.32. There was no significant correlation between C/D and gestational age or birth weight. Vertical disc diameter was greater than horizontal disc diameter, with a mean ratio (horizontal/vertical) of 4/5, lending an oval shape to the optic disc. Nineteen infants had retinopathy of prematurity in both eyes; ninety-three percent had peripapillary atrophy. CONCLUSION: In our study, optic disc morphology in premature newborns was not influenced by gestational age, birth weight or presence of premature retinopathy.

Perfusion magnetic resonance imaging in pediatric brain tumors.

PURPOSE: The use of DSC-MR imaging in pediatric neuroradiology is gradually growing. However, the number of studies listed in the literature remains limited. We propose to assess the perfusion and permeability parameters in pediatric brain tumor grading. METHODS: Thirty children with a brain tumor having benefited from a DSC-MR perfusion sequence have been retrospectively explored. Relative CBF and CBV were computed on the ROI with the largest lesion coverage. Assessment of the lesion's permeability was also performed through the semi-quantitative PSR parameter and the K2 model-based parameter on the whole-lesion ROI and a reduced ROI drawn on the permeability maps. A statistical comparison of high- and low-grade groups (HG, LG) as well as a ROC analysis was performed on the histogram-based parameters. RESULTS: Our results showed a statistically significant difference between LG and HG groups for mean rCBV (p < 10-3), rCBF (p < 10-3), and for PSR (p = 0.03) but not for the K2 factor (p = 0.5). However, the ratio K2/PSR was shown to be a strong discriminating factor between the two groups of lesions (p < 10-3). For rCBV and rCBF indicators, high values of ROC AUC were obtained (> 0.9) and mean value thresholds were observed at 1.07 and 1.03, respectively. For K2/PSR in the reduced area, AUC was also superior to 0.9. CONCLUSIONS: The implementation of a dynamic T2* perfusion sequence provided reliable results using an objective whole-lesion ROI. Perfusion parameters as well as a new permeability indicator could efficiently discriminate high-grade from low-grade lesions in the pediatric population.

[Sensory and motor clinical presentation of congenital retraction syndromes: Stilling-Duane and Brown syndrome]. / Aspects cliniques sensoriels et moteurs des syndromes de rétractions congénitaux : syndrome de Stilling-Duane et syndrome de Brown.

INTRODUCTION: Congenital Brown syndrome and Stilling-Duane syndrome, two rare causes of strabismus are caused by fibrosis of one or more extraocular muscles. This series aims to report the clinical sensory and motor features of patients with Brown or Stilling-Duane syndrome. METHODS: Seventeen patients' records were retrospectively assessed for: the ocular deviation in primary position and in the 9 positions of gaze, head tilt, visual acuity and binocular vision. RESULTS: Eleven patients with Stilling-Duane syndrome had a mean age of 12 years, and monocular involvement, most frequently of type I. The ocular deviation was variable; 16 patients had an abnormal head position, while 50 % presented with amblyopia, and only 37 % achieved fusion in the compensatory head posture. Six patients presented with congenital Brown syndrome at mean age of 6 years. Three had a moderate form, 3 had a severe form with vertical deviation in primary position, compensatory head position, amblyopia and binocular vision impairment. DISCUSSION: The motility impairments depend highly on the identified syndrome, its classification and its severity. Therefore, these two retraction syndromes present some common features. Strabismus in primary position may lead to amblyopia and binocular vision impairment. CONCLUSION: Clinical motility and sensory assessment is essential, though difficult, to establish the diagnosis and the management of patients with retraction syndromes.

[Retinopathy of prematurity]. / Rétinopathie du prématuré.

