ABSTRACT
PURPOSE: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). METHODS: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol - light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. RESULTS: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. CONCLUSION: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury.
Subject(s)
Electroretinography , Retinal Neoplasms , Retinoblastoma , Humans , Retinoblastoma/drug therapy , Retinoblastoma/physiopathology , Retinoblastoma/diagnosis , Electroretinography/methods , Retinal Neoplasms/drug therapy , Retinal Neoplasms/physiopathology , Retinal Neoplasms/diagnosis , Male , Female , Child, Preschool , Infant , Retina/physiopathology , Antineoplastic Combined Chemotherapy Protocols , Child , Vincristine/therapeutic use , Vincristine/administration & dosage , Follow-Up Studies , Antineoplastic Agents/administration & dosageABSTRACT
Purpose: Current melphalan-based regimens for intravitreal chemotherapy for retinoblastoma vitreous seeds are effective but toxic to the retina. Thus, alternative agents are needed. Based on the known biology of histone deacetylases (HDACs) in the retinoblastoma pathway, we systematically studied whether the HDAC inhibitor belinostat is a viable, molecularly targeted alternative agent for intravitreal delivery that might provide comparable efficacy, without toxicity. Methods: In vivo pharmacokinetic experiments in rabbits and in vitro cytotoxicity experiments were performed to determine the 90% inhibitory concentration (IC90). Functional toxicity by electroretinography and structural toxicity by optical coherence tomography (OCT), OCT angiography, and histopathology were evaluated in rabbits following three injections of belinostat 350 µg (2× IC90) or 700 µg (4× IC90), compared with melphalan 12.5 µg (rabbit equivalent of the human dose). The relative efficacy of intravitreal belinostat versus melphalan to treat WERI-Rb1 human cell xenografts in rabbit eyes was directly quantified. RNA sequencing was used to assess belinostat-induced changes in RB cell gene expression. Results: The maximum nontoxic dose of belinostat was 350 µg, which caused no reductions in electroretinography parameters, retinal microvascular loss on OCT angiography, or retinal degeneration. Melphalan caused severe retinal structural and functional toxicity. Belinostat 350 µg (equivalent to 700 µg in the larger human eye) was equally effective at eradicating vitreous seeds in the rabbit xenograft model compared with melphalan (95.5% reduction for belinostat, P < 0.001; 89.4% reduction for melphalan, P < 0.001; belinostat vs. melphalan, P = 0.10). Even 700 µg belinostat (equivalent to 1400 µg in humans) caused only minimal toxicity. Widespread changes in gene expression resulted. Conclusions: Molecularly targeted inhibition of HDACs with intravitreal belinostat was equally effective as standard-of-care melphalan but without retinal toxicity. Belinostat may therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma.
Subject(s)
Disease Models, Animal , Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/therapeutic use , Neoplasm Seeding , Retina/drug effects , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy , Sulfonamides/therapeutic use , Animals , Annexin A5 , Antineoplastic Agents, Alkylating/therapeutic use , Electroretinography , Fluorescein Angiography , Histone Deacetylase Inhibitors/pharmacokinetics , Histone Deacetylase Inhibitors/toxicity , Hydroxamic Acids/pharmacokinetics , Hydroxamic Acids/toxicity , Intravitreal Injections , Maximum Tolerated Dose , Melphalan/therapeutic use , Rabbits , Retina/physiology , Retinal Neoplasms/diagnosis , Retinal Neoplasms/physiopathology , Retinoblastoma/diagnosis , Retinoblastoma/physiopathology , Retrospective Studies , Sulfonamides/pharmacokinetics , Sulfonamides/toxicity , Tomography, Optical Coherence , Vitreous Body/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Inactivation of RB is one of the hallmarks of cancer, however gaps remain in our understanding of how RB-loss changes human cells. Here we show that pRB-depletion results in cellular reprogramming, we quantitatively measured how RB-depletion altered the transcriptional, proteomic and metabolic output of non-tumorigenic RPE1 human cells. These profiles identified widespread changes in metabolic and cell stress response factors previously linked to E2F function. In addition, we find a number of additional pathways that are sensitive to RB-depletion that are not E2F-regulated that may represent compensatory mechanisms to support the growth of RB-depleted cells. To determine whether these molecular changes are also present in RB1-/- tumors, we compared these results to Retinoblastoma and Small Cell Lung Cancer data, and identified widespread conservation of alterations found in RPE1 cells. To define which of these changes contribute to the growth of cells with de-regulated E2F activity, we assayed how inhibiting or depleting these proteins affected the growth of RB1-/- cells and of Drosophila E2f1-RNAi models in vivo. From this analysis, we identify key metabolic pathways that are essential for the growth of pRB-deleted human cells.
