Search

Retinoblastoma is the most common intraocular tumour of the eye in children. It constitutes 11% of all cancers within the first year of life. In one-third of cases, it occurs bilaterally; usually, before 5 years of age without any gender predilection.[1 2][1] Trilateral retinoblastoma term is used

Retinoma or retinocytoma is a spontaneously arrested or spontaneously regressed variant of retinoblastoma. With the advent of the latest non-invasive imaging techniques, it is possible to evaluate the microstructural and microvascular changes associated with this tumour. Although there are a few reports which describe the imaging findings in retinocytoma, information regarding retinocytoma on the multicolour imaging is lacking. Here, we describe the multimodal imaging features in a patient with classic features of retinocytoma with special emphasis on its multicolour imaging features.

To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China.Retrospective cohort study.This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors.A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P.001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P.001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure.Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

AimTo investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding.MethodsMulticentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method.ResultsClinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; pConclusionThis international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

Purpose This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. Design Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. Participants One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. Methods Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. Main Outcome Measures Overall survival and final eye preservation. Results After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85–1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10–5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. Conclusions Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.

Retinoblastoma is the most common ocular malignancy of childhood. It is present in childhood with leukocoria and strabismus. Most patients are diagnosed under 3 years of age. Funduscopic examination can reveal an intraocular mass, but imaging is essential for complete evaluation of the lesion. Although ultrasound is a non-invasive and relatively inexpensive screening tool, cross-sectional imaging is required to assess the involvement of optic nerve and intracranial spread. We report a case of retinoblastoma in a 5 year old male child who presented with headache diminution of vision in both eyes. Contrast enhanced magnetic resonance imaging (MRI) revealed an enhancing soft tissue mass in the right eye with involvement of optic nerve and optic chiasma and contiguous with a large suprasellar mass causing hydrocephalus. Non-contrast computed tomography (CT) showed extensive calcifications in the mass lesion.

Upon completion of this activity, participants will be able to: In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Springer Nature. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at www.medscape.org/journal/eye ; (4) view/print certificate. 1.0 Release date: Expiration date: Post-test link: https://medscape.org/eye/posttest957229 Sobha Sivaprasad, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Allergan, Inc.; Apellis; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Heidelberg Pharma GmbH; Novartis Pharmaceuticals Corporation; Oculis; Optos; Oxurion; Roche. Served as a speaker or a member of a speakers bureau for: Allergan, Inc.; Bayer AG; Novartis Pharmaceuticals Corporation; Optos. Received grants for clinical research from: Allergan, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos. Meghana Tanwar, DNB, FRCS, has disclosed no relevant financial relationships. Sekaran Balaji, BSc, MSc, has disclosed no relevant financial relationships. Ayyasamy Vanniarajan, MSc, PhD, has disclosed no relevant financial relationships. Usha Kim, DO, DNB, has disclosed no relevant financial relationships. Gunja Chowdhury, DO, DNB, has disclosed no relevant financial relationships. Laurie Barclay, MD, has disclosed no relevant financial relationships. To determine the association between the parental age gap and the absolute parental age with the risk of retinoblastoma (RB) development in an offspring. RB individuals diagnosed between March 2013 and December 2019 in a single tertiary eye care centre were included. We recorded the demographic data, parental age and RB1 gene mutation status in the patient’s tumour, blood and the parental blood. We categorised RB1 mutation inheritance as sporadic RB with somatic mutations (only present in tumour), heritable RB with de novo (present in patient’s blood) and familial (present in patient and parents’ blood) germline mutations. The statistical significance was confirmed by Fisher’s exact/Chi-square test. Out of 259 RB patients, 247 were included in our study. Heritable RB with de novo germline mutations was significantly less common (p value: 0.0387; 95% CI: 0.2676–0.9329) and sporadic RB with somatic mutations was more common (p value: 0.0545; 95% CI: 1.025–3.39), if the parental age gap was

The review article presents the literature data concerning the history of the use of thermotherapy in the treatment of intraocular tumors, in particular, retinoblastoma (Rb). The article describes the historical aspects of the use of transpupillary thermotherapy (TTT) and the possibility of using this method in the treatment of RB nowadays. The analysis of Russian and foreign publications on the main parameters of laser radiation and the multiplicity of TTT was carried out. The efficacy of TTT as an independent method of Rb treatment has been demonstrated. The frequency of the main complications of TTT in Rb is presented. Key words: ophthalmology, retinoblastoma, transpupillary thermotherapy, laser treatment, pediatric oncology.

Retinoblastoma (RB) is an intraocular childhood cancer develops due to inactivation of RB1 gene. Identification of RB1 genetic variants, correlating and confirming genetic test results with clinical outcomes are crucial for effective RB management.Retrospective study of 62 RB patients and 14 family members who underwent genetic testing either by next generation sequencing (NGS) or multiplex ligation-dependent probe amplification (MLPA) or by both for screening RB1 germline mutations present in peripheral blood. Mutational outcomes were correlated with clinical outcomes evaluated over a follow-up period of 12 months.Of the 62 patients, 35 (56%) had bilateral RB and 27 (44%) had unilateral RB. Out of 24 (52%) variants detected by NGS, 9 (37.5%) were novel and 15 (62.5%) were known in 46 probands. Six (18%) gross deletions were detected by MLPA in 34 probands. The mutation detection rate by NGS and MLPA in unilateral cases was 15% (The mutations screening is important for risk assessment in future siblings and offspring of RB patients and most important in unilateral RB for determining if hereditary or not hereditary RB. Its role in predicting clinical outcomes is yet to be determined.

