Histopathological assessment of optic nerve invasion guided by radiological findings in enucleated globes with retinoblastoma.

BACKGROUND: Optic nerve (ON) invasion is an important high-risk feature, and an indicator for neoadjuvant chemotherapy and prognosis. We aim through this study to correlate the detected-ON invasion by Magnetic resonance imaging (MRI) with the corresponding confirmed histopathological level of invasion. METHODS: A retrospective study of enucleated globes with the diagnosis of retinoblastoma received in the histopathology department(s) from January 2015 to December 2016 (2 years). Slides were reviewed for ON invasion assessment, charts were reviewed for basic demographic data. All patients underwent MRI under sedation upon diagnosis and MRI findings were collected for the above correlation. RESULTS: A total of 38 patients were included: 21 males and 17 females. 29 (77.3%) had unilateral involvement, 7 (18.4%) had bilateral involvement and 2 cases had trilateral disease. The overall mean age at diagnosis was 22.63 ± 15.15 months. Histopathological examination revealed ON invasion in 28 cases (74%) distributed as follows: prelaminar (31.6%), laminar (18.4%), and post-laminar (23.7%). MRI confirmed post-laminar ON invasion in 8 cases (true positive) but failed to detect this in 1 case. Additionally, MRI detected another 8 cases of ON invasion that were false positive on histopathology (accuracy: 63.3%; sensitivity: 88.9%; specificity: 72.4%; Positive predictive value (PPV): 50%; Negative predictive value (NPV): 95.5%). CONCLUSIONS: MRI is found to be less sensitive in evaluating prelaminar and laminar ON invasion (0.0 and 42.9%) compared to post-laminar invasion (88.9%). MRI has generally better specificity in detecting ON invasion irrespective of the invasion level. In our study, obtaining deeper and/or additional histologic sections from the other surface of the tissue block in cases where a post-laminar ON invasion by MRI is found but not confirmed histopathologically in routine sections is essential to avoid missing such an important high-risk feature.

Evaluation of Racial, Ethnic, and Socioeconomic Associations With Treatment and Survival in Uveal Melanoma, 2004-2014.

Importance: Identifying disparities in uveal melanoma (UM) treatment patterns and survival across racial, ethnic, and socioeconomic (SES) groups reveals possible inequities in ophthalmologic health care. Objective: To examine the association of race, ethnicity, and SES with UM treatment and survival. Design, Setting, and Participants: A retrospective cohort analysis of 28% of the US population using the Surveillance, Epidemiology, and End Results (SEER) 18 registries from January 1, 2004, to December 31, 2014, was conducted. Data analysis was performed from April to July 2018. SEER identified 4475 individuals using International Classification of Diseases for Oncology, Third Edition site and morphology codes. Exposures: Race, ethnicity, and SES estimated by tertile using Yost Index composite scores. Main Outcomes and Measures: Treatment odds ratios (ORs), 1-year and 5-year survival estimates, mortality hazard ratios (HRs), and Kaplan-Meier survival curves. Hypothesis was formulated before data collection. Results: Multivariate analyses of 4475 individuals (2315 [51.7%] men; non-Hispanic white, 4130 [92.3%]; nonwhite, 345 [7.7%]) showed that patients who were nonwhite (OR, 1.45; 95% CI, 1.12-1.88) and socioeconomically disadvantaged (lower SES: OR, 2.21; 95% CI, 1.82-2.68; middle SES: OR, 1.86; 95% CI, 1.56-2.21) were more likely to receive primary enucleation. No interactions were observed between race/ethnicity, SES, and stage at diagnosis. From 2004 to 2014, rates of primary enucleation decreased across all racial/ethnic and SES groups, but disparities persisted. Socioeconomically disadvantaged patients had lower 5-year all-cause survival rates (lower SES: 69.2%; middle SES: 68.1%; and upper SES: 73.8%), although disease-specific survival did not vary significantly by racial/ethnic or SES strata. Mortality risk was associated with older age at diagnosis (56-68 years: HR, 1.70; 95% CI, 1.44-2.01; ≥69 years: HR, 3.32; 95% CI, 2.85-3.86), advanced stage of UM (stage 2: HR, 1.40; 95% CI, 1.19-1.65; stage 3: HR, 2.26; 95% CI, 1.87-2.73; and stage 4: HR, 10.09; 95% CI, 7.39-13.77), and treatment with primary enucleation (HR, 2.14; 95% CI, 1.88-2.44) with no racial/ethnic or SES variation. Conclusions and Relevance: In this study, SEER data from 2004 to 2014 suggest that nonwhite and socioeconomically disadvantaged patients with UM are more likely to be treated with primary enucleation, although no such variation appears to exist in disease-specific survival. These differences reveal opportunities to address issues regarding treatment choice in UM.

Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis.

PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.

Associations among Socioeconomic Factors, Lag Time, and High-Risk Histopathologic Features in Eyes Primarily Enucleated for Retinoblastoma.

Purpose/Aim: To determine the associations among socioeconomic factors, delay in management, and high-risk histopathologic features in eyes primarily enucleated for retinoblastoma. Materials and Methods: A single-site survey was conducted from January 2016 through January 2018. Eyes primarily enucleated for unilateral retinoblastoma were reviewed for the presence of high-risk histopathologic features. Information on clinical characteristics, socioeconomic factors, and lag time were collected during hospitalization. Results: Of the 138 children analyzed, 60 (43.5%) carried high-risk histopathologic features. Compared to children with a standard risk, those with a high risk had a longer median lag time before treatment (21.5 vs 15.0 days, P = .007), but their overall lag time (54.0 vs 50.0 days, P = .062) and delay in the initial visit (7.0 vs 10.0 days, P = .782) were comparable. Logistic regression analysis showed that children with a lag time ≥ 30 days were at a significantly higher risk of extraocular invasion (odds ratio [OR] = 2.38 and 95% confidence interval [CI] = 1.08-5.37 for treatment delay; OR = 2.12 and 95% CI = 1.01-4.62 for overall delay). Neither high-risk histopathologic features nor lag time was associated with any demographic or major socioeconomic factors, including sex, age at diagnosis or enucleation, ethnicity, household income, parents' education level, medical insurance coverage, and left-behind status. Conclusions: For children with advanced unilateral retinoblastoma, there is no statistical difference in overall lag time between standard and high-risk groups. Major socioeconomic parameters have little impact on the delay and histopathologic outcomes, thus implying that children with varied socioeconomic status may be at a similar risk of advanced tumor invasion.

Racial, Ethnic, and Socioeconomic Disparities in Retinoblastoma Enucleation: A Population-Based Study, SEER 18 2000-2014.

PURPOSE: To determine the effect of race, ethnicity, and census tract-level composite socioeconomic status (SES) on retinoblastoma enucleation. This study augments Truong and associates, providing multivariate analyses combining sociodemographic and clinical characteristics with more accurate SES measures. We hypothesized that children from nonwhite, Hispanic, and lower socioeconomic backgrounds would have increased adjusted odds of enucleation. DESIGN: Retrospective cohort analysis. SETTING: Multicenter population-based study using the Surveillance, Epidemiology, and End Results (SEER) 18 Registries. STUDY POPULATION: Children aged 18 years and younger diagnosed with retinoblastoma between 2000 and 2014. Subjects were identified using International Classification of Diseases-Oncology (ICD-O) site and morphology codes. MAIN OUTCOME MEASURES: Enucleation odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Analysis of 959 retinoblastoma patients revealed that 70.8% were enucleated. Adjusted analyses showed associations between enucleation and Asian (OR 2.00, CI 1.08-3.71) or black (2.42, 1.41-4.16) race, Hispanic ethnicity (1.69, 1.16-2.46), and low SES (1.68, 1.09-2.58). Significantly increased enucleation risk was associated with older age at diagnosis (age 1-2 years 2.55, 1.80-3.61; >2 years 4.88, 2.57-9.25), unilateral disease (5.00, 3.45-7.14), and advanced stage (regional 4.71, 2.51-8.84; distant 3.15, 1.63-6.08). No interactions were observed between race, ethnicity, SES, and stage at diagnosis. Enucleation rates decreased over time across all racial, ethnic, and socioeconomic groups. CONCLUSIONS: Children from nonwhite, Hispanic, and lower socioeconomic backgrounds are more likely to receive enucleation. These associations are independent of stage of diagnosis, suggesting larger systemic disparities in retinoblastoma care. The origin of these differences requires further study and attention by clinicians and policy makers.

