Retinoblastoma Staging Research Articles

Retinoblastoma presenting as total hyphema: Three year follow-up

Retinoblastoma very rarely presents as total hyphema. Our patient presented at an early age of 7months. Follow-up of 3years shows that unilateral group E retinoblastoma was treated successfully with enucleation and adjuvant chemotherapy. The fellow eye remained normal during this period. The factors associated with delay in treatment are also described. Reports like the present case add to the information available about advanced staging of retinoblastoma at the time of presentation, seen in cases with spontaneous hyphema due to the tumor.

The value of "en toto" globe submission in the assessment of high-risk retinoblastoma cases and staging.

To evaluate the importance of "en toto" globe submission in the assessment of high-risk pathological findings in retinoblastoma cases, aiming at identifying the additional value from full globe examination of enucleated eyes (including the calottes). Retrospective histopathological case series of eighty-one enucleated globes with the clinical diagnosis of retinoblastoma, histopathologically examined at King Khaled Eye Specialist Hospital (KKESH) between January 2010 and December 2013. We included retinoblastoma eyes with any type of invasion (more than pT1) in which the globe was submitted "en toto." All cases were histopathologically classified according to the American Joint Cancer Classification (AJCC TNM classification, 2009 6th edition). 81 enucleated globes were examined, out of which 30 globes were classified as high-risk cases (more than pT1). 8 cases had massive choroidal invasion in both the PO sections and calottes. 5 cases had focal choroidal invasion in both. One case has massive choroidal invasion in calottes with very superficial ON head invasion. Two cases were found to have focal choroidal invasion in the calottes with prelaminar ON invasion. In these three cases (10%), the presence of focal or massive choroidal invasion in the calottes has affected the classification. This study consolidates the guidelines recommended in the consensus meeting: from the International Retinoblastoma Staging Working Group on the pathology guidelines for the examination and evaluation of prognostic risk factors in retinoblastoma eyes. Full globe submission and examination should be the routine accepted practice universally even in underdeveloped countries.

High-Risk Histopathology Features in Primary and Secondary Enucleated International Intraocular Retinoblastoma Classification Group D Eyes

To evaluate the rate and identify the risk factors for high-risk histopathologic features in group D retinoblastoma eyes enucleated as primary or secondary treatment. Retrospective analysis. A total of 64 enucleated group D eyes (62 patients), of which 40 (40 patients) were primary and 24 (22 patients) were secondary to other treatments. Clinicopathologic correlation of consecutive group D eyes enucleated from 2002 to 2014. High-risk histopathologic features were defined as the presence of anterior chamber seeds, iris infiltration, ciliary body/muscle infiltration, massive (≥3 mm) choroidal invasion, retrolaminar optic nerve invasion, or combined non-massive choroidal and prelaminar/laminar optic nerve invasion. High-risk histopathologic features, metastasis, and death. Of the 64 group D eyes, 37 (58%) were classified as cT2bN0M0H0, 24 (38%) were classified as cT2bN0M0H1, and 3 (5%) were classified as cT2aN0M0H1, according to the 8th edition cTNMH Retinoblastoma Staging. High-risk histopathologic features were detected in 10 eyes (16%) in the entire cohort, 5 eyes (13%) of the primary enucleated group (pT3aNxM0, n= 2 and pT3bNxM0, n= 3, 8th edition pTNM), and 5 eyes (21%) of the secondary enucleated group (pT2bNxM0, n= 2, pT3aNxM0, n= 2 and pT3cNxM0, n= 1). Absence ofvitreous seeds at presentation was the only predictive factor found for high-risk histopathologic features in the primary enucleation group (P= 0.042), whereas none were found in the secondary group (P ≥ 0.179). Invasion of the anterior structures (anterior chamber, iris, ciliary body/muscle) was detected significantly more after secondary enucleation (P= 0.048). All patients with high-risk histopathologic features were treated with adjuvant chemotherapy, and no metastases were recorded in a median follow-up time of 73.2 months (mean, 71.5; range,13.7-153.0). The choice of primary treatment for group D retinoblastoma should be carefully weighed, because according to this study, 13% of eyes harbor high-risk histopathologic features at presentation, with the absence of vitreous seeds being a potential risk factor. It is of special importance in group D eyes being considered for nonsystemic treatment, such as primary intraophthalmic artery chemotherapy. Secondary enucleated group D eyes with high-risk histopathologic features more commonly involved anterior structures, warranting meticulous clinical and histologic examinations for this subset of patients.