Purpose. Determine the nature of tumor regression and possible complications associated with the retinotoxic effect of melphalan and carboplatin with local chemotherapy.Methods. A histological analysis of 19 enucleated eyes from 19 patients with retinoblastoma was performed after combined organ-preserving treatment, including systemic chemotherapy and local chemotherapy in various doses. The enucleated eyes were fixed in 10 % formalin and processed routinely for histological examination.Results. Significant changes in the tumor tissue such as tumor regression associated with the destruction of the tumor tissue and its replacement with fibrous tissue, glia proliferation, and the formation of petrificates were revealed. Complete regression of the tumor was detected in 3 out of 19 eyes, partial in 13 eyes. There were no signs of regression in 3 eyes. Tumor invasion into the choroid was found in 5 cases, into the anterior sector — in 3 cases, into the optic nerve — in 3 cases. The retrobulbar tumor was presented in 1 case. Retinotoxic complications revealed. Hemorrhagic changes associated with focal necrosis of the central retinal vessels (n = 4), destructive changes in retinal pigment epithelium (RPE; n = 10) associated with the accumulation of melphalan in RPE leading to atrophic processes in the retina. Complications in the form of secondary glaucoma, severe fibrosis and retinal detachment, despite the complete resorption of the tumor, led not only to loss of vision, but also hindered visualization of the fundus and substantiated the need for enucleation in 3 cases. In other cases, enucleation was performed due to continued tumor growth (n = 16) or progression during treatment (n = 3).Conclusions. Retinoblastoma can be controlled with local chemotherapy. However, clinical and morphological examinations of enucleated eyes revealed and confirmed, along with tumor resorption, intraocular complications as a result of the toxic effect of the drugs and the presence of active tumor tissue to varying degrees of therapeutic pathomorphism, which can be explained by the resistance of RB to these drugs. Thus, a further search is needed for drugs that destroy the tumor and minimize the retinotoxic effect.

Retinoblastoma is the prototypic genetic tumor. Caused by mutations in the RB1 gene, retinoblastomas are heritable in 40% of the cases and, in such cases, tumors are bilateral in 80%, unilateral in 15%, and trilateral in 5% of the cases. Trilateral retinoblastoma is a term that describes bilateral retinoblastomas plus a midline suprasellar or pineal neuroectodermal tumor. Patients with a germline RB1 mutation have 45% chance of having an offspring with retinoblastoma. Prenatal diagnosis is important because the doubling time is fast, ranging from 7 to 15 days. Thus, late diagnosis during infancy is associated with larger tumors and increased risk of death, need for globe enucleation and vision loss. We report a case of bilateral retinoblastomas diagnosed by targeted high-resolution ultrasonography of the orbits at 32 weeks of gestation in a patient at risk. This report demonstrates the feasibility of accurately detecting even tiny retinoblastomas by ultrasound with current technology. We also review prenatally published cases to date and comment on the technical strengths and limitations of ultrasound and fetal MRI for prenatal diagnosis of retinoblastomas.

Purpose. To present results of cataract surgery in children with retinoblastoma. Material and methods. Within the period from 2012 to 2020, cataract surgery was performed in 21 children (22 eyes) with retinoblastoma aged 28 to 155 months (average – 65 months). Tumors of group B occurred in 2 cases, group C – in 4, group D – in 14, group E – in 1. In 8 cases, cataract occurred in a single eye. Posterior capsular cataract was observed in 18 patients, total – in 3. In all cases, the presence of cataract impeded the control of the tumor. Before cataract surgery all children underwent systemic chemotherapy, some of them also underwent intra-arterial and/or intravitreal chemotherapy, external beam radiotherapy, Gamma Knife stereotactic radiosurgery and local treatment modalities (episcleral plaque brachytherapy, thermotherapy, cryotherapy). There were no signs of tumor progression in all cases at the time of cataract surgery. The mean interval between complete tumor regression and cataract surgery was 23 months (range 6–75 months). Results. Full transparency of optical media was achieved in all eyes after surgery. No intraoperative and postoperative complications occurred. The final visual acuity was improved in 12 eyes, in the rest visual acuity could not be determined due to age. There were no signs of tumor recurrence or metastases in mean follow-up after surgery of 29 months (range 3–60). Conclusion. Our experience of cataract surgery in children with complete regression of retinoblastoma was proved to be a safe and effective way to improve visual functions and achieve transparency of optical media. Key words: retinoblastoma, cataract surgery, ophtalmooncology, functional results

Aim & method: Tropheryma whipplei causes Whipple’s disease. Children are reservoirs of this bacterium. The aim of this study was to investigate the presence of T. whipplei in children with immunodeficiency in central Iran from July 2018 to February 2019. Stool samples were tested by SYBR Green and Taq-Man real-time PCR assays. For confirmation, the isolated DNA was sequenced. Results: One hundred and thirty children were enrolled. Acute lymphocytic leukemia was the most reported immunodeficient disease (77%), followed by non-Hodgkin lymphoma and retinoblastoma. Thirteen (10%) children had T. whipplei DNA in the stool; 11.4% of the children under 5 years old were positive. Conclusion: This is the first study showing the circulation of T. whipplei in Iran.

Purpose: To describe the feasibility of a new one-step approach to aspirate the aqueous and apply melphalan in a single-go without repeated entries into the anterior chamber. Methods: This retrospective non-comparative study was conducted at a referral center and included 12 patients. The one-step approach is described in a step-wise manner. No complications were observed among the patients. Results: One single injection of intracameral melphalan proved to be a successful treatment in nine cases. Two patients required a second injection, which was administered two weeks after the first one following the same technique. Conclusions: This proved to be a reasonable technique for the smooth application of melphalan in the anterior chamber studded with retinoblastoma seeds. Our outcomes revealed that it is an effective, quick, and cost-effective technique. Longer-term data collection is underway, though initial findings are encouraging.

Retinoblastoma eyes with choroidal invasion may not have to be enucleated and may be successfully managed with OAC using Melphalan, Carboplatin and Topotecan without compromising patient survival.

Purpose The purpose of this study was to describe the academic performance of childhood retinoblastoma (RB) survivors. Design Retrospective cohort study. Methods Retrospective chart review of children followed in a survivorship clinic. Results A total of 73 patients with RB (median age at diagnosis: 9.97 months; range: 0.29-65.1) were followed for a median of 6.4 years (0.2-1.76). A total of 48 patients (65.8%) had unilateral RB; 43 patients (63.0%) received systemic chemotherapy; and 57 patients (78.1%) underwent enucleation. At last follow-up, 5 children (6.8%) had bilateral visual acuity (VA) Conclusions Academic difficulties in childhood RB survivors are associated with chemotherapy treatment, a risk factor independent of VA.

