Treatment Outcomes and Definition Inconsistencies in High-Risk Unilateral Retinoblastoma: Outcomes and Definition Variances in High-Risk Rb.

PURPOSE: To compare the clinical outcomes of children with unilateral retinoblastoma (Rb) and high-risk histopathology features (HRHF) following upfront enucleation with/without adjuvant chemotherapy, and investigate cases locally considered non-HRHF but converted to a standardized HRHF definition. DESIGN: Retrospective multinational clinical cohort study. METHODS: Children with Rb who presented to 21 centers from 12 countries between 2011-2020, and underwent primary enucleation were recruited. Centers retrieved clinical data and were asked to report detailed histopathology findings, as well as indicate cases defined locally as high-risk. For analysis, only unilateral cases with standardized HRHF, defined as retrolaminar optic nerve invasion, massive choroidal invasion, scleral invasion, anterior-segment involvement, and/or combined non-massive choroidal and prelaminar/laminar optic nerve invasion, were included. Main Outcome Measures included orbital tumor recurrence, systemic metastasis, survival and number and outcome of cases converted to standardized HRHF. RESULTS: A total of 600 children presenting to 14 centers in 9 countries were included. Of these, 505 (84.2%) were considered locally as HRHF and received adjuvant chemotherapy. After a median follow-up period of 39.2±1.6 months (range: 0.8-60.0 months), 36 (6.0%) had orbital tumor recurrence, 49 (8.2%) metastasis, and 72 (12.0%) children died. Children not receiving adjuvant chemotherapy were at significantly increased risk of orbital tumor recurrence, metastasis, and death (p ≤0.002). Of the study children, 63/600 (10.5%) were considered locally non-HRHF, but converted to standardized HRHF and included in the analysis. Of these, 6/63 (9.5%) had orbital tumor recurrence, 5/63 (7.9%) metastasis, and 6/63 (9.5%) children died. Isolated minor choroidal invasion with prelaminar/laminar optic nerve invasion was reported in 114 (19.0%) children, but considered locally as HRHF only in 68/114 (59.6%). Of these, 6/114 (5.3%) children developed metastasis and subsequently died, yielding a number needed to treat of 15. CONCLUSION: Based on this multinational cohort of children with Rb, we recommend the use of adjuvant chemotherapy following upfront enucleation and diagnosis of HRHF. Variation exists worldwide among centers when defining HRHF, resulting in adverse patient outcomes, warranting standardization.

Is It Possible to Preserve Vision without Compromising Metastases-Free Survival by Use of Fully Fractionated Stereotactic Radiotherapy for Posterior Choroidal Melanoma?

Introduction: Stereotactic radiotherapy (SRT) is used for choroidal melanoma (CM) abutting the optic nerve. Visual acuity (VA) deterioration to ≤6/60 is common. We report a pilot study of reduced-dose SRT using 2 Gy/day, aiming to preserve vision without compromising survival. Method: 60 Gy SRT was delivered in 30 fractions over 6 weeks. Liver metastasis surveillance was annual ultrasound. The primary endpoint was 5-year metastasis-free survival (5yMFS). Secondary endpoints were 2-year freedom from local progression (2yFFLP), VA, enucleation rate, and radiation toxicity. Results: Twenty adults aged ≤70 years with T1-T2M0 CM without diabetes mellitus were enrolled. Median follow-up was 5.1 years. About 85% and 90% of tumours were ≤3 mm of the macula and optic disc, respectively. Median tumour height was 2.2 mm (range 1.0-4.4 mm), and median basal diameter was 8.2 mm (range: 4.3-15.0 mm). 5yMFS was 88% (95% CI: 61-97), and the 2yFFLP rate was 90% (95%: CI 66-97). There were three enucleations for disease progression. Final VA in retained eyes was ≥6/7.5 in 6 (30%), 6/9 to 6/12 in 5 (25%), 6/15 to 6/48 in 2 (10%), and ≤6/60 in 4 (20%) eyes. Retinopathy was the main cause of vision loss besides tumour progression. Conclusion: Meaningful vision was preserved 5 years after SRT, despite high-risk tumour locations for vision loss. 2yFFLP and 5yMFS were acceptable. This dose fractionation warrants further investigation.

