Peripheral subretinal pigment accumulation following transpupillary thermotherapy for choroidal melanoma.

Transpupillary thermotherapy (TTT) used as either an adjunct to plaque brachytherapy or a primary treatment for choroidal melanoma can cause several intraocular complications, particularly in the retina. A 61-year-old woman had a macular choroidal melanoma measuring 8 x 7.5 X 3.6 mm and received TTT in three sessions, each 6 months apart. After the second treatment, pigmented material began to accumulate on the peripheral retina with an increasing pace. The tumor gradually regressed for 16 months, followed by a sudden regrowth. Enucleation of the eye revealed that the peripheral subretinal pigmented deposits consisted of pigment-laden macrophages and retinal pigment epithelial cells without viable tumor cells. The rare complication of peripheral subretinal pigment dispersion following TTT should not be alarming, but close monitoring is recommended.

Expression of vascular endothelial growth factor-A, matrix metalloproteinase-9, and extravascular matrix patterns and their correlations with clinicopathologic parameters in posterior uveal melanomas.

PURPOSE: To assess extravascular matrix patterns (EMP) and expression of vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in posterior uveal melanomas and their correlations with histopathologic parameters and metastasis. METHODS: This study was conducted on 100 consecutive eyes enucleated for posterior uveal melanomas. All tumors were examined by immunohistochemical techniques for VEGF-A and MMP-9 expression, and the presence of EMPs was assessed on routine paraffin sections stained with reticulin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration, and scleral and optic nerve invasion were analyzed by using light microscopy. No eyes had received prior treatment such as radiotherapy or transpupillary thermotherapy. RESULTS: Identified histopathologically, cell types were spindle cells in 60% of the cases, mixed cells in 14%, and epithelioid cells in 26% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 84% and 72% of the tumors, respectively. Microvascular loops and/or networks were seen in 34% of the tumors, with the remaining 16% of the tumors displaying an arc pattern, 21% displaying a parallel pattern, and 29% displaying the normal pattern. The relationships between VEGF-A and MMP-9 expression and necrosis, the degree of lymphocyte infiltration, mitotic rate, and the formation of loop and network patterns were found to be statistically significant (P < 0.05). Metastatic disease developed in 14 patients during follow up. CONCLUSIONS: The incidence of metastatic melanoma increased with the increasing expression of VEGF-A and MMP-9. Our data suggest that increasing VEGF-A and MMP-9 expression and the EMP can be used as independent prognostic factors in the management of posterior uveal melanoma following enucleation.

Clinicopathological parameters and expression of P-glycoprotein and MRP-1 in retinoblastoma.

PURPOSE: The immunohistochemical expressions of two multidrug resistance proteins, P-glycoprotein (P-gp) and multidrug resistance-related protein-1 (MRP-1), were studied in retinoblastoma and the correlations with the clinicopathological parameters were assessed. METHOD: Sixty-five enucleated eyes containing retinoblastoma were included in the study. Following hematoxylin-eosin staining, tumor differentiation, presence of choroidal invasion, optic nerve invasion, retinal invasion, necrosis and presence of calcification were evaluated with the light microscope. P-gp and MRP-1 expressions were evaluated immunohistochemically. RESULTS: Fifty-three eyes were enucleated primarily and 12 eyes were operated after failure of chemotherapy. P-gp and MRP-1 expressions were positive in 69.3 and 73.4% of specimens, respectively. There was no statistically significant relationship between the expressions of P-gp and MRP-1, and tumor differentiation, presence of tumor invasion or treatment with chemotherapy. CONCLUSION: Retinoblastoma intrinsically expresses both P-gp and MRP-1 and their expressions are not related to tumor differentiation. The expressions of P-gp and MRP-1 do not seem to be induced by chemotherapy and are not related to the degree of tumor invasion.

Simultaneous conjunctival, uveal, and orbital involvement as the initial sign of acute lymphoblastic leukemia.

BACKGROUND: A case of acute lymphoblastic leukemia with an initial presentation of unilateral simultaneous conjunctival, uveal, and orbital infiltration is reported. CASE: A 9-year-old girl presented with mild proptosis and chemosis and total exudative retinal detachment in the right eye. OBSERVATIONS: B-mode ultrasonography showed diffuse uveal thickening and a retrobulbar mass. Magnetic resonance imaging scans demonstrated a well-circumscribed peribulbar orbital mass. Incisional biopsy from the conjunctiva and bone marrow sampling established the diagnosis of acute lymphoblastic leukemia L1 type. CONCLUSION: Blast-cell infiltration of three distinct ocular structures simultaneously in the absence of any peripheral signs is an extremely rare initial manifestation of acute lymphoblastic leukemia.