Retinopathy of prematurity is a retinal vasoproliferative disease affecting extremely preterm infants exposed to high concentrations of oxygen therapy. Infants born before 32 post-menstrual weeks or with a birth weight of less than 1500g should systematically have a dilated fundus examination. The time of screening and schedule for follow-up are guided by the various risk factors. This disease results from immaturity of the peripheral retinal vessels at the time of premature birth. The classification of ROP depends on the anteroposterior extent of involvement (from center to periphery: zone I, II and III), its extension in 30° sectors (clock hours) and its stage (stage 1 to 5). "Plus" disease is defined as dilation and tortuosity of the retinal blood vessels in the posterior pole of the eye and represents a major risk factor for rapid unfavorable progression. A majority of patients will spontaneously recover, but patients with a high risk of progression will require treatment to prevent retinal detachment and blindness. The indications for treatment are threshold disease and type 1 pre-threshold disease. The current treatment of choice is peripheral retinal ablation with transpupillary laser, but ab externo cryotherapy may be used instead. Intravitreal injection of vascular endothelial growth factor inhibitors may be an attractive therapeutic option and is currently under investigation. After laser treatment, unfavorable outcomes occur in only 9 to 14 % of eyes, but at the price of peripheral retinal destruction. For all patients, whether treated or not, a regular fundus examination should be insured until complete retinal vascularization has occurred.

Tolerability of intracameral cefuroxime during cataract surgery in case of penicillin allergy.

INTRODUCTION: Since the results of the ESCRS study in 2007 and then the AFSSAPS recommendations of 2011, postoperative endophthalmitis prophylaxis in cataract surgery has evolved toward intracameral cefuroxime. Penicillin allergy is frequent and is not considered as a contra-indication to cefuroxime injection, but cross-reactions do exist. The goal of this study was to assess the tolerability of intracameral cefuroxime in patients with a penicillin allergy. MATERIALS AND METHODS: In this monocentric open prospective study, adult patients undergoing cataract surgery and declaring themselves penicillin-allergic were included. A subcutaneous test of cefuroxime was performed preoperatively. If negative, patients received the intracameral injection of cefuroxime at the conclusion of the surgical procedure. The primary assessment criteria, evaluated on the day after the surgery, was the occurrence of allergic reactions. RESULTS: Forty-eight eyes of 40 patients, 72 ± 8 years old, were included. Forty-three skin tests were performed: 1 was positive and one was unreliable. Thirty-six patients were examined in our center the day after the surgery: 2 presented a conjunctival allergic reaction. No severe anaphylactic reaction was reported. DISCUSSION: Of our patients, 95.3% declaring a penicillin allergy had a negative pre-operative cefuroxime test. According to literature, 80 to 90% of presumed penicillin allergic patients would not actually be allergic to cefuroxime. In our population, we reported 2 benign conjunctival cross-reactions. CONCLUSION: Intracameral cefuroxime injection during cataract surgery seems well-tolerated in penicillin-allergic patients with a negative preoperative skin test.

[Pediatric orbital cellulitis without sinusitis: report of four cases]. / Cellulites orbitaires atypiques d'origine non sinusienne de l'enfant : à propos de quatre cas.

INTRODUCTION: Pediatric orbital cellulitis is most often caused by ethmoid sinusitis. We present a description of 4 atypical cases of orbital cellulitis without sinusitis. PATIENTS AND METHODS: A 4-day-old girl presented with medical canthal swelling and preseptal cellulitis caused by bilateral congenital dacryocystoceles. The second patient was an 8-year-old boy seen for infectious conjunctivitis complicated by preseptal cellulitis without sinusitis. Conjunctival cultures revealed Neisseria gonorrheae. The next patient, a 5-month-old boy, presented with lid swelling, fever, proptosis and epiphora. It was caused by dacryocystitis extending into the ethmoid and complicated by a sub-periostal abscess with mass effect on the globe. The fourth patient was a 10-year-old boy referred for inflammatory eyelid edema and severe non-axial proptosis. Imaging revealed an orbital tumor; the diagnosis of rhabdomyosarcoma was confirmed by anatomopathology. DISCUSSION: Thorough etiologic work-up of orbital cellulitis in children will prevent missing a non-sinus-based cause such as lacrimal infections, conjunctivitis secondary to atypical pathogens, or even tumors. All patients should undergo a detailed clinical examination, orbital imaging and microbiological testing. CONCLUSION: Orbital cellulitis in children poses diagnostic and therapeutic difficulties due to the many possible etiologies. Aside from sinusitis, the most important etiologies to pursue are lacrimal system infections and tumors. When confronted with a non-specific clinical presentation, thorough etiologic work-up is essential, in view of the potential life-threatening, functional and social implications.