[Adjuvant contact radiotherapy for conjunctival malignancies: Preliminary results of a series of 14 patients treated with the Papillon 50 machine]. / Radiothérapie de contact adjuvante des tumeurs malignes de la conjonctive : résultats préliminaires d'une série de 14 patients traités avec l'appareil Papillon 50.

PURPOSE: To evaluate the results of an adjuvant contact irradiation using 50kV photons after resection of conjunctival malignancies. MATERIALS AND METHOD: From 2012 to 2014, 14 patients (male: nine; female: five) have been treated by contact irradiation after resection of a malignant tumor of the conjunctiva (melanoma: five patients; malignant fibrous histiocytoma: one patient; carcinoma: eight patients) The treatment was performed using the Papillon 50 machine (Ariane). Three to four sessions were delivered, each giving a dose of 10Gy. The median follow-up in survivors was 33 months. RESULTS: The tolerance was good. A cataract was seen in one patient, and a moderate eye dryness in one. There was no corneal ulcer. One patient died of intercurrent disease. One patient with carcinoma recurred locally. CONCLUSION: Adjuvant contact radiotherapy provides a good local control after resection of conjunctival malignancies (melanoma, malignant histiocytofibroma, carcinoma). Thanks to its precision, this technique is well tolerated with a low rate of complications. Furthermore, it is delivered on an ambulatory basis.

[Intensity-modulated radiotherapy of head and neck cancers: Dose effects on the ocular, orbital and eyelid structures]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures : dose de tolérance de l'œil et des voies optiques.

Radiation-induced damage of ocular, orbital and eyelid structures are mainly reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume relationships are, however, inaccurate due to the small volume of most of the organs at risk involved and limited ability of irradiation techniques to spare these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The ability of newest radiation techniques including IMRT and proton therapy to generate steep dose gradients may yield more accurate models in the future. Some toxicities are severe and irreversible, leading to vision loss, as in the case of radiation-induced optic neuropathy for which curative treatments are suboptimal. Other toxicities can lead to reversible vision loss but can be surgically corrected, as is the case for radiation-induced cataract. In this paper, we will review the dose effects for the ocular; orbital and eyelid structures.

[Application of gene therapy to oncologic ophthalmology]. / Application de la thérapie génique à l'onco-ophtalmologie.

Since the discovery of the structure of DNA in 1953 by Watson and Crick, our understanding of the genetic causes and the regulations involved in tumor development have hugely increased. The important amount of research developed since then has led to the development of gene therapy, which specifically targets and treats cancer cells by interacting with, and correcting their genetic material. This study is a review of the most accomplished research using gene therapy aimed at treating malignant ophthalmologic diseases, and focuses more specifically on uveal melanoma and retinoblastoma. Such approaches are remarkable regarding the efficiency and the cellular targeting specificity. However, gene therapy-based treatments are so recent that many long-term interrogations subsist. The majority of the reviewed studies are conducted in vitro or in murine models, thereby requiring several years before the resulting therapies become part of the daily ophthalmologists' arsenal. However, the recent spectacular developments based on advanced scientific knowledge justify an up-to-date review that would benefit the ophthalmologist community.

[Intravitreal injection of bevacizumab for naive myopic choroidal neovascularization: 19-month results]. / Néovaisseaux choroïdiens du myope fort naïfs traités par injections intravitréennes de bévacizumab : résultats à plus de 12 mois.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of bevacizumab in the first-line treatment of myopic choroidal neovascularization. PATIENTS: We report a retrospective study of patients with subfoveal or juxtafoveal choroidal neovascularization associated with pathologic myopia treated with intravitreal injection of bevacizumab in Lyon, France, from January 2009 to June 2010. Best-corrected visual acuity, ocular pressure, fundus examination, optical coherence tomography, and fluorescein angiography were performed for each patient at baseline and monthly. Indications for retreatment were persistent or recurrence of exsudative activity. RESULTS: The study included eight eyes of eight patients. The mean follow-up time was 19 months. The mean number of intravitreal injections was three at the end of the first year. Six patients maintained or improved their vision. No injection complications or drug-related side effects were noted during the follow-up period. CONCLUSIONS: In this study, intravitreal injection of bevacizumab seems to be a safe and effective treatment for myopic choroidal neovascularization.

[Late metastasis development in two cases of small choroidal melanoma]. / Neskorý rozvoj metastáz u pacientov s malým melanómom choroidey - 2 kazuistiky.

