Analysis of Long-term Outcomes of Radiotherapy and Verteporfin Photodynamic Therapy for Circumscribed Choroidal Hemangioma.

PURPOSE: To determine the long-term therapeutic outcome for different treatments of circumscribed choroidal hemangioma (CCH). DESIGN: Retrospective observational study. SUBJECTS: Patients with newly diagnosed CCH. METHODS: Observation, verteporfin (Visudyne) photodynamic therapy (PDT), lens-sparing external beam radiotherapy (LS-EBRT), or plaque brachytherapy. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at baseline and throughout follow-up, tumor dimensions, and OCT central thickness (where available) at baseline and throughout follow-up were recorded. RESULTS: There were 60 treatment-naïve consecutive cases with CCH between January 2000 and June 2014; 42 (70%) received treatment. These were LS-EBRT (23/60 [38%]; mean follow-up, 45.5 months), PDT (16/60 [27%]; mean follow-up, 38 months), and plaque radiotherapy (3/60 [5%]; mean follow-up, 92 months). Macular location, mottled or orange pigment, and absence of drusen were significantly more frequent in the treatment group. In the LS-EBRT group, median thickness reduction on ultrasound B scan was 1.6 mm (mean ± standard deviation, 1.65±1.6; range, -6.5 to +0.7). The mean ± standard deviation BCVA gain was 0.22±0.34, with >3 Snellen lines in 48% of cases. Kaplan-Meier estimates were 80% for any gain and 40% for >3 Snellen lines gain at 5 years. In the PDT group, the median decrease in thickness was 0.95 mm (mean ± standard deviation, 1.0±0.8; range, -2.5 to +0.2). The mean ± standard deviation BCVA gain was at 0.3±0.51, with >3 Snellen lines in 30% of cases. Kaplan-Meier estimates were 93% for any gain and 68% for >3 Snellen lines at 5 years. Double versus single duration PDT had more favorable outcomes with a greater reduction in tumor thickness (P = 0.04), central retinal thickness (P = 0.02), and improvement in visual acuity (median, 0.33 vs -0.05). There was no difference in decrease in tumor thickness or BCVA gain between the LS-EBRT and PDT groups. With plaque brachytherapy, the mean decrease in thickness was 2.5 mm, but BCVA loss of >2 Snellen lines was noted in all 3 cases at the end of follow-up. Radiation complications developed in 10 of 23 cases (43.5%) from the LS-EBRT group and 2 of 3 cases (67%) from the plaque brachytherapy group. CONCLUSIONS: LS-EBRT is equivalent to PDT in CCH management for post-treatment BCVA and tumor thickness reduction. The risk of LS-EBRT and plaque brachytherapy was late radiation-related complications. Double duration PDT was more favorable than single duration.

MESECTODERMAL LEIOMYOMA OF THE CILIARY BODY PRESENTING AS ANTERIOR STAPHYOMA.

PURPOSE: To report two cases of mesectodermal leiomyoma of the ciliary body presenting as anterior staphyloma. METHODS: Two case reports with cytopathologic correlation. RESULTS: First patient (15-year-old boy) presented with a nodular lesion in the sclera. Second patient (31-year-old woman) was found to have a brown ciliary body mass. Growth of the lesion and extrascleral extension was noticed after several years of follow-up. Ultrasonography, light microscopy, and immunohistochemistry of both cases are described confirming mesectodermal leiomyoma of the ciliary body. CONCLUSION: Mesectodermal leiomyoma, despite its rarity, should be considered in the differential diagnosis of uveal tract tumors. Clinically, the diagnosis is difficult and histopathological and immunohistochemical assesment is necessary to avoid inappropriate diagnosis and erroneous treatment.

Endovascular treatment for AIS with underlying ICAD.