Subject(s)
Retinal Neoplasms/physiopathology , Retinoblastoma Binding Proteins/genetics , Retinoblastoma/physiopathology , Ubiquitin-Protein Ligases/genetics , Animals , Cell Line, Tumor , Humans , Mice , Retinoblastoma Binding Proteins/metabolism , Ubiquitin-Protein Ligases/metabolismABSTRACT
Primary vitreoretinal lymphoma (PVRL) is a rare form of primary central nervous system (CNS) lymphoma (PCNSL) arising in the intraocular compartment without brain involvement. Despite its apparent indolent clinical course, PVRL can cause permanent vision loss and CNS relapse, the major cause of death in patients with PVRL. The pathophysiology of PVRL is unknown. As in PCNSL, the transformation of the tumor cells likely originates outside the CNS, before the cells migrate to the eye and proliferate within an immune-permissive microenvironment. PVRL exhibits a biased immunoglobulin repertoire, suggesting underlying antigen selection. The diagnosis remains challenging, requiring close coordination between ophthalmologists and cytologists. Because of their rarity and fragility in the vitreous, lymphoma cells cannot always be identified. Interleukin levels, molecular biology, and imaging are used in combination with clinical ophthalmological examination to support the diagnosis of PVRL. Multi-institutional prospective studies are urgently needed to validate the equivocal conclusions regarding treatments drawn from heterogeneous retrospective or small cohort studies. Intravitreal injection of methotrexate or rituximab or local radiotherapy is effective at clearing tumor cells within the eyes but does not prevent CNS relapse. Systemic treatment based on high-dose methotrexate chemotherapy, with or without local treatment, might reduce this risk. At relapse, intensive consolidation chemotherapy followed by stem cell transplantation can be considered. Single-agent ibrutinib, lenalidomide, and temozolomide treatments are effective in patients with relapsed PVRL and should be tested as first-line treatments. Therapeutic response assessment based on clinical examination is improved by measuring cytokine levels but still needs to be refined.
Subject(s)
Retina/pathology , Retinal Neoplasms/diagnosis , Vitreous Body/pathology , Animals , Disease Management , Humans , Retina/physiopathology , Retinal Neoplasms/pathology , Retinal Neoplasms/physiopathology , Retinal Neoplasms/therapy , Vitreous Body/physiopathologyABSTRACT
Purpose: Circular RNAs (circRNAs) are essential regulators in tumorigenesis and development. In this study, we focused on the functions of circRNA muskelin 1 (circMKLN1) in retinoblastoma (RB) progression.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the levels of circMKLN1, microRNA-425-5p (miR-425-5p) and programmed cell death 4 (PDCD4). The characteristic of circMKLN1 was analyzed using RNase R assay. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed to explore cell proliferation ability. The transwell assay was utilized for cell migration and invasion. A Western blot assay was performed for protein levels. The dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to demonstrate the relationships among circMKLN1, miR-425-5p and PDCD4. Murine xenograft model assay was adopted to investigate the role of circMKLN1 in vivo.Results: CircMKLN1 was downregulated in RB tissues and cells. High levels of circMKLN1 were related to a favorable outcome of RB patients. CircMKLN1 was resistant to RNase R digestion and circMKLN1 overexpression repressed RB cell proliferation, migration and invasion in vitro. MiR-425-5p was identified as the target of circMKLN1 and miR-425-5p elevation reversed the effects of circMKLN1 overexpression on RB cell malignant behaviors. Furthermore, as the target gene of miR-425-5p, PDCD4 silencing could ameliorate the suppressive roles of circMKLN1 in RB cell growth and metastasis. Additionally, circMKLN1 overexpression hampered tumor growth in vivo.Conclusions: CircMKLN1 overexpression decelerated the progression of RB through sponging miR-425-5p and elevating PDCD4.