PURPOSE: To present data pointing out that small tumour size might not be a sufficient predictor of good prognosis of choroidal melanoma and present a new promising therapy of hepatic metastasis. METHODS: Retrospective, noncomparative case report of two patients with small choroidal melanoma. RESULTS: Two cases of small choroidal melanoma which developed metastases are described. Both patients underwent radiotherapy of the primary tumour. Metastases were treated by combined therapy in patient 1 while in patient 2 a new therapeutic modality of stereotactic radiotherapy, Cyberknife, was applied. Patient 1 died from metastatic spread 7,6 years after primary therapy despite a very good local tumour control. Patient 2 died 11,3 years after primary therapy due to intercurrent disease with a very good local eye findings and hepatic metastasis in regression. CONCLUSION: Choroidal melanoma of a small size can develop into metastatic disease even long time after satisfactory primary treatment. Further studies are required to assess the risk factors of metastatic spread in small uveal melanomas. Cyberknife stereotactic radiotherapy seems to be a promising therapeutic method of a solitary hepatic metastasis. Key words: choroidal melanoma, metastasis, prognostic factors, stereotactic radiotherapy.

Bevacizumab versus ranibizumab in the treatment of exudative age-related macular degeneration: a retrospective study of 58 patients.

AIM: To compare the efficacy and safety of bevacizumab versus ranibizumab in the treatment of patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Retrospective case-controlled series of 30 patients treated with intravitreal bevacizumab and 28 patients treated with intravitreal ranibizumab for exudative AMD. Main outcomes measured included best-corrected visual acuity (BCVA), central macular thickness (CMT) and foveal thickness, quantity of subretinal fluid, neovessel size and total number of injections over the first year treatment period. A secondary outcome was the report of any adverse events in both groups. RESULTS: BCVA stabilized and increased from LogMAR 0.70 to 0.47 in the bevacizumab group and from 0.55 to 0.54 in the ranibizumab group (P>0.05). CMT decreased in the bevacizumab group from 369 to 284 µm and in the ranibizumab group from 340 to 271 µm (P>0.05). The number of injection was significantly lower (4.8) in the bevacizumab group than in the ranibizumab group (5.8) (P<0.05). No serious ocular adverse events were noted in both groups. CONCLUSION: This retrospective study failed to show a difference in visual and anatomic outcomes between bevacizumab and ranibizumab. The number of re-treatment was lower in the bevacizumab group (P=0.03).

[Choroidal metastases of lung neoplasm treated with external radiotherapy and polychemotherapy: a study of four clinical cases]. / Métastases choroïdiennes de néoplasme bronchopulmonaire traitées par radiothérapie externe et cures de polychimiothérapie : étude de quatre cas cliniques.

AIM: To report the efficacy of external local radiotherapy in the treatment of choroidal metastases. PATIENTS AND METHODS: The study reports four cases of patients with choroidal metastases of lung neoplasm confirmed by the bronchial biopsy. Polychemotherapy was associated with external radiotherapy of the ocular metastases. DISCUSSION AND CONCLUSION: The external radiotherapy dose of 30 Gy to the posterior segment of the eye in 10 fractions was effective and seemed to be the most appropriate management of choroidal metastasis despite the use of the newest molecules in chemotherapy.

[Clinical and etiological aspects of uveitis: a retrospective study of 121 patients referred to a tertiary centre of ophthalmology]. / Aspects cliniques et étiologiques des uvéites: étude rétrospective de 121 patients adressés à un centre tertiaire d'ophtalmologie.

PURPOSE: Uveitis consists of a large group of diseases characterized by intraocular inflammation involving the uveal tract. This heterogeneity makes the diagnosis and the treatment of uveitis frequently challenging. The purpose of this study was to describe the various clinical and etiologic aspects of uveitis, through the new standardized uveitis classification and the use of modern investigations for its diagnostic work-up. METHODS: The medical records of 121 new patients with uveitis referred to our tertiary ophthalmologic centre between January 2002 and December 2006 were retrospectively reviewed. Uveitis associated to human immunodeficiency virus and secondary to exogenous endophthalmitis were excluded. All patients had a complete ophthalmological examination and appropriate clinical and paraclinical examination. The diagnosis was established according to the recent international criteria. RESULTS: One hundred and twenty-one patients were included. The four main etiologies were: toxoplasmosis (14%), sarcoidosis (11.6%), spondylarthritis or HLA B27-associated uveitis (13.2%) and Herpes virus infections (9.1%) that represented almost half of the uveitis causes (47.9%). Various diseases constituted the remaining causes of the uveitis (20.9%). Uveitis remained unexplained in the remaining 36 patients (29.7%). Overall, associated systemic diseases were diagnosed in 35.5% of our uveitis patients (34 patients), associated infectious conditions in 26.4% (32 patients) and specific ocular diseases in 8.3% (12 patients). CONCLUSION: Despite a limited number of patients, our study showed an etiologic distribution similar to that of the main series reported in the literature. Nevertheless, we observed an elevated frequency of sarcoidosis and systemic diseases, which emphasizes a management that takes into account standardized clinical and paraclinical criteria and the usefulness of a collaboration with the internist.

