Intravitreal injection of anti-VEGF and diagnosis of primary intraocular central nervous system lymphoma.

We report a case of primary intraocular central nervous system (CNS) lymphoma in a patient previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD). An 88-year-old woman, with past medical history significant for bilateral age-related macular degeneration (AMD) treated with intravitreal ranibizumab injections for 1 year, was referred to our department for bilateral vitritis diagnosed 10 days after the last anti-VEGF injection. A complete uveitis work-up including aqueous humour analysis, brain MRI and vitreous biopsy enabled us to confirm the diagnosis of primary intraocular CNS lymphoma. To the best of our knowledge, this is the first report of the diagnosis of primary intraocular CNS lymphoma in a patient treated with anti-VEGF for AMD. The differential diagnosis of vitritis in elderly patients is relatively broad. Endophthalmitis and uveitis have been described after anti-VEGF injections. In such a situation, there is actually a risk of missing the diagnosis of intraocular lymphoma in the mistaken belief that the observed vitritis may be a reaction to administered anti-VEGFs. If no direct time-relationship with the anti-VEGF injections can be found, a classic vitritis work-up should be performed. Our observation suggests that ranibizumab, at the dosage used for AMD, does not impede the spread of CNS lymphoma in the eye nor interfere with cytological diagnosis.

[Combined treatment with photodynamic therapy and intravitreal dexamethasone implant (Ozurdex(®)) for circumscribed choroidal hemangioma]. / Traitement combiné par photothérapie dynamique et implant intravitréen de dexaméthasone (Ozurdex(®)) pour un hémangiome choroïdien circonscrit.

PURPOSE: We report a case of symptomatic circumscribed choroidal hemangioma (CCH) treated by photodynamic therapy (PDT) combined with injection of an intravitreal dexamethasone implant (IDI) (Ozurdex(®)). CASE REPORT: A 39-year-old woman was referred to our outpatient clinic for a progressive decrease in vision of her right eye, measured at 20/25, due to subretinal exudation (SRE) associated with juxtapapillary CCH. Basal diameter of the CCH was 6mm, and its height was 2mm. Treatment consisted of injection of an IDI followed 15 days later by PDT with a single spot covering the tumor (intensity of 600 mW/cm(2) for 83 seconds [50 J/cm(2)]). Six weeks after PDT, we noted improvement of the vision to 20/20, complete resolution of SRE, and tumor flattening. No side-effects were observed. Anatomic and functional results remained unchanged over 9 months of follow-up. CONCLUSIONS: This case suggests that IDI (Ozurdex(®)) potentiates the effect of PDT with less risk of local side-effects than triamcinolone acetonide. Further evaluation of this protocol remains necessary. Nonetheless, combined treatment with injection of IDI followed 15 days later by PDT for the treatment of symptomatic CCH may prove to be a sound alternative to radiotherapy and may be more efficacious than PDT alone.

[Management of neovascular glaucoma related to the persistence after retinal detachment surgery of a circumferential peripheral retinal detachment]. / Traitement du glaucome néovasculaire lié à la persistance après chirurgie du décollement de rétine d'un décollement de rétine périphérique annulaire.

OBSERVATION: A 41-year-old male with a medical history of high myopia and several retinal detachment (RD) surgeries was referred for vitreous hemorrhage coexisting with neovascular glaucoma occurring 2 months after uncomplicated silicone oil removal on his left and single eye. The right eye had been lost to RD. The retina behind the equator was reattached on ultrasonography. We performed a washout pars plana vitrectomy on the left eye, revealing a chronic circumferential RD of the anterior retina stopped in its posterior spread by dense photocoagulation scars. We combined a retinectomy of the detached retina with an intracamerular injection of bevacizumab, resulting in complete disappearance of rubeosis and normalization of the intraocular pressure. CONCLUSIONS: The retinal ischemia related to the persistence of a chronic and circumferential RD anterior to dense photocoagulation scars after ab-interno RD surgery, whereas the rest of the retina appears reattached, is probably the causative factor of neovascular glaucoma. In the present case, the removal of RD by circumferential retinectomy combined with an intraocular injection of anti-VEGF allowed the complete and definitive regression of neovascular glaucoma.

