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PubMed2006

Sustained upregulation of glial fibrillary acidic protein in Müller cells in pigeon retina following disruption of the parasympathetic control of choroidal blood flow.

Choroidal blood flow in pigeon eyes is light driven and controlled by a parasympathetic input from ciliary ganglion (CG) neurons that receive input from the medial subdivision of the ipsilateral nucleus of Edinger-Westphal (EWM). EWM lesions diminish basal ChBF and irreversibly prevent ipsilateral light-evoked increases in ChBF, presumably rendering the retina mildly ischemic. To characterize the location, severity, and time course of the retinal abnormality caused by an EWM lesion, we quantitatively analyzed the cellular and regional extent of Müller cell glial fibrillary acidic protein (GFAP) immunolabeling up to nearly a year after an EWM lesion. We found that unilateral EWM lesions greatly increased Müller cell GFAP throughout the entire retinal depth and topographic extent of the affected eye, up to nearly a year post lesion. By contrast, destruction of the pupilloconstrictive pretectum or of the pupilloconstrictive part of lateral EW (EWL) did not appreciably increase Müller cell GFAP. Thus, the large increase in Müller cell GFAP following an EW lesion is attributable to an ongoing defect in choroidal vasodilatory function rather than to chronic pupil dilation. The Müller cell GFAP increase was greater ipsilateral than contralateral to the EWM destruction for the retinal territory deep to the heavily CG-innervated superior and temporal choroid, but not for the retinal territory deep to the poorly CG-innervated inferior and nasal choroid. The GFAP increase was light-dependent, since it did not occur in EW-lesioned birds housed in dim illumination. Our results show that the chronic vascular insufficiency caused by the loss of the EWM-mediated parasympathetic control of choroidal blood flow leads to a significant and sustained increase in retinal Müller cell GFAP. This increase could be a sign of a disturbance in retinal homeostasis that eventually leads to retinal injury and impaired visual function.

Animals↗
PubMed2006

Alterations in the choroid in hypercholesterolemic rabbits: reversibility after normalization of cholesterol levels.

Endothelial damage in atherosclerosis is characterized by abnormal vascular functionality. Hyperlipidemic patients show alterations in ocular vascularization. However, it is not known whether these alterations are reversible after the lipid profile returns to normal. This study evaluates a rabbit model of hypercholesterolemia, examining the ultrastructural changes in the choroid, and the changes in it after a period of normal blood-cholesterol values induced by a standard diet. Rabbits were divided into three groups: G0, fed a standard diet; G1A, fed a 0.5% cholesterol-enriched diet for 8 months; and G1B, fed a 0.5% cholesterol-enriched diet for 8 months followed by a standard diet for a further 6 months. Eyes were processed for transmission electron microscopy. G1A had a buildup of lipids at the suprachoroidea that compressed the vascular layers, and hypertrophy of endothelial and vascular smooth muscle cells. In G1B there was less lipid accumulation than in G1A, but this was not followed by reversal of the choroidal damage. The suprachoroidea thickness of G1B was still greater than in G0 due to abundant collagen fibers. The intervascular spaces of the choroid had fewer lipids than G1A but more collagen fibers than G0. The large- and medium-sized vessel layers and choriocapillaris were less compressed than in G1A but exhibited basal membrane and endothelial changes similar to those in G1A. Normalization of serum cholesterol levels is not enough to reverse cholesterol-induced vascular damage to the choroid. These choroidal changes could be compatible with a chronic ischemia that could produce retinal degeneration.

Animals↗
PubMed2005

A novel role for the choroid plexus in BMP-mediated inhibition of differentiation of cerebellar neural progenitors.

Cerebellar granule cells, the most abundant neurons in the mammalian brain, arise in the rhombic lip located at the roof of the brain's fourth ventricle. Bordering the rhombic lip is the choroid plexus, a non-neuronal structure, composed of blood vessels enveloped by epithelial cells. Here, we show a striking decrease in neural differentiation of rhombic lip-derived cells, which failed to extend neuritic processes and attenuate Math1 promoter activity, when co-cultured with choroid plexus cells. Moreover, a blocking antibody against BMP7, a morphogenetic protein expressed in the choroid plexus, blocked the inhibitory effect of the choroid plexus, whereas purified BMP7 mimicked this effect, demonstrating causal involvement of BMP. On the other hand, the BMP antagonist NBL1 promoted neurogenesis in rhombic lip cultures from Math1 null mice displaying arrested differentiation. Our data indicate that besides its secretory and barrier functions, the choroid plexus has a novel role in attenuating the differentiation of adjacent neural progenitors.

