Vasoproliferative Tumor Secondary to Sarcoidosis-Associated Intermediate Uveitis.

We report the visual and clinical outcomes of a middle-aged woman who presented with exudative retinal detachment (ERD) secondary to a vasoproliferative tumor (VPT) in an eye with sarcoidosis-associated intermediate uveitis. A 55-year-old woman previously diagnosed with sarcoidosis presented with decreased vision in the left eye (LE). Visual acuity in the LE was counting fingers. She had active vitritis, and a peripheral retinal vascular mass was noted in the superotemporal periphery. The mass was associated with ERD involving the posterior pole. The patient was managed with systemic and intravitreal steroids, and cyclosporine was subsequently added as a steroid-sparing agent. Because of recurrence of ERD, the patient underwent pars plana vitrectomy, and cryotherapy and laser photocoagulation were applied to the VPT. Two months postoperatively, visual acuity in the LE improved to 6/10. There was marked regression of the VPT and total resolution of the ERD. In conclusion, we report a favorable visual and clinical outcome in a patient with VPT-associated ERD who responded to a combination of medical therapy and surgical intervention. VPT may lead to different remote complications, so timely diagnosis of these tumors and proper management of their complications is warranted.

Role of apparent diffusion map in the evaluation of retinoblastoma.

PURPOSE: This study aimed to analyze the association between magnetic resonance imaging apparent diffusion coefficient map value and histopathological differentiation in patients who underwent eye enucleation due to retinoblastomas. METHODS: An observational chart review study of patients with retinoblastoma that had histopathology of the lesion and orbit magnetic resonance imaging with apparent diffusion coefficient analysis at Hospital de Clínicas de Porto Alegre between November 2013 and November 2016 was performed. The histopathology was reviewed after enucleation. To analyze the difference in apparent diffusion coefficient values between the two major histopathological prognostic groups, Student's t-test was used for the two groups. All statistical analyses were performed using SPSS version 19.0 for Microsoft Windows (SPSS, Inc., Chicago, IL, USA). Our institutional review board approved this retrospective study without obtaining informed consent. RESULTS: Thirteen children were evaluated, and only eight underwent eye enucleation and were included in the analysis. The others were treated with photocoagulation, embolization, radiotherapy, and chemotherapy and were excluded due to the lack of histopathological results. When compared with histopathology, magnetic resonance imaging demonstrated 100% accuracy in retinoblastoma diagnosis. Optic nerve invasion detection on magnetic resonance imaging showed a 66.6% sensitivity and 80.0% specificity. Positive and negative predictive values were 66.6% and 80.0%, respectively, with an accuracy of 75%. In addition, the mean apparent diffusion coefficient of the eight eyes was 0.615 × 103 mm2/s. The mean apparent diffusion coefficient value of poorly or undifferentiated retinoblastoma and differentiated tumors were 0.520 × 103 mm2/s and 0.774 × 103 mm2/s, respectively. CONCLUSION: This study revealed that magnetic resonance imaging is useful in the diagnosis of retinoblastoma and detection of optic nerve infiltration, with a sensitivity of 66.6% and specificity of 80%. Our results also showed lower apparent diffusion coefficient values in poorly differentiated retinoblastomas with a mean of 0.520 × 103 mm2/s, whereas in well and moderately differentiated, the mean was 0.774 × 103 mm2/s.

Captains on call: A qualitative investigation of an intervention to support children with retinoblastoma undergoing regular eye examinations.

