Extraocular Extension Research Articles

Single- Versus Triple-Agent Intra-Arterial Chemotherapy for Retinoblastoma

To compare the ocular and systemic outcomes of single- (melphalan) versus triple-agent (melphalan, topotecan, carboplatin) intra-arterial chemotherapy (IAC) for retinoblastoma (RB) eye salvage. Retrospective single-institutional clinical cohort study. Children <18 years with RB who underwent one or more IAC procedures between 2016 and 2024 with minimum 6-month follow-up were reviewed. Data included clinical features, IAC procedural details, additional eye-saving treatments, complications, and follow-up. Primary outcomes included ocular and systemic complications of IAC, intraocular recurrence, extraocular extension, metastasis, and death. Secondary outcomes were tumor response, ocular survival, and recurrence-free ocular survival. Comparative analysis was performed for single- versus triple-agent groups. A SWIMMERrb plot graphically illustrated additional treatments following IAC. Thirty-eight eyes of 37 children (24 unilateral RB) were reviewed. Two eyes (2 children) had single- followed by multi-agent IAC and were excluded. Of 35 included children, one had bilateral triple-agent IAC. IAC (median, 3 doses; range, 1-4) was employed as primary (n=21 eyes) or secondary (n=15 eyes) treatment. Chemotherapy was single-agent in 13 eyes and triple-agent in 23 eyes. Following IAC, 25 eyes required additional eye-saving treatments (69% single- v 70% triple-agent, p=0.983). At final follow-up, the triple-agent group was more likely to achieve very good partial or complete tumor response (91% v 62%, p=0.030). Two-year recurrence-free ocular survival was 63.3% (95% CI 45.7-80.9), similar for both groups (p=0.700). Globe salvage was 72%. Two-year ocular survival was 72.2% (95% CI 57.2-87.2), higher for the triple-agent group (82.6% v 53.8%; p=0.059). Ocular complications occurred in 31% of eyes in the single- and 52% of eyes in the triple-agent group (p=0.215). The rate of systemic complications was 38% v 74% in the single- versus triple-agent groups, respectively (p=0.036). No extraocular extension, metastasis, or death were observed at median 34.2 months (range, 14.5-87.0) follow-up. Triple-agent IAC was associated with improved RB tumor response and ocular survival, though similar recurrence-free ocular survival compared to single-agent. While there were more complications with triple-agent IAC, most were mild or transient.

Retinoblastoma with and without Extraocular Tumor Extension: A Global Comparative Study of 3435 Patients

PurposeTo study the treatment, and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). DesignMulticenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naïve patients. Cases with microscopic orbital extension detected post-enucleation were excluded from the study. ParticipantsA total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE Intervention(s)Chemotherapy, enucleation, exenteration, radiotherapy. Main outcomes(s)Systemic metastasis and death. ResultsOf the 3435 RB patients included in this study, 309 (9%) were from low-income countries, 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from low-income countries, 197 (6%) lower middle-income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (p=0.0001). The outcomes were statistically significant for RB-EOE compared to RB-w/o-EOE: systemic metastasis (32% vs 4% respectively; p=0.0001) and metastasis-related death (63% vs 6% respectively; p=0.0001). Multimodal treatment was the most common form of treatment (n=177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n=97; 30%). Adjuvant external beam radiotherapy after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan-Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk for death from RB-EOE was greater in patients aged >4 years than <2 years (hazard ratio (HR)=2.912; p<0.001) and for unimodal (surgery or intravenous chemotherapy) and bimodal (surgery and intravenous chemotherapy) treatment than trimodal treatment (surgery, intravenous chemotherapy and external beam radiotherapy) (HR=2.023; p=0.004 and HR 1.819; p=0.027 respectively). ConclusionRetinoblastoma with extraocular tumor extension is associated with a higher risk for metastasis and death. Patients with RB-EOE are likely to benefit from trimodal treatment (intravenous chemotherapy, surgery, and external beam radiotherapy) rather than treatment protocols excluding external beam radiotherapy.

