Neuroblastoma with orbital metastasis: ophthalmic presentation and role of ophthalmologists

INTRODUCTION: Neuroblastoma is predominantly a tumour of early childhood, which metastasises to the orbits. In such cases, ophthalmologists are involved in the multidisciplinary management. This unique series from a tertiary referral centre is used to elaborate the ophthalmic associations and the ophthalmologist's role in this rare condition. METHODS: A review of case notes was performed on six patients who presented to the paediatric ophthalmology - oncology liaison service at the Leeds teaching hospitals between 1998 and 2003. The ophthalmic outcome and role of the ophthalmologist were assessed. RESULTS: Average age of presentation was 29.8 months (range 15-69 months). Average duration of follow-up was 19.5 months (range 2-58 months). One child died during treatment. Two have completed treatment and are under follow-up. Presenting features of the six children were proptosis in four, periorbital ecchymosis in two, ocular motility restriction in two, and subconjunctival haemorrhage in one. Only one case developed blindness. CONCLUSIONS: The role of the ophthalmologist in patients with metastatic orbital neuroblastoma can vary from a supportive role to one of active intervention and management of ophthalmic complications. The ophthalmologist is involved in diagnosis and staging as well as monitoring response to treatment of both the primary disease and secondary ophthalmic complications.     

Metastatic tumours to the conjunctiva: report of 10 cases.

AIMS/BACKGROUND: Ten patients with metastatic tumours to the conjunctiva and the clinical aspects of this rare form of ocular metastasis are described in this study. METHOD: All patients with ocular and adnexal metastatic tumours referred to an ocular oncology service were reviewed and those having conjunctival metastases were studied for the site of their primary tumour, clinical features, and treatment of the conjunctival tumour, associated ocular and systemic findings, and the patients' outcome. RESULTS: The primary malignancy was carcinoma of the breast in four, lung cancer in two, laryngeal carcinoma in one, cutaneous melanoma in two, and unknown in one patient. The conjunctival metastases appeared after the primary tumour over a mean period of 44 (8-130) months. They were solitary in eight cases, located in bulbar conjunctiva in six, palpebral conjunctiva in two, and in limbus and forniceal conjunctiva in one patient each. The tumour was yellow in colour in seven patients, red in two, and brown in one. Eight patients also had metastases to other ocular structures. Seven patients received external beam radiotherapy to the affected eye, two were managed by excisional biopsy, and one with chemotherapy. The mean survival after the diagnosis of conjunctival metastasis was nine (range 2-26) months. CONCLUSION: Metastatic tumours to the conjunctiva appear at an advanced stage of the systemic disease when there are other ocular and organ metastases. The presence of a conjunctival mass in a patient with a prior systemic cancer should alert the ophthalmologist to the possibility of a conjunctival metastasis and evaluation should be pursued.     

Thermotherapy in the management of choroidal melanoma

During the past 20 years of enucleation, which was the standard treatment for choroidal melanoma over more than a century, has largely been replaced by eye salvaging therapies such as radiotherapy or local resection. In 1995 transpupillary thermotherapy (TTT) using an infrared diode laser was introduced as a new conservative therapy for patients with choroidal melanoma. TTT can be defined as a heat treatment modality, which is delivered through a dilated pupil to the tumour surface. The technique uses a wide diode laser beam diameter with a low irradiance and a long exposure time. TTT induces tumour necrosis at sub-photocoagulation levels by a direct cell destructive effect with only a few ocular complications. TTT can be performed as sole therapy or combined with plaque radiotherapy, thus permitting a lower radiation dose. For amelanotic tumours dye-enhanced TTT with indocyanine green can be used. In this paper we review the role of sole or combined TTT, related to the current other treatment modalities for choroidal melanoma.     