[Conjunctival epidermoid carcinoma revealed by a chronic limbic corneal ulceration]. / Un carcinome épidermoïde de la conjonctive révélé par une ulcération chronique du limbe cornéen.

PURPOSE: Conjunctival epidermoid carcinoma (CEC) is a rare tumor affecting mainly the perilimbal region of the bulbar conjunctiva. We report an atypical presentation of a CEC mimicking a Mooren pseudo-ulcer. CASE REPORT: A 78-year-old man presented a limbic corneal ulcer of the left eye that had appeared a few months before. Ophthalmologic examination showed a thinning limbic corneal ulceration, associated with substantial conjunctival thickening. The diagnosis of Mooren pseudo-ulcer was first suspected. Etiological investigations were negative. The worsening of the corneal ulcer led us to perform surgical excision on the conjunctiva around the ulcer. Histologic examination concluded in an invasive conjunctival carcinoma. Adjuvant radiotherapy was required because of incomplete surgical excision and chorion tumoral invasion.

[Central retinal vein and artery occlusions related to intraocular involvement of an anaplastic optochiasmatic glioma]. / Occlusion vasculaire mixte de la veine et de l'artère centrale de la rétine liée à l'envahissement intraoculaire d'un gliome anaplasique optochiasmatique.

Malignant optic tract gliomas are very aggressive and extremely rare tumors progressing to blindness and death in a few months. We report here the case of a 73-year-old patient who presented a sudden decrease in visual acuity in his left eye associated with papilledema and headache: it revealed an optochiasmatic anaplastic glioma. A few months later, the glioma had grown, with infiltration of the right optic nerve and right peripapillary intraocular invasion. Through this case, we discuss the importance of achieving imaging for atypical optic neuropathies and stress the exceptional nature of intraocular invasion by a glioma.

[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.

Epistaxis or epiphora as a sign for extension of a conjunctival melanoma. A series of six patients with nasolacrimal recurrence.

PURPOSE: To characterise malignant conjunctival melanomas with extension and recurrence in the nasolacrimal system. METHODS: Localisation of the primary tumour and recurrences of 210 conjunctival melanomas treated in The Netherlands were reviewed for orbital and nasal tumours (1978-2008). Based of these cases and literature data, characteristics for nasolacrimal system extension and metastasis were reviewed. RESULTS: Six patients (3%) showed a recurrence of the primary conjunctival melanoma in the nasolacrimal system. Two of the six primary tumours were limbal tumours; the other four were diffuse tumours involving the fornix. In all six patients, the primary conjunctival melanomas were associated with primary acquired melanosis. During the follow-up period (11.6±3 years, range 3.4-28.5 years, median 8.7 years) two patients developed metastases and died. CONCLUSIONS: Patients should be advised to contact their treating ophthalmologist in the case of symptoms of epiphora, nose obstructions and epistaxis, especially non-bulbar and diffuse cases associated with primary acquired melanosis.

[Surgery of perforating ocular injuries of the posterior segment by lead shot: two case studies]. / Chirurgie des traumatismes oculaires perforants du segment postérieur par plombs: à propos de deux cas.

INTRODUCTION: Treatment of retinal detachment secondary to perforating ocular trauma (POT) is difficult due to the fragility of the sclera, the number, size, and location of the retinal wounds, the vitreoretinal incarceration into the scleral wound, and the high risk of vitreoretinal proliferation. We report our experience of pars plana vitrectomy to prevent secondary retinal detachment in two cases of POT of the posterior segment caused by lead shot. OBSERVATIONS: Two males, about 20 years old, suffered from a perforating ocular injury caused by a single pellet. In both cases, the entrance wound was more than 5mm posterior to the corneoscleral limbus and the exit wound was located in the posterior pole. In both cases, initial visual acuity was limited to perception of hand motions and the Ocular Trauma Score (OTS) was 2. Both patients underwent two surgical procedures, the first procedure consisting only in entrance wound closure. The second procedure was delayed 17 days (case 1) and 10 days (case 2). It consisted in pars plana vitrectomy including careful shaving of the incarcerated vitreous into the wounds and detachment of the posterior hyaloid. Surgery was completed by cryopexy of the retina beneath the entrance wound and by focal scleral buckling between the entrance and the exit wound. Cryopexy was not done on the exit wound. Final visual acuity was 40/200 (case 1) and 30/200 (case 2) after 36 and 8 months, respectively. No retinal detachment was observed. CONCLUSION: This report highlights the advantage of early pars plana vitrectomy to prevent retinal detachment in POT related to lead shot.