Association Between Uveal Melanoma and Allostatic Load.

Allostatic load (AL) is a measure of chronic stress that is associated with worse cancer outcomes. The purpose of this retrospective cohort study was to investigate the relationship between AL and uveal melanoma (UM) clinical features. AL score was calculated as a composite of ten biomarkers in 111 patients with UM from the University of Illinois Hospital. One point was assigned to an AL score for each biomarker based on predetermined cutoff values. Linear and logistic regression analyses evaluated the relationship between AL score and several tumor clinical characteristics. High AL score had a significant relationship with extraocular extension (p=0.015). There was also a significant difference in mean blood glucose levels between the different tumor size groups (p=0.029). Higher AL scores also had a trend of being associated with a smaller tumor size (p=0.069). AL score was significantly associated with the presence of extraocular extension for uveal melanoma, while the smallest tumor size group was associated with the highest blood glucose level. No other significant correlations were found between AL and other clinical features of UM. The relationship between AL score and extraocular extension warrants further investigation. Additional research is needed to evaluate socioeconomic factors and their effect on the relationship between chronic stress and the clinical features of UM.

Impact of Tumor Pigmentation in 6934 Patients with Uveal Melanoma at a Single Center

PurposeTo evaluate clinical features and outcomes associated with degree of tumor pigmentation in patients with uveal melanoma (UM) of the choroid and ciliary body. DesignRetrospective observational study. Subjects6,934 consecutive patients with choroidal or ciliary body melanoma between 1971 and 2007 from a single ocular oncology center. MethodsData on patient demographics, tumor characteristics, treatment approach, and clinical outcomes were collected. Comparisons between pigmented (>80% pigmentation by surface area), partially pigmented (20-80%), and non-pigmented tumors (<20%) were performed using relevant hypothesis testing. Survival analyses for metastasis and melanoma-related death were conducted using the Kaplan-Meier method with log-rank tests for univariate comparisons. A multivariate Cox regression analysis was performed to assess the independent effects of multiple covariates on time-to-metastasis. Main Outcome MeasuresExtraocular extension, ocular melanocytosis, time to tumor recurrence, tumor location, and melanoma-related metastasis and death. ResultsThere were 6,934 eyes with UM and the degree of tumor pigmentation was classified as pigmented (n=3,762; 54%), partially pigmented (n=2,115; 31%) or non-pigmented (n=1,057; 15%). Pigmented UM was associated with extraocular extension (p<0.001), ocular melanocytosis (p=0.003), earlier tumor recurrence (p<0.001), and more anterior tumor epicenter location (ciliary body, and equator to ora serrata) (p<0.001). Pigmented UMs also exhibited the highest 10-year metastasis rate at 26%, compared to 19% for partially pigmented UMs and 16% for non-pigmented UMs (p<0.001). Kaplan-Meier survival curves demonstrated differences among the tumor pigmentation groups for melanoma-related metastasis (p<0.001) and melanoma-related death (p<0.001). Multivariate Cox regression analysis for melanoma-related metastasis showed that pigmented UMs had a 29% higher relative risk of developing metastasis compared to partially pigmented UMs (p=0.002) and a 54% higher relative risk of developing metastasis compared to non-pigmented UMs (p<0.001). ConclusionPigmented choroidal and ciliary body melanoma is more often associated with ocular melanocytosis, extraocular extension, anterior tumor epicenter, and earlier tumor recurrence. We also revealed that patients with pigmented UMs demonstrate a higher 10-year rate of metastatic disease and have decreased metastatic survival relative to partially pigmented and non-pigmented UMs.

