The Latino Eyelid: Anthropometric Analysis of a Spectrum of Findings.

PURPOSE: Published anthropometric measurements of the Latino eyelid are limited. This study describes features spanning the morphologic range from non-Latino whites to East Asians in the spectrum of the Latino eyelid. METHODS: A cross-sectional study of 68 people (32 Latinos, 18 non-Latino whites, and 18 East Asians, ages 18-39), approved by the Institutional Review Board and HIPAA-compliant, was performed. Saliva samples determined genetic components. Indirect anthropometric measurements were performed with ImageJ software. Eyelid measurements included margin reflex distance, palpebral fissure height, eyelid crease height, orbital height, horizontal fissure length, inner and outer canthal distances, medial and lateral canthal angles, and lateral canthal angle of inclination. Additionally, exophthalmometry and epicanthal folds were recorded. RESULTS: Analysis of 184 markers from HumanExome Chip data revealed distinct clustering patterns. Genetically, the Asian participants were in 1 group, the whites in another group, and the Latinos spanned the spectrum between these 2 groups. In Latinos, the inner canthal distance and lateral canthal angle of inclination were similar to Asians, whereas the eyelid crease spanned the range from Asians to whites. Half of the Latinos had epicanthal folds. CONCLUSIONS: Latinos possess a spectrum of eyelid features spanning the morphologic characteristics from those of non-Latino whites to those of East Asians. These normative data on Latinos from Texas and Mexico aid in the diagnoses of Latino eyelid disorders and are a reference for optimizing oculofacial surgery outcomes.

Haemolacria: A Novel Approach to Lesion Localization.

PURPOSE: To report the use of punctal plugs as a new modality to assist in the localization of lesions providing symptomatic relief in patients with haemolacria during their workup. METHODS: Retrospective case series. RESULTS: One boy and one girl, ages 16 and 20, respectively, reported spontaneous bloody tearing. Workup included probing and irrigation of the nasolacrimal system, blood and coagulation profiles, blood typing, serum hormone levels, conjunctival biopsy, and imaging. All findings were normal and failed to suggest a cause in any of the cases. Punctal plugs were inserted into each patient's inferior punctum OS without complication. On initial follow-up visits, each patient reported cessation of bloody tears OS with continued bloody tears OD. Over time, both patients experienced complete cessation of haemolacria in both eyes. CONCLUSIONS: Haemolacria is a condition caused by a group of disorders that result in the production of tears that are partially composed of blood. The large majority of cases result in a specific diagnosis. Only rarely does workup result in undetermined etiology. The novel approach of utilizing punctal plugs in the management of haemolacria may not only provide symptomatic relief for lesions distal to and including the punctum, but also assists in anatomic localization in idiopathic cases.

Pathologic risk-based adjuvant chemotherapy for unilateral retinoblastoma following enucleation.

BACKGROUND: There are no standardized diagnostic or treatment guidelines for patients with advanced unilateral retinoblastoma. MATERIALS AND METHODS: Patients with advanced unilateral retinoblastoma were prospectively treated after enucleation using a risk-based protocol. Patients were assigned to low risk (LR), intermediate risk (IR), or high risk (HR) based on pathology. LR patients underwent observation. IR patients received 4 courses of chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VDC). In the HR group, patients received 3 courses of VDC alternating with 3 courses of vincristine, carboplatin, and etoposide (VCE) and irradiation when indicated. RESULTS: Fifty patients with advanced unilateral retinoblastoma were treated (LR, n=36; IR, n=7; HR, n=7). All eyes were Reese-Ellsworth group V. All bone scans (n=81), lumbar punctures (n=16), and bone marrow aspirates (n=16) were negative. Chemotherapy was well tolerated. Grades 3/4 hematologic toxicities were seen in all patients; grades 3/4 nonhematologic toxicities were seen in half the patients. Only one patient in the HR group received radiation therapy. All patients were alive at the time of analysis with no signs of disease recurrence. Median follow-up was 3.4 years (range, 0.8 to 6.4 y). CONCLUSIONS: Patients with nonmetastatic unilateral retinoblastoma undergoing primary enucleation can be cured with a graduated intensity approach based on pathology.

Pediatric anophthalmic sockets and orbital implants: outcomes with polymer-coated implants.

