Shields CL, Kaliki S, Al-Dahmash S, et al.
Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases.
JAMA Ophthalmol. 2013; 131(3):328-34 [PubMed]

OBJECTIVE: To compare the clinical features of primary vs secondary retinal vasoproliferative tumors (VPTs).
METHODS: Retrospective case series of 334 tumors in 295 eyes of 275 patients.
RESULTS: Of 275 patients with VPT, 41% (n = 113) were male and 59% (n = 162) were female, with a mean age of 44 years at presentation. Primary VPT occurred in 80% (n = 219) and secondary VPT, in 20% (n = 56) of patients. Secondary VPT (n = 67) occurred in eyes with retinitis pigmentosa (n = 15, 22%), pars planitis (n = 14, 21%), Coats disease (n = 11, 16%), previous retinal detachment surgery (n = 8, 12%), idiopathic peripheral retinal vasculitis (n = 4, 6%), familial exudative vitreoretinopathy (n = 3, 4%), and others (n = 12, 18%). The mean interval between diagnosis of underlying ocular condition and secondary VPT was 160 months. Statistically significant differences (P < .05) in clinical features (primary vs secondary VPTs) included mean age at presentation (46 vs 38 years), visual symptoms (74% vs 87%), poor visual acuity worse than 20/200 (15% vs 28%), bilaterality (4% vs 20%), multifocality (5% vs 15%), postequatorial tumor location (20% vs 33%), tumor basal dimension (6 vs 7 mm), anterior chamber cells (16% vs 30%), and vitreous cells (19% vs 48%).
CONCLUSIONS: Retinal vasoproliferative tumor can be primary (80%) or secondary (20%). Compared with primary VPT, secondary VPT is more often bilateral, multiple, and larger and occurs at an earlier age associated with poorer visual acuity.

McCannel TA
Fine-needle aspiration biopsy in the management of choroidal melanoma.
Curr Opin Ophthalmol. 2013; 24(3):262-6 [PubMed]

PURPOSE OF REVIEW: Fine-needle aspiration biopsy of choroidal melanoma offers an opportunity to determine the prognosis for metastasis and provide tissue resources for further study to develop molecular-based targeted therapies. Patients increasingly desire as much information as possible about their cancer so that they may plan their lives and investigate new treatments. Physicians who treat choroidal melanoma must become skilled in the technique so that even the smallest tumors, in patients who might benefit most from early treatment, may be safely biopsied. Individualized molecular therapies of the future will be predicated on the results of a patient's fine-needle biopsy.
RECENT FINDINGS: Fine-needle aspiration biopsy for metastatic prognostication was first performed in North America at the Jules Stein Eye Institute, the University of California, Los Angeles in 2004. Subsequent reports from the major ophthalmic oncology centers have since evaluated several platforms for prognostication using mainly DNA-based approaches. Monosomy 3 of the primary tumor is the cytogenetic abnormality most strongly associated with the development of metastasis. The longest clinical follow-up of a cohort of patients at the Jules Stein Eye Institute who underwent biopsy for prognostication reported in 2012 revealed no increase in ocular morbidity or metastatic risk.
SUMMARY: Fine-needle aspiration biopsy for prognostication in choroidal melanoma is the current standard of care because of new molecular knowledge and a more patient-centered approach to healthcare. Future targeted molecular therapies and metastatic surveillance in patients with choroidal melanoma may be directed by the results of fine-needle aspiration biopsy of the primary tumor.

Gichuhi S, Irlam JH
Interventions for squamous cell carcinoma of the conjunctiva in HIV-infected individuals.
Cochrane Database Syst Rev. 2013; 2:CD005643 [PubMed]

BACKGROUND: Squamous cell carcinoma of the conjunctiva is described in the ophthalmic literature as a rare, slow-growing tumour of the eye, normally affecting elderly men around 70 years of age. In Africa, however, the disease is different. The incidence is rising rapidly, affecting young persons (around 35 years of age), and usually affecting women. It is more aggressive, with a mean history of three months at presentation. This pattern is related to the co-existence of the HIV/AIDS pandemic, high HPV exposure, and solar radiation in the region. Various interventions exist, but despite therapy, there is a high recurrence rate (up to 43%) and poor cosmetic results in late disease. This review was conducted to evaluate the interventions for treatment of conjunctival squamous cell carcinoma in HIV-infected individuals.
OBJECTIVES: To evaluate the effect of interventions for treating squamous cell carcinoma of the conjunctiva in HIV-infected individuals on local control, recurrence, death, time to recurrence, and adverse events.
SEARCH METHODS: Using a sensitive search strategy, we attempted to identify all relevant trials, regardless of language or publication status, from the following electronic databases; PubMedPubMed, EMBASE and The Cochrane Library. We also searched clinical trial registries; WHO International Clinical Trials Registry Platform (ICTRP) and the US National Institutes of Health Clinicaltrials.gov. We searched the international conference proceedings of HIV/AIDS and AIDS-related cancers from the AIDS Education Global Education System (AEGIS). Searches were conducted between January and February 2012.
SELECTION CRITERIA: Randomised controlled trials (RCTs) involving HIV-infected individuals with ocular surface squamous neoplasia.
DATA COLLECTION AND ANALYSIS: We independently screened the results of the search to select potentially relevant studies and to retrieve the full articles. We independently applied the inclusion criteria to the potentially relevant studies. No studies were identified that fulfilled the selection criteria.
MAIN RESULTS: No RCTs of interventions currently used against conjunctival squamous cell carcinoma in HIV-infected individuals were identified.There is one ongoing RCT in Kenya that was registered in July 2012.
AUTHORS' CONCLUSIONS: Implications for practice: Current clinical practice in treatment of squamous cell carcinoma of the conjunctiva rests on a weak evidence base of case series and case reports.Implications for research: Randomised controlled trials for treatment of this disease are needed in settings where it occurs most frequently. Preventive interventions also need to be identified. HIV/AIDS research has not focused on treatment of this tumour.

