Publications by authors named "Yacoub A Yousef"

48 Publications

The Predictive Value of the Eighth Edition of the Clinical TNM Staging System for the Likelihood of Eye Salvage for Intraocular Retinoblastoma by Systemic Chemotherapy and Focal Therapy.

J Pediatr Hematol Oncol 2021 Mar 23. Epub 2021 Mar 23.

Departments of Surgery (Ophthalmology) Pediatrics Oncology Pathology and Laboratory Medicine Radiation Oncology, King Hussein Cancer Centre, Amman, Jordan Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.

Background: The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) cTNM staging is emerging as a universal staging for all cancers, including retinoblastoma.

Methods: Here we evaluated the predictive value of the eighth edition AJCC/UICC cTNM staging in comparison with the International Intraocular Retinoblastoma Classification for eye globe salvage by primary systemic chemotherapy and focal therapy (CRD) using logistic regression model for the probability of treatment failure.

Results: The eye salvage rate for 565 treated eyes was 95% (n=139/147) for T1 tumors (98% for T1a and 93% for T1b), 56% (n=230/410) for T2 (81% for T2a and 53% for T2b), and 0% for T3 tumors, and was 98%, 93%, 76%, and 44% for group A, B, C, and D tumors, respectively. As estimated by odds ratios, T2 were 13.6-fold more likely to fail treatment than T1, and T1b, T2a, and T2b were 2.8-, 9.4-, and 35.1-fold more likely to fail treatment than T1a, respectively. Group B, C, and D tumors were 2.8-, 12.7-, and 50.1-fold more likely to fail treatment than group A tumors, respectively. Eye salvage rate was 62% for eyes with focal seeds (3 mm close to the tumor), and 42% for eyes with diffuse seeds (clouds more than 3 mm from tumor edge) (P<0.0001).

Conclusion: Both, the eighth edition cTNM classification and the International Intraocular Retinoblastoma Classification systems, can effectively predict eye salvage rates for retinoblastoma by CRD. Eyes with higher cT stages are more likely to experience treatment failure. Because the cT2b group is very heterogeneous, our findings suggest further division of this group based on the severity of vitreous/subretinal seeds, this should be revised in the next edition of cTNM system.
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http://dx.doi.org/10.1097/MPH.0000000000002144DOI Listing
March 2021

Delayed Intravitreal Anti-VEGF Therapy for Patients During the COVID-19 Lockdown: An Ethical Endeavor.

Clin Ophthalmol 2021 17;15:661-669. Epub 2021 Feb 17.

Department of Surgery (Ophthalmology), King Hussein Cancer Center, Amman, Jordan.

Purpose: To assess the impact of Jordanian's Corona Virus Disease (COVID-19) lockdown on visual acuity and macular thickness in patients with macular edema receiving intravitreal injections, and to assess the ethical endeavor of lockdown among serious sight threatening conditions.

Patients And Methods: This retrospective observational study included patients planned for intravitreal injections who did not complete the planned course before the lockdown (ie, before 20th of March 2020). Data included demographics, indication for the intravitreal injection, corrected distance visual acuity (CDVA), and central macular thickness on Optical Coherence Tomography (OCT) before and after the lockdown.

Results: One-hundred and sixty-six eyes of 125 patients were studied, 68 (54.4%) patients were males, and the mean (± standard deviation, SD) age was 64.79 (±9.41) years. Mean (±SD) duration of delay in the planned injection was 60.97 (±24.35) days. The change in visual acuity was statistically significant for patients with diabetic macular edema (p= 0.045 improvement), patients with central retinal vein thrombosis (CRVO) (p= 0.05 deterioration), and patients with age-related macular degeneration (AMD) (p= 0.005 deterioration). Of interest, delay of more than 2 months and the previous need for 3 or more injections were significant poor prognostic factors for visual outcome for patients with diabetic macular edema (p=0.027 and 0.045).

Conclusion: The impact of delay in the scheduled intravitreal injections resulted in variable outcomes depending on the indication. Triaging the urgency of patients should be based on the indication to support the equity principle of bioethics, where those in need are prioritized against others, depending on potential adverse outcome.
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http://dx.doi.org/10.2147/OPTH.S289068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898208PMC
February 2021

Prognostic Factors for Eye Globe Salvage by External Beam Radiation Therapy for Resistant Intraocular Retinoblastoma.

Oman J Ophthalmol 2020 Sep-Dec;13(3):123-128. Epub 2020 Nov 2.

Department of Surgery, Ophthalmology, and King Hussein Cancer Center, Amman, Jordan.

Purpose: To analyse the prognostic factors for eye salvage for eyes with intra-ocular retinoblastoma (RB) that is resistant to systemic chemotherapy and focal therapy by external beam radiation therapy (EBRT).

Methods: A retrospective analysis of 28 eyes with intra-ocular RB that was resistant for systemic chemotherapy and focal consolidation therapy and received EBRT. Outcome measures included tumor stage at diagnosis, stage migration, type of tumor seeds, treatment modalities, eye globe salvage, metastasis, and survival.

Results: Most of the patients (83%) had bilateral RB, and 42% were females. All eyes were treated initially by combination of systemic chemotherapy and focal consolidation therapy. The dose of EBRT was 45 Gy. The mean follow-up was 6.5 years, and the overall eye globe salvage rate post EBRT was 46%: 67% (2/3) for group B, 71% (5/7) for group C, and 33% (6/18) for group D. Patient's gender, tumor site, laterality, and tumor stage at diagnosis were not significant prognostic factors (p> 0.05) for final outcome. The significant poor prognostic factors were tumor stage migration during systemic chemotherapy (p= 0.03) and presence of vitreous seeds at time of EBRT (p=0.001). Post EBRT complication rate was 68% (19/28) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), radiation retinopathy (2), and second malignancy (2).

Conclusion: EBRT is an alternative for enucleation when RB is resistant to combined chemoreduction/focal consolidation therapy in absence in vitreous seeds. The known risks for EBRT are not justified for patients with unilateral RB and for those who have functional vision in the other eye.
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http://dx.doi.org/10.4103/ojo.OJO_250_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852425PMC
November 2020

Management and Outcomes of Unilateral Group D Tumors in Retinoblastoma.

Clin Ophthalmol 2021 7;15:65-72. Epub 2021 Jan 7.

Department of Surgery (Ophthalmology), King Hussein Cancer Centre (KHCC), Amman, Jordan.

Purpose: Retinoblastoma presents most commonly as advanced unilateral disease, particularly in developing countries for which primary enucleation has been the preferred method of treatment. However, with the evolution of newer treatment modalities including intravitreal chemotherapy, intra-arterial chemotherapy and newer chemotherapeutic combinations, a trend towards more conservative approaches is being observed. Our aim is to evaluate outcomes of group D eyes following conservative and non-conservative treatment options.