PURPOSE: To compare wrapped and polymer-coated hydroxyapatite implants in children undergoing primary enucleation with no adjuvant therapies. DESIGN: Retrospective, interventional cohort study. PARTICIPANTS: All children undergoing primary enucleation without adjuvant therapies between 1999 and 2009 at a tertiary pediatric cancer hospital. METHODS: Review and analysis of patient records. MAIN OUTCOME MEASURES: Implant exposure, extrusion and migration, socket contracture, and formation of pyogenic granuloma. RESULTS: Sixty consecutive patients undergoing primary enucleation with no adjuvant chemotherapy or radiation with follow-up of at least 12 months were included. Retinoblastoma was the diagnosis in 59 eyes (98.3%). Median follow-up was 3.6 years (range, 1.0-9.3 years). Two implant sizes were used: 20 mm in 47 patients (78.3%) and 18 mm in 13 patients (21.7%). Overall, 52 patients (86.7%) had an event-free recovery. Polymer-coated hydroxyapatite implants (43/60, 71.7%), when compared with wrapped ones (17/60, 28.3%), had a trend toward greater event-free recovery (odds ratio [OR], 1.6; 95% confidence interval [CI], 0.3-7.7) and lower exposure rate (OR, 2.1; 95% CI, 0.4-10.5). CONCLUSIONS: The use of polymer-coated hydroxyapatite implants is associated with favorable outcomes in the pediatric population. Despite observed complications, long-term implant retention is possible in most children. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topotecan and vincristine combination is effective against advanced bilateral intraocular retinoblastoma and has manageable toxicity.

BACKGROUND: New, effective chemotherapeutic agents are needed for intraocular retinoblastoma. METHODS: This institutional clinical trial sought to estimate the rate of response to 2 courses of vincristine and topotecan (VT) window therapy in patients with bilateral retinoblastoma and advanced disease (Reese-Ellsworth group IV or V) in at least 1 eye. The topotecan dose started at 3 mg/m(2) /day for 5 days and was adjusted to target a systemic exposure of 140 ± 20 ng/mL · hour. The vincristine dose was 0.05 mg/kg for patients <12 months of age and 1.5 mg/m(2) for those >12 months of age at diagnosis. RESULTS: From February 2005 to June 2010, 27 patients received VT window therapy. Median age at enrollment was 8.1 months (range, 0.7-22.1 months). Twenty-four patients (88.9%) responded to window therapy (95% confidence interval = 71.3%-96.9%). Hematologic toxicity comprised grade 4 neutropenia (n = 27), grade 3 anemia (n = 19), and grade 3/4 thrombocytopenia (n = 16). Thirteen patients had grade 3 nonhematologic toxicity. Granulocyte colony-stimulating factor support was added after 10 patients had been treated, and it significantly reduced the duration of grade 4 neutropenia (median, 7 vs 24 days; P < .001). Pharmacokinetic studies showed rapid changes in topotecan clearance rates during the first year of life. CONCLUSIONS: The combination of topotecan and vincristine is effective for the treatment of advanced intraocular retinoblastoma. Granulocyte colony-stimulating factor treatment alleviates the duration of grade 4 neutropenia. Appropriate topotecan starting doses for patients 0-3, 3-6, 6-9, 9-12, and >12 months of age are specified.

The effect of cancer therapies on pediatric anophthalmic sockets.

PURPOSE: To determine the impact of chemotherapy or external beam radiotherapy (EBRT) on pediatric anophthalmic sockets. DESIGN: A retrospective, nonrandomized, interventional cohort study. PARTICIPANTS: A total of 135 sockets of 133 children undergoing enucleation from late 1999 to early 2009 at the St. Jude Children's Research Hospital were included. METHODS: A retrospective chart review of outcomes after enucleation in patients treated with systemic chemotherapy or orbital EBRT either before or after removal of the eye compared with patients who received no other treatment. MAIN OUTCOME MEASURES: Incidence of implant exposure, migration, extrusion, socket contracture, and pyogenic granuloma formation. RESULTS: Retinoblastoma was the primary diagnosis in 128 eyes (95%). Median follow-up was 3.6 years (range, 0.1-9.3 years). Event-free course was observed in 94 sockets (69.6%). Complications included implant exposure (n = 28, 20.7%), socket contracture (n = 16, 11.9%), pyogenic granuloma (n = 9, 6.7%), implant extrusion (n = 3, 2.2%), and migration (n = 2, 1.5%). Exposure resolved in 21 sockets (77.8%) and improved in 2 sockets (11.1%); 1 patient with exposure died. Use of prior, adjuvant, or subsequent chemotherapy increased the long-term risk of exposure (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.4-9.4), and contracture (OR could not be calculated, P<0.0001). External beam radiotherapy greatly increased the risk of contracture (OR 24.0; 95% CI, 6.9-82.8) and exposure (OR 2.89; 95% CI, 1.1-7.9). CONCLUSIONS: In this unique pediatric population with cancer, chemotherapy and EBRT had an additive effect, significantly increasing the incidence of exposure and socket contracture. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ophthalmic complications following treatment of paranasal sinus rhabdomyosarcoma in comparison to orbital disease.

