Livia Lumbroso

Chemothermotherapy in the management of retinoblastoma

OBJECTIVE To evaluate the results of chemothermotherapy for the treatment of retinoblastoma. DESIGN Non-comparative interventional case series. PATIENTS Fifty-one children (65 eyes and 103 tumors) were treated with chemothermotherapy in a single institution from January 1995 to May 1998. METHODS Chemothermotherapy consists of a combination of transpupillary thermotherapy delivered shortly after intravenous (IV) injection of carboplatin (560 mg/m(2)). Each tumor is treated separately with a diode laser using a microscope. Laser intensity, spot size, and duration are adapted to the size of each tumor and to the clinical response. After 8 days, thermotherapy alone is repeated. This cycle is performed from one to six times, every 28 days. The treatment data and outcome are analyzed separately. MAIN OUTCOME MEASURES Assessment of local tumor control. RESULTS One hundred three tumors were treated in 65 eyes of 51 children. Age at diagnosis was 0 to 60 months (median, 7 months). Median tumor diameter at the time of treatment was 3.5 mm (range, 1.5-12 mm). Laser modalities were as follows: median intensity, 450 mW (range, 150-1000 mW); median spot size, 1.2 mm (range, 0.3-2.0 mm); and median number of cycles required to obtain tumor control, three. Tumor regression was obtained for 99 tumors (96.1%) after a median follow-up of 30 months (17-61 months). Seven tumors relapsed after initial control (6.8%). Salvage treatment (external beam radiation, iodine plaques, or enucleation) was necessary for a total of 11 tumors (10.7%). The only risk factor for relapse was the initial diameter of the lesion greater than 3.5 mm, whereas the other tumor characteristics or treatment variables were not significantly correlated with relapse. Ninety-seven percent of treated eyes were able to be preserved, and 92% of cases were treated without external beam radiation. CONCLUSIONS Chemothermotherapy is an effective technique to treat small- to medium-sized retinoblastomas in children, avoiding external beam irradiation.

Acute posterior multifocal placoid pigment epitheliopathy associated with Wegener's granulomatosis.

PURPOSE To report acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in the course of systemic Wegeners granulomatosis. METHODS A complete ophthalmologic evaluation was undertaken, including fluorescein and indocyanine green angiography. RESULTS Two patients diagnosed with Wegeners granulomatosis developed multiple white-yellow subretinal areas with smooth margins typical of APMPPE. Case 1 presented with bilateral choroidal involvement and a granulomatous anterior uveitis. In Case 2, placoid lesions were diagnosed 2 months after onset of systemic Wegeners granulomatosis. In both cases, fluorescein angiography showed an early hypofluorescence and a late staining of the lesions. Indocyanine green angiography revealed early and late hypofluorescence corresponding to the areas seen clinically. Wegeners granulomatosis was diagnosed histologically in both cases. After combined steroid and cyclophosphamide therapy, the lesions healed, and after a follow-up period of 1.5 and 4 years, respectively, funduscopic and angiographic examinations showed cicatricial lesions. CONCLUSION Acute posterior multifocal placoid pigment epitheliopathy is a rare manifestation of Wegeners granulomatosis and should be considered a possible systemic involvement of the disease. A prompt, thorough investigation should be undertaken for an underlying systemic disorder.

Ultrasound biomicroscopy in peripheral retinovitreal toxocariasis.

PURPOSE To report ultrasound biomicroscopic features in peripheral retinovitreal Toxocara uveitis. METHODS Three patients with unilateral vitreitis suspected to be caused by peripheral toxocariasis were referred for ultrasound biomicroscopic examination of the peripheral retina, pars plana, and adjacent vitreous. RESULTS In two of the three patients, characteristic pseudocystic transformation of the peripheral vitreous was seen. In both patients, Toxocara serology was positive and eosinophilia was present. In the third patient, no pseudocystic transformation of the peripheral vitreous was seen; however, there was the dense thickening adjacent to the pars plana usually seen by ultrasound biomicroscopy in pars planitis and corresponding to clinically visible snowbanks. The third patient had a negative Toxocara serology and later developed bilateral intermediate uveitis of the pars planitis type. In none of 48 patients with diverse inflammatory conditions of the retroiridal space that were examined by ultrasound biomicroscopy were the characteristic Toxocara-associated pseudocystic images seen. CONCLUSIONS Pseudocystic transformation of the peripheral vitreous appears to be a rather specific and sensitive ultrasound biomicroscopic sign in patients with presumed peripheral toxocariasis that will likely aid diagnosis in difficult cases.

