Optimizing Surgical Management for Rhegmatogenous Retinal Detachment in Eyes with Active Retinoblastoma: A Safety-Driven Approach.

Introduction: Intraocular surgeries are conventionally contraindicated for patients with active retinoblastoma (Rb) due to the potential risk of tumor dissemination. However, surgery is occasionally necessary to preserve vision in patients with a single eye when the eye is complicated by rhegmatogenous retinal detachment (RRD). Objective: This study aims to evaluate the outcomes of surgical repair for RRD in pediatric patients with active Rb utilizing a non-drainage scleral buckling approach. Results: This cohort included six eyes from six patients who harbored active Rb and presented with RRD; one had a concurrent tractional component. All eyes (100%) had active intraocular Rb and were undergoing active therapy (systemic chemotherapy, cryotherapy, and thermal laser therapy) when RRD developed. RRD consistently manifested at the site of recent cryotherapy in all cases. RRD repair in the affected eyes was performed by scleral buckling without subretinal fluid drainage. Five of the six eyes (83%) achieved complete retinal reattachment. One eye (17%) with a tractional component exhibited partial reattachment and was eventually enucleated due to persistent active disease. At a median follow-up of 15 months (range 12-180 months) after scleral buckling, all five eyes had persistent retinal attachment, and no case developed orbital or distant metastasis. Conclusions: Our study demonstrates that nondrainage scleral buckling is an effective and safe method for the surgical repair of RRD in eyes harboring active Rb, as most cases achieved persistent complete retinal reattachment without the risk of tumor spread.

The Impact of Tumor Laterality (Unilateral vs. Bilateral) on Presentation and Management Outcome in Patients with Retinoblastoma.

Background: This study compares the outcomes of managing retinoblastoma between patients with unilateral and bilateral presentations. Methods: The study, conducted at the King Hussein Cancer Center in Amman, Jordan, retrospectively analyzed cases of retinoblastoma treated between March 2003 and December 2019. Evaluation criteria included clinical features, disease stage, treatment methods, and overall management outcomes. Results: The study comprised 697 eyes from 478 patients with retinoblastoma, with 52% being males. Bilateral disease was observed in 70% of patients, and a family history of retinoblastoma was more prevalent in cases with bilateral disease (20%) compared to those with unilateral disease (4%). Unilateral cases had a median age at diagnosis of 28 months, whereas bilateral cases were diagnosed at a median age of 6 months. Extra-ocular retinoblastoma was detected in 1% of eyes. According to the International Intraocular Retinoblastoma Classification (IIRC), 88% of unilateral cases presented with advanced disease (IIRC group D/E), compared to 46% in bilateral cases. Primary enucleation was performed in 29% of unilateral cases and 16% of bilateral cases (p-value 0.0007). Eye salvage rates were 31% in unilateral cases and 68% in bilateral cases (p-value < 0.0001). At 120 months of follow-up, 5% of patients died from secondary neoplasms or metastases, 81% were alive, and 14% were lost to follow-up. There was no significant difference in metastasis, secondary neoplasms, or mortality between patients with unilateral and bilateral retinoblastoma. Conclusions: This study highlights the nuanced differences in clinical characteristics and outcomes between unilateral and bilateral retinoblastoma, emphasizing the necessity of customized management and early detection strategies. It demonstrates that while bilateral retinoblastoma benefits from earlier detection and has a higher rate of eye salvage, there is no significant difference in metastasis or mortality rates when compared to unilateral cases. The critical roles of primary enucleation in advanced cases, along with effective communication and patient education, are also underscored to improve treatment adherence. Overall, these findings point to the importance of tailored approaches in optimizing outcomes for the diverse patient population affected by retinoblastoma.

Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.

BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.

Declining incidence and improving survival of ocular and orbital lymphomas in the US between 1995 and 2018.

This epidemiological study examined ocular and orbital lymphomas in the United States from 1995 to 2018, using data from the North American Association of Central Cancer Registries database of 87,543 patients with ocular and adnexal malignancies. We identified 17,878 patients (20.4%) with ocular and orbital lymphomas, with an age-standardized incidence rate (ASIR) of 2.6 persons per million (ppm). The incidence was the highest in the orbit (ASIR = 1.24), followed by the conjunctiva (ASIR = 0.57). Non-Hodgkin B-cell lymphoma was the most prevalent subtype (85.4%), particularly marginal-zone lymphoma (45.7%). Racial disparities were noted, with Asia-Pacific Islanders showing the highest incidence (orbit, 1.3 ppm). The incidence increased significantly from 1995 to 2003 (Average Percent Change, APC = 2.1%) but declined thereafter until 2018 (APC = - 0.7%). 5-year relative survival (RS) rates varied, with the highest rate for conjunctival lymphoma (100%) and the lowest for intraocular lymphoma (70.6%). Survival rates have generally improved, with an annual increase in the 5-year RS of 0.45%. This study highlights the changing epidemiological landscape, pointing to initial increases and subsequent decreases in incidence until 2003, with survival improvements likely due to advancements in treatment. These findings underscore the need for further research to investigate the root causes of these shifts and the declining incidence of ocular lymphoma.

