Differential gene expression profile of retinoblastoma compared to normal retina.

PURPOSE: The retinoblastoma gene (RB1) is a tumor suppressor gene that was first discovered in a rare ocular pediatric tumor called retinoblastoma (RB). The RB1 gene is essential for normal progression through the cell cycle and exerts part of its function through the family of transcription factors (E2F) and many other intermediaries. In the absence of normal RB1, genomic instability and chromosomal aberrations accumulate, leading to tumor initiation, progression, and ultimately metastasis. The purpose of this report was to identify the molecular pathways that are deregulated in retinoblastoma. METHODS: We compared gene expression signatures of matched normal retinal tissue and retinoblastoma (RB) tumor tissue from six individuals, using microarray analysis followed by statistical and bioinformatic analyses. RESULTS: We identified 1,116 genes with increased expression and 837 with decreased expression in RB tumor tissue compared to matched normal retinal tissue. Functional categories of the cognate genes with the greatest statistical support were cell cycle (309 genes), cell death (437 genes), DNA replication, recombination and repair (270 genes), cellular growth and proliferation (464 genes), and cellular assembly and organization (110 genes). The list included differentially expressed retinal cone-cell-specific markers. These data indicated the predominance of cone cells in RB and support the idea that the latter group of cells may be the cells of origin for RB. CONCLUSIONS: The genes differentially expressed in RB as compared to normal retina belong mainly to DNA damage-response pathways, including, but not limited to, breast cancer associated genes (BRCA1, BRCA2), ataxia telangiectasia mutated gene (ATM), ataxia telangiectasia and Rad3 related gene(ATR), E2F, checkpoint kinase 1 (CHK1) genes. In addition, novel pathways, such as aryl hydrocarbon receptor (AHR) signaling, polo-like kinase and mitosis, purine metabolism pathways were involved. The molecules AHR, CHK1, and polo-like kinases are of particular interest because there are several currently available drugs that target these molecules. Further studies are needed to determine if targeting these pathways in RB will have therapeutic value. It is also important to evaluate the relative importance of these pathways in different cells that make up the normal retina

Association of Disease Location and Treatment With Survival in Diffuse Large B-Cell Lymphoma of the Eye and Ocular Adnexal Region.

Importance: Primary diffuse large B-cell lymphoma (DLBCL) of the ocular region is rare, and the utility of surgery and radiation therapy remains unresolved. Objective: To explore the clinical characteristics and determine factors associated with overall survival in primary vitreoretinal lymphoma (PVRL) and ocular adnexal (OA)-uveal DLBCL. Design, Setting, and Participants: This retrospective analysis included 396 patients with ophthalmic DLBCL from January 1, 1973, through December 31, 2014, using the Surveillance, Epidemiology, and End Results database. The median follow-up was 39.0 months (interquartile range, 5.1-72.9 months). All patients diagnosed with primary DLBCL of the eye or retina (PVRL) or the eyelid, conjunctiva, choroid, ciliary body, lacrimal gland, or orbit (OA-uveal lymphoma) were included. Patients diagnosed at autopsy or with additional neoplastic disease were excluded. Main Outcomes and Measures: Patient demographic characteristics, disease location, treatment modalities, and overall survival. Results: Forty-seven patients with PVRL (24 women [51.1%] and 23 men [48.9%]) and 349 with OA-uveal DLBCL (192 women [55.0%] and 157 men [45.0%]) had a similar mean (SD) age at diagnosis (69.6 [12.3] vs 66.1 [17.7] years). No difference in the use of surgery or radiation therapy by location was found. For all PVRL and OA-uveal DLBCL, a Cox proportional hazards regression model affirmed that age older than 60 years was associated with increased risk for death (hazard ratio [HR], 2.7; 95% CI, 1.9-4.0; P \u3c .001). Gross total resection was associated with a decreased risk for death (HR, 0.5; 95% CI, 0.3-0.9; P = .04), whereas radiation therapy was not. The 5-year overall survival among patients with PVRL was 41.4% (SE, 8.6%); among those with OA-uveal DLBCL, 59.1% (SE, 2.8%; Mantel-Cox test, P = .007). Median overall survival was lower in PVRL (38.0 months; 95% CI, 14.2-61.8 months) than in OA-uveal DLBCL (96.0 months; 95% CI, 67.3-124.7 months; Mantel-Cox test, P = .007). In addition, median overall survival in ophthalmic-only disease was higher (84.0 months; 95% CI, 63.2-104.8 months) than that in primary DLBCL that occurred outside the central nervous system and ophthalmic regions (46.0 months; 95% CI, 44.4-47.6 months; Mantel-Cox test, P \u3c .001). Conclusions and Relevance: The 5-year survival in PVRL vs OA-uveal DLBCL differed by 17.7%, and overall survival was greater in ophthalmic DLBCL than in DLBCL located outside the central nervous system and ophthalmic regions. Younger age (≤60 years) and gross total resection were associated with increased survival

Lacrimal gland tumors in Turkey: types, frequency, and outcomes.