Orbital Implants in Enucleation Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To compare the motility and complication rates of porous and nonporous implants after enucleation surgery. METHODS: Literature searches of the PubMed and Cochrane Library databases were last performed in February 2017 to identify studies published between 2003 and 2017 on outcomes after enucleation surgeries in which a variety implants were used. The searches were limited to the English language with abstracts and yielded 43 articles, which the Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel reviewed for relevancy. Twenty-five articles were considered to have met the search strategy, and the panel methodologist assigned ratings to them according to the level of evidence. RESULTS: Only 2 of the 25 articles identified met the criteria for level I evidence. Eighteen of the studies did not assess motility after enucleation surgery, and the 7 that did evaluate this metric involved porous implants. The studies that analyzed this outcome reported favorable results, but the results were not uniformly based on objective analysis. Both porous and nonporous implants were well tolerated, and complication rates were generally low for both types. CONCLUSIONS: In keeping with increasing surgeon preference for porous implants, most studies identified in this literature search involved the use of this type of implant. These implants resulted in excellent motility after enucleation surgery, although many studies did not assess this outcome. Regardless of implant type, major complications were rare, and infection was exceptionally uncommon after enucleation. Given the paucity of data on motility and the absence of direct, objective comparisons of porous and nonporous implants, definitive conclusions about the impact of implant material on motility cannot be made. Since few studies evaluated nonporous implants, direct comparisons cannot be made definitively between implant types, and future investigations are needed to enable a critical assessment.

The value of "en toto" globe submission in the assessment of high-risk retinoblastoma cases and staging.

PURPOSE: To evaluate the importance of "en toto" globe submission in the assessment of high-risk pathological findings in retinoblastoma cases, aiming at identifying the additional value from full globe examination of enucleated eyes (including the calottes). METHODS: Retrospective histopathological case series of eighty-one enucleated globes with the clinical diagnosis of retinoblastoma, histopathologically examined at King Khaled Eye Specialist Hospital (KKESH) between January 2010 and December 2013. We included retinoblastoma eyes with any type of invasion (more than pT1) in which the globe was submitted "en toto." All cases were histopathologically classified according to the American Joint Cancer Classification (AJCC TNM classification, 2009 6th edition). RESULTS: 81 enucleated globes were examined, out of which 30 globes were classified as high-risk cases (more than pT1). 8 cases had massive choroidal invasion in both the PO sections and calottes. 5 cases had focal choroidal invasion in both. One case has massive choroidal invasion in calottes with very superficial ON head invasion. Two cases were found to have focal choroidal invasion in the calottes with prelaminar ON invasion. In these three cases (10%), the presence of focal or massive choroidal invasion in the calottes has affected the classification. CONCLUSIONS: This study consolidates the guidelines recommended in the consensus meeting: from the International Retinoblastoma Staging Working Group on the pathology guidelines for the examination and evaluation of prognostic risk factors in retinoblastoma eyes. Full globe submission and examination should be the routine accepted practice universally even in underdeveloped countries.

Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye.