Clinical factors in the identification of small choroidal melanoma

The detection and treatment of choroidal melanoma early in its natural course is critical to providing the patient with the best prognosis. Studies of tumour doubling time have indicated that metastasis from choroidal melanoma can occur quite early in the course of the disease, when the tumour is about 3.0 mm in basal dimension and 1.5 mm in thickness. Clinical studies have shown that, at 5 years, metastasis occurs in 16% of patients with small choroidal melanomas (less than 4 mm thick), compared with 32% of those with medium-sized (4-8 mm thick) choroidal melanomas and 53% of those with large (more than 8 mm thick) choroidal melanomas.The difficulty with early detection of choroidal melanoma relates to its clinical similarity to benign choroidal nevus. Factors that assist in differentiating small choroidal melanoma from choroidal nevus can be remembered using the mnemonic "TFSOM" (to find small ocular melanoma), where T = thickness greater than 2 mm, F = subretinal fluid, S = symptoms, O = orange pigment and M = margin touching optic disc. Choroidal melanocytic tumours that display none of these factors have a 3% risk of growth into melanoma at 5 years and most likely represent choroidal nevi.Tumours that display one factor have a 38% risk of growth, and those with two or more factors show growth in over 50% of cases. Most tumours with two or more risk factors probably represent small choroidal melanomas, and early treatment is generally indicated.Therefore, ophthalmologists should be aware of the clinical factors that identify small choroidal melanoma so that early treatment and better prognosis can be achieved for their patients.     

Predictive factors of visual outcome after local resection of choroidal melanoma.

Local resection of choroidal melanomas is not widely performed so that the indications for this operation have not previously been defined statistically. Univariate and multivariate Cox regression analyses were used to identify the factors influencing visual acuity after 163 completed local resections for choroidal melanoma in patients with a preoperative visual acuity of counting fingers or better. The variables included in the analyses were patient age and sex; eye laterality and preoperative visual acuity; location of anterior and posterior tumour margins; tumour location (coronal and sagittal); tumour diameter, thickness, and cell type; ocular decompression by vitrectomy; and adequacy of surgical clearance. The surgical resections were performed using a lamellar scleral flap for eye closure, hypotensive anaesthesia for haemostasis, and, in the later years, ocular decompression by pars plana vitrectomy to improve access. The patients (94 men, 69 women) had a mean age of 50 years. The tumours had a mean diameter of 13.3 mm and a mean thickness of 7.4 mm, with 38 tumours extending to within 1 disc diameter (DD) of the optic disc, fovea or both (that is, 'posterior tumour extension'). Cox multivariate analysis showed that the most significant preoperative factors for predicting retention of good vision (6/12 or better) were nasal tumour location (p = 0.002) and distance of more than 1 DD between the tumour and the optic disc or fovea (p = 0.010). The most significant predictive risk factor for severe visual loss (hand movements or worse) was posterior tumour extension to within 1 DD of the optic disc and/or fovea (p = 0.009). One year post-operatively, all 28 patients with nasal tumours not extending to within 1 DD of the optic disc or fovea retained the eye with 57% having vision of 6/12 or better and 93% having vision of counting fingers or better. In 68 patients with temporal tumours, 90% retained the eye at 1 year with preservation of vision of counting fingers or better in 82% of 56 eyes without posterior tumours extension and in 50% of 12 eyes with posterior tumour extension. In patients with choroidal melanoma, conservation of the eye and vision can be achieved by local resection, especially if the tumour is located nasally and does not extend close to the disc or fovea.     

Measurement of choroidal melanoma basal diameter by wide-angle digital fundus camera: a comparison with ultrasound measurement

PURPOSE: To compare the measurement of the basal diameter of choroidal melanoma, an important parameter for planning treatment and as a prognostic factor, by standardized ophthalmic ultrasound versus that obtained using a wide-angle fundus camera. METHODS: The longest and shortest basal diameters of 104 consecutive choroidal melanomas of patients seen at the ocular oncology service of the Hadassah University Hospital were measured by B-scan ultrasound and compared with those measured by a wide-angle fundus camera (Panoret-1000). Each diameter was measured thrice by two ophthalmic photographers, and intra-observer and interobserver reproducibility were calculated as well. RESULTS: The measurements of both the long and short diameters of the choroidal melanomas were significantly larger when measured by Panoret-1000 as compared with the B-scan ultrasound. There was no significant difference among the three measurements of each of the photographers. The interobserver reproducibility between the two photographers was high. CONCLUSIONS: Our findings can be attributed to the larger extent of the pigmentation of the melanoma compared to its recognized elevation. Since pigmentation of choroidal melanoma is easier to recognize than its elevation, we assume that measurement by a wide-angle fundus camera is more accurate in pigmented tumors, and should be adopted for measuring the basal diameter of choroidal melanomas in planning treatment and follow-up.     