PURPOSE: To identify the type and frequency of ocular and orbital complications observed following treatment for primary rhabdomyosarcoma of the paranasal sinuses or the orbit. METHODS: An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective chart review was conducted to identify all patients treated at one institution from 1966 to 2005 with biopsy-proven primary paranasal sinus or orbital rhabdomyosarcoma. Pretreatment, treatment, and follow-up data were collected. RESULTS: Forty-four patients (25 male) of a median age of 7.8 years (range 1.0-18.0 years) with primary paranasal sinus (17) or orbital (27) rhabdomyosarcoma were treated and followed for a median period of 5.3 years (range 0.6-32.0 years). The three most frequently observed ophthalmic complications were persistent eyelid erythema or cellulitis (12), epithelial keratitis (7), and conjunctival injection (6) in the paranasal sinus and epithelial keratitis (18), conjunctival injection (11), and cataract (10) in the orbit. Overall survival after treatment trended higher for the orbital rhabdomyosarcoma group (23 of 27) than the paranasal sinus group (9 of 17). CONCLUSIONS: The most frequently observed treatment-induced ophthalmic complications in the paranasal sinus group were manageable with minimal patient morbidity, as in the patients with orbital disease. Vision-threatening complications were infrequently encountered. Despite maximal therapy, the mortality rate was higher in the paranasal sinus rhabdomyosarcoma group than in the orbital rhabdomyosarcoma group.

Lack of correlation between the histologic and magnetic resonance imaging results of optic nerve involvement in eyes primarily enucleated for retinoblastoma.

PURPOSE: To correlate the histologic and magnetic resonance imaging results of the optic nerve in eyes primarily enucleated for retinoblastoma. DESIGN: Retrospective, clinicopathologic correlation. PARTICIPANTS: Sixty-seven consecutive patients with retinoblastoma who underwent primary enucleation. METHODS: The histologic results of 67 eyes from 67 patients with retinoblastoma who underwent primary enucleation between March 1997 and January 2008 were studied for evidence of optic nerve invasion. Two neuroradiologists independently reviewed available preoperative magnetic resonance imaging studies with special emphasis on nonenhanced T2-weighted and gadolinium-enhanced T1-weighted imaging for evidence of optic nerve invasion. A weighted kappa statistic was used to assess agreement between observers. MAIN OUTCOME MEASURES: Correlation between neuroradiologists and histologic results. RESULTS: Of the 67 eyes studied, 60 had preoperative magnetic resonance images, 58 of which were deemed appropriate for review by both neuroradiologists. Review of the histologic results showed optic nerve involvement in 62 (93%) of 67 eyes: 28 prelaminar (42%), 24 laminar (36%), and 10 postlaminar (15%). On review of the magnetic resonance scans, the first neuroradiologist identified optic nerve involvement in 57 (95%) of 60 eyes: 26 prelaminar (43%), 10 laminar (17%), and 11 postlaminar (18%). The second neuroradiologist identified optic nerve involvement in 46 (77%) of 60 eyes: 33 prelaminar (55%), 9 laminar (15%), and 4 postlaminar (7%). Moderate agreement existed between neuroradiologists (kappa, 0.55). Poor and fair agreement existed between each of the 2 neuroradiologists and histologic results, respectively (kappa, 0.29 and 0.17). Exophytic tumors showed the greatest disparity (kappa, -0.20 and -0.13) between magnetic resonance imaging and histologic results. CONCLUSIONS: Limited correlation was found between magnetic resonance imaging and histologic results in assessing optic nerve invasion in eyes with retinoblastoma. Magnetic resonance imaging using routine imaging technologies, although useful in the evaluation of retinoblastoma, has limited usefulness in assessing the exact extent of optic nerve invasion; high-risk features of retinoblastoma such as postlaminar invasion remain best defined by histologic analysis. This study demonstrates that the interpretation of optic nerve involvement by a radiologist should not be the determining factor to defer enucleation in favor of neoadjuvant therapy.

