Orbital exenteration and conjunctival melanoma: a 14-year study at the Jules Gonin Eye Hospital.

PURPOSE: To report our 14-year experience with orbital exenteration and assess risk factors for poor prognosis by focusing on conjunctival melanoma. PATIENTS AND METHOD: A retrospective study was conducted in our tertiary care centre (Jules Gonin Eye Hospital, Lausanne, Switzerland) between 2003 and 2017. Inclusion criteria were patients aged ≥18 years with a follow-up >12 months, without metastatic spread at the time of surgery. Data recorded were age, gender, tumour histology, surgical technique, postoperative complications, surgical margin status, local recurrence, postoperative radiation beam therapy and metastatic status. RESULTS: Twenty-five patients with a mean age of 63.2 years (38-92) were included. Conjunctival melanoma was the most frequently identified tumour (n = 14, 56%) followed by conjunctival squamous cell carcinoma (n = 4, 16%), sebaceous carcinoma (n = 3, 12%), choroidal melanoma (n = 2, 8%) and basal cell carcinoma (n = 2, 8%). Eighteen tumours (72%) originated from the conjunctival tissue. Clear surgical margins were achieved in 21 (84%) patients. Fourteen (56%) patients experienced distant metastases and died from metastatic spread after a mean follow-up of 52.3 months (6-120). The 1-, 3- and 5-year overall survival (OS) was 96%, 72% and 60%, respectively. In the univariate analysis, positive surgical margins, local recurrence and metachronous metastases were associated with a decreased OS (p = 0.002, p = 0.005 and p = 0.007, respectively). In the multivariate analysis, positive surgical margins and metachronous metastases were also associated with a decreased OS (p = 0.02 and p = 0.042, respectively). Conjunctival melanoma was not associated with a poorer prognosis (p = 0.280). CONCLUSION: Free surgical margins are needed to increase OS. To achieve clearer surgical margins, neoadjuvant targeted therapies/immunotherapies may be considered.

"En face" OCT in Small Pigmented Choroidal Tumors.

Background "En face" optical coherence tomography (OCT) is an imaging technique with optic sections parallel to the retinal pigment epithelium (RPE). This study aims to define the use of this technique in the evaluation of small pigmented choroidal tumors. Patients and Methods Investigation of 27 small pigmented choroidal tumors with "en face" OCT. Following manual segmentation, the optic sections performed with a spectral domain OCT at 30, 80 and 130 µ under the RPE were selected for morphological and statistical analysis. Results Internal tumor reflectance is variable (hyper-, iso-, or hypo-reflective), with a uniform or a bull's eye appearance. The reflectance becomes progressively lower towards the centre of the tumor. The margins of the pigmented tumors appear similar or less extensive than ophthalmoscopically. Peritumoral vascularization appears distinct from the 80 µ section downwards. Conclusions On "en face" OCT, small pigmented choroidal tumors present with a uniform or bull's eye internal reflectance, and are of variable intensity relative to the surrounding choroid. Their margins can appear more restrained than those on colour fundus photography.

Pitfalls in colour photography of choroidal tumours.

Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

Scleritis after proton therapy in uveal melanoma.

BACKGROUND: Sclera is a very radioresistant tissue and scleritis after proton therapy has not been described so far. HISTORY AND SIGNS: Four female patients, aged between 31 and 74 years, were treated with proton therapy for uveal melanoma (height range: 2.2 - 3.5 mm), located in the macula, the superior equator and 2 in the ciliary body. All patients had a history of a previous or active inflammatory disease and developed scleritis after radiotherapy. THERAPY AND OUTCOME: Two patients had infectious scleritis and were treated with adequate antibiotic therapy. After systemic corticotherapy, 3 patients recovered completely; the remaining patient was managed with additional immunosuppressive treatment as well as a conjunctival and scleral graft, but has not become pain free yet. CONCLUSION: Scleritis is a possible complication after proton therapy, probably on an ischemic basis, where there is a predisposing factor such as inflammatory systemic disease.