Patients And Methods: The ocular oncology database was used to identify eyes with unilateral retinoblastoma that fulfilled the International Intraocular Retinoblastoma Classification (IIRC) group D criteria from August 2010 to August 2018 and these were retrospectively reviewed. Overall, 39 eyes were identified.

Results: Nineteen (49%) eyes underwent primary enucleation and 20 (51%) received eye-conserving treatment. Eye salvage was possible in 15 (75%) eyes in the attempted salvage group. None of the patient revealed signs of metastasis. All eyes received conventional chemotherapy (carboplatin, vincristine, etoposide) and focal laser therapy. Additional treatment modalities offered included intravitreal chemotherapy, intra-arterial chemotherapy and topotecan. Three (11%) eyes in the primary enucleation group showed high-risk features on histopathology and none developed metastasis.

Conclusion: The results of the study seem promising and conservative measures can be adopted in selected unilateral group D eyes.
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http://dx.doi.org/10.2147/OPTH.S282741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802086PMC
January 2021

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

Ophthalmology 2020 Sep 29. Epub 2020 Sep 29.

Retinoblastoma Unit, Department of Oncology, Hospital Sant Joan de Déu. Esplugues de Llobregat, Barcelona, Spain.

Purpose: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels.

Design: International, multicenter, registry-based retrospective case series.

Participants: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents.

Methods: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes.

Main Outcome Measures: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy).

Results: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001).

Conclusions: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.
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http://dx.doi.org/10.1016/j.ophtha.2020.09.032DOI Listing
September 2020

Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study.

Br J Ophthalmol 2020 Sep 5. Epub 2020 Sep 5.

Calle Ophthalmic and Orbit Center, Bogota D.C., Colombia.

Background: To relate conjunctival melanoma characteristics to local control.

Methods: Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system.

Results: 288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence.

Conclusion: This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316293DOI Listing
September 2020

SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings.

Pediatr Blood Cancer 2020 Aug 13:e28493. Epub 2020 Aug 13.

Department of Pediatric Oncology, Great North Children's Hospital, Newcastle upon Tyne, UK.

Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.
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http://dx.doi.org/10.1002/pbc.28493DOI Listing
August 2020

How Telemedicine and Centralized Care Changed the Natural History of Retinoblastoma in a Developing Country: Analysis of 478 Patients.

Ophthalmology 2021 01 16;128(1):130-137. Epub 2020 Jul 16.

St. Jude Children's Research Hospital, Memphis, Tennessee; Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee.

Purpose: To evaluate the efficacy of integrating a telemedicine-based twinning partnership and centralized care for retinoblastoma on survival and eye salvage.

Design: Four hundred seventy-eight retinoblastoma patients treated at a tertiary referral cancer center (King Hussein Cancer Centre [KHCC]) from 2003 through 2019.

Participants: Four hundred seventy-eight retinoblastoma patients treated at KHCC after implementing a telemedicine-based program with St. Jude Children's Research Hospital.

Methods: We reviewed the outcomes of retinoblastoma patients who were treated at KHCC after implementing a telemedicine-based eye salvage program with St. Jude Children's Research Hospital, and we compared that with outcomes for retinoblastoma patients who were treated before implementing a telemedicine-based retinoblastoma service at KHCC.

Main Outcome Measures: We analyzed patient demographics, clinical characteristics, treatments received, consultation type and duration, and long-term patient outcomes before and after implementing the twinning program.

Results: Over 17 years, 813 eyes from 478 children with retinoblastoma were treated at KHCC. Three hundred thirty-five patients (70%) had bilateral disease. Six patients (4%) with unilateral disease and 66 patients (20%) with bilateral disease had a family history of retinoblastoma. After the twinning program was established in 2003, the mortality rate decreased from 38% to 5% (P < 0.0001), and the overall eye salvage rate increased from 4% to 61% (98% for group A, 93% for group B, 81% for group C, and 48% for group D; P < 0.0001). Initially, all cases were discussed via telemedicine, but as knowledge transfer increased, the proportion of cases that required discussion decreased to less than 3% 10 years later. Similarly, treatment changes based on consultations decreased from 70% to 7% after 10 years. Both survival and eye-salvage rates were comparable at the early and later stages of implementing the twinning program. At a median follow-up of 120 months, 5% of patients had died of metastases or secondary neoplasms, 81% were alive, and 14% were lost to follow-up.

Conclusions: Centralization of care at a single center in developing countries can achieve patient outcomes comparable with those of developed countries via twinning and telemedicine. This benefit can extend to a large region because two thirds of patients treated at KHCC were non-Jordanians.
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http://dx.doi.org/10.1016/j.ophtha.2020.07.026DOI Listing
January 2021

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

Ophthalmology 2020 12 8;127(12):1733-1746. Epub 2020 Jun 8.

Retinoblastoma Unit, Department of Oncology, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.

Purpose: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB).

Design: International, multicenter, registry-based retrospective case series.

Participants: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.

Methods: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included.

Main Outcome Measures: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC).

Results: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001).

Conclusions: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.
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http://dx.doi.org/10.1016/j.ophtha.2020.05.051DOI Listing
December 2020

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part I: Metastasis-Associated Mortality.

Ophthalmology 2020 12 6;127(12):1719-1732. Epub 2020 Jun 6.

Retinoblastoma Unit, Department of Oncology, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.

Purpose: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB).

Design: International, multicenter, registry-based retrospective case series.

Participants: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.

Methods: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied.

Main Outcome Measures: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait.

Results: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease.

Conclusions: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.
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http://dx.doi.org/10.1016/j.ophtha.2020.05.050DOI Listing
December 2020

Programmed screening for retinoblastoma enhances early diagnosis and improves management outcome for high-risk children.

Ophthalmic Genet 2020 08 20;41(4):308-314. Epub 2020 May 20.

Departments of Surgery (Ophthalmology), King Hussein Cancer Centre (KHCC) , Amman, Jordan.

Purpose: To study the impact of a Retinoblastoma (Rb) screening program in the absence of genetic testing on the management and outcome of high-risk children.

Methods: This is a retrospective, clinical case series of 76 children from families involved in a Rb screening program as they had higher than normal risk as calculated by the conventional ways without genetic testing. Data included calculated risk, method of diagnosis, demographics, tumor features, treatment modalities, and management outcome.

Results: Out of the 76 children screened, 46 children were diagnosed with Rb (12 by screening and 34 had signs of Rb), the other 30 were free of disease. Patients diagnosed by screening were younger (mean; 2.4 months vs 15.8 months for the group with signs of Rb), had significantly earlier tumor stage at diagnosis ( = .0001), higher eye salvage rate ( = .0001), less need for systemic chemotherapy ( = .022), and better visual outcome ( = .0017) than the other group. None of the eyes were group D or E, enucleated or irradiated. Six (50%) patients were cured without chemotherapy, and the visual acuity was 0.5 or better in 55% of eyes. Of interest, 71% of tumors were diagnosed by the age of 6 months, 90% by the age of 1 year, and no new tumor appeared after the age of 2 years.