Subject(s)
Apoptosis Regulatory Proteins/genetics , Cell Adhesion Molecules/physiology , Gene Expression Regulation, Neoplastic/physiology , Intracellular Signaling Peptides and Proteins/physiology , MicroRNAs/genetics , RNA, Circular/physiology , RNA-Binding Proteins/genetics , Retinal Neoplasms/physiopathology , Retinoblastoma/physiopathology , Animals , Blotting, Western , Cell Count , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colony-Forming Units Assay , Disease Progression , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Real-Time Polymerase Chain Reaction , Retinal Neoplasms/genetics , Retinoblastoma/genetics , Transfection , Xenograft Model Antitumor AssaysABSTRACT
AIMS: To investigate the association of peripheral retinal non-perfusion with retinal haemangioblastoma. METHODS: Medical and widefield fluorescein angiography records of patients diagnosed with retinal haemangioblastoma from 1990 to 2018 were reviewed for patient demographics, tumour features, fluorescein angiography features and characteristics of peripheral retinal non-perfusion. RESULTS: There were 41 eyes of 40 patients with retinal haemangioblastoma imaged by widefield fluorescein angiography during this time period. Of 41 eyes, 14 (34%) had haemangioblastoma-associated peripheral retinal non-perfusion on fluorescein angiography. A comparison of eyes with versus without non-perfusion revealed younger mean age at presentation (28 vs 43 years old, p=0.05), increased prevalence of von Hippel-Lindau (VHL) disease (62% vs 22%, p=0.01), greater mean largest tumour basal diameter (3.7 vs 2.5 mm, p=0.04), greater tumour distance from optic nerve (8.4 vs 1.9 mm, p<0.01) and increased prevalence of vascular leakage from the tumour (86% vs 52%, p=0.03). After mean follow-up of 97 versus 71 months (p=0.52), eyes with non-perfusion were significantly more likely to develop neovascularisation (40% vs 0%, p<0.01) and experience a three-line or greater decrease in visual acuity (60% vs 11%, p<0.01). CONCLUSION: Peripheral retinal non-perfusion can be associated with retinal haemangioblastoma, and could be more common with larger, more peripheral tumours in younger patients with VHL disease. Eyes with haemangioblastoma-associated peripheral non-perfusion could be more likely to develop neovascularisation and lose visual acuity.
Subject(s)
Hemangioblastoma/pathology , Retina/pathology , Retinal Neoplasms/pathology , Retinal Vessels/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Fluorescein Angiography/methods , Hemangioblastoma/physiopathology , Humans , Infant , Male , Middle Aged , Retinal Neoplasms/physiopathology , Visual Acuity/physiology , Young AdultABSTRACT
IMPORTANCE: Retinoblastoma is a life- and sight-threatening malignancy. BACKGROUND: To assess the relationship between tumour perfusion and intra-arterial chemotherapy (IAC) requirements to achieve retinoblastoma control. DESIGN: Retrospective case series at the Ocular Oncology Service of Wills Eye Hospital (Philadelphia, Pennsylvania). PARTICIPANTS: Fifty-nine eyes of 55 patients. METHODS: Review of medical and fluorescein angiography (FA) records for retinoblastoma treated with primary or secondary IAC from 2012 to 2017. Vascular supply of the main tumour was evaluated in the pre-treatment FA. MAIN OUTCOME MEASURES: Tumour fluorescence was classified as partial <67% or complete tumour perfusion >67%. Partially vs completely perfused tumours were compared for IAC cycle requirements. RESULTS: There were 59 eyes of 55 patients with pre-treatment FA managed with IAC. Partially perfused tumours (n = 20, 34%) required fewer IAC infusions than completely perfused tumours (n = 39, 66%) (2.5 vs 3.7 infusions, P = .02), even after adjustment for confounding factors (tumour diameter, thickness and drug scheme, adjusted P = .04). Tumour perfusion correlated with number of IAC cycles required for tumour control (r = 0.46, P < .001). For primary IAC (n = 18, 31%), tumour perfusion was not associated with number of IAC cycles (P = .63). For secondary IAC (n = 41, 69%), partially perfused tumours (n = 15, 37%) required fewer IAC infusions than completely perfused tumours (n = 26, 63%) (2.1 vs 3.7 infusions, P < .01). CONCLUSIONS AND RELEVANCE: FA demonstrating partial retinoblastoma tumour perfusion is associated with fewer IAC cycle requirements for secondary but not primary IAC. FA might be useful in judging anticipated treatment cycles of retinoblastoma managed with primary or secondary IAC.