Severe pseudo-preseptal cellulitis following sub-Tenon's carboplatin injection for intraocular retinoblastoma.

Sub-Tenon or subconjunctival administration of carboplatin is used to consolidate tumor regression by achieving high intraocular concentrations, without incurring systemic toxicity, in selected patients with intraocular retinoblastoma. Mild transient periocular edema is a common side effect of this treatment. We describe four patients with severe local soft-tissue toxic reaction mimicking preseptal cellulitis following subtenon carboplatin injections. The development of this complication after injecting through the inferior conjunctiva and unexpectedly severe signs are the unusual features of these patients. We did not encounter this complication after injections through the superior conjunctiva in 22 other patients using the same technique and identical drug dosage.

Expression of vascular endothelial growth factor a, matrix metalloproteinase 9 and extravascular matrix patterns in iris and ciliary body melanomas.

PURPOSE: It was the aim of this study to assess the expression of vascular endothelial growth factor (VEGF)-A, matrix metalloproteinase (MMP)-9 and extravascular matrix patterns (EMPs) in iris and ciliary body melanomas and their correlations with histopathologic parameters. METHODS: The study was conducted on 3 iris and 15 ciliary body melanomas. All tumors were subjected to immunohistochemical techniques for VEGF-A and MMP-9 expressions, the presence of EMPs was assessed, and routine paraffin sections were stained with hematoxylin-eosin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration and sclera invasion were analyzed using light microscopy. RESULTS: The mean patient age at the time of treatment was 43 years (range 19-69, median 39.5); 10 (55.6%) patients were males and 8 (44.4%) females. Histopathological cell types were spindle cells in 55.6%, mixed cells in 16.7%, and epithelioid cell types in 27.8% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 66.7 and 72.3% of the tumors, respectively. Microvascular loops and/or networks were seen in 33.4% of the tumors, with the remaining 66.7% of tumors displaying one or more of the other patterns. Metastatic disease developed in only 1 patient during follow-up. Tumor cell type, tumor size, mitotic rate, degree of pigmentation and EMPs were not correlated with metastasis. CONCLUSIONS: This study suggests that VEGF-A and MMP-9 were positive in the majority of iris and ciliary body melanomas. No correlation was found between VEGF-A and MMP-9 immunoreactivity and EMPs and occurrence of metastases in cases of anterior uveal melanoma.

Dermoid cyst of the lacrimal gland.

The case of a 33-year-old-woman with a recent onset of left upper eyelid swelling is described. Imaging studies demonstrated a cystic lesion in the left lacrimal gland fossa. Excisional biopsy of the mass showed a dermoid cyst entirely surrounded by a thin layer of normal lacrimal gland tissue. The authors present a highly unusual case of a soft tissue orbital dermoid cyst arising from the lacrimal gland.

Transconjunctival approach for retrobulbar intraconal orbital cavernous hemangiomas. Orbital surgeon's perspective.

BACKGROUND: Cavernous hemangioma is the most common benign intraorbital tumor found in adults. Most cavernous hemangiomas are located within the intraconal space. When indicated, complete surgical removal is the only treatment option. Several surgical techniques have been refined over the past decades. We describe our experience over transconjunctival approach in 24 patients with retrobulbar intraconal orbital cavernous hemangiomas. METHOD: This retrospective study includes 24 nonrandomly selected patients who had retrobulbar intraconal tumors. The presumptive preoperative diagnosis was based on magnetic resonance imaging findings. Compression on the optic nerve and/or the globe and proptosis constituted indications for surgery. The tumor was exposed via a transconjunctival route after temporarily disinserting an extraocular muscle depending on the location of the lesion. RESULTS: In all patients, the tumor was in touch with the globe and in most cases extended to the orbital apex. All tumors were removed intact. In 14 patients, tumors were extirpated with the aid of a cryoprobe. Visual acuity increased in 8 patients and remained stable in the rest. No serious or permanent complications were observed during or after the operation. CONCLUSIONS: Retrobulbar intraconal cavernous hemangiomas can be removed successfully through a transconjunctival approach with minimal damage to surrounding tissues. This method is best for tumors whose anterior borders are in contact or very close to the eye even if the posterior border abuts the orbital apex.

Serum melatonin levels following enucleation and transpupillary thermotherapy in patients with choroidal melanoma.