Purpose: Spontaneous regression is a rare but well-known feature of retinoblastoma, which is predicted in approximately 2 of every 100 cases. Unilateral, unifocal spontaneous regression of retinoblastoma is infrequent; bilateral multifocal spontaneous regression of retinoblastoma is even more extraordinary. In many of the previously reported cases, the eye (or eyes) containing the spontaneously regressed tumor has been phthisical and blind. Herein, we describe the case of a young woman with unilateral, spontaneously regressed retinoblastoma (RB), with inflamed, blind, and phthisis in the left eye as an uncommon presentation of spontaneously regressed retinoblastoma Methods: This is a case report: An 18-year-old woman came to the outpatient clinic with a chief complaint of pain in the left eye since 1 month prior and a history of dysfunctional “cat’s” eye since childhood. Results: Exotropia and atrophy bulbi was noticed in the left eye. Anterior segment examination revealed signs of inflammation including conjunctival hyperemia, shallow anterior chamber, rubeosis iridis, and posterior synechia with white “chalky” mass suggestive calcification. B-scan ultrasonography showed a point like lesion and solitary solid intraocular mass with calcification in vitreus. Orbital computed tomography scan (CT-Scan) showed atrophy of the left eye with intraocular calcification without optic nerve and extraocular muscle involvement. Enucleation and histopathology examination were done and revealed undifferentiated retinoblastoma beyond the sign of metastasis in other parts of the eye. Conclusion: Blind painful eye may present as the main feature of spontaneously regressed retinoblastoma that possibly caused by an inflammatory reaction.

Background. Retinoblastoma is a malignant intraocular tumor developing from the retinal neuroectoderm and diagnosed primarily in young children. This type of cancer is associated with a high risk of multiple primary tumors emerging after treatment completion. Multiple primary tumors are two or more independent tumors developing in one patient. Treatment of this disease is challenging.Objective – to evaluate the impact of risk factors on the efficacy of therapy for multiple primary tumors and to analyze treatment outcomes.Materials and methods. A 2-year-old boy was diagnosed with bilateral retinoblastoma (OD – stage T3bN0M0 and OS – stage T3cN0M0). He received special treatment from September 2005 to November 2006. In 2012, the patient underwent cataract surgery: the lens was removed, then an intraocular lens was installed, and laser dissection of the posterior capsule of the lens was performed. Six years later, in August 2018, the patient was diagnosed with osteosarcoma. The boy received combination organ-sparing therapy according to the EURAMOS-1 treatment protocol for osteosarcoma. During therapy, he developed a secondary tumor, namely osteoblastic osteosarcoma. Both the boy and his father were found to have a mutation in the RB1 gene.Results. Currently, patient’s condition is satisfactory; he has no complains. The boy is in remission for 2 years.Conclusion. The development of secondary tumors depends on the genetic factors, type of treatment for primary tumor, and environmental factors. Therefore, it is extremely important to assess risk factors for multiple primary tumors at the moment of primary retinoblastoma detection. The results of such assessment will help to choose an optimal treatment strategy.

Purpose: Bilateral enucleation is rarely used to manage retinoblastoma (Rb). We present the health-related quality of life (HQL) and the associated factors among individuals who underwent bilateral surgical enucleation for retinoblastoma. Methods: Patients were interviewed via telephone in January 2020. A retinoblastoma registry was used to select patients who underwent bilateral enucleation/exenteration during 33 years. Data included age, gender, literacy, occupation, marital status, and health issues. Patients were asked eight questions on HQL. The responses were graded as 0–10. The percentage proportion of the HQL score was correlated to the determinants. Results: Twenty-one out of 24 participants were interviewed (median age, 23 years). Fourteen participants answered the HQL question themselves, and for 7, their parents answered. Twenty patients (95%) had an ocular prosthesis. The median HQL score was 58 (out of a maximum score of 80) (interquartile range (IQR): 49; 70; minimum, 0 and maximum, 74). The HQL score was positively correlated to: self-reporting than parents reporting (Mann Whitney U (MW) p = 0.05); among students versus individuals in other occupations (MW p = 0.03); interval between eye removal and interview ( p = 0.02). Age at enucleation of the second eye ( p = 0.001), students ( p Conclusions: HQL of individuals having bilateral eye enucleation for retinoblastoma was reasonably good and positively correlated to self-reporting, learning as students to cope and age at 2nd eye removal. Anaplasty services to improve cosmetics seem to benefit such disabled persons.

Purpose To determine prospectively the efficacy and to assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. Design Phase 2 nonrandomized, prospective study. Participants Patients with unilateral retinoblastoma group B, C, or D of the International Classification for Intraocular Retinoblastoma (IRC). Group D eyes with massive vitreous seeding were not eligible. Methods Melphalan SOAC associated with diode laser thermotherapy, cryotherapy, or both at 4-week intervals (3–6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy also was used. Main Outcome Measures The primary outcome was globe preservation rate. Secondary outcomes were tumor relapse rate, occurrence of ocular or systemic adverse events, and measurement of the dose area product (DAP). Results Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were included prospectively. Three included patients did not receive SOAC (2 catheterization failures and 1 case of viral syndrome) and were considered failures. At diagnosis, IRC groups for the 36 treated patients were: B, n = 4 (11%); C, n = 13 (36%); and D, n = 19 (53%); median age was 21.5 months (range, 3.2–61.6 months). Median number of SOAC cycles was 3.9 (range, 1–6 cycles), and median melphalan dose was 4.9 mg/procedure. The median DAP was 1.24 Gy.cm2/procedure. Median follow-up was 63 months (range, 34–93 months). SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them and cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients because of severe ophthalmic (ptosis, n = 2; retinal ischemia, n = 2) or systemic (hypotension, n = 1) adverse events. At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% (range, 68.6%–94.6%). After a follow-up of at least 30 months, the ocular preservation rate was 69% (n = 24 preservations). Conclusions This first prospective trial demonstrated that SOAC with melphalan alone as first-line treatment for retinoblastoma is efficient and well tolerated with no metastatic events, although ocular ischemic complications were observed.