[Genomic profiling by comparative genomic hybridization: analysis of ten enucleated uveal melanoma cases]. / Apport de l'analyse par hybridation comparative génomique dans le mélanome uvéal : étude de dix cas énucléés.

AIM: To detect major chromosomal aberrations from enucleated uveal melanoma and relate them to hepatic metastasis and survival. PATIENTS AND METHODS: Ten uveal melanomas enucleated between 2005 and 2008 in the Lyon Croix-Rousse Hospital were retrospectively analyzed using a 19 000-clone comparative genomic hybridization microarray. RESULTS: The most frequent imbalances were the loss of chromosome 3 (8/10), gain of the 8q arm (7/10) or the entire chromosome 8 (2/10), and gain of the 6p arm (2/10). Most metastatic tumors (6/7) and all cases of death (5/5) concerned melanoma with monosomy 3 and gain of the 8q arm. DISCUSSION AND CONCLUSION: Genome-wide array comparative genomic hybridization is a reliable tool for identifying uveal melanoma genomic imbalances. Gains of the 8q arm with monosomy 3 are frequent and are strongly associated with poor outcome. Gains of the 6p arm are rare and have a better prognosis. There is a mutually exclusive relationship between monosomy 3 and chromosome 6 abnormalities in our study. These results confirm previously published reports.

[Treatment of circumscribed choroidal haemangiomas by photodynamic therapy: a review]. / Traitement des hémangiomes choroïdiens circonscrits par photothérapie dynamique : revue de la littérature.

Circumscribed choroidal hemangioma (CCH) is an uncommon benign vascular tumor of the choroid that is usually diagnosed when it causes a decrease in vision due to exudative retinal detachment. The classical treatments of CCH were photocoagulation and radiotherapy, which induced additional chorioretinal damage, explaining the poor visual prognosis even in adequately treated patients. It is difficult to compare these two therapeutic options, laser photocoagulation having been abandoned for many years due to the retractile retinal scars that it induced. Conventional radiotherapy and proton therapy with a total dose of 20 Gy gave and give good results but can be performed only by teams used to these types of treatment. Recently, photodynamic therapy (PDT), which allows a selective occlusion of vascular lesions without damaging overlying retinal structures, has emerged as a sound alternative for the treatment of CCH. Most of the clinicians used the standard treatment of age related macular degeneration by photodynamic therapy (TAP) study protocol with or without variations. The main variations brought to the TAP study protocol were the duration of the verteporfin infusion, and/or the increase of the laser power settings, and/or the increase of the duration of exposure, and/or the number of PDT spots (single spot or multiple spots, overlapping or not). Mid-term PDT results are very encouraging. PDT has been reported to bring about resolution of subretinal fluid and to reduce tumor thickness in almost all cases. Visual acuity was improved or stabilized in at least 80% of the cases. Several studies reported on minor local side effects following PDT, consisting of atrophy and proliferation of the retinal pigment epithelium, atrophy of the choroid, transient choroidal effusion, and mild subretinal fibrosis. Published data demonstrated that PDT is a safe and effective alternative to radiotherapy or photocoagulation as first-line therapy for CCH.

[Use of sorafenib in patients with hepatocellular or renal carcinoma]. / Bon usage du sorafénib chez les patients pris en charge pour un carcinome hépatocellulaire ou un cancer du rein.

Therapeutic approaches of cancers have been recently improved by the development of targeted therapies. Amongst these new drugs, some anti-angiogenic molecules have been approved by either the EMEA or the Food and Drug Administration. Sorafenib, one of these inhibitors of angiogenesis, has been established as the standard of care for advanced hepatocellular and renal carcinoma. This paper reviews the safety profile of sorafenib and presents guidelines for the prevention and the treatment of the main side effects associated with this molecule.