The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Apical dose versus volume dose of Ruthenium-106 brachytherapy for uveal melanoma.

OBJECTIVE: Ruthenium-106 brachytherapy is commonly used to treat uveal melanomas. Most centres prescribe a radiation dose to the tumour apex that is calculated with the tumour located in the centre of the plaque. Recent work suggests that D99%-the minimum radiation dose delivered to 99% of tumour volume-may be a better predictor of tumour control than apex dose. Both dosing regimens may be affected by tumour and treatment variables differently. We explored the effect of differences in these variables on volume and apex dose using a 3-dimensional planning model. METHODS: The time required to deliver 100 Gy to the tumour apices of representative tumours ranging from 2- to 6-mm thickness with central plaque positioning was calculated in Plaque Simulator™. This treatment time was used for further calculations, including D99% with central plaque placement, and apical and tumour volume doses when tumour and plaque characteristics were altered, including eccentric plaque placement, either away from (tilt) or along (offset) scleral surface, tumour shape, and plaque type. RESULTS: D99% was always greater than the apex dose when plaques were placed centrally, and the difference increased with tumour thickness. Increasing degrees of tumour offset reduced apical dose and D99%, with a greater effect on apical dose for thicker and D99% for thinner tumours, respectively. Differences in tumour shape and plaque type had idiosyncratic effects on apical and volume dosing. CONCLUSION: D99% and apex dose are affected by tumour and treatment characteristics in different ways, highlighting the complexity of radiation delivery to uveal tumours.

Globe Salvage and Vision Preservation by Neoadjuvant Darovasertib and Crizotinib in Uveal Melanoma.

PURPOSE: To report the effective use of neoadjuvant darovasertib and crizotinib in a patient with a large uveal melanoma (UM) in his only functional eye. DESIGN: Case report. SUBJECTS: One patient with T4b UM. INTERVENTION: Neoadjuvant darovasertib and crizotinib, followed by plaque brachytherapy. MAIN OUTCOME MEASURES: Objective tumor response and conversion from planned enucleation to placement of fovea- and optic nerve-sparing plaque brachytherapy. RESULTS: A patient with a history of left eye blindness from retinal artery occlusion presented with rapidly declining right eye vision due to a primary UM measuring 18 mm in maximal diameter and 16.5 mm in maximal thickness. To salvage vision, neoadjuvant treatment was initiated using darovasertib and crizotinib. After 6 months of neoadjuvant treatment, which included intraocular lens replacement for tumor-associated cataract, the tumor regressed to 14.1 mm in maximal diameter and 2.6 mm in maximal thickness, enabling treatment with plaque brachytherapy rather than enucleation. CONCLUSIONS: The combination of darovasertib and crizotinib for UM is an effective neoadjuvant strategy that warrants further investigation as an approach to improve visual outcomes from the treatment of primary UM. FINANCIAL DISCLOSURE: The other authors have no proprietary or commercial interest in any materials discussed in this article.

Predictability of Neutrophil to Lymphocyte Ratio in preoperative elderly hip fracture patients for post-operative short-term complications: a retrospective study.