BACKGROUND: Chemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including number of examinations under anaesthesia (EUAs), of group D patients treated by enucleation versus chemotherapy. METHODS: A retrospective analysis of 92 group D patients, of which 40 (37 unilateral) underwent primary enucleation and 52 (17 unilateral) were treated with intravenous chemotherapy. Number of EUAs was compared between the treatment groups with respect to the whole cohort, using univariate and multivariate analysis, and to unilateral cases only. RESULTS: Patients were followed up for a median of 61 months (mean: 66, range: 14-156), in which time primary enucleated patients had on average seven EUAs and chemotherapy-treated patients 21 EUAs (p<0.001). Chemotherapy, young age, bilateral disease, multifocal tumours, familial and germline retinoblastoma were found on univariate analysis to correlate with increased number of EUAs (p≤0.019). On multivariate analysis, however, only treatment type and presentation age were found significant (p≤0.001). On subanalysis of the unilateral cases, patients undergoing primary enucleation had in average seven EUAs, as compared with 16 in the chemotherapy group (p<0.001). Of the 55 unilateral-presenting patients, a new tumour developed in the fellow eye only in a single familial case. CONCLUSION: Group D patients' families should be counselled regarding the significant difference in number of EUAs following primary enucleation versus chemotherapy when deciding on a treatment strategy. In this regard, primary enucleation would be most beneficial for older patients with unilateral disease.

Correlation of Insurance, Race, and Ethnicity with Pathologic Risk in a Controlled Retinoblastoma Cohort: A Children's Oncology Group Study.

PURPOSE: To determine whether insurance status, race, and ethnicity correlate with increased retinoblastoma invasiveness as a marker of both risk and time to diagnosis. DESIGN: Retrospective case-control study. PARTICIPANTS: All 203 patients from the United States enrolled in the Children's Oncology Group (COG) trial ARET0332, a study of patients with unilateral retinoblastoma requiring enucleation. MAIN OUTCOME MEASURES: All surgical specimens underwent pathologic review to determine the presence of well-defined histopathologic features correlating with a higher risk of disease progression. Insurance status, race, and ethnicity were compiled from the study record for each patient. RESULTS: On institutional pathologic review, nonprivate insurance, nonwhite race, and Hispanic ethnicity all correlated significantly with a greater rate of high-risk pathologic findings. Hispanic ethnicity remained a significant predictor on multivariate analysis. On central pathologic review, these correlations remained but did not reach statistical significance. The differences in results from institutional versus central pathologic reviews appeared to be due to a higher likelihood of patients in minority groups of being misclassified as high risk by institutional pathologists. CONCLUSIONS: In this controlled study population of patients with retinoblastoma who had central pathologic review, our findings suggest a higher rate of more advanced disease associated with nonprivate insurance, nonwhite race, and Hispanic ethnicity; these findings may be due to delays in diagnosis for these groups. Future work should use direct methods to study the impact of other variables, including English-language proficiency and socioeconomic status. Further effort also should focus on where in the diagnostic process potential delays exist, so that interventions can be designed to overcome barriers to care for these groups. In addition, potential systematic differences in pathologic reads based on demographic variables deserve further study.

Gender and Racial Disparities in Cases of Autoenucleation.

OBJECTIVE: This review demonstrates the gender and racial disparities among patients who have committed ocular autoenucleation. DESIGN: Peer-reviewed articles were identified and reviewed on the basis of a literature search in PubMed/MEDLINE and Ovid/EMBASE databases from all available literature to date. RESULTS: We identified 60 cases of autoenucleation published in contemporary literature with nine attempted cases. The ratio of men to women who have committed autoenucleation is 8:1. Only 28 cases of autoenucleation included confirmed reports of racial makeup. 17 out of 28 cases were White, eight out of 28 cases were Hispanic or Asian, and only three cases were Black. White patients account for 61% of the cases, while Black patients make up 11% and other races constitute 28%. The common underlying psychiatric motivations among autoenucleation patients include biblical interpretations, religious delusions, and paranoia of the eye. The most common associated psychiatric disorders among patients with autoenucleation include schizophrenia, major depressive disorder, and bipolar disorder. CONCLUSION: Autoenucleation largely occurs amongst male patients with active psychiatric disorders. Our findings challenge previously published reviews where the incidence of autoenucleation is reported as equal for the two sexes. A higher incidence among the White population is also suggested. This is the first time gender and racial disparity have been demonstrated with respect to autoenucleation.

Ethnic, Racial, and Socioeconomic Disparities in Retinoblastoma.

