Yacoub A. Yousef

Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review

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.

Failure of Systemic Propranolol Therapy for Choroidal Hemangioma of Sturge-Weber Syndrome: A Report of 2 Cases

Propranolol was incidentally discovered to induce accelerated involution of infantile cutaneous hemangioma. Thereafter, reports have demonstrated a favorable response to propranolol as a first-line treatment for cutaneous, orbital, and ocular hemangioma in different ages. We report the outcome of oral propranolol therapy in 2 cases with choroidal hemangioma of SturgeWeber syndrome (SWS).

Intravitreal bevacizumab in the treatment of diabetic ocular neovascularization.

Purpose: To evaluate the efficacy of intravitreal bevacizumab for treating diabetic retinal and/or iris neovascularization. Methods: Consecutive, prospective, interventional case series study of 60 eyes with diabetic retinal and/or iris neovascularization. Patients had a complete ocular examination before receiving 1.25 mg (0.05 mL) of intravitreal bevacizumab. Abnormal new vessels elsewhere in the retina, optic disk, or iris were graded by size and associated hemorrhage or glaucoma. Patients had complete postinjection ophthalmic evaluations with regrading of the abnormal new vessels at 3 months and 6 months. The main outcome measures included clinical partial or total regression of abnormal new vessels, changes in visual acuity, and complications related to the intravitreal injections. Results: Twenty-six patients (47.3%) were men (mean age, 59 years). Abnormal new vessel regression at 6 months occurred in 65% of new vessels of the iris (P = 0.001), 45% of new vessels of the optic disk (P = 0.009), and 43% of new vessels elsewhere (P = 0.008). The visual acuity improved in 20% of eyes, which was not significant (P = 0.235); the visual acuity deteriorated in 23% of eyes (P = 0.163). No systemic or ocular side effects developed except for postinjection hypotony in one eye. Conclusion: Intravitreal bevacizumab is a well-tolerated medication that causes regression of abnormal diabetic neovascularization. New vessels of the iris responded more than new vessels of the optic disk and new vessels elsewhere.

Choroidal metastasis as the sole initial presentation of metastatic lung cancer

Choroidal metastasis as an initial presenting feature of metastatic lung cancer is exceedingly rare. External beam radiotherapy (EBRT) is an effective and widely accepted therapeutic modality. However, data addressing the effectiveness of other treatment strategies is limited. We present a patient with choroidal metastases secondary to lung cancer and review the relevant literature. A 25-year-old male presented with deterioration of vision. His evaluation revealed bilateral choroidal metastasis secondary to adeno- carcinoma of the lung. Unfortunately, his vision continued to deteriorate despite treatment with EBRT and chemotherapy. Choroidal metastasis as an initial presentation of metastatic lung cancer is exceedingly rare, as only 30 cases have been reported. EBRT and systemic chemotherapy are effective therapeutic modalities. This case report could prove helpful to clinicians faced with a similar exceedingly rare scenario.

Familial Retinoblastoma: Raised Awareness Improves Early Diagnosis and Outcome

Purpose. To study the impact of awareness of retinoblastoma in the affected families on the management and outcome of familial retinoblastoma patients. Methods and Materials. This is a retrospective, clinical case series of 44 patients with familial retinoblastoma. Collected data included patients demographics, laterality, family history, age at diagnosis, presenting signs, treatment modalities, tumor stage, eye salvage rate, metastasis, and mortality. Results. 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 (p = 0.00206). Patients diagnosed by screening (38%) had excellent visual outcome, and both eyes were salvaged. Conclusion. 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.

Management and outcome of uveal melanoma in a single tertiary cancer center in Jordan

Abstract 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.

External Beam Radiation Therapy for RetinoblastomaResistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors

External Beam Radiation Therapy for Retinoblastoma Resistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors Abstract: Purpose: To evaluate the outcome of external beam radiation therapy (EBRT) for treatment of retinoblastoma resistant to chemotherapy and focal therapy. Methods and Materials: A retrospective case series of 24 eyes for 20 retinoblastoma patients treated by EBRT after failure of tumor control by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival. Results: The median age at diagnosis was 12 months. There were 12 (60%) males and 16 (80%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range: 6-8 cycles). The dose of 45Gy was used in all eyes. The mean follow-up was 55months. Eye salvage rate after EBRT was 45% (11eyes); 67% ( 2/3) for IIRC group B, 63% (5/8) for group C, and 31% (4/13) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control (p=0.0327 and 0.0333 consecutively). Post EBRT complication rate was 80% (19/24) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), and radiation retinopathy (2). Conclusion: Eyes with retinoblastoma that failed chemotherapy were controlled with EBRT. However the presence of vitreous seeds, stage migration during chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.