PURPOSE: Neutrophil to Lymphocyte Ratio (NLR) is a simple biomarker of systemic inflammatory response. We investigated predictability of NLR for early adverse outcome after surgery for hip fracture in elderly population. METHODS: We reviewed a total of 971 elderly patients with hip fracture who underwent emergency surgery between January 2017 and July 2020 in the Department of Orthopaedics Surgery at the Wollongong Hospital. After considering exclusion criteria, data from a total of 834 patients included in our study. Socio-demographic data, NLR in admission, updated Charlson comorbidity index (uCCI), biochemical markers, mortality rate and 15 short term post-operative complications were collected to determine predictability of NLR for post-operative complications and mortality. RESULTS: After hip surgery, Hospital in-patient case fatality rate was 3.7% (31). In addition, 63.1% (511) of the patients had at least one complication or more. Logistic regression demonstrated that raised NLR (P-value < 0.001, OR 1.05) and uCCI≥4 (P-Value < 0.001, OR 1.75) are associated with post-operative complications. Moreover, decreased haemoglobin was associated with adverse effects (P-value < 0.001, OR 0.97). No association was found for any of these variables with in-patient mortality except for albumin (P-value: 0.03). In addition, despite significant association, ROC analyses showed a low predictability for each of the above variables including NLR (AUC 0.59) for post-operative complications. CONCLUSIONS: Despite significant association, NLR was unable to prognosticate early adverse outcomes. However, it can be considered as a risk factor in admission for postoperative complications in combination with other risk factors and clinical context.

Quantifying the effect of eccentric ruthenium plaque placement on tumor volume dose.

Purpose: Ruthenium-106 brachytherapy is a common treatment for small to medium-sized uveal melanomas. In certain clinical contexts, plaques may be placed eccentrically to tumor center. The effect of plaque decentration, a common radiation dose measurement in radiotherapy: D98%, the percentage of the tumor volume receiving at least 98% of the prescribed dose (a commonly used term in radiation oncology), is unknown. We investigated this using two commonly used plaques (CCA and CCB; Eckert & Ziegler, BEBIG GmbH) in silico. Material and methods: Using a Plaque Simulator™ (Eye Physics) plaque modelling software, treatment time required to deliver 100 Gy D98% with central plaque placement was calculated for both plaque models, treating tumors with basal dimensions of 10 mm (CCB plaque only) and 7 mm (CCA and CCB plaques), and a range of thicknesses. D98% was calculated for plaque-tumor edge distances of 0-5 mm. Additionally, we defined minimum plaque-tumor edge distances, at which D98% fell by 10% and 5% (safety margins). Results: D98% decreased as plaque-tumor edge distance decreased, i.e. as plaque eccentricity increased. Minor (< 1 mm) plaque decentration caused minimal D98% changes across tumor thicknesses. Safety margins did not follow a consistent pattern. Conclusions: Eccentric plaque placement reduces the radiation dose delivered to choroidal tumors. Both tumor (thickness, diameter) and plaque (size, location) characteristics are important D98% modulators. Further investigation of the effect of these characteristics and dose to organs at risk is essential.

Case Series: Presumed Choroidal Melanoma Diagnosis Expedited by Documented Growth on Serial Optical Coherence Tomography.

SIGNIFICANCE: These cases highlight the importance of monitoring choroidal nevi with benign imaging characteristics and the potential to quantify horizontal growth using optical coherence tomography (OCT), in the absence of color fundus photography. PURPOSE: This study aimed to present reports of two patients with pigmented choroidal tumors with low malignant potential based on their multimodal imaging features at the time of referral, but access to prior OCT imaging confirmed horizontal growth consistent with melanoma. CASE REPORTS: Two patients with pigmented, dome-shaped, subfoveal tumors were referred. Both tumors had basal diameters greater than 5 mm but no other risk factor for growth at the time of referral. Screening OCT scans had been taken of each patient's macula more than 5 years before referral, but color fundus photography was not available for either. Repeat OCT scanning at the time of referral showed horizontal growth of the tumors consistent with melanoma. As per the "To Find Small Ocular Melanoma-Do Imaging" risk factor assessment, the 5-year risk of growth of both tumors would be estimated at 11% at the time of referral, and in the absence of the documented horizontal growth on OCT scanning, the patients would have been monitored for growth. After discussion of the risks and benefits, both patients elected for their tumors to be managed as choroidal melanomas and underwent ruthenium plaque brachytherapy. CONCLUSIONS: Horizontal growth of choroidal tumors can be established using sequential OCT scans in the absence of color fundus photography. Access to prior imaging can expedite the diagnosis of choroidal melanoma, potentially allowing patients to be treated earlier.