Expression of FOXO3a and Correlation With Histopathologic Features in Retinoblastoma.

Forkhead box (FOX) transcription factors are a class of highly conserved proteins, which serve critical cellular functions including cell cycle regulation. The downstream mechanisms of cell cycle regulation involve preservation of retinoblastoma protein function. Its deactivation by phosphorylation and translocation from nucleus to cytoplasm leads to cell proliferation. FOXO3a has been found to be dysregulated in few cancers. However, no study has been reported on role of FOXO3a in retinoblastoma. We assessed the expression of FOXO3a in sections of archived tissue blocks of enucleated/exenterated specimens of retinoblastoma by immunohistochemistry. The histopathologic features were reviewed and correlated with its expression. Effect of FOXO3a expression on survival was assessed. FOXO3a expression was assessed in 100 sections. Six samples did not contain any viable tissue. Retrospective data of 94 patients revealed that median age at presentation was 36 months with male:female ratio of 1.9:1. Fifty-one percent of patients were International Retinoblastoma Staging System stage 1. Of the 94 sections, 68 (72%) showed cytoplasmic expression. Choroidal invasion was associated with cytoplasmic FOXO3a (P=0.04). A trend was also noted in optic nerve cut end involvement (P=0.07). No other histopathologic features were found to be associated with FOXO3a expression. The overall survival and progression-free survival were not found to be affected by FOXO3a expression. Cytoplasmic expression of FOXO3a is frequently found in retinoblastoma and may be involved in pathogenesis. Activation by relocation of FOXO3a to nucleus may activate nonmutated retinoblastoma and may be a potential target of treatment in retinoblastoma.

Clinical Presentation and Outcomes of Stage III or Stage IV Retinoblastoma in 80 Asian Indian Patients.

To describe the clinical features and outcomes of patients with stage III or IV retinoblastoma. This was a retrospective study of 80 patients. Based on the International Retinoblastoma Staging System (IRSS), the tumors (n = 81) belonged to stage IIIa (n = 38, 47%), IIIb (n = 1, 1%), IVa2 (n = 10, 12%), IVb1 (n = 14, 17%), and IVb3 (n = 18, 22%). Of 80 patients, 42 (53%) were compliant to treatment and 38 (47%) were non-compliant. All 38 patients who were non-compliant to treatment died of the disease at a mean duration of 13 months from diagnosis. Of the 42 patients compliant to treatment, 22 (52%) died before completion of treatment. Twenty patients with stage III disease (25%) could complete the multimodal treatment and 17 (71%) were alive and well at a median follow-up duration of 77 months. Compliant multimodality treatment is beneficial in patients with IRSS stage III disease. IRSS stage IV retinoblastoma has poor prognosis despite treatment. [J Pediatr Ophthalmol Strabismus. 2017;54(3):177-184.].

The efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in retinoblastoma therapy

Iris burns happened in one eye, obvious vitreous proliferation in one eye and mild vitreous hemorrhage occurred in two eyes, which did not affect the treatment of laser. However, obvious tumor hemorrhage happened in two eyes and affected laser therapy. There was no complicated cataract, iatrogenic retinal hole and tumor intravitreal implant caused by laser blasting effect. Conclusions: Indirect ophthalmoscope laser in 810-nm diode laser with large-spot alone or combined with systemic chemotherapy may be effective treatment for retinoblastoma in earlier than stage C of international classification. It is suitable for large and multiple retinoblastoma.(Chin J Ophthalmol, 2016, 52: 745-748).

