Victoria Cohen

Primary intraocular lymphoma

Primary intraocular lymphoma (PIOL) is an ocular malignancy that is a subset of primary central system lymphoma (PCNSL). Approximately one-third of PIOL patients will have concurrent PCNSL at presentation, and 42-92% will develop PCNSL within a mean of 8-29xa0months. Although rare, the incidence has been rising in both immunocompromised and immunocompetent populations. The majority of PIOL is diffuse large B-cell lymphoma, though rare T-cell variants are described. Recently, PIOL has been classified by main site of involvement in the eye, with vitreoretinal lymphoma as the most common type of ocular lymphoma related to PCNSL. Diagnosis remains challenging for ophthalmologists and pathologists. PIOL can masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other neoplasms such as metastatic cancers. Laboratory diagnosis by cytology has been much aided by the use of immunocytochemistry, flow cytometry, biochemical finding of interleukin changes (IL10:IL6 ratio > 1), and cellular microdissection with polymerase chain reaction amplification for clonality. Use of several tests improves the diagnostic yield. Approaches to treatment have centered on systemic methotrexate-based chemotherapy, often with cytarabine (Ara-C) and radiotherapy. Use of intravitreal chemotherapy with methotrexate (0.4xa0mg/0.1xa0mL) is promising in controlling ocular disease, and intravitreal rituximab (anti-CD20 monoclonal antibody) has also been tried. Despite these advances, prognosis remains poor.

Vitreous seeding from retinal astrocytoma in three cases.

Purpose: To report three cases of vitreous seeding from retinal astrocytoma. Methods: Retrospective, single-center case series. Results: An asymptomatic 8-year-old boy (Case 1) presented with a white juxtapapillary retinal tumor and extensive overlying large vitreous seeds. Fine-needle aspiration biopsy (FNAB) confirmed the diagnosis of benign retinal astrocytoma. A 5-year-old boy (Case 2) presented with a large, multilobulated, tan juxtapapillary retinal tumor. The mass had grown from 6.6 mm to 9.0 mm in thickness. Overlying localized vitreous seeds were present. FNAB revealed cells of astrocytic origin. Histopathologic analysis of the enucleated globe supported the diagnosis of retinal astrocytoma. A 14-year-old girl (Case 3) was referred with a white gelatinous mass overlying the optic disk and producing vitreous seeds. FNAB revealed cells of astrocytic origin. The tumor height increased from 2.5 mm to 5.5 mm, and total retinal detachment developed. After enucleation, the diagnosis of retinal astrocytoma was confirmed. In all three cases, the vitreous seeds were round to oblong and stringy in configuration. No patient manifested tuberous sclerosis. Conclusions: Retinal astrocytoma can produce vitreous seeds, sometimes associated with tumor growth. Care should be taken to exclude the diagnosis of retinoblastoma.

Evaluation of iris and iridociliary body lesions with anterior segment optical coherence tomography versus ultrasound B-scan

Aims To compare anterior segment optical coherence tomography (AS-OCT) with ultrasound B-scan (USB) in evaluating iris and iridociliary body lesions. Methods Image features and resolution comparison between AS-OCT and USB in 126 patients (126 eyes) presenting with iris or iridociliary body lesion. Bland–Altman plots were generated to assess the level of agreement between the two techniques. Results The three most common diagnoses were iris naevi (62 (49.2%)), iris pigment epithelial cysts (23 (18.3%)) and iris melanoma (11 (8.7%)). Image feature comparison for USB was better than AS-OCT in visualising all tumour margins (81 (64.3%) vs 59 (46.8%)), posterior tumour margin (54 (42.9%) vs 16 (12.7%)) and producing less posterior shadowing (121 (96%) vs 43 (34.1%)). Image resolution comparison revealed USB to be slightly better for resolving the overall tumour (45 (35.7%) vs 43 (34.1%)) and posterior tumour surface (70 (55.6%) vs 32 (25.4%)) but AS-OCT was better for resolving the anterior (62 (49.2%) vs 4 (3.2%)) and lateral tumour surface (62 (49.2%) vs 31 (24.6%)). Comparing the three most common diagnoses, USB was better for visualising iris pigment epithelial cysts (12 (52.2%) vs 2 (8.7%)) and iris melanoma (7 (63.6%) vs 1 (9.1%)) but AS-OCT was better (28 (45.2%) vs 15 (24.2%)) for visualising iris naevi. Bland–Altman plots showed good agreement between the two techniques for lesions smaller than 3u2005mm in base and 2u2005mm in elevation. Conclusions AS-OCT is superior to USB for imaging small lesions pertaining to the anterior iris but USB is better for imaging larger iris lesions with posterior or ciliary body extension.