Amelanotic Choroidal Melanoma with Extraocular Extension in a 51 Year-Old Female: A Rare Case

Introduction: Melanoma is a dangerous malignancy primarily involving the choroid, ciliary body, or iris. The most frequent primary intraocular malignant tumor is choroidal melanoma. The tumor most often affects Caucasians of Northern Europe ranging between the ages of 50 and 80. Most choroidal melanomas are pigmented, however, non-pigmented or mixed pigmented and non-pigmented forms can also happen. Compared with other amelanotic choroidal lesions, amelanotic choroidal melanoma showed markedly greater basal diameter, thickness, frequent connection with subretinal fluid, and ultrasonic hollowness. Extrascleral extension is currently detected in 10% to 28% of choroidal melanoma patients, and the mortality rate is much greater than in those without the extension. Case Presentation: We reported a rare case of extraocular extension in a 51-year-old female patient with amelanotic melanoma. The primary complaint was a painful and bleeding mass on her left eye that had developed two months prior to admission. On the conjunctiva of the left eye, there was a solid, palpable mass measuring 4 x 3.5 x 1 cm. It was red, well-defined, and had a hard, solid consistency. It was fixed at the base, had minimal bleeding, and pressed on her eyeball from the inferolateral direction. The cornea appears clear, and there is no light perception in visual acuity. The orbital focus computed tomography scan revealed an Enhancing solid mass containing a fat component. The mass was in the left intraocular, extending from intraconal to extraconal. Conclusions: Amelanotic melanoma with extraocular extension is a rare condition that can be difficult to detect due to its unclear clinical symptoms and wide range of possible causes. Patients and their families must be educated to receive the appropriate first therapy and prevent the illness from worsening. Melanoma management depends on several factors: tumor size, location, related characteristics, opposite eye status, systemic status, and patient preference. Orbital exenteration is one of the management options for choroidal melanoma with significant extraocular extension. By the time ocular treatment begins, the patient's survival may already be predetermined, and this realization could impact how uveal melanoma is treated in the years to come.

Delays between Uveal Melanoma Diagnosis and Treatment Increase the Risk of Metastatic Death

To investigate if the interval between diagnosis and treatment of posterior uveal melanoma (UM) is associated with metastatic death. Retrospective, single-center cohort study. A total of 1145 patients consecutively diagnosed with posterior UM at St. Erik Eye Hospital, Stockholm, Sweden, from 2012 to 2022, with recorded dates of diagnosis and primary treatment. This cohort represents 81% of all diagnosed patients in Sweden during this period. Data on the interval between diagnosis and treatment were collected for all patients. Its prognostic importance was examined with univariate and multivariate competing risks regressions, and cumulative incidence analyses. Incidence of metastatic death (UM mortality) for patients with prompt (< 1 month from diagnosis) versus delayed treatment (≥ 1 month) and subdistribution hazard ratios (exp(βj)) for every additional 10-day delay in treatment. The mean interval between diagnosis and treatment was 34 days (SD, 56, range, 0-932). Patients treated promptly had larger tumors at diagnosis, but there were no differences in patient age, tumor distance to the optic disc, rates of ciliary body involvement (CBI) or extraocular extension (EXE), or symptom duration before diagnosis. Those who were treated more than 1 month after diagnosis had greater UM mortality in American Joint Committee on Cancer (AJCC) stage II and III. In stage I, UM mortality for delayed treatment was lower for the first 10 years, followed by a marked spike in the 11th year. In multivariate competing risks regressions of all 1145 patients with tumor diameter, thickness, CBI, and EXE as covariates, the risk for UM mortality increased with 1% for every additional 10-day delay in treatment (exp(βj) 1.01). Among 355 patients treated with enucleation, this delay was associated with UM mortality, independent of AJCC stage, cytomorphology, and level of immunohistochemical BAP-1 expression. Increasing time between diagnosis and treatment of UM is associated with a higher risk of metastatic death. These results challenge a central concept in the understanding of metastatic progression and may indicate the existence of late metastatic seeding. They also underscore the importance of prompt treatment. Validation in independent cohorts is recommended. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Causes of death and survival analysis for patients with retinoblastoma in Jordan.

To analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan. We reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death. Twenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4-38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p < 0.0001), the presence of high-risk pathological features in the enucleated eyes (p = 0.013), parental refusal of the recommended primary treatment plan (p < 0.0001), and extraocular extension (p < 0.0001). The 5-year survival rates of Rb patients in Jordan are as high as those in high-income countries. However, 5% are still dying from metastatic disease, prompting the need for awareness campaigns to educate the public about the high cure rates and to prevent treatment abandonment.

Clinical features and outcome of retinoblastoma at the Vietnam National Cancer Hospital.

To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

Epidemio-Clinical Aspect of Intraocular Retinoblastoma at Sikasso Regional Hospital

Introduction: Intraocular retinoblastoma is a malignant neuroepithelial tumor occurring in infants and young children. It is the most common intraocular tumor. The early clinical sign is unilateral strabismus. Leukocoria already corresponds to a locally advanced stage. It is most often unilateral. In Mali, it represents 33.1% of all solid tumors. The aim of this work is to study the epidemiological and clinical aspects of intraocular retinoblastoma in the pediatric and ophthalmology department of Sikasso hospital. Patients and method: This is a retrospective study over 8 years which collected the intraocular forms of Rb. The intraocular forms without signs of clinical and radiological extraocular extension were included. The cases benefited from an ophthalmological and oncological assessment. The clinical stage of Rb was determined according to the IIRC classification. Results: Over 8 years, we have collected 29 out of 61 cases of ocular tumors, a frequency of 48%. The male sex predominated with 55% (sex ratio of 1.2). The average age was 1.23 years. 17.24% of patients had a family history of cancer. The first sign was leucocoria (68.96%) and the average consultation time was 3 months. The left eye was the most affected in 56%. The fundus shows 65.52% endophytic form. 68.97% were at stage D of the ABC classification. Conclusion: Retinoblastoma is the most common ocular tumor in children and the diagnostic delay was too long, compromising the patient's functional and vital prognosis. Early diagnosis is of utmost importance.

Esophageal Adenocarcinoma Metastatic to the Choroid with Extrascleral Extension

A 78-year-old man with history of esophageal adenocarcinoma, in remission 9 months after resection, chemotherapy, and radiation, presented with a peripapillary choroidal lesion with leopard-spot pigmentation and disc edema (A). Extraocular extension was demonstrated on B-scan and magnetic resonance imaging (B, C). A transconjunctival orbitotomy approach was performed rather than choroidal fine-needle biopsy to maximize tissue yield. Histopathology revealed expression of keratin (D), cytokeratin 20, caudal-related homeobox transcription factor 2 (CDX-2), and cytokeratin 7, consistent with metastatic esophageal adenocarcinoma. Positron emission tomography scan showed no primary tumor recurrence or additional metastases (Magnified version of Figure A-D is available online at www.aaojournal.org).

Impact of COVID-19 on a rare disease (uveal melanoma) in a national reference unit of intraocular tumors in Spain

ObjectiveTo analyse the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumour included in the Orphanet catalogue of rare diseases) in a Spanish national reference unit for intraocular tumours during the first year of the pandemic. MethodAn observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analysing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumour size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. ResultsEighty-two patients with uveal melanoma were included, of which 42 (51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumour size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p < 0.05). Multivariable logistic regression demonstrated that both medium-large tumour size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69–2256.37; p < 0.01 and OR 10; 95%CI, 1.10–90.25; p = 0.04, respectively). ConclusionsThe increase in tumour size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

Impacto del COVID-19 en una enfermedad rara (melanoma uveal) en una unidad de referencia nacional de tumores intraoculares en España

ObjectiveTo analyze the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumor included in the Orphanet catalog of rare diseases) in a Spanish national reference unit for intraocular tumors during the first year of the pandemic. Material and methodsAn observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analyzing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumor size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. ResultsEighty-two patients with uveal melanoma were included, of which 42(51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumor size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p<0.05). Multivariable logistic regression demonstrated that both medium-large tumor size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p<0.01 and OR 10; 95% CI,1.10-90.25; p=0.04, respectively). ConclusionsThe increase in tumor size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