Epibulbar osseous choristoma: a clinicopathological case series and review of the literature.

BACKGROUND: Choristomas are benign, congenital tumours composed of normal tissue in an abnormal location. Osseous choristomas represent the rarest form of epibulbar choristomas, with now 65 cases reported in the literature. We did a retrospective clinicopathological study of all patients with epibulbar osseous choristoma observed at our institution since 1982 and updated the last review of the literature. HISTORY AND SIGNS: Three Caucasian male patients, aged between 3 months and 11 years, were identified. All osseous choristomas were located under the superotemporal bulbar conjunctiva of the right eye. THERAPY AND OUTCOME: All lesions were managed with surgical excision. Histopathology revealed the presence of lamellar bone in all cases, one of which was associated with a dermolipoma. CONCLUSIONS: We report a small rare case series of 3 epibulbar osseous choristomas and did a review of the literature. In one patient, the osteoma was associated with a dermolipoma, corresponding to the fourth reported complex choristoma of this type, in an otherwise normal eye, in the literature.

Intravitreal ranibizumab in the treatment of predominantly hemorrhagic lesions in exudative age-related macular degeneration.

BACKGROUND: Submacular hemorrhage is a manifestation of neovascular age-related macular degeneration (AMD) that has a very poor natural history leading to severe visual loss. We have evaluated the safety and efficacy of intravitreal ranibizumab in the treatment of predominantly hemorrhagic AMD. PATIENTS AND METHODS: A retrospective study of patients with predominantly hemorrhagic AMD treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between December 2006 and December 2008 was undertaken. Baseline and monthly follow-up exams included visual acuity (VA), fundus exam and optical coherence tomography (OCT) while fluorescein and indocyanine green angiography were performed at least every three months. RESULTS: The study included 8 eyes. The mean follow-up was 13 months (SD: 6.3). The mean number of intravitreal injections administered for each patient was 6.4 (SD: 2). 50 % of the patients demonstrated stable or improved VA. The size of hemorrhage at baseline was inversely correlated to the final VA (two-tailed p value = 0.038) and positively correlated to the final central macular thickness (two-tailed p value = 0.021). Anticoagulation treatment was inversely correlated to the time of hemorrhage resolution (two-tailed p value = 0.039). CONCLUSIONS: Intravitreal ranibizumab may be an effective treatment for predominantly hemorrhagic lesions due to neovascular AMD.

[New strategies in pediatric ophthalmic oncology]. / Nouvelles stratégies thérapeutiques en oncologie ophtalmo-pédiatrique.

Retinoblastoma represents 11% of all cancers during the first year of life. New drugs and focal treatments have been developed in order to avoid the side effects of systemic chemotherapy and external radiotherapy. New targeted and local administration strategies such as periocular chemotherapy (topotecan) or direct ophthalmic artery delivery (carboplatin), are already used today in selected resistant cases. Radiotherapy, presently indicated only as a second-line treatment, is also subject to new techniques, targeting tumors more closely to avoid involving healthy tissue and reduce the risk of radio-induced nonocular tumors. Stereotactic conformal radiotherapy and proton therapy may thus be included in the new range of treatment methods in retinoblastoma.

Methylation of CpG island promoters in uveal melanoma.

BACKGROUND: Inactivation of tumour-related genes by promoter hypermethylation is a common epigenetic event in the development of a variety of tumours. AIM: To investigate in primary uveal melanoma the status of promoter methylation of genes thought to be involved in tumour development: p16, TIMP3, RASSF1, RARB, FHIT, hTERT and APC. METHODS: Gene promoter methylation was studied by methylation-sensitive single-strand conformation analysis and dot-blot assay in a series of 23 primary uveal melanomas. All DNA samples were obtained from paraffin-embedded formalin-fixed tissue blocks. RESULTS: hTERT promoter methylation was found with a relatively high frequency (52%). Promoter methylation of p16, TIMP3, RASSF1, RARB, FHIT and APC was a rare event. For none of these genes did promoter methylation exceed 15% of tumour samples, and, for some genes (FHIT and APC), no methylation was found at all. Furthermore, promoter methylation was absent in 39% (9/23) of cases. In only 22% (5/23) of cases was hypermethylation of at least two promoters observed. CONCLUSIONS: Promoter methylation of hTERT is a regular event in uveal melanoma. Hypermethylation of the other genes studied does not seem to be an essential element in the development of this tumour. As promoter methylation of APC, RASSF1 and RARB is often observed in cutaneous melanoma, these results suggest that different epigenetic events occur in the development of cutaneous and uveal melanoma.