A nurse-led ocular oncology clinic in Liverpool: results of a 6-month trial

Purpose

To describe the design and implementation of a nurse-led clinic in a tertiary adult ocular oncology service and to assess its feasibility and patient satisfaction.

Methods

Patients with a melanocytic uveal tumour attending for review during an initial 6-month trial period were assessed in a dedicated ocular oncology clinic by an ophthalmic nurse practitioner. These were: (1) patients who would have been discharged back to the referring hospital but whose ophthalmologist refused to continue their follow-up; (2) patients who preferred to be reviewed in our clinic; and (3) patients with a risk of metastatic disease that was increased but not enough for them to be referred to our medical oncologist. Quality assurance mechanisms were established to ensure safe practice. Patient satisfaction was assessed by means of anonymised questionnaires.

Results

A total of 65 patients were seen between 1 November 2011 and 31 May 2011. The mean age was 58 years (range 16–82 years). Most lesions seen were choroidal suspicious naevi (54%) and treated choroidal malignant melanomas (20%). Nine (14%) patients with an increased risk of metastatic disease attended the clinic. Nine patients (14%) were referred back to the ophthalmologist''s ocular oncology clinic, because of tumour growth in two patients, macular oedema in one, cataract in five, and conjunctival melanosis at the plaque site in one. Questionnaires showed high levels of satisfaction with the service.

Conclusion

A nurse-led adult ocular oncology clinic is feasible, thanks to developments in ocular photography. It is well accepted by patients.     

Nondiagnosed uveal melanomas

PURPOSE: To determine the proportion of nondiagnosed uveal melanomas after evaluation by optometrists or ophthalmologists. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Four hundred thirty-three ophthalmic oncology patients with uveal melanoma. METHODS: This was a retrospective study of uveal melanoma patients from a single ophthalmic oncology center. We sent questionnaires to living patients we had treated between 1980 and 2000 for uveal melanoma. Patients were divided into those who had an examination within 1 year before diagnosis of a melanoma in which the tumor was not detected, those patients who were being observed with a known pigmented uveal tumor, and those who had not had an eye examination for at least 10 years. MAIN OUTCOME MEASURE: The detection of unsuspected melanomas. RESULTS: We determined that 37% of patients referred to us with a newly discovered uveal melanoma had been examined within a year, without a uveal melanoma being detected. Of patients whose medical records were obtained, 71% had eyes that had been dilated and the tumor not found. The patients in whom the tumors were nondiagnosed within 1 year of referral to us had a mean tumor thickness of 6 mm and a mean tumor diameter of 12 mm. Ninety percent of the tumors were partially posterior to the equator. Patients who had been observed by their outside ophthalmologist with a choroidal pigmented tumor had significantly smaller tumors (P<0.005). CONCLUSIONS: There are a notable number of patients seen by general ophthalmologists with symptomatic uveal melanomas in whom the diagnosis is not established. It is likely that screening efforts for this relatively rare condition are often not efficacious.     

Tumour location affects the incidence of cataract and retinopathy after ophthalmic plaque radiation therapy

AIM: To examine how tumour location affects ocular morbidity after ophthalmic plaque radiotherapy for uveal melanoma. METHODS: 69 eyes were irradiated and followed for a mean 42 months. There were 23 anterior uveal melanomas and 46 were posterior to the equator. Anterior and posterior tumours had similar basal dimensions. Their mean apical heights were 4.8 mm (anterior) and 3.5 mm (posterior) which received a mean 88 Gy and 83.4 Gy respectively. RESULTS: Only one patient (4%) plaqued for an anterior uveal melanoma developed secondary retinopathy (cystoid macular oedema). In contrast, 24 (52%) of the posterior choroidal melanoma patients developed retinopathy (p value <0.0001). Cataract developed in 18 (86%) eyes with phakic anterior tumour compared with seven (17%) eyes with posterior tumours (p value <0.0000). No posterior nasal tumours lost more than two lines of vision though 45% developed retinopathy. CONCLUSION: While plaque radiation of anterior melanomas is more likely to cause reversible vision loss secondary to cataract, treatment of posterior tumours is more likely to be associated with irreversible loss because of retinopathy. Nasal location is also protective against severe loss of vision.     