Subject(s)
Antineoplastic Agents/administration & dosage , Regional Blood Flow/physiology , Retinal Neoplasms/diagnosis , Retinal Vessels/physiopathology , Retinoblastoma/diagnosis , Child , Child, Preschool , Female , Fluorescein Angiography/methods , Fundus Oculi , Humans , Infant , Infusions, Intra-Arterial , Male , Retinal Neoplasms/drug therapy , Retinal Neoplasms/physiopathology , Retinal Vessels/diagnostic imaging , Retinoblastoma/drug therapy , Retinoblastoma/physiopathology , Retrospective StudiesABSTRACT
PURPOSE: To investigate outcomes in vitreoretinal lymphoma (VRL) presenting with or without sub-retinal pigment epithelial (sub-RPE) infiltration. DESIGN: Retrospective, comparative analysis. SUBJECTS: Patients with VRL at a single center from January 1, 1984, through July 30, 2018. METHODS: Record review was conducted for clinical features, treatments, and outcomes of tumor control, visual acuity (VA), and death. MAIN OUTCOME MEASURES: Ocular tumor control and VA outcome. RESULTS: The study involved 168 eyes of 95 patients with VRL, of which 45 (27%) eyes of 32 patients had sub-RPE infiltration. Comparison (of patients with vs. without sub-RPE infiltration) showed similar presenting features of mean patient age (65 vs. 68 years, P = 0.30), percentage of males (53% vs. 56%, P = 0.83), white race (84% vs. 87%, P = 0.77), bilateral ocular involvement (78% vs. 75%, P = 0.80), and VA of 20/40 or better (40% vs. 50%, P = 0.30), 20/50 to 20/200 (42% vs. 31%, P = 0.20), or worse than 20/200 (18% vs. 19%, P = 0.99). Lymphoma subtype was diffuse large B cell (59% vs. 52%) or unspecified (41% vs. 44%, P = 0.85). Follow-up data were available for 125 eyes of 70 patients. Overall treatment included systemic chemotherapy (53% vs. 64%, P = 0.29), intravitreal chemotherapy (59% vs. 28%, P = 0.005), and external beam radiotherapy (59% vs. 94%, P < 0.001). Initial ocular tumor control occurred (91% vs. 94%, P = 0.68) with subsequent recurrence (35% vs. 17%, P = 0.07). Outcomes at final follow-up (mean 24 vs. 25 months, P = 0.82) revealed ocular tumor complete regression (68% vs. 86%, P = 0.03), partial regression (3% vs. 7%, P = 0.44), or active persistent or recurrent disease (29% vs. 7%, P = 0.002). Final VA was 20/40 or better (39% vs. 53%, P = 0.18), 20/50 to 20/200 (26% vs. 34%, P = 0.53), or worse than 20/200 (34% vs. 13%, P = 0.007). Vitreoretinal lymphoma was associated with central nervous system lymphoma (41% vs. 59%, P = 0.13) or systemic lymphoma (16% vs. 21%, P = 0.60). Death occurred (63% vs. 54%, P = 0.51) at mean age (69 vs. 69 years, P = 0.94). CONCLUSION: Sub-RPE infiltration in VRL is associated with more persistent or recurrent ocular tumor and poorer VA outcome, but no difference in frequency of central nervous system/systemic lymphoma or death. Further studies are required to determine whether earlier, more aggressive, or prolonged ocular therapy for patients with VRL presenting with sub-RPE infiltration could improve these factors.