Multimodal Therapy for Stage III Retinoblastoma (International Retinoblastoma Staging System): A Prospective Comparative Study

To compare the efficacy of 2 chemotherapeutic drug combinations as part of multimodal therapy for orbital retinoblastoma. Prospective, comparative, study. Patients with stage III retinoblastoma (International Retinoblastoma Staging System). Demographic and clinical features were recorded at presentation. Treatment consisted of a multimodal protocol with neoadjuvant chemotherapy, enucleation, orbital external-beam radiotherapy, and adjuvant chemotherapy. For chemotherapy, patients were randomized into 2 groups: group A patients were treated with vincristine, etoposide, and carboplatin (VEC) and group B patients were treated with carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Treatment outcomes and adverse effects were recorded. Efficacy parameters were compared between the groups. Survival probability, cause of death, and chemotherapy-related toxicity. A total of 54 children were recruited (27 in each group). The mean ± SD follow-up was 21.3±11.34 months. The overall Kaplan-Meier survival probability was 80% (95% confidence interval [CI], 0.67-0.89) and 42% (95% CI, 0.24-0.59) at 1 year and 4 years, respectively. There were 9 deaths in group A and 15 deaths in group B. The Kaplan-Meier survival probability at 1 year was similar between the groups: 81% (95% CI, 0.60-0.91) and 79% (95% CI, 0.58-0.9) for groups A and B, respectively. At 4 years, the survival probability for group A was higher (63% [95% CI, 0.41-0.79] vs. 25% [95% CI, 0.08-0.46] for groups A and B, respectively), with a strong trend of better survival in group A over time (P= 0.05). The major cause of death was central nervous system relapse (8 patients in group A and 7 patients in group B). Two patients in group B died of sepsis after febrile neutropenia. Grade 3 and grade 4 hematologic toxicities were more common in group B, with a significant difference in grade 4 neutropenia (P= 0.002). This study compared the outcomes of VEC chemotherapy with a 5-drug combination of etoposide and carboplatin, alternating with cyclophosphamide, idarubicin, and vincristine, for stage III retinoblastoma. The VEC combination was found to be more effective and may be recommended as neoadjuvantand adjuvant chemotherapy.

The Evolution of Radiation Therapy for Retinoblastoma: The MD Anderson Cancer Center Experience.

The role of radiation therapy (RT) for retinoblastoma (Rb) has significantly evolved from first-line to salvage therapy. The objectives of our study were to evaluate efficacy of proton RT (PRT) and other advanced RT techniques for Rb and to observe evolving trends in RT use. An analysis of patients with Rb who received RT between 1990 and 2012 was conducted. Thirty-nine patients with 70 affected eyes were identified. Of these, 47 eyes were treated with RT with photon or electron RT (ERT), PRT, or brachytherapy (BRT). The clinical history, treatment details, and tumor outcomes were reviewed for all patients. Radiation therapy was first-line treatment in 14 eyes, second-line in 4, postoperative in 4, and salvage in 25. Median length of follow-up was 8 years for all patients, and 10, 3, and 5 years for ERT, PRT, and BRT, respectively. Overall survival was 97.4%. In total, 16 (34.0%) eyes required enucleation after RT. Median PRT dose was 36 Gy (RBE) (range, 36-45 Gy [RBE]), ERT dose was 45 Gy (range, 36-46 Gy), and BRT dose was 45 Gy (range, 36-45 Gy). A higher proportion of PRT patients (93.8%) than ERT patients (51.9%) were treated in the salvage setting (P < .01). Among patients with International Classification for Intraocular Retinoblastoma stage D and E disease, 6 of 11 (54.5%) ERT patients required enucleation and 5 of 13 (38.5%) PRT patients required enucleation. This study represents a large series of patients treated with PRT, ERT, and BRT for Rb and reports favorable efficacy and toxicity. Patients treated with salvage PRT are typically heavily pretreated and have advanced disease. Despite more advanced disease, patients treated with PRT with lower RT doses achieve comparable salvage and enucleation-free rates to ERT. Chemoreduction followed by focal treatments should be standard of care when clinically feasible, with PRT considered in the salvage setting.

NEWLY DIAGNOSED ACTIVE RETINOBLASTOMA IN ADULTS.