BACKGROUND: Acute large vessel occlusion (LVO) can result from thromboemboli or underlying intracranial atherosclerotic disease (ICAD). Although the technique for revascularization differs significantly for these two lesions (simple thrombectomy for thromboemboli and balloon angioplasty and stenting for ICAD), the underlying etiology is often unknown in acute ischemic stroke (AIS). OBJECTIVE: To evaluate whether procedural complications, revascularization rates, and functional outcomes differ among patients with LVO from ICAD or thromboembolism. METHODS: A retrospective review of thrombectomy cases from 2008 to 2015 was carried out for cases of AIS due to underlying ICAD. Thirty-six patients were identified. A chart and imaging review was performed to determine revascularization rates, periprocedural complications, and functional outcomes. Patients with ICAD and acute LVO were compared with those with underlying thromboemboli. RESULTS: Among patients with ICAD and LVO, mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 12.9±8.5, revascularization (Thrombolysis In Cerebral Infarction, TICI ≥2b) was achieved in 22/34 (64.7%) patients, 11% had postprocedural intracerebral hemorrhage (PH2), and 14/33 (42.4%) had achieved a modified Rankin Scale (mRS) score of 0-2 at the 3-month follow-up. Compared with patients without underlying ICAD, there was no difference in NIHSS on presentation, or in the postprocedural complication rate. However, procedure times for ICAD were longer (98.5±59.8 vs 37.1±34.2 min), there was significant difference in successful revascularization rate between the groups (p=0.001), and a trend towards difference in functional outcome at 3 months (p=0.07). CONCLUSIONS: Despite AIS with underlying ICAD requiring a more complex, technically demanding recanalization strategy than traditional thromboembolic AIS, it appears safe, and good outcomes are obtainable.

Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique.

OBJECTIVE: To investigate the associations between Alberta Stroke Program Early CT Score (ASPECTS) or distribution and sidedness of acute infarction and clinical outcomes following intervention with a direct aspiration first pass technique (ADAPT). METHODS: A review was performed of patients who had undergone thrombectomy with ADAPT for emergent large vessel occlusions of the middle cerebral artery (MCA) between December 2012 and May 2015. Preintervention CT scans were reviewed by a blinded radiologist to calculate ASPECTS and determine the distribution of infarction. Clinical outcomes were compared for subsets of patients depending upon ASPECTS and regional infarction distribution (cortical, subcortical, or both). RESULTS: One hundred and fifty-four patients (50% female, mean age 67) underwent thrombectomy using ADAPT for MCA emergent large vessel occlusion. The median presenting National Institute of Health Stroke Scale score was 15. Fifty-five per cent of patients had left-side occlusions. Similar good outcomes were achieved for patients with perfect and non-perfect ASPECTS (modified Rankin Scale (mRS) 0-2: 63% vs 51%, respectively; p=0.20). Similar outcomes were also achieved for patients with 'poor' ASPECTS (≤6) compared with those with ASPECTS >6 (mRS 0-2: 52% vs 53%, respectively; p=0.91). Regional distribution and sidedness of core infarction on preintervention CT also did not correlate with worse outcomes. CONCLUSIONS: Patients with moderate-sized core infarcts involving various distributions in either hemisphere can potentially achieve similar good outcomes compared with those with no core infarction at presentation. A treatment algorithm for acute ischemic stroke, which employs hardline ASPECTS thresholds or excludes patients with basal ganglia infarcts, might preclude patients who would potentially benefit from mechanical thrombectomy with ADAPT.

Anterior Segment Seeding in Eyes With Retinoblastoma Failing to Respond to Intraophthalmic Artery Chemotherapy.

IMPORTANCE: Anterior chamber seeding following intraophthalmic artery chemotherapy is rarely reported. OBJECTIVES: To describe clinicopathologic observations in eyes in which intraophthalmic artery chemotherapy for retinoblastoma failed and to report anterior chamber involvement. OBSERVATIONS: A retrospective case series of 12 enucleated eyes (11 patients) with retinoblastoma refractory to intraophthalmic artery chemotherapy between March 1, 2010, and October 31, 2013, at University College London Institute of Ophthalmology and the Retinoblastoma Service, Royal London Hospital. Data analysis was conducted from June 1, 2014, to March 1, 2015. The International Classification of Retinoblastoma groups were B in 1 eye (8%), C in 4 eyes (33%), and D in 7 eyes (58%). Systemic chemotherapy with vincristine sulfate, etoposide, and carboplatin had failed in 10 patients (91%) and 6 eyes (50%) received additional local treatments. In 6 eyes (50%) anterior chamber invasion was clinically detectable. On histopathologic examination, 4 eyes (33%) had no viable retinal tumor; the remainder had poorly differentiated tumor (6 eyes [50%]) or moderately differentiated tumor (2 eyes [17%]). Anterior segment involvement occurred in the ciliary body and/or ciliary muscle (7 eyes [58%]), iris (6 eyes [50%]), and cornea (4 eyes [33%]). CONCLUSIONS AND RELEVANCE: Intraophthalmic artery chemotherapy can fail in eyes with retinoblastoma. In contrast to previous reports on outcomes following intraophthalmic artery chemotherapy, our series shows involvement of the anterior segment of the eye, including the ciliary body, iris, and cornea. Careful case selection and follow-up are advised.

Thyroid Doses and Risks to Adult Patients Undergoing Neck CT Examinations.