Almeida A, Kaliki S, Shields CL
Autofluorescence of intraocular tumours.
Curr Opin Ophthalmol. 2013; 24(3):222-32 [PubMed]

PURPOSE OF REVIEW: Fundus autofluorescence is a noninvasive technique for evaluation of intrinsic autofluorescence of the tissues within the eye. In recent years, autofluorescence has become an important diagnostic tool for the assessment of various ocular diseases such as age-related macular degeneration and retinal dystrophies. In this report, we review the recent literature on autofluorescence of intraocular tumours.
RECENT FINDINGS: The autofluorescence features of intraocular tumours range from bright hyperautofluorescence to dark hypoautofluorescence. The fundus autofluorescence generally represents the status of the overlying retinal pigment epithelium (RPE). Choroidal nevi typically have overlying hypoautofluorescence from chronic RPE atrophy as opposed to choroidal melanoma that exhibits hyperautofluorescence from overlying lipofuscin within RPE (orange pigment) and free fluorophores within fresh subretinal fluid. Choroidal metastases demonstrate overlying hyperautofluorescence that correlates to focal RPE accumulation of lipofuscin as well as subretinal fluid, particularly on the fresh advancing tumour margin. Choroidal haemangioma displays overlying hyperautofluorescence from lipofuscin within RPE and fresh subretinal fluid, but when choroidal haemangioma is chronic with resolved fluid, there is often overlying hypoautofluorescence from RPE atrophy. Congenital hypertrophy of the RPE is characterized by marked hypoautofluorescence of the RPE lesion and trace hyperautofluorescence within the lacunae.
SUMMARY: Autofluorescence is a noninvasive, valuable diagnostic tool for assessment of intraocular tumours, based primarily on the effects on the overlying RPE. Some findings are strongly characteristic of certain tumours, particularly the bright hyperautofluorescence overlying small choroidal melanoma and the dark hypoautofluorescence of congenital hypertrophy of the RPE.

Waldman CW, Waldman SD, Waldman RA
Pain of ocular and periocular origin.
Med Clin North Am. 2013; 97(2):293-307 [PubMed]

Most diseases of the eye and periocular regions that cause blindness are relatively painless. Headache pain of ocular and periocular origin represent a special challenge to the clinician. For patients with ocular and periocular pain that is unrelated to primary eye disease, identification and treatment of the painful condition usually become the responsibility of the clinician.

Malinvaud D, Badoual C, Rubio MT, et al.
Extraosseous plasmacytoma of the lacrimal duct.
B-ENT. 2012; 8(4):285-8 [PubMed]

OBJECTIVE: Extraosseous plasmacytoma (EOP) is a rare plasma cell proliferative disorder that commonly affects the head and neck region. We report the first case of a plasmacytoma of the lacrimal duct.
METHODS: A 66-year-old man presented with an isolated plasmacytoma of the right lacrimal duct and was treated surgically.
RESULTS: The tumour grew slowly for a few months. CT scan and MRI showed a right lateral nasal mass extending from the right lacrimal duct toward the floor of the right maxillary sinus. The lesion was removed completely by endoscopic nasal surgery.
DISCUSSION: EOP accounts for up to 3% of all plasma cell tumours. Management of this rare lesion involves surgery and radiotherapy with or without adjuvant chemotherapy. Guided by a literature review, we discuss the diagnostic and therapeutic management of EOP.

Chen X, He D, Dong XD, et al.
MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma.
Invest Ophthalmol Vis Sci. 2013; 54(3):2248-56 [PubMed]

PURPOSE: MicroRNA-124a (miR-124a), an abundant microRNA in the central neuron system, has been linked to tumor progression. Here, we investigated the role of miR-124a in uveal melanoma development.
METHODS: Expression of miR-124a in uveal melanoma cells was examined using real time RT-PCR. The effect of miR-124a on cell proliferation, migration, and invasion was analyzed using MTS assay, flow cytometry, and transwell experiments. The ability of miR-124a to repress tumor growth was tested in vivo. Target genes of miR-124a were first predicted by bioinformatics, confirmed using a luciferase assay, and their expression determined by Western blotting. DNA methylation and histone modification of miR-124a was analyzed by methylation-specific PCR and ChIP assay. Finally, epigenetic drugs were used to alter the expression of miR-124a.
RESULTS: miR-124a expression was downregulated in both uveal melanoma cells and clinical specimens. Transient transfection of miR-124a into uveal melanoma cells inhibited cell growth, migration, and invasion. Moreover, introduction of miR-124a suppressed in vivo growth of tumor. Potential targets of miR-124a were found to include CDK4, CDK6, cyclin D2, and EZH2. Knockdown of EZH2 by siRNA resulted in inhibition of uveal melanoma cell migration and invasion. In addition, miR-124a expression was found to be regulated via epigenetic mechanisms, with its expression restored when cells were treated with a DNA hypomethylating agent, 5-aza-2'-deoxycytidine, and a histone deacetylase inhibitor, trichostatin A.
CONCLUSIONS: Our results demonstrated that miR-124a could function as a potent tumor suppressor by regulation of multiple targets, and was epigenetically silenced in the development of uveal melanoma.