AIM: To evaluate the clinical, radiological, and treatment features of lacrimal gland tumors. METHODS: Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were evaluated. RESULTS: The mean patient age was 40.3 (range: 7-80)y. The diagnosis was made histopathologically in 91 (91.9%) tumors and on a clinical and radiological basis in 8 (8.1%) tumors. Final diagnoses included idiopathic orbital inflammation (pseudotumor) in 46 (46.5%) lesions, pleomorphic adenoma in 14 (14.1%), adenoid cystic carcinoma in 12 (12.1%), granulomatous inflammation in 10 (10.1%), lymphoma in 5 (5.0%), benign reactive lymphoid hyperplasia in 3 (3.0%), dacryops in 3 (3.0%), carcinoma ex pleomorphic adenoma in 2 (2.0%), adenocarcinoma in 1 (1.0%), dermoid cyst in 1 (1.0%), cavernous hemangioma in 1 (1.0%), and leukemic infiltration in 1 (1.0%). Non-epithelial tumors comprised 64.6% ( CONCLUSION: Overall, 65% of lacrimal gland tumors were of non-epithelial origin and 32% of epithelial origin. By histopathology and clinical evaluation, 79% of lacrimal gland tumors were benign. The most common lacrimal gland tumors include idiopathic orbital inflammation (46.5%), epithelial (32.3%), and lymphoproliferative (8.1%) lesions

Optical Coherence Tomography Angiography Features of Iris Racemose Hemangioma in 4 Cases.

Importance: Optical coherence tomography angiography (OCTA) allows visualization of iris racemose hemangioma course and its relation to the normal iris microvasculature. Objective: To describe OCTA features of iris racemose hemangioma. Design, Setting, and Participants: Descriptive, noncomparative case series at a tertiary referral center (Ocular Oncology Service of Wills Eye Hospital). Patients diagnosed with unilateral iris racemose hemangioma were included in the study. Main Outcomes and Measures: Features of iris racemose hemangioma on OCTA. Results: Four eyes of 4 patients with unilateral iris racemose hemangioma were included in the study. Mean patient age was 50 years, all patients were white, and Snellen visual acuity was 20/20 in each case. All eyes had sectoral iris racemose hemangioma without associated iris or ciliary body solid tumor on clinical examination and ultrasound biomicroscopy. By anterior segment OCT, the racemose hemangioma was partially visualized in all cases. By OCTA, the hemangioma was clearly visualized as a uniform large-caliber vascular tortuous loop with intense flow characteristics superimposed over small-caliber radial iris vessels against a background of low-signal iris stroma. The vascular course on OCTA resembled a light bulb filament (filament sign), arising from the peripheral iris (base of light bulb) and forming a tortuous loop on reaching its peak (midfilament) near the pupil (n = 3) or midzonal iris (n = 1), before returning to the peripheral iris (base of light bulb). Intravenous fluorescein angiography performed in 1 eye depicted the iris hemangioma; however, small-caliber radial iris vessels were more distinct on OCTA than intravenous fluorescein angiography. Conclusions and Relevance: Optical coherence tomography angiography is a noninvasive vascular imaging modality that clearly depicts the looping course of iris racemose hemangioma. Optical coherence tomography angiography depicted fine details of radial iris vessels, not distinct on intravenous fluorescein angiography

Pilomatrix carcinoma of the lacrimal caruncle: a case report.

A 45-year-old man presented with a 3-month history of a mass located in the caruncle of his right eye. An incisional biopsy had been performed one month prior by another specialist, and the histopathology report showed basal cell carcinoma. The mass was completely excised with a 2 mm safety margin, and the large conjunctival defect was reconstructed with one sheet of amniotic membrane allograft. A histological diagnosis of pilomatrix carcinoma was established. To prevent recurrence after surgery, we added bevacizumab (25 mg/mL, 1.25 mg/mL per drop) eye drops four times per day for three months. At the one-year follow-up, the patient showed no evidence of local recurrence or distant metastasis after initial excision and remains under close follow-up. Pilomatrix carcinoma should be considered in the differential diagnosis of a caruncular mass

Ciliary Body Seeding after Pars Plana Transvitreal Fine-Needle Aspiration Biopsy of Choroidal Melanoma

Purpose: To report ciliary body seeding 20 years after pars plana transvitreal fine needle aspiration biopsy (FNAB) of choroidal melanoma. Case Report: 67-year-old man with choroidal melanoma in left eye was previously managed with pars plana FNAB using a 25-gauge needle followed by plaque radiotherapy. Twenty years later, choroidal melanoma was regressed but there was a small flat focus of scleral pigment 3.0mm from the limbus at the FNAB site. Ultrasound biomicroscopy showed a contiguous ciliary body mass measuring 3.1mm in thickness. Tumor seeding in the anterior chamber angle was noted inferiorly. These findings suggested melanoma recurrence along the needle tract. Treatment was performed with Iodine-125 radioactive plaque covering entire anterior segment and ciliary body recurrence. The tumor regressed to 2.2mm over one year. Conclusion: Pars plana transvitreal FNAB of choroidal melanoma resulted in needle tract seeding in ciliary body and episcleral region 20 years later

Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma.