IMPORTANCE: Most children with retinoblastoma in the United States are diagnosed as having a large intraocular tumor burden that requires intensive ocular-salvage treatment or enucleation. OBJECTIVE: To investigate the effect of socioeconomic status, race, and ethnicity on the extent of disease and the outcomes of retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS: A population-based review of 18 Surveillance, Epidemiology, and End Results (SEER) registries. From January 1, 2000, through December 31, 2010, 830 cases of retinoblastoma were recorded for children aged 0 to 9 years. Data were collected and analyzed from January 1, 2000, through December 31, 2010, with the last follow-up on December 31, 2010. EXPOSURES: County-based socioeconomic variables analyzed included poverty level, educational attainment, language isolation, crowding, unemployment, and percentage of immigrants. MAIN OUTCOMES AND MEASURES: Extent of disease, ocular outcome, and children's survival. RESULTS: Of the 830 individuals included, Hispanic children had a higher percentage of extraocular disease (86 of 261 [33.0%] vs. 102 of 510 non-Hispanic children [20.0%]; odds ratio [OR], 1.97 [95% CI, 1.38-2.79]). The percentage of extraocular cases was also higher in counties with the following low socioeconomic status indicators: higher vs. lower poverty status (115 of 413 [27.8%] vs. 73 of 358 [20.4%]; OR, 1.51; 95% CI, 1.06-2.14); lower vs. higher educational attainment (115 of 400 [28.7%] vs. 73 of 371 [19.7%]; OR, 1.65; 95% CI, 1.16-2.34); higher vs. lower levels of crowding (124 of 398 [31.2%] vs. 64 of 373 [17.2%]; OR, 2.18; 95% CI, 1.53-3.13); higher vs. lower unemployment (119 of 411 [28.9%] vs. 69 of 360 [19.2%]; OR, 1.72; 95% CI, 1.21-2.45); higher vs. lower language isolation (117 of 388 [30.2%] vs. 71 of 383 [18.5%]; OR, 1.89; 95% CI, 1.34-2.70); and higher vs. lower percentage of immigrants (109 of 386 [28.2%] vs. 79 of 385 [20.5%]; OR, 1.52; 95% CI, 1.08-2.16). Higher rates of enucleation were associated with low educational attainment (265 of 401 [66.1%] vs 309 of 421 [73.4%]; OR, 1.42; 95% CI, 1.04-1.93), a higher level of crowding (316 of 416 [76.0%] vs. 258 of 406 [63.5%]; OR, 1.81; 95% CI, 1.32-2.48), and Hispanic origin (202 of 271 [74.5%]; OR, 1.41; 95% CI, 1.01-1.98). Relative survival at 5 years was lower among black compared with non-Hispanic white children (92.7% vs. 99.2%; P < .001). CONCLUSIONS AND RELEVANCE: Significant disparities exist in the care and outcomes of children with retinoblastoma. A low socioeconomic status negatively affects disease extent and ocular outcomes, presumably by limiting access to primary and cancer-directed care. Hispanic children in particular have more advanced disease and higher rates of enucleation.

Evaluación de secuelas visuales y cosméticas del tratamiento conservador con terapia radiante externa en pacientes con retinoblastoma bilateral en el Hospital de Pediatría Garrahan / Assessment of visual and cosmetic sequelae of conservative treatment of external beam radiation of patients with bilateral retinoblastoma at the Pediatric Hospital Garrahan