The management of retinoblastoma is complex. With increasing treatment modalities and increasing experience with each treatment modality, the globe salvage rates have drastically improved with time. Aqueous seeding in an eye with retinoblastoma is classified as group E based on International Classification of Intraocular Retinoblastoma, and most group E eyes were enucleated a decade earlier. Newer modalities of treatment have improved the globe salvage rates in group E eyes including those with aqueous seeding. Various globe salvage treatment modalities attempted for the management of aqueous seeds include external beam radiotherapy, plaque radiotherapy, intra-arterial chemotherapy, periocular chemotherapy, intravitreal chemotherapy and intracameral chemotherapy. Of all treatment modalities, intracameral chemotherapy holds promise for the management of aqueous seeds in selected patients, but it should be done with the utmost care by a trained ocular oncologist. Enucleation is still the preferred modality of treatment for eyes with advanced retinoblastoma and anterior segment invasion. This review focuses on the current evidence on aqueous seeding, highlighting the pathogenesis, classification, clinical presentation, treatment and outcomes.

Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

Introduction: This study was conducted to evaluate the clinical presentations and management of various Orbito-ocular malignancies in Nepal. Materials and methods: This is a prospective study of ocular malignant cases conducted at a tertiary care eye hospital in Kathmandu, Nepal. One hundred and seventeen newly diagnosed eyes with ocular malignancy of 106 patients presenting to the clinic in a year from September 2018 to August 2019 were included for analysis. Patients’ demography, clinical features, various types of malignancies seen in eyes and their management were evaluated. Results: The mean age of patients was 30.35 years with a range from 1 month to 84 years and standard deviation of 26.63. 56% of the total were male. Red eyes and visible mass were the most common symptoms in 23% with intraocular contents in 48% being the most common site involved. Different types of ocular malignancies were detected, among which retinoblastoma was the most common in 38% of patients. Diagnosis in most patients was clinical and/or radiological; incision biopsy was required in 1.7% patients only. Surgical excision of the tumor was the most common treatment done in 29% followed by enucleation in 27% of eyes. Bilateral involvement of the eyes was seen in 10% of the patients. Conclusion: Malignant orbito-ocular tumors can be seen in any age group. Retinoblastoma is the commonest malignancy seen. With the help of imaging, diagnosis is near accurate; hence biopsy is not required in most cases before commencing treatment.

Background: The Red Reflex is described as the red to orange reflection of light from the fundus of the eye, observed while using a retinoscope or an ophthalmoscope. Red Eye Reflex Test is determined by the optical media transparency which includes vitreous humor, aqueous humor, cornea and tear film and reflection of light from the back of the eye (fundus) through optical media and into the aperture of the ophthalmoscope. Factors that will block or impede the passage of light through this transparent media or affects its reflection back from fundus will produce an abnormal Red Eye Reflex. Red Eye Reflex (RER) testing is important & effective tool for early detection of ocular abnormalities such as retinal abnormalities, cataract, retinoblastoma and glaucoma. Red reflex is cost effective, can be performed very easily, requires minimal setting, can screen important ocular abnormalities and facilitate their early detection with prompt intervention to prevent long term sequelae associated with the disease. Aim: To find out the diagnostic accuracy of Red Reflex test for diagnosing ocular abnormalities in newborns. Methodology: Ours will be a prospective cross-sectional study where RER examination will be performed within one week of birth of a newborn in a darkened and will correlate the examination findings with respect to ocular findings determined by ophthalmologist to determine its efficacy, sensitivity and specificity in detecting neonatal ocular abnormalities. Expected results: After completion of the study we will be able to determine the accuracy of RRT for ocular abnormality detection in the neonates. We will be able to determine the sensitivity, specificity, PPV & NPV of the red reflex test. If the specificity and the sensitivity is good then we can use RRT as a routine screening method for detection of intraocular abnormalities. Conclusion: To find the Red reflex Test efficacy in screening of the ocular abnormalities in the new born.

This case series highlights the possibility of retinoblastoma in children with a history of trauma. Retinoblastoma commonly presents with leukocoria. In our series, the history of blunt trauma led to a misdiagnosis. The delay in correctly diagnosing retinoblastoma was made more difficult with hyphaema and vitreous haemorrhage obscuring the fundus view. Hyperdensities in imaging tests were mistaken for intraocular foreign bodies and post-trauma insult rather than calcification of an intraocular tumour. Both patients underwent anterior chamber washout. The patients were referred to our centre when their condition worsened. Retinoblastoma was highly suspected and confirmed from histopathological examination after enucleation. An accurate diagnosis can only be achieved by exercising a high index of suspicion. Misdiagnosis and mismanagement will lead to poor prognosis.

Background. To describe an extensive untreatable choroidal metastasis by retinoblastoma in the treated patient which was clinically indistinguishable from regular tumor recurrence. Methods. A 24-month-old girl without a family history of retinoblastoma (RB) was discovered to have group C RB in her right eye and group D in her left eye. The patient received 12 cycles of intravenous chemotherapy, intra-arterial chemotherapy (IAC), and intravitreal chemotherapy for the left eye and focal adjuvant therapy (laser thermotherapy and cryotherapy) for both eyes. Six months after the last treatment, fundus examination showed a regressed tumor in both eyes. Ten months after the last treatment, except for in addition to tumor recurrence, rising intraocular pressure was noticed in the left eye. While doing IAC for the left eye, a very rapid growing yellowish dome-shaped mass was found which had doubled in size in two weeks. Enucleation was considered for her. Results. Pathology evaluation of the enucleated eye revealed a very massive dome-shaped choroidal metastasis invasion with poorly differentiated RB tumor. Prophylactic systemic chemotherapy was performed for the patient. Conclusion. Choroidal metastasis in RB patients is often diagnosed based on pathology reports, but it may rarely be seen in clinical examinations especially if the pattern of tumor recurrence and growth is abnormal.