From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma.

Molecular biology studies of uveal melanoma have resulted in the development of novel immunotherapy approaches including tebentafusp-a T cell-redirecting bispecific fusion protein. More biomarkers are currently being studied. As a result, combined immunotherapy is being developed as well as immunotherapy with bifunctional checkpoint inhibitory T cell engagers and natural killer cells. Current trials cover tumor-infiltrating lymphocytes (TIL), vaccination with IKKb-matured dendritic cells, or autologous dendritic cells loaded with autologous tumor RNA. Another potential approach to treat UM could be based on T cell receptor engineering rather than antibody modification. Immune-mobilizing monoclonal T cell receptors (TCR) against cancer, called ImmTAC TM molecules, represent such an approach. Moreover, nanomedicine, especially miRNA approaches, are promising for future trials. Finally, theranostic radiopharmaceuticals enabling diagnosis and therapy with the same molecule bring hope to this research.

Metastatic esophageal carcinoma to the eye masquerading as inflammatory vitreo-retinitis: A case report and literature review.

We report an unusual case of metastatic esophageal carcinoma to the vitreous associated with focal retinitis in a 44-year-old male. A 44-year-old male patient, known case of locally advanced esophageal carcinoma, presented with a 3-day history of left eye floaters. The initial diagnosis was inflammatory vitreo-retinitis that responded to systemic steroids. Four months later, the patient presented with relapsed intraocular inflammation, vitreous biopsy using a 25G needle was performed, and cytology confirmed the presence of metastatic carcinoma consistent with his primary esophageal cancer. The patient received external beam radiotherapy to his ocular and brain metastasis, and his eye examination was stable. Five months later, the patient passed away due to progressive brain metastasis.

Optic Disc Swelling in Cancer Patients: Etiology and Implications.

PURPOSE: To analyze the etiology and implications of optic disc swelling in cancer patients treated at a specialized tertiary cancer center in Jordan. METHODS: This was a retrospective study of all cancer patients who had optic disc swelling between January 2019 and December 2020 at King Hussein Cancer Center (KHCC). Patients' data included age, sex, laterality, visual acuity, and the underlying cause and management for the optic disc swelling. RESULTS: Optic disc swelling was present in 58 cancer patients (96 eyes), with 38 (65%) having bilateral involvement. Among these, 33 (57%) were female, and 43 (74%) were ≤40 years old. At diagnosis, 58 (63%) eyes had a best-corrected visual acuity (BCVA) better than 0.5, improving to 73 (76%) eyes at the last follow-up. High intracranial pressure (ICP) was the most common primary cause (30 patients/52%), followed by tumor infiltration of the optic nerve (10 patients/17%), optic nerve compression (7 patients/12%), and optic nerve inflammation (5 patients/9%). Four patients had pseudopapilledema. Among the 30 patients with high ICP, CNS tumors were predominant (21 patients/70%), with only 3 having idiopathic intracranial hypertension. Medications, including ATRA (All-Trans Retinoic Acid) and systemic steroids, contributed to increased ICP in six patients (20%). BCVA was less than 0.5 in all eyes (100%) affected by tumor infiltration, optic nerve inflammation, and ischemic optic neuropathy, while only eight eyes (14%) with optic disc swelling due to elevated ICP had a BCVA less than 0.5 (p < 0.0001). Management included steroids (53 patients/91%), acetazolamide (30 patients/52%), chemotherapy (20 patients/34%), radiation therapy (13 patients/22%), frequent lumbar punctures (12 patients/21%), and surgery (28 patients/48%). Visual acuity improved in 40 eyes (42%), with only 4 eyes (4%) experiencing deterioration. At a 12-month median follow-up period, 11 (19%) patients were dead, 10 (10%) eyes had poor vision (BCVA less than 0.1), and 21 (22%) eyes had BCVA 0.5 or better. CONCLUSIONS: Various underlying pathologies can induce optic disc swelling in cancer patients, a grave condition capable of causing vision loss. Notably, tumor infiltration of the optic nerve tends to result in more profound visual impairment compared to papilledema due to elevated ICP. Timely detection is crucial, and immediate symptomatic treatment followed by addressing the underlying cause is essential to prevent irreversible optic nerve damage and vision loss in cancer patients.