Temming P, Viehmann A, Biewald E, Lohmann DR
Sporadic unilateral retinoblastoma or first sign of bilateral disease?
Br J Ophthalmol. 2013; 97(4):475-80 [PubMed]

BACKGROUND: A small number of children with unilateral retinoblastoma later develop retinoblastoma in the contralateral eye (metachronous bilateral retinoblastoma).
METHODS: We analysed the clinical and genetic characteristics of children with sporadic unilateral retinoblastoma to identify risk factors for the development of metachronous bilateral disease.
RESULTS: Fifteen (3.1%) of 480 children with unilateral retinoblastoma later developed metachronous bilateral retinoblastoma (latency period  >30 days). The maximum latency period was 2.3 years after initial diagnosis. Nine (22.5%) of 40 children with a RB1 mutation detectable in blood developed metachronous bilateral disease while all 155 children proved to be without a germline RB1 mutation remained unilaterally affected. Clinically, the risk of developing metachronous bilateral retinoblastoma was higher for age at diagnosis ≤0.5 years compared with >0.5 years (19.6% vs 1.2%), and for multifocal compared with unifocal unilateral retinoblastoma (17.1% vs 2.2%).
CONCLUSIONS: This study shows that an oncogenic RB1 mutation in the blood is a risk factor for metachronous bilateral retinoblastoma. Additional clinical risk factors for metachronous bilateral disease are diagnosis at young age (≤0.5 years) and multifocal unilateral retinoblastoma. Early genetic analysis may identify children at high risk of developing metachronous bilateral disease and may help to preserve vision using risk-adapted follow-up and early treatment.

Horwath-Winter J, Schneider MR, Wackernagel W, et al.
Influence of single-fraction Gamma-Knife radiosurgery on ocular surface and tear function in choroidal melanoma patients.
Br J Ophthalmol. 2013; 97(4):466-70 [PubMed]

AIM: To evaluate ocular surface and tear function in patients with choroidal melanoma treated with single-fraction radiosurgery.
METHODS: 36 patients (median age 62 years; range 26-84 years) were enrolled between 2001 and 2006 at a single institution. They were treated with the Leksell Gamma Knife in one fraction with a median dose of 30 Gy (range 25-35 Gy). In both eyes of all patients treated subjective symptom score (visual analogue scale) was evaluated, central corneal sensitivity testing, Schirmer test without local anaesthesia, and corneal and conjunctival staining were performed before therapy and 3, 6, 12, 24 and 36 months thereafter. The respective untreated fellow eye served as control.
RESULTS: Three months after radiosurgery, the subjective dry eye symptom score and lissamine green staining score of the ocular surface were significantly higher in the treated eyes compared with the fellow eyes (p<0.001, p=0.028, respectively). After 12 months, a significant difference between the treated and the fellow eyes in corneal sensitivity (p=0.041) and corneal fluorescein staining (p=0.002) was found when compared with pretreatment values. After 24 months Schirmer test values without local anaesthesia were significantly reduced in the treated eyes vis-à-vis untreated fellow eyes and pretreatment values (p=0.004). The dose applied to the lacrimal gland was significantly correlated to ocular surface staining scores (p=0.001) and Schirmer test values (p=0.026) at 24 months after irradiation.
CONCLUSIONS: Stereotactic single-fraction Gamma-Knife radiotherapy of choroidal melanoma with a median dose of 30 Gy significantly affected ocular surface and tear function and increased dry eye symptoms and signs.

Mierzwa-Dobranowska M, Romanowska-Dixon B
Assessment of the influence of one's education on early diagnosis of multiple primary cancer in patients with uveal melanoma.
Klin Oczna. 2012; 114(2):111-4 [PubMed]

PURPOSE: This study will show a comparison of two groups of patients with uveal melanoma; one group with multiple primary cancer, and a second group with no identifiable second cancer, in terms of education and occupation.
MATERIAL AND METHODS: Study concerns 240 patients, who were isolated from patients being treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology Jagiellonian University Medical College in the period from 1998 to 2007. On the basis of medical history and medical records 97 patients were diagnosed with the one or more independent primary cancers. These patients were subjected to comparative analysis with a group of 143 patients with uveal melanoma as a control group.
RESULTS: Analyzing the impact of education on the recognition of multiple primary cancer, there were significantly more frequent diagnoses of second primary cancers among patients with secondary and higher education than among those who had primary and vocational education. Among the obtained data on patients in the study group, the largest occupational group (according to the ISCO-88 (COM)) constituted "professionals". In the control group prevailed "craft and related trades workers".
CONCLUSIONS: The results suggest the great importance of knowledge about risk factors for the development of cancer among patients with uveal melanoma and the ensuing more scrupulous search for succesive primary neoplasm and indicate the neccesity of organizing broad prophylactic actions. uveal melanoma, multiple primary cancer.