PURPOSE: To study serum melatonin levels in patients with choroidal melanoma preoperatively and following enucleation and transpupillary thermotherapy. METHODS: Forty patients with preoperative choroidal melanoma were included in the study. Of these, 15 patients underwent enucleation (group 1) and 25 patients received transpupillary thermotherapy (group 2). A further 20 patients without melanoma acted as age-matched controls. Serum melatonin levels were determined 1 day preoperatively, and at the first and sixth months postoperatively using ELISA. RESULTS: Preoperative serum melatonin levels were highest in group 2 followed by group 1, but this was not statistically significant compared to controls. Postoperatively, a constant decrease of serum melatonin was observed in both groups after the first month, which reached statistical significance at the sixth month (P = 0.003). Also, a significant regression in tumour thickness was documented in group 2 (P = 0.003). Three patients in group 1 developed hepatic metastases. CONCLUSIONS: Patients with choroidal melanomas had higher levels of serum melatonin compared to individuals without tumours. Smaller tumours were associated with more elevated melatonin levels compared to larger tumours. Serum melatonin levels fell considerably following enucleation and transpupillary thermotherapy.

Quantitative analysis of proliferation, apoptosis, and angiogenesis in retinoblastoma and their association with the clinicopathologic parameters.

PURPOSE: Quantitative analyses of proliferation, apoptosis, and angiogenesis, which may be important for the prognosis of retinoblastoma, were performed and possible associations with some well-known clinicopathologic parameters were investigated. METHODS: Fifty-three pathology specimens (43 enucleations, 10 exenterations) were evaluated by immunohistochemical methods. The proliferative index was detected by Ki67 antibody staining. The apoptotic index was calculated by the in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and angiogenesis was detected by CD34 antibody staining. RESULTS: The mean proliferative index was 37.63+/-11.12, the mean apoptotic index was 2.67+/-1.18, and the microvessel density and mean vascular area were determined as 3.14+/-1.4 and 38.73+/-12.70, respectively. Statistical analysis showed that the proliferative index was directly proportional to the tumor dimensions (P=.001). In addition, the tumor dimensions were larger in cases where the apoptotic index was below 2.4% (P=.011). In cases where the apoptotic index was over 2.4%, no metastasis was observed and also a lower proliferative index was found (P=.014). CONCLUSIONS: Proliferation appears to be more important than apoptosis and angiogenesis in determining the tumor dimensions. The apoptotic index may be an important predictor of metastasis, and may be useful in the follow-up of bilateral cases with 1 eye enucleated.

Intramuscular hemangiomas of extraocular muscles.

PURPOSE: To report two patients, 3 and 40 years of age, respectively, each of whom had an isolated intramuscular hemangioma of an extraocular muscle. DESIGN: Two retrospective, interventional case reports. INTERVENTION: Incisional biopsy and short-term oral corticosteroids. MAIN OUTCOME MEASURES: Clinical observation and pathologic examination of specimens and tumor status, visual acuity, and ocular motility at final follow-up. RESULTS: Orbital magnetic resonance imaging revealed that, compared with other extraocular muscles, the tumor was isointense on T1-weighted scans and hyperintense on T2-weighted images. Marked homogeneous enhancement was observed after contrast agent administration. Biopsy results showed a hemangioma of the lateral rectus muscle with predominantly capillary-like small vessels in the child and a mixed small and large vessel type hemangioma of the medial rectus muscle in the adult. CONCLUSIONS: Intramuscular hemangiomas may cause painless, isolated extraocular muscle enlargement in children and in adults without disturbing the ocular motility. The tumors do not seem to be sensitive to systemic corticosteroid therapy.

Intramuscular hydatid cyst of the medial rectus muscle.

PURPOSE: To describe a unique case of orbital hydatid cyst that was located solely within the medial rectus muscle. DESIGN: Retrospective, interventional case report. METHODS: A 20-year-old woman presented with right periocular pain induced by ocular movements. Magnetic resonance imaging studies showed a focal, well-circumscribed intramuscular cystic lesion of the right medial rectus muscle. The cyst was completely extirpated from the muscle, but some of the fluid content escaped into the surrounding tissues. Irrigation with hypertonic saline was performed. RESULTS: Histopathologic examination showed an acellular cyst wall with inner germinal layer, diagnostic for hydatid cyst. Two cycles of oral albendazole were administered with no recurrence. CONCLUSIONS: In the orbit, hydatid cyst may be localized primarily within an extraocular muscle and produce painful eye movements. Hydatid cyst must be considered in the differential diagnosis of solitary cystic enlargements of extraocular muscles.