Causes of death and survival analysis for patients with retinoblastoma in Jordan.

Purpose: To analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan. Methods: We reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death. Results: Twenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4-38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p < 0.0001), the presence of high-risk pathological features in the enucleated eyes (p = 0.013), parental refusal of the recommended primary treatment plan (p < 0.0001), and extraocular extension (p < 0.0001). Conclusion: The 5-year survival rates of Rb patients in Jordan are as high as those in high-income countries. However, 5% are still dying from metastatic disease, prompting the need for awareness campaigns to educate the public about the high cure rates and to prevent treatment abandonment.

The Impact of Color Vision Deficiency on the Capability of Ophthalmologists to Diagnose Benign and Malignant Choroidal Tumors.

BACKGROUND: Color vision deficiency (CVD) is an under-reported problem among medical personnel, and its impact is still not well characterized. We aim to assess the impact of CVD among ophthalmologists on the accuracy of diagnosing different benign and malignant choroidal lesions. METHODS: This is a cross-sectional study conducted on ophthalmologists. We used a web-based survey to collect responses through professional ophthalmology society social media. The survey included a set of five images for normal fundus, choroidal nevus, circumscribed choroidal hemangioma, choroidal metastasis, and choroidal melanoma, wherein each image simulated the three main types of CVD: protanopia, deuteranopia, and tritanopia, in addition to a non-simulated image. RESULTS: Forty-one participants were included, with a mean age of 40 (±9.2) years. They were 28 (68%) men and 13 (32%) women. Participants showed significantly low accuracy for definite diagnosis for circumscribed choroidal hemangioma, nevus, melanoma, and metastasis when the images simulated protanopia and deuteranopia, but not tritanopia. Nevertheless, participants maintained the capability to recognize the nature of the lesions for both simulated and non-simulated images if they were benign or malignant, thereby ensuring immediate referral for specialized care. The exception was with simulated choroidal nevi images, wherein participants incorrectly assigned simulated protanopia and deuteranopia nevi images to malignant lesions. CONCLUSION: Protanopia and deuteranopia affected the accuracy of diagnosing several choroidal lesions; however, ophthalmologists with those two simulated CVDs were still able to discriminate between benign and malignant tumors.

A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma.

AIM: To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. METHODS: A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis-to-enucleation, results of pathology, metastasis, and mortality were retrieved. RESULTS: Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). CONCLUSION: Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.

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

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.

Retinoblastoma and uveal melanoma in Jordan: incidence, demographics, and survival (2011-2020).

PURPOSE: We present an epidemiologic analysis of retinoblastoma (RB) and uveal melanoma (UM) in Jordan to aid national strategies for improved ocular cancer surveillance and control. METHODS: A retrospective cohort of all Jordanian patients with RB and UM diagnosed over 10 years (2011-2020). Outcome measures included incidence, demographics, and outcomes. RESULTS: Retinoblastoma (n = 124) was more common than UM (n = 82); there was no sex predilection for either group. The median age at diagnosis of RB was 15 months(Six and 28 months for bilateral and unilateral cases, respectively), and the mean age-adjusted incidence was 8.2 cases per-million-children per year for children aged five years or less(one per 15,620 newborn per year). Fifty-one(41%) had bilateral disease, and 18(15%) had familial disease. Ninety-six(55%) eyes were group D or E(78% were T3/T4), and the five-year survival rate was 96%.For UM, the median age at diagnosis was 45 years with an incidence of 1.39 new cases per year per one million population. All(100%) had nonfamilial unilateral disease. Seventy-three(89%) had the tumor in the choroid, and 48(58%) had an advanced tumor that had invaded the sclera or the orbit (T3/T4) tumor. Sixty-two(76%) were treated by I-125 radioactive plaque, with globe salvage in 59(95%); the five-year survival rate was 85%. CONCLUSION: In Jordan, RB is more common and has better survival than UM. RB in Jordan and Western countries is equal in terms of incidence, globe salvage, and survival. UM is less common, with lower age at diagnosis (that was associated with better survival) in Jordan than in Western countries.

Anterior Ocular Biometrics as Measured by Ultrasound Biomicroscopy.