Animals↗
PubMed2005

Primary choroidal melanoma in phakomatosis pigmentovascularis IIa.

PURPOSE: To describe a previously unreported association between phakomatosis pigmentovascularis (PPV) IIa and primary choroidal melanoma. DESIGN: Case series. PARTICIPANTS: Three patients with PPV type IIa and choroidal melanoma. RESULTS: Nevus flammeus was present unilaterally in each patient, involving the hemiface, the hemithorax, or both. Ocular melanocytosis also was present unilaterally in all patients involving the sclera, the iris, the choroid, the distribution of the trigeminal nerve, or a combination thereof. Renal cysts were noted in patient 1, and a nevus anemicus of the neck was noted in patient 3. A unilateral choroidal melanoma was detected in each of these 3 patients, in each patient involving the same eye in which melanocytosis had been seen. No metastases were found in any patient. CONCLUSIONS: Clinicians should be aware of the possibility that PPV, and in particular that occurring in patients with ocular melanocytosis, can be associated with choroidal melanoma.

Adult↗
PubMed2005

Forecasting the prognosis of choroidal melanoma with an artificial neural network.

PURPOSE: To develop an artificial neural network (ANN) that will forecast the 5-year mortality from choroidal melanoma. DESIGN: Retrospective, comparative, observational cohort study. PARTICIPANTS: One hundred fifty-three eyes of 153 consecutive patients with choroidal melanoma (age, 58.4+/-14.6 years) who were treated with ruthenium 106 brachytherapy between 1988 and 1998 at the Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. METHODS: Patients were observed clinically and ultrasonographically (A- and B-mode standardized ultrasonography). Metastatic screening included liver function tests and liver imaging. Backpropagation ANNs composed of 3 or 4 layers of neurons with various types of transfer functions and training protocols were assessed for their ability to predict the 5-year mortality. The ANNs were trained on 77 randomly selected patients and tested on a different set of 76 patients. Artificial neural networks were compared based on their sensitivity, specificity, forecasting accuracy, area under the receiver operating curves, and likelihood ratios (LRs). The best ANN was compared with the results of logistic regression and the performance of an ocular oncologist. MAIN OUTCOME: The ability of the ANNs to forecast the 5-year mortality from choroidal melanoma. RESULTS: Thirty-one patients died during the follow-up period of metastatic choroidal melanoma. The best ANN (one hidden layer of 16 neurons) had 84% forecasting accuracy and an LR of 31.5. The number of hidden neurons significantly influenced the ANNs' performance (P<0.001). The performance of the ANNs was not significantly influenced by the training protocol, the number of hidden layers, or the type of transfer function. In comparison, logistic regression reached 86% forecasting accuracy, with a very low LR (0.8), whereas the human expert forecasting ability was <70% (LR, 1.85). CONCLUSIONS: Artificial neural networks can be used for forecasting the prognosis of choroidal melanoma and may support decision-making in treating this malignancy.

Brachytherapy↗
PubMed2005

Outcomes of iodine 125 plaque radiotherapy after initial observation of suspected small choroidal melanomas: a pilot study.

PURPOSE: To determine the visual and survival outcomes for patients undergoing plaque radiotherapy of suspected small choroidal melanomas after observation for growth in a pilot study. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Forty-five patients with suspected small choroidal melanomas who were seen at the Bascom Palmer Eye Institute between 1974 and 2001 and had iodine 125 (I125) plaque radiotherapy between 1991 and 2002. METHODS: Patients with suspected small choroidal melanomas were monitored by clinical examination, photography, and echography. When the melanoma grew or developed orange pigment, patients were treated with I125 plaque radiotherapy. Outcomes included visual acuity, ocular complications, tumor dimensions, metastasis, and death. MAIN OUTCOME MEASURE: Melanoma-specific mortality. RESULTS: In our pilot study, 1 patient died from metastatic melanoma. One patient developed metastatic disease and is still alive. One patient developed marginal tumor recurrence after treatment and after enucleation was performed. Globe conservation was achieved in 97.8% of patients. In patients with tumor margins >2 mm from the optic nerve, vision was preserved with less than a doubling of the visual angle (within approximately 2 Snellen lines of preoperative acuity) in 90.6% (29/32) of patients at 1 year postoperatively, 65.6% (21/32) at 2 years, and 52.2% (12/23) in the long term (4-11 years). CONCLUSIONS: Five-year melanoma-specific mortality after I125 plaque radiotherapy of suspected small choroidal melanomas was 3.9% (95% confidence interval, 0%-11.2%). This information can be used to counsel patients with small suspected choroidal melanomas and to compare with other treatment modalities.

