J. L. Hungerford

Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases.

A series of 256 consecutive cases of invasive primary conjunctival malignant melanomas was examined to identify clinical and histopathological prognostic factors. The follow up period varied between 0.3 and 45.9 years (mean 9 years, median 6.3 years). The 5 year survival rate was estimated at 82.9%, the 10 year survival rate at 69.3%. Multiple regression analysis with the Cox proportional hazards model was used to assess sex, age, and a number of baseline features of conjunctival malignant melanoma as possible prognostic factors influencing melanoma related mortality. In assessing each potential prognostic factor, the effects of all other factors were taken into account in the modelling process. Tumours in unfavourable locations--that is, those involving the palpebral conjunctiva, fornices, plica, caruncle, and lid margins, were associated with 2.2 times higher mortality compared with (epi)bulbar melanomas. Patients with mixed cell type tumours had about three times higher mortality compared with those with pure spindle cell melanomas, and histological evidence of lymphatic invasion by tumour cells was also a prognostic feature, carrying a fourfold increase in the death rate. Multifocal tumours were associated with a fivefold increase in mortality among those with tumours in favourable (epi)bulbar locations, but were not prognostic in patients with melanomas in unfavourable sites. The death rate was significantly higher in those with initial tumour thickness of more than 4 mm, but only among patients with unfavourably located melanomas. Sex, age, and clinical origin of the tumour (primary acquired melanosis, pre-existing naevus, or de novo) were not useful prognostic indicators in this study.

Choroidal Hemangiomas: Visual and Anatomic Results of Treatment by Photocoagulation or Radiation Therapy

PURPOSE Choroidal hemangioma is a benign hamartoma that causes accumulation of subretinal fluid and resultant visual loss. Although photocoagulation can result in resolution of subretinal fluid, some have found that recurrence is common and final visual acuity often is poor. The purpose of this study is to evaluate the visual and anatomic results of radiation therapy and photocoagulation in treating patients with visual loss from choroidal hemangiomas. METHODS A retrospective review was performed of patients with circumscribed choroidal hemangiomas (CCH) or diffuse choroidal hemangiomas (DCH) treated for visual loss caused by accumulation of subretinal fluid. Of 23 patients with CCH, 13 were treated by photocoagulation, 8 by plaque brachytherapy, and 2 by lens-sparing external beam radiation therapy (LSRT). All five patients with DCH were treated by LSRT. RESULTS Of patients with CCH treated by brachytherapy, six (75%) of eight had visual acuity of 6/12 or better at 1 year and 8 (100%) of 8 had no subretinal fluid. Of patients with CCH treated by photocoagulation, 5 (38%) of 13 had visual acuity of 6/12 or better at 1 year and 6 (46%) of 13 had no subretinal fluid. Of patients with CCH treated by LSRT, none of two had visual acuity of 6/12 or better at 1 year and one of two had no subretinal fluid. Of the five patients with DCH treated by LSRT, all had complete resolution of subretinal fluid. Two had marked visual improvement and in the other three, vision was stabilized. CONCLUSIONS Plaque brachytherapy is an effective alternative to photocoagulation for treatment of subretinal fluid caused by CCH. Lens-sparing external beam radiation therapy is effective treatment in patients with DCH.

Orbital exenteration in 95 cases of primary conjunctival malignant melanoma.

The role of orbital exenteration in the management of malignant melanoma of the conjunctiva has been underexplored. The outcome in 95 patients with this condition, who underwent exenteration as a primary treatment (n = 36) or after failure of other treatment (n = 59) for early to advanced stages of the disease, was evaluated. The majority of treated cases had multicentric melanomas sited at prognostically unfavourable locations. In the group of tumours with a maximum thickness of 1.0 mm no melanoma related mortality was noted. Melanomas thicker than 1.0 mm were associated with a mortality varying between 33% and 50%, independent of whether exenteration was performed as primary or secondary treatment. An especially poor outcome was noted for the group of caruncular melanomas despite exenteration. These findings indicate that total eradication of tumour should be performed at an early stage. For this purpose, a combination of debulking surgery and adjunctive cryotherapy or beta radiotherapy is more appropriate than orbital exenteration which causes disfigurement and blindness. Exenteration of the orbit should be reserved as a palliative procedure for advanced stages of neoplastic disease.

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.

Retinoblastoma treated with primary chemotherapy alone: The significance of tumour size, location, and age

Aims: To evaluate how tumour size, retinal location, and patient age affect the outcome of retinoblastoma foci treated with chemotherapy. Methods: Retrospective review of retinoblastoma foci treated with primary chemotherapy alone. Individual tumours were coded with regard to their largest basal diameter, location within the eye (macula, macula to equator, equator to ora serrata), and patients age at diagnosis. Successfully treated tumours required no further intervention while those requiring additional treatment were coded as failures. Results: 56 (72%) tumours responded successfully to chemotherapy alone while 22 (28%) required additional therapy. 26 of 31 macular tumours (84%) and 30 of 47 extramacular tumours (64%) responded to chemotherapy (p <0.060). Relative to size, 46 of 60 tumours (77%) greater than 2 mm in basal diameter were successfully treated with chemotherapy, while only 10 of 18 tumours (56%) less than or equal to 2 mm responded (p <0.088). Among the eight tumour foci diagnosed in children less than 2 months of age, five (63%) failed to respond to chemotherapy alone (p <0.032). Conclusion: Retinoblastoma is more likely to respond to primary chemotherapy if it is located in the macula and if the patient is older than 2 months of age. Tumours measuring less than 2 mm in diameter may be less responsive to this treatment.