Predictive factors of invasion in eyes with retinoblastoma enucleated after eye salvage treatments.

BACKGROUND: The impact of chemotherapy, focal therapies, radiation and co-existing ocular morbidities on histology of eyes with retinoblastoma enucleated following chemoreduction is not well known. PROCEDURE: Twenty-five eyes (23 patients) with retinoblastoma enucleated after failing eye-salvage therapy were evaluated. Reasons for enucleation (tumor progression, subretinal or vitreous seeds) and co-morbid conditions (neovascular glaucoma, cataract, vitreous hemorrhage and retinal detachment) were documented. All specimens were reviewed for evidence of ciliary body, choroidal, optic nerve, and scleral invasion. RESULTS: The median age at diagnosis was 14 months (range, 1-37 months). Twenty eyes were classified as Reese-Ellsworth Group IV-V at diagnosis. Twenty-four eyes had recurrent disease at enucleation; one eye was enucleated for neovascular glaucoma and vitreous hemorrhage. Co-existing ocular morbidities at enucleation included vitreous hemorrhage (n = 6), retinal detachment (n = 9), neovascular glaucoma (n = 9) and cataracts (n = 3). Histologic findings included choroidal invasion (n = 7), ciliary body invasion (n = 4), optic nerve invasion (n = 6) and scleral invasion (n = 3). The median time from diagnosis to enucleation was 11 months. Co-existing retinal detachment and vitreous hemorrhage significantly increased the likelihood of optic nerve invasion (P = 0.014 and P = 0.011, respectively). Prolonged time to enucleation was significantly associated with the likelihood of choroidal (P = 0.010) and ciliary body (P = 0.021) invasion as well as invasion of multiple sites. CONCLUSION: In eyes with retinoblastoma enucleated after chemoreduction, co-existing ocular morbidities and time to enucleation are predictive of extra-retinal extension.

Development of retinoblastoma programs in Central America.

BACKGROUND: Retinoblastoma, a curable eye tumor, is associated with poor survival in Central America (CA). To develop a retinoblastoma program in El Salvador, Guatemala, and Honduras, twinning initiatives were undertaken between local pediatric oncology centers, nonprofit foundations, St. Jude Children's Research Hospital, and the University of Tennessee Hamilton Eye Institute. PROCEDURE: The retinoblastoma program focused on developing early diagnosis programs in Honduras with national vaccination campaigns, developing treatment protocols suited to local conditions, building local networks of oncologists and ophthalmologists, training local healthcare providers, using modern donated equipment for diagnosis and treatment, and the ORBIS Cybersight consultation program and Internet meetings to further education and share expertise. Pediatric ophthalmologists and oncologists worked with foundations to treat patients locally with donated equipment and Internet consultations, or at the center in Guatemala. RESULTS: Number of patients successfully treated increased after the program was introduced. For 2000-2003 and 2004-2007, patients abandoning/refusing treatment decreased in Guatemala from 20 of 95 (21%) to 14 of 123 (11%) and in Honduras from 13 of 37 (35%) to 7 of 37 (19%). Survival in El Salvador was good and abandonment/refusal low for both periods. Of 18 patients receiving focal therapy for advanced disease, 14 have single remaining eyes. CONCLUSION: Development of the program in CA has decreased abandonment/refusal and enabled ophthalmologists at local centers to use modern equipment to provide better treatment. This approach might serve as a guide for developing other multispecialty programs.

An unusual case of retinoblastoma.

The authors describe the treatment and complications of a case of retinoblastoma with an atypical presentation. A 20-month-old girl was diagnosed as having unilateral retinoblastoma by cytopathology during pars plana vitrectomy and the right eye was enucleated. Following the enucleation, computed tomography detected a questionable focus of retinoblastoma in the residual optic nerve. Exploration of the orbit and sampling of the optic nerve stump had to be performed because the enucleated globe was lost. Histopathology of the optic nerve stump showed granulation tissue and fibrosis but no evidence of retinoblastoma. Histopathology of the enucleated globe and transected optic nerve is the gold standard for staging retinoblastoma and formulating a treatment plan. Treatment of the patient with retinoblastoma becomes more complex when histopathologic findings are not available.

Team management, twinning, and telemedicine in retinoblastoma: a 3-tier approach implemented in the first eye salvage program in Jordan.