El Retinoblastoma es la neoplasia ocular más frecuente en pediatría. La Terapia radiante externa fue hasta hace una década el tratamiento conservador de elección. Luego se incluyó la quimio reducción; en un intento de evitar la radioterapia externa y sus complicaciones. En este estudio retrospectivo evaluamos los resultados del tratamiento conservador con terapia radiante externa o con quimio reducción en el servicio de oftalmología del Hospital Nacional de Pediatría Juan P. Garrahan, desde 1987 a 2009. De un total de 571 pacientes con diagnóstico de Retinoblastoma, 341 fueron unilaterales y 217 bilaterales. De estos últimos se analizaron 166 pacientes cuya edad media al diagnostico fue de 12 meses. Se trataron 332 ojos de 166 pacientes con Retinoblastoma bilateral, 157 ojos (47,3%) recibieron quimioreducción como tratamiento inicial, 115 ojos (34,6%) fueron enucleados al inicio, 45 ojos (13,6%) recibieron radioterapia externa como único tratamiento y 15 ojos (4,5%) recibieron tratamiento local solo (laser o crioterapia) como primera elección. Se analizaron los datos con el programa estadístico STATA 12.0 stataCorp Texas.USA. La agudeza visual final fue superior a 20/70 en el 51,5% de los pacientes e inferior en el 48,5%. Se encontró una relación significativa (p=0,005) entre el estadio al diagnóstico y la agudeza visual final; los pacientes con discapacidad visual se presentaron con estadios avanzados. Se evaluaron todas las orbitas enucleadas (157); de ellas el 74,5% recibieron radioterapia externa antes o después de la enucleación. El 24,8% de las orbitas irradiadas presentaron deformidad de la cavidad, con mala adaptación de prótesis y retracción orbitaria, el 70,1% presentaron cambios que permitían una adaptación de prótesis aceptable con alguna limitación de movilidad y solo 6 orbitas (5,12%) presentaban una muy buena cavidad para adaptación cosmética. Cuarenta de 157 orbitas enucleadas no recibieron radioterapia en ningún momento (25,5%), el 92,5% de ellas presentaron buena adaptación y solo el 7,5% tuvieron problemas de adaptación debido a complicaciones postoperatorias. El diagnóstico precoz, el tratamiento oportuno, y el uso de quimio reducción como terapia inicial en Retinoblastoma intraocular, permiten aumentar la tasa de preservación del globo ocular y reducen o eliminan la necesidad de recibir Terapia radiante externa, evitando sus secuelas (AU)

Retinoblastoma is the most common ocular neoplasia in childhood. External beam radiation therapy was the conservative treatment of choice until a decade ago. Subsequently, chemoreduction was added trying to avoid external beam radiation therapy and its complications. In this retrospective study we assess the results of conservative therapy with external beam radiation therapy or with chemoreduction at the Department of Ophthalmology at the Pediatric Hospital Juan P. Garrahan between 1987 and 2009. Of a total of 571 patients with a diagnosis of retinoblastoma, 341 had unilateral and 217 bilateral retinoblastoma. Of the latter patients, 166 patients were analyzed with a mean age at diagnosis of 12 months. Overall, 332 eyes of 166 patients with bilateral retinoblastoma were treated; at initial treatment 157 eyes (47.3%) underwent chemoreduction, 115 eyes (34.6%) were enucleated, 45 eyes (13.6%) underwent external beam radiation therapy as the only treatment, and 15 eyes (4.5%) only received local treatment (laser or cryotherapy) as a first choice. Data were analyzed using STATA 12.0 stataCorp Texas.USA. Final visual acuity was more than 20/70 in 51.5% and less in 48.5% of the patients. A significant relationship (p=0.005) between stage at diagnosis and final visual acuity was found; patients with visual impairment presented with advanced stages. All enucleated orbits were assessed (157); 74.5% underwent external beam therapy before or after enucleation. Of all irradiated orbits, 24.8% presented with cavity deformity, poor prosthesis fit, or contraction of the socket. Of all patients, 70.1% presented with changes that allowed acceptable fitting of the prosthesis with slight movement limitation and only 6 orbits (5.12%) had a good cavity for cosmetic appearance. Forty of 157 enucleated orbits did not receive radiation therapy at any moment (25.5%); 92.5% of them had a good fitting and in only 7.5% fitting problems due to postoperative complications were found. Early diagnosis, adequate treatment, and use of chemoreduction as initial therapy of intraocular retinoblastoma allow for an increased rate of preservation of the eye and reduce or eliminate the need for external beam therapy and its sequelae (AU)

Socioeconomic and psychological impact of treatment for unilateral intraocular retinoblastoma.

