Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model.

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.

Integrated multi-omics analysis of RB-loss identifies widespread cellular programming and synthetic weaknesses.

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.

CircMKLN1 Suppresses the Progression of Human Retinoblastoma by Modulation of miR-425-5p/PDCD4 Axis.

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.

Knockdown of lncRNA HOTTIP Inhibits Retinoblastoma Progression by Modulating the miR-101-3p/STC1 Axis.

OBJECTIVE: Retinoblastoma (RB) is a frequent eye cancer in children. Long non-coding RNA (LncRNA) HOXA transcript at the distal tip (HOTTIP) is aberrantly expressed in cancer tissues. This study explores the underlying mechanism of lncRNA HOTTIP in RB. METHODS: HOTTIP expression in normal retinal cells and RB cell lines was detected using qRT-PCR. The proliferation of RB cells was measured using CCK-8 and EdU assays, and apoptosis was detected using flow cytometry and Western blotting after the transfection of si-HOTTIP into Y79 cells and pc-HOTTIP into HXO-RB-44 cells. The target relationships between HOTTIP and miR-101-3p, and miR-101-3p and STC1 were predicted by bioinformatics website and verified using dual-luciferase reporter gene assay. The binding of HOTTIP and miR-101-3p was verified using RNA pull-down assay. STC1 mRNA and protein in RB cells were measured using qRT-PCR and Western blotting. Moreover, si-HOTTIP and in-miR-101-3p/in-NC, and si-HOTTIP and pc-STC1/pcDNA were co-transfected into Y79 cells respectively to evaluate cell proliferation and apoptosis. Xenograft study was conducted, and Ki67-positive expression was detected using immunohistochemical staining. RESULTS: HOTTIP expression was promoted in RB tissues and cells. Downregulation of HOTTIP inhibited proliferation and promoted apoptosis of Y79 cells, while upregulation of HOTTIP promoted proliferation and inhibited apoptosis of HXO-RB-44 cells. There were target relationships between HOTTIP and miR-101-3p, and miR-101-3p and STC1. Inhibition of miR-101-3p or overexpression of STC1 reversed the effect of si-HOTTIP on the proliferation and apoptosis of RB cells. Xenograft study showed that knockdown of HOTTIP suppressed the growth of RB in vitro. CONCLUSION: It could be concluded that HOTTIP sponged miR-101-3p to upregulate STC1 expression, thereby promoting RB cell proliferation and inhibiting apoptosis.

Combined association of massive choroidal and optic nerve invasion as a prognostic relevance in primary retinoblastoma: A 10-year study.

PURPOSE: To determine the significance of both massive choroidal invasion and optic nerve invasion (retrolaminar [(RL]+cut end [CE]) as a criterion for classifying high metastatic potential retinoblastoma and their relationship with other known histopathological high-risk features. METHODS: A retrospective review of 650 eyes diagnosed as retinoblastoma over a 10-year period. In our study, there is male predominance and a higher percentage of the poorly differentiated tumors. The age of most of the patients ranges from 1 month to 8 years with a median age of 2 years. RESULTS: There were 24% of eyes with massive choroidal invasion and 18% of eyes with optic nerve invasion up to the cut end. On performing Cox-proportional hazard analysis, it was found that massive choroidal invasion in association with optic nerve invasion up to the cut end was an independent prognostic parameter. On Kaplan-Meier analysis, overall survival had reduced in patients having both massive choroidal invasion and an optic nerve cut end invasion along with orbital invasion (P < .05). CONCLUSION: The presence of massive choroidal invasion in association with optic nerve cut end invasion (RL+CE) could be used as a better prognostic predictor in assessing retinoblastoma patients with high metastatic potential and need to be kept for longer follow up.

Retinoblastoma vascular perfusion and intra-arterial chemotherapy cycle requirements.

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.

Health-related quality of life of Brazilian children and adolescents with benign and malignant solid tumours: A prospective cohort study during the first year after hospital admission.