Objective To establish the success rate of salvage intra-arterial chemotherapy (IAC), defined as the percentage of eyes that achieved tumoral remission and avoided enucleation. The second objective was the clinical characterization, catheterization results, and associated local and systemic complications. Methods Retrospective, interventional case series of 29 patients (35 eyes) with persistent or recurrent retinoblastoma. Results A total of 73 salvage IAC procedures with topotecan and melphalan were carried out. Success rate was 77% at a mean follow-up of 41.4 months. All patients with only one remaining eye avoided enucleation (10 cases). Catheterization was successful in 98.6% of cases. The types of catheterizations were as follows: 71.2% supraselective ophthalmic artery, 12.3% occlusion pump assisted supraselective ophthalmic artery, 16.4% selective external carotid with retrograde flow. 14% of patients suffered local adverse effects: 1 (2.8%) transitory ptosis, 1 (2.8%) transitory oculomotor nerve palsy, 2 (5.7%) aseptic cellulitis and 1 (2.8%) periorbitary pigmentation. 4.1% (3 cases) suffered neutropenia due to medullar chemosuppression. There were no cases of severe anemia or thrombocytopenia. There were no cerebral ischemic events or mortality associated to the procedure. Conclusion IAC with melphalan and topotecan is a safe and effective treatment option for persistent or recurrent retinoblastoma, able to reduce enucleation rates.

Background Retinoblastoma (RB) outcomes in Thailand are unfavorable compared to those of developed countries. This study aims to determine whether the clinical outcomes of patients with RB significantly improved after the implementation of new therapeutic approaches and which clinical factors affect survival and globe-saving outcomes. Methods The medical records of patients newly diagnosed with RB and treated at Siriraj Hospital between January 2005 and December 2018 were reviewed retrospectively. Clinical data, treatments, and outcomes were collected and analyzed. Results In 194 eyes (144 patients), leukocoria was the most common presenting feature (76.8%); 129 (66.5%) eyes were staged in group E of the International Classification of Intraocular Retinoblastoma. Of the 149 enucleated eyes, 35 had high-risk histopathological features, mostly choroidal invasion; 45 eyes (23.2%) could be salvaged. The 5-year overall survival rate was 90.3%, an improvement compared to the previous study. The 5-year enucleation-free survival rates of Groups A and B, C, D and E were 100%, 83.1%, 36.7% and 16.6% respectively. Factors associated with a lower survival rate were interval from symptom onset to diagnosis >3 months (hazard ratio (HR): 5.8: 95% confidence interval (CI): 1.637, 20.579) and buphthalmos (HR: 12.57: 95% CI: 3.936, 40.153). Factors associated with high-risk features were secondary glaucoma (HR: 11.016: 95% CI: 1.24, 98.10) and pseudohypopyon (HR: 14.110: 95% CI: 2.16, 92.05). Conclusions Survival rates and globe-saving rates appear to have improved; however, advanced-stage presentation remains the major hindrance. Further studies with a larger cohort and longer follow-up are warranted.

PurposeTo explore the risk factors for ophthalmic artery (OA) stenosis and occlusion after intra-arterial chemotherapy (IAC) with selective ophthalmic artery catheterisation (OAC) in the treatment of retinoblastoma.DesignRetrospective, single centre case-control study.MethodsThe study was conducted including consecutive patients with unilateral or bilateral intraocular retinoblastoma undergoing IAC between June 2016 and June 2019 with a follow-up time of 4 years. Main outcomes are rate of IAC-induced OA occlusion and OA diameter.Results346 attempted OAC infusions were successful. The total incidence of OA occlusion was 15.89%. The occlusion and control groups were similar in patients’ age, sex and disease stage. Median OA diameter was 0.49 mm in those with OA occlusion, and 0.66 mm in those without occlusion. In the occlusion group, the OA diameter difference was significantly larger between the first IAC and the final IAC (0.22mm vs 0.12mm, p=0.001). In both groups, the median number of IAC treatments was 3. Multivariate Cox regression models included initial OA diameter (OR: 0.005, p=0.001), ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter (OR: 4.661, p=0.003), and number of IAC (OR: 1.538, p=0.042) as clinical features significantly associated with OA occlusion.ConclusionsThe OA diameter at first IAC treatment, the ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter and total number of IAC treatments may be three main clinical predictors for OA occlusion after IAC for retinoblastoma.

Background: Retinoblastoma (Rb) is a childhood tumor of the developing retina where predisposition is caused by RB1 pathogenic variants. MYCN amplification (MYCNA) has been implicated in around 2% of sporadic unilateral Rb tumors with no detectable RB1 variants. We audited data from tumors collected between 1993 and 2019 to determine if this is the case for patients treated at Barts Health NHS Trust, and how often it occurred alongside RB1 variants. Materials and methods: Screening for MYCNA was carried out by Multiple Ligation Probe Analysis of tumor and blood samples collected for RB1 genetic screening. The cohort consisted of 149 tumors, of which 114 had matched blood samples. Results: 10/149 (6.7%) tumors were positive for MYCNA in a population containing a disproportionate number of cases negative for RB1 pathogenic variants. Of 65 unbiased tumors collected from 2014 to 2019, 2 (3.1%) had MYCNA. All MYCNA samples were from sporadic, unilateral patients and 3/10 (30%) had RB1 pathogenic variants. MYCNA was not detected in any blood sample. No MYCNA tumor had 6p gain which is usually a common alteration in Rbs. Conclusions: MYCNA occurs in a small fraction of Rbs and can occur in the presence of pathogenic RB1 variants. However, where it occurs alongside RB1 alterations, the age of onset appears to be later. MYCNA has yet to be seen as a heritable change. In sporadic cases with early diagnosis, Rbs with no RB1 pathogenic variant identified should be tested for MYCNA. Conversely, tumors with MYCNA should still be screened for RB1 pathogenic variants.