[Giant nodular posterior scleritis compatible with ocular sarcoidosis simulating choroidal melanoma]. / Escleritis nodular posterior gigante compatible con sarcoidosis ocular simulando un melanoma de la coroides.

CASE REPORT: A 30-year-old man was referred to our ocular oncology service with a diagnosis of amelanotic choroidal melanoma of the left eye. The following tests were performed: ophthalmoscopy, fluorescein angiography, indocyanine green angiography, ultrasonography, magnetic resonance imaging and biopsy. DISCUSSION: The diagnosis of giant nodular posterior scleritis, as suggested by ultrasonography, was confirmed by biopsy. A comprehensive medical evaluation was performed, but no etiology was found. The histology revealed a granuloma compatible with ocular sarcoidosis. A rapid response was obtained by systemic steroid administration (1 mg/kg). Sarcoidosis continues to be a challenge in diagnosis. It is important to distinguish nodular posterior scleritis from choroidal melanoma.

[Iris granulomas of unknown aetiology]. / Irisgranulome ungeklärter Aetiologie.

BACKGROUND: Non-pigmented tumours of the iris are rare and their clinical classification can be difficult, especially in the absence of systemic manifestations. HISTORY AND SIGNS: We report the case of a unilateral vascular, non-pigmented iris tumour in a 47-year-old patient. Clinically, the iris lesion showed progressive growth and tumour vascularisation. THERAPY AND OUTCOME: A systemic work-up failed to reveal any underlying systemic disease. Biopsy showed a non-necrotising granuloma. The lesion responded well to systemic corticosteroid therapy. CONCLUSIONS: Isolated granulomas of the iris are rare and clinically often indistinguishable from malignant tumours like melanoma. Due to the clinical course and the regression under corticosteroid therapy we concluded that this iris granuloma may be an isolated ocular manifestation of sarcoidosis.

Interferon-associated retinopathy--a case report.

BACKGROUND: Interferon alpha is used for treatment in oncology and for chronic hepatitis C. Interferon-associated retinopathy is not infrequent and typically includes cotton wool spots, haemorrhages, rarely macular or papillary oedema, capillary non-perfusion and sometimes retinal or even choroidal vascular occlusion. The latter may be irreversible, while uncomplicated forms are usually reversible. We report an atypical case of interferon-associated retinopathy, associated with microaneurysms, Roth spots, and retinal pigment changes. HISTORY AND SIGNS: A 63-year-old asymptomatic patient presented with partially white centred, flame-shaped haemorrhages, some cotton wool spots and microaneurysms on both fundi. In addition, the left eye presented chronic pigment epithelium abnormalities surrounding the fovea without signs of exudation, most likely secondary to a previous central retinal exudative detachment combined with choroidal hypoperfusion. Interferon alpha 2a therapy for chronic hepatitis C had been given for 6 months. He was known for arterial hypertension (risk factor), mild microcytic anaemia and mild glucose intolerance, which may be responsible for some unusual features of the retinopathy. THERAPY AND OUTCOME: The patient was closely followed, while the interferon therapy was continued on reduced dosage. No vision-threatening complication was observed. CONCLUSIONS: Interferon-associated retinopathy may show atypical features. Early diagnosis and careful follow-up are recommended in order to avoid progression to irreversible changes. Dose-reduction or even interruption of interferon treatment needs to be considered in cases of interferon-associated retinopathy.