CSIG-33. BCOR LOSS PROMOTES RETINOBLASTOMA GROWTH AND DISSEMINATION BY MODULATING INSULIN-LIKE GROWTH FACTOR 2

Abstract While loss of RB function is the most common genetic alteration in the pediatric embryonal eye tumor retinoblastoma, mutations leading to BCL-6 corepressor (BCOR) loss of function are the second most common alteration. BCOR mutations are found in more aggressive tumors, and are associated with metastasis and poor prognosis. We investigated the effects of BCOR loss or overexpression in retinoblastoma cells in order to better understand its functional role, and to determine if it represents a new therapeutic target in these tumors. Six established retinoblastoma cell lines were examined, and BCOR protein was most highly expressed in WERI-RB1, but absent in Y79 and two other lines. BCOR knock down in WERI-RB1 cells using shRNA caused markedly increased migration and proliferation. BCOR was also knocked out in these cells using CRSPR, resulting in more than three-fold increased size of intraocular murine xenografts and extensive extraocular extension of tumors. In terms of mechanism, BCOR loss of function induces IGF2 transcription, resulting in an activation of IGF1R and the ERK signaling pathway. In contrast, overexpressing BCOR in Y79 retinoblastoma cells with no baseline protein had opposite effects on IGF2. Targeting IGF2/IGF1R signaling pharmacologically using Lincitinib inhibited proliferation and migration in BCOR-negative retinoblastoma cells. Increased IGF2 transcription was regulated at least in part by hyper methylation of CCCTC-binding factor (CTCF)-binding regions in the IGF2/H19 imprinting control region (ICR), suggesting that BCOR knock down promotes increased methylation at this site. In summary, our studies revealed that BCOR loss promotes the growth and invasion of retinoblastoma cells in vitro and in vivo, at least in part via modulating IGF2 transcription, suggesting new potential therapeutic targets for these aggressive childhood tumors of the eye.

Clinical Features, Treatment, and Outcomes of Retinoblastoma in China

Background This review determined clinical features and treatment outcomes of retinoblastoma patients in China, which ranks second in incidence globally and is among the countries listed to produce 4,000 new cases of the estimated world's retinoblastoma cases in 2023. Methods A search was done using different databases for literatures on retinoblastoma in China published from 2010 to 2020. The articles were then reviewed for clinical features, treatment, and outcomes. Results Ten articles that included 3,702 patients involving ∼4,412 eyes seen in China from 1957 to 2019 were analyzed. Median age at consult ranged from 18 to 30 months and mean lag of consultation was 4 to 6 months. More males were affected (58%). Seventy-nine percent had unilateral disease. Retinoblastoma was assumed intraocular in 4,123(89%) eyes with ≥996(22%) belonging to group E of International Intraocular Retinoblastoma Classification/International Classification of Retinoblastoma. Extraocular extension was present in 415 (9%) eyes with 845 patients having direct extraocular extension, while 54 had distant metastasis. Enucleation was the most used treatment procedure specially in unilateral disease done in at least 2,781 (74%) eyes. Median follow-up period ranged from 14 to 47 months. Functional vision was retained in 48 (2%) eyes. Globe salvage rate for group A to D eyes ranged from 56 to 100%. Highest globe salvage rate for group D was 87% and 70% for group E. Overall survival rate was 1,655/1898 (87%), ranging from 81 to 100%. Overall mortality was 4%. Discussion Clinical profile and management options for retinoblastoma in China changed overtime improving outcomes. Globe salvage and survival rate were high for those with intraocular disease.

A prognostic classification system for uveal melanoma based on a combination of patient age and sex, the American Joint Committee on Cancer and the Cancer Genome Atlas models.