Mierzwa-Dobranowska M, Romanowska-Dixon B
One's location of residence as an important factor related to the occurrence of multiple primary cancer among patients with uveal melanoma.
Klin Oczna. 2012; 114(2):107-10 [PubMed]

PURPOSE: This study has attempted to analyze the impact of where one lives related to the incidence of multiple primary cancer among patients with uveal melanoma.
MATERIAL AND METHODS: The group that was studied consisted of 240 patients. They were separated from other patients who had been diagnosed and treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology at Jagiellonian University Medical College in the period between January 1998 to December 2007. Ninety seven patients, diagnosed with another primary cancer, was defined as a test group. The remaining 143 patients constituted the control group.
RESULTS: In the test group individuals were mostly residents of large cities, most often with population of more than 500 thousand inhabitants. The control group represented residents of small towns, each having less than 10000 persons population.
CONCLUSIONS: The findings of this study are pointing to the dependence of the detectability of multiple primary cancer among patients with uveal melanoma on the availability of modern diagnostic methods. uveal melanoma, multiple primary cancer.

Krema H, Heydarian M, Beiki-Ardakani A, et al.
A comparison between ¹²⁵Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma.
Br J Ophthalmol. 2013; 97(3):327-32 [PubMed]

AIMS: To compare the treatment efficacy and radiation complications between (125)Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma.
METHODS: Consecutive juxtapapillary melanoma patients treated with radiotherapy were included. Patients were divided into two cohorts: patients treated with (125)Iodine brachytherapy and patients with stereotactic radiotherapy. Comparison included the rates postradiotherapy local recurrence, secondary enucleation, metastasis and radiotherapy complications. Kaplan-Meier estimates were used to determine the actuarial rates, and logrank test to compare between the estimates.
RESULTS: We included 94 patients with juxtapapillary melanoma treated with radiotherapy. The brachytherapy cohort included 30 patients and stereotactic radiotherapy was 64. The median follow-up was 46 months in both cohorts. No statistically significant differences existed between the two cohorts on comparing pretreatment clinical data and tumour characteristics. On comparing treatment efficacy, the actuarial rates at 50 months for tumour recurrence were 11% and 7% (p=0.61), secondary enucleation was 11% and 21% (p=0.30) and for metastasis were 4% and 16% (p=0.11), respectively. On comparing treatment complications, the actuarial rates at 50 months for cataracts were 62% and 75% (p=0.1), for neovascular glaucoma 8% and 47% (p=0.002), for radiation retinopathy 59% and 89% (p=0.0001), and for radiation papillopathy 39% and 74% (p=0.003), respectively.
CONCLUSIONS: Both (125)Iodine brachytherapy and stereotactic radiotherapy demonstrate comparable efficacy in the management of juxtapapillary choroidal melanoma. However, stereotactic radiotherapy shows statistically significant higher radiation-induced ocular morbidities at 4 years postradiotherapy.

Pecorella I, Toth J, Lukats O
Ancient schwannoma of the orbit.
Pathologica. 2012; 104(4):182-4 [PubMed]

Schwannoma, also referred to as neurilemmoma or peripheral neurinoma, is an unusual orbital benign tumour that may pose diagnostic challenges. Awareness of the clinical features that may be associated with the tumour and prompt surgical excision with histopathologic examination enable correct diagnosis. The authors describe a progressively increasing inferolateral orbital mass in a 32-year-old patient that was demonstrated to be an orbital ancient schwannoma.

Harbour JW, Roberson ED, Anbunathan H, et al.
Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma.
Nat Genet. 2013; 45(2):133-5 [PubMed]

Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas.

Prabhulkar S, Matthews J, Rawal S, Awdeh RM
Molecular histopathology using gold nanorods and optical coherence tomography.
Invest Ophthalmol Vis Sci. 2013; 54(2):1192-200 [PubMed] Article available free on PMC after 01/08/2013

PURPOSE: To examine the novel application of a commercially available optical coherence tomography (OCT) system toward molecular histopathology using gold nanorod (GNR) linked antibodies as a functionalized contrast agent to evaluate ocular surface squamous neoplasia (OSSN).
METHODS: GNRs were synthesized and covalently attached to anti-glucose transporter-1 (GLUT-1) antibodies via carbodiimide chemistry. Three specimens from each of three distinct categories of human conjunctival tissue were selected for analysis, including conjunctiva without epithelial atypia (controls); conjunctival intraepithelial neoplasia, carcinoma in situ (CIS); and conjunctival squamous cell carcinoma (SCC). Tissue sections were incubated initially with GNR tagged anti-GLUT-1 antibodies and then with a fluorescent-tagged secondary antibody. Immunofluorescence and OCT imaging of the tissue was performed and the results were correlated to the light microscopic findings on traditional hemotoxyin and eosin stained sections.
RESULTS: No binding of the functionalized GNRs was observed within the epithelium of three normal conjunctiva controls. While immunofluorescence disclosed variable binding of the functionalized GNRs to atypical epithelial cells in all six cases of OSSN, the enhancement of the OCT signal in three cases of CIS was insufficient to distinguish these specimens from normal controls. In two of three cases of SCC, binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to atypical epithelial cells which stained intensely on immunofluorescence imaging. Binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to regions of erythrocytes and hemorrhage which stained intensely on immunofluorescence imaging within all nine tested samples.
CONCLUSIONS: We have demonstrated the use of OCT for molecular histopathology using functionalized gold nanorods in the setting of OSSN. Our results suggest a threshold concentration of functionalized GNRs within tissue is required to achieve a detectable enhancement in scattering of the OCT signal.

