How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

Postnatal microcephaly and retinal involvement expand the phenotype of RPL10-related disorder.

Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X-linked syndrome presenting with intellectual disability (ID), autism spectrum disorder, epilepsy, dysmorphic features, and multiple congenital anomalies. Among 15 individuals with RPL10-related disorder reported so far, only one patient had retinitis pigmentosa and microcephaly was observed in approximately half of the cases. By exome sequencing, three Italian and one Spanish male children, from three independent families, were found to carry the same hemizygous novel missense variant p.(Arg32Leu) in RPL10, inherited by their unaffected mother in all cases. The variant, not reported in gnomAD, is located in the 28S rRNA binding region, affecting an evolutionary conserved residue and predicted to disrupt the salt-bridge between Arg32 and Asp28. In addition to features consistent with RPL10-related disorder, all four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10-related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

PURPOSE: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. METHODS: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). CONCLUSIONS: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

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

PURPOSE: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. MAIN OUTCOME MEASURES: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. RESULTS: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease. CONCLUSIONS: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

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

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

INCIDENCE AND RELATION WITH ANATOMICAL AND FUNCTIONAL VARIABLES OF POSTOPERATIVE MACULAR DISPLACEMENT IN RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To investigate the incidence of postsurgical retinal displacement in patients treated with pars plana vitrectomy for rhegmatogenous retinal detachment and to assess the influence of displacement on macular function. METHODS: Observational prospective study of 20 consecutive cases of rhegmatogenous retinal detachment who underwent 23-G pars plana vitrectomy with gas (C3F8 or SF6) tamponade, and prone resting. Three months after surgery, retinal displacement was evaluated by fundus autofluorescence. Macular function was evaluated with optical coherence tomography, multifocal electroretinogram, best-corrected visual acuity, and stereopsis. RESULTS: Postoperative retinal displacement was observed in 60% of cases. No correlation between the type of tamponade used and retinal displacement was observed. Similarly, no association between retinal displacement and postoperative stereopsis or visual acuity was found. A lower amplitude in P1 wave on the multifocal electroretinogram was observed in eyes with rhegmatogenous retinal detachment compared with the contralateral eye. However, no statistically significant differences between groups with or without retinal displacement were found. CONCLUSION: Retinal displacement in patients who undergo pars plana vitrectomy to treat rhegmatogenous retinal detachment is common. However, this displacement does not seem to affect macular function.

INTRAVITREAL DEXAMETHASONE IMPLANT FOR RADIATION MACULOPATHY SECONDARY TO PLAQUE BRACHYTHERAPY IN CHOROIDAL MELANOMA.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implant 0.7 mg (Ozurdex) in radiation maculopathy secondary to plaque brachytherapy in choroidal melanoma. METHODS: Twelve eyes diagnosed of radiation maculopathy secondary to plaque brachytherapy and treated with intravitreal dexamethasone implant were included. Visual acuity, foveal thickness using spectral domain optical coherence tomography, and grade of macular edema, using Horgan classification, were evaluated. RESULTS: Mean age was 65.5 ± 28 years (range, 40-82 years). Mean follow-up was 8.2 ± 7.8 months (range, 2-28 months). Mean visual acuity before treatment was, in logarithm of the minimum angle of resolution scale, 1 ± 0.58 (range, 0.4-2) and mean final visual acuity 0.8 ± 0.58 (range, 0.2-2), showing a nonsignificant trend to improvement (P = 0.091; Wilcoxon's test). Foveal thickness before treatment was 416 ± 263 µm (range, 222-725 µm) and final foveal thickness 254 ± 170 µm (range, 145-750), showing a significant decrease (P = 0.016; Wilcoxon's test). Referring to Horgan classification, a significant reduction in grades before and after treatment was demonstrated (P = 0.007; Wilcoxon's test). CONCLUSION: Ozurdex is a useful treatment for radiation maculopathy associated to plaque brachytherapy for uveal melanoma, with a significant decrease in foveal thickness and a significant improvement in Horgan classification. This anatomical improvement was correlated with a moderate improvement in visual acuity.

Subthreshold transpupillary thermotherapy in management of foveal subretinal fluid in small pigmented choroidal lesions.