Conclusion: Even in the absence of genetic testing, screening for children with high risk for Rb is effective in enhancing early diagnosis, improving visual outcome, and increasing eye salvage rate with limited exposure to treatment burden.
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http://dx.doi.org/10.1080/13816810.2020.1766085DOI Listing
August 2020

Coats' disease: characteristics, management, outcome, and scleral external drainage with anterior chamber maintainer for stage 3b disease.

Medicine (Baltimore) 2020 Apr;99(16):e19623

Departments of Surgery (Ophthalmology) King Hussein Cancer Center.

To report on the characteristics and outcome of management of Coats' disease, and to describe a novel surgical technique for management of stage 3B with total retinal detachment (RD) by scleral external drainage with anterior chamber (AC-maintainer) placement before the drainage without pars plana vitrectomy.A retrospective study of 26 eyes from 25 Coats' patients. Outcome measures included: demographics, presentation, laterality, stage, treatment, and outcome.The median age at diagnosis was 3.5 years. Twenty patients (80%) were males, and all except 1 girl had unilateral disease. The presenting complaint was impaired vision in 13 (50%) eyes, leukocoria in 6 (23%) eyes, and strabismus in 7 (27%) eyes. Based on the Shields classification; 3(12%) eyes were stage 1, 9 (35%) eyes were stage 2, 10 (38%) eyes were stage 3, 2 (8%) eyes were stag e4, and 2 (8%) eyes were stage 5. Primary management included cryotherapy (54%), laser photocoagulation (27%), intravitreal anti-vascular endothelial growth factor (23%), intravitreal steroids (23%), and surgical drainage (12%). The 3 eyes in stage 3B (with total exudative RD) underwent subretinal fluid drainage with AC maintainer, and all had the retina reattached completely for 6 months follow up after the surgery. At mean follow up 21 months, 4 (15%) eyes were enucleated, 19 (73%) eyes had improvement or stabilization in visual acuity.Coats' disease usually presents at advanced stage with poor visual prognosis, individualized management with close follow up are mandatory to save the eye. Subretinal fluid drainage with AC maintainer is a safe and useful technique for repairing total RD in eyes with stage 3B Coats' disease.
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http://dx.doi.org/10.1097/MD.0000000000019623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220322PMC
April 2020

Impact of RB1 gene mutation type in retinoblastoma patients on clinical presentation and management outcome.

Hematol Oncol Stem Cell Ther 2020 Sep 23;13(3):152-159. Epub 2020 Mar 23.

Department of Surgery, King Hussein Cancer Center, Amman, Jordan. Electronic address:

Objective/background: Retinoblastoma (RB), the most common intraocular malignancy in children, is caused by biallelic inactivation of the human retinoblastoma susceptibility gene (RB1). We are evaluating the impact of the type of RB1 gene mutation on clinical presentation and management outcome.

Methods: A retrospective case series of 50 patients with RB. Main outcomes were clinical and pathologic features and types of RB1 gene mutations detected using quantitative multiplex polymerase chain reaction (PCR), allele-specific PCR, next-generation sequencing analysis, and Sanger sequencing.

Results: Twenty (40%) patients had unilateral RB and 30 (60%) had bilateral RB. Overall, 36 (72%) patients had germline disease, 17 (47%) of whom inherited the disease. Of these 17 inherited cases, paternal origin of the RB1 mutation was seen in 15 (88%). The overall eye salvage rate was 74% (n = 49/66; 100% for Groups A + B + C, and 79% for Group D eyes). The most frequent type of mutation was a nonsense mutation generating a stop codon (15/36, 42%). Other mutations that result in a premature stop codon due to deletions or insertions with donor splice site or receptor splice site mutations were detected in 7/36 (19%), 10/36 (28%), and 2/26 (6%) patients, respectively. The remaining two (6%) patients had frameshift mutation. Patients with deletion, acceptor splice site, and frameshift mutations presented with more advanced ICRB (International Classification of Retinoblastoma) stage (75% diagnosed with Group D or E), even though there was no significant difference in eye salvage rate or tumor invasiveness between patients with different types of mutations.

Conclusion: Despite the heterogeneous nature of RB1 gene mutations, tumor stage remains the most important predictive factor for clinical presentation and outcome. Furthermore, acceptor splice site and frameshift mutations are associated with more advanced tumor stage at diagnosis.
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http://dx.doi.org/10.1016/j.hemonc.2020.02.006DOI Listing
September 2020

Global Retinoblastoma Presentation and Analysis by National Income Level.