Subretinal pigment dispersion following transpupillary thermotherapy for choroidal melanoma.

PURPOSE: To report the case of a patient who developed considerable subretinal pigment/debris dispersion following transpupillary thermotherapy (TTT). This type of tumour response is extremely rare with this relatively new therapeutic modality. METHODS: A 50-year-old man with a left juxtapapillary choroidal melanoma measuring 8 x 6 x 4.3 mm was treated with 810 nm diode laser TTT administered in two sessions. Spot size was 3 mm and the power setting was 450 mW. RESULTS: Four months after the first treatment session, a considerable amount of pigment/debris was seen to have dispersed in the subretinal space, accumulating mainly in the macular area. Over a 12-month follow-up, the tumour showed progressive shrinkage without any change in the amount or location of the shed pigment/debris. No new tumour formation, recurrence or systemic metastases were detected. CONCLUSION: Subretinal pigment/debris dispersion is an unusual complication after TTT and requires close follow-up. There has been no short-term compromise on the life or visual acuity of this patient.

Spontaneous regression of retinal astrocytic hamartoma in a patient with tuberous sclerosis.

PURPOSE: To report the complete regression of a retinal astrocytic hamartoma in conjunction with tuberous sclerosis. DESIGN: Observational case report. METHODS: A 12-year-old boy with tuberous sclerosis, diagnosed early in life, was found to have a retinal astrocytic hamartoma in his left eye. He had bilateral optic atrophy because of long-standing increased intracranial pressure due to a cerebral giant cell astrocytoma. He was followed on a yearly basis with fundus photography and fluorescein angiography. RESULTS: At the time of initial presentation, the minimally elevated intraretinal tumor measured 2 x 1.5 mm. A year later, the same tumor measured 1.5 x 1 mm. Two years after initial presentation, the tumor totally disappeared. CONCLUSION: This patient has demonstrated that retinal astrocytic hamartoma may undergo spontaneous regression.

Quantitative analysis of apoptosis in retinoblastoma.

PURPOSE: The rate of apoptosis in retinoblastoma (Rb) and the factors that may influence this rate, such as therapy prior to surgery, amount of necrosis in tumour tissue, differentiation and laterality of the tumour, were investigated. METHODS: Thirty-one specimens (25 enucleation, six exenteration) with Rb were studied. Prior to final surgery, three patients received systemic chemotherapy, one intravitreal chemotherapy, one transpupillary thermotherapy, one external beam radiotherapy and one high-dose oral methylprednisolone therapy. The apoptotic index (AI,%) was calculated by counting at least 1000 cells under light microscopy (x 100) using TUNEL (terminal deoxynu-cleotidyl transferase-mediated dUTP nick-end labelling) method. RESULTS: The mean AI was 2.75 plus minus 1.2. No statistically significant association was observed between rate of apoptosis and the presurgical treatment, extent of necrosis, tumour differentiation and laterality. CONCLUSION: Apoptosis is an important mechanism of cell death, and may be a limiting factor for tumour progression. In this study, the rate of apoptosis was not affected by any of the studied parameters.

An unusual clinical course of adenoid cystic carcinoma of the lacrimal gland.

The case of a 25-year-old woman with adenoid cystic carcinoma of the lacrimal gland is reported. Her complaints, including pain and localized swelling, first started six years earlier. She was diagnosed elsewhere as orbital pseudotumor based on clinical and computed tomographic features and was prescribed oral corticosteroids. The regimen completely relieved her signs and symptoms, which regularly recurred in the ensuing years. When she finally presented with rapidly worsening proptosis and pain, she underwent incisional biopsy followed by exenteration and 6000 cGy of radiotherapy. This patient is a rare example of adenoid cystic carcinoma of the lacrimal gland with an atypical clinical course of long duration during which corticosteroids completely suppressed the clinical signs and symptoms.

Combined treatment of periorbital arteriovenous malformation: a case report.

A 54-year-old woman had a gradually growing subcutaneous mass for more than three decades over her right zygomatic bone and below the right inferior orbital rim. The tumor was slightly pulsatile and non-tender. MRI scans demonstrated an unusually vascularized soft tissue mass with many large-caliber vessels. Selective angiography showed the mass to be an arteriovenous malformation with the principal feeder being the internal maxillary artery. A combined treatment scheme which consisted of an initial embolization of the lesion followed by surgical extirpation was carried out. This sequential approach allowed safer surgery and a satisfactory cosmetic outcome.