PURPOSE: To evaluate the effect of subthreshold transpupillary thermotherapy (sTTT) in foveal subretinal fluid of small pigmented choroidal lesions. METHODS: Retrospective, noncomparative, interventional case series. We reviewed patients with small pigmented choroidal lesions presenting foveal subretinal fluid and treated with sTTT to evaluate fluid regression. RESULTS: We treated 13 patients with small pigmented choroidal lesions with a mean height of 2.02 ± 0.54 mm (range, 1.4-2.9 mm) and a mean largest diameter of 7.60 ± 1.98 mm (range, 5-11 mm). In 11 cases, foveal subretinal fluid was completely resolved (84.6%), with a mean follow-up of 42.46 ± 26.29 months (range, 12-103 months). The mean number of sTTT sessions applied was 1.38 ± 0.77 (range, 1-3 sessions), at a mean spot size of 1,570.59 ± 795.1 µm (range, 500-3,000 µm), and overall exposure time of 2.32 ± 1.2 minutes (range, 1-6 minutes). Mean laser power applied was 370.63 ± 162.87 mW (range, 200 to 600 mW). Best-corrected visual acuity at the time of diagnosis was maintained or improved in 69.3% of patients after sTTT treatment. During follow-up, tumor progression was reported in 5 cases, regardless of the presence of subretinal fluid. These cases were treated promptly with brachytherapy. CONCLUSION: However, sTTT may be effective in solving foveal subretinal fluid in small pigmented choroidal lesions, attaining satisfactory visual acuity in most cases.

Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker.

One-year results of a flexible regimen with ranibizumab therapy in macular degeneration: relationship with the number of injections.

PURPOSE: To evaluate the efficacy and safety of a flexible regimen with intravitreal injections of ranibizumab in patients with naive choroidal neovascularization secondary to age-related macular degeneration and to determine whether the final outcome is related to the number of injections. METHODS: Prospective, noncomparative, consecutive case series study. We included 90 eyes of 88 patients that were initially treated with 3 consecutive monthly intravitreal injections of ranibizumab, and thereafter, follow-up visits were progressively spread out to a maximum of 8 weeks apart in the absence of visual acuity loss and signs of lesion activity. The primary end points were changes in visual acuity (Early Treatment Diabetic Retinopathy Study letters), foveal thickness measured by spectral-domain optical coherence tomography, and lesion size (LS) measured by fluorescein angiography. RESULTS: The median visual acuity improved from 53 letters at baseline to 60 letters at Month 1 (P < 0.0001), 63 letters at Month 3 (P < 0.0001), and 60 letters at Month 12 (P < 0.0001). A significant reduction was also observed in foveal thickness and LS (P < 0.0001). The mean number of injections was 4.4, and the mean number of visits was 8.0. Treatment consisted of 3 injections for 40% of patients, and 60% of patients received more than 3 injections. No significant association was observed between the visual acuity improvement and the number of injections. No relevant side effects were observed. CONCLUSION: A flexible regimen with ranibizumab therapy is efficacious and safe in patients with neovascular age-related macular degeneration, reducing both the burden of injections and follow-up visits. The visual acuity improvement was independent of the number of injections.

Intravitreal ranibizumab for choroidal neovascularization secondary to pathological myopia: 12-month follow-up.

PURPOSE: To evaluate the efficacy and safety of intravitreal ranibizumab in the treatment of choroidal neovascularization (CNV) due to pathological myopia (PM). METHODS: This retrospective case series studied outcomes in patients with CNV secondary to PM who were treated with intravitreal ranibizumab. Patients underwent complete ophthalmic evaluation, which included best-corrected visual acuity testing measured with Early Treatment Diabetic Retinopathy Study charts, optical coherence tomography (OCT) and baseline fluorescein angiography (FA). Indications for retreatment included the persistence of subretinal fluid on OCT as well as hemorrhages and new CNV on FA. Patients were followed for a minimum of 12 months. RESULTS: We treated 29 eyes in 29 patients; the mean age was 56.8 years. Thirteen eyes were naïve, while 16 had been previously treated with photodynamic therapy or intravitreal bevacizumab. The mean initial visual acuity was 44.8 letters; at the 12-month follow-up, it was 53.7 letters. The mean OCT foveal thickness decreased by 35.3 µm. Patients received an average of 1.38 injections. Statistically significant differences were observed both in visual acuity and in central foveal thickness. All subgroups had favorable outcomes. None of the patients developed injection-induced complications or drug-related side effects. CONCLUSION: Intravitreal injection of ranibizumab appears to be safe and efficacious in patients with CNV secondary to PM followed over a 12-month period.

Prepapillary vascular loop-a new classification.

BACKGROUND/OBJECTIVES: To analyze the ophthalmic characteristics of congenital prepapillary vascular loop (PVL) and to propose a new morphologic classification dividing the loops into six types. SUBJECTS/METHODS: Collaborative multinational multicentre retrospective study of PVL cases. RESULTS: There was a total of 49 cases (61 eyes), 37 unilateral (75.5%) and 12 bilateral (24.5%), 32 arterial type (65.3%) and 18 venous type (36.7%) (one patient had either kind in each eye). The mean number of loops per eye was 2.7 (range, 1-7). The loops were asymptomatic in 42 cases (85.7%). Other findings included: the presence of cilioretinal artery (14 cases), retinal vascular tortuosity (26 cases), amaurosis fugax (1 case), branch retinal artery occlusion (1 case) and vitreous haemorrhage (3 cases). Six morphologic loop types could be discerned based on elevation (flat vs. elevated), shape (figure of 8 or corkscrew with hyaline sheath), number (multiple or single), location (central or peripheral), lumen size (arterial vs. arteriolar) and presence of vascular tortuosity or vitreous traction. CONCLUSIONS: PVL are usually asymptomatic and can be divided into six morphologic types with different pathogenesis during early embryogenesis.