Wen JC, Sai V, Straatsma BR, McCannel TA
Radiation-related cancer risk associated with surveillance imaging for metastasis from choroidal melanoma.
JAMA Ophthalmol. 2013; 131(1):56-61 [PubMed]

OBJECTIVE: To estimate the lifetime attributable risk of cancer associated with whole-body positron emission tomography (PET)/computed tomography (CT) and with CT of the chest, abdomen, and pelvis if performed at various frequencies and for different durations for surveillance of patients with primary choroidal or ciliary body melanoma for distant metastasis.
METHODS: Effective radiation doses for whole-body CT and for CT of the chest, abdomen, and pelvis were calculated using Monte Carlo simulation studies. The effective dose of the PET scan was estimated by multiplying fludeoxyglucose F18 radioactivity with dose coefficients. Lifetime attributable risks of cancer were calculated using the approach described in the Biological Effects of Ionizing Radiation VII report.
RESULTS: For a 50-year-old patient, an annual CT of the chest, abdomen, and pelvis for 10 years carries an estimated lifetime attributable risk of cancer of 0.9% for male patients and 1.3% for female patients, whereas an annual PET/CT each year for 10 years carries an estimated lifetime attributable risk of cancer of 1.6% for male patients and 1.9% for female patients. Lifetime risk was found to be higher in younger, female patients. The lifetime attributable risk of cancer was estimated to be as high as 7.9% for a 20-year-old female patient receiving a PET/CT scan every 6 months for 10 years.
CONCLUSIONS: Aggressive surveillance protocols incorporating CT scanning or PET/CT scanning for detection of metastasis from primary choroidal or ciliary body melanoma appear to confer a significant substantial risk of a secondary malignant tumor in patients who do not succumb to metastatic melanoma within the first few posttreatment years.

Levasseur SD, Wittenberg LA, White VA
Vitreoretinal lymphoma: a 20-year review of incidence, clinical and cytologic features, treatment, and outcomes.
JAMA Ophthalmol. 2013; 131(1):50-5 [PubMed]

OBJECTIVES: To determine the incidence and clinical and cytologic diagnostic accuracy of vitreoretinal lymphoma (VRL) and to evaluate its clinical features, management, and outcomes in a cohort of patients who underwent diagnostic vitrectomy.
METHODS: Retrospective medical record review of 463 diagnostic vitrectomy specimens from 430 patients collected from October 1, 1990, through December 31, 2010, from Vancouver General Hospital and the British Columbia Cancer Agency.
RESULTS: A total of 22 patients were diagnosed as having VRL with a preoperative clinical diagnostic sensitivity of 77%, specificity of 73%, positive predictive value of 13%, and negative predictive value of 98%. The cytologic diagnostic sensitivity was 87% (27 of 31 specimens). The incidence of VRL in British Columbia doubled from 1990 to 2010, with a final incidence of 0.047 cases per 100 000 people per year. The mean age at diagnosis was 66 years. Seventeen patients (77%) were women. The initial diagnosis of lymphoma was VRL in 19 patients (86%), of whom 7 (37%) had concurrent central nervous system lymphoma. Recurrent disease was found in 11 patients. Large B-cell lymphoma was diagnosed in 20 patients (91%). The median progression-free survival was 11 months, and the median survival was 33 months from the initial diagnosis.
CONCLUSIONS: Vitreoretinal lymphoma remains a clinical diagnostic challenge. Early clinical suspicion with subsequent diagnostic vitrectomy for cytologic analysis and collaboration with the oncology department is critical to appropriate and prompt staging and treatment. More interdisciplinary studies are required to further characterize VRL and maximize the therapeutic options, thus improving the morbidity and mortality associated with the disease.

Konstantinidis L, Roberts D, Errington RD, et al.
Whole anterior segment proton beam radiotherapy for diffuse iris melanoma.
Br J Ophthalmol. 2013; 97(4):471-4 [PubMed]

AIM: To report the results of whole anterior segment proton beam radiotherapy (PBR) for diffuse iris melanoma.
METHODS: Between 2000 and 2011, 12 patients with iris melanoma received PBR to the entire iris and ciliary body.
RESULTS: Patients had a mean age of 57 years and a median follow-up of 3.5 years (range 1-11.6 years). Tumour iris involvement was 1-4 h in five patients, 5-8 h in four and 9-12 h in three. Angle involvement was 6-8 h in five patients and 9-12 h in seven. The visual acuity (VA) before treatment was 6/5-6/6 in six patients, 6/8-6/9 in three and 6/18-6/38 in three. No tumour recurrence occurred during the follow-up period. Glaucoma treatment was required in 11 of 12 patients. The visual acuity at the last follow-up was 6/5-6/9 in five patients, 6/18-6/24 in three, 6/60-1/60 in two and no light perception in two. Four patients developed varying non-severe degrees of limbal stem cell deficiency, which was treatable with conservative measures.
CONCLUSIONS: Whole anterior segment PBR is a useful alternative to enucleation for diffuse iris melanoma. Most patients will need treatment for glaucoma and some may require treatment for tear-film instability and/or stem cell failure.