BACKGROUND: Retinoblastoma is a rare childhood ophthalmic cancer that requires frequent eye examinations under anaesthesia and painful or distressing procedures. This can cause significant anxiety for children and their families. OBJECTIVE: We evaluated a Starlight Children's Foundation programme, 'Captains on Call', at the Queensland Children's Hospital, which aims to provide positive distraction and reduce stress, anxiety and pain during the perioperative journey for children in the retinoblastoma treatment pathway. This study examined the impact of the programme on the perioperative experience of the children and their families, using a qualitative design. METHODS: This study was conducted in a paediatric operating suite at a tertiary-level children's hospital in Australia. We interviewed a parent from 20 families (from a cohort of 40 families, including 44 children), whose children received treatment or screening for retinoblastoma, focusing on the programme's impact on the child and family at various stages during the perioperative journey. We undertook a thematic analysis of transcribed interviews. RESULTS: We identified two themes, each with two sub-themes: (1) the programme positively contributed to the overall treatment journey, by addressing different needs at different times, and helping to reframe a traumatic medical experience, and (2), the programme supported the whole family unit by empowering children through play, and adopting a family systems approach which recognised the impact of cancer treatment on the whole family. CONCLUSION: This study highlights the value of the Captains on Call programme in supporting children with retinoblastoma and their families during perioperative visits. The Captains, particularly as non-medicalised professionals in a healthcare setting, built trust and rapport with the children through play over repeated episodes of care. The interprofessional collaborative approach with a reflective cycle of practice extended it beyond a programme providing simple distraction. Other retinoblastoma services may benefit from implementing a similar approach.

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics.

Retinoblastoma (RB) is an aggressive tumor of the infant retina. However, the ineffective targeting of its theranostic agents results in poor imaging and therapeutic efficacy, which makes it difficult to identify and treat RB at an early stage. In order to improve the imaging and therapeutic efficacy, we constructed an RB-targeted artificial vesicle composite nanoparticle. In this study, the MnO2 nanosponge (hMNs) was used as the core to absorb two fluorophore-modified DNAzymes to form the Dual/hMNs nanoparticle; after loaded with the artificial vesicle derived from human red blood cells, the RB-targeted DNA aptamers were modified on the surface, thus forming the Apt-EG@Dual/hMNs complex nanoparticle. The DNA aptamer endows this nanoparticle to target the nucleolin-overexpressed RB cell membrane specifically and enters cells via endocytosis. The nanoparticle could release fluorophore-modified DNAzymes and supplies Mn2+ as a DNAzyme cofactor and a magnetic resonance imaging (MRI) agent. Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

INTRODUCTION: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. METHOD: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. RESULTS: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. CONCLUSIONS: Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Global retinoblastoma studies: A review.

In the current era of global health awareness for retinoblastoma (RB), the challenge that lies ahead of us is providing optimal care for children affected with RB in underdeveloped nations. The understanding of similarities and disparities between various nations across the world aids in achieving comparable outcomes. With dissolving geographic barriers and evolving collaboration, global collaborative studies on RB are becoming increasingly common. They provide real-world, robust evidence on several aspects of RB. This review discusses insights gained from global RB studies regarding the demographics, certain aspects of etiopathogenesis and epidemiology, international travel burden, disparities in clinical presentations based on national income levels, management protocols, pathology, treatment outcomes, and the effect of COVID-19 on RB care across the world. These insights are likely to impact individual practice as well as inform policy reforms.

Association of Neighborhood Opportunity With Severity of Retinoblastoma at Presentation.

PURPOSE: To examine the relationship between the Child Opportunity Index (COI) and severity of retinoblastoma at presentation. DESIGN: Cross-sectional study. METHODS: Children (age <18 years) treated for retinoblastoma at a tertiary care center between January 2000 and May 2023 were included. Residential census tract was used to determine the overall and domain-specific COI score for each child. Collected variables included age, sex, race/ethnicity, insurance type, and the International Classification of Retinoblastoma (ICRB) Group at initial examination. The primary outcome was Group D or E retinoblastoma at presentation. Mixed effects regression models were used to estimate the association of COI scores with disease severity at presentation. RESULTS: This study included 125 children (51.2% male). Median age at diagnosis was 13 months (IQR, 5-24 months). One hundred nine (87.2%) children presented with Group D or E retinoblastoma and 33 (26.4%) resided in low or very low opportunity neighborhoods. Children residing in neighborhoods with low overall COI scores (OR, 1.62; 95% CI, 1.01-2.58; P = .044) and low education COI scores (OR, 1.77; 95% CI, 1.13-2.79; P = .013) were at increased odds of presenting with ICRB Group D or E retinoblastoma after adjusting for individual-level socioeconomic factors. CONCLUSION: Children residing in low opportunity neighborhoods-particularly low education opportunity-more often presented with advanced stage retinoblastoma than children residing in neighborhoods with higher opportunity scores. Efforts to improve preventative vision care and access to eye specialty care for children residing in low-resource areas are needed to reduce existing disparities in retinoblastoma.