PURPOSE: To identify the socioeconomic and psychosocial impacts of clinical treatment decisions for advanced unilateral intraocular retinoblastoma. DESIGN: Retrospective observational case series. SETTING: institutional study at Alexandria Main University Hospital. STUDY POPULATION: records of 66 unilateral retinoblastoma cases treated from May 2005 to May 2013 were retrospectively reviewed. Sixty cases were eligible (International Intraocular Retinoblastoma Classification [IIRC] group C, D or E). PROCEDURES: two treatment groups were compared: enucleation vs. salvage treatment. Salvage treatment eyes were further subdivided based on IIRC group. Six socioeconomic parameters (financial burden, financial impact, psychological, social, medical and tumor impacts) were scored. Parameter scores ranged from 0 to 3, for overall score range 0 (no adverse impact) to 18 (severe adverse impact). MAIN OUTCOME MEASURES: derived Socioeconomic scores were correlated with treatment and outcomes. RESULTS: The enucleation group (28 eyes) had a median overall Socioeconomic score of 4/18, significantly lower than the salvage treatment group (32 eyes), median score 11/18 (P<0.01). Socioeconomic score varied with IIRC group. Attempted eye salvage failed in 25 children, due to uncontrolled tumor (44%) and socioeconomic impact of cumulative therapies (56%). Treatment duration and Socioeconomic score were higher for the 5 children in the salvage treatment group who developed metastatic disease compared to those without metastasis (P<0.01). CONCLUSIONS: The socioeconomic and psychosocial impacts of attempted ocular salvage for unilateral intraocular retinoblastoma are severe, in comparison to primary enucleation. Primary enucleation is a good treatment for unilateral retinoblastoma.

Cost-effectiveness of proton beam therapy for intraocular melanoma.

PURPOSE: Proton beam therapy is a commonly accepted treatment for intraocular melanomas, but the literature is lacking in descriptions of patient preferences of clinical outcomes and economic impact. In addition, no economic evaluations have been published regarding the incremental cost-effectiveness of proton beam therapy compared with enucleation or plaque brachytherapy, typical alternative treatments. We, therefore, conducted a cost-utility analysis of these three approaches for the treatment of intraocular melanomas. MATERIALS AND METHODS: A Markov model was constructed. Model parameters were identified from the published literature and publicly available data sources. Cost-effectiveness of each treatment was calculated in 2011 US Dollars per quality-adjusted life-year. Incremental cost-effectiveness ratios were calculated assuming enucleation as reference. One-way sensitivity analyses were conducted on all model parameters. A decision threshold of $50,000/quality-adjusted life-year was used to determine cost-effectiveness. RESULTS: Enucleation had the lowest costs and quality-adjusted life-years, and plaque brachytherapy had the highest costs and quality-adjusted life-years. Compared with enucleation, the base-case incremental cost-effectiveness ratios for plaque brachytherapy and proton beam therapy were $77,500/quality-adjusted life-year and $106,100/quality-adjusted life-year, respectively. Results were highly sensitive to multiple parameters. All three treatments were considered optimal, and even dominant, depending on the values used for sensitive parameters. CONCLUSION: Base-case analysis results suggest enucleation to be optimal. However, the optimal choice was not robust to sensitivity analyses and, depending on the assumption, both plaque brachytherapy and proton beam therapy could be considered cost-effective. Future clinical studies should focus on generating further evidence with the greatest parameter uncertainty to inform future cost-effectiveness analyses.

Secondary orbital ball implants after enucleation and evisceration: surgical management, morbidity, and long-term outcome.