Zhao H, Yang M, Zhang X, et al.
The first case of omental metastasis from primary choroidal melanoma.
Jpn J Clin Oncol. 2013; 43(3):314-7 [PubMed]

Choroidal melanoma is the most common intraocular malignancy and can be fatal in half of the patients because of metastatic disease. Metastasis of choroidal melanoma to the omentum is extremely rare and, to our knowledge, no such case has ever been described in the literature. Here we present a 41-year-old Chinese man with an omental metastasis, 5 years after he was diagnosed with a spindle-cell-type malignant melanoma of the choroid and had his left eye enucleated. The patient demonstrated some uncommon symptoms, but the diagnosis was confirmed histopathologically. The cells were positive for S-100, HMB-45 and Melan-A proteins. He underwent a complete tumor resection and concomitantly received chemotherapy, biological treatment and traditional Chinese medicine. At 2-year follow-up, this patient continues to do well.

Dimaras H, Parulekar MV, Kwok G, et al.
Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child.
Br J Ophthalmol. 2013; 97(3):323-6 [PubMed]

AIMS: To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis.
METHODS: The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome.
RESULTS: The tumour had predominantly epithelioid histology. Karyotype analysis showed none of the poor prognosis features normally associated with uveal melanoma. single nucleotide polymorphism analysis revealed no imbalance at chromosome 3. Gene expression profiling indicated low risk disease.
CONCLUSIONS: We report a child remaining relapse-free 6 years after diagnosis of a very rare uveal melanoma, with poor prognosis epithelioid histology, but gene expression profiling that accurately predicted low risk disease.

Kocher M, Treuer H, Hoevels M, et al.
Endocrine and visual function after fractionated stereotactic radiotherapy of perioptic tumors.
Strahlenther Onkol. 2013; 189(2):137-41 [PubMed]

PURPOSE: To find out whether the use of stereotactic techniques for fractionated radiotherapy reduces toxicity to the endocrine and visual system in patients with benign perioptic tumors.
PATIENTS AND METHODS: From 1993 to 2009, 29 patients were treated with fractionated stereotactic radiotherapy. The most frequent tumor types were grade I meningioma (n = 11) and pituitary adenoma (n = 10, 7 nonfunctioning, 3 growth hormone-producing). Patients were immobilized with the GTC frame (Radionics, USA) and the planning target volume (PTV; median 24.7, 4.6-58.6 ml) was irradiated with a total dose of 52.2 Gy (range, 45.0-55.8 Gy) in 1.8-Gy fractions using a linear accelerator (6 MeV photons) equipped with a micro-multileaf collimator. Maximum doses to the optic system and pituitary gland were 53.4 Gy (range, 11.5-57.6 Gy) and 53.6 Gy (range, 12.0-57.9 Gy).
RESULTS: Median follow-up was 45 months (range, 10-105 months). Local control was achieved in all but 1 patient (actuarial rate 92% at 5 years and 10 years). In 9 of 29 patients (31%), partial remission was observed (actuarial response rate 40% at 5 years and 10 years). In 4 of 26 patients (15%) with at least partial pituitary function, new hormonal deficits developed (actuarial rate 21% at 5 years and 10 years). This rate was significantly higher in patients treated for a larger PTV (< /> 25 ml: 0% vs. 42% at 5 years and 10 years, p = 0.028). Visual function improved in 4 of 15 patients (27%) who had prior impairment. None of the patients developed treatment-related optic neuropathy, but 2 patients experienced new disease-related visual deficits.
CONCLUSION: Fractionated stereotactic radiotherapy for benign tumors of the perioptic and sellar region results in satisfactory response and local control rates and does not affect the visual system. The assumption that patients can be spared hypophyseal insufficiency only holds for small tumors.

Perri P, Fiorica F, D'Angelo S, et al.
Ruthenium-106 eye plaque brachytherapy in the conservative treatment of uveal melanoma: a mono-institutional experience.
Eur Rev Med Pharmacol Sci. 2012; 16(14):1919-24 [PubMed]

BACKGROUND: Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision.
PATIENTS AND METHODS: From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera.
RESULTS: One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%.
CONCLUSIONS: 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.

Bhatia S, Moon J, Margolin KA, et al.
Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
PLoS One. 2012; 7(11):e48787 [PubMed] Article available free on PMC after 01/08/2013

BACKGROUND: Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma.
METHODS: Twenty-five patients with stage IV uveal melanoma who had received 0-1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m(2)) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS).
RESULTS: No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0-14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1-6 months] and the 6-month PFS was 29% [95% CI: 13%-48%]. The median OS was 11 months [95% CI: 7-14 months].
CONCLUSION: In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients.
TRIAL REGISTRATION: ClinicalTrials.govNCT00329641.

