Eye enucleation activates the transcription nuclear factor kappa-B in the rat superior colliculus

Ocular enucleation produces significant morphological and physiological changes in central visual areas. However, our knowledge of the molecular events resulting from eye enucleation in visual brain areas remains elusive. We characterized here the transcription nuclear factor kappa-B (NF-kappa B) activation induced by ocular enucleation in the rat superior colliculus (SC). We also tested the effectiveness of the synthetic glucocorticoid dexamethasone in inhibiting its activation. Electrophoretic mobility shift assays to detect NF-kappa B indicated that this transcription factor is activated in the SC from 1 h to day 15 postlesion. The expression of p65 and p50 proteins in the nuclear extracts was also increased. Dexamethasone treatment was able to significantly inhibit NF-kappa B activation. These findings suggest that this transcriptional factor is importantly involved in the visual system short-term processes that ensue after retinal lesions in the adult brain. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Inflammatory responses in the rat superior colliculus after eye enucleation

Ocular enucleation induces profound morphological alterations in central visual areas. However, little is known about the response of glial cells and possible inflammatory processes in visual brain areas resulting from eye enucleation. In this study, immunoblotting and immunostaining assays revealed increased expression of astrocyte and microglia markers in the rat superior colliculus (SC) between 1 and 15 days after contralateral enucleation. A transient increase of neuronal COX-2 protein expression was also found in the SC. To evaluate the role of an anti-inflammatory drug in attenuating both COX-2 and glial cell activation, the synthetic glucocorticoid dexamethasone (DEX) was administered (1mg/kg i.p., for 3 days) to enucleated rats. Immunoblotting data revealed that DEX treatment significantly inhibited COX-2 protein expression. Postlesion immunostaining for astrocyte and microglia markers was also significantly reduced by DEX treatment. These findings suggest that the removal of retinal ganglion cell input generates inflammatory responses in central retinorecipient structures

Lance-headed viper (Bothrops moojeni) bite wounding the eye

A 5-year-old girl was bitten in her left eye by a lance-headed viper identified as Bothrops moojeni, measuring 115 cm of length. There was severe facial swelling and left exophthalmus, and enucleation of the eye was necessary. The patient apparently had mild systemic envenoming, but local inflammatory signs and histological evidence of necrosis suggest that both the mechanical trauma and the local action of the venom had a role in the genesis of the eye lesion. It is arguable if the loss of the eye could be prevented even if the antivenom was administered earlier.

First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of first-line chemotherapy (CT) in preventing external-beam radiotherapy (EBR) and/or enucleation in patients with retinoblastoma (Rbl). PATIENTS AND METHODS: Twenty-four patients with newly diagnosed unilateral or bilateral Rbl received CT associated with local treatment (LT). Two to five courses of etoposide and carboplatin were administered at 3- to 4-week intervals, depending on tumor response, and were completed each time by LT. RESULTS: Tumor response was observed in all eyes. Twenty-one of 24 patients showed a complete response (CR) that persisted at a median follow-up (FU) of 31 months (range, 4 to 41 months). Among the three patients who relapsed, two were lost to FU and one died of progressive disease. CR was achieved by CT and LT alone in 15 (71.4%) of 21 patients with less advanced disease (groups I to III). Six other patients with advanced disease (groups IV and V) experienced treatment failure and needed salvage treatment by EBR and/or enucleation. The difference between the two patient groups with regard to disease stage was statistically significant (P <.0001). EBR could be avoided in 13 (68.4%) of 19 patients, who presented with groups I to III (15 eyes) and group V (one eye) disease, whereas enucleation could be avoided in only two (40%) of five. CONCLUSION: CT combined with intensive LT is effective in patients with groups I to III Rbl, permitting the avoidance of EBR in the majority of these young children and, thus, reducing the risk of long-term sequelae. This is in contrast with the disappointing results for patients with groups IV and V Rbl, in whom EBR and/or enucleation was needed.

Effective temporary analgesia for severe painful blind eye.

There are various methods of providing pain relief for painful blind eyes. We wish to recommend this effective method of providing temporary analgesia in patients suffering from a severe painful blind eye before undergoing enucleation.

Altérations anatomopathologiques liées au traitement par cerclage des globes oculaires atteints de décollement de rétine [Histological changes related to scleral buckling for treatment of retinal detachment].