Familial retinoblastoma: variations in clinical presentation and management based on paternal versus maternal inheritance.

BACKGROUND: Several studies have demonstrated the effect of parent-of-origin on retinoblastoma penetrance. The purpose of the current study was to assess differences in clinical presentation of paternally versus maternally inherited retinoblastoma. METHODS: The clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. RESULTS: A total of 179 patients with familial retinoblastoma were included. Paternal inheritance (PI) was identified in 109 (61%) patients and maternal inheritance (MI) in 70 patients (39%). A comparison (PI vs MI) revealed PI patients were older at presentation (57.2 vs 24.4 months [P = 0.002]) with no difference in patient sex (53% females vs 57% males [P = 0.606]) or number of family members affected (3.2 vs 3.0 family members [P = 0.255]). PI patients had more advanced classification according to the International Classification of Retinoblastoma (ICRB) (group E: 31% vs 8% [P = 0.012)] and greater largest tumor in basal diameter (9.0 vs 6.2 mm [P = 0.040]) and thickness (5.6 vs 4.0 mm [P = 0.038]); they were also less likely to be located in the macula (40% vs 60% [P = 0.004]). There was no difference in tumor laterality (69% vs 64% bilaterality [P = 0.530]). PI patients required enucleation more frequently (34% vs 14% [P = 0.007]). There was no difference in need for plaque radiotherapy (P = 0.86) or chemotherapy (P = 0.85). One PI patient developed metastatic retinoblastoma, and there were no retinoblastoma-related deaths. CONCLUSIONS: Patients with paternally inherited retinoblastoma presented at an older age, with larger, more peripheral tumors and more advanced ICRB group, and were more likely to require enucleation compared to those with maternally inherited retinoblastoma.

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma.

Retinoblastoma (RB) is a rare malignant tumor that arises in the developing retina in one or both eyes of children. Pathogenic variants of the RB1 tumor suppressor gene drive the majority of germline and sporadic RB tumors. Considering the risk of tumor spread, the biopsy of RB tumor tissue is contraindicated. Advancement of chemotherapy has led to preservation of more eye globes. However, this has reduced access to tumor material from enucleation specimens. Recently, liquid biopsy of aqueous humor (AH) has advanced the RB tumor- or eye-specific genetic analysis. In particular, nucleic acid analysis of AH demonstrates the genomic copy number profiles and RB1 pathogenic variants akin to that of enucleated RB eye tissue. This advance reduces the previous limitation that genetic assessment of the primary tumor could be done only after enucleation of the eye. Additionally, nucleic acid evaluation of AH allows the exploration of the genomic landscape of RB tumors at diagnosis and during and after treatment. This review explores how AH sampling and AH nucleic acid analysis in RB patients assist in diagnosis, prognosis, and comprehending the pathophysiology of RB, which will ultimately benefit individualized treatment decisions to carefully manage this ocular cancer in children.

Presentation, Diagnostic Testing and Initial Treatment of Vitreoretinal Lymphoma.