BackgroundCurrent melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.MethodsRabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction. Patients: retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.ResultsIntravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC90 across the rabbit vitreous. Three weekly topotecan injections (either 15 µg or 30 µg) caused no retinal toxicity in rabbits, whereas melphalan 12.5 µg (equals 25 µg in humans) reduced ERG amplitudes 42%–79%. Intravitreal topotecan 15 µg was equally effective to melphalan to treat WERI-Rb1 cell xenografts in rabbits (96% reduction for topotecan vs saline (p=0.004), 88% reduction for melphalan vs saline (p=0.004), topotecan vs melphalan, p=0.15). In our clinical study, patients received 881 monotherapy injections (48 topotecan, 833 melphalan). Patients receiving 20 µg or 30 µg topotecan demonstrated no significant ERG reductions; melphalan caused ERG reductions of 7.6 μV for every injection of 25 µg (p=0.03) or 30 µg (pConclusionsTaken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.

Introduction Genomic profiling provides useful information for diagnosis, treatment, and prognosis, and detection of certain defects, such as DNA repair gene aberrations or microsatellite instability, can possibly lead to optimal treatment, but this testing has not been widely used to inform prostate cancer treatment. Case presentation A 55-year-old man sequentially treated for prostate cancer was diagnosed as neuroendocrine prostate cancer from prostate specimens resected because of urinary retention. Subsequently, he received five cycles of platinum-based chemotherapy in total and responded well. We also performed next-generation sequencing of a sample from the prostate specimen and identified a breast cancer susceptibility gene mutation with Murine Double Minute 2 amplification and loss of heterozygosity in retinoblastoma 1. Conclusion We report a neuroendocrine prostate cancer patient with Murine Double Minute 2 amplification who experienced an aggressive course and for whom platinum-based chemotherapy was effective, and one of the reasons for the good response might be the breast cancer susceptibility gene mutation.

To figure out the impact of national health insurance program and treatment modalities on the clinical outcomes of patients with retinoblastoma. Retrospective cohort study. Enrolled patients were classified into three groups according to the time period in which their initial diagnosis was performed: patients diagnosed before 1995 (group 1), patients diagnosed in the time period 1995–2010 (group 2), patients diagnosed after 2010 (group 3). Comparison was made of clinical features including presenting signs, tumor spreading, and treatment modes. Survival and globe salvage rates were analyzed within each group. There were 157 patients (202 eyes) enrolled from 1978 to 2015. The overall mortality rate was 24.2%. The overall 5-year survival rate was 63.4%, 73.8%, 89.1% in the three time periods respectively (P = 0.007). The 5-year survival improved continuously in both unilateral and bilateral disease (P = 0.057; P = 0.015). Patients without extraocular spreading or diagnosed before 2 years of age had a better 5- year survival of 97.4% and 81.1% respectively. The globe salvage rate improved from 8.2%, 14.5%, to 35.1% (P

Several neoplastic processes can involve the eye, either primarily or secondary to a systemic malignancy. The most common primary tumors of the eye include conjunctival and uveal melanoma, retinoblastoma, conjunctival and intraocular lymphoma, and ocular surface squamous neoplasia. Metastatic spread from systemic malignancies, especially of the breast and lung, also can involve the eye. A combination of ophthalmologic examination, ancillary testing, and cytologic/histopathologic evaluation leads to accurate diagnosis. Management consists of surgery, radiotherapy, chemotherapy, and immunotherapy delivered in various forms.

Background: Although survival rates for retinoblastoma (RB) are over 95% in high-income countries, its high mortality rate in low and middle-income countries remains a great concern. Few studies investigated treatment outcome and factors contributing to RB survival in these latter settings. Aims of this study are to determine treatment outcome of Indonesian children diagnosed with RB and to explore factors predictive of treatment outcome. Methods: This study was a retrospective medical records review combined with an illustrative case report. Children newly diagnosed with RB between January 2011 and December 2016 at a tertiary care referral hospital in Indonesia were included. A home visit was conducted to perform an in-depth interview with a mother of two children affected by RB. Results: Of all 61 children with RB, 39% abandoned treatment, 21% died, 20% had progressive or relapsed disease and 20% event-free survival. Progressive or relapsed disease was more common in older (≥ 2 years at diagnosis, 29%) than young (

Purpose: Retinoblastoma is the most common intraocular tumor of children. Globe salvaging conservative management is gaining popularity with advances in early diagnosis and advent of focal and systemic therapies. Materials and Methods: This study is retrospective noncomparative interventional study at oculoplasty and ocular oncology department of Tilganga Institute of ophthalmology, Nepal in 2017-18. Results: Thirty-five retinoblastoma patients with forty-five affected eyes were treated during the study period. Twelve eyes were salvaged and twenty-six lives were saved though more than sixty five percent of eyes were in group D or E. We could avoid exenteration and minimize enucleation in the study. Conclusion: Globe salvaging management is possible with early diagnosis and multimodal management. Keywords: Eye Neoplasms, Pediatric Cancer, Periocular Chemotherapy, Retinoblastoma, Transpupillary Thermotherapy.

Purpose: To describe, retrospectively, the visual outcome, feasibility, and safety of cataract surgery in a pediatric population affected by iatrogenic cataract, secondary to systemic oncological treatment for malignancies other than retinoblastoma. Methods: Young patients, affected by radiation-induced cataract, who were referred to the San Paolo Ophthalmic Center in Padova between 2010 and 2017, were included in the study. All patients had previously received radiotherapy and/or chemotherapy treatment for malignancies, between 2004 and 2013. All medical records of infants who underwent cataract surgery were accurately reviewed. Results: Eighteen eyes out of 11 patients included in the study underwent cataract surgery. The mean age at surgery was 9.7 ± 3.6 years. The interval between tumor diagnosis and cataract development was around 3 years. Mean follow-up after surgery was 15.4 ± 6.3 months. All eyes underwent posterior chamber intraocular lens implantation, posterior capsulotomy, and anterior vitrectomy in one time surgery. No intraoperative complications were shown. Post-operatively, only one eye received laser capsulotomy due to posterior capsule opacification. At the end of follow up, best-corrected visual acuity was 20/20 (LogMAR 0) in all eyes and significantly improved ( p Conclusions: Iatrogenic-cataract surgery in pediatric oncological patients is a safe and effective way to improve visual acuity. Posterior capsulotomy and anterior vitrectomy at the time of surgery reduce the rate of posterior lens opacification and guarantee an excellent visual acuity in these patients.