Treatment of retinal detachment frequently uses biocompatible materials to obtain scleral buckling. These materials are not devoid of consequences on surrounding tissues. In 3 eyes enucleated for failure of surgical treatment using scleral buckling materials, the changes prompted by episcleral implants could be observed. The sclera underwent both an inversion of its curvature and a reduction of its thickness under the material, as well as an encapsulation of the material was observed. While a silicone sponge was used in part to encircle one of these eyes, its capsular inner surface was regular and smooth. In contrast, hydrogel implants used in the three eyes showed a peripheral fragmentation prompting in two of them a typical foreign body giant cell granulomatous reaction. Changes in scleral curvature and scleral thinning were observed reflecting the consequences of the buckling procedure. The capsule formation occurred as it does for any nonabsorbable matérial implanted in tissues. Degradation and fragmentation of the hydrogel material suscitated a granuloma in response to fragments. These hydrogel specific changes should be recognized on microscopic examination of slides of either capsule or eyes previously in contact with this implanted material. They attested of the instability of hydrogel after implantation.

Ultrasound biomicroscopy evaluation of anterior extension in retinoblastoma: a clinicopathological study.

BACKGROUND: Extension of retinoblastoma cells into the posterior chamber is a criterion for group E according to the international classification of intraocular retinoblastoma. Currently, the anterior extension of retinoblastoma is based on the presence of tumour cells in the anterior chamber assessed by biomicroscopy. AIM: To determine the value of ultrasound biomicroscopy (UBM) in the assessment of posterior chamber involvement in advanced retinoblastoma. METHODS: Retrospective review of all retinoblastoma cases enucleated at the Jules Gonin Eye Hospital from January 1996 to December 2009 for which UBM (35 MHz) evaluation was available. The patients' records were reviewed for patient and tumour features and histopathological findings. UBM findings were compared with histopathological features. RESULTS: UBM documentation was available in 31 cases. Retinoblastoma was detected by UBM in the posterior chamber in 18 cases and was absent in 13 cases while histopathological analysis demonstrated its presence in the posterior chamber in 22 cases and its absence in 9 cases. Among the 18 UBM-positive cases, 7 had biomicroscopic detectable involvement of the anterior chamber. There was a significant correlation between echodensities consistent with retinoblastoma on UBM in the posterior chamber and histopathological tumorous involvement of the posterior chamber (p=0.0001). The sensitivity of UBM in the assessment of posterior chamber invasion by retinoblastoma was 81% and the specificity was 100%. CONCLUSION: In selected cases of advanced retinoblastoma, UBM appears to represent a valuable tool in the precise evaluation of anterior extension of disease, with good sensitivity and specificity for the assessment of posterior chamber involvement. UBM may provide useful criteria governing the indication for enucleation.

Clinicopathologic and molecular analysis of a choroidal pigmented schwannoma in the context of a PTEN hamartoma tumor syndrome.

PURPOSE: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog (PTEN) and neurofibromin 2 (NF2) genes in this rare intraocular tumor. DESIGN: Observational case report. PARTICIPANT: A 10-year-old girl diagnosed with PHTS. METHODS: The enucleated specimen underwent histologic, immunohistochemical, and transmission electronic microscopy. The expression of PTEN and NF2 and their protein products were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Somatic mutations of PTEN and NF2, as well as allelic loss, were investigated by direct sequencing of DNA extracted from the tumor. PTEN epigenetic silencing was investigated by pyrosequencing. MAIN OUTCOME MEASURES: Histopathologic and molecular characterization of a choroidal pigmented schwannoma. RESULTS: Histopathologic, immunohistochemical, and electron microscopic analysis demonstrated features consistent with a pigmented cellular schwannoma of the choroid. We found no loss of heterozygosity at the genomic level for the PTEN germline mutation and no promoter hypermethylation or other somatic intragenic mutations. However, we observed an approximate 40% reduction of PTEN expression at both the mRNA and the protein level, indicating that the tumor was nonetheless functionally deficient for PTEN. Although DNA sequencing of NF2 failed to identify any pathologic variants, its expression was abolished within the tumor. CONCLUSIONS: We report the first description of a pigmented choroidal schwannoma in the context of a PHTS. This rare tumor showed a unique combination of reduction of PTEN and absence of NF2 expression.