The Impact of Growth Patterns of Retinoblastoma (Endophytic, Exophytic, and Mixed Patterns) / Retinoblastomda Büyüme Paternlerinin Etkisi (Endofitik, Ekzofitik ve Karışık Paternler)

ABSTRACT Objective: To study the impact of the retinoblastoma growth pattern (endophytic vs. exophytic) on the clinical and pathological features after primary enucleation. Material and Method: A retrospective case series of 42 eyes of 41 patients who had pathologically confirmed retinoblastoma. The main outcome measures included demographics, laterality, international intraocular retinoblastoma (IIRC) group, vitreous seeding, neovascular glaucoma, choroid invasion, optic nerve invasion, metastasis, and survival. Results: The median age at diagnosis was 30 months. Nineteen (46%) patients were males, and 17(41%) patients had bilateral retinoblastomas. Eight (19%) eyes were IIRC group C, 20 (48%) eyes were IIRC group D, and 14 (33%) eyes were IIRC group E. Nineteen (45%) tumors were endophytic, 14 (33%) were exophytic, and 9 (21%) were mixed. Choroid invasion was seen in 4 (21%) of the endophytic tumors, 5 (36%) of the exophytic tumors, and 8 (89%) of the mixed tumors (p=0.025). A mixed growth pattern was associated with massive choroid invasion in 5 (56%) of eyes. Neovascular glaucoma was seen in 5 (56%) of the mixed tumors (p=0.0376). Vitreous seeds were seen in 6 (67%) of the mixed tumors (p=0.0448). Optic nerve invasion as well as patients’ age at diagnosis, gender, and tumor laterality had no correlation with tumor growth pattern. At a median follow up of 36 months, no single case had metastasis or was dead. Conclusion: Exophytic tumors have higher risk of choroid invasion, while endophytic tumors have higher risk of vitreous seeding. The mixed tumor growth pattern is associated with more advanced IIRC group, more risk of neovascular glaucoma, and more risk of massive choroid invasion. ÖZ Amaç: Primer enükleasyon sonrası retinoblastomanın büyüme paternlerinin (endofitik, ekzofitik ve karışık) klinik ve patolojik özelliklere etkisini araştırmak. Gereç ve Yöntem: Retinoblastoması patolojik olarak onaylanmış 41 hastaya ait 42 gözden oluşan retrospektif olgu serisi. Dahil edilen ana ölçümler: Demografik bilgiler, lateralite, uluslararası intraoküler retinoblastoma grubu (UİRG/IIRC) sınıfandırması, vitröz yayılım, neovasküler glokom, koroid invazyonu, optik sinir invazyonu, metastaz ve yaşam süresi. Bulgular: Tanı anında medyan yaş 30 ay idi. Ondokuz (%46) hasta erkekti ve 17 (%41) hasta bilateral retinoblastomalıydı. Sekiz (%19) göz IIRC grup C, 20 (%48) göz IIRC grup D ve 14 göz IIRC grup E idi. Ondokuz (%45) tümör endofitik, 14 (%33) ekzofitik ve 9 (%21) karışıktır. Koroid inazyonu endofitik tümörlerin 4 (%21)’ünde, ekzofitik tümörlerin 5 (%36)’inde ve karışık tümörlerin 8 (%89)’inde görülmüştür (p=0,025). Karışık büyüme paterni gözlerin beşinde (%56) massif koroid invazyonu ile ilişkilidir. Neovasküler glokom karışık paternli tümörlerin 5 (%56)’inde görülmüştür (p=0,0376). Vitröz yayılım karışık tümörlerin 6 (%67)’sında görülmüştür (p=0,0448). Optik sinir invazyonu yanı sıra tanı anında yaş, cinsiyet ve tümör lateralitesi tümör büyüme paterni ile ilişkili değildir. Medyan 36 aylık takipte hiç bir olguda ölüm veya metastaz görülmemiştir. Sonuç: Ekzofitik tümörlerin daha fazla koroid invazyon riski, endofitik tümörlerin ise daha fazla vitröz yayılım riski vardır. Karışık büyüme paterni daha ileri IIRC grubu, daha fazla neovasküler glokom ve massif koroid invazyonu ile ilişkilidir.

