Scleral ectasia stabilization following intra-arterial chemotherapy in an eye with recurrent retinoblastoma.

Purpose: To report a case of recurrent retinoblastoma following transpupillary thermotherapy (TTT) with development of scleral ectasia, as well as their successful treatment with intra-arterial chemotherapy. Observations: A 15-month-old girl with bilateral retinoblastoma presented with recurrent retinoblastoma and associated scleral ectasia with concern for extraocular extension after receiving multiple round of systemic chemotherapy and TTT. Given her negative systemic evaluation, decision was made to pursue intra-arterial chemotherapy. After completion of six rounds of 3-agent intra-arterial chemotherapy, the recurrent retinoblastoma had completely regressed and the scleral ectasia had improved and fibrosed. Conclusions and importance: The sclera is classically viewed as hyperthermy-resistant to TTT. Here, we describe scleral ectasia due to aggressive TTT with recurrence of the retinoblastoma. Our treatment with intra-arterial chemotherapy not only caused complete regression of the recurrent retinoblastoma, but it also contributed to the stabilization and improvement of the weakened scleral.

High-dose dual therapy is effective as first-line treatment for Helicobacter pylori infection.

BACKGROUND/AIMS: Although many regimens, including quadruple, sequential, and concomitant treatment, are used and recommended as first-line or rescue therapies for Helicobacter pylori infection, eradication rates are still below 90% in intention-to-treat analyses. Treatment protocols with substantially high eradication rates and low antibiotic resistance are needed. In this study, we investigated the efficacy of high-dose dual therapy as first-line treatment in a Turkish population. MATERIALS AND METHODS: All patients underwent upper gastrointestinal endoscopy for the initial H. pylori status because of dyspeptic symptoms. All patients received a 14-day, high-dose dual therapy comprising rabeprazole (20 mg t.i.d.) and amoxicillin (1 g t.i.d.) for H. pylori eradication. H. pylori stool antigen tests of eradication were administered to all participants at least 4 weeks after the completion of the treatment. RESULTS: The high-dose dual therapy demonstrated a 91.3% rate of successful eradication of H. pylori infection. Per-protocol success was 94.4% among female patients (n=51) and 89.6% among male patients (n=86); in terms of gender, the differences were not significant (p=0.310). No side effects were observed during the study in any patient. Six other patients did not take adequate doses of the treatment protocol. CONCLUSION: High-dose dual therapy with rabeprazole and amoxicillin was highly effective and well tolerated as a first-line therapy for H. pylori eradication.

Integrative Exome and Transcriptome Analysis of Conjunctival Melanoma and Its Potential Application for Personalized Therapy.

Importance: Greater understanding of molecular features of conjunctival melanoma (CM) may improve its clinical management. Objective: To evaluate molecular features of CM and application of this information into clinical care. Design, Setting, and Participants: In a prospective case series of CM with integrative exome and transcriptome analysis, 8 patients at an academic ocular oncology setting were evaluated. The study was conducted from November 2015 to March 2018. Interventions/Exposures: Integrative exome and transcriptome analysis of CMs and clinical management of a patient's care by using this information. Main Outcomes and Measures: Molecular characterization of CM and its potential clinical application. Results: In the 8 patients (4 men) included in analysis, 4 subgroups of CM were observed, including the BRAF V600E mutation in 1 tumor, NRAS Q61R mutation in 3 tumors, NF1 mutations (Q1188X, R440X, or M1215K+ S15fs) in 3 tumors, and triple-wild type (triple-WT) in 1 tumor. The triple-WT case had CCND1 amplification and mutation in the CIC gene (Q1508X). Five tumors, including the triple-WT, also harbored mutations in MAPK genes. In addition to the genes linked to mitogen-activated protein kinase and phosphoinositol 3-kinase pathways, those involved in cell cycle and/or survival, ubiquitin-mediated protein degradation, and chromatin remodeling/epigenetic regulation (ATRX being the most frequently mutated: noted in 5 tumors) may play an important role. Other frequently mutated genes included PREX2 (n = 3), APOB (n = 4), and RYR1/2 (n = 4), although their relevance remains to be determined. The mutation burden ranged from 1.1 to 15.6 mutations per megabase (Mut/Mb) and was 3.3 Mut/Mb or less in 3 tumors and more than 10 Mut/Mb in 2 tumors. A patient with a large tumor and BRAF V600E mutation was treated with combined systemic BRAF (dabrafenib) and MEK (trametinib) inhibitors. After 3 months of therapy, her CM responded substantially and the residual tumor was removed by local surgical excision. Conclusions and Relevance: The NRAS Q61R and NF1 mutations were more common than the BRAF V600E mutation in this series. Although small tumors (where incisional biopsy is not indicated) are treated with surgical excision regardless of mutational profile, in large tumors carrying the BRAF V600E mutation, neoadjuvant therapy with combined systemic BRAF and MEK inhibitors followed by local excision may be used as an alternative to exenteration. Integrative omics analysis of CM may be informative and guide clinical management and treatment in selected cases.