Authors:
Ido Didi Fabian Elhassan Abdallah Shehu U Abdullahi Rula A Abdulqader Sahadatou Adamou Boubacar Dupe S Ademola-Popoola Adedayo Adio Armin R Afshar Priyanka Aggarwal Ada E Aghaji Alia Ahmad Marliyanti N R Akib Lamis Al Harby Mouroge H Al Ani Aygun Alakbarova Silvia Alarcón Portabella Safaa A F Al-Badri Ana Patricia A Alcasabas Saad A Al-Dahmash Amanda Alejos Ernesto Alemany-Rubio Amadou I Alfa Bio Yvania Alfonso Carreras Christiane Al-Haddad Hamoud H Y Al-Hussaini Amany M Ali Donjeta B Alia Mazin F Al-Jadiry Usama Al-Jumaily Hind M Alkatan Charlotta All-Eriksson Ali A R M Al-Mafrachi Argentino A Almeida Khalifa M Alsawidi Athar A S M Al-Shaheen Entissar H Al-Shammary Primawita O Amiruddin Romanzo Antonino Nicholas J Astbury Hatice T Atalay La-Ongsri Atchaneeyasakul Rose Atsiaya Taweevat Attaseth Than H Aung Silvia Ayala Baglan Baizakova Julia Balaguer Ruhengiz Balayeva Walentyna Balwierz Honorio Barranco Covadonga Bascaran Maja Beck Popovic Raquel Benavides Sarra Benmiloud Nissrine Bennani Guebessi Rokia C Berete Jesse L Berry Anirban Bhaduri Sunil Bhat Shelley J Biddulph Eva M Biewald Nadia Bobrova Marianna Boehme H C Boldt Maria Teresa B C Bonanomi Norbert Bornfeld Gabrielle C Bouda Hédi Bouguila Amaria Boumedane Rachel C Brennan Bénédicte G Brichard Jassada Buaboonnam Patricia Calderón-Sotelo Doris A Calle Jara Jayne E Camuglia Miriam R Cano Michael Capra Nathalie Cassoux Guilherme Castela Luis Castillo Jaume Català-Mora Guillermo L Chantada Shabana Chaudhry Sonal S Chaugule Argudit Chauhan Bhavna Chawla Violeta S Chernodrinska Faraja S Chiwanga Tsengelmaa Chuluunbat Krzysztof Cieslik Ruellyn L Cockcroft Codruta Comsa Zelia M Correa Maria G Correa Llano Timothy W Corson Kristin E Cowan-Lyn Monika Csóka Xuehao Cui Isac V Da Gama Wantanee Dangboon Anirban Das Sima Das Jacquelyn M Davanzo Alan Davidson Patrick De Potter Karina Q Delgado Hakan Demirci Laurence Desjardins Rosdali Y Diaz Coronado Helen Dimaras Andrew J Dodgshun Craig Donaldson Carla R Donato Macedo Monica D Dragomir Yi Du Magritha Du Bruyn Kemala S Edison I Wayan Eka Sutyawan Asmaa El Kettani Amal M Elbahi James E Elder Dina Elgalaly Alaa M Elhaddad Moawia M Ali Elhassan Mahmoud M Elzembely Vera A Essuman Ted Grimbert A Evina Zehra Fadoo Adriana C Fandiño Mohammad Faranoush Oluyemi Fasina Delia D P G Fernández Ana Fernández-Teijeiro Allen Foster Shahar Frenkel Ligia D Fu Soad L Fuentes-Alabi Brenda L Gallie Moira Gandiwa Juan L Garcia David García Aldana Pascale Y Gassant Jennifer A Geel Fariba Ghassemi Ana V Girón Zelalem Gizachew Marco A Goenz Aaron S Gold Maya Goldberg-Lavid Glen A Gole Nir Gomel Efren Gonzalez Graciela Gonzalez Perez Liudmira González-Rodríguez Henry N Garcia Pacheco Jaime Graells Liz Green Pernille A Gregersen Nathalia D A K Grigorovski Koffi M Guedenon D Sanjeeva Gunasekera Ahmet K Gündüz Himika Gupta Sanjiv Gupta Theodora Hadjistilianou Patrick Hamel Syed A Hamid Norhafizah Hamzah Eric D Hansen J William Harbour M Elizabeth Hartnett Murat Hasanreisoglu Sadiq Hassan Shadab Hassan Stanislava Hederova Jose Hernandez Lorelay Marie Carcamo Hernandez Laila Hessissen Diriba F Hordofa Laura C Huang G B Hubbard Marlies Hummlen Kristina Husakova Allawi N Hussein Al-Janabi Russo Ida Vesna R Ilic Vivekaraj Jairaj Irfan Jeeva Helen Jenkinson Xunda Ji Dong Hyun Jo Kenneth P Johnson William J Johnson Michael M Jones Theophile B Amani Kabesha Rolande L Kabore Swathi Kaliki Abubakar Kalinaki Mehmet Kantar Ling-Yuh Kao Tamar Kardava Rejin Kebudi Tomas Kepak Naama Keren-Froim Zohora J Khan Hussain A Khaqan Phara Khauv Wajiha J Kheir Vikas Khetan Alireza Khodabande Zaza Khotenashvili Jonathan W Kim Jeong Hun Kim Hayyam Kiratli Tero T Kivelä Artur Klett Jess Elio Kosh Komba Palet Dalia Krivaitiene Mariana Kruger Kittisak Kulvichit Mayasari W Kuntorini Alice Kyara Eva S Lachmann Carol P S Lam Geoffrey C Lam Scott A Larson Slobodanka Latinovic Kelly D Laurenti Bao Han A Le Karin Lecuona Amy A Leverant Cairui Li Ben Limbu Quah Boon Long Juan P López Robert M Lukamba Livia Lumbroso Sandra Luna-Fineman Delfitri Lutfi Lesia Lysytsia George N Magrath Amita Mahajan Abdul Rahim Majeed Erika Maka Mayuri Makan Emil K Makimbetov Chatonda Manda Nieves Martín Begue Lauren Mason John O Mason Ibrahim O Matende Miguel Materin Clarissa C D S Mattosinho Marchelo Matua Ismail Mayet Freddy B Mbumba John D McKenzie Aurora Medina-Sanson Azim Mehrvar Aemero A Mengesha Vikas Menon Gary John V D Mercado Marilyn B Mets Edoardo Midena Divyansh K C Mishra Furahini G Mndeme Ahmed A Mohamedani Mona T Mohammad Annette C Moll Margarita M Montero Rosa A Morales Claude Moreira Prithvi Mruthyunjaya Mchikirwa S Msina Gerald Msukwa Sangeeta S Mudaliar Kangwa I Muma Francis L Munier Gabriela Murgoi Timothy G Murray Kareem O Musa Asma Mushtaq Hamzah Mustak Okwen M Muyen Gita Naidu Akshay Gopinathan Nair Larisa Naumenko Paule Aïda Ndoye Roth Yetty M Nency Vladimir Neroev Hang Ngo Rosa M Nieves Marina Nikitovic Elizabeth D Nkanga Henry Nkumbe Murtuza Nuruddin Mutale Nyaywa Ghislaine Obono-Obiang Ngozi C Oguego Andrzej Olechowski Scott C N Oliver Peter Osei-Bonsu Diego Ossandon Manuel A Paez-Escamilla Halimah Pagarra Sally L Painter Vivian Paintsil Luisa Paiva Bikramjit P Pal Mahesh Shanmugam Palanivelu Ruzanna Papyan Raffaele Parrozzani Manoj Parulekar Claudia R Pascual Morales Katherine E Paton Katarzyna Pawinska-Wasikowska Jacob Pe'er Armando Peña Sanja Peric Chau T M Pham Remezo Philbert David A Plager Pavel Pochop Rodrigo A Polania Vladimir G Polyakov Manca T Pompe Jonathan J Pons Daphna Prat Vireak Prom Ignatius Purwanto Ali O Qadir Seema Qayyum Jiang Qian Ardizal Rahman Salman Rahman Jamalia Rahmat Purnima Rajkarnikar Rajesh Ramanjulu Aparna Ramasubramanian Marco A Ramirez-Ortiz Léa Raobela Riffat Rashid M Ashwin Reddy Ehud Reich Lorna A Renner David Reynders Dahiru Ribadu Mussagy M Riheia Petra Ritter-Sovinz Duangnate Rojanaporn Livia Romero Soma R Roy Raya H Saab Svetlana Saakyan Ahmed H Sabhan Mandeep S Sagoo Azza M A Said Rohit Saiju Beatriz Salas Sonsoles San Román Pacheco Gissela L Sánchez Phayvanh Sayalith Trish A Scanlan Amy C Schefler Judy Schoeman Ahad Sedaghat Stefan Seregard Rachna Seth Ankoor S Shah Shawkat A Shakoor Manoj K Sharma Sadik T Sherief Nandan G Shetye Carol L Shields Sorath Noorani Siddiqui Sidi Sidi Cheikh Sónia Silva Arun D Singh Niharika Singh Usha Singh Penny Singha Rita S Sitorus Alison H Skalet Hendrian D Soebagjo Tetyana Sorochynska Grace Ssali Andrew W Stacey Sandra E Staffieri Erin D Stahl Christina Stathopoulos Branka Stirn Kranjc David K Stones Caron Strahlendorf Maria Estela Coleoni Suarez Sadia Sultana Xiantao Sun Meryl Sundy Rosanne Superstein Eddy Supriyadi Supawan Surukrattanaskul Shigenobu Suzuki Karel Svojgr Fatoumata Sylla Gevorg Tamamyan Deborah Tan Alketa Tandili Fanny F Tarrillo Leiva Maryam Tashvighi Bekim Tateshi Edi S Tehuteru Luiz F Teixeira Kok Hoi Teh Tuyisabe Theophile Helen Toledano Doan L Trang Fousseyni Traoré Sumalin Trichaiyaporn Samuray Tuncer Harba Tyau-Tyau Ali B Umar Emel Unal Ogul E Uner Steen F Urbak Tatiana L Ushakova Rustam H Usmanov Sandra Valeina Milo van Hoefen Wijsard Adisai Varadisai Liliana Vasquez Leon O Vaughan Nevyana V Veleva-Krasteva Nishant Verma Andi A Victor Maris Viksnins Edwin G Villacís Chafla Vicktoria Vishnevskia-Dai Tushar Vora Antonio E Wachtel Werner Wackernagel Keith Waddell Patricia D Wade Amina H Wali Yi-Zhuo Wang Avery Weiss Matthew W Wilson Amelia D C Wime Atchareeya Wiwatwongwana Damrong Wiwatwongwana Charlotte Wolley Dod Phanthipha Wongwai Daoman Xiang Yishuang Xiao Jason C Yam Huasheng Yang Jenny M Yanga Muhammad A Yaqub Vera A Yarovaya Andrey A Yarovoy Huijing Ye Yacoub A Yousef Putu Yuliawati Arturo M Zapata López Ekhtelbenina Zein Chengyue Zhang Yi Zhang Junyang Zhao Xiaoyu Zheng Katsiaryna Zhilyaeva Nida Zia Othman A O Ziko Marcia Zondervan Richard Bowman