Larina IV, Syed SH, Sudheendran N, et al.
Optical coherence tomography for live phenotypic analysis of embryonic ocular structures in mouse models.
J Biomed Opt. 2012; 17(8):081410-1 [PubMed] Article available free on PMC after 01/08/2013

Mouse models of ocular diseases provide a powerful resource for exploration of molecular regulation of eye development and pre-clinical studies. Availability of a live high-resolution imaging method for mouse embryonic eyes would significantly enhance longitudinal analyses and high-throughput morphological screening. We demonstrate that optical coherence tomography (OCT) can be used for live embryonic ocular imaging throughout gestation. At all studied stages, the whole eye is within the imaging distance of the system and there is a good optical contrast between the structures. We also performed OCT eye imaging in the embryonic retinoblastoma mouse model Pax6-SV40 T-antigen, which spontaneously forms lens and retinal lesions, and demonstrate that OCT allows us to clearly differentiate between the mutant and wild type phenotypes. These results demonstrate that OCTin utero imaging is a potentially useful tool to study embryonic ocular diseases in mouse models.

Poole Perry LJ, Jakobiec FA, Zakka FR, et al.
Reactive retinal astrocytic tumors (so-called vasoproliferative tumors): histopathologic, immunohistochemical, and genetic studies of four cases.
Am J Ophthalmol. 2013; 155(3):593-608.e1 [PubMed]

PURPOSE: To evaluate the cellular nature of and diagnostic terminology used in connection with acquired retinal "vasoproliferative tumors."
DESIGN: Retrospective clinicopathologic study.
METHODS: Clinical records and microscopic slides of 4 enucleated globes were reviewed. Special stains and immunohistochemical probes for CD31, CD34, p53, glial fibrillary acidic protein (GFAP), CD163, and Ki67 (cell replication) were employed; ultrastructural and fluorescence in situ hybridization (FISH) analyses were performed.
RESULTS: Tumors were located inferotemporally in middle-aged patients. They were uniformly composed of compacted elongated, GFAP-positive spindle cells (due to intermediate filaments identified ultrastructurally) with a Ki67 index of less than 1%. Rosenthal fibers and eosinophilic granular bodies were observed. Hyalinized periodic acid-Schiff-positive vessels were widely separated. CD31 and CD34 revealed a sparse microvasculature. Tumor-associated exudate spread predominantly subretinally. The retinal pigment epithelium had undergone extensive placoid fibrous metaplasia with focal ossification. P53 upregulation, BRAF-KIAA gene rearrangement, and IDH1R132H mutation typically associated with low-grade astrocytic neoplasms were absent.
CONCLUSIONS: Retinal "vasoproliferative" tumors have been mischaracterized, because they actually display a paucity of microvessels. Proliferating fibrous astrocytes with a very low proliferation index predominate, without immunohistochemical or genetic evidence favoring a neoplasm. Subretinal exudate appeared capable of provoking widespread fibrous metaplasia of the pigment epithelium that was mainly responsible for secondary retinal damage. The term "reactive retinal astrocytic tumor" is proposed as more appropriate for this entity. In carefully selected progressive lesions, consideration should be given to earlier surgical intervention before extensive subretinal exudate accumulates and pigment epithelial proliferation with fibrous metaplasia ensues.

Hoguet A, Warrow D, Milite J, et al.
Mucin-producing sweat gland carcinoma of the eyelid: diagnostic and prognostic considerations.
Am J Ophthalmol. 2013; 155(3):585-592.e2 [PubMed]

PURPOSE: To describe the clinical and pathologic characteristics of mucin-producing sweat gland carcinoma of the eyelid and to determine whether neuroendocrine differentiation is of prognostic significance.
DESIGN: Retrospective interventional case series.
METHODS: Search of the New York Eye and Ear Infirmary pathology database between 1990 and 2011 identified 16 patients with mucin-producing sweat gland carcinoma. Clinical, histopathologic, and immunohistochemical analyses were performed on all identified cases.
RESULTS: The patients presented with vascularized, focally cystic, nonulcerated eyelid margin lesions. Histopathologic evaluation showed that 4 lesions (25%) had a cystic, papillary, and solid growth pattern with an in situ component, 7 (44%) were pure invasive mucinous carcinomas, and 5 (31%) demonstrated both growth patterns. Immunohistochemical analysis of 15 tumors showed that pure cystic/papillary lesions had a significantly greater percentage of synaptophysin-immunoreactive cells (P = .036). There was no significant difference in the number of neuroendocrine markers expressed or in the intensity of immunostaining among the 3 different growth patterns. Re-excision for margin clearance was performed in 8 of 13 cases (61.5%). Two of 13 lesions recurred (15%); 1 of these was an in situ tumor with cystic morphology and neuroendocrine differentiation and the other was pure invasive mucinous carcinoma. None of the lesions metastasized.
CONCLUSIONS: Mucin-producing sweat gland carcinoma pathologically represents a continuum, from an in situ lesion to a classic, invasive mucinous carcinoma. Immunohistochemical evidence of neuroendocrine differentiation can be observed in all lesions and does not appear to have a prognostic significance, arguing against the utility of immunohistochemical subtyping of mucinous sweat gland carcinomas.