Biopsy for molecular risk stratification in uveal melanoma: Yields and molecular characteristics in 119 patients.

BACKGROUND: Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples. METHODS: A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n = 57) and post-enucleation (n = 62). Patient and tumour features were collected including age, sex, primary tumour location, basal diameter and tumour height. Prognostic outcomes measured include cell morphology, chromosomal status and immunohistochemistry. RESULTS: Post-enucleation biopsies accounted for just over half of our samples (52%). Post-enucleation samples had a more successful genetic yield than in vivo biopsies (77% vs. 50%, p = 0.04) though there was no difference for cytological yields. There was no difference in cytological or microarray yields between instruments. The vitrector biopsy group had the smallest tumour thickness (5 mm vs. 10 mm [fine-needle aspirate biopsy], p = 0.003). There was a strong correlation between monosomy 3, BAP1 aberrancy and epithelioid cell type in post-enucleation samples (Tb  = 0.742, p = 0.005). However, epithelioid morphology was not associated with either monosomy 3 (p = 0.07) or BAP1 aberrancy (p = 0.24) for in vivo biopsies. CONCLUSIONS: All three biopsy instruments provide similar cytological yields as post-enucleation sampling, although post-enucleation samples had a more successful chromosome microarray yield. Epithelioid cytomorphology alone is insufficient for prognostication in in vivo biopsies, immunohistochemistry would be a useful surrogate test.

Defining High-risk Retinoblastoma: A Multicenter Global Survey.

IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

Superselective intra-arterial chemotherapy for advanced retinoblastoma complicated by metastatic disease.

We present a case of a child with unilateral group E retinoblastoma (according to the International Classification of Retinoblastoma) who received superselective intra-arterial chemotherapy as primary therapy. Although the tumor showed signs of regression, the patient developed orbital metastases requiring surgical excision and chemotherapy. Eventually the affected eye progressed to total retinal detachment and required enucleation.

Impact of perinatal health and socio-demographic factors on school education outcomes: A population study of Indigenous and non-Indigenous children in the Northern Territory.

AIM: This study investigated the association between early-life risk factors and school education outcomes. METHODS: This is an historical cohort study of 7601 children (61% were Indigenous) born in the Northern Territory between 1999 and 2004. Information was linked, for each child on: perinatal health, student enrolment and National Assessment Program - Literacy and Numeracy (NAPLAN) Year 3 results. Logistic regression was used to estimate the association between selected risk factors and a NAPLAN result 'below' the national minimum standard (NMS) in reading and numeracy. RESULTS: Indigenous children had much higher odds, than non-Indigenous children, of a result below the NMS for both reading (odds ratio (OR): 8.58, 95% confidence interval (CI): 7.55-9.74) ) and numeracy (OR: 11.52, 95% CI: 9.94-13.35). When adjusted for all other variables, the increased odds were attenuated for both reading (OR: 2.89, 95% CI: 2.46-3.40) and numeracy (OR: 3.19, 95% CI: 2.65-3.84). Common risk factors for Indigenous and non-Indigenous children included higher birth order, maternal smoking in pregnancy and being a boy. There were gradients of decreasing risk with increasing education level of primary care giver and increasing maternal age. Among Indigenous children only, risks increased when living in remote areas, with younger age (<8 years) and low birthweight. CONCLUSIONS: The study highlights that many of the risk factors associated with poor education outcomes among Indigenous children are shared with the general population. The results inform a targeted, cross-agency response to address modifiable early-life risk factors for educational disadvantage. Data linkage, using existing administrative datasets, provides a useful addition to methods that identify priority areas for prevention and early intervention.

Managing fetuses at high risk of retinoblastoma: lesion detection on screening MRI.