OBJECTIVE: The purpose of this study was to estimate absorbed thyroid dose and consequent cancer risks in adult patients undergoing neck CT examinations. MATERIALS AND METHODS: We used data from neck CT examinations of 68 consecutive adult patients to calculate the thyroid dose and estimate the corresponding cancer risk. Age and sex were recorded along with the volume CT dose index (CTDIvol) that was used to perform the examination. CTDIvol values were used to estimate thyroid doses in the mathematic phantom used in the ImPACT patient CT dosimetry calculator. Corresponding doses in patients were estimated by modeling each patient's neck as an equivalent cylinder of water and applying correction factors for varying neck size and scanning length and the variation of radiation intensity due to automatic exposure control. RESULTS: The mean (± SD) adult patient age was 59 ± 16 years, and the mean equivalent water cylinder diameter used for modeling the patient neck was 19.4 ± 4.2 cm. The average adult patient neck size was about 3 cm larger than the mathematic anthropomorphic phantom (16.5 cm), decreasing the estimated thyroid doses by 15%. Thyroid doses were independent of age and sex, with an average of 50 ± 23 mGy. The average cancer risk for a 20-year-old woman was six times higher than the corresponding risk for a 20-year-old man. Increasing patient age of either sex from 40 to 60 years reduced the cancer risk by approximately an order of magnitude. CONCLUSION: Patient sex and age are the most important factors in determining thyroid cancer risk, with the thyroid dose being secondary.

The breadth of imaging findings of groove pancreatitis.

The pathogenesis of groove pancreatitis involves progressive cystic degeneration of hamartomatous pancreas rests which lie within the duodenal wall. Hamartomatous pancreatic rests can occur in other locations, but when located within the pancreaticoduodenal groove can lead to a particular clinical presentation following the development of fibrotic and inflammatory tissue. Although this is not a disease of the pancreas itself, the pancreatic duct and biliary system is frequently secondarily involved in this regional process. Identification of this entity and its varied appearances as a distinct pathology is essential given the unique management issues of groove pancreatitis.

Spectrum of RB1 mutations identified in 403 retinoblastoma patients.

BACKGROUND: Retinoblastoma (RB) is a malignant, childhood tumour of the developing retina that occurs with an estimated frequency of 1 in 20 000. Identification of oncogenic mutations in the RB1 gene aids in the clinical management of families with a heritable predisposition to RB. Here we present the spectrum of genetic and epigenetic changes identified in 194 tumours and 209 blood samples, from 403 unrelated RB patients. METHODS: Mutation screening was carried out across all 27 RB1 exons and their associated splice sites. Small coding sequence changes were detected using fluorescent conformation analysis followed by sequencing. Large exonic deletions were detected by quantitative fluorescent PCR. Methylation specific PCR of the RB1 promoter was performed to detect epigenetic alterations. Polymorphism analysis was used to determine loss of heterozygosity in tumour samples. RESULTS: 95% of the expected mutations were identified in the tumour samples, with 16 samples exhibiting only one mutation, while two samples had no detectable RB1 mutation. 96% of bilateral/familial RB blood samples and 9.5% of unilateral sporadic blood samples, yielded mutations. 111 were novel mutations. CONCLUSIONS: The full range of screening techniques is required to achieve a high screening sensitivity in RB patients.

Prospective study of sentinel lymph node biopsy for conjunctival melanoma.

BACKGROUND: To report our experience with sentinel lymph node biopsy for staging patients with conjunctival melanoma. METHODS: A prospective review of patients with conjunctival melanoma who underwent sentinel lymph node biopsy at St Bartholomew's Hospital from May 2008 to May 2012. The selection criterion for sentinel node biopsy depended on the tumour thickness (≥2 mm) and location of the conjunctival melanoma. The main outcome measures were the incidence of sentinel lymph node positivity and the procedure-related complications. RESULTS: In 4 years, 26 out of 70 patients met the selection criteria for sentinel lymph node biopsy. 4 patients declined and 22 patients consented for the procedure. Technetium-99m failed to identify a sentinel lymph node in four of the 22 patients (18%). Of the remaining 18 patients, two were found to have subclinical micrometastasis in regional lymph nodes. Median follow-up was 20 months (range 6-36 months). No false-negative events were observed. Complications of the procedure included transient blue staining of the epibulbar surface in five patients and transient facial nerve palsy in one patient. CONCLUSIONS: Sentinel lymph node biopsy is a safe procedure with minimal complications. It should be considered for the staging of conjunctival melanomas, especially melanomas in non-limbal location or conjunctival melanomas ≥2 mm thick.