Adult↗
PubMed2006

Fluorescent in situ hybridization for monosomy 3 via 30-gauge fine-needle aspiration biopsy of choroidal melanoma in vivo.

OBJECTIVE: To report the feasibility of intraoperative transscleral fine-needle aspiration biopsy at plaque surgery to obtain cells for monosomy 3 analysis in patients with choroidal melanoma. DESIGN: Consecutive interventional case series. PARTICIPANTS: Eighteen patients (18 eyes) with choroidal melanoma who had fine-needle aspiration biopsy performed with a 30-gauge needle at time of iodine 125 plaque placement. INTERVENTION: Cytology and cytogenetic analysis for monosomy 3 were obtained from biopsy specimens. MAIN OUTCOME MEASURES: Cytology, cytogenetic analysis for monosomy 3, and complications and feasibility of transscleral fine-needle aspiration biopsy of choroidal melanoma in vivo. RESULTS: Fine-needle aspiration biopsy was diagnostic of choroidal melanoma in 14 of 18 cases and resulted in viable cell cultures for fluorescent in situ hybridization (FISH) analysis in 9 cases. Fluorescent in situ hybridization for monosomy 3 was positive in 4 of the 9 cases. One patient had a mild vitreous hemorrhage. Tumors between 2 and 3 mm in height and those that yielded cells that did not attach in culture were most likely to have insufficient growth for FISH analysis. CONCLUSIONS: Transscleral fine-needle aspiration biopsy and FISH for monosomy 3 may provide important prognostic information on patients who undergo plaque radiotherapy for choroidal melanoma.

Adult↗
PubMedDate not supplied

Transpupillary thermotherapy in the management of circumscribed choroidal hemangioma.

Laser photocoagulation and various radiation therapy methods have been used in the treatment of circumscribed choroidal hemangioma that produce visual loss. Recently, transpupillary thermotherapy has been employed in the management of choroidal hemangioma. Thirty-six cases of choroidal hemangioma treated with transpupillary thermotherapy are reviewed. Twenty-eight cases were reported in the literature and 10 cases were managed by the author. Transpupillary thermotherapy has been used as a primary treatment (36 cases) or secondary treatment (2 cases) for choroidal hemangioma. The goal of transpupillary thermotherapy is to achieve resolution of exudative detachment of the fovea and improvement of vision. In all eyes the foveal detachment subsided. In 26 eyes having pretreatment visual acuity >or=0.05 (20/400), the visual acuity increased in 20 (77%) eyes and remained unchanged in 6 (23%) eyes. After transpupillary thermotherapy, 16 (42%) cases showed complete regression, 20 (53%) demonstrated partial regression, and in 2 (5%) there was no change in tumor thickness at follow-ups ranging from 2 to 44 months. Complications of transpupillary thermotherapy of choroidal hemangioma included cystoid macular edema (3 eyes), preretinal fibrosis (2 eyes), focal iris atrophy (3 eyes), and retinal vascular occlusion (1 eye). Although the follow-up in many studies is limited, transpupillary thermotherapy has not been associated with any significant complications.

Choroid Neoplasms↗
PubMed2006

The transcription factors Emx1 and Emx2 suppress choroid plexus development and promote neuroepithelial cell fate.

The transcription factors Emx1 and Emx2 exert important functions during development of the cerebral cortex, including its arealization. Here, we addressed their role in development of the derivatives of the midline region in the telencephalon. The center of the midline region differentiates into the choroid plexus, but little is known about its molecular specification. As we noted a lack of Emx1 or 2 expression in the midline region early in development, we interfered by misexpressing Emx1 and/or Emx2 in this region of the chick telencephalon. Ectopic expression of either Emx1 or Emx2 prior to HH 13 instructed a neuroepithelial identity in the previous midline region instead of a choroidal fate. Thus, Gli3 and Lhx2 normally restricted to the neuroepithelium expanded into the Emx misexpressing region. This was accompanied by down-regulation of Otx2 and BMP7, which implicates that these factors are essential for choroid plexus specification and differentiation. Interestingly, the region next to the ectopic Emx-misexpression then acquired a hybrid identity with some choroidal features such as Bmp7, Otx2 and Ttr gene expression, as well as some neuroepithelial features. These observations indicate that the expression levels of Emx1 and/or Emx2 restrict the prospective choroid plexus territory, a novel role of these transcription factors.