Choroidal naevi complicated by choroidal neovascular membrane and outer retinal tubulation

Aims To present the outcomes of a series of patients with choroidal neovascular membrane (CNV) secondary to a choroidal naevus and report the presence of outer retinal tubulation. Methods In this retrospective series, patients underwent a complete clinical and imaging assessment (fundus photo, fluorescein angiography and optical coherence tomography) and were observed or managed with intravitreal anti-VEGF injections dependent on whether visual acuity was affected. Results Seventeen patients were included in this study. Of this, 46% (8/17) had classic or predominantly classic CNV and 53% (9/17) had occult or minimally classic CNV. Active treatment with intravitreal anti-VEGF injections was required in 35% (6/17). Visual acuity improved in three eyes by 2–4 Snellen lines, remained stable in one eye and worsened in two eyes by 2 Snellen lines. CNV partially regressed in five cases. In the observation group (65%, 11/17), visual acuity did not change during follow-up period. Outer retinal tubulation was found in 18% (3/17). Conclusions Anti-VEGF treatment is effective in the management of vision threatening CNV secondary to a choroidal naevus. Functional or anatomical improvement was obtained in 66% of treated eyes. Outer retinal tubulation, noted in 18%, showed the clinical importance of this sign in determining continuation of anti-VEGF treatment.

Secondary Enucleations for Uveal Melanoma: A 7-Year Retrospective Analysis.

PURPOSEnTo describe the indications for secondary enucleations in uveal melanoma and analyze associations and outcomes.nnnDESIGNnRetrospective interventional case series.nnnMETHODSnData of patients who underwent secondary enucleation for uveal melanoma in the London Ocular Oncology Service, between 2008 and 2014, were retrieved from medical records analyzed. Cox regression model was performed to analyze associations with secondary enucleation and metastases and Kaplan-Meier estimates to assess the probability of metastatic spread and death.nnnRESULTSnDuring the study period 515 enucleations were performed for uveal melanoma, 99 (19%) of which were secondary enucleations. Tumors were located at the ciliary body in 21 eyes (21%), juxtapapillary in 31 (31%), and choroid elsewhere in 47 (48%). Primary treatment included Ru(106) plaque radiotherapy, proton beam radiotherapy, and transpupillary thermotherapy in 85, 11, and 3 eyes, respectively. Indications for secondary enucleation were tumor recurrence in 60 (61%), neovascular glaucoma in 21 (21%), and tumor nonresponse in 18 eyes (18%). Twenty patients (20%) were diagnosed with metastasis and 12 out of 20 died of metastatic spread. On multivariate analysis, juxtapapillary tumor location was found to associate with tumor nonresponse (Pxa0= .004) and nonresponding patients with metastatic spread (Pxa0= .04).nnnCONCLUSIONSnIndications for secondary enucleations for uveal melanoma were tumor recurrence, neovascular glaucoma, and tumor nonresponse. This review identified a possible high-risk group (nonresponse), which proved radioresistant to treatment. These tumors were more frequently found in the juxtapapillary location and were associated with metastatic spread.

Adjuvant Dendritic Cell Vaccination in High-Risk Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults with an annual incidence of 4 to 10 per million in the white population. The 5-year overall survival (OS) rate is approximately 70% to 80%. Up to 50% of patients with UM develop metastases, usually after a long disease-free interval (2-5 years). If metastatic disease is present, the prognosis is dismal with a 1-year OS rate of 10% to 40%. Currently, no effective systemic treatment improving OS is available for patients with metastatic UM, nor has any adjuvant treatment shown survival benefit. nOur research group and others have performed several prospective dendritic cell (DC) vaccination studies in patients with cutaneous melanoma showing little toxicity and promising immunologic and clinical results. [...]