Subject(s)
Eye Neoplasms/therapy , Intraocular Lymphoma/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Retinal Neoplasms/therapy , Retinal Pigment Epithelium/pathology , Visual Acuity/physiology , Vitreous Body/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Eye Neoplasms/drug therapy , Eye Neoplasms/physiopathology , Eye Neoplasms/radiotherapy , Female , Humans , Intraocular Lymphoma/drug therapy , Intraocular Lymphoma/physiopathology , Intraocular Lymphoma/radiotherapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/physiopathology , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Male , Medical Oncology , Middle Aged , Neoplasm Invasiveness , Radiotherapy , Retinal Neoplasms/drug therapy , Retinal Neoplasms/physiopathology , Retinal Neoplasms/radiotherapy , Retrospective StudiesSubject(s)
Intraocular Pressure/physiology , Neoplasm Staging , Retinal Neoplasms/pathology , Retinoblastoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Eye Enucleation , Female , Follow-Up Studies , Humans , Infant , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retinal Neoplasms/physiopathology , Retinal Neoplasms/surgery , Retinoblastoma/physiopathology , Retinoblastoma/surgery , Retrospective Studies , Risk Factors , Young AdultABSTRACT
BACKGROUND/AIM: To report the outcomes of retinoblastoma group E eyes with neovascular glaucoma (NVG) treated conservatively with intravenous chemotherapy and investigate factors associated with eye salvage and secondary enucleation. METHODS: This is a retrospective, comparative, interventional case series. The outcome measures were life salvage, eye salvage and vision salvage. RESULTS: Of the 37 eyes managed by intravenous chemotherapy, secondary enucleation was necessary in 21 eyes (group 1) and eye salvage was possible in 16 eyes (group 2). A comparison of both groups revealed significant difference with group 1 demonstrating greater duration of symptoms (18.8 weeks vs 5.4 weeks, p=0.016), greater intraocular pressure (IOP) at presentation (36 mm Hg vs 30 mm Hg, p=0.044), greater increase in corneal diameter (1.52 mm vs 0.50 mm, p=0.013) and the presence of sterile orbital cellulitis (9 vs 1, p=0.023). Further, the risk factors for secondary enucleation by univariate analysis were duration of symptoms >10 weeks (p=0.003), presenting IOP >26 mm Hg (p=0.045), buphthalmos (p=0.014) and sterile orbital cellulitis (p=0.023) and by multivariate analysis were age at presentation >6 months (p=0.012) and buphthalmos (p=0.017). At a mean follow-up of 20.5 months, none of the patients in either group developed systemic metastasis. CONCLUSION: For retinoblastoma group E eyes presenting with NVG, the chance of eye salvage with intravenous chemotherapy is better when the age at diagnosis is <6 months, duration of symptoms is <10 weeks, IOP is <26 mm Hg, and in the absence buphthalmos and sterile orbital inflammation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Glaucoma, Neovascular/drug therapy , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy , Age Factors , Carboplatin/therapeutic use , Child, Preschool , Etoposide/therapeutic use , Eye Enucleation , Female , Follow-Up Studies , Glaucoma, Neovascular/physiopathology , Humans , Infant , Infusions, Intravenous , Intraocular Pressure/physiology , Male , Retinal Neoplasms/physiopathology , Retinoblastoma/physiopathology , Retrospective Studies , Risk Factors , Salvage Therapy , Treatment Outcome , Vincristine/therapeutic use , Visual Acuity/physiologyABSTRACT
BACKGROUND: Monocular vision has been found to have a negative effect on children's motion processing and motor functions. Yet, knowledge of motor function of survivors of retinoblastoma (RB) with monocular vision (due to enucleation, for example) is limited. This study examined motor function and its relationship to visual-related and health-related quality of life (HRQOL) in survivors of RB with monocular vision. PROCEDURE: Parents of 27 survivors of RB, who underwent an enucleation of one eye resulting in monocular vision, and of 21 typically developing children between the ages of 6 and 12, were administered questionnaires relating to their children's motor function (DCDQ), as well as vision-related function (CVFQ) and HRQOL (PedsQL). RESULTS: Of the 27 survivors of RB, 7 (25.6%) were found to have difficulties in motor functions, compared with 1 (4.8%) child in the control group. The difficulties were faced mainly in daily function requiring control during movement, including jumping, running, and ball playing. Additionally, significant correlations were found between motor functions and children's QOL. Finally, survivors of RB with monocular vision were found to have lower QOL, specifically physical- and school-related QOL. CONCLUSION: Survivors of RB who have monocular vision have a higher rate of decreased motor function and lower QOL. These results point to a need for ongoing assessment of survivors of RB to allow timely detection of motor deficits and to institute appropriate therapeutic interventions.