JAMA Oncol 2020 05;6(5):685-695

International Centre for Eye Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

Design, Setting, And Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

Main Outcomes And Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

Conclusions And Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
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http://dx.doi.org/10.1001/jamaoncol.2019.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047856PMC
May 2020

The role of external beam radiation therapy for retinoblastoma after failure of combined chemoreduction and focal consolidation therapy.

Ophthalmic Genet 2020 02 19;41(1):20-25. Epub 2020 Feb 19.

Departments of Surgery, King Hussein Cancer Center, Amman, Jordan.

: To study the role of external beam radiation therapy (EBRT) for the treatment of retinoblastoma eyes that were not cured by combined systemic chemotherapy and focal consolidation therapy.: A retrospective case series of 28 eyes for 24 retinoblastoma patients treated by EBRT after the failure of tumor controlled by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma classification stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival.: The median age at diagnosis was 11 months. There were 14 (58%) males and 20 (83%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range; 6-8 cycles). The dose of radiation used for all eyes was 45 Gray (Gy).The mean follow-up was 75months, and the overall eye salvage rate after EBRT was 13 (46%) eyes: 67% (2/3) for IIRC group B, 71% (5/7) for group C, and 33% (6/18) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control ( = .001 and 0.033, respectively).: Eyes with retinoblastoma that failed chemotherapy followed by focal therapy were controlled with EBRT. However, the presence of vitreous seeds, stage migration during the course of chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.
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http://dx.doi.org/10.1080/13816810.2020.1719519DOI Listing
February 2020

Intravitreal Melphalan Chemotherapy for Vitreous Seeds in Retinoblastoma.

J Ophthalmol 2020 24;2020:8628525. Epub 2020 Jan 24.

Departments of Surgery/Ophthalmology, King Hussein Cancer Centre (KHCC), Queen Rania Al-Abdullah Street, P.O. Box 1269, Amman 11941, Jordan.

Objective: To evaluate our experience with intravitreal melphalan chemotherapy as a second-line regimen for RB patients with refractory or recurrent vitreous seeds.

Methods: A retrospective case series of 16 eyes from 16 patients with intraocular RB who received intravitreal melphalan chemotherapy using the antireflux injection technique. Data included demographics, stage at diagnosis, treatment modalities, side effects, eye salvage, and survival.

Results: The total number of injections was 64 (median, 3 injections per eye; range, 3-8), and the median age at time of injection was 22 months (range, 9-63 months). Nine (56%) patients were males, and 13 (81%) patients had bilateral RB. Complete response was seen in 13 (81%) eyes: in 9 (100%) eyes with focal vitreous seeds and in 4 (57%) eyes with diffuse vitreous seeds (=0.062). At a median follow-up of 18 months (range, 6-48 months), the eye salvage rate was 81%, local retinal toxicity confined to the site of injection was seen in 2/3 of the eyes, 2 (12%) eyes had cataract, and none of the patients had orbital recurrence and distant metastasis or was dead.

Conclusion: Intravitreal melphalan is a promising modality for treatment of vitreous seeds, and the dose of 20-30 g of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.g of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.
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http://dx.doi.org/10.1155/2020/8628525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003283PMC
January 2020

Heterochromia irides and mistaken identity of retinoblastoma.

BMJ Case Rep 2019 Oct 25;12(10). Epub 2019 Oct 25.

Ophthalmology Department, University Hospital of Wales, Cardiff, UK.

Retinoblastoma is the most common intraocular malignancy of infancy which frequently manifests with a white pupillary reflex. We report a case of delayed presentation of a child with retinoblastoma in his left eye because parents thought the change in iris colour in this eye was due to the innocent heterochromia irides that was previously diagnosed in his elder sibling. This late presentation necessitated enucleation of the affected eye followed by chemotherapy.
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http://dx.doi.org/10.1136/bcr-2019-231091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827771PMC
October 2019

Multicenter, International Assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for Conjunctival Melanoma.

JAMA Ophthalmol 2019 Jun 6. Epub 2019 Jun 6.

Department of Ophthalmology, Calle Ophthalmic and Orbit Center, Bogota, Distrito Capital, Colombia.

Importance: Eye cancer staging systems used for standardizing patient care and research need to be validated.

Objective: To evaluate the accuracy of the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual in estimating metastatis and mortality rates of conjunctival melanoma.

Design, Setting, And Participants: This international, multicenter, registry-based case series pooled data from 10 ophthalmic oncology centers from 9 countries on 4 continents. A total of 288 patients diagnosed with conjunctival melanoma from January 1, 2001, to December 31, 2013, were studied. Data analysis was performed from July 7, 2018, to September 11, 2018.

Interventions: Treatments included excision biopsy, cryotherapy, topical chemotherapy, radiation therapy, enucleation, and exenteration.

Main Outcomes And Measures: Metastasis rates and 5-year and 10-year Kaplan-Meier mortality rates according to the clinical T categories and subcategories of the eighth edition of the AJCC Cancer Staging Manual.