OBJECTIVE: This study aimed to describe tumour identification on magnetic resonance imaging (MRI) in a 35-week fetus with familial retinoblastoma (RB) and report the use of prenatal ultrasound (US) and MRI screening in the management of fetuses at high risk of RB. METHOD: This is a retrospective review of the prenatal course and immediate postnatal findings in all children considered at high risk of RB who had prenatal imaging with both US and MRI at our institution over a 5-year period. RESULTS: Five patients met the inclusion criteria. No lesions were identified on US in any patients. Fetal MRI identified bilateral posterior pole lesions in one patient at 35 weeks' gestation. Of the four remaining patients, three developed lesions by 5 weeks of age. Only one fetus was delivered early following detection of RB. CONCLUSION: We present the first reported case of RB detected in a high-risk fetus on screening MRI at 35 weeks' gestation. A protocol for screening this population using both imaging modalities is presented.

A propósito del consenso para el manejo de las disfunciones tiroideas mínimas / About the consensus for the management of thyroid minimal dysfunctions

Subclinical hypothyroidism and its clinical consequences have been debated during several decades. With the publication of the Consensus Declaration about subclinical thyroid dysfunction by the Endocrine Society, the American Association of Clinical Endocrinologists (AACE), and the American Thyroid Association (ATA), a new field was open for endocrinologist in the management of some long ignored thyroid dysfunctions that did not have any therapeuticsolution. The authors describe the paradigm shift and the changes in the diagnostic and therapeutic approaches. Later they recount some experiences developed in Colombia, S.A. Finally, they suggest some guidelines from their own experience and from other sources obtained in different fields of modern endocrinology.

Hipotiroidismo subclínico y sus consecuencias clínicas ha sido objeto de debate científico por espacio de varias décadas. A raíz de la publicación de la declaración de consenso acerca de la disfunción tiroidea subclínica en el año 2005, realizada por la Sociedad Americana de Endocrinologìa (The Endocrine Society), la Asociación Americana de Endocrinólogos Clínicos (AACE) y la AsociaciónAmericana de la Tiroides (ATA) se abrió un nuevo espacio para los endocrinólogos en el manejo de algunas disfunciones tiroideas que no habían sido tenidas en cuenta dentro del campo de accion terapéutico. Los autores hacen un recuento de cómo se produce el cambio en los paradigmas y en el enfoque diagnostico y terapéutico. Luego hacen un recuento de algunas de las experiencias desarrolladas en Colombia. Finalmente sugieren algunos derroteros a partir de su propia experiencia y también basados en logros científicos de otras fuentes obtenidos en otros campos de la Endocrinologìa moderna.

Artificial ultraviolet radiation and ocular melanoma in Australia.

We examined risk of ocular melanoma with exposure to artificial sources of exposure to ultraviolet radiation (UVR) in a population-based epidemiologic study of 290 cases of ocular melanoma and 893 controls aged 18-79 years in Australia in 1996-1998. Cases were identified through a prospective survey of all ophthalmologists and cancer registries in Australia; 91.8% participated. Controls were sourced from electoral rolls; 67.4% of those who were eligible and contactable participated, while 27.3% could not be contacted. Exposure to welding and use of sunlamps, including sunbeds and tanning booths, was measured by telephone interview. Analyses used unconditional logistic regression and included age, sex, region of birth, eye color, ocular and cutaneous sun sensitivity and personal sun exposure as covariates. Risk of choroid and ciliary body melanoma in 246 cases increased significantly with longer duration of use of sunlamps, first use before 21 years of age and first use after 1980. These effects were independent of personal sun exposure. Risk of these melanomas also increased with increasing duration of welding exposure, although the trend was not significant overall. There was no evidence that these exposures increased the risk of iris (n = 25) or conjunctival (n = 19) melanomas. Personal exposure to sunlamps and welding predicts risk of choroid and ciliary body melanoma in Australia.

Retinoblastoma in Victoria, 1976-2000: changing management trends and outcomes.