Pars Plana vitrectomy and epiretinal membrane peeling for vitreoretinal traction associated with combined hamartoma of the retina and retinal pigment epithelium (CHRRPE).

BACKGROUND: Combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) are rare, benign tumours that typically appear slightly elevated and are characterised by varying amounts of pigmentation, vascular tortuosity, and epiretinal membrane formation that can be related to macular distortion. The importance of changes at the vitreoretinal interface in this condition as a risk for visual loss was early recognised but controversy exists concerning the benefits of surgical removal of the tractional component. We describe 2 cases of CHRRPE who demonstrated significant visual acuity improvement after pars plana vitrectomy and epiretinal membrane peeling. HISTORY AND SIGNS: A 12-year-old girl and a 14-year-old boy presented with progressive unilateral visual loss related with a CHRRPE. In both instances the hamartoma was associated with a thickened posterior hyaloid and epiretinal membrane inducing considerable vitreomacular traction as shown by optical coherence tomography (OCT). Best-corrected pre-operative visual acuity was 0.2 in both cases. THERAPY AND OUTCOME: Vitrectomy and epiretinal membrane peeling were performed in both cases. Relief of vitreomacular traction and macular distortion was achieved and documented on OCT. Visual acuity at the latest follow up was 0.5 and 0.8, respectively. CONCLUSIONS: Surgical dissection can be effective in the treatment of vitreomacular traction associated with CHRRPE with a good functional and anatomical outcome.

Retinal angiomatous proliferation treated with a combination of intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin.

PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive form of exudative age-related macular degeneration. Response to laser photocoagulation or to photodynamic therapy (PDT) alone is often disappointing. The purpose of this study was to determine whether intravitreal triamcinolone acetate (TA) injections followed by PDT in eyes with early stage RAP may be effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11 eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT. Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing glaucoma and known steroid responders were excluded. All patients underwent a complete ophthalmic examination including fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, and 12 months. Informed consent was obtained from all patients. RESULTS: Mean follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four patients a small pigment epithelium detachment was found on tomography. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating the logarithmic values the authors found an initial mean VA of logMAR 0.61, which improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. Although the VA gain from baseline tended to decrease with time, only 2 patients (18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5 eyes. CONCLUSIONS: In this prospective pilot study examining the use of intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP, without a large pigment epithelium detachment, the authors found a potential benefit in terms of stabilization or even improvement of vision.

Diagnosis and current management of retinoblastoma.

Retinoblastoma represents the prototypic model for inherited cancers. The RB1 gene was the first tumor suppressor gene to be identified. It represents the most frequent primary eye cancer in children under 15 years old, habitually occurring in infancy, even in utero, but can be observed in older children or young adults. Many other retinal lesions may also simulate retinoblastoma. The two major presenting signs are leukocoria and strabismus, but other ocular or general signs may be observed. A highly malignant tumor, retinoblastoma can nowadays be cured. The heritable form, however, carries a high risk of second nonocular tumors. Treatment in the early stages of disease holds a good prognosis for survival and salvage of visual function. In very late stages, however, the prognosis for ocular function and even survival is jeopardized.

[New trends in corneal surgery. Grafting stem cells and performing lameliar graft]. / Ophtalmologie. Chirurgie cornéenne: greffes de cellules souches et greffes lamellaires.

Epithelial, stromal or endothelial diseases can generate corneal opacity. A lake of corneal epithelial cells leads to corneal opacity and low visual acuity. In these cases, corneal epithelial stem cells from the limbus of the healthy eye or from relatives or other people must be grafted to regenerate corneal epithelium. It is also possible to cultivate corneal stem cells harvested from the sick eye, the healthy eye (autologous culture) or from relatives (allotypic culture). Renewing epithelial cells is not always sufficient to restore corneal transparency. It can also be necessary to replace a part or the entire corneal stroma. We can use today surgical lamellar graft technics to replace only stromal corneal layers involved in the disease we cure.

Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients.

BACKGROUND: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. PATIENTS AND METHODS: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. RESULTS: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. CONCLUSIONS: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.