Results: A total of 288 eyes from 288 patients (mean [SD] age, 59.7 [16.8] years; 147 [51.0%] male) with conjunctival melanoma were studied. Clinical primary tumors (cT) were staged at presentation as cT1 in 218 patients (75.7%), cT2 in 34 (11.8%), cT3 in 15 (5.2%), and cTx in 21 (7.3%). There were no T4 tumors. Pathological T categories (pT) were pTis in 43 patients (14.9%), pT1 in 169 (58.7%), pT2 in 33 (11.5%), pT3 in 12 (4.2%), and pTx in 31 (10.8%). Metastasis at presentation was seen in 5 patients (1.7%). Metastasis during follow-up developed in 24 patients (8.5%) after a median time of 4.3 years (interquartile range, 2.9-6.0 years). Of the 288 patients, 29 died (melanoma-related mortality, 10.1%) at a median time of 5.3 years (interquartile range, 1.8-7.0 years). The cumulative rates of mortality among patients with cT1 tumors were 0% at 1 year, 2.5% (95% CI, 0.7%-7.7%) at 5 years, and 15.2% (95% CI, 8.1%-27.4%) at 10 years of follow-up; among patients with cT2 tumors, 0% at 1 year, 28.6% (95% CI, 12.9%-58.4%) at 5 years, and 43.6% (95% CI, 19.6%-77.9%) at 10 years of follow-up; and among patients with cT3 tumors, 21.1% (95% CI, 8.1%-52.7%) at 1 year of follow-up and 31.6% (95% CI, 13.5%-64.9%) at 5 years of follow-up. Patients with cT2 and cT3 tumors had a significantly higher cumulative mortality rate compared with those presenting with cT1 tumors (log-rank P < .001). Patients with ulcerated melanomas had significantly higher risk of mortality (hazard ratio, 7.58; 95% CI, 1.02-56.32; P = .04).

Conclusions And Relevance: This multicenter, international, collaborative study yielded evidence that the conjunctival melanoma staging system in the eighth edition of the AJCC Cancer Staging Manual can be used to accurately estimate metastasis and mortality rates. These findings appear to support the use of AJCC staging as a tool for patient care and research.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.1640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555476PMC
June 2019

Retinoblastoma awareness among first contact physicians in Jordan.

Ophthalmic Genet 2019 06 28;40(3):191-195. Epub 2019 May 28.

a Department of Surgery (Ophthalmology) , King Hussein Cancer Center , Amman , Jordan.

: Early diagnosis and timely management of Retinoblastoma (RB) patients are essential to improve eye salvage and survival rates. The objective of this study is to evaluate the level of knowledge regarding retinoblastoma among first-contact physicians, namely students in last year of medical school, pediatricians, and ophthalmologists. : A questionnaire about RB, preluded by a photograph of a child with leukocoria was completed by 138 medical students, 65 pediatricians, and 65 ophthalmologists. Descriptive statistics from the population were obtained and all answers were analyzed. : The majority (n = 253, 94%) of participants in the 3 groups recognized leukocoria as an abnormal sign. However, 62 (45%) medical students did not recognize it as a sign of a life-threatening disease. Only 3 (2%) medical students, 1(2%) pediatrician, and 9 (14%) ophthalmologists achieved a proficiency grade, compared to 136 (67%) medical students and pediatricians who failed to achieve the sufficiency score (70%) in this questionnaire. Ophthalmologists showed a better level of knowledge about RB than medical students and pediatricians, however, 27(42%) of them failed to achieve the sufficiency score. Of interest, only 72 (52%) of medical students, 41 (63%) of pediatricians, and 46 (71%) of ophthalmologists knew that RB needs urgent management. : Most medical students and pediatricians involved in this study lack the sufficient knowledge to detect and timely-refer patients with signs of RB. It is necessary to develop continuous medical education programs for first-contact physicians.
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http://dx.doi.org/10.1080/13816810.2019.1605387DOI Listing
June 2019

Characteristics, management, and outcome of squamous carcinoma of the conjunctiva in a single tertiary cancer center in Jordan.

Int J Ophthalmol 2018 18;11(7):1132-1138. Epub 2018 Jul 18.

Department of Surgery (Ophthalmology), King Hussein Cancer Centre (KHCC), Amman 11941, Jordan.

Aim: To evaluate the features and outcome of management of malignant conjunctival squamous tumors in King Hussein Cancer Center (a referral tertiary cancer center in the Middle East).

Methods: Retrospective case series of 31 eyes for 31 patients with conjunctival squamous neoplasia. Main outcome measures included: age, gender, laterality, tumor location, pathological features, tumor stage, treatment modality, and outcome.

Results: Twenty (65%) patients were males and median age was 58y. Twenty-two (71%) eyes had the tumor in the nasal quadrant. Tumor invasion to nearby structures was seen in 19 (61%) eyes, including the cornea, fornix, eyelid, and orbit in 17 (55%), 1 (3%), 2 (6%), and 3 (10%) eyes, respectively. Eye salvage was achieved by surgical excision with cryotherapy followed by topical chemotherapy in 28 (90%) eyes, and orbital exenteration was necessary in 3 (10%) eyes due to orbital tumor invasion. Tumor recurrence was seen in 7 (23%) eyes, and the significant predictive factors for recurrence were tumor extension onto the nearby structures (=0.04), tumor invasiveness (=0.038), and tumor TNM stage (=0.031). No significant change in visual acuity was seen, and disease related mortality was 6% (2 patients, both had orbital invasion by invasive squamous carcinoma).

Conclusion: Conjunctival squamous carcinoma is more common in males. Advanced American Joint Committee on Cancer (AJCC) T-stage, tumor local invasion, more pathologically aggressive tumors, and surgical treatment alone (without adjuvant therapy) are associated with higher risk for recurrence, and orbital invasion is the most important poor prognostic factor for metastasis and death. Treatment strategies should be affected by tumor characteristics at presentation.
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http://dx.doi.org/10.18240/ijo.2018.07.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048346PMC
July 2018

Characteristics, management, and outcome of patients with uveal melanoma treated by Iodine-125 radioactive plaque therapy in a single tertiary cancer center in Jordan.

Saudi J Ophthalmol 2018 Apr-Jun;32(2):130-133. Epub 2017 Dec 24.

Department of Surgery (Ophthalmology), King Hussein Cancer Centre (KHCC), Amman, Jordan.

Objective: To evaluate King Hussein Cancer Center experience in using Iodine-125 COMS radioactive plaque for treatment of Uveal Melanoma in Jordan.

Methods: Retrospective case series of eyes with uveal melanoma treated by Iodine-125 COMS radioactive plaque therapy. Data collection required access to medical, radiology, Labs and pathology reports. Main outcomes studied includes: Demographics, tumor features, eye salvage, visual outcome, metastasis, and mortality.