To describe the clinical features, treatment, and outcome of retinoblastoma in adults. Retrospective case series. The mean age at initial presentation of retinoblastoma was 30 years (median, 26 years; range, 22-48 years). There were four males and four females, and all manifested unilateral retinoblastoma. The mean duration of symptoms was 22 months (median, 12 months; range, 1-100 months). Six patients had intraocular retinoblastoma, and 2 had secondary orbital involvement. The eyes with intraocular retinoblastoma were classified according to the International Classification of Retinoblastoma as Group D (n = 3) or Group E (n = 3). The primary treatment for intraocular retinoblastoma (n = 6) included systemic chemotherapy (n = 1), external beam radiotherapy (n = 2), and enucleation (n = 3). Secondary treatment for tumor recurrence included enucleation (n = 2), and combination of intraarterial chemotherapy, intravitreal chemotherapy, and plaque radiotherapy (n = 1). The eyes with orbital extension of retinoblastoma were classified according to the International Retinoblastoma Staging System as Stage 3a (n = 2). The primary treatment for those with orbital extension of retinoblastoma included multimodality treatment (combination of systemic chemotherapy, orbital exenteration, and external beam radiotherapy). Systemic metastasis and related death occurred in one case. Retinoblastoma in adults is uncommon. Active tumor in this age group is usually advanced, necessitating enucleation and/or orbital exenteration.

Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

Background: Sirtuin1 (Sirt1) is a member of highly conserved proteins and has been implicated as a tumor promoter as well as a tumor suppressor. One of the mechanisms involves deacetylation of retinoblastoma protein, thereby inhibiting the tumor suppressor function. No study has been reported on the expression of Sirt1 in retinoblastoma. Methods: We assessed the expression of Sirt1 in sections of archived tissue blocks of enucleated and exenterated specimens of retinoblastoma patients by immunohistochemistry. The histopathological features were reviewed and correlated with the expression of Sirt1. The effect of Sirt1 expression on survival was also assessed. Results: Retrospective data of 94 patients revealed that the median age at presentation was 36 months, with a male:female ratio of 1.9:1. Fifty-one percent of the patients had International Retinoblastoma Staging System (IRSS) stage 1 disease. Of the 94 sections, 89 (95%) expressed Sirt1. Forty-eight percent of the specimens showed grade 3 staining (>75% of the cells), and the intensity was 3+ in 53%. No association between Sirt1 expression and any histopathological feature was noted. Further, Sirt1 expression did not affect the overall and progression-free survival. Conclusions: Sirt1 was expressed in most of the retinoblastoma samples. However, the degree of Sirt1 expression was not associated with any high-risk histopathological feature or survival.

Abstract 3753: An integrated approach to identify functional signaling modules in retinoblastoma cancer progression

Abstract This study illustrates a multi-omics approach combining transcriptomics and metabolomics datasets to study molecular events leading to progression of retinoblastoma. Retinoblastoma is a pediatric ocular cancer affecting children usually less than five years of age. It is a complex disease predisposed primarily by biallelic inactivating mutations in the RB1 gene. This gene has essential roles in cell cycle, differentiation, chromosome stability and is implicated in other functions. From a cohort of 9 patients undergoing enucleation of the affected eyes, we obtained tumor, aqueous humor, vitreous humor and tear samples. We obtained retina, aqueous humor and vitreous humor from enucleated eyes of 2 deceased pediatric controls, whose cause of death is not due to any eye related disease. The patients comprise of both high and low clinical and pathological risks. In the first stage of the study, we performed mRNA and miRNA gene expression using microarrays followed by pathway analysis to identify gene enrichment that would enable functional characterization of tumors. Differential expression analysis was carried out using moderated t-test with Benjamini Hochberg multiple testing correction. 108 (p≤0.05, fold change≥10) genes were found to be unique to patients possessing high risk of metastasis. Pathway analysis revealed key pathways that are known to be involved in the progression of retinoblastoma including cell cycle and Rap1 signaling pathway. Many of these responders were verified by RT-PCR and corroborated by immuno histochemistry studies. The study also revealed 18 novel miRNAs which had not been previously implicated in the disease, with a significant overlap of the miRNA target list with our mRNA expression data set. Metabolomics studies were performed using monophasic solvent extraction of aqueous, vitreous and tear samples. The extracted metabolites were analyzed on Accurate Mass QTOF mass spectrometer in positive and negative mode on a reverse phase C18 and HILIC columns. Data dependent MS/MS analysis was performed to confirm the compounds. Pathway analysis of the differentially expressed metabolites revealed enrichment of several pathways, including nucleotide metabolism and amino acids among others. Combined pathway analysis of metabolomics and transcriptomics data was performed in order to gain an understanding of the interrelationship between changes in gene expression and metabolomic profile. The results show overlap of key cellular pathways which can be mechanistically linked to disease progression. The study provide new biological insights that are made accessible by combining data from different biological and biochemical domains with a comprehensive integrated method. The information is useful not only to correlate expression markers with disease mechanism but also to better predict appropriate chemotherapy regimens and identify new mechanisms to treat even advanced stages of retinoblastoma. Citation Format: Nilanjan Guha, Deepak SA, Syed Lateef, Seetaraman Gundimeda, Arunkumar Padmanabhan, Carolina B Livi, Nigel Skinner, Arkasubhra Ghosh, Ashwin Mallipatna, Vishnu Suresh Babu, Arun Sreekumar. An integrated approach to identify functional signaling modules in retinoblastoma cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3753. doi:10.1158/1538-7445.AM2015-3753