Utility of a biopsy in suspicious pigmented iris tumors.

BACKGROUND: In the presence of pigmented iris lesions evocative of malignant melanoma and implying oncological treatment, a foregoing biopsy to exclude a benign lesion may seem a reasonable approach. After examining patient files, the utility of such a diagnostic approach was explored. MATERIAL AND METHODS: Retrospective, consecutive histopathologic case series of 10 pigmented iris tumor specimens excised since 1993. Histopathologic diagnosis was compared with final diagnosis and outcome in the patient's medical chart. RESULTS: Five biopsies had only nevus cells, whereas ulterior clinical data or histopathologic examinations were compatible with the diagnosis of malignant melanoma. One biopsy contained insufficient sample tissue. Four biopsies confirmed clinical suspicion of iris melanoma. CONCLUSION: In the current case series, 6 out of 10 biopsies provided a falsely reassuring negative or an inconclusive result. Modern management techniques such as ultrasound biomicroscopy and proton therapy of the whole anterior segment have equally diminished indications for a biopsy. In cases clinically evocative of iris melanoma, a biopsy has only a relative value.

Chiasmatic infiltration secondary to late malignant transformation of retinoma.

PURPOSE: To report the lethal course of malignant transformation of retinoma in an adult. METHODS: Case report. A 40-year-old patient presented with retinoma in his right eye and retinoblastoma in his left eye. Enucleation was recommended but refused and the patient received whole eye radiotherapy elsewhere. Five years later he presented again, with temporal hemianopsia of the left eye secondary to chiasmatic invasion. RESULTS: Diagnosis of retinoblastoma infiltration was confirmed by stereotactic biopsy of the chiasmatic lesion. Treatment with intravenous and intrathecal chemotherapy led to partial remission, and was followed by stereotactic irradiation of the chiasmatic mass and right optic nerve. The left eye was enucleated. Death occurred one year later due to cerebrospinal fluid metastases. CONCLUSION: Extraocular extension of retinoblastoma diagnosed in adulthood has never, to our knowledge, been reported. This case stresses the importance of lifelong retinoma monitoring and the necessity for radical treatment in the event of malignant transformation.

Treatment of Retinoblastoma in 2015: Agreement and Disagreement.

The management of intraocular retinoblastoma is rapidly changing, and even recent reviews on the subject are behind existing practices. The 4 authors of this report collectively represent their management strategies with an emphasis on areas of agreement and disagreement. Ophthalmic artery chemosurgery and intravitreous chemotherapy have completely replaced external beam radiotherapy, reduced the use of systemic chemotherapy, and diminished enucleations by 90% without evidence of compromising patient survival.

Avaliação da gordura orbitária de coelhos após enucleação e evisceração

OBJETIVO: Avaliar os adipócitos da gordura orbitária de coelhos após enucleação e evisceração. MÉTODOS: Foram estudados vinte e três espécimes de gordura orbitária, provenientes de 23 coelhos com idade de 42 dias, sendo 11 submetidos à cirurgia de enucleação e 12 à evisceração. Os animais foram sacrificados 30, 90 e 180 dias após a cirurgia, avaliando-se a gordura orbitária ao microscópio óptico (aumento de 200x) e usando o programa IpWin 32. A área média celular foi calculada a partir do número de adipócitos por campo e da área de cada adipócito, tendo sido comparados os resultados dos grupos (enucleação e evisceração) usando teste estatístico não paramétrico para avaliação da área dos adipócitos. RESULTADOS: Não houve diferença significativa entre a área média dos adipócitos quando considerado o procedimento cirúrgico (enucleação e evisceração), ou quando considerado o momento de sacrifício. CONCLUSÃO: Tendo em vista que a área dos adipócitos foi semelhante e não variou significativamente após a enucleação ou a evisceração, em período de observação de até 180 dias, a diminuição de volume orbitário que ocorre nas cavidades anoftálmicas deve ser conseqüência de outros mecanismos, como mudanças na distribuição espacial da gordura da órbita.