Uveal Melanoma Associated With Myotonic Dystrophy: A Report of 6 Cases

Importance Patients with myotonic dystrophy (MD) have an increased risk of malignancy including uveal melanoma. This case series further explores the association between these 2 diseases. Objective To describe a cohort of patients with uveal melanoma associated with MD, including a case of iris melanoma, and MD-associated uveal melanoma in relatives. Design, Setting, and Participants Retrospective case series at 3 tertiary referral centers (Wills Eye Hospital, Philadelphia, Pennsylvania; Mayo Clinic, Rochester, Minnesota; and Moorfields Eye Hospital, London, England), between January 1, 2000, and August 31, 2017. The study included 6 patients with MD and uveal melanoma. Main Outcomes and Measures Melanoma response to treatment and development of metastatic disease. Results There were 6 patients, 4 men and 2 women, with MD and uveal melanoma. The mean patient age at melanoma diagnosis was 47 years (median, 43 years; range, 30-67 years), and the tumor involved the choroid in 5 patients (83%) and iris in 1 patient (17%). The diagnosis of MD was known since young adulthood in 2 patients (33%) and was discovered in adulthood in 4 patients (67%). The main clinical features of MD included muscle weakness (n = 5; 83%), myotonia (n = 4; 67%), polychromatic cataract (n = 4; 67%), complications with general anesthesia (n = 4; 67%), myalgia (n = 3; 50%), cardiac arrhythmia (n = 2; 33%), and frontal baldness (n = 2; 33%). Genetic testing revealed MD type 1 (4 of 4 tested patients), and 2 patients demonstrated positive family history of MD with classic clinical features and preferred no testing. Melanoma treatment included plaque radiotherapy (nu2009=u20094; 67%), photodynamic therapy (nu2009=u20091; 17%), and declined treatment (nu2009=u20091; 17%). At follow-up of 6, 6, 41, 42, and 87 months (5 patients), findings included melanoma regression (4 of 5 tumors), melanoma recurrence (1 of 5 tumors), and no metastatic disease (5 of 5 patients). Conclusions and Relevance Six adult patients with MD demonstrated uveal melanoma involving the choroid or iris, emphasizing the association between these 2 diseases. Further research seems warranted to explore the pathogenesis of uveal melanoma in MD. These findings support the consideration of ophthalmic examination for uveal melanoma in patients with MD.

Ocular oncology: advances in retinoblastoma, uveal melanoma and conjunctival melanoma.

BackgroundnRetinoblastoma, uveal and conjunctival melanomas are important malignancies within the remit of ocular oncology. Outlined are the diagnostic features and management principles, as well as advancements in the field and current challenges.nnnSources of datanOriginal papers, reviews and guidelines.nnnAreas of agreementnMost eyes with retinoblastoma (International Intraocular Retinoblastoma Classification (IIRC) Group A-D) are salvaged, whereas advanced cases (Group E) remain a challenge. Despite a high rate of local tumour control in uveal melanoma, metastatic spread commonly occurs. Conjunctival melanoma is treated by complete resection, but high rates of local recurrence occur, with the possibility of systemic relapse and death.nnnAreas of controversynUse of the IIRC in retinoblastoma, and systemic screening in melanomas.nnnGrowing pointsnUtilization of novel treatment modalities in retinoblastoma and an increasing understanding of the genetic basis of melanomas.nnnAreas timely for developing researchnImprovements in chemotherapy delivery in retinoblastoma and prognostic tests in melanomas.

Extremely Invasive Conjunctival Melanoma.

Originally received: April 11, 2016. Final revision: April 27, 2016. Accepted: April 27, 2016. Available online: June 1, 2016. Manuscript no. 2016-739. 1 Singapore National Eye Centre, Singapore, Republic of Singapore. 2 Singapore Eye Research Institute, Singapore, Republic of Singapore. 3 Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Singapore, Republic of Singapore. 4 Department of Ophthalmology, National University Health System, Singapore, Republic of Singapore. Financial Disclosure(s): The author(s) have made the following disclosure(s): J.S.M.: Patent e Endoglide (North Yorkshire, UK) (royalties to Network Medical) D.T.: Patent e Endoglide (royalties to Network Medical)

Detection of extrascleral extension in uveal melanoma with histopathological correlation

ABSTRACT Purpose: Uveal melanoma is the most common primary intraocular malignancy. Extrascleral extension (ESE) is rare, but associated with an increased rate of orbital recurrence and an overall poor prognosis. Clinical studies show low rates when compared with histological studies. Due to the prognostic importance of ESE, we sought to compare our clinical, intraoperative, and histological detection rates. Design: A retrospective cross-sectional case series. Methods: A list of eyes enucleated for uveal melanoma was compiled from the admissions records of the London Ocular Oncology Service during the 28-month period, i.e. January 2010–April 2012. The surgical and clinical notes of patients with histopathology proven ESE were reviewed to determine when it was first diagnosed or suspected. The subsequent management of these cases is discussed. Results: A total of 16 out of 174 (9%) eyes had histologically proven ESE. Eight of 16 cases were detected preoperatively at clinical examination, including the use of ocular ultrasound, 3 of 16 were discovered intra-operatively, and 5 of 16 deemed microscopic ESE, were first detected on histological examination. Seven of 7 (100%) of cases with anterior ESE were detected clinically by slit lamp biomicroscopy, while only 1 out of 9 (11%) of cases with posterior ESE was detected preoperatively with ultrasound. Conclusions: Slit lamp biomicroscopy is sensitive for detecting anterior ESE. Most posterior ESE is microscopic, but macroscopic posterior ESE may also be missed by B-scan ocular ultrasound. Orbital surgeons should be suspicious of clinically undetected posterior ESE, and consider adjuvant orbital radiotherapy in cases with macroscopic ESE.