Ectopic intracranial retinoblastoma in childhood.

Twelve out of a series of 630 children with retinoblastoma, treated in the ocular oncology units at St Bartholomews and Moorfields Eye Hospitals during the past 30 years, have developed ectopic intracranial retinoblastoma. The ectopic tumour occurred in the pineal region in eight children and in the suprasellar region in four. Ten patients had bilateral retinoblastoma, one unilateral disease, and one child presented with an isolated suprasellar tumour but no evidence of retinal disease. The interval from the initial diagnosis of retinoblastoma to the development of ectopic intracranial disease ranged from 4 to 70 months, median 34 months. Methods of treatment for the ectopic tumour varied, but all 12 children died with a median survival of only 8 months following the diagnosis of ectopic retinoblastoma. Subsequent spread of tumour to other sites within the central nervous system proved to be the most frequent cause of death. Ectopic intracranial retinoblastoma is a potentially curable neoplasm, but it requires adequate therapy to the whole neuraxis as well as high dose equivalent radiotherapy to the primary tumour.

External beam radiotherapy for retinoblastoma: I. Whole eye technique.

A retrospective analysis has been performed of the results of external beam radiotherapy for retinoblastoma using a whole eye technique. Local tumour control has been assessed in a consecutive series of 175 eyes in 142 children all of whom received external beam radiotherapy as the primary treatment for retinoblastoma. Follow up ranged from 2 to 17 years (median 9 years). Tumour control rates have been analysed with respect to the Reese Ellsworth classification and the series includes eyes in groups I to V. Focal salvage therapy was given for persistent, recurrent, or new tumours after radiotherapy. Following whole eye radiotherapy alone, the overall ocular cure rate was 57%, though with salvage therapy 80% of eyes could be preserved.

External beam radiotherapy for retinoblastoma: II. Lens sparing technique.

A retrospective analysis is presented of the results of external beam radiotherapy for retinoblastoma utilising an accurate lens sparing technique. Local tumour control has been assessed in a consecutive series of 67 eyes in 53 children all of whom received external beam radiotherapy as the primary treatment of retinoblastoma. Follow up ranged from 12 to 82 months (median 35 months) with 76% of the children followed for more than 2 years. Tumour control rates have been analysed with respect to the Reese-Ellsworth classification. The role of adjuvant and salvage focal therapy is emphasised. Following lens sparing radiotherapy with prior adjuvant treatment of anterior tumours, where appropriate, the overall ocular cure rate was 72%. With salvage therapy of persistent, recurrent, or new tumours, 93% of eyes could be preserved in this series which includes mainly eyes classified in Reese-Ellsworth groups I-III. These results compare favourably with those of whole eye external beam radiotherapy for comparable tumours, and with those of lens and anterior segment sparing using other techniques. They were achieved without the ocular morbidity associated with whole eye external beam radiotherapy.

Impression cytology of conjunctival melanosis and melanoma.

Impression cytology using cellulose acetate paper has been used in various ocular surface disorders as a simple non-invasive diagnostic test. To assess its value in differentiating melanocytic tumours, 24 patients with a range of pigmented lesions of the conjunctiva were examined using this technique. Cytological and histological diagnoses were compared in 23 cases. In 73% of cases impression cytology predicted the histological diagnosis by detection of superficial atypical melanocytes and their proportion relative to benign epithelial cells. This pilot study shows impression cytology to be a useful diagnostic aid in the differentiation of pigmented tumours of the bulbar conjunctiva.

Orbital recurrence of retinoblastoma.

There were 16 cases of orbital recurrence in a consecutive series of 317 children with retinoblastoma referred to a specialist centre. The incidence of orbital relapse amongst children treated at the centre from the outset of their disease was 2.5%. In every case the patient was the first affected family member. The ocular tumour was therefore not anticipated and had commonly been detected at an advanced stage. Systemic staging investigations detected extraorbital spread in six of the 16 and none of these children survived. One of the remaining ten children with no evidence of dissemination at the time of diagnosis of orbital recurrence is a long-term survivor. No child survived after orbital exenteration or radical orbital radiotherapy alone. Three children received a combination of radiotherapy and adjuvant chemotherapy. Only one of the three was free from systemic disease at relapse and this child is the only survivor. In children apparently free from widespread retinoblastoma at diagnosis of orbital recurrence, distant relapse was the commonest cause of death though several children died from direct intracranial extension. It is advocated that orbital recurrence of retinoblastoma is treated by excision biopsy of the tumour mass followed by radical orbital radiotherapy to a dose of 50 Gy. This should be combined with adjuvant chemotherapy and, where a risk of direct intracranial extension exists, by neuraxis irradiation. No other child in this series with evidence of local extraocular extension of retinoblastoma at enucleation and who had received radical orbital radiotherapy to a full dose of 50 Gy subsequently recurred in the orbit.(ABSTRACT TRUNCATED AT 250 WORDS)