The association between quality of life and complementary and alternative medicine use in patients with diabetes mellitus.

AIM: In the current study, we aimed to evaluate the relationship between life quality and use of complementary and alternative medicine (CAM) in patients with diabetes mellitus. METHODS: The Audit of Diabetes-Dependent Quality of Life (ADDQOL-19) scale was applied to 453 diabetic patients. Socio-demographic characteristics of the patients and their CAM usage were recorded. RESULTS: The rate of CAM use among diabetic patients was 46.1%. The most preferred practices were herbal medicine, including black cumin (26.6%), cinnamon (23.3%) and olive leaf (12.5%). 'Freedom to eat' (p = 0.002), 'drinking freedom' (p = 0.001) and 'physical health' (p = 0.001) were the most negatively affected items that may drive patients to use CAM. CONCLUSIONS: In this sampling, the use of CAM among patients with diabetes mellitus is high. The association between CAM usage and eating and drinking freedom and physical health should be studied in detail in further studies.

Influence of vitamin C and E supplementation on the eradication rates of triple and quadruple eradication regimens for Helicobacter pylori infection.

BACKGROUND/AIMS: In our study, we aimed to assess the effect of vitamin E and C supplementation to triple and quadruple Helicobacter pylori eradication regimens. MATERIALS AND METHODS: Four hundred patients with H. pylori infection were classified into four groups. Patients in group A (n=100) received amoxicillin, clarithromycin, and lansoprazole for 2 weeks. In group B, patients (n=100) received vitamins C and E for a month, in addition to amoxicillin, clarithromycin, and lansoprazole for 2 weeks. Patients in group C (n=100) received amoxicillin, clarithromycin, lansoprazole, and bismuth subcitrate for 2 weeks, whereas those in group D (n=100) received vitamins C and E for a month, in addition to amoxicillin, clarithromycin, lansoprazole, and bismuth subcitrate for 2 weeks. H. pylori eradication was assessed with the C14 urea breath test 2 months after the end of the therapy. The eradication rate was assessed using per-protocol (PP) and intention-to-treat (ITT) analyses. RESULTS: Three hundred forty-eight patients finished the study. The eradication of H. pylori was achieved in 63 of 84 patients (75%) by PP and 63 of 100 (63%) by ITT analysis in group A, 60 of 84 (71.4%) by PP and 60 of 100 (60%) by ITT analysis in group B, 72 of 89 (80.9 %) by PP and 72 of 100 (72%) by ITT analysis in group C, and 76 of 91 (83.5%) by PP and 76 of 100 (76%) by ITT analysis in group D. There was no remarkable change between groups A and B (p>0.05). Similar results were also found between groups D and C (p>0.05). CONCLUSION: This study revealed that supplementing vitamins C and E to either the triple or quadruple therapies did not provide an additional advantage for achieving significantly higher eradication rates for H. pylori.

Sclerochoroidal calcification in a patient with classic Bartter's syndrome.

PURPOSE: To report sclerochoroidal calcification in a patient with classic Bartter's syndrome. DESIGN: Observational case report. METHODS: A 42-year-old woman with a 26-year history of classic Bartter's syndrome was found to have bilateral fundus tumors. The patient presented initially with quivering lips and hand stiffness at age 6 years but was not diagnosed until age 16 years. Treatment included magnesium and potassium supplementation and Amiloride therapy. RESULTS: On ocular examination, there were multifocal, yellow-white, geographic, solid choroidal lesions along the superior and inferior retinal vascular arcades in both eyes. Ultrasonography showed echogenic, placoid calcified lesions at the level of the sclera and choroid, consistent with bilateral sclerochoroidal calcification. CONCLUSIONS: Sclerochoroidal calcification can be associated with classic Bartter's syndrome.

Changing concepts in management of circumscribed choroidal hemangioma: the 2003 J. Howard Stokes Lecture, Part 1.