BACKGROUND: This study evaluated the outcome of retinoblastoma patients, when employing a telemedicine-based twinning program in Jordan. PROCEDURE: This cohort study included patients at the King Hussein Cancer Centre (KHCC; Amman, Jordan) who received consultations for retinoblastoma from March 2003 to September 2006. A collaborative program was established with the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee. Cases were discussed using an Internet consultation service where fundus images, clinical history, and proposed treatment were reviewed. Selected cases were further discussed via videoconferencing and electronic mail. RESULTS: Thirty-three children with retinoblastoma (20 bilateral) were treated at KHCC. The median age at diagnosis was 7 months for patients with bilateral retinoblastoma and 35 months for patients with unilateral retinoblastoma. Of the 20 patients with bilateral disease, 12 were newly diagnosed and 8 had received prior treatment. Our success in the bilateral cases was most evident in the previously untreated group, in which only six eyes (25%) were enucleated and four eyes (17%) were irradiated. Of the 13 patients with unilateral retinoblastoma, 12 underwent enucleation, and 6 required radiation. Neither group experienced mortality. CONCLUSIONS: Twinning has positively impacted survival and ocular salvage in Jordan. By partnering a team of professionals with mentors willing to provide close supervision, the highly specialized management of retinoblastoma can be successfully implemented in a developing country.

Incidence of new tumor formation in patients with hereditary retinoblastoma treated with primary systemic chemotherapy: is there a preventive effect?

PURPOSE: To report the incidence of new tumor formation in hereditary retinoblastoma patients treated with primary systemic chemotherapy. DESIGN: Noncomparative retrospective case series. PARTICIPANTS: Fifty-eight consecutive patients with hereditary retinoblastoma treated with primary systemic chemotherapy. METHODS: The charts of 58 consecutive patients with hereditary retinoblastoma treated between January 1996 and August 2005 were reviewed. Data extracted included gender, age at diagnosis, family history of retinoblastoma, laterality of disease, tumors per eye, Reese-Ellsworth grouping of affected eyes, starting and ending dates for chemotherapy, number of cycles of chemotherapy, chemotherapy regimen, need for external beam radiotherapy and/or enucleation, and development and location (macula, midzone, and periphery) of new tumors after the start of systemic chemotherapy. MAIN OUTCOME MEASURE: New tumor formation after treatment with primary systemic chemotherapy. RESULTS: Of the 58 patients, 48 had bilateral involvement at diagnosis. Median age at diagnosis was 6.6 months. Thirteen patients had a positive family history. Of the eyes with tumor (n = 106) at diagnosis, 52 (49%) were in Reese-Ellsworth groups I to III, whereas 54 (51%) were in group IV or V. Seven patients (12%) with a median age of 1.6 months at diagnosis formed 36 new tumors in 11 eyes after the start of chemotherapy. Median time from initiation of chemotherapy to detection of the first new tumor was 3 months (range, 1-15). Cumulative incidence of new tumor formation at 2 years was 10+/-3%. An age of <6 months at diagnosis, family history of retinoblastoma, and Reese-Ellsworth grouping of I to III were found to correlate significantly with an increased incidence of new tumor formation (P<0.001, P<0.001, and P = 0.021, respectively). Median follow-up for all patients was 5 years (range, 1-10.1). CONCLUSION: New tumors continue to form in patients with hereditary retinoblastoma despite treatment with primary systemic chemotherapy. Younger patients and those with a positive family history are more likely to have new tumors formed. However, chemotherapy may impact small previously undetected lesions by slowing their growth and facilitating later focal consolidation.

Low-dose cyclophosphamide and interferon alfa 2a for the treatment of capillary hemangioma of the orbit.