Intra-arterial chemotherapy is a new retinoblastoma treatment associated with high rates of globe salvage that has been widely adopted for primary treatment of retinoblastoma but is less frequently used as secondary treatment for refractory retinoblastoma. This systematic review aims to summarize the reported outcomes of intra-arterial chemotherapy for refractory retinoblastoma. We conducted a systematic review of studies published on PubMed, Medline, and Embase from 2011 to 2021 reporting globe salvage rates following intra-arterial chemotherapy for secondary treatment of refractory retinoblastoma. Our search yielded 316 studies, and 24 met inclusion criteria. The 24 included studies were comprised of 1366 patients and 1757 eyes. Among these, 1184 (67%) eyes received secondary indication treatment, and globe salvage was achieved for 776 of these 1184 eyes (64%). Sixteen studies reported cannulation success rates from 71.8 to 100%. Pooled analysis of subjects revealed 21 patients (2.6%) with metastatic disease and 26 deaths (3%) during study follow-up periods (7–74 months). The most common ocular complications were vitreous hemorrhage (13.2%), loss of eyelashes (12.7%), and periocular edema (10.5%). The most common systemic complications were nausea/vomiting (20.5%), neutropenia (14.1%), fever (8.2%), and bronchospasm (6.2%). Intra-arterial chemotherapy is associated with high rates of globe salvage and low rates of serious complications in patients with refractory retinoblastoma. Unfortunately, current literature is predominantly comprised of retrospective case studies, and further high-quality evidence is necessary to inform clinical practice.

This review presents a cosmetic rehabilitation method in children with enucleated eye due to retinoblastoma – primary orbital endoprosthetics. General surgical approaches, implant types, cosmetic outcomes and complications are described within review. Primary orbital endoprosthetics in children with enucleated eye due to retinoblastoma is considered as safe and necessary method of pediatric rehabilitation. Key words: retinoblastoma, primary endoprosthesis replacement of the orbit, implants, chemotherapy, external beam therapy, pediatric rehabilitation.

Retinopathy of prematurity (ROP) and retinoblastoma (RB) are well-described entities in premature babies. Although their pathogeneses are different, with ROP representing a disorder of interrupted development and RB a genetic disease, a few co-occurring cases have been reported, raising the possibility that the 2 conditions. Here, we report the sixth such case of co-occurring ROP and RB in an 8-month-old infant conceived by in vitro fertilization (IVF) who developed bilateral retinoblastoma a few months after treatment for advanced-stage ROP. While the ROP was initially adequately managed, bilateral RB necessitated bilateral enucleation. This case raises a number of important questions about whether IVF, ROP, and RB are causally related. Although the associations between IVF, ROP, and RB are likely to be coincidental, this case nevertheless highlights that ROP patients require regular follow-up for early diagnosis and treatment of ocular sequelae including RB.

BACKGROUND: Our study aimed to comprehensively investigate the age of onset, magnetic resonance imaging (MRI) features, and prognosis of children with trilateral retinoblastoma (TRB). METHODS: We included 14 patients with TRB diagnosed or followed up in our hospital. The age of onset and MRI features of the intraocular tumor and intracranial lesions were evaluated. A follow-up study was also conducted. RESULTS: A total of 11 participants were diagnosed with concurrent TRB at the age of 11.1±7.4 months, and 3 participants had late-onset TRB at age 37±19.1 months. The incidence of TRB with unilateral eye involvement was 7.1% (1/14). The intraocular tumors showed intense enhancement in contrast-enhanced T1-weighted images (WI) and significant diffusion restriction in diffusion WI (DWI) with an apparent diffusion coefficient (ADC) of (0.619±0.22)×10(−3) mm(2)/s. The intracranial lesions showed similar DWI aspects with an ADC value of (0.680±0.206)×10(−3) mm(2)/s. Therapeutically, 8 participants had a period of intraocular tumor stabilization and significant intracranial lesion volume reduction after chemotherapy, and 6 participants had given up treatment. Only 2 participants who simultaneously received high-dose chemotherapy and autologous hematopoietic stem cell rescue were still alive with no recurrence at 24 and 54 months of follow-up. The 1-, 2-, and 3-year overall survival (OS) rates were 80%, 18.75%, and 12.5%, respectively. CONCLUSIONS: Patients with unilateral or bilateral RB can develop TRB. The intraocular and intracranial tumors showed slightly different ADC values. High-dose chemotherapy, combined with stem cell rescue can significantly improve survival. A long term and scheduled follow-up before 60 months of age is necessary for screening later-onset TRB patients.

Retinoblastoma is the most common primary intraocular malignancy in children.1 Incidence of retinoblastoma is constant worldwide at one case per 15000–20000 live births, which corresponds to about 9000 new cases every year.2,3 It usually occurs in children under five years of age and can lead to loss of vision, and in extreme cases, death.4 The common signs of its presentation are leukocoria, strabismus, secondary glaucoma, proptosis, anterior chamber inflammatory signs and spontaneous hyphaema.1 Prognosis for vision and survival has significantly improved due to timely diagnosis and improved treatment methods.5