BACKGROUND: Analysis of 52 eyes with high-risk retinoblastoma managed with postenucleation adjuvant chemotherapy using vincristine sulfate, etoposide phosphate, and carboplatin showed no evidence of systemic metastasis in any case during a mean (range) follow-up of 66 (12-202) months. PURPOSE: To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma. METHODS: Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea and optic nerve involvement. RESULTS: Of 51 consecutive patients with high-risk retinoblastoma, there were 30 males (59%) and 21 females (41%), with a median age of 28 months at diagnosis. All 52 eyes were classified as group E. The main histopathologic risk factors included anterior segment invasion (7 [13%]), isolated massive posterior uveal invasion of 3 mm or greater (6 [12%]), isolated postlaminar optic nerve invasion (15 [29%]), or any posterior uveal invasion with any optic nerve involvement (24 [46%]). There was additional invasion into the sclera (3 [6%]) and extrascleral structures, including the orbit (1 [2%]). A single histopathologic high-risk factor was present in 32 eyes (62%), whereas 20 eyes (38%) manifested 2 or more high-risk characteristics. Based on previously published series, untreated high-risk retinoblastoma carries at least a 24% risk for metastatic disease. In the present series, using vincristine, etoposide, and carboplatin in all cases, there was no metastasis during a mean follow-up of 66 months (median [range], 55 [12-202] months). CONCLUSIONS: Retinoblastoma with invasion into the postlaminar optic nerve and/or posterior uvea is at high risk for metastasis and death. In this study, postenucleation chemotherapy using vincristine, etoposide, and carboplatin was effective in preventing metastasis in every case (100%)

Conjunctival Melanoma: Features Based on the Fitzpatrick Skin Type (FST) in 540 Patients at a Single Ocular Oncology Center

Background: The Fitzpatrick skin type (FST) is a classification system for skin pigmentation that has been used to stratify risk for cutaneous melanoma; however, it has not yet been explored in the context of conjunctival melanoma. Herein, we examine FST and its association with the clinical features of conjunctival melanoma. Methods: A retrospective review was conducted on 540 medical records of patients with pathologic diagnosis of conjunctival melanoma. The patients were categorized according to the FST classification based on their external facial photographs at presentation. This includes: Type I (white skin color), Type II (fair skin color), Type III (average skin color), Type IV (light-brown skin color), Type V (brown skin color), and Type VI (black skin color). Other clinical features (namely tumor characteristics, tumor location, and tumor color) were also noted. Results: The FST included Types I (n=126, 23%), II (n=337, 62%), III (n=56, 10%), IV (n=8, 2%), V (n=12, 2%), and VI (n=1, \u3c1%). Statistical analysis (FST I vs. FST II vs. FST III, IV, V, and VI) revealed FST I and II tumors had smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p=0.01) and less eyelid involvement (13% vs. 13% vs. 28%, p=0.02). Discussion: In this analysis, we found that the majority of patients with conjunctival melanoma are FST I or II; they also had smaller tumor thickness and less eyelid involvement than FST III, IV, V, and VI. Thus, patients with FST I and II should be considered a phenotype at risk for conjunctival melanoma and be observed accordingly

Microvascular Capillary Plexus Findings of Commotio Retinae on Optical Coherence Tomography Angiography

Optical coherence tomography (OCT) and histopathology features of commotio retinae (CR) have been established, but alterations of the microvascular macular capillary plexus on OCT angiography (OCTA) has not been previously studied. We present a 46-year-old man who sustained a tennis ball injury to the right eye with visual acuity reduction to 20/30 and grey-white deep macular discoloration, suggestive of CR. Spectral-domain OCT (SD-OCT) showed increased reflectivity and thickness of the ellipsoid zone (junction of photoreceptor inner and outer segments). OCTA revealed no apparent microvascular alterations (right versus left eye) in the foveal avascular zone superficial (0.42 vs. 0.43 mm2) and deep (0.45 vs. 0.44 mm2), superficial foveal capillary density (34.1 vs. 32.6%), and superficial parafoveal capillary density (55.2 vs. 52.2%). Deep macular capillary plexus and choriocapillaris were qualitatively comparable between the two eyes. At 2 months’ follow-up, SD-OCT had normalized. CR is characterized by disruption of the ellipsoid zone without detectable alteration of the capillary plexuses