To revisitthe independent importance of ciliary body involvement (CBI), monosomy 3 (M3), tumour size, histological and clinical factors in uveal melanoma (UM) and to devise a new prognostic classification based on a combination of the American Joint Committee on Cancer (AJCC) and the Cancer Genome Atlas (TCGA) models. Two cohorts with a total of 1796 patients were included. Clinicopathological factors were compared between patients with and without CBI and M3. Development of the prognostic classification was performed in a training cohort and was then tested in two independent validation cohorts. Tumours with CBI were more common in women, had greater apical thickness, greater basal tumour diameter, greater rates of vasculogenic mimicry and greater rates of M3, were more often asymptomatic at diagnosis and had poorer 5- and 10-year globe conservation rates (p < 0.023). In multivariate logistic regression, patient age at diagnosis, tumour diameter and CBI were independent predictors of M3 (p < 0.001). In multivariate Cox regression, male sex, age at diagnosis, tumour diameter, M3 and CBI were independent predictors of metastasis. The proposed prognostic classification combined patient age, sex, CBI, extraocular extension, M3, 8q (optional) and tumour size, and demonstrated greater prognostic acumen than both AJCC 4 T categories and TCGA groups A to D in validation cohorts. Tumour size does not confound the prognostic implication of CBI, M3, male sex and age at diagnosis in UM. These factors were included in a new prognostic classification that outperforms AJCC T category and TCGA groups.

Le rétinoblastome au Centre Hospitalier Universitaire-Campus de Lomé, Togo, de 2014 à 2018

Retinoblastoma is a curable cancer when management is early and prompt. To describe the epidemiological, clinical and therapeutic aspects of retinoblastoma. A retrospective study was carried out from January 2014 to December 2018 (5 years) at the department of ophthalmology in Campus-University Teaching Hospital, Lomé, Togo. It focused on children with retinoblastoma. It included patients with diagnosis supported by ocular ultrasonography, orbito-cerebral computed tomography scan and/or histopathological examination. Among the 75 children with ocular cancer, 26 (34.7%) were diagnosed with retinoblastoma. The mean age at presentation was 31 months. The mean time from symptom onset to diagnosis was 15 months. A predominance of proptosis (65.4%), unilateral involvement (76.9%), extraocular tumor extension (65.4%) and endophytic form (96.15%) was found. Of the 32 eyes with retinoblastoma, 7 (21.9%) were enucleated after a mean time from diagnosis to enucleation of 6 months. Two cases of complete remission, 3 cases of tumor recurrence, and 2 cases lost to follow-up were noted. In our setting, retinoblastoma is a frequent childhood ocular cancer. It is important to improve the management of retinoblastoma as well as education of the parents.

Iris melanoma: factors predictive of post-management secondary glaucoma in 271 cases at a Single Ocular Oncology Centre.

To identify factors predictive of post-management secondary glaucoma in eyes with iris melanoma. Patients with iris melanoma who were conservatively managed on the Ocular Oncology Service, Wills Eye Hospital from 1970 to 2016 were included. Charts were retrospectively reviewed, and binary logistic regression analysis was performed. Main outcome measures were factors predictive of post-management glaucoma, defined as intraocular pressure (IOP) > 22 mmHg following melanoma treatment. Of 271 patients with iris melanoma, melanoma-related glaucoma was identified in 40 (15%) at presentation and post-management glaucoma developed in 75 (28%) at a mean of 103.7 months (range:1.0-120.0). Comparison (post-management glaucoma vs. no glaucoma) revealed patients with post-management glaucoma presented with worse visual acuity (20/50-20/150) (17% vs. 5%, p = 0.001), increased mean tumour basal diameter (5.1 mm vs. 4.3 mm, p = 0.004), greater melanoma-related increased IOP on presentation (24.1 mmHg vs. 16.2 mmHg, p < 0.001), diffuse tumour shape (9% vs. 4%, p = 0.01), American Joint Committee on Cancer (AJCC) T4 category (7% vs. 2%, p = 0.03), and extraocular tumour extension (7% vs. 2%, p = 0.03). Risk factors for post-management glaucoma identified by multivariate analysis included melanoma-related increased IOP at presentation (OR:1.1, [1.08-1.22] per 1-mmHg increase, p < 0.001), increased mean tumour basal diameter (OR:1.17, [1.02-1.33] per 1-millimetre increments, p = 0.03), advanced AJCC clinical T subcategory (OR:1.23, [1.04-1.46] per 1-subcategory increments, p = 0.02) and plaque radiotherapy treatment (OR:2.32, [1.13-4.75], p = 0.02). Features of iris melanoma that predicted post-management glaucoma included melanoma-related increased IOP on presentation, advanced AJCC clinical T subcategory, increased mean tumour basal diameter, and plaque radiotherapy treatment.