Animals↗
PubMed2000

Choroidal neovascularization with granulomatous inflammation in ocular histoplasmosis syndrome.

PURPOSE: To report pathologic examination of an excised choroidal neovascular membrane in a patient with ocular histoplasmosis syndrome that demonstrated granulomatous inflammation. METHOD: Case report. A 50-year-old woman with sudden vision loss in her left eye demonstrated clinical and fluorescein angiographic findings characteristic of choroidal neovascularization secondary to ocular histoplasmosis syndrome. RESULTS: Histopathologic examination of the surgically excised choroidal neovascular membrane disclosed granulomatous inflammation. CONCLUSIONS: This case suggests an important role of mononuclear phagocytic cells as primary mediators of angiogenesis or modifiers of choroidal neovascularization. This association of choroidal neovascularization with granulomatous inflammation did not respond to treatment with systemic corticosteroids.

Choroidal Neovascularization↗
PubMed2000

Bilateral diffuse choroidal hemangiomas with unilateral facial nevus flammeus in Sturge-Weber syndrome.

PURPOSE: To report bilateral choroidal hemangiomas associated with unilateral facial nevus flammeus in Sturge-Weber syndrome. METHODS: Case report. RESULTS: A 6-year-old male with a left facial nevus flammeus and a history of a left cerebral angioma had been followed 2 years for increasing esotropia. Examination demonstrated bilateral diffuse choroidal hemangiomas with overlying exudative retinal detachments. After bilateral external beam radiotherapy, the retinal detachments resolved and vision improved. CONCLUSION: Patients with Sturge-Weber syndrome and unilateral facial nevus flammeus may harbor bilateral choroidal hemangiomas. Clinical manifestations of the Sturge-Weber syndrome are characteristically unilateral and ipsilateral to the facial nevus flammeus. Bilateral choroidal hemangiomas associated with bilateral facial nevus flammeus are rare. 1,2 We report bilateral diffuse choroidal hemangiomas associated with unilateral facial nevus flammeus in Sturge-Weber syndrome.

Child↗
PubMed2000

Bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type.

PURPOSE: To report a patient with bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type. METHODS: Case report. RESULTS: A 55-year-old woman complained of visual field loss and decreasing vision. Seven months earlier, uterocervical carcinoma of the squamous cell type was diagnosed and treated with chemotherapy and irradiation. Serous retinal detachment and choroidal masses were present in both eyes. Retinal detachment was lessened in both eyes after radiotherapy. The patient died of respiratory insufficiency 3 months after the appearance of choroidal metastases. At autopsy, there was no second cancer to cause the choroidal metastases. Tumor embolization was present in the choriocapillaries. CONCLUSION: Choroidal metastasis may develop from hematogenous spread of uterocervical squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed2000

Ultrasonographic evidence of a mushroom-shaped choroidal metastasis.

PURPOSE: To describe the evolution of a "collar-button" or mushroom-shaped choroidal metastasis. METHODS: Case report. RESULTS: A 52-year-old woman with known primary colon cancer and widespread extraocular metastases developed bilateral choroidal masses with neurosensory retinal detachments. Clinical and ultrasound evaluation demonstrated evolution of a choroidal metastasis with a "collar-button" configuration in the right eye. CONCLUSION: A choroidal metastasis may develop a mushroom-shaped configuration. This "collar-button" configuration is not pathognomonic for choroidal melanoma.

Choroid Neoplasms↗
PubMed2001

Extramedullary plasmacytoma confined to the choroid.