Subject(s)
Motor Skills , Parents/psychology , Quality of Life , Retinal Neoplasms/physiopathology , Retinoblastoma/physiopathology , Survivors/psychology , Vision, Monocular , Child , Female , Follow-Up Studies , Humans , Male , Prognosis , Retinal Neoplasms/psychology , Retinoblastoma/psychology , Surveys and QuestionnairesABSTRACT
Assessing the visual capabilities that remain to children affected with bilateral retinoblastoma has relied on psychophysical tests based on recognition visual acuity. We report a case in which fundus-driven perimetry and swept-source optical coherence tomography was performed in a patient with a macular tumor in the remaining eye as a novel way of further assessing fixation after oncological disease and treatment.
Subject(s)
Macula Lutea/diagnostic imaging , Retinal Neoplasms/diagnostic imaging , Retinoblastoma/diagnostic imaging , Child , Female , Fixation, Ocular/physiology , Humans , Retinal Neoplasms/physiopathology , Retinoblastoma/physiopathology , Tomography, Optical Coherence/methods , Visual Acuity/physiology , Visual Field Tests , Visual Fields/physiologyABSTRACT
Retinoblastoma generally occurs before 5 years of age and often requires enucleation (surgical removal of one eye) of the cancerous eye. We have previously shown using behavioural methods that this disruption in binocular vision during the critical period of visual development results in impaired face perception. In this case series study, we sought to determine the underlying neural correlates of this face perception deficit by examining brain activity in regions of cortex that preferentially respond to visual images of faces and places in 6 adults who had one eye enucleated early in life due to retinoblastoma. A group of 10 binocularly-intact adult controls were recruited for comparison. Functional magnetic resonance imaging (fMRI) was conducted over two separate runs for each participant in one scanning session. Each run consisted of 6 blocks each of face, place, and object images. Region-of-interest analyses were conducted to locate face-preferential [fusiform face area (FFA), occipital face area (OFA)] and place-preferential [parahippocampal place area (PPA), transverse occipital sulcus (TOS)] regions-of-interest. Descriptive statistics are reported. Results. Enucleated adults exhibited reduced functional activation in face-preferential regions (left FFA, right OFA, left OFA), but similar activation within the face-preferential right FFA and the place-preferential regions (bilateral PPA and TOS). Conclusions. These results indicate that early monocular enucleation prevents robust development of late-maturing face processing capabilities and that this disruption is specific to face networks and not to networks supporting other visual image categories.
Subject(s)
Eye Enucleation , Facial Recognition/physiology , Retinal Neoplasms/surgery , Retinoblastoma/surgery , Vision, Monocular/physiology , Visual Cortex/physiopathology , Visual Perception/physiology , Adult , Discrimination, Psychological , Female , Humans , Magnetic Resonance Imaging , Male , Photic Stimulation , Retinal Neoplasms/diagnosis , Retinal Neoplasms/physiopathology , Retinoblastoma/diagnosis , Retinoblastoma/physiopathology , Visual Cortex/diagnostic imaging , Young AdultABSTRACT
BACKGROUND/AIMS: To assess tumour control, vision and anatomical visual potential in eyes with perifoveal retinoblastoma treated by sequential photocoagulation from the antifoveal tumour edge inwards, avoiding treatment near the fovea. Patients were monitored for tumour control, foveal and perifoveal anatomy at each treatment session by optical coherence tomography (OCT) and treated for amblyopia when the other eye had better vision. METHODS: Eyes with perifoveal retinoblastoma treated between 1 January 2011 and 31 May 2017 with laser therapy after chemotherapy for juxtafoveal (fovea clear of tumour but <3000 µm from tumour edge) or foveolar retinoblastoma (tumour underlying fovea) were retrospectively reviewed for tumour control without recurrence, anatomical success (foveal pit preservation and/or restoration with ≥500 µm perifoveal retina free of tumour and scar) and functional success (acceptable (>0.1 decimal) or good (>0.3 decimal) visual acuity (VA)). RESULTS: Twenty-two eyes (14 juxtafoveal, 8 foveolar tumours) of 20 patients (19 bilateral, 1 familial and 11 females) were included. No juxtafoveal tumour had tumour recurrence, and 13/14 patients showed foveal pit preservation with ≥500 µm of perifoveal retina tumour free. Foveolar tumours had significant worse anatomical outcomes: failure to restore foveal pit or perifoveal retina (8/8, p=0.001) and tumour recurrences (5/8, p=0.001). Functional success with acceptable VA was achieved in 12/14 juxtafoveal and 5/8 foveal tumours eyes (p=0.01). Amblyopia therapy data were insufficient to evaluate impact on VA. CONCLUSIONS: Anatomical visual potential and functional vision were better in juxtafoveal than foveolar retinoblastoma treated with foveal-sparing laser photocoagulation guided by OCT. The role of amblyopia therapy requires a prospective study.