PURPOSE: To report the use of a combination of low-dose cyclophosphamide and interferon alfa 2a (IFNalpha2a) for the treatment of orbital juvenile capillary hemangioma. DESIGN: Retrospective case series. PARTICIPANTS: Five patients with juvenile capillary hemangiomas of the orbit. METHODS: Five patients with a median age of 9 weeks presented with a rapidly enlarging orbital mass. Two patients also had involvement of the upper eyelid obstructing the visual axis. Patients underwent biopsy to confirm the diagnosis before starting combination therapy with low-dose oral cyclophosphamide (10 mg/kg per day for 3 days repeated every 2 weeks) and subcutaneous IFNalpha2a (3 million units/m2 per day once daily) for a maximum treatment time of 4 to 6 months. Patients underwent serial ophthalmic, hematologic, and neurologic evaluations. MAIN OUTCOME MEASURE: Regression of lesions after combination therapy. RESULTS: Four of 5 patients had marked regression of the hemangioma by 40% to 60% with subsequent reduction in proptosis, corneal exposure, and obstruction of the visual axis. None of the 4 patients developed amblyopia. Side effects included mild neutropenia and uncomplicated infections. There was no neurologic toxicity after a median follow-up of 10 months. One patient failed to respond to treatment and required further treatment with intralesional steroid injections. CONCLUSIONS: Combination of low-dose cyclophosphamide with IFNalpha2a for a short period of time induced early and lasting regression of orbital juvenile capillary hemangiomas with minimal side effects. This regimen may be a suitable alternative that avoids the toxicity of long-term administration of interferon only. However, the experience reported here does not show if cyclophosphamide alone may be sufficient and allow complete avoidance of interferon and its potential serious side effects, and longer follow-up is needed to determine if cyclophosphamide causes any long-term harm.

Systematic review of the current status of programs and general knowledge of diagnosis and management of retinoblastoma.

BACKGROUND: This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients with Rb at select hospitals with Rb programs or that treat and refer patients with Rb, and identified the gaps in practice. We propose solutions to improve diagnosis, provide adequate treatment, and improve patient uptake. METHODS: A general review was conducted on PubMed of peer-reviewed literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb programs at seven hospitals in Mexico were contacted for data available on their patients with Rb. RESULTS: Five hospitals provided clinical data on 777 patients with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4% underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced intraocular stage of development. Knowledge of the disease is limited, despite the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment guidelines and is developing a national Rb registry. Especially in the Southern states, prevalence and outcomes are comparable to African and Asian countries, and only few patients are referred to national treatment centers. Only three institutions have comprehensive Rb programs. CONCLUSIONS: There is an immediate need in Mexico to expand primary care providers' knowledge of Rb and to expand and upgrade current Rb programs to meet the needs of the population adequately. Diagnosis and care of Rb patients in Mexico can also be improved by the establishment of a national Rb registry and a national early detection program, and by increased use of the national treatment protocol.

Treatment of intraocular retinoblastoma with vincristine and carboplatin.

PURPOSE: To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) or enucleation in patients with intraocular retinoblastoma. PATIENTS AND METHODS: Twenty-five patients (43 eyes) with newly diagnosed intraocular retinoblastoma received primary treatment with eight courses of vincristine and carboplatin. Focal treatments were delayed until documentation of disease progression. Outcome measures for each eye were length of time to disease progression, avoidance or delay of EBRT, and globe survival. Event-free survival was defined as the length of time to EBRT or enucleation. RESULTS: Disease in all eyes responded to chemotherapy and progressed in only two patients before completion of the eight courses of therapy. Disease in all but four eyes progressed and required focal treatments. Event-free survival estimates at 2 years were 59.2% +/- 12.0% for Reese-Ellsworth group I, II, and III eyes and 26.3% +/- 9.2% for group IV and V eyes. Nineteen eyes (44.2%) required EBRT and 13 eyes (30.2%) were enucleated. The ocular salvage rate was 83.3% for Reese-Ellsworth group I to III eyes and 52.6% for group IV and V eyes. For those patients receiving EBRT, the median time from enrollment to EBRT was 9.5 months (median age at EBRT, 21 months). CONCLUSION: In combination with appropriate early intensive focal treatments, chemoreduction with vincristine and carboplatin, without etoposide, may be an alternative treatment for patients with early-stage intraocular retinoblastoma, although additional studies are needed. Patients with advanced intraocular disease require more aggressive treatments.

Effect on ocular survival of adding early intensive focal treatments to a two-drug chemotherapy regimen in patients with retinoblastoma.

PURPOSE: To evaluate vincristine and carboplatin with intensive focal treatments in the management of intraocular retinoblastoma. DESIGN: Noncomparative, retrospective interventional case series. SETTING: Institutional. PATIENT POPULATION: Sixteen patients (11 bilateral, 5 unilateral) with intraocular retinoblastoma. Interventional procedures: Patients were treated with eight courses of vincristine and carboplatin. Intensive focal treatments were administered after two courses of chemotherapy. MAIN OUTCOME MEASURES: Avoidance of external beam radiotherapy (EBRT) and eye survival. RESULTS: Twenty eyes (74.1%) were classified as Reese-Ellsworth Group V. All eyes responded to chemotherapy. With a median follow-up of 23 months (range 10 to 33 months) and a median of 5.5 focal treatments per eye (range 0 to 19 treatments), ocular survival was 81%. Eight eyes (30%) in five patients received EBRT. CONCLUSIONS: Vincristine and carboplatin combined with intensive focal treatments is an effective regimen for patients with intraocular retinoblastoma. This treatment regimen has outcomes comparable to those of more toxic regimens and merits further evaluation.