Cystoid macular oedema and cytomegalovirus retinitis in patients with HIV disease treated with highly active antiretroviral therapy

BACKGROUND Although cystoid macular oedema (CMO) is a rare cause of visual loss in AIDS related cytomegalovirus (CMV) retinitis, nine cases are reported of CMO occurring in HIV infected patients with a prior diagnosis of CMV who were receiving highly active antiretroviral therapy (HAART). METHODS Medical and ophthalmological records of nine AIDS patients with inactive CMV retinitis were retrospectively analysed. Ophthalmic examination data, laboratory findings, and the systemic antiviral treatment were studied. Ophthalmic examination included visual acuity, anterior chamber flare measured with the laser flare cell meter (LCFM), vitreous haze quantification according to the Nussenblatt grading system, and fluorescein angiography. RESULTS Nine HIV infected patients, eight men and one woman, mean age 39 years (range 29–53 years) presented with inactive CMV retinitis and CMO. On fluorescein angiography, CMO was present only in eyes (14 eyes) with signs of previous CMV retinitis. CMV retinitis was inactive in all of them. Visual acuity ranged from 20/200 to 20/30. In 10 eyes with CMV retinitis, anterior chamber flare measured with the LCFM ranged from 18.5 to 82 photons/ms (mean 35.42 ph/ms). A significant vitreous inflammation (1.5+) was observed in eight eyes. All patients had been treated with anti-CMV drugs for a mean period of 18 months (range 12–36 months). All nine patients received HAART with a combination of two nucleotide analogue reverse transcriptase inhibitors and one protease inhibitor for a mean period of 14 months (range 9–18 months). The HIV viral load was below detectable levels (<200 copies/ml) in eight patients and low (3215 copies/ml) in one. At the time of CMO, the median CD4+ lymphocyte count was 232 cells × 106/l (range 99–639). CONCLUSION In AIDS patients, the usual absence of intraocular inflammation in eyes affected by CMV retinitis has been tentatively explained by the profound cellular immunodeficiency. In these patients, treated with HAART, CD4+ counts were increased for several months (mean 14 months). In their eyes, CMV retinitis was associated with significant ocular inflammation and CMO. These findings could be related to the restoration of immune competence after HAART as recently shown.

ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY ASSOCIATED WITH WEGENERʼS GRANULOMATOSIS

Purpose:To report acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in the course of systemic Wegeners granulomatosis.Methods:A complete ophthalmologic evaluation was undertaken, including fluorescein and indocyanine green angiography.Results:Two patients diagnosed with Wegeners g

Imagerie des tumeurs du segment antérieur : avantages respectifs de l’échographie (10, 20 et 50 MHz) et de la tomographie en cohérence optique

But Preciser le role des differents types d’imagerie pour le diagnostic des tumeurs de l’iris. Materiel et methodes Soixante et une tumeurs de l’iris ont beneficie d’une exploration par echographie a 10 et 20 MHz (Cinescan de BVI Quantel Medical) et 50 MHz (UBM de Paradigm) et par tomographie en coherence optique (OCT) (Humphrey Zeiss). Resultats L’echographie doit beneficier d’une frequence au moins egale ou superieure a 20 MHz afin de pouvoir caracteriser, localiser et mesurer avec precision une lesion. La biomicroscopie ultrasonore (BMU) est insuffisante pour mesurer les tumeurs volumineuses (s’etendant vers l’arriere au corps ciliaire), du fait de la cellule d’exploration et d’une attenuation importante par la lesion. L’echographie seule ne permet pas de caracteriser une lesion solide, en particulier de differencier une lesion benigne d’une lesion maligne, et les notions cliniques sont egalement importantes pour le diagnostic et la prise en charge therapeutique. L’OCT permet de reconnaitre la nature liquide ou solide d’une lesion dans certains cas. Conclusion Devant une tumeur d’allure solide, il faut pratiquer rapidement un examen de BMU a 50 MHz, et si la lesion est difficile a voir en totalite, une echographie a 20 MHz. Devant une saillie de l’iris, l’echographie de haute frequence et l’OCT permettent de differencier une lesion kystique d’une masse solide, mais seule la BMU permet une mesure precise et une surveillance reguliere de la tumeur.

Intraocular inflammation after proton beam irradiation for uveal melanoma

AIM To describe the inflammatory reaction that can occur following proton beam irradiation of uveal melanomas based on a large series of patients and to try to determine the risk factors for this reaction. METHODS Data from a cohort of patients with uveal melanoma treated by proton beam irradiation between 1991 and 1994 were analysed. The presence of inflammation was recorded and evaluated. Kaplan-Meier estimates and statistical analysis of general and tumour related risk factors were performed. RESULTS 28% of patients treated during this period presented with ocular inflammation (median follow up 62 months). Risks factors were essentially tumour related and were correlated with larger lesions (height > 5 mm, diameter > 12 mm, volume > 0.4 cm3). Multivariate analysis identified initial tumour height and irradiation of a large volume of the eye as the two most important risk factors. Ocular inflammation usually consisted of mild anterior uveitis, resolving rapidly after topical steroids and cycloplegics. The incidence of inflammation after proton beam irradiation of melanomas seems higher than previously reported and is related to larger lesions. Evidence of inflammation associated with uveal melanoma has been described and seems to be associated with tumour necrosis (spontaneous or after irradiation). The appearance of transient inflammation during the follow up of these patients may be related to the release of inflammatory cytokines during tumour necrosis. CONCLUSION Inflammation following proton beam irradiation is not unusual. It is correlated with larger initial tumours and may be related to tumour necrosis.