PURPOSE: Vitreoretinal lymphoma is a malignancy with high mortality. Incidence is rare, and there is a lack of medical evidence to direct management. This work describes presentation, diagnostic testing, and first treatment approaches in a recently diagnosed and treated patient cohort. DESIGN: Clinical registry-based observational study. SUBJECTS: Forty-eight women and 32 men (age range, 32-91 years; median age, 64 years) diagnosed with vitreoretinal lymphoma. METHODS: An international network of ophthalmologists reported clinical features and management of patients presenting with vitreoretinal lymphoma between January 1, 2020 and December 31, 2022 via an electronic platform. MAIN OUTCOME MEASURES: Visual acuity at presentation (logarithm of the minimum angle of resolution [logMAR]); basis for diagnosis; first treatment. RESULTS: Vitreoretinal lymphoma was bilateral at presentation in 65% of patients (n = 52) and an initial site of lymphoma in 78% (n = 62). Of 127 eyes with lymphoma at presentation, vitreous was involved in 89% (n = 113) and was the only involved eye tissue in 40% (n = 51), and retina was involved in 46% (n = 59) and was the only involved eye tissue in 9% (n = 11). Median logMAR visual acuity of the worse-seeing eye was 0.50. The lymphoma was diagnosed from ocular specimens in 80% of patients (64/80), usually vitreous (57/64 patients [89%]), and on other clinical information in 20% of patients (16/80). Cellular studies were performed on ocular specimens from 59 of 64 patients (92%), most often cytology. Tumor gene analysis was used in 21 of 64 patients (33%), and cytokine assays were used in 13 of 64 patients (20%). For 76 patients (95%), treatment was initiated within 6 months of diagnosis and included ocular (38/76 [48%]), extraocular (17/76 [21%]), and ocular plus extraocular (21/76 [26%]) approaches. Intravitreal methotrexate was the most common ocular treatment (83/87 eyes [95%]). CONCLUSIONS: Using data collected from 80 patients diagnosed with vitreoretinal lymphoma since 2020, we show that visual impairment is common, and that management often involves diagnosis by cellular tests and treatment with intravitreal chemotherapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PATIENT-RELATED FACTORS AND CLINICAL MANAGEMENT OUTCOMES OF RETINOBLASTOMA IN CALABAR, NIGERIA.

Background: Retinoblastoma is curable in industrialized countries. However, it is associated with mortality in resource-poor nations due to disparities and poor access to eye care. Aim was to determine the relationships between patient-related factors and clinical outcomes of Retinoblastoma management in a tertiary hospital in Nigeria. Materials and methods: This was a retrospective study of all children who were diagnosed and treated for Retinoblastoma from January 2017 through December 2022. Information obtained from their records included biosocioeconomic data, symptoms, lag time from initial symptoms, staging, treatment and outcome (dead or alive). Results: Fifty-three patients, aged 6 to 88 months on first hospital presentation were recruited. There were 29(54.7%) females and 20(37.7%) patients died. Parental low socioeconomic class, rural residence and poor nutrition occurred more in those that survived, though not significantly (p>0.05). Median(interquartile) age at diagnosis [24(18-36) months, p=0.005] and lag time [13(6-20) months, p=0.274] were low in the survived group. Bilateral Retinoblastoma (20.8%,p=0.002), brain metastasis (22.6%,p<0.001), IRSS IV (18.9%,p=0.01) and relapse (34%,p<0.001) occurred more among the patients that died. The overall survival (OS) was 22(11.77-32.23) months with 1-year OS of 63%. Treatment with only chemotherapy [HR 4.76(95%CI:1.726-13.128)], incomplete chemotherapy [HR 5.61(95%CI:1.271-24.741)], relapse [HR 5.98(95%CI:1.376-25.983)] and eye surgery after 3 chemotherapy cycles [HR 8.22(95%CI:1.087-62.239)] were predictors of mortality. Conclusion: Early presentation of retinoblastoma especially of advanced and bilateral disease may lead to improved survival if chemotherapy and eye surgery are appropriately performed. Routine screening and immediate referral of retinoblastoma particularly in rural areas are recommended.

The Use of rAAV2-RB1-Mediated Gene Therapy in Retinoblastoma.

Purpose: Retinoblastoma (RB) is a life-threatening malignancy that arises from the retina and is activated upon homozygous inactivation of the tumor suppressor RB1. Gene therapy targeting RB1 is an effective strategy to treat RB. However, it is difficult to target the RB1 gene by site-specific repair, with up to 3366 gene mutation sites identified in RB1. Thus, it is necessary to construct a promising and efficacious gene therapeutic strategy for patients with RB. Methods: To recover the function of the RB1 protein, we constructed a recombinant adeno-associated virus 2 (rAAV2) expressing RB1 that can restore RB1 function and significantly inhibit RB progression. To confirm the clinical feasibility of rAAV2-RB1, the RB1 protein was validated in vitro and in vivo after transfection. To further evaluate the clinical efficacy, RB patient-derived xenograft models were established and applied. The biosafety of rAAV2-RB1 was also validated in immunocompetent mice. Results: rAAV2-RB1 was a rAAV2 expressing the RB1 protein, which was validated in vitro and in vivo. In vitro, rAAV2-RB1 was effectively expressed in patient-derived RB cells. In mice, intravitreal administration of rAAV2-RB1 in a population-based patient-derived xenograft trial induced limited tumor growth. Moreover, after transfection of rAAV2-RB1 in immunocompetent mice, rAAV2-RB1 did not replicate and was expressed in other important organs, except retinas, inducing minor local side effects. Conclusions: Our study suggested a promising efficacy gene therapeutic strategy, which might provide a chemotherapy-independent treatment option for RB.