PURPOSE: To describe changes in the management of retinoblastoma in Victoria and to review the effect of newer, conservative treatments on preservation of eyes, visual outcome and mortality by comparing a similar group of patients treated over successive time intervals. METHODS: A retrospective analysis of all cases of retinoblastoma diagnosed and treated in Victoria between 1956 and 2000 was conducted. Historical data on 77 cases previously published by O'Day et al. was used for the period 1956-1976 (series 1). Data on 88 cases recorded in the Royal Children's Hospital (Melbourne) Retinoblastoma Database was used for the period 1976-2000. The latter group was subdivided into those treated between 1976 and 1989 (series 2), prior to the advent of modern eye saving treatments, and those treated subsequent to their introduction from 1990 to 2000 (series 3). RESULTS: In unilateral retinoblastoma, final enucleation rates for 1956-1976 (series 1) and 1976-1989 (series 2) were almost identical, being 98% and 97% of affected eyes, respectively (P = 1.00). Despite the newer treatments used after 1990 (series 3), 88% of affected eyes were still enucleated, representing a statistically similar outcome to series 2 (P = 0.33). In bilateral retinoblastoma, primary enucleation of the more involved eye was similar for series 1 (84%) and 2 (80%) but series 3 (41%) was substantially less than series 2 (P = 0.04) following the increased use of conservative treatments. In series 3, 59% of more involved eyes were treated conservatively compared with 16% (P = 0.007) and 20% (P = 0.04) for series 1 and 2, respectively. Despite attempts at eye salvage, the failure rate was higher in series 3 (29%) yielding a final enucleation rate of 70%, which represented a modest downward trend in the numbers of eyes finally enucleated; 84% (series 1), 73% (series 2) and 70% (series 3) (test for trend, P = 0.33). Bilateral enucleation rates were significantly lower, from 36% and 30% in series 1 and 2, respectively, to 7% in series 3 (test for trend, P = 0.02). As a consequence, more eyes were preserved over time, being 20/50 (40%) in series 1, 15/30 (50%) in series 2 and 21/34 (62%) in series 3. Comparison of visual outcome was hampered by incomplete data in series 1 but it appeared series 2 and 3 achieved better visual acuities with 67% and 62% of preserved eyes in bilateral cases measuring equal to or better than 6/12. Mortality rates in all series were low, being 7.8% in series 1, 4.5% in series 2 and nil in series 3. CONCLUSIONS: Following the introduction of new conservative treatments, there has been an increase in preservation of eyes and improved visual outcome, and a dramatic decrease in numbers of bilateral enucleations without adversely affecting survival.

Sunlight exposure and pathogenesis of uveal melanoma.

Uveal melanoma is the most frequent primary malignant intraocular tumor of adults. Among various non-modifiable risk factors, Caucasian race seems to be the most significant with light skin color, blond hair, and blue eyes being specific risk factors. The racial predisposition to uveal melanoma have been explained on the basis of susceptibility of Caucasian race to oncogenic effects of sunlight. Although there is ample evidence in support of this hypothesis in regard to skin melanoma, the evidence in regard to uveal melanoma is insufficient and contradictory. In the following review, we examine physiologic, epidemiological, and genetic data in order to determine the role of sunlight exposure in the pathogenesis of uveal melanoma.

Retinoblastoma: review of 30 years' experience with external beam radiotherapy.

A review of the experience at the Peter MacCallum Cancer Centre (Peter Mac), Melbourne, Australia in treating retinoblastoma with external beam radiotherapy was conducted. Outcomes of particular interest were tumour control, vision preservation and treatment late effects. The review was restricted to patients that had intact eyes treated at Peter Mac from 1965 until 1997 with at least 2 years of follow up. Histories were reviewed regarding patient and tumour characteristics and treatment details. Thirty-five patients were identified in whom 47 eyes were treated. Of the tumours, 47% were Reese-Ellsworth stage IV or V and the majority of others were at high risk for vision loss because of tumour location. The radiation treatment technique became increasingly sophisticated during the study period. Radiation dose and fraction size have similarly evolved but most patients received 30-50 Gy. Since 1989, a highly accurate contact lens immobilization technique has been used to deliver 40 Gy in 20 fractions. Thirteen eyes required additional local therapy. Of the treated eyes, 34 (72%) remain intact and 74% of these have useful vision. One patient died from retinoblastoma and three from second malignant neoplasms. With modern radiotherapy, late toxicities other than growth arrest and non-progressive cataract did not occur during the study period. Tumour control was high and a very acceptable rate of organ and vision preservation was achieved in a relatively high-risk population. Modern radiotherapy continues to develop in an attempt to improve treatment accuracy and minimize late radiation toxicity.