BACKGROUND AND OBJECTIVE: To review trends in the management of circumscribed choroidal hemangioma (CCH) and to propose treatment guidelines based on review of recent literature and the authors' personal experience with more than 250 METHOD: The English-language literature on the management of CCH was reviewed, with emphasis on changing concepts in recent years. RESULTS: Xenon arc and argon laser photocoagulation and thermotherapy have been used to treat CCH with localized retinal detachment, but there has recently been enthusiasm for photodynamic therapy (PDT) using fluorescein angiography and optical coherence tomography to monitor subretinal fluid and cystoid retinal edema before and after treatment. Tumors with extensive retinal detachment have been managed by surgical attempts at retinal reattachment followed by photocoagulation or cryotherapy, and more recently by radiotherapy. Management currently includes observation, argon laser photocoagulation, transpupillary thermotherapy, PDT, and radiotherapy. Enucleation may be necessary in rare cases. The goal of treatment should be to induce resolution of existing retinal detachment and to improve or stabilize visual loss. CONCLUSIONS: There is increasing use of PDT for CCH with localized retinal detachment and radiotherapy for CCH with more extensive detachment. Although follow-up is short, current methods may achieve better tumor control and better visual outcome. However, caution is advised because long-term follow-up is still not available.

Chemoreduction for unilateral retinoblastoma.

OBJECTIVE: To evaluate conservative management of unilateral retinoblastoma using chemoreduction and focal treatment. DESIGN: Prospective nonrandomized single-center clinical trial. SETTING: Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, Philadelphia, Pa, in conjunction with the Division of Oncology at The Children's Hospital of Philadelphia. PARTICIPANTS: Thirty eyes of 30 patients with unilateral retinoblastoma treated with chemoreduction between June 1, 1994, and August 31, 1999, that would otherwise have been managed with enucleation or external beam radiotherapy. INTERVENTION: All patients received treatment for retinoblastoma with a planned 6 cycles of chemoreduction using vincristine sulfate, etoposide, and carboplatin, combined with focal treatment (cryotherapy or thermotherapy) to each retinal tumor. MAIN OUTCOME MEASURES: The main outcome measure was the postchemoreduction need for external beam radiotherapy or enucleation. The cumulative probability of each outcome was estimated using Kaplan-Meier survival analysis. A secondary outcome measure was final visual acuity in the affected eye. The clinical features at the time of patient presentation were analyzed for their impact on the main outcomes using a series of Fisher exact tests and Cox proportional hazards regressions. RESULTS: Eighteen eyes (60%) were classified as having Reese-Ellsworth (RE) groups I through IV retinoblastoma and 12 eyes (40%), group V retinoblastoma. By using Kaplan-Meier estimates, we found a need for either external beam radiotherapy or enucleation in 68% of eyes by 5 years. In fact, 38% of those in groups I through IV required either treatment, whereas all of those in group V required the additional use of either treatment. Specifically, the need for external beam radiotherapy occurred in 27% of eyes by 5 years. Eleven percent of those in groups I through IV and 50% of group V required external beam radiotherapy by 5 years. The factors predictive of the need for external beam radiotherapy included RE group V disease, tumor thickness greater than 5 mm, and presence of vitreous seeds. The need for enucleation occurred in 47% of eyes by 5 years using Kaplan-Meier analysis. Specifically, 29% of those in groups I through IV and 67% of group V required enucleation by 5 years. The factors predictive of the need for enucleation included age at diagnosis older than 12 months, RE group V disease, tumor base diameter greater than 15 mm, and tumor thickness greater than 5 mm. At a mean follow-up of 29 months, the final visual acuity was 20/200 or better in 6 eyes (20%) and worse than 20/200 in 14 (47%); enucleation was needed in 10 (33%). Of the 26 eyes with initial macular involvement of retinoblastoma, final visual acuity was 20/200 or better in 6 (23%). No patient developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms. CONCLUSIONS: Chemoreduction is an option for selected eyes with unilateral retinoblastoma. Those with advanced RE group V retinoblastoma showed poorest results, while those with less advanced groups I through IV disease showed best results, maintaining the globe in 71% of eyes, sometimes with satisfactory functional visual acuity.

Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation.