Retinoblastoma in Mexico: part I. A review of general knowledge of the disease, diagnosis, and management.

This is the first of a two-part review that aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico (including the authors' experience at the leading Rb centers), identify the gaps in practice, and propose solutions to improve diagnosis, treatment, and patient uptake. In this first part, general knowledge of Rb diagnosis and management is summarized with a focus on the latest advances in chemotherapy. A general review of peer-reviewed literature of Rb was conducted on PubMed. Key findings were summarized. Provided there is early detection and referral of patients followed by appropriate conservative management, Rb is curable. In developed countries, the primary treatment outcome is ocular salvage with sight preservation. Advanced chemotherapeutic options such as intra-arterial and intravitreal chemotherapy can now save even the most advanced tumors. Advances in Rb therapy are generally limited to developed countries. The implications in Mexico, of the findings from this review will be discussed in Part 2, which will be a comprehensive situational analysis of the state of Rb programming in Mexico, including a review of current demographic data available from hospitals that have Rb programs or treat Rb.

Comparison of high-risk histopathological features in eyes with primary or secondary enucleation for retinoblastoma.

AIMS: To compare high-risk histopathology of eyes with primary versus secondary enucleation from patients with retinoblastoma. PATIENTS AND METHODS: A retrospective histopathology review identified 207 eyes enucleated from 202 patients between March 1997 and August 2013. Our review considered high-risk histopathological features to include extraocular disease or invasion of the anterior chamber, iris, ciliary body, choroid (massive), postlaminar optic nerve or sclera. RESULTS: Most eyes (144, 70%) were primarily enucleated; 63 (30%) were secondarily enucleated after neoadjuvant therapy. The primary enucleation group had more advanced disease (Reese-Ellsworth group V: 95% vs 59%; International Classification Group D/E: 97% vs 59%; p<0.001). The incidence of high-risk histopathology features was similar between groups (32% vs 21%, n=59; p=0.132). The type of prior therapy was not associated with high-risk histopathology features. Time to enucleation was longer for secondarily enucleated eyes with high-risk features. Choroid and postlaminar optic nerve invasion were more frequent in eyes primarily enucleated (p<0.001). Forty-six of the 59 (78%) patients with high-risk features received adjuvant chemotherapy and/or external beam radiation therapy. Three patients who received primary enucleation and adjuvant therapy died of metastatic recurrence. CONCLUSIONS: Despite the more favourable classification of eyes treated with neoadjuvant therapy, the risk of high-risk histopathology features at enucleation was comparable with eyes undergoing primary enucleation. Delayed enucleation was associated with these features, and the majority of patients required further adjuvant therapy. Caution must be exercised in treating recalcitrant intraocular retinoblastoma to promptly pursue definitive enucleation in an effort to minimise further treatment exposures and metastases.

A rapidly growing choroidal melanoma.

PURPOSE: We describe a rapidly growing choroidal melanoma that failed to respond to consecutive globe-sparing treatments in an individual with ocular melanocytosis. DESIGN: Interventional case report. METHODS: A 53-year-old man with right ocular melanocytosis, decreased vision in the right eye, and right eye pain was referred for suspected choroidal melanoma. The lesion, which measured 2.4 mm x 6.6 mm x 6.0 mm, was treated with transpupillary thermotherapy on two occasions and with iodine-125 (I-125) plaque brachytherapy, both of which failed. Enucleation allowed histologic analysis. RESULTS: At enucleation, the choroidal melanoma in the right eye measured 13.6 mm x 16.5 mm x 16.9 mm, which demonstrated the most rapid growth and doubling time reported in a tumor of this type thus far. Pathologic analysis classified the tumor as a mixed-cell type. CONCLUSION: This case reiterates the association between ocular melanocytosis and choroidal melanoma, provides additional evidence that rapid growth and doubling time may be associated with transpupillary thermotherapy and I-125 plaque failure, and highlights the need to follow those tumors closely.