BACKGROUND: High frequency ultrasonography (ultrasound biomicroscopy; UBM) is an ophthalmic diagnostic tool that can be used to measure the depth of the anterior segment (ASD), the anterior chamber angle (ACA), as well as thicknesses of the iris and the ciliary body (CB). METHODS: The anterior segment dimensions and thicknesses were measured by Sonomed 35-MHz. RESULTS: Measurements for 95 eyes from 52 adults were analyzed. The mean and median ASD and ACA were 2.91, 2.92 ± 0.41 mm and 34.1, 34.3 ± 12.1 degrees, respectively. The angle superiorly was wider than inferiorly (p = 0.04). At the root of the iris, the mid of the iris, and the juxtapupillary edge of the iris, the iris thicknesses (median, mean) were 0.40, 0.41 ± 0.1, 0.50, 0.51 ± 0.1, and 0.70, 0.71 ± 0.1 mm, respectively. The thicknesses of CB and CB together with the ciliary processes (median, mean), were 0.70, 0.71 ± 0.15 mm and 1.36, 1.41 ± 0.15 mm, respectively. The upper quadrant of both the iris and the CB was significantly thicker than the lower quadrant (p = 0.04). CONCLUSIONS: Our biometric measurements for the anterior segment can be used as normative data for anterior segment depth and angle and iris and ciliary body thickness in normal eyes.

Imaging of Uveal Melanoma-Current Standard and Methods in Development.

Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, a biopsy followed by a pathological exam is used only in certain cases. Therefore, an early and noninvasive diagnosis is essential to enhance patients' chances for early treatment. We reviewed imaging modalities currently used in the diagnostics of uveal melanoma, including fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), as well as positron emission tomography/computed tomography (PET/CT) or magnetic resonance imaging (MRI). The principle of imaging techniques is briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities are explained. We describe UM imaging innovations, show their current usage and development, and explain the possibilities of utilizing such modalities to diagnose uveal melanoma in the future.

Improving Medical Students' Awareness About Retinoblastoma: A Practical Strategy.

Background: Eye salvage and survival for patients with retinoblastoma (RB) can be improved by enhancement of early diagnosis. This study aims to investigate the impact of modifying the teaching curriculum for medical students about awareness of this condition. Methods: Medical students completed a questionnaire about RB, preluded by a photograph of a child with leukocoria. Participants were divided into group A (138 participants) and group B (151 participants) who are medical students who have completed the ophthalmology rotation before and after implementing modifications on teaching curriculum that focuses on the red flags of RB consecutively. Results: Most participants considered leukocoria an abnormal sign. Group A had significantly lower knowledge about diagnosis for RB (P=0.0001). Participants scored higher in group B for the critical questions, such as knowing that RB is a fatal disease (P=0.041) that needs urgent treatment (P=0.042). Only three (2%) students adopted the "watch and wait" strategy in group B, compared to 16 (12%) in group A (P=0.0013). Overall, proficiency score (≥90%) was achieved by 12 (8%) students in group B, but only three (2%) students in group A. Only 41 (27%) students in group B, compared to 90 (65%) students in group A, failed to obtain a sufficiency score (≥70%) in the questionnaire. Conclusion: Modifying the teaching curriculum of the ophthalmology rotation with an intensified focus on awareness of the life-threatening condition retinoblastoma improved medical students' knowledge of this malignancy. This intervention is one of the modalities that can lead to a reduction in diagnosis and referral delays and improvement in outcome and survival.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7th and 8th Editions.

Importance: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual incorporated new changes from its 7th edition for classifying retinoblastoma (RB). Objective: We assessed the comparative prognostic values of the 7th and 8th editions of the AJCC clinical (cTNM) staging manuals for RB and suggested modifications for future edition accordingly. Design: A retrospective, observational study. Setting: King Hussein Cancer Centre. Participants: A cohort of 478 patients and 565 eyes with RB. Main Outcomes and Measures: Main outcome measures included demographics; tumor features, AJCC cTNM stage, and eye salvage rates. The prognostic performance of the different staging systems was assessed with the concordance index (C-index) and likelihood ratio χ2 tests. Results: The overall eye salvage rate was 65%. Stage migration occurred for 330 (48%) eyes with the AJCC Staging Manual, 8th edition. Based on the 7th edition AJCC staging, the eye salvage rate was 94% (n=177) for T1 tumors (98% for T1a, 93%for T1b, and 90%for T1c), 69% (n=204) for T2 tumors (73% for T2a and 62%for T2b), and 51% (n=40) for T3 tumors. Based on the 8th edition AJCC staging, the eye salvage rate was 95% (n=139) for T1 tumors (98% for T1a and 93% for T1b), 68% (n=281) for T2 tumors (90%for T2a and 66%for T2b), and 12% (n=1) for T3 tumors. With our proposed cTNM modifications, the eye salvage rate was 94% (n=177) for T1 tumors (98%for T1a, 93%for T1b, and 90% for T1c), 66% (n=243) for T2 tumors (73% for T2a, 62% for T2b, and 55% for T2c), and 12% (n=1) for T3 tumors. As estimated by odds ratios, more advanced cTNM stage (regardless of the cTNM staging system) was significantly associated with an increased chance of treatment failure (P < .0001). The C-index for both the 8th edition and the proposed modifications were approximately equal, and both were higher than that of the 7th edition. However, the proposed modifications had the highest likelihood ratio χ2 value and the best bootstrap 95% confidence interval. Conclusions and Relevance: Our proposed modifications on the clinical TNM Staging System for RB harbor more detailed subgroup classification criteria that provides better prognostic value for eye globe salvage than the published similar (but not identical) AJCC Staging Manual, 7th and 8th editions, furthermore these modifications may resolve the discrepancies in the previously published different classification systems for RB.