Uveal effusion induced by topical travoprost in a patient with Sturge-Weber-Krabbe syndrome.

PURPOSE: To report a case of uveal effusion with subtotal exudative retinal detachment induced by topical administration of travoprost. CASE REPORT: A 20-year-old woman with a medical history of right-sided Sturge-Weber-Krabbe syndrome and bilateral aphakia secondary to congenital cataract extraction was referred to our department for retinal detachment associated with uveal effusion of the right eye. The ocular manifestations of Sturge-Weber-Krabbe syndrome in her right eye were glaucoma and diffuse choroidal hemangioma. Antiglaucomatous medications using topical travoprost 0.004%/timolol 0.5% (fixed combination) had been begun 1 week before. An adverse effect of travoprost was suspected and the drug was discontinued. Three weeks later, a fundus examination showed total disappearance of the uveal effusion. CONCLUSIONS: Interaction of the effects of topical prostaglandin analogs (blood-aqueous barrier disruption, enhancement of uveoscleral outflow) with both the diffuse choroidal hemangioma and the elevated episcleral venous pressure may lead to uveal effusion in Sturge-Weber-Krabbe syndrome. In spite of their efficiency, prostaglandin F2 analogs (latanoprost, travoprost and bimatoprost) should be used with caution in Sturge-Weber-Krabbe syndrome and particularly in cases of proved diffuse choroidal hemangioma.

[Outcome of photodynamic therapy for subretinal neovascularization secondary to choroidal nevi]. / Résultats de la photothérapie dynamique dans le traitement des néovaisseaux sous-rétiniens secondaires aux naevi choroïdiens.

INTRODUCTION: Choroidal nevi are the most common benign intraocular tumors. However, the occurrence of subretinal neovascularization secondary to choroidal nevus is very rare. Our goal was to assess the efficacy and the safety of photodynamic therapy (PDT) for treatment of subretinal neovascularization related to choroidal nevi. PATIENTS AND METHOD: We conducted a retrospective study including subretinal neovascularization secondary to choroidal nevi treated by PDT from 1999 to 2005. PDT was performed according to the standard protocols used for treating neovascularization due to age-related macular degeneration (ARMD). Post-PDT follow-up was also done according to the guidelines used in ARMD. Moreover, tumors were followed up every 3 months. RESULTS: Six subretinal neovascularizations secondary to choroidal nevi were included in our study. All nevi were localized in the posterior choroids. The median diameter of tumors was 3mm and their thickness was less than 2mm in all cases. Subretinal neovascularizations were classic in five cases. The last case was a small vascularized pigment epithelium detachment. Locations were subfoveal in two cases, juxtafoveal in three cases, and extrafoveal in one case. In half the cases, the size of subretinal neovascularization was 1-disk-diameter or less. A mean of 3.3 sessions of PDT were necessary to obtain the stabilization of subretinal neovascularization on both fluorescein angiography and OCT. The average follow-up period was 35 months with no patients lost to follow-up. Visual outcomes were extremely variable. Large or subfoveal neovascularization but also a history of atrophic ARMD were related to worse functional results. No growth of the nevi was observed. CONCLUSIONS: Subretinal neovascularization is reassuring from the oncologist's point of view because it is considered a relative indicator of benignity of the nevus. However, it often marks a definitive turning point in visual function. PDT appears to be a safe and effective procedure for the treatment subretinal neovascularization secondary to choroidal nevus, with results similar to those observed in ARMD.

Phenotypic expression of ferroportin disease in a family with the N144H mutation.

Ferroportin is a putative transmembrane channel involved in the exit of iron out of the enterocytes, the macrophages and the hepatocytes. Mutations in the human gene coding ferroportin have been linked to an unusual form of iron overload, now referred to as "hemochromatosis type IV" or "ferroportin disease" characterized by a prevalent iron overload of macrophages and liver Küpffer cells. We report four patients from a same family with ferroportin disease associated with the N144H mutation. We show that in this family the mutation which is fully penetrant, may act through an increased iron export from macrophages as suggested by the unexpected absence of iron overload in the spleen and bone marrow detected by magnetic resonance imaging, that it co-segregates with a phenotype close to the classical form of HFE-associated hemochromatosis and was associated, in the oldest patient, with the development of hepatocellular carcinoma in a non cirrhotic liver. Our findings illustrate the existence of a genotype-phenotype relationship in "ferroportin disease", suggest that MRI may be useful in determining this phenotype and show that hepatocellular carcinoma may occur in these patients even without cirrhosis. This observation justifies careful follow-up of this subgroup of patients.

Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402).

The FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P=.68), respectively. Multivariate analysis identified four independent prognostic factors for survival: alpha-fetoprotein (AFP)>400ng/mL (P=.008), abdominal pain (P=.011), hepatomegaly (P=.023) and Child-Pugh score (P=.032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P=.70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P=.58). In this subgroup, two prognostic factors were statistically significant for survival: AFP>400ng/mL (P=.004) and Spitzer Index (P=.013) as shown by multivariable analysis. In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.

Influence of intraocular lens material on the development of acute endophthalmitis after cataract surgery?

PURPOSE: To investigate the causal relationship between acute postoperative endophthalmitis (POE) after cataract surgery and the biomaterial properties of the intraocular lens (IOLs) implanted. METHODS: This retrospective cohort study included all patients who had undergone cataract surgery with IOL implantation at the Lyon Croix-Rousse University Hospital between 1st January 1994 and 31st December 2004. Details respecting the type of IOL implanted (material and manufacturer) were meticulously recorded. The number of patients presenting with POE within 6 weeks of cataract surgery was documented together with their medical characteristics. These data were then compared, and Fisher's exact test was used to establish the significance of any apparent associations. RESULTS: Eight of the 5837 eyes manifested acute POE (0.14%). Seven of these were composed of polymethylmethacrylate (PMMA) and one of heparinized PMMA. Patients with PMMA IOLs carried a higher risk of developing POE than did those implanted with either heparinized PMMA (P=0.001), hydrophilic acrylic, or hydrophobic acrylic IOLs (P=0.002). CONCLUSIONS: The incidence of acute POE after cataract surgery in our hospital is similar to that currently reported for other institutions in developed countries. Our results add further evidence that IOL material and type are factors contributing to the risk to develop an acute POE after cataract surgery, and that PMMA IOLs may be associated with an increased risk of POE.

[Gonococcal conjunctivitis complicated by perforating corneal abscess in an adult]. / Conjonctivite à gonocoque compliquée d'abcès cornéen perforant chez un adulte.

We present a case of bilateral purulent conjunctivitis complicated by ocular perforation of the right eye secondary to fulminant corneal melt in a 29-year-old man. He developed urethritis after a sexual contact with a prostitute 3 weeks previously. Microbiological analyses of conjunctival and urinary cultures were positive for Neisseria gonorrhoeae resistant to penicillins, tetracyclines, and fluoroquinolones. Progression was favorable with a 15-day course of high doses of parenterally administered antibiotics associating imipenem and fosfomycin. Keratoplasty was done after 3 months. This observation is a good example of the problems raised by gonococcal conjunctivitis in adults. Extremely rare in developed countries, it remains widely unrecognized by ophthalmologists. It is a sexually transmitted disease usually resulting from autoinoculation from an infected genital site. The risk of marginal purulent corneal melt, which can lead to fulminant perforation, warrants prompt microbiological analysis and early parenteral antibiotic treatment.

[Ring melanoma revealed by spontaneous hyphema]. / Mélanome annulaire révélé par un hyphéma spontané.

INTRODUCTION: Ring melanoma is a rare form of uveal melanoma characterized by the circumferential involvement of the ciliary body. Unilateral chronic and refractory glaucoma is a classic circumstance of diagnosis. OBSERVATION: We report a case of ring melanoma revealed by acute intraocular hypertonia secondary to spontaneous hyphema. Iris and iridocorneal angle were diffusely invaded by the tumor. The fundus was masked but B-scan ultrasonography revealed a voluminous ciliochoroidal tumor. The patient had been enucleated. Pathological examination confirmed the diagnosis of ring melanoma. The tumor involved angle structures. The patient died 1 year later because of metastasis. DISCUSSION: Acute or chronic ocular hypertonia is a classic but rare circumstance of uveal melanoma diagnosis. Many mechanisms exist: neovascular glaucoma, secondary angle closure, involvement of angle structures, and trabecular obstruction by tumor cells or pigment. Acute intraocular hypertonia secondary to hyphema is more exceptional. Our observation highlights that apart from the classic situation of acute angle closure glaucoma, intraocular hypertonia requires meticulous fundus examination, if necessary using B-scan ultrasonography.