Retinoblastoma.

Retinoblastoma is the most common primary intraocular malignancy of childhood. It typically presents with leukocoria or strabismus. In later stages of the disease, the child may exhibit proptosis, buphthalmos, or hypopyon. The pathognomonic molecular aberration is a loss of function mutation in the RB1 gene on chromosome 13q. The degree of tumor involvement within the eye is defined by its group. Grouping was historically done with Reese-Ellsworth System. Recent therapeutic advances have led to the development of a new grouping system, the International Classification of Retinoblastoma (ICRB). In cases of extraocular extension and metastatic disease, the degree of tumor involvement outside of the eye is defined by its stage. Retinoblastoma is staged using the International Retinoblastoma Staging System (IRSS). Children with intraocular retinoblastoma have an excellent overall and ocular survival. In order to avoid the morbidity of enucleation and external beam radiation, treatments for isolated intraocular retinoblastoma have progressively moved toward targeted local modalities. Patients with extraocular involvement, such as those with trilateral retinoblastoma, have a poorer prognosis. The majority of these higher stage patients are now able to be cured with combination chemotherapy.

The potential of 3T high-resolution magnetic resonance imaging for diagnosis, staging, and follow-up of retinoblastoma

We demonstrate the value of high-resolution magnetic resonance imaging (MRI) in diagnosing, staging, and follow-up of retinoblastoma during eye-saving treatment. We have included informative retinoblastoma cases scanned on a 3T MRI system from a retrospective retinoblastoma cohort from 2009 through 2013. We show that high-resolution MRI has the potential to detect small intraocular seeds, hemorrhage, and metastatic risk factors not visible with fundoscopy (e.g., optic nerve invasion and choroidal invasion), and treatment response. Unfortunately, however, the diagnostic accuracy of high-resolution MRI is not perfect, especially for subtle intraocular seeds or minimal postlaminar optic nerve invasion. The most important application of MRI is the detection of metastatic risk factors, as these cannot be found by fundoscopy and ultrasound.

External Beam Radiation Therapy for Retinoblastoma Resistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors

External Beam Radiation Therapy for Retinoblastoma Resistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors Abstract: Purpose: To evaluate the outcome of external beam radiation therapy (EBRT) for treatment of retinoblastoma resistant to chemotherapy and focal therapy. Methods and Materials: A retrospective case series of 24 eyes for 20 retinoblastoma patients treated by EBRT after failure of tumor control by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival. Results: The median age at diagnosis was 12 months. There were 12 (60%) males and 16 (80%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range: 6-8 cycles). The dose of 45Gy was used in all eyes. The mean follow-up was 55months. Eye salvage rate after EBRT was 45% (11eyes); 67% ( 2/3) for IIRC group B, 63% (5/8) for group C, and 31% (4/13) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control (p=0.0327 and 0.0333 consecutively). Post EBRT complication rate was 80% (19/24) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), and radiation retinopathy (2). Conclusion: Eyes with retinoblastoma that failed chemotherapy were controlled with EBRT. However the presence of vitreous seeds, stage migration during chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.

Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation.

To assess the accuracy of high-resolution (HR) magnetic resonance imaging (MRI) in diagnosing early-stage optic nerve (ON) invasion in a retinoblastoma cohort. This IRB-approved, prospective multicenter study included 95 patients (55 boys, 40 girls; mean age, 29 months). 1.5-T MRI was performed using surface coils before enucleation, including spin-echo unenhanced and contrast-enhanced (CE) T1-weighted sequences (slice thickness, 2 mm; pixel size <0.3 × 0.3 mm(2)). Images were read by five neuroradiologists blinded to histopathologic findings. ROC curves were constructed with AUC assessment using a bootstrap method. Histopathology identified 41 eyes without ON invasion and 25 with prelaminar, 18 with intralaminar and 12 with postlaminar invasion. All but one were postoperatively classified as stage I by the International Retinoblastoma Staging System. The accuracy of CE-T1 sequences in identifying ON invasion was limited (AUC = 0.64; 95 % CI, 0.55 - 0.72) and not confirmed for postlaminar invasion diagnosis (AUC = 0.64; 95 % CI, 0.47 - 0.82); high specificities (range, 0.64 - 1) and negative predictive values (range, 0.81 - 0.97) were confirmed. HR-MRI with surface coils is recommended to appropriately select retinoblastoma patients eligible for primary enucleation without the risk of IRSS stage II but cannot substitute for pathology in differentiating the first degrees of ON invasion. • HR-MRI excludes advanced optic nerve invasion with high negative predictive value. • HR-MRI accurately selects patients eligible for primary enucleation. • Diagnosis of early stages of optic nerve invasion still relies on pathology. • Several physiological MR patterns may mimic optic nerve invasion.

Rétinoblastome : résultats préliminaires du protocole national de prise en charge au CHU de Casablanca

Retinoblastoma is the most frequent intraocular cancer, affecting almost exclusively children. We report prospective study results assessing the national protocol for retinoblastoma treatment in Morocco. Treatment included, depending on stage and laterality, primary chemotherapy either to facilitate enucleation or to make conservative treatment possible, postoperative chemotherapy, enucleation and conservative treatments such as transpupillary thermotherapy, thermochemotherapy and cryotherapy. Radiation was used in a few cases. Close supervision was performed until the age of 5. The incidence of retinoblastoma within the study period was 18 new cases per year in our department. Observations of 32 children were included in the study: 18 unilateral retinoblastomas (56%) and 14 bilateral retinoblastomas (44%), for a total of 46 eyes. Leucocoria was the most frequent presenting symptom (69%). Buphthalmia or proptosis were present in 47% of cases. The stage of retinoblastoma was V/D or E (Reese-Elsworth/ABC) in 69.5% of cases. Enucleation was necessary for 28 eyes. Transpupillary thermotherapy or thermochemotherapy were used for 13 eyes (11 children) and cryotherapy for 13 eyes (10 children). After an average follow-up period of 52 months, among 32 children, 4 died and 2 abandoned treatment. Ocular salvage rate was 85.7% (12 eyes out of 14, among which 11 without radiation). Retinoblastoma is a genetic tumor, which occurs in two forms: sporadic, always unilateral, and hereditary, often bilateral. The latter is the most challenging case. Current treatment protocols rely primarily on chemotherapy and local treatments. The future is oriented toward purely local treatments such as intra-arterial chemotherapy and intraocular chemotherapy.

Colorimetric and longitudinal analysis of leukocoria in recreational photographs of children with retinoblastoma.