Clinical Patterns And Outcomes Of Retinoblastoma In A Tertiary Care Centre Of A Developing Country.

A retrospective study was conducted for which records of patients with Retinoblastoma (RB), treated at Lahore General Hospital between 2017 and 2021, were retrieved on February 1, 2022. Staging of RB, neuroimaging, RetCam images, and treatment were analysed. The study included 47 patients (22 females and 25 males). Mean age of presentation was 26.5±15 months. Records of 84 eyes (37 bilateral and 10 unilateral) were examined. Family history was positive in only (n=3) 6.3% cases. Mean follow-up was 22.94±14.4 months. Leucocoria was the commonest presentation, seen in 72 (85.7%) eyes, proptosis in 8 (9.5%), huge fungating mass in 2 (2.4%), while tumour was diagnosed because of screening in 2 (2.4%) patients. Posttreatment complications included cataract in two patients, Ischaemic chorioretinal toxicity, transient macular oedema, orbital oedema and transient intra cranial oedema in one patient each. Two patients had metastasis and underwent systemic chemotherapy. The study showed that patients with retinoblastoma can achieve better results if diagnosed early and treated with newer treatment options.

Retinoblastoma: present scenario and future challenges.

With an average incidence of 1 in every 18,000 live births, retinoblastoma is a rare type of intraocular tumour found to affect patients during their early childhood. It is curable if diagnosed at earlier stages but can become life-threateningly malignant if not treated timely. With no racial or gender predisposition, or even environmental factors known to have been involved in the incidence of the disease, retinoblastoma is often considered a clinical success story in pediatric oncology. The survival rate in highly developed countries is higher than 95% and they have achieved this because of the advancement in the development of diagnostics and treatment techniques. This includes developing the already existing techniques like chemotherapy and embarking on new strategies like enucleation, thermotherapy, cryotherapy, etc. Early diagnosis, studies on the etiopathogenesis and genetics of the disease are the need of the hour for improving the survival rates. According to the Knudson hypothesis, also known as the two hit hypothesis, two hits on the retinoblastoma susceptibility (RB) gene is often considered as the initiating event in the development of the disease. Studies on the molecular basis of the disease have also led to deciphering the downstream events and thus in the discovery of biomarkers and related targeted therapies. Furthermore, improvements in molecular biology techniques enhanced the development of efficient methods for early diagnosis, genetic counseling, and prevention of the disease. In this review, we discuss the genetic and molecular features of retinoblastoma with a special emphasis on the mutation leading to the dysregulation of key signaling pathways involved in cell proliferation, DNA repair, and cellular plasticity. Also, we describe the classification, clinical and epidemiological relevance of the disease, with an emphasis on both the traditional and innovative treatments to tackle retinoblastoma. Video Abstract.

PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.

PURPOSE: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. METHODS: Observational case report. RESULTS: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. CONCLUSION: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

The functional role of circular RNAs in the pathogenesis of retinoblastoma: a new potential biomarker and therapeutic target?

Retinoblastoma (RB) is a common cancer in infants and children. It is a curable disease; however, a delayed diagnosis or treatment makes the treatment difficult. Genetic mutations have a central role in the pathogenesis of RB. Genetic materials such as RNAs (coding and non-coding RNAs) are also involved in the progression of the tumor. Circular RNA (circRNA) is the most recently identified RNA and is involved in regulating gene expression mainly through “microRNA sponges”. The dysregulation of circRNAs has been observed in several diseases and tumors. Also, various studies have shown that circRNAs expression is changed in RB tissues. Due to their role in the pathogenesis of the disease, circRNAs might be helpful as a diagnostic or prognostic biomarker in patients with RB. In addition, circRNAs could be a suitable therapeutic target to treat RB in a targeted therapy approach (AU)