Subject(s)
Fovea Centralis/pathology , Laser Coagulation/methods , Retinal Neoplasms/surgery , Retinoblastoma/surgery , Surgery, Computer-Assisted/methods , Tomography, Optical Coherence/methods , Visual Acuity , Female , Follow-Up Studies , Humans , Infant , Male , Postoperative Period , Retinal Neoplasms/diagnosis , Retinal Neoplasms/physiopathology , Retinoblastoma/diagnosis , Retinoblastoma/physiopathology , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVE: To describe the microvascular features of treated, clinically regressed, or reactivated retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system. PATIENTS AND METHODS: Single-center, prospective, cross-sectional, consecutive case-series of children with previously treated retinoblastoma who underwent portable OCTA of posterior retinoblastoma lesions. RESULTS: Eight tumors from seven eyes of five children with retinoblastoma were included. Tumors with types 1 (calcified remnant, n = 3), 2 (non-calcified remnant, n = 1), and 3 (both calcified and noncalcified remnants, n = 1) regression revealed persistent intrinsic superficial vasculature on OCTA (five of five lesions; 100%). Lesions with type 4 regression (atrophic scar, n = 2) had complete vascular flow voids in the involved retina and underlying choriocapillaris. A reactivated tumor (n = 1) showed a distinct area of vascularity with prominent feeder/draining vessels. CONCLUSIONS: OCTA revealed that significant vascularity exists in inactive retinoblastoma lesions. Dilated feeder vessels may suggest continued disease activity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:43-49.].
Subject(s)
Antineoplastic Agents/therapeutic use , Fluorescein Angiography , Retinal Neoplasms/physiopathology , Retinal Vessels/pathology , Retinoblastoma/physiopathology , Tomography, Optical Coherence , Child, Preschool , Cross-Sectional Studies , Female , Humans , Hyperthermia, Induced , Infant , Infusions, Intra-Arterial , Male , Microcirculation/physiology , Prospective Studies , Regional Blood Flow , Retinal Neoplasms/diagnostic imaging , Retinal Neoplasms/drug therapy , Retinal Vessels/diagnostic imaging , Retinoblastoma/diagnostic imaging , Retinoblastoma/drug therapyABSTRACT
Purpose: To use color Doppler to analyze blood flow in the retrobulbar central retinal artery (CRA) and central retinal vein (CRV) in monocular retinoblastoma. Methods: This prospective study included patients with group D and E retinoblastomas managed with only enucleation. Peak blood velocities were assessed in the CRA and CRV of tumor-containing eyes (CRAv and CRVv, respectively). The resistivity index in the CRA (RIa) and pulse index in the CRV (PIv) were calculated and related to optic nerve invasion (ONi), choroid invasion (mCHi), and tumor volume. RIa and PIv were also calculated for healthy eyes. Results: In total, 25 patients with a mean age of 30.8-months old were included. The means (SD) for CRAv, CRVv, RIa, and PIv were 26.94 (12.32) cm/s, 16.2 (9.56) cm/s, 0.88 (0.12) and 0.79 (0.29), respectively. Tumor volume was significantly correlated with CRAv (P = 0.025) and RIa (P = 0.032). ONi was present in 19 eyes and correlated with a smaller PIv (P < 0.001). A PIv less than 0.935 had a sensitivity of 89.5% and specificity of 83.3% for predicting ONi. mCHi was not correlated with flow values. Healthy eyes had a significantly lower RIa (P < 0.001) and lower PIv than eyes with (P = 0.009) and without (P < 0.001) ONi. Conclusions: In advanced-stage monocular retinoblastoma, tumor volume was directly correlated with CRAv and RIa, and lower PIv was correlated with optic nerve invasion when a predictive cut-off value of less than 0.935 was applied. Comparisons with healthy eyes showed that tumor-containing eyes were associated with higher RIa and PIv values.