The survival gene MED4 explains low penetrance retinoblastoma in patients with large RB1 deletion

Retinoblastoma is a non-hereditary as well as an inherited pediatric tumor of the developing retina resulting from the inactivation of both copies of the RB1 tumor suppressor gene. Familial retinoblastoma is a highly penetrant genetic disease that usually develops by carrying germline mutations that inactivate one allele of the RB1 gene, leading to multiple retinoblastomas. However, large and complete germline RB1 deletions are associated with low or no tumor risk for reasons that remain unknown. In this study, we define a minimal genomic region associated with this low penetrance. This region encompasses few genes including MED4 a subunit of the mediator complex. We further show that retinoblastoma RB1 -/- cells cannot survive in the absence of MED4, both in vitro and in orthotopic xenograft models in vivo, therefore identifying MED4 as a survival gene in retinoblastoma. We propose that the contiguous loss of the adjacent retinoblastoma gene, MED4, explains the low penetrance in patients with large deletions that include both RB1 and MED4. Our findings also point to another synthetic lethal target in tumors with inactivated RB1 and highlight the importance of collateral damage in carcinogenesis.

Résultats du traitement du mélanome malin de l’uvée par faisceau de protons : 10 ans de recul

Introduction Nous avons etudie les resultats a long terme du traitement par faisceau de protons du melanome malin de l’uvee sur une serie de patients ayant un recul minimum de 10 ans. Patients et methodes Les patients ont ete traites par faisceau de protons entre septembre 1991 et decembre 1992. Ils ont eu un bilan initial comprenant une acuite visuelle, un fond d’œil, une echographie et une biometrie de l’œil, des photographies du fond d’œil et une angiographie ainsi qu’un bilan general comprenant une radiographie pulmonaire et une echographie hepatique. Nous avons delivre une dose de 60 Gray equivalent cobalt en 4 fractions sur 4 jours successifs au centre de protontherapie d’Orsay. Resultats Cent soixante-sept patients ont ete traites avec un recul median de 116 mois. L’âge median etait de 59 ans. Treize tumeurs etaient anterieures a l’equateur, 76 a cheval sur l’equateur et 78 en arriere de l’equateur. Un decollement de retine etait note dans 41 cas ; la papille etait envahie dans 10 cas. Le diametre tumoral median etait de 12 mm et l’epaisseur tumorale mediane de 5,8 mm. L’acuite visuelle initiale moyenne etait de 4/10 e . La survie globale a 10 ans etait de 62,9 %. 72,9 % des deces etaient en relation avec des metastases du melanome. Les facteurs influencant la survie de maniere statistiquement significative en analyse multivariee etaient un diametre tumoral superieur a 12 mm (p = 0,0004) et un âge superieur a 60 ans (p = 0,0001). Le taux de metastases a 10 ans etait de 31 %. Les metastases touchaient le foie dans 97,8 % des cas. Les facteurs de risque en analyse multivariee pour l’apparition de metastases etaient le siege anterieur de la tumeur, un volume superieur a 0,4 cm 3 et la presence d’un decollement retinien initial. Le taux d’enucleation secondaire a 10 ans de 13,2 % etait lie principalement a des complications post therapeutiques notamment le glaucome neovasculaire. Le taux de recidives locales etait de 6 %. 42,1% des patients avaient une acuite visuelle superieure a 1/10 e a 10 ans. La baisse visuelle etait liee principalement a une maculopathie ou a une papillopathie postradique. Conclusion Cette etude confirme les resultats de la litterature concernant le traitement par faisceau de protons a long terme. Cette therapeutique permet un bon controle local de la tumeur, un excellent taux de conservation oculaire et le maintien d’une acuite visuelle utile pour presque la moitie des cas.

Les rétinopathies radio-induites

Radiation retinopathy is a retinal microangiopathy, observed after irradiation of the eye. It can rarely lead to neovascular glaucoma and enucleation due to pain. It is due to a progressive retinal capillary then vascular occlusion. Total irradiation dose, dose fraction, and surface of the irradiated retina seem to be strong predictive factors for radiation retinopathy. Patients who underwent an irradiation near the eye (skull base tumors, nasal and paranasal tumors, or brain tumors) should be followed by periodic ophthalmologic examination to detect and treat when necessary the non perfusion areas.