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.

[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.

Survival after primary enucleation for choroidal melanoma: changes induced by the introduction of conservative therapies.

BACKGROUND: Most uveal melanomas are currently treated by eye-preserving radiotherapies. However, for melanomas of the largest size or with initial complications, enucleation remains the reference treatment. Enucleation is called primary when it is proposed as the only local treatment option for a melanoma. There is very little literature on the use of primary enucleation after the introduction of conservative treatments. Our main goal was to evaluate the survival of melanoma patients treated by primary enucleation since the introduction of proton-beam therapy in France in 1991. METHODS: All melanoma patients undergoing primary enucleation in our department between 1991 and 2002 were included in this retrospective study. The 5-year melanoma-specific survival rate was calculated using the Kaplan-Meier method. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: Forty patients, representing 8% of all patients with choroidal uveal melanoma diagnosed and followed up in our department during an 11-year period, were included in the study. No patient was lost to follow-up. The 5-year melanoma-specific survival rate was 31.45% (SE: 7.8) after primary enucleation. Significant prognosis factors in the multivariate analysis were: tumor thickness > 12 mm (p = 0.03), anterior margin of the tumor involving the iris (p = 0.018), and presence of epithelioid cells (p = 0.02). CONCLUSIONS: The very low survival rate reported reflects the evolution of primary enucleation, which is currently indicated only for melanomas with the worst prognosis. The knowledge of current post-enucleation survival rates represents an essential achievement for both correct assessment of conservative therapies and patient counseling.

[Panuveitis following intravesical bacille Calmette-Guerin therapy]. / Pan-uvéite dans les suites d'instillations intravésicales de BCG (Bacille de Calmette et Guérin).

Uveitis occurring after bacille Calmette-Guerin (BCG) intravesical therapy for bladder carcinoma is rare: only nine cases have been described. In two previous reports, vitreous cultures proved Mycobacterium bovis presence. We describe the case of an 85-year-old woman who presented with bilateral panuveitis 2 months after the last BCG intravesical instillation, with no other systemic symptom. There was no evidence for any other etiology for this uveitis. She was given oral antibiotics that were effective against Mycobacterium species, oral steroids, and anti-inflammatory drops. Her ophthalmologic status dramatically improved. This case highlights that these patients may have a good visual outcome, as long as diagnosis and treatment are not delayed.

[Conjunctival biopsy: a useful procedure for the diagnosis of sarcoidosis]. / Biopsie conjonctivale: une aide précieuse pour le diagnostic de sarcoïdose.

PURPOSE: To highlight the advantages of conjunctival biopsy in order to confirm the diagnosis of sarcoidosis. CASE REPORT: A 78-year-old woman presented with unilateral vitreitis. The examination of the conjunctive of right and left eyes revealed multiple, translucent, pale yellow nodules the size of millet grains located in the lower fornix. The diagnosis of sarcoidosis was suspected by an increased level of angiotensin-converting enzyme and bilateral hilar lymphadenopathies. A biopsy from conjunctival nodules showed noncaseating epithelioid and gigantocellular granulomas, confirming the diagnosis of sarcoidosis. CONCLUSION: Although underused, conjunctival biopsy seems to be both a safe and effective tool in the diagnosis of sarcoidosis.

[Multidrug resistance in uveal melanoma]. / Multichimiorésistance du mélanome uvéal.