PURPOSE: To report the results of chemoreduction and focal therapy for retinoblastoma with determination of factors predictive of the need for treatment with external beam radiotherapy or enucleation. DESIGN: Interventional case series. METHODS: One-hundred three patients with retinoblastoma (158 eyes with 364 tumors) at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University in conjunction with the Division of Oncology at Children's Hospital of Philadelphia from June 1994 to August 1999 were enrolled for this prospective clinical trial. The patients received treatment for retinoblastoma with six planned cycles (one cycle per month) of chemoreduction using vincristine, etoposide, and carboplatin combined with focal treatments (cryotherapy, thermotherapy, or plaque radiotherapy). The two main outcome measures after chemoreduction and focal therapy were the need for external beam radiotherapy and the need for enucleation. The clinical features at the time of patient presentation were analyzed for impact on the main outcome measures using a series of Cox proportional hazards regressions. RESULTS: Using Reese-Ellsworth (RE) staging for retinoblastoma, there were nine (6%) eyes with group I disease, 26 (16%) eyes with group II disease, 16 (10%) eyes with group III disease, 32 (20%) eyes with group IV disease, and 75 (48%) eyes with group V retinoblastoma. All eyes showed initial favorable response with tumor regression. The median follow-up was 28 months (range, 2-63 months). Failure of chemoreduction and need for treatment with external beam radiotherapy occurred in 25% of eyes at 1 year, 27% at 3 years, and no further increase at 5 years. More specifically, external beam radiotherapy was necessary at 5 years in 10% of RE groups I-IV eyes and 47% of RE group V eyes. Multivariate factors predictive of treatment with external beam radiotherapy included non-Caucasian race, male sex, and RE group V disease. Failure of chemoreduction and the need for treatment with enucleation occurred in 13% eyes at 1 year, 29% at 3 years, and 34% at 5 years. More specifically, enucleation was necessary in 15% of RE groups I-IV eyes at 5 years and in 53% of RE group V at 5 years. Multivariate factors predictive of treatment with enucleation included patient age older than 12 months, single tumor in eye, and tumor proximity to foveola within 2 mm. Overall, of the 158 eyes, 50% required external beam radiotherapy or enucleation and 50% were successfully managed without these treatments. No patient developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms over the 5-year follow up. CONCLUSIONS: Chemoreduction offers satisfactory retinoblastoma control for RE groups I-IV eyes, with treatment failure necessitating additional external beam radiotherapy in only 10% of eyes and enucleation in 15% of eyes at 5-year follow-up. Patients with RE group V eyes require external beam radiotherapy in 47% and enucleation in 53% at 5 years.

Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma.

OBJECTIVE: To identify the clinical features of eyes with retinoblastomas that predict the recurrence of retinal tumors, vitreous seeds, and subretinal seeds following treatment with chemoreduction. DESIGN: Prospective nonrandomized single-center clinical trial. SETTING: Ocular oncology service at Wills Eye Hospital of Thomas Jefferson University (Philadelphia, Pa) in conjunction with the division of oncology at Children's Hospital of Philadelphia. PARTICIPANTS: There were 158 eyes with 364 tumors in 103 consecutive patients with retinoblastoma managed with chemoreduction between June 1994 and August 1999. INTERVENTION: All patients received treatment for retinoblastoma with 6 cycles of chemoreduction using vincristine, etoposide, and carboplatin combined with focal treatment (cryotherapy, thermotherapy, or plaque radiotherapy) for each retinal tumor. MAIN OUTCOME MEASURES: The 3 main outcome measures included recurrence of retinal tumors, recurrence of vitreous seeds, and recurrence of subretinal seeds. The clinical features at the initial examination were analyzed for their association with the main outcome measures using a series of Cox proportional hazards regressions. RESULTS: All retinal tumors, vitreous seeds, and subretinal seeds showed an initial favorable response of regression during this treatment regimen. Using Kaplan-Meier estimates, at least 1 retinal tumor recurrence per eye was found in 37% of eyes at 1 year, 51% at 3 years, and no further increase at 5 years. By multivariate analysis, the only factor predictive of retinal tumor recurrence was the presence of tumor-associated subretinal seeds at the initial examination. Of the 54 eyes that had vitreous seeds at the initial examination, vitreous seed recurrence was found in 26% of eyes at 1 year, 46% at 3 years, and 50% at 5 years. By univariate analysis, the only factor predictive of vitreous seed recurrence was the presence of tumor-associated subretinal seeds at the initial examination. Of the 71 eyes that had subretinal seeds at the initial examination, subretinal seed recurrence was detected in 53% of eyes at 1 year, 62% at 3 years, and no further increase at 5 years. By multivariate analysis, factors predictive of subretinal seed recurrence included a tumor base greater than 15 mm and a patient age of 12 months or younger at diagnosis. There were no patients who developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms. CONCLUSIONS: Chemoreduction combined with focal therapy is effective for selected eyes with retinoblastomas. Eyes with subretinal seeds at initial examination are at particular risk for recurrence of retinal tumor and vitreous seeds. Younger patients with large tumors are at risk for recurrence of subretinal seeds. Retinal tumor and subretinal seed recurrence seems to manifest within 3 years of follow-up. Close follow-up of all patients treated with chemoreduction is warranted.