Incidence of ocular melanoma in Australia from 1990 to 1998.

Routinely collected incidence data have often lacked specific identification of ocular melanoma in the past and with increasing diagnosis and management of this disease by noninvasive techniques may now underestimate the true incidence. We attempted to accurately measure the incidence of ocular melanoma in Australia from 1990 to 1998 using 2 population-based sources, cancer registries and ophthalmologists. We examined the distribution across the continent, by latitude and in subpopulations, and evaluated the extent of nonnotification to cancer registries. One-half (51%) of the incident cases from 1996 to 1998 were diagnosed clinically and had no tissue diagnosis. An estimated 20% of melanomas, mainly those lacking a tissue diagnosis, were not notified to Australian cancer registries, but only 1.3% were not notified by ophthalmologists. Expert reviewers agreed that a high proportion (95%) of clinically diagnosed lesions were probable or possible melanomas. Incidence was significantly higher in men than in women, especially at older ages, relatively uniform across the Australian states with only weak evidence of a latitude gradient, and higher in rural than in urban areas. The incidence of ocular melanoma in people born in Southern Europe was half and in those born in Asia only 20% of the rate in people born in Australia and New Zealand. We concluded that it was possible to identify a high proportion of cases by surveying relevant sources additional to cancer registries and to be reasonably confident of the accuracy of the clinical diagnoses. The higher incidence in older men, who probably have higher sun exposure, than in older women and in residents of rural areas, where outdoor work is more prevalent, than in urban areas; the low incidence in dark-eyed populations, who may have a lower sensitivity to or less transmission of solar radiation to the choroid; and the preferential location of ocular melanomas in ocular sites known to receive the highest exposure to solar radiation all support a role for solar radiation in the aetiology of ocular melanoma. The absence of a strong latitude gradient in incidence does not argue against such a role because exposure of the eye to solar UV is probably determined most by the horizon sky, where ambient solar UV is less affected by latitude.

Sun exposure predicts risk of ocular melanoma in Australia.

Previous studies examining sun exposure and ocular melanoma have produced inconsistent results. We investigated this association in a population-based case-control study in Australia. Cases (n = 290) aged 18-79 years were diagnosed between January 1996 and July 1998. Controls (n = 893) were randomly selected from the electoral rolls and frequency-matched to cases by age, sex and state. A self-administered questionnaire and a telephone interview measured sun exposure on weekdays and weekends at 10, 20, 30 and 40 years of age and over the whole of life for specific jobs and recreations. Multivariate logistic regression models of ocular melanoma and sun exposure contained age, sex, region of birth, eye color and measures of ocular and cutaneous sun sensitivity as covariates. Choroid and ciliary body melanoma (n = 246) was positively associated with time outdoors on weekdays and, less persuasively, total time outdoors but not ambient solar irradiance. Odds ratios increased with increasing exposure to OR 1.8 (95% confidence interval 1.1-2.8) for the highest quarter of sun exposure on weekdays up to 40 years of age for men and women together. The strongest positive associations were for total exposure up to 40 years of age, lifetime occupational exposure and total exposure at about 20 years of age in men; all had odds ratios between 2 and 3 in the highest exposure categories. There was inconclusive evidence for an association between sun exposure and iris (n = 25) or conjunctival (n = 19) melanomas. Sun exposure is an independent risk factor for choroidal and ciliary body melanoma in Australia.