PURPOSE: To investigate effectiveness of a simplified surgical technique for secondary ball implantation in anophthalmic sockets and to compare long-term results of secondary ball implantation in patients previously enucleated or eviscerated. METHODS: The study is a case series analysis of the clinical charts of 110 consecutive patients who underwent secondary ball implantation after enucleation or evisceration, from January 1998 to December 2011, under the care of 1 surgeon. Patients undergoing primary evisceration and implant exchange were excluded. Primary surgery was due to trauma in 48.8% patients, endophthalmitis and phthisis bulbi in 25.6%, tumors in 22.1%, and orbital vascular malformations in 3.5%. This study adheres to the principles outlined in the Declaration of Helsinki. RESULTS: Of 110 identified cases, 24 were excluded for insufficient follow-up (less than 2 years); mean follow-up was 6.4 years. Group A patients (previously enucleated) received a polyglactin mesh-wrapped implant. Group B patients (previously eviscerated) kept their own sclera as a secondary anterior capping on the polyglactin mesh-wrapped implant. There were 2 implant exposures (4.9%; 2 of 41) in group A. Hard palate graft was used to repair the exposed implant successfully. No exposure was noted in group B. No statistically significant between-group difference in exposure rate was found. CONCLUSIONS: Stable secondary ball implantation can be achieved long term, and a reliable surgical technique is the most important factor in predicting implant stability. In patients who had secondary implants following evisceration, sclera and polyglactin mesh may act as duplicate barriers between anterior surface of implants and overlying tissues.

Update on intra-arterial chemotherapy for retinoblastoma.

The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC) to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

Causes, outcome and prevention of abandonment in retinoblastoma in India.

BACKGROUND: The high-cure rates of 90% in retinoblastoma are not replicated in developing countries due to late presentation and poor compliance to treatment. The present study takes a closer look at causes of abandonment of therapy and effectiveness of counselling in reducing abandonment. PROCEDURE: A retrospective study of children with retinoblastoma registered at our centre from March 2008 through August 2011. RESULTS: Fifty (49.50%) of 101 children registered for treatment abandoned therapy. Abandonment rates were significantly higher in rural as compared to urban children (P = 0.02). There was no significant difference in rate of abandonment between stages or laterality of disease and other socio-demographic factors. Telephone calls were more effective than letters in tracing patients (31.2% vs. 2.4%). Major reasons cited behind abandonment were financial problems (30%) and unwillingness to enucleate (20%). Of the 12 children who returned and were retreated 6 (50%) died of progressive disease. Nineteen (73%) of those who did not return died at home. Abandonment rates steadily declined from 71.42% in 2008 to 16.66% in 2011 (P = 0.01) due to effective pre-abandonment counselling by a support team under the National Retinoblastoma Registry of India from 2009. CONCLUSIONS: Abandonment rates for children with retinoblastoma continue to be unacceptably high. Rural background, financial constraints and hesitancy to enucleate were important causes behind abandonment. Outcome of patients who abandoned treatment was uniformly dismal. Inclusion of support team and intensified initial counselling helped in improving compliance.

Trabecular meshwork length in men and women by histological assessment.

PURPOSE: To evaluate the length of the trabecular meshwork (TM) from the scleral spur (SS) to Schwalbe's line (SL) and assess the detectability of the SS in histopathology specimens. METHODS: This study included 158 angle images from 79 cross-sectional slides derived from eyes enucleated for melanoma. The slides were stained with hematoxylin-eosin (HE) or periodic acid schiff (PAS). Two ophthalmologists evaluated the TM length by using the slides stained with HE to assess the interobserver reproducibility. For intraobserver reproducibility, the first observer assessed 79 images in a different session. Also, 30 images that were randomly selected for PAS stain were evaluated to assess the agreement of the measurements between HE and PAS staining. Interclass correlation coefficients (ICC) were calculated to evaluate reproducibility of measurements. The images were also evaluated for detectability of the scleral spurs. RESULTS: Among the 79 included subjects, 40 were male and 39 were female. The average trabecular meshwork length was 694.9 ± 109.0 µm in the male group and 713.2 ± 106.9 µm in the female group (p = 0.29). Intraobserver and interobserver ICC were 0.89 and 0.62, respectively. ICC for agreement between HE and PAS was 0.89. Among the 158 angles graded, the first observer graded 40 images (25.3%) and the second observer graded 45 (28.5%) as difficult to identify the scleral spur. CONCLUSIONS: There was no statistically significant difference between the average trabecular meshwork length in men and women. Among the angles evaluated, 25.3-28.5% were graded as difficult to identify the scleral spur.