Aim: To assess and compare the diagnostic accuracy of magnetic resonance imaging (MRI) and computed tomography (CT) for detecting the extent of tumor invasion in eyes with advanced retinoblastoma prior to enucleation using histopathologic analysis as a reference.Methods: A total of 56 patients (68 eyes) enucleated for retinoblastoma were reviewed. Eyes with complete data (CT 28, MRI 16) were included for analysis. Imaging data were reviewed by a pediatric radiologist, blinded to histopathology results. Four high-risk factors which included scleral, choroidal, anterior eye segment invasion, and postlaminar optic nerve invasion were assessed.Results: For CT, the diagnostic odds ratio (DOR), sensitivity, and specificity for detecting postlaminar optic nerve invasion were 1.7%, 25%, and 83.3%. Choroidal invasion was correctly identified in only 2 of 10 eyes (DOR 0.5, sensitivity 20%, specificity 66.7%). For scleral invasion, CT showed a diagnostic ratio of 1.5%, sensitivity 40%, specificity 69.6% whereas for anterior segment invasion DOR was 9.2%, sensitivity 100%, and specificity 65.4%. MRI showed a higher DOR for detecting postlaminar optic nerve invasion of 39%, sensitivity 77.8%, and specificity 100%. Choroidal and scleral invasion on MRI had a DOR of 6.5% (sensitivity 25%, specificity 100%) and 6% (sensitivity 33.3%, specificity 92.3%) respectively while DOR for anterior segment invasion was 1.3% (sensitivity 50%, specificity 57.1%).Conclusion: CT showed a poor diagnostic accuracy for all four high-risk factors in advanced retinoblastoma and therefore may not be a useful tool for assessment of tumor extension. For MRI, detection of postlaminar optic nerve invasion was moderately accurate although less accurate for detection of other risk factors. Decision-making for each child should not be based on any single parameter but rather on consideration of clinical factors in combination with radiologic findings.

External beam radiotherapy (EBR) remained for a long time the only method of treatment in children with recurrent and resistant retinoblastoma (RB). This method often leads to serious complications, including the occurrence of secondary malignant tumors. Currently, EBR is used as second-line (salvage) therapy. There is no data in the literature of using Gamma Knife stereotactic radiosurgery (GKRS) in RB treatment. Purpose. To present 5-year experience of using GKRS in patients with RB. Material and methods. 16 children (17 eyes) were treated using GKRS in the period from 2015 to 2019. Mean patient age was 34.7 months (range, 12–114 months). The eyes were classified as group B (n=4), C (n=1), D (n=12). 3 children had the last eye. All patients received systemic and local chemotherapy, all types of local treatment modalities before using GKRS. Recurrent and resistant RB was the indication for GKRS. Marginal 50% mean dose was 22 Gу (range, 20–24 Gу), depending on tumour type and location. Radiation doses were evaluated accounting critical eye structures and the orbit bones. Results. Complete regression was achieved in 11 patients, partial in 2. Four patients underwent enucleation after GKRS. Indications for enucleation were retinoblastoma recurrence (n=2) and vitreous hemorrhage with total retinal detachment (n=2). 13 eyes were salvaged with no signs of keratopathy, uveitis or damage of orbital and surrounding tissues during mean follow-up 30.6 months (range, 7–60 months). Сomplications of different severity occurred in 13 patients, including vitreous hemorrhage in 6 patients, which was successfully treated both conservative (n=3) and using pars plana vitrectomy with simultaneous melphalan irrigation (n=3). Conclusion. The first experience of GKRS as an alternative to enucleation in patients with RB was proved to be reasonable and successful. Key words: retinoblastoma, gamma-knife, stereotactic radiosurgery.

Simple Summary Currently survival from retinoblastoma exceeds 95% in high-income/resource countries. Life expectancy within the heritable retinoblastoma population is mainly threatened by trilateral retinoblastoma in early childhood and subsequent malignant neoplasms throughout life. In this review the risks of specific subsequent malignant neoplasms and trilateral Rb, age at onset and influence of therapy are examined. Furthermore, long-term surveillance guidelines in the heritable retinoblastoma survivors are discussed. Abstract Retinoblastoma (Rb) is a pediatric malignant eye tumor. Subsequent malignant neoplasms (SMNs) and trilateral Rb (TRb) are the leading cause of death in heritable Rb patients in developed countries. The high rate of SMNs in heritable Rb patients is attributed to the presence of a mutation in the RB1 tumor suppressor gene. In addition, Rb therapy choices also influence SMN incidence in this patient group. The incidence rates and age of occurrence for the most frequent SMNs and TRb will be discussed. In addition, the impact of genetic predisposition and Rb treatments on the development of SMNs will be evaluated. Furthermore, screening and other prevention methods will be reviewed.

Zain Hussain Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USACorrespondence: Zain Hussain Email zain.hussain@ttuhsc.eduBackground: Retinoblastoma is an intraocular cancer with potentially severe clinical consequences if left untreated. Diagnostic and clinical management guidelines are strictly dependent on nature of laterality. This analysis aims to characterize the influence of laterality on survival in patients diagnosed with retinoblastoma.Methods: This retrospective cohort analysis utilized the Surveillance, Epidemiology, and End Results (SEER) program for population-based clinical data from 1975 to 2016, a period of 41 years. Univariable and multivariable Cox regression assessed survival with laterality as the primary independent predictor of mortality. Adjustment for demographical and clinical variables was performed.Results: N = 1925 patients with a valid cause of death classification. Mean±SD age was 2.35± 2.020 years (range 0– 74). At the time of diagnosis, 819 (42.1%) patients were between 0 and 1 year of age, 469 (24.1%) patients were between 1 and 2 years, 350 (18.0%) patients were between 2 and 3 years, 147 (7.6%) patients were between 3 and 4 years, and 68 (3.5%) patients were between 4 and 5 years of age. The hazard of univariable cause-specific death is 55.6% and 52.9% lower for retinoblastoma patients with left-sided origin and right-sided origin as compared to patients with bilateral origin, respectively (HR = 0.444, CI 0.247– 0.800, p = 0.007; HR = 0.471, CI 0.267– 0.832, p = 0.009). After adjusting for confounding variables, the hazard of other-cause death for retinoblastoma patients is significantly less for left-sided origin (HR = 0.364, CI 0.140– 0.946, p = 0.038) and right-sided origin (HR = 0.190, CI 0.066– 0.549, p = 0.002) as compared to patients with retinoblastomas of bilateral origin.Conclusion: Prognostication of survival is significantly influenced by the nature of laterality in retinoblastoma. Unilateral retinoblastomas showcase increased promise for long-term cause-specific and other-cause survival compared to cases of retinoblastoma arising from bilateral origin.Keywords: retinoblastoma, survival, laterality