Autonomic cardio-respiratory reflex reactions and superselective ophthalmic arterial chemotherapy for retinoblastoma.

OBJECTIVE: To describe our experience with superselective ophthalmic artery chemotherapy (SOAC) in retinoblastoma and to report the serious adverse cardio-respiratory reactions we have observed. METHODS: SOAC was performed using a standardized protocol for general anesthesia, ophthalmic artery catheterization, and pulsed infusion of melphalan. Adverse reactions were defined as those in which the patient required active treatment to maintain cardio-respiratory stability. RESULTS: Between December 2008 and May 2012, 54 eyes in 52 patients were treated. 143 catheterization procedures were performed, with a technical success rate of 93% (n = 133). There were no deaths or major complications. Adverse cardio-respiratory reactions developed during 35 procedures (24%; 95% CI, 18-32%). All reactions occurred during second or subsequent catheterization procedures (39%; 95% CI, .29-49%) and were characterized by hypoxia, reduced lung compliance, systemic hypotension and bradycardia. Adverse events were successfully treated in all patients. One procedure was abandoned due to prolonged hemodynamic instability. CONCLUSION: Adverse cardio-respiratory reactions are commonly observed in SOAC for retinoblastoma. We believe that the adverse clinical signs represent an autonomic reflex response, akin to the trigemino-cardiac or oculo-respiratory reflexes, and all patients should be considered at-risk. Reactions occur only during second or subsequent procedures and can be life-threatening. The routine use of intravenous atropine does not seem to have altered the incidence or severity of these reactions. Anesthetists and interventional neuroradiologists involved in SOAC must be vigilant to ensure adverse reactions, when they develop, are treated quickly and effectively.

The use of strontium-90 Beta radiotherapy as adjuvant treatment for conjunctival melanoma.

Background/Aims. To report the safety and efficacy of strontium (Sr(90)) beta radiotherapy as adjuvant treatment for conjunctival melanoma. Methods. A retrospective cohort study was undertaken from 1999 to 2007 of all patients who underwent Sr(90) beta radiotherapy for incompletely excised conjunctival melanoma. Failure of treatment was defined as recurrence of a conjunctival melanoma at the same location following beta radiotherapy. Results. Twenty patients underwent Sr(90) beta radiotherapy for incompletely excised conjunctival melanoma. Median follow-up interval was 59 months (8-152). All patients had conjunctival melanoma involving the bulbar conjunctiva. Underlying diagnoses included PAM with atypia in 60% (12 of 20), PAM without atypia in 15% (3 of 20), and de novo conjunctival melanoma in 25% (5 of 20). Following Sr(90) beta radiotherapy, in 90% (18 out of 20) local control was achieved and visual acuity was not affected in any patient. Three patients (15%) had dry eye symptoms, episcleritis, and descemetcoele, respectively. No cataract or secondary glaucoma was reported. Conclusions. Sr(90) treatment is a very effective adjuvant treatment after excisional biopsy and cryotherapy for conjunctival melanoma with a local success rate of 90%. The treatment is not associated with significant side effects and visual acuity is not affected.

Distal protection for treatment of complete cervical internal carotid occlusion.

Distal protection devices (DPD) have been advocated for carotid artery stenting to reduce the risk of distal embolization. These devices were designed for deployment in the straight cervical segment of the internal carotid artery. We present a case of total cervical carotid occlusion recanalized with the aid of a distal protection device deployed 'distally' in the intracranial internal carotid artery.

The biology of micrometastases from uveal melanoma.

BACKGROUND: The aim of this study was to investigate the possible causes of tumour latency in uveal melanoma primarily through the analysis of micrometastases in tissue obtained from donors postmortem. Various explanations have been proposed but there is no clear answer from animal studies and few human data. The main hypotheses may be divided into several areas--immunological control of metastatic cells, lack of angiogenesis within micrometastases and reduced cell turnover. METHODS: 196 patients were recruited to the study between 2003 and 2007. Patients were invited to take part and their relatives agreed to postmortem examination of their liver and lungs in the event of their death, including tissue sampling to assess the presence of micrometastases and their biology. Metastatic cells were detected by immunohistochemistry using a pan-melanoma antibody reagent, and by quantitative reverse transcriptase (qRT)-PCR for three melanoma-associated genes (tyrosinase Melan-A, and gp100) and a housekeeping gene (HMBS/PBGD) in samples stored in RNAlater or as formalin-fixed paraffin-embedded tissue. RESULTS: 22 deaths were investigated at autopsy as part of the study. Sixteen patients died with large deposits of metastatic melanoma, while six patients died of other causes. In addition, a liver resection for hepatic adenoma provided further tissue from a case without clinical evidence of metastasis. Metastatic melanoma cells were identified by immunohistochemistry of the liver samples in one case and by qRT-PCR in two further cases without macrometastases. There was no evidence of multicellular micrometastases sufficiently large to require angiogenesis and no associated inflammation was observed. CONCLUSION: The most likely explanation for latency in this setting is the inability of uveal melanoma cells in metastatic sites to grow.