Ultrasound detection of posterior scleral bowing in young patients with choroidal melanoma

BACKGROUND: In evaluating young patients with choroidal melanomas, which are uncommon in people less than 30 years old, we noted that some had the ultrasound appearance of posterior scleral bowing. The purpose of this study was to determine the incidence of posterior scleral bowing in young patients with choroidal melanoma. METHODS: We reviewed the ultrasonograms of 24 patients less than 30 years of age (mean age 25 years [standard deviation (SD) 4.7 years]) who presented to an ocular oncology service in Toronto between May 1984 and May 1997. In all cases the diagnosis was choroidal melanoma. Histologic specimens were available in six cases. RESULTS: Scleral indentation posterior to the normal curvature of the globe was identified in 14 patients (58%). These patients had a mean tumour height of 4.4 mm (SD 2.0 mm) and mean tumour diameter of 9.5 mm (SD 2.9 mm). In the 10 patients with no scleral bowing the mean tumour height was 5.7 mm (SD 3.1 mm) and mean tumour diameter 11.5 mm (SD 3.8 mm). Pathological study (results available in nine cases in the scleral bowing group and four cases in the group without bowing) showed that all the tumours in the former group and three of those in the latter group were of the more indolent cell types, either mixed with predominantly spindle cells, or spindle cell. The six patients with histologic specimens were all in the scleral bowing group. The histologic features supported the ultrasound finding of posterior scleral bowing. No transscleral invasion occurred over the tumour region. INTERPRETATION: Posterior bowing of the sclera at the tumour site was observed in over half of young patients with choroidal melanoma. This phenomenon can be detected by ultrasonography and has a different appearance from that of choroidal excavation.     

Treatment considerations for primary uveal melanoma with choroidal metastasis to the fellow eye

We report two cases of primary uveal melanoma with metastatic involvement of the contralateral eye. Two female patients presented with primary choroidal melanoma. In the first case, primary enucleation of the affected eye was performed. Two years later, systemic tumor spread with contralateral choroidal melanoma was detected. A decision for observation of the ocular metastasis was made. In the second case, systemic tumor spread was already evident at time of initial diagnosis of the ocular melanoma. Six months later, a choroidal metastasis was detected in the fellow eye. Again, observation was recommended. In conclusion, systemic spread of primary choroidal melanoma may include a choroidal metastasis to the contralateral eye. Observation of the second affected eye may be prescribed.     

Craniofacial surgery for orbital malformations

Paediatric craniofacial surgery is a highly specialised field requiring a multidisciplinary team input. Orbital and ocular involvement is relatively common in craniofacial patients. This is more in syndromic patients. In nonsyndromic patients, orbital involvement is common in frontal plagiocephaly and trigonocephaly. The management of these conditions requires close working between the craniofacial surgeon and ophthalmologist. An outline of the management of these deformities is discussed.     

Treatment Considerations for Primary Uveal Melanoma with Choroidal Metastasis to the Fellow Eye

We report two cases of primary uveal melanoma with metastatic involvement of the contralateral eye. Two female patients presented with primary choroidal melanoma. In the first case, primary enucleation of the affected eye was performed. Two years later, systemic tumor spread with contralateral choroidal melanoma was detected. A decision for observation of the ocular metastasis was made. In the second case, systemic tumor spread was already evident at time of initial diagnosis of the ocular melanoma. Six months later, a choroidal metastasis was detected in the fellow eye. Again, observation was recommended. In conclusion, systemic spread of primary choroidal melanoma may include a choroidal metastasis to the contralateral eye. Observation of the second affected eye may be prescribed.     