A histopathologic analysis of 50 eyes primarily enucleated for retinoblastoma in a tertiary cancer center in Jordan.

Abstract Objective: To analyze the histopathologic features of the eyes with intraocular retinoblastoma primarily treated by enucleation in a tertiary cancer center in Jordan. Material and Method: A retrospective case series of 50 eyes for 49 patients who had pathologically confirmed retinoblastoma after enucleation as primary therapy. The main outcome measures included demographics, laterality, international classification of intraocular retinoblastoma, choroid invasion, optic nerve invasion, anterior chamber invasion, and tumor differentiation. Results: The median age at enucleation was 30 months. Twenty-seven (55%) patients were males, and 19 (39%) patients had bilateral retinoblastoma. High risk pathological features were seen as massive choroid invasion in 9 (18%) eyes, post-laminar optic nerve invasion in 7 (14%) eyes, and anterior chamber, iris or ciliary body invasion in 7 (14%) eyes. Thirty-seven (74%) tumors were well/moderately differentiated, and 13 (26%) were poorly differentiated. Poorly differentiated tumors presented later (median 31 months) than well/ moderately differentiated tumors (26 months) and were associated with a higher incidence of high-risk pathological features. No single ICRB group C eye had high-risk pathological features, while 17% and 4% of group D eyes and 28% and 33% of group E eyes had massive choroid invasion and post-laminar optic nerve invasion, respectively. Eighteen (36%) patients received adjuvant chemotherapy for high risk pathological features, and at median follow up of 40 months, no single case had metastasis or was dead. Conclusion: Our pathologic findings were similar to the developed world. They were supportive of the predictive power of the international classification of retinoblastoma staging system for the likelihood of high risk pathological features. Poorly differentiated tumors were associated with a higher incidence of high risk pathological features than well/moderately differentiated tumors. Öz Amaç: Ürdün’ de üçüncü basamak kanser merkezinde primer olarak enükleasyon ile tedavi edilen intraoküler retinoblastomalı gözlerin histopatolojik özelliklerinin araştırılması. Gereç ve Yöntem: Primer tedavi olarak enükleasyon uygulandıktan sonra patolojiyle retinoblastoma tanısı alan 49 hastaya ait 50 gözden oluşan retrospektif olgu serisi. Demografik bulgular, lateralite, Uluslararası Retinoblastoma Sınıflaması, koroid invazyon, optik sinir invazyonu, ön kamera invazyonu ve tümör farklılaşması ana sonuç verileri olarak dahil edildi. Bulgular: Enükleasyon sırasında ortalama yaş 30 aydı. Yirmi yedi (%55) hasta erkekti ve 19 (%39) hastanın bilateral retinoblastoması vardı. Yüksek riskli patolojik özellikler; 9 (%18) gözde massif koroid invazyonu, 7’sinde (%14) post-laminar optik sinir invazyonu ve 7’sinde (%14) ön kamera, iris veya silier cisimcik invazyonu şeklindeydi. Otuz yedi (%74) tümör iyi/orta derecede diferansiye ve 13 (%26) az diferansiye idi. Az diferansiye tümörler (ortalama 31 ay), iyi/orta derecedeki tümörlere göre daha geç (ortalama 26 ay) ortaya çıkmakta ve yüksek riskli patolojik özellikler ile daha sıkı ilişki göstermektedir. Uluslararası Retinoblastoma Sınıflandırmasına göre grup D olanların %17 ve %4’ünde, grup E olanların %28 ve %33’ünde sırasıyla massif koroid invazyonu ve post-laminar optik sinir invazyonu varken, grup C olanlarda ise yüksek riskli patolojik özellik yoktu. On sekiz (%36) hasta yüksek riskli patolojik özellikler için adjuvan kemoterapi aldı ve 40 aylık ortalama takip süresince hiçbir olgunun metastazı yoktu ve hiçbiri ölmemişti. Sonuç: Sonuçlarımız, gelişmiş ülkelere benzerdir. Yüksek risk faktörleri için Uluslararası Retinoblastoma Sınıflandırma evreleme sisteminin öngörü değerini destekleyicidir. İyi/orta derecede diferansiye tümörlere göre az diferansiye tümörler, yüksek risk faktörleri ile daha sıkı ilişkilidir.

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

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.