INTRODUCTION: This study aims to assess the impact of paediatric benign and malignant solid tumours and its treatment on the health-related quality of life of children and adolescents who were followed up in a Reference Center in Pediatric Oncology in Rio de Janeiro. METHODS: It is a prospective cohort study. Quality of life assessment was performed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ 3.0 Cancer Module protocols three times: during hospital admission (T1), 6 months after admission (T2) and 1 year after admission (T3). RESULTS: We evaluated 132 patients, 59 men and 73 women, aged 2-17 years. In PedsQL™4.0, the Emotional Functioning scale was the one with the worst scores, while the scores on the Social Functioning scale was the best. In PedsQL™ 3.0, the worst domains were Procedural Anxiety and Worry. Patients with malignant bone tumours had the worst health-related quality of life. The group who received only surgery had better results. Total scores of PedsQL™4.0 and PedsQL™ 3.0 improved between T1 and T3. CONCLUSION: Children and adolescents with malignant and benign neoplasms undergo changes in quality of life as a result of the disease and treatment, but an improvement has been observed over time.

Preservation of retinoblastoma group E eyes with neovascular glaucoma using intravenous chemotherapy: risk factors and outcomes.

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.

The impact of monocular vision on motor function and quality of life in survivors of retinoblastoma.

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.

Vision and visual potential for perifoveal retinoblastoma after optical coherence tomographic-guided sequential laser photocoagulation.

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.

Microperimetry and swept-source optical coherence tomography in the assessment of the preferred retinal locus in a child with macular retinoblastoma in the remaining eye.

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.

Early monocular enucleation selectively disrupts neural development of face perception in the occipital face area.

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.

Microvascular Features of Treated Retinoblastoma Tumors in Children Assessed Using OCTA.

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.].

Blood Flow in Monocular Retinoblastoma Assessed by Color Doppler and Correlations With High-Risk Pathologic Features.

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.

Downregulation of microRNA­198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN.

A number of studies have highlighted that aberrantly expressed microRNAs (miRNAs/miRs) serve crucial roles in the tumorigenesis and tumor development of retinoblastoma (RB). Hence, a full investigation of the biological roles and regulatory mechanisms of miRNAs in RB may provide novel therapeutic targets for patients with this malignancy. miR­198 is frequently abnormally expressed in various types of human cancers. However, the expression level, biological roles and underlying mechanisms of miR­198 in RB remain to be elucidated. In the present study, miR­198 expression was upregulated in RB tissues and cell lines. Silencing of miR­198 attenuated cell proliferation and invasion in RB. In addition, phosphatase and tensin homolog deleted on chromosome ten (PTEN) was predicted as a potential target of miR­198 using bioinformatics analysis. Subsequent luciferase reporter assay indicated that the 3'­untranslated region of PTEN can be directly targeted by miR­198. Furthermore, miR­198 inhibition increased the PTEN expression at the mRNA and protein levels in RB cells. In addition, PTEN mRNA expression was downregulated in RB tissues, and this downregulation was inversely associated with the expression level of miR­198. PTEN knockdown rescued the inhibitory effects of miR­198 underexpression on cell proliferation and invasion in RB. Notably, the downregulation of miR­198 inactivated the phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT) signaling pathway in RB. These results demonstrated that miR­198 may serve oncogenic roles in RB by directly targeting PTEN and regulating the PI3K/AKT signaling pathway. Hence, miR­198 may be a promising therapeutic target for patients with RB.

Vision-Targeted Health-Related Quality of Life in Adult Survivors of Retinoblastoma.

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.

Coats' disease - disease of the eye rarely encountered by pathologists.

Coats' Disease is an idiopathic condition of the eye affecting young children although it can be seen in adults. Most patients present early in life with unilateral decreased vision, strabismus or leukocoria. The most important differential diagnosis is unilateral retinoblastoma. In this study we report a case of coat's disease in an young girl, and evaluate histopathological and clinical findings.

Clinical pattern of Retinoblastoma in Pakistani population: Review of 403 eyes in 295 patients.

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. .