Uso de 2-octil-cianoacrilato na reconstrução da cavidade anoftálmica de coelhos

OBJETIVO: Avaliar a ligação entre músculos oculares extrínsecos e esferas de polietileno poroso usando um bioadesivo. MÉTODOS: Estudo experimental envolvendo 8 coelhos albinos submetidos a enucleação do olho direto com colocação de implante esférico de polietileno poroso de 12 mm de diâmetro unido aos músculos oculares extrínsecos por meio do bioadesivo 2-octil-cianoacrilato. Noventa dias após a cirurgia os animais foram sacrificados e o conteúdo orbitário removido. em 4 animais foi realizado estudo biomecânico, avaliando-se a força de ruptura entre a musculatura e a esfera (grupo implante) e entre a musculatura e a esclera nos olhos contralaterais (grupo controle). Nos outros 4 animais foi realizada análise histológica. RESULTADO: A avaliação biomecânica revelou que a força de ruptura entre esfera-músculo e esclera-músculo foram semelhantes quando se usa o adesivo de cianoacrilato. O exame histológico mostrou reação fibrovascular no local da adesão entre a musculatura e a esfera, sem efeitos deletérios aos tecidos. Ao redor dos implantes foi possível observar pseudocápsula e no interior, neovasos e tecido fibrovascular preenchendo os espaços entre os grânulos do polietileno. CONCLUSÃO: O adesivo 2-octil-cianoacrilato mantém boa força de adesão na união entre os músculos e as esferas de polietileno poroso, com redução do tempo cirúrgico e sem efeitos deletérios aos tecidos orbitais. Desta forma, deve-se considerar o uso do bioadesivo na reconstrução da cavidade anoftálmica.

Implantes de polietileno gel e poroso em cavidade anoftálmica de coelhos

OBJETIVO: Comparar implantes de polietileno poroso no estado sólido e gel em cavidades enucleadas. MÉTODOS: Trinta e seis coelhos albinos foram submetidos à enucleação do olho direito, recebendo esferas de polietileno poroso (18 animais) ou gel (18 animais), de 12 mm de diâmetro. Os animais foram avaliados semanalmente por exame clínico e mensalmente por ultra-sonografia modo B, realizada 30, 60 e 90 dias após a cirurgia, tendo sido os animais sacrificados aos 90 dias. Após o sacrifício, o conteúdo orbitário foi removido e examinado histologicamente. RESULTADOS: Cinco animais (27,2%) que receberam os implantes de polietileno poroso tiveram extrusão do implante. Houve extrusão em 94,4% dos animais que receberam a esfera de polietileno gel, tendo-se observado que o diâmetro das esferas gel extruídas encontrava-se aumentado em relação ao diâmetro da esfera implantada. A ultra-sonografia mostrou que o implante de polietileno poroso se vascularizou e que o gel não, o que foi confirmado pelo exame histológico. CONCLUSÃO: Esferas de polietileno no estado gel sofrem hidratação e aumentam de volume, sendo necessário conhecer o seu tamanho final antes da implantação. A ultra-sonografia permite conhecer a vascularização do implante, podendo ser usada na avaliação da integração esfera-hospedeiro.

Estudo comparativo entre as esferas de silicone gelatinosas e rígidas em cavidade eviscerada de coelho

OBJETIVO: Avaliar e comparar a biocompatibilidade de esferas de silicone gelatinosas e rígidas em cavidades evisceradas de coelhos. MÉTODOS: Trinta coelhos tiveram o olho direito eviscerado com implantação de esferas de silicone gelatinosas (Grupo I) ou rígidas (Grupo II). Foi realizada avaliação clínica diária, ultrassonografia da cavidade orbitária, análise histológica e morfométrica da pseudocápsula que se formou ao redor dos implantes aos 7, 30 e 90 dias após a cirurgia, com avaliação estatística dos resultados. RESULTADOS: Houve boa integração das esferas com os tecidos orbitários e semelhança de resposta tecidual com ambas as esferas. Duas esferas de silicone gelatinosas e uma rígida extruíram. A pseudocápsula que se formou ao redor das esferas gelatinosas foi mais organizada, com espessura e reação inflamatória menores que a observada nas esferas rígidas. CONCLUSÕES: Esferas de silicone gelatinosas e rígidas tiveram boa integração tecidual em cavidades evisceradas de coelhos.