Retinoblastoma is the most common primary intraocular tumor in children. The first sign that is often reported by parents is the appearance of recurrent leukocoria (i.e., “white eye”) in recreational photographs. A quantitative definition or scale of leukocoria – as it appears during recreational photography – has not been established, and the amount of clinical information contained in a leukocoric image (collected by a parent) remains unknown. Moreover, the hypothesis that photographic leukocoria can be a sign of early stage retinoblastoma has not been tested for even a single patient. This study used commercially available software (Adobe Photoshop®) and standard color space conversion algorithms (operable in Microsoft Excel®) to quantify leukocoria in actual “baby pictures” of 9 children with retinoblastoma (that were collected by parents during recreational activities i.e., in nonclinical settings). One particular patient with bilateral retinoblastoma (“Patient Zero”) was photographed >7, 000 times by his parents (who are authors of this study) over three years: from birth, through diagnosis, treatment, and remission. This large set of photographs allowed us to determine the longitudinal and lateral frequency of leukocoria throughout the patient's life. This study establishes: (i) that leukocoria can emerge at a low frequency in early-stage retinoblastoma and increase in frequency during disease progression, but decrease upon disease regression, (ii) that Hue, Saturation and Value (i.e., HSV color space) are suitable metrics for quantifying the intensity of retinoblastoma-linked leukocoria; (iii) that different sets of intraocular retinoblastoma tumors can produce distinct leukocoric reflections; and (iv) the Saturation-Value plane of HSV color space represents a convenient scale for quantifying and classifying pupillary reflections as they appear during recreational photography.

Comparison of Staging Systems for Extraocular Retinoblastoma

Different staging systems for extraocular retinoblastoma have been published, but to date they have not been validated in large cohorts. To review 533 patients (and pathology slides) with retinoblastoma included in 4 protocols (January 1, 1988, to December 31, 2009) who received uniform treatment. Retrospective review in a hospital setting. A critical analysis for detecting inconsistencies and omissions was performed. Patients were reclassified according to the modified St Jude Children's Research Hospital staging system, Grabowski-Abramson staging system, International Retinoblastoma Staging System (IRSS), and American Joint Committee on Cancer TNM staging system. The main outcome measure was disease-free survival (DFS), considering only extraocular relapse as an event. In the IRSS and the St Jude system, higher stages correlated with poorer DFS. For intraocular disease, only the TNM system and the IRSS included pathological definitions, and all systems except for the IRSS included substages without differences in DFS. Omissions of factors significantly associated with lower DFS included scleral invasion by the TNM system and massive choroidal invasion by the Grabowski-Abramson system. The St Jude system omits postlaminar optic nerve involvement, but this omission did not correlate significantly with lower DFS because these patients received intensive therapy. No differences in DFS were observed among substages for metastatic disease except for the presence of central nervous system involvement. All staging systems had inconsistencies in definitions of extent of disease. No system provides guidelines for imaging. Only the IRSS and the St Jude system allowed for grouping of patients with increasing risk of extraocular relapse. For lower stages, only the IRSS considers all unequivocal pathological prognostic factors. For higher stages, all systems had redundant information, resulting in an excess of substages.

Extraocular retinoblastoma in Indian children: clinical, imaging and histopathological features.

TO STUDY EYES WITH EXTRAOCULAR DISSEMINATION (EORB), WITH THE FOLLOWING AIMS: first to establish the mean lag period and to understand various reasons for delayed presentation, second to study their imaging profiles and third to analyze histopathological features of eyes enucleated after neoadjuvant chemotherapy. Prospective study of clinical and imaging features of EORBs (stage III and IV International Retinoblastoma Staging System) presenting to a tertiary eye care centre. Histopathological features of eyes enucleated after receiving neoadjuvant chemotherapy were analyzed. A pictorial illustration of the varied imaging profile of EORB was also presented. Over a period of one year, 97 eyes were diagnosed with retinoblastoma; 32 children (36 eyes) (37.1%) had EORB. Mean age 3.6±1.9 years, 71.9% males, 71.9% unilateral, 3.1% with positive family history and 40.6% with metastasis. On imaging, there was extrascleral involvement in 22.2%, involvement of orbital part of optic nerve in 33.3%, involvement of central nervous system in 27.8% and orbital wall involvement in 2.9% eyes. On histopathological analysis of eyes enucleated after neoadjuvant chemotherapy, 25.0% had no residual viable tumour tissue and rest all tumours were poorly differentiated. There are very few human malignancies where definitive treatment is started without any confirmed histopathological diagnosis and imaging plays an important role in diagnosis and appropriate staging of the disease. Chemotherapy has a variable effect on EORB, 75.0% of eyes with EORB had residual viable tumour tissue when enucleated after receiving neoadjuvant chemotherapy.