Results: Between September 2008 and March 2015, 28 eyes for 28 patients had intraocular uveal melanoma and treated by Iodine-125 radioactive plaque therapy. The mean age at diagnosis was 48 years and 16(57%) were males. The mean tumor thickness was 8 mm (range: 4-13 mm), and 27(96%) patients had medium or large size tumor. The radioactive plaques used had a median size of 16 mm (range: 12-20 mm). The mean apical dose was 83.5 Gy (range 81-87 Gy), and the median radiation rate was 7.25 (range: 4.5-13). At median follow up of 2 years (range 0.5-7 years), eye salvage rate was 93%. Four (15%) patients had distance metastasis, and 3(11%) were dead. Fifty percent of patient had visual acuity better than 20/200 at the last date of follow up.

Conclusion: Our preliminary results are encouraging and are comparable to another countries worldwide. The use of Iodine-125 COMs plaque therapy at the inspection of implementation of plaque therapy in the developing countries can lead to eye salvage in more than 90% of cases, and reserves functional vision in more than 50% of cases.
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http://dx.doi.org/10.1016/j.sjopt.2017.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010601PMC
December 2017

Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature.

Hematol Oncol Stem Cell Ther 2020 Dec 15;13(4):238-241. Epub 2018 Jun 15.

Department of Surgery, King Hussein Cancer Center, Amman, Jordan.

Objective/background: Intra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease.

Methods: An 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment.

Results: Histopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma.

Conclusion: RDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.
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http://dx.doi.org/10.1016/j.hemonc.2018.05.005DOI Listing
December 2020

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features.

Eur J Ophthalmol 2019 Mar 11;29(2):262-268. Epub 2018 Jun 11.

1 Department of Surgery/Ophthalmology, King Hussein Cancer Center, Amman, Jordan.

Purpose:: To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features.

Methods:: A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features.

Results:: Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%).

Conclusions And Relevance:: Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.
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http://dx.doi.org/10.1177/1120672118781200DOI Listing
March 2019

Concomitant Intraocular Retinoblastoma and Choroidal Hemangioma in a 1-Year-Old Boy.

Turk Patoloji Derg 2019 ;35(3):258-262

We report a case of concomitant choroidal hemangioma in an eye that harbored intraocular retinoblastoma (RB) in a 1-year-old child. A 12-month-old boy presented with right white pupil (Leukocoria). The initial clinical diagnosis was unilateral intraocular RB Group C. The eye was treated initially by systemic chemotherapy combined with focal consolidation therapy followed by I-125 plaque radiotherapy. Massive sub-retinal recurrence was seen 4 months later, and Magnetic Resonance Imaging (MRI) showed extra-scleral invasion of the tumor, and therefore enucleation was performed. Microscopic examination revealed a differentiated retinoblastoma associated at the site of the base of the tumor with choroidal hemangioma with trans-scleral invasion. Orbit MRI was repeated 3 months after the surgery, and there was no orbital tumor recurrence. We are reporting a rare case of pathologically concomitant choroidal hemangioma with trans-scleral invasion in an eye that harbored active recurrent intraocular RB. This trans-scleral extension of hemangioma was misinterpreted by MRI as extraocular retinoblastoma and resulted in enucleation.

We report a case of concomitant choroidal hemangioma in an eye that harbored intraocular retinoblastoma (RB) in a 1-year-old child. A 12-month-old boy presented with right white pupil (Leukocoria). The initial clinical diagnosis was unilateral intraocular RB Group C. The eye was treated initially by systemic chemotherapy combined with focal consolidation therapy followed by I-125 plaque radiotherapy. Massive sub-retinal recurrence was seen 4 months later, and Magnetic Resonance Imaging (MRI) showed extra-scleral invasion of the tumor, and therefore enucleation was performed. Microscopic examination revealed a differentiated retinoblastoma associated at the site of the base of the tumor with choroidal hemangioma with trans-scleral invasion. Orbit MRI was repeated 3 months after the surgery, and there was no orbital tumor recurrence. We are reporting a rare case of pathologically concomitant choroidal hemangioma with trans-scleral invasion in an eye that harbored active recurrent intraocular RB. This trans-scleral extension of hemangioma was misinterpreted by MRI as extraocular retinoblastoma and resulted in enucleation.
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http://dx.doi.org/10.5146/tjpath.2017.01411DOI Listing
February 2020

Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan.

Fam Cancer 2018 04;17(2):261-268

Department of Surgery/Ophthalmology, King Hussein Cancer Center, Queen Rania Al-Abdullah Street, P.O Box 1269, Amman, 11941, Jordan.

Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.
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http://dx.doi.org/10.1007/s10689-017-0027-5DOI Listing
April 2018

Management outcome(s) in eyes with retinoblastoma previously inadequately treated with systemic chemotherapy alone without focal therapy.

Oman J Ophthalmol 2017 May-Aug;10(2):70-75

Department of Surgery, King Hussein Cancer Center, Amman, Jordan.

Objective: The objective of this study was to evaluate the outcome of management in eyes with intraocular retinoblastoma (RB) that had received inadequate initial therapy (chemotherapy without focal therapy) before eventually receiving necessary consolidation therapy at a tertiary referral center.

Methods: A retrospective observational case series of 30 eyes from 26 RB patients who had initially received systemic chemotherapy as a sole therapy. The main outcome measures were demographics, laterality, International Classification of RB (ICRB), treatments, tumor control, and survival.

Results: The median age at diagnosis was 24 months and the median delay between time at diagnosis and time at referral to a tertiary center that has adequate focal therapy for RB was 9.5 months (range 5-20 months). Sixteen (62%) patients were monocular from enucleation of the contralateral eye. Features of ICRB Group A tumors were seen in 3 (10%) eyes, Group B in 7 (23%) eyes, Group C in 2 (7%) eyes, Group D in 16 (53%) eyes, and Group E in 2 (7%) eyes. Eighteen (69%) patients required more systemic chemotherapy (median, 4.4 cycles; range, 2-8 cycles), and 8 (26%) eyes received local chemotherapy (subtenon, intravitreal, or intra-arterial). All treated eyes received consolidation therapy as transpupillary thermotherapy and/or cryotherapy. Radioactive plaque therapy was used in 1 (3%) eye and external beam radiation therapy in 3 (10%) eyes. At a mean follow-up of 13 months (median, 11.5 months; range, 9-27 months), enucleation was avoided in 25 (83%) eyes. Two (7%) eyes were enucleated initially, and 3 (10%) were enucleated after failure of additional therapy. Twenty-three (77%) eyes did not show any viable tumor after a median of 11.5 months of follow-up after the last treatment, and 2 (7%) eyes still have residual tumor recurrences that need more consolidation focal therapy.

Conclusion: Chemotherapy alone cannot eradicate RB cells in effected eyes without combination with consolidation therapy by a multidisciplinary team to salvage the affected eye as well as its vision. Nonetheless, chemotherapy can be initiated (to keep the tumor at a less invasive stage) for patients from centers or countries where combination therapy is not available until they gain access to adequate management of RB.
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http://dx.doi.org/10.4103/ojo.OJO_225_2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516466PMC
August 2017

Familial Retinoblastoma: Raised Awareness Improves Early Diagnosis and Outcome.