PURPOSE: To report a case of an extramedullary plasmacytoma confined to the choroid. METHODS: Interventional case report with cytopathologic correlation. RESULTS: A 76-year-old asymptomatic woman presented with 2 globular orange and amelanotic choroidal lesions in the right eye. Fine needle aspiration biopsy of one of the choroidal lesions followed by immunocytochemical studies revealed monoclonal plasma cells, diagnostic of plasmacytoma. Systemic evaluation was negative, except for increased serum gamma globulin with immunoglobulin kappa spike on electrophoresis. The patient was managed by ocular external beam radiotherapy. At 9 years follow-up, she was free of local disease and never developed multiple myeloma. CONCLUSION: Extramedullary plasmacytoma confined to the choroid is rare. It may present simulating other common amelanotic choroidal lesions. Fine needle aspiration biopsy and proper systemic evaluation are critical in establishing the diagnosis.

Aged↗
PubMed2001

Absence of type I estrogen receptors in choroidal melanoma: analysis of Collaborative Ocular Melanoma Study (COMS) eyes.

PURPOSE: To evaluate choroidal melanomas in enucleated eyes for the presence of type I estrogen receptors. METHODS: Fourteen consecutive eyes with large choroidal melanomas (defined as >16-mm basal diameter and >8 mm thickness) from 14 patients (eight women and six men with a mean age of 57 years; range, 25--74 years) enucleated in accordance with the Collaborative Ocular Melanoma Study (COMS) protocol were investigated. Immunohistochemical techniques were employed to label the choroidal melanomas for the presence of type I estrogen receptors. Each specimen was then evaluated in a masked fashion by an experienced ophthalmic pathologist for positive nuclear staining. RESULTS: No tumors showed immunohistochemical evidence of a type I estrogen receptor. CONCLUSION: Type I estrogen receptors are not present in choroidal melanoma. Estrogens are not likely to influence choroidal melanoma growth through traditional receptors.

Adult↗
PubMed2001

Choroidal neovascularization associated with aplasia of the optic nerve.

PURPOSE: To report an unusual case of unilateral aplasia of the optic nerve associated with choroidal neovascularization. DESIGN: Observational case report. METHODS: In a 29-year-old female with optic nerve aplasia of the right eye and no choroidal neovascularization at age 23 years, choroidal neovascularization of the right eye was present by ophthalmoscopy and fluorescein angiography. RESULTS: Fluorescein angiography disclosed de novo choroidal neovascularization corresponding to fibrovascular proliferation evident on ophthalmoscopy at age 29 years. CONCLUSION: Choroidal neovascularization may develop de novo during adult life in an eye with optic nerve aplasia.

Adult↗
PubMed2002

Intraoperative choroidal hemorrhage in the Osler-Rendu-Weber syndrome.

PURPOSE: To describe a patient with Osler-Rendu-Weber syndrome who developed a nonsimultaneous intraoperative choroidal hemorrhage in each eye. METHOD: Interventional case report. A 65-year-old Caucasian woman with Osler-Rendu-Weber syndrome developed a choroidal hemorrhage in the left eye during vitrectomy for a complicated retinal detachment with a poor visual outcome. Fifteen years later, she developed a macula on retinal detachment in the right eye, which also had a dense cataract. Immediately after uncomplicated phacoemulsification and intraocular lens implantation, under monitored anesthesia care and retrobulbar block, and without valsalva stress, ophthalmoscopy demonstrated a choroidal hemorrhage. A planned scleral buckle was replaced by pneumatic retinopexy. RESULTS: Seven months postoperatively, the retina remained attached with resolution of the choroidal hemorrhage. Visual acuity was 20/30. CONCLUSION: Choroidal hemorrhage may occur more commonly in individuals with Osler-Rendu-Weber syndrome. Recognition of this possible association and institution of appropriate intraoperative precautions may facilitate a good visual outcome.

Aged↗
PubMed2002

Mesectodermal leiomyoma exclusively involving the posterior choroid.

PURPOSE: To report a mesectodermal leiomyoma of the posterior choroid. DESIGN: Observational case report. METHODS: A 23-year-old man was referred to us because of a progressive blurred vision in his left eye. Ophthalmologic examination revealed the presence of a 12 x 10 x 7.2-mm amelanotic choroidal mass in his left posterior pole. Fluorescein angiography, A-scan ultrasonography, and B-scan echography findings were suggestive for a diagnosis of choroidal amelanotic melanoma. These clinical features prompted us to enucleate the left eye. RESULTS: Histopathological and immunohistochemistry examinations established a definitive diagnosis of mesectodermal leiomyoma of the posterior choroid. CONCLUSION: This case represents the first report describing the occurrence of an intraocular mesectodermal leiomyoma that may exclusively involve the posterior choroid.

Adult↗