Ocular phototherapy

Phototherapy can be translated to mean ‘light or radiant energy-induced treatment.'' Lasers have become the exclusive source of light or radiant energy for all applications of phototherapy. Depending on the wavelength, intensity, and duration of exposure, tissues can either absorb the energy (photocoagulation, thermotherapy, and photodynamic therapy (PDT)) or undergo ionization (photodisruption). For phototherapy to be effective, the energy has to be absorbed by tissues or more specifically by naturally occurring pigment (xanthophyll, haemoglobin, and melanin) within them. In tissues or tumours that lack natural pigment, dyes (verteporphin, Visudyne) with narrow absorption spectrum can be injected intravenously that act as focal absorbent of laser energy after they have preferentially localized within the tumour. Ocular phototherapy has broad applications in treatment of ocular tumours. Laser photocoagulation, thermotherapy, and PDT can be delivered with low rates of complications and with ease in the outpatient setting. Review of the current literature suggests excellent results when these treatments are applied for benign tumours, particularly for vascular tumours such as circumscribed choroidal haemangioma. For primary malignant tumours, such as choroidal melanoma, thermotherapy, and PDT do not offer local tumour control rates that are equivalent or higher than those achieved with plaque or proton radiation therapy. However, for secondary malignant tumours (choroidal metastases), thermotherapy and PDT can be applied as a palliative treatment. Greater experience is necessary to fully comprehend risks, comparative benefits, and complication of ocular phototherapy of ocular tumours.     

A retrospective analysis of primary eye cancer at the University of Alabama at Birmingham 1958-1988. Part I: Eye and orbital cancer.

Records of 99 patients with 100 primary eye cancers seen at the University of Alabama Hospital for the years 1958-1988 were reviewed. Three ocular cancers were found to predominate: 1) choroidal melanoma, 2) retinoblastoma, and 3) squamous cell carcinoma. Epidemiologic distribution of the population is presented and compared to that of tumors commonly seen in general ophthalmic practice.     

Ocular manifestations of pulmonary hypertension

Pulmonary hypertension, if left untreated, may result in increasing cardiac back pressures and lead to right heart failure and death. An increase in venous pressure in cases of pulmonary hypertension influences other organs. Ocular complications occur as a result of elevated venous pressure in the superior vena cava and in the ophthalmic veins, which cause dilation of the ocular veins, resulting in congestion of the choroid and leading to complications such as ciliary detachment, central retinal vein occlusion, acute serous retinal detachment, macular edema, retinal neovascularization, choroidal effusions, chemosis, angle-closure glaucoma, transient myopia, and proptosis. Other ophthalmic disorders are the results of side effects of treatment. Patients may present primarily to an ophthalmologist, who may diagnose these diseases. Patients with pulmonary hypertension should be taught careful self-observation of visual function, and if it deteriorates, they should immediately report this to an ophthalmologist. Before initiation of any target-oriented therapy, the patient must be informed about possible sight-threatening complications. We review ophthalmological disorders that may develop in the course of pulmonary hypertension and emphasize multidisciplinary cooperation.     

Options for management of intra ocular tumors

The management of intra ocular tumors has undergone a sea change from the era of enucleation or external beam radiation. With the advent of new chemotherapy protocols, globe and vision salvage have become possible in a majority of cases of retinoblastoma. This article is an overview of the various modalities available for the management of intra ocular tumors and their indications. Chemotherapy has been covered elsewhere in this series of articles on ocular oncology. Photocoagulation and cryopexy are easily administered modalities of treatment for small tumors and totally within the ophthalmologist''s domain. Slightly larger tumors are treatable with brachytherapy. The susceptibility of the tumors to chemotherapy and radiation decide the choice of treatment and the dosage. Management of intra ocular tumors very often needs a multidisciplinary approach including ophthalmologist, oncologist, radiation physicist, and radiotherapist.     