Subject(s)
Retinal Artery/physiology , Retinal Neoplasms/physiopathology , Retinal Vein/physiology , Retinoblastoma/physiopathology , Blood Flow Velocity , Child , Child, Preschool , Female , Hemodynamics , Humans , Infant , Magnetic Resonance Imaging , Male , Prospective Studies , Regional Blood Flow/physiology , Retinal Neoplasms/diagnostic imaging , Retinoblastoma/diagnostic imaging , Risk Factors , Ultrasonography, Doppler, ColorABSTRACT
Importance: Retinoblastoma survivors are at risk for adverse oculo-visual outcomes. Limited data are available regarding long-term vision-targeted health-related quality of life (HRQoL) of adult retinoblastoma survivors. Objective: To examine vision-targeted HRQoL as reported on the 25-item National Eye Institute Visual Field Questionnaire for overall and specific scale scores among adult survivors of retinoblastoma. Design, Setting, and Participants: The Retinoblastoma Survivor Study is a retrospective cohort of adult retinoblastoma survivors treated at 3 academic medical centers in New York between 1932 and 1994. Participants completed a comprehensive questionnaire between April 2008 and June 2010. Items were scored in January 2013 and preliminary analyses were performed in July 2015. Models were finalized in May 2017. Main Outcomes and Measures: Self-reported vision-targeted HRQoL as reported on the 25-item National Eye Institute Visual Field Questionnaire. Items are scored from 0 to 100, with 100 representing the highest quality of life. Results: Among 470 adult retinoblastoma survivors (53.6% with bilateral disease; 52.1% female; 86.4% white and non-Hispanic; mean age at study, 43.3 years; range, 18.0-77.0 years), 86% had at least 1 eye removed (1 eye, 74.5%; both eyes, 11.5%); 56.5% were previously treated with radiotherapy; and 61.3% rated their eyesight as excellent/good while 16.2% reported complete blindness. The overall mean (SD) VFQ composite score for all survivors was 81.1 (17.2) (mean [SD] score for unilateral retinoblastoma survivors, 91.4 [7.7]; bilateral retinoblastoma survivors, 72.3 [18.2]; difference between survivors with unilateral and bilateral disease, 19.1 [95% CI, 16.5-21.7; P < .001]). Prior exposure to radiotherapy was not associated with decreased overall VFQ (ß = -0.08; 95% CI, -0.15 to 0.002; P = .06) but was related to a few specific subdomains of visual functioning. Conclusions and Relevance: These findings suggest retinoblastoma-related oculo-visual problems are associated with functional status and vision-targeted HRQoL of adult survivors, particularly among those with bilateral disease.
Subject(s)
Quality of Life/psychology , Retinal Neoplasms/psychology , Retinoblastoma/psychology , Survivors/psychology , Vision, Ocular/physiology , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , Radiotherapy , Retinal Neoplasms/physiopathology , Retinal Neoplasms/therapy , Retinoblastoma/physiopathology , Retinoblastoma/therapy , Retrospective Studies , Sickness Impact Profile , Surveys and Questionnaires , Young AdultABSTRACT
OBJECTIVE: To document clinical pattern of retinoblastoma in Pakistani population. METHODS: This retrospective study, which was conducted at Department of Ophthalmology, Dow University of Health Sciences, Karachi, reviewed clinical records of patients with retinoblastoma from 1997 to 2012. Staging of disease was done by referring to retinal diagrams, RetCam images, and first magnetic resonance imaging. Ophthalmic notes, imaging reports and histopathology reports of enucleated eyes established optic nerve involvement. SPSS 21 was used for statistical analysis. RESULTS: Clinical records of 295 patients with retinoblastoma in 403 eyes were reviewed, and male to female ratio was 1.3:1. Retinoblastoma was bilateral in 106(35.93%) patients, while 118(40%) patients had hereditary pattern. Mean age at presentation was 35.98+27.63 months, while mean follow-up was 3±2 months. Leucokoria was the most common presenting feature 173(58.64%) followed by proptosis 72(24.41%). Optic nerve involvement was seen on magnetic resonance imaging or histopathology in 81(20.10%) eyes. Distant metastasis was noted in 32(10.85%) patients on first presentation. Chemotherapy with or without adjuvant treatment was given to 238(80.68%) patients. Enucleation and exentration were performed in 164(40.69%) and 12(2.98%) eyes, respectively. CONCLUSIONS: Most common presenting symptom was leucokoria followed by proptosis. Hereditary retinoblastoma was frequently seen in Pakistani children. .