J Ophthalmol 2017 2;2017:5053961. Epub 2017 Mar 2.

Department of Surgery, King Hussein Cancer Center, Amman, Jordan.

. To study the impact of awareness of retinoblastoma in the affected families on the management and outcome of familial retinoblastoma patients. . This is a retrospective, clinical case series of 44 patients with familial retinoblastoma. Collected data included patient's demographics, laterality, family history, age at diagnosis, presenting signs, treatment modalities, tumor stage, eye salvage rate, metastasis, and mortality. . Out of 200 retinoblastoma patients in our registry, 44 (22%) patients were familial, 18 were probands, and 26 were second, third, or fourth affected family members. There were 76 affected eyes: 31 eyes of probands and 45 eyes of the other affected family members. Among probands, all patients (100%) had at least one eye enucleated: 58% (18 eyes) of the affected eyes were enucleated and 32% (10 eyes) of the affected eyes were radiated. On the other hand, among the nonprobands, only 20% had one eye enucleated, and only 4 eyes (9%) received radiation. The eye salvage rate was significantly higher in the nonprobands than in the probands in this series ( = 0.00206). Patients diagnosed by screening (38%) had excellent visual outcome, and both eyes were salvaged. . Awareness of families of the possibility of retinoblastoma and adequate screening led to a significantly higher rate of eye salvage in patients with familial retinoblastoma.
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http://dx.doi.org/10.1155/2017/5053961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350530PMC
March 2017

Management and Outcome of Uveal Melanoma in a Single Tertiary Cancer Center in Jordan.

Turk Patoloji Derg 2016 ;32(3):186-92

Departments of Ophthalmology, King Hussein Cancer Centre (KHCC), Amman, Jordan.

Objective: The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an example of a referral tertiary cancer center in the Middle East.

Material And Method: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality.

Results: There was slight female preference, and the median age at diagnosis was 45 years. Eighteen (39%) eyes were treated by primary enucleation, and 28 (61%) eyes were treated by I-125 radioactive plaque. The melanoma was in the choroid in 40 (87%) eyes and in the ciliary body in 6 (13%) eyes, with no single tumor in the iris. According to the 7th edition of the American Joint Committee on Cancer staging system (UICC/AJCC); 8 (17%) were T1, 17 (36%) were T2, 16 (35%) were T3, and 5 (11%) were T4. One (2%) patient showed lymph node metastasis (N1), and 6 (13%) patients showed distant metastasis (M1). Pathologically, 2 (10%) of the enucleated eyes were spindle cell type, 4 (20%) were epithelioid cell type, and 14 (70%) were mixed type. Extrascleral extension was seen in three (15%) eyes, and optic nerve invasion in two (10%) eyes. After brachytherapy, 26 (93%) eyes were salvaged, and 2 eyes were consecutively enucleated; one for tumor recurrence, and one for uncontrolled painful neovascular glaucoma. The eye salvage rate post plaque was 93% (26/28), and the visual acuity for the salvaged eyes was equal or better than 0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than 0.1 in 10 (38%) eyes.

Conclusion: The incidence of uveal melanomas in our region is low compared to that in the West with a younger age at presentation. Candidate tumors for radioactive plaque therapy were successfully controlled in 93% of cases.
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http://dx.doi.org/10.5146/tjpath.2015.01357DOI Listing
April 2017

Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review.

JAMA Ophthalmol 2016 May;134(5):584-591

Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada6Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.

Importance: Intra-arterial chemotherapy has emerged as a treatment for intraocular retinoblastoma and has been quickly adopted by centers worldwide.

Objective: To conduct a systematic review and attempt a meta-analysis to summarize the reported outcomes of intra-arterial chemotherapy.

Evidence Review: In January 2015, we performed comprehensive searches in Medline, Embase, Cochrane, and Web of Science from inception through January 2015, including any peer-reviewed English-language publication that described outcomes related to toxicity or efficacy in at least 4 patients.

Findings: From a total of 208 identified publications, 28 met inclusion criteria. Twelve reports with discernable nonduplicative information were included, reporting 655 patients, 757 eyes, and 2350 catheterizations. All were single-arm case series, and 67% (8 of 12) were retrospective. Across all studies, globe salvage was achieved for 502 (66%) of all eyes. Most common reported toxicities were chorioretinal atrophy and vascular occlusions. There were at least 13 reports of children with metastases. After publication, 7 additional children had metastases. The 4 different classification systems used challenged the comparison of disease severity at presentation. Visual outcome was not addressed in most studies. Meta-analyses were not possible because no study had a comparative group. Assessment of risk of bias was not possible because no validated tool for single-arm studies was available.

Conclusions And Relevance: Intra-arterial chemotherapy is a promising new treatment associated with high rates of globe salvage. However, the literature is limited by the predominance of retrospective case series, absence of comparison groups, short median follow-up, heterogeneous definitions and tumor classifications, and frequent duplicate reporting. Metastases have been observed, and long-term follow-up is needed. Until the results of clinical, prospective studies are available, it is recommended that intra-arterial chemotherapy be offered selectively among other options, with fully informed discussion about all possible risks, benefits, and uncertainties.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.0244DOI Listing
May 2016

Surgical repair of rhegmatogenous retinal detachment in eyes harboring active retinoblastoma.

Ophthalmic Genet 2016 09 5;37(3):314-7. Epub 2016 Feb 5.

a Department of Surgery , King Hussein Cancer Center , Amman , Jordan.

Background: Intraocular surgeries are classically contraindicated for patients with active Retinoblastoma (RB) due to the risk of tumor dissemination. Unfortunately, RB treatment may be complicated by rhegmatogenous retinal detachment (RD) that necessitates surgical repair especially in a child who is monocular from enucleation of the contralateral eye.

Objective: To assess the outcome of surgical repair of rhegmatogenous RD in children with RB using non-drainage scleral buckling.

Results: Rhegmatogenous RD was diagnosed in three eyes of three children during treatment of RB; one of which had associated tractional RD. All patients received systemic chemotherapy, cryotherapy, and thermal therapy. RD was present at the site of the most recent cryotherapy in all of the three eyes. RD was repaired externally with a scleral buckling procedure without subretinal fluid drainage in each of the three eyes. The retina reattached completely after surgery in two eyes and only partially in one eye. In one eye, which had the tractional component, complete retinal attachment was not achieved and thus enucleation was performed. Orbital or metastatic retinoblastoma was detected in none of the cases on follow-up at 6-36 months.

Conclusions: Scleral buckling without subretinal fluid drainage is a useful technique for repairing rhegmatogenous RD in eyes with RB mainly in the absence of a tractional component.
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http://dx.doi.org/10.3109/13816810.2015.1046556DOI Listing
September 2016