Ultrasound Biomicroscopy Measurements of the Normal Thickness for the Ciliary Body and the Iris in a Middle East Population.

PURPOSE: Ciliary body (CB) and iris thicknesses may change with certain eye diseases as well as between different populations. Here, we report Ultrasound Biomicroscopy Measurements (UBM) of the normal thickness for the CB and the iris from a homogenous population in the Middle East. PATIENTS AND METHODS: Sonomed 35-MHz (SONOMED, INC. New York, USA) images were obtained at 4 radial meridians, and the thickness was measured at 3 locations along the radial length of the iris and at the thickest part of the CB. Parameters included mean thickness, median thickness, range, and standard deviation. RESULTS: Of 46 adult patients, 83 normal eyes were included in this analysis. The overall mean, median iris thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin in mm were 0.42, 0.41 ± 0.08, 0.52, 0.51± 0.08, and 0.72, 0.71± 0.1, respectively. The overall mean, median thicknesses of the CB and CB + ciliary processes in mm were 0.72, 0.71 ± 0.1, and 1.42, 1.37 ± 0.2 respectively. Gender, age, side, and height had no impact on iris and/or CB thickness (p>0.05). However, the iris thickness was significantly thicker in the superior quadrant than inferiorly, and in the nasal quadrant than the temporal quadrant (p=0.04), and the CB thickness and the CB + ciliary processes thickness were significantly thicker in the superior quadrant than inferiorly (P = 0.04 and 0.02 consecutively). CONCLUSION: We measured in this study the normal thickness of the CB and the iris in normal eyes from homogenous population in the Middle East using ultrasound biomicroscopy. Our findings are essential for the ophthalmic community worldwide and in the Middle East region and can be used as a normative thickness data for the iris and CB in healthy eyes.

Presentation and management outcomes of Retinoblastoma among Syrian refugees in Jordan.

Purpose: The humanitarian crisis in Syria has had a profound impact on the entire region. In this study, we report the patterns of presentation and management outcomes of Syrian patients with Retinoblastoma (Rb) treated at a single tertiary cancer center in Jordan. Methods and Materials: This is a retrospective comparative study of Syrian refugees and Jordanian citizens who had Rb between 2011 and 2020. Collected data included patient demographics, presentation, tumor stage, treatment modalities, eye salvage rate, metastasis, and mortality. Results: Thirty Syrian refugees (16 (53%) had bilateral disease) and 124 Jordanian citizens (51(41%) had bilateral disease) were diagnosed with Rb during this period. The median age at diagnosis for refugees was 10 and 32 months for patients with bilateral and unilateral Rb consecutively, compared to 6 and 28 months for citizens. The median lag time between signs of disease and initiation of treatment was 3 months for refugees, compared to 1 month for citizens.Refugees were more likely to present with a more advanced stage (p=0.046). Out of 46 affected eyes in refugees; 32 (70%) eyes were group D or E, while out of 175 affected eyes among citizens; 98 (56%) eyes were group D or E. Therefore, refugees with Rb were more likely to mandate primary enucleation (48%) compared to citizens (25%) (p=0.003). However, out of 24 eyes among refugees who received conservative therapy, 15 (62%) eyes were successfully salvaged, while out of 131 affected eyes among citizens who received conservative therapy, 105 (80%) eyes were successfully salvaged (p=0.06). Two (7%) of the refugees and four (3.2%) of the citizens with Rb died from metastasis. Conclusion: Syrian refugees with Rb presented with more advanced disease due to delay in diagnosis and referral that increased the treatment burden by decreasing the chance for eye globe salvage. However, patients who received the timely intervention had a similar outcome to citizens with Rb; probably a reflection of the management of all patients at a single specialized center. We advocate for the timely referral of refugees with this rare life-threatening tumor to a specialized cancer center for the best possible outcome.