Accuracy of choroidal melanoma diagnosis by general ophthalmologists: a prospective study

PURPOSE: To estimate the proportion of 'false positives' in patients referred with a diagnosis of suspected choroidal melanoma by general ophthalmologists to an ocular oncology centre. METHODS: A prospective study of patients referred by general ophthalmologists to an ocular oncology centre was undertaken over a 14-week period. The diagnosis was made clinically in patients receiving radiotherapy or phototherapy and was confirmed by histopathology in patients requiring fine needle aspiration biopsy (FNAB) or enucleation. RESULTS: A total of 132 new patients were seen in 10 consecutive ocular oncology clinics between 29 March 2004 and 5 July 2004. The mean age was 62 years (range 28-88 years) and 60 (55%) were female. Among the 83 suspected malignant posterior segment lesions, the suspected diagnosis included choroidal melanoma (73), choroidal metastasis (6), 'choroidal tumour' (3), and 'Solid retinal detachment' (1). Only 50 of the 73 suspected melanomas were confirmed (68.5%; 95% CI, 57-78%), the oncologist's diagnosis in the remaining 23 being choroidal naevus (10), choroidal metastasis (1), circumscribed choroidal haemangioma (2) and others (10). Only one of six patients with suspected metastases had this condition, the remainder having melanoma (1), lymphoma (1), circumscribed choroidal haemangioma (1), and others (2). The 'choroidal tumours' and 'solid detachments' were found to be chorio-retinal disciform scar (1), varix of vortex vein (1), eccentric CNV (1), and subretinal haemorrhage (1) CONCLUSION: Approximately 30% of patients referred to an ocular oncology service with the diagnosis of choroidal melanoma have an incorrect diagnosis.     

Combined plaque radiotherapy and transpupillary thermotherapy in choroidal melanoma: 5 years' experience

AIM: To evaluate the results of combined plaque radiotherapy and transpupillary thermotherapy (TTT) in 50 consecutive patients 5 years after treatment. METHODS: 50 adult patients with choroidal melanoma were treated with ruthenium-106 ((106)Ru) plaque radiotherapy combined with TTT. A flat scar was the preferred end point of treatment. The mean tumour thickness was 3.9 mm (range 1.5-8.0 mm), the mean tumour diameter was 11.3 mm (range 5.8-15.0 mm). TTT was performed with an infrared diode laser at 810 nm, a beam diameter of 2-3 mm, and 1 minute exposures. Tumours >5 mm thick received an episcleral contact dose of 800 Gy (106)Ru; tumours 3 mm thick (log rank test p = 0.01). Eight melanomas were amelanotic, seven of which required multiple TTT sessions. In one patient the tumour recurred at the central margin of the treated area; this eye was enucleated. In one patient the tumour failed to regress 6 months after treatment and enucleation was performed at the patient's request. Three eyes developed severe proliferative retinopathy. Radiation maculopathy caused a loss of the best corrected visual acuity: before treatment 31 patients had a best corrected visual acuity of 20/60 or better but in only 12 patients did it remain in this range 5 years after treatment. Three patients developed distant metastasis to the liver. CONCLUSION: The 5 year results for combined plaque radiotherapy and TTT as treatment for choroidal melanoma are favourable in terms of complete tumour regression and low rate of recurrences; however, there was considerable loss of visual acuity as a result of radiation maculopathy.     

Alternatives to enucleation in the management of choroidal melanoma

Over the past 15 years 140 patients with choroidal melanoma have been treated by local surgical resection of the tumour. The method appears worth considering for tumours up to 15 mm in diameter not involving more than one-third of the ciliary body. Sixty percent of patients retained useful vision and 25% good vision. Eighty-two percent retained a cosmetically satisfactory eye. The total tumour-related mortality in this group of patients was 9%, almost all of the 12 patients dying having had tumours larger than would now be recommended for local resection. The five-year survival rate among patients undergoing local resection was 84%. Low-energy long-exposure laser has been used to treat a small number of choroidal tumours. The technique appears useful for tumours up to 10 mm in diameter and not more than 3 mm in thickness. Ruthenium plaque therapy has also been used in some cases and appears a suitable method of treatment for tumours up to 10 mm in diameter and not more than 6 mm in thickness. The options for conservative management of choroidal tumours are greater with small tumours than with large ones except in only eyes, tumours of over 15 mm in diameter are best treated with enucleation. The long-term survival after all forms of conservative management has not yet been established. At present the use of controversial techniques such as local resection should be restricted to a few centres so that adequate statistical evaluation of the method may be made.