Chang M, Lee Y, Baek S, Lee TS
Orbital glomus tumor in an Asian patient.
BMC Ophthalmol. 2012; 12:62 [PubMed] Article available free on PMC after 01/08/2013

BACKGROUND: This report describes a recurrent orbital glomus tumor in an Asian patient.
CASE PRESENTATION: A healthy 50-year-old Korean man had progressive right exophthalmos and a soft mass on his right lower lid for 6 months. We evaluated the mass using CT and MRI, and performed excisional biopsy and pathologic examination. Pathologically, the mass was a glomus tumor. Although proptosis of the right eye decreased, one month after surgery it increased to almost the same level as before surgery.
CONCLUSIONS: This is the first report of an Asian patient with an orbital glomus tumor that demonstrated rapid re-growth after incision without pain or visual problems.

Kang DW, Lee SC, Park YG, Chang JH
Long-term results of Gamma Knife surgery for uveal melanomas.
J Neurosurg. 2012; 117 Suppl:108-14 [PubMed]

OBJECT: Gamma Knife surgery (GKS) is currently believed to be a safe and minimally invasive modality in the treatment of uveal melanomas. It could be used as an alternative treatment to enucleation, preserving the eyeball as well as visual function. The authors report their experiences with GKS for uveal melanomas for the period from February 1998 to December 2006.
METHODS: Twenty-two patients with uveal melanoma were enrolled in this study. The population consisted of 12 men and 10 women with a mean age of 53.4 years (range 24-79 years). The mean tumor volume was 877 mm(3), and the mean margin dose was 45.6 Gy. The median follow-up period was 67 months (range 3-126 months). All of the patients had received a diagnosis and referral from an ophthalmology clinic; the patients underwent a preoperative orbital examination that included MRI.
RESULTS: Tumor regression was achieved in 20 patients (90.9%), whereas tumor progression was observed in 2 patients (9.1%) 3 years after GKS. The cumulative 1-year and 2-year mean rates of tumor thickness reduction were 18.8% and 42.8%, respectively. The mean rate of tumor volume reduction was 63.7%. The rate of eye retention 5 years after radiosurgery was 77.3% (17 of 22 patients). Overall visual acuity was reduced after GKS in all patients; 14 patients (63.6%) displayed preserved visual function better than hand-movement perception. The most frequent side effect was cataract, which was detected in 9 patients (40.9%); this was followed in frequency by radiation-induced retinopathy in 5 patients (22.7%).
CONCLUSIONS: Gamma Knife surgery provides excellent local control of uveal melanomas with a decrease in volume over time. This procedure not only preserves the eyeball and its potential visual function, but also decreases the potential for hematological dissemination and achieves sufficient local tumor control with a gradual reduction in volume.

Jo KI, Im YS, Kong DS, et al.
Multisession Gamma Knife surgery for benign orbital tumors.
J Neurosurg. 2012; 117 Suppl:102-7 [PubMed]

OBJECT: The goal of this study was to investigate the safety and efficacy of multisession Gamma Knife surgery (GKS) in the treatment of benign orbital tumors.
METHODS: Twenty-three patients who retained their vision despite having tumors touching their optic nerve were treated with multisession (4-fraction) GKS. The median tumor volume was 2800 mm(3) (range 211-10,800 mm(3)), and the median cumulative margin dose was 20 Gy (range 18-22 Gy).
RESULTS: The median clinical follow-up duration in these patients was 38 months (range 9-74 months). No patient experienced tumor progression in this study. In particular, a higher degree of tumor shrinkage was found in the 7 patients with cavernous hemangiomas than in patients with other types of lesions (p < 0.05). Of the 23 patients whose preoperative vision was preserved, 11 showed improvement in visual acuity and/or visual field and 12 showed stable visual acuity. No GKS-related adverse events were noted during or after treatment.
CONCLUSIONS: Multisession radiosurgery using the Gamma Knife may be a good strategy for tumors in direct contact with the optic nerve. A cumulative margin dose of up to 22 Gy delivered in 4 sessions is safe for preservation of visual function with a high probability of tumor control.

Sira M, Malhotra R
Reconstruction of orbital exenteration defects by primary closure using cheek advancement.
Br J Ophthalmol. 2013; 97(2):201-5 [PubMed]

INTRODUCTION: Orbital exenteration is a highly disfiguring procedure which, although providing local control of invasive orbital malignancy also results in marked visual, psychological and social disability. We present three consecutive total exenteration cases over 1 year where all 3, including extended exenteration defects, were repaired by primary closure by way of cheek advancement. This technique may be considered where succinct management with minimal follow-up is required and maybe preferable if considering rapidity of rehabilitation with a short time to fitting definitive prostheses.
METHODS: Retrospective review of three consecutive patients who presented with neglected basal cell carcinoma with orbital invasion and subsequently underwent total orbital exenteration with repair by cheek advancement flap.
RESULTS: All underwent repair with primary skin closure using a cheek advancement flap. Patient 2 developed a small area of central flap dehiscence noted at 2 months with almost complete granulation of the orbital cavity at 3 months. Patients 1, 2 and 3 were fitted with final prosthesis at 7, 6 and 12 months, respectively.
CONCLUSIONS: Reconstruction of the exenterated orbit using cheek advancement represents an evolution of the cervico-facial flap repair. The cheek advancement avoids creating a secondary defect and because it involves less dissection and additional skin incisions, is an easier procedure to perform with fewer facial scars. It does not preclude osseointegration if required at a later date and as such we recommend it as an option in repairing the exenterated orbit.