Axenfeld-Rieger ocular anomaly and retinoblastoma caused by constitutional chromosome 13q deletion.

Axenfeld-Rieger (AR) ocular anomaly might be due to deletions of different chromosomes. No association between AR, mental retardation, and retinoblastoma has been described. We report a 2-month-old female with general development delay and dysmorphic features. AR anomaly was detected, and a retinoblastoma (RB) was diagnosed in a very early stage. De novo 13q deletion was identified. Systemic chemotherapy, focal cryotherapy, transpupillary thermotherapy, brachytherapy, and intra-arterial chemotherapy were needed to control the RB. This is the first report of an association of AR, 13q deletion, and retinoblastoma, to be disclosed in patients born with such ocular and dysmorphic features.

Intravitreal infliximab in patients with macular degeneration who are nonresponders to antivascular endothelial growth factor therapy.

PURPOSE: The purpose of this study was to determine the efficacy and safety of intravitreal infliximab in the treatment of choroidal neovascularization secondary to age-related macular degeneration in patients who are nonresponders to antivascular endothelial growth factor therapy. METHODS: Prospective, noncomparative, interventional case series. The primary inclusion criteria for patients consisted of previous treatment with five or more intravitreal injections of bevacizumab and/or ranibizumab, visual loss, angiographic leakage, and intraretinal and/or subretinal fluid on spectral domain optical coherence tomography. At Day 0, a single intravitreal injection of infliximab (2 mg/0.05 mL) was administered. Best-corrected visual acuity testing measured with Early Treatment Diabetic Retinopathy Study charts and spectral domain optical coherence tomography scans were performed on Days 0, 3, 7, 30, 60, and 90. Fluorescein angiography was performed at days 0 and 90. The development of systemic antibodies against infliximab (human antichimeric antibodies) was not sought. Main outcome measures were changes in best-corrected visual acuity, foveal thickness, and lesion size. RESULTS: We included four patients. At Day 90, the best-corrected visual acuity change was -18, +3, +4, and -4 letters, respectively. Intraretinal and/or subretinal fluid on spectral domain optical coherence tomography scans was not significantly reduced in any case. Lesion size was not reduced in any case. Two patients developed intraocular inflammation with high intraocular pressure 3 and 5 weeks after the infliximab injection, respectively. One case was controlled with topical medication, and one case required posterior vitrectomy. CONCLUSION: Intravitreal infliximab showed no significant visual or anatomical benefit for the treatment of choroidal neovascularization secondary to age-related macular degeneration in patients who were nonresponders to antivascular endothelial growth factor therapy. In addition, half of the cases developed intraocular inflammation.

Clinical predictors of survival in metastatic uveal melanoma.

PURPOSE: To determine the clinical factors that influence survival in patients with metastatic uveal melanoma. STUDY DESIGN: Single-center, retrospective review of patients' medical records. METHODS: The following data of ninety-nine consecutive patients (49 men, 50 women) with metastatic uveal melanoma were registered: patient demographics; primary tumor characteristics; features of first melanoma-related metastasis; symptoms and patient status at distant disease debut and metastasis treatment. Overall survival was analyzed by Kaplan-Meier estimates. A Cox proportional hazards regression model was applied to identify independent predictors associated with survival. RESULTS: Mean patient age at metastatic diagnosis was 60.7 years (standard deviation, 12.8). The liver was the first metastatic site in most (92.9%) cases. The median disease-free interval was 26 months (interquartile range, 34). Median overall survival after detection of the first metastasis was 8 months (interquartile range, 14). The baseline characteristics of the primary uveal melanoma were not associated with survival in patients with stage IV disease. In the multivariate analysis, the following factors at first metastatic diagnosis were associated with improved overall survival: disease-free interval > 36 months; better performance status; and normal serum lactate dehydrogenase and gamma glutamyl transpeptidase levels. Overall survival was not influenced by specific metastatic treatment. CONCLUSION: Although metastatic uveal melanoma has a poor prognosis, this study reveals the existence of several independent prognostic factors for prolonged overall survival. These findings may help improve survival estimates in patients with advanced disease.

Proliferative diabetic retinopathy and hemovitreous: red flag for blindness.