Extraocular Extension of a Regressed Choroidal Melanoma after Vitrectomy and Scleral Buckle for Rhegmatogenous Retinal Detachment

A 53-year-old man with a history of choroidal melanoma (Fig A-B) treated with brachytherapy presented 18 months post-plaque with a giant retinal tear and rhegmatogenous retinal detachment. The melanoma had shown regression at prior visits, and ultrasound confirmed a decrease in thickness from 5.7 to 4.7 mm (Fig C). Because the melanoma appeared regressed, he was treated with vitrectomy/silicone oil placement and scleral buckle. Seven months later, his condition was stable and the retina was attached.

Identification of extraocular extension in uveal melanoma by ophthalmological ultrasound.

Uveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound. A descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study. Ten patients with an average age of 72.3 years were included. The largest proportion of them were medium-sized tumours, followed by large and small ones. The most frequent morphology of the primary tumour was cupuliform. All the EE presented lower internal reflectivity compared to the primary tumour. No trans-scleral connection bridges were found between the primary tumour and the EE in the ultrasound studies. 50% of patients underwent primary enucleation at the time of diagnosis of intraocular MU due to the presence of the EE, and the remaining 50% presented the EE after initial treatment of the primary tumour with I125 brachytherapy. Sixty percent of the patients presented with posterior EE, and were therefore diagnosed with ultrasound A and B. The most frequent histopathological pattern with 87.5% of patients was the epithelioid pattern. Ultrasound scanning in patients with MU is mandatory for diagnosis and follow-up of EE. BMU and A and B ultrasound are the test of choice for anterior and posterior EE, respectively. EE have particular ultrasound characteristics such as low internal reflectivity, regularity of their contour and their location usually adjacent to the base of the primary intraocular tumor.

A descriptive neuroimaging study of retinoblastoma in children: magnetic resonance imaging features.

PurposeRetinoblastoma (RB) is the most common intraocular malignancy of childhood. Magnetic resonance imaging (MRI) is essential for initial diagnosis, tumour extension, staging, and treatment planning of RB. Awareness of neuro-imaging findings and determining local extent are essential for early diagnosis and therapy guidance. The purpose of this study is to evaluate and to provide a detailed list of neuroimaging features of RB to improve the diagnostic work-up of children with RB.Material and methodsRetrospective review was performed among children with confirmed RB diagnosis. MRI features were identified to evaluate: 1) growth pattern; 2) intraocular extension; 3) extraocular extension; 4) central nervous system disease; 5) conventional MRI characteristics of the RB lesions; and 6) DWI and ADC characteristics. These features were compared between unilateral and bilateral RB lesions.ResultsTwenty-four children (male/female: 18/6) were included in this study. The mean age at the time of diagnosis was 14.7 (11.4) months. In total, 34 RB lesions (bilateral = 18) were evaluated for the study. The most common features on MRI were: 1) endophytic RB lesion (50%); 2) subretinal haemorrhage (38%); 3) scleral involvement (3%); 4) leptomeningeal disease (12%); 5) contrast enhancement (97%); and 6) restricted diffusion (88%). The mean ADC value was 0.64 (0.15) × 10-3 mm2/s. Choroidal invasion (p = 0.05) and scleral involvement (p = 0.04) were significantly higher for bilateral RB lesions.ConclusionsContrast enhancement and restricted diffusion are the most common neuroimaging features of RB. Choroidal invasion and scleral involvement are more frequently seen in bilateral disease.