Transpositional Autokeratoplasty in a Patient with Unilateral Choroidal Melanoma and Contralateral Exposure Keratopathy.

Penetrating keratoplasty was required to improve corneal clarity in the left eye, which had suffered chronic exposure keratopathy following a cerebellopontine angle tumor with facial nerve involvement. The right eye had a large choroidal melanoma, which had failed brachytherapy, but the cornea was transparent and healthy. The right eye corneal button was sutured to the left eye host and a donor corneal button was sutured to the right eye rim. The right eye was subsequently enucleated. Two years later, the patient had 6/12 visual acuity with a clear graft and no tumor seeding in the host eye. Although limited opportunities arise to employ transpositional autokeratoplasty, where appropriate, it offers an alternative to conventional allokeratoplasty with a lower risk of immune rejection.

Histopathologically proven mucinous cystadenocarcinoma metastatic to the choroid.

PURPOSE: To report the first case of conventional transcleral choroidal biopsy in the diagnosis of ovarian carcinoma metastatic to the choroid and to summarize the published cases of ovarian carcinoma metastatic to the choroid. METHODS: Case report and Medline literature review. RESULTS: This is the tenth case reported in the literature and the only case that underwent conventional transcleral choroidal biopsy. Transcleral choroidal biopsy allowed the diagnosis of metastatic mucinous cystadenocarcinoma of the ovary. Choroidal metastases are not associated with central nervous system involvement; however, investigations may reveal distal boney or pulmonary metastases. CONCLUSION: Ovarian carcinoma rarely metastases to the choroid and unlike breast carcinoma, concurrent central nervous system disease has not been reported. When systemic investigations fail to reveal active intraperitoneal disease or distal metastases, the clinician should consider referral to an ocular oncology center for a choroidal biopsy.

Recurrence of treated ciliary body melanoma following trabeculectomy.

A 69-year-old man was treated for a right ciliary body melanoma with plaque radiotherapy. One year later, he had uncomplicated cataract extraction but developed prolonged postoperative inflammation and secondary glaucoma. The tumour remained unchanged on yearly ultrasound B scans but intraocular pressures became uncontrolled despite maximal medical therapy. After radiotherapy, he underwent trabeculectomy with 5-fluorouracil and revision with mitomycin C 2 years later. The melanoma recurred with extrascleral extension under the trabeculectomy bleb 14 years after plaque radiotherapy and 5 years after trabeculectomy surgery. Enucleation was performed and histological analysis showed a ring melanoma involving the root of the iris, filling the trabecular meshwork and extending into the anterior chamber. The predominant cell type was epithelioid with large nuclei and prominent nucleoli. Trabeculectomy surgery may increase the risk of extrascleral extension of ciliary body melanoma even after apparently successful plaque radiotherapy and long-term local tumour control.

Retinoblastoma: one world, one vision.

Retinoblastoma is curable when diagnosed early and treated appropriately; however, the prognosis is dismal when the basic elements of diagnosis and treatment are lacking. In developing countries, poor education, lower socioeconomic conditions, and inefficient health care systems result in delayed diagnosis and suboptimal care. Furthermore, the complexity of multidisciplinary care required is seldom possible. Whereas ocular salvage is a priority in the Western world, death from retinoblastoma is still a major problem in developing countries. To bring the 2 ends of this spectrum together and provide a forum for discussion, the "One World, One Vision" symposium was organized, at which clinicians and researchers from various cultural, geographic, and socioeconomic backgrounds converged to discuss their experiences. Strategies for early diagnosis in developing countries were discussed. Elements of the development of retinoblastoma centers in developing countries were discussed, and examples of successful programs were highlighted. An important component in this process is twinning between centers in developing countries and mentor institutions in high-income countries. Global initiatives by nongovernmental organizations such as the International Network for Cancer Treatment and Research, Orbis International, and the International Agency for Prevention of Blindness were presented. Treatment of retinoblastoma in developing countries remains a challenge; however, it is possible to coordinate efforts at multiple levels, including public administrations and nonprofit organizations, to improve the diagnosis and treatment of retinoblastoma and to improve the outcome for these children.