A 54-year-old male patient experienced sudden painless visual loss in his left eye. He had been diagnosed with diabetes mellitus 8 years prior with poor metabolic control. Diabetic retinopathy was diagnosed 2 years ago and was treated with mild scattered retinal photocoagulation.

Prognostic Factors and Decision Tree for Long-Term Survival in Metastatic Uveal Melanoma.

PURPOSE: The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. MATERIALS AND METHODS: The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristicswere assessed in both groups. RESULTS: Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. CONCLUSION: The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.

Tumor Volumes in Choroidal Melanoma: Agreement Between Three-Dimensional Ultrasound and Two Mathematical Models.

PURPOSE: To determine the degree of agreement between 2 mathematical models and 3-dimensional ultrasonography (3DUS) in estimating choroidal melanoma tumor volumes. DESIGN: Reliability analysis. METHODS: Tumor measurements estimated by 2 mathematical models (designated Formula 1 and Formula 2) were compared to those obtained by 3DUS in 45 consecutive patients with primary choroidal melanoma to determine the percentage agreement between the models and 3DUS. RESULTS: Both formulas tended to overestimate the tumor volume. Overall, the mean volume differences between 3DUS and Formula 1 and between 3DUS and Formula 2, respectively, were 51.7 mm(3) (95% confidence interval [CI], 187.6 to 84.3) and 23.8 mm(3) (95% CI, 122.5 to 74.8). Excluding mushroom-shaped tumors, the mean volume differences were 52.0 mm(3) (95% CI, 194.9 to 91.0) and 23.0 mm(3) (95% CI, 127.0 to 81.0), respectively. In mushroom-shaped tumors, mean volume differences were 49.9 mm(3) (95% CI, 135.7 to 35.9) and 29.3 mm(3) (95% CI, 87.6 to 29.0), respectively. CONCLUSIONS: The agreement between these mathematical models and the measured 3DUS volume was high. The data obtained in this study show that both formulas provide a simple, fast, and accurate method of estimating tumor volumes in the clinical setting, suggesting that these models could be used as a reliable and inexpensive alternative to time-consuming procedures such as 3DUS or magnetic resonance imaging. The accurate tumor volume values provided by these formulas may help to provide more reliable estimates of tumor regression or regrowth following globe-preserving treatment of choroidal melanomas, and may be a valuable prognostic indicator.

Preclinical platform of retinoblastoma xenografts recapitulating human disease and molecular markers of dissemination.

Translational research in retinoblastoma - a pediatric tumor that originates during the development of the retina - would be improved by the creation of new patient-derived models. Using tumor samples from enucleated eyes we established a new battery of preclinical models that grow in vitro in serum-free medium and in vivo in immunodeficient mice. To examine whether the new xenografts recapitulate human disease and disseminate from the retina to the central nervous system, we evaluated their histology and the presence of molecular markers of dissemination that are used in the clinical setting to detect extraocular metastases. We evaluated GD2 synthase and CRX as such markers and generated a Taqman real-time quantitative PCR method to measure CRX mRNA for rapid, sensitive and specific quantification of local and metastatic tumor burden. This approach was able to detect 1 human retinoblastoma cell in 100.000 mouse brain cells. Our research adds novel preclinical tools for the discovery of new retinoblastoma treatments for clinical translation.

Swept source optical coherence tomography imaging of a series of choroidal tumours.

OBJECTIVE: This pilot study aimed to describe the swept-source optical coherence tomography (SS-OCT) features of a series of choroidal tumours. DESIGN: This was an observational case series. PARTICIPANTS: Patients in our ocular oncology unit were recruited: 32 eyes belonging to 31 patients. METHODS: All of the patients underwent fundus photography, ultrasonography (US), fundus autofluorescence (FAF), and SS-OCT. The main assessed characteristics were maximal tumour diameter and thickness, inner structure, and disturbances in the choroidal layers, sclera, retinal pigment epithelium, and retina. RESULTS: The tumours examined consisted of 16 nevi, 6 lesions with risk factors for growth, 4 melanomas, 4 hemangiomas, and 2 choroidal metastases. SS-OCT provided an accurate measurement of the tumour's maximum diameter in every case. Choroidal nevi displayed a compact, regular structure with a preserved choriocapillaris. Choroidal melanomas showed a more irregular inner structure, with an ablated choriocapillaris. Choroidal hemangiomas had a regular spongelike pattern. Choroidal metastases had an irregular inner structure organized in clumps and an ablated outer retina. In most of the pigmented tumours, the sclerochoroidal interface was not identifiable by SS-OCT. The presence of lipofuscin, detected by funduscopy and FAF, was also correlated with the SS-OCT findings. CONCLUSIONS: SS-OCT provided a view of the inner structures of a series of choroidal tumours and assessed their associated structural anomalies, as well as obtained measurements of the diameter and thickness in most cases.