In spite of important progress in the local treatment of uveal melanoma, the most frequent primitive intraocular tumor, 15%-30% of patients still die because of tumor metastasis. This tumor is characterized by constitutive chemoresistance, thwarting any attempt to control it using the usual chemotherapy protocols. The chemoresistance of uveal melanoma is mainly due to the typical multidrug resistance phenotype (MDR), which is linked to overexpression of membrane proteins that actively extrude anticancer drugs from the cell. Typical MDR is particularly complex in this tumor since several chemoresistance-related proteins are simultaneously produced. The negative prognostic significance of the overexpression of P-glycoprotein, the main representative among the typical MDR-related proteins, was shown in uveal melanoma. The atypical MDR phenotype, which refers to other chemoresistance mechanisms such as resistance to apoptosis also contributes to the chemoresistance of uveal melanoma. Thanks to the recent progress in molecular biology, the chemosensitization strategies of gene therapy approaches, which aim at weakening the pathological activity of MDR genes in cancer cells, are currently on the rise. This approach will disrupt current therapeutic strategies and necessarily improve and standardize the methods used to characterize the chemoresistance profile of this cancer. Indeed, we will have to know the genes to be targeted for each melanoma in order to induce cell chemosensitivity.

[Toward monosomy 3 as the main prognosis factor of uveal melanoma: current cytogenetic data]. / Données cytogénétiques actuelles: vers la monosomie du chromosme 3 comme principal facteur pronostique du mélanome uvéal.

Uveal melanoma is the most frequent intraocular cancer. The recent development of new technologies such as microsatellite analysis and comparative genomic hybridization have elucidated both the cytogenetics and the natural history of this disease. Fifty to 60% of uveal melanomas are linked to monosomy 3, which appears as an early and determinant event in tumor progression. Tumors with this anomaly have a very poor prognosis. Recent work suggests that this category of uveal melanomas represents a distinct pathological entity from that associated with normal disomy 3. Chromosome 6 aberrations probably make up a second entry point into the process of carcinogenesis, while gains in 8q seem to appear later in the natural history of uveal melanoma because of their higher frequency in larger tumors. Progress in genome analysis has identified regions in chromosomes 3, 6, and 8 as those most probably involved in tumorigenesis. It is to be hoped that this will soon lead to the discovery of the genes responsible.

[Buphthalmia secondary to congenital pigmented epithelial iris cyst]. / Buphtalmie secondaire à un kyste congénital de l'épithélium pigmentaire de l'iris.

We report the case of a 2-day-old child with buphthalmia caused by a congenital pigmented epithelial iris cyst. The use of ultrasound biomicroscopy (UBM) and high-resolution echography (20MHz) specified the diagnosis before general anesthesia for complete examination and treatment. Surgery can control intraocular pressure and the opening of the visual axis; there is, however, relative amblyopia. This case confirms the advantage of UBM in examining tumors of the anterior segment. The early diagnosis, facilitated by use of the UBM, provided quick and well-adapted treatment.

[Ciliary body melanomas. Survival and prognostic aspects after brachytherapy or proton therapy]. / Mélanomes uvéaux impliquant le corps ciliaire. Analyse de la survie après protonthérapie ou bêta-curiethérapie par ruthénium-106. A propos de 106 cas.

INTRODUCTION: Our main goals were to study the survival of patients with uveal melanomas involving the ciliary body 5 and 10 years after treatment and to review prognosis. MATERIAL AND METHODS: This study investigated 106 tumors (27 ciliary body melanomas and 79 choroidal-ciliary melanomas) of patients treated between June 1983 and April 1998. Seventy-two patients were treated with 106-ruthenium applicators and 34 were treated with proton therapy. Some large tumors or recurrences required a second treatment. The mean follow-up period was 91 months. RESULTS: The mean tumor sizes before treatment were 6,6mm for melanoma thickness and 10.3mm for mean largest basal melanoma diameters (LTD). Of the patients studied, 71% were still alive at 5 years, 35% had metastasis and 27.7% developed recurrences. Multivariate analysis showed that the risk factors for melanoma-related death were LTD greater than 13mm, presence of exudative retinal detachment, macroscopic iris root involvement at the time of diagnosis, and choroidal-ciliary location. DISCUSSION AND CONCLUSION: With 71% of patients still alive at 5 years, this review shows that melanomas involving the ciliary body do not seem less severe than more posterior uveal tumors. Because of size differences between ciliary body melanomas and choroidal-ciliary melanomas, we cannot come to the conclusion that choroidal-ciliary melanomas have a poorer prognosis than ciliary body melanomas. Largest tumor diameter over 13mm, presence of exudative retinal detachment, and macroscopic iris root involvement at the time of diagnosis are important risk factors for melanoma-related death, as shown by the multivariate analysis.