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1.
Ophthalmology ; 121(7): 1406-13, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24661864

RESUMO

PURPOSE: To describe a new classification of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR). DESIGN: Retrospective case series and literature review. PARTICIPANTS: A total of 17 patients from 5 institutions. METHODS: Detailed case history, multimodal imaging, and genetic testing were reviewed for patients with macular schisis without a known predisposing condition. Patients with a stellate appearance centered on the fovea with correlating confirmed expansion of the outer plexiform layer (OPL) by optical coherence tomography (OCT) were included. Exclusion criteria included a family history of macular retinoschisis, a known genetic abnormality associated with retinoschisis, myopic traction maculopathy, epiretinal membrane, vitreoretinal traction, optic or scleral pit, or advanced glaucomatous optic nerve changes. MAIN OUTCOME MEASURES: Clinical features, anatomic characteristics, and visual acuity. RESULTS: A total of 22 eyes from 16 female patients and 1 male patient with foveomacular schisis were reviewed from 5 institutions. Initial visual acuity was ≥ 20/50 in all eyes (mean, 20/27), but visual acuity in a single eye decreased from 20/20 to 20/200 after the development of subfoveal fluid. The refractive status was myopic in 16 eyes, plano in 3 eyes, and hyperopic in 2 eyes. Three eyes had a preexisting vitreous separation, and 19 eyes had an attached posterior hyaloid. Follow-up ranged from 6 months to >5 years. CONCLUSIONS: In this largest known series of patients with SNIFR, all patients demonstrated splitting of the OPL in the macula with relatively preserved visual acuity (≥ 20/40) except in a single patient in whom subretinal fluid developed under the fovea.


Assuntos
Imagem Multimodal , Retina/patologia , Retinosquise/classificação , Retinosquise/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas do Olho/genética , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Retinosquise/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
2.
Ophthalmology ; 119(8): 1596-603, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22521086

RESUMO

PURPOSE: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). DESIGN: Prospective, multicenter study. PARTICIPANTS: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. TESTING: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. MAIN OUTCOME MEASURES: Patients were managed for their primary tumor and monitored for metastasis. RESULTS: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. CONCLUSIONS: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Melanoma/genética , Neoplasias Uveais/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 3/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Uveais/patologia , Adulto Jovem
4.
Retina ; 31(1): 148-53, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20921926

RESUMO

PURPOSE: To report the macular hole closure rate and visual outcomes of patients with residual triamcinolone acetonide in the fovea after macular hole repair. METHODS: We reviewed the medical records of consecutive patients who underwent macular hole surgery at our institution between 2005 and 2008. Only patients with visible triamcinolone in the fovea in the first postoperative month were included. RESULTS: Six patients with Stage III or IV macular holes were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. Triamcinolone acetonide was used to visualize the vitreous in every patient, and diluted indocyanine green was used to stain the internal limiting membrane in five patients. The median preoperative best-corrected visual acuity was 20/200, which improved to a median of 20/40 at the last follow-up. Five patients eventually developed retinal pigment epithelial alterations. Anatomic hole closure was achieved in every patient. The mean follow-up was 23 months (range, 3-36 months). CONCLUSION: Residual triamcinolone sequestered in the fovea after macular hole surgery did not affect hole closure or prevent improvement in visual acuity. It is unclear whether the retinal pigment epithelial alterations in our patients represent toxicity or are unrelated to the triamcinolone exposure.


Assuntos
Fóvea Central/metabolismo , Glucocorticoides/farmacocinética , Perfurações Retinianas/metabolismo , Perfurações Retinianas/cirurgia , Triancinolona Acetonida/farmacocinética , Vitrectomia , Corantes , Progressão da Doença , Membrana Epirretiniana/cirurgia , Óculos , Feminino , Seguimentos , Fundo de Olho , Gases/administração & dosagem , Humanos , Verde de Indocianina , Injeções Intraoculares , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/fisiopatologia , Coloração e Rotulagem , Distribuição Tecidual , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Vitrectomia/métodos , Corpo Vítreo
5.
Eye (Lond) ; 35(2): 425-432, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32291404

RESUMO

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.


Assuntos
Anormalidades do Olho , Malformações Vasculares , Humanos , Vasos Retinianos/anormalidades , Estudos Retrospectivos , Malformações Vasculares/diagnóstico
6.
Ocul Oncol Pathol ; 6(5): 360-367, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123530

RESUMO

INTRODUCTION: The prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) predicts metastatic risk based on primary tumor biology. Here we report outcomes from a prospective registry of 15-GEP-tested patients, and a meta-analysis with published cohorts. OBJECTIVES: Management and 5-year clinical outcomes following 15-GEP testing were evaluated. METHODS: Eighty-nine patients with 15-GEP results were prospectively enrolled at four centers. Physician-recommended management plans were collected, and clinical outcomes tracked every 6 months. RESULTS: Eighty percent of Class 1 (low-risk) patients underwent low-intensity management; all Class 2 (high-risk) patients underwent high-intensity management (p < 0.0001). Median follow-up for event-free patients was 4.9 years. Five Class 1 (10%) and 23 Class 2 (58%) tumors metastasized (p < 0.0001). Five-year Class 1 and 2 metastasis-free survival rates were 90% (81-100%) and 41% (27-62%; p < 0.0001), and melanoma-specific survival rates were 94% (87-100%) and 63% (49-82%; p = 0.0007). Class 2 was the only independent predictor of metastasis and was associated with increased risk for metastasis and mortality by meta-analysis. CONCLUSIONS: UM patient management is guided by 15-GEP testing. Class 2 patients were managed more intensely, in accordance with an observed metastatic rate of >50%; Class 1 patients were safely spared intensive surveillance, resulting in appropriate utilization of healthcare resources.

7.
Ophthalmology ; 116(8): 1531-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19501405

RESUMO

OBJECTIVE: To evaluate the incidence, effect on visual recovery, and predisposing risk factors of postvitrectomy macular edema (ME). DESIGN: Prospective cohort study. PARTICIPANTS: One-hundred nine eyes undergoing nonemergent vitrectomy surgery. METHODS: Eyes were evaluated for postoperative day 1 inflammation, 1-month retinal thickness using optical coherence tomography, and preoperative and 1-month postoperative best-corrected visual acuity (BCVA). Macular edema was defined as central subfield thickness > or =272 microm. MAIN OUTCOME MEASURES: Retinal thickness, inflammation, and BCVA. RESULTS: Incidence of ME on optical coherence tomography was 47% (95% confidence interval [CI], 37%-56%). Mean 1-month visual acuity improved 3.3 lines (0.33 logarithm of minimum angle of resolution [logMAR] units) to 20/80(+1) (0.58+/-0.46 logMAR units) from 20/150(-2) (0.91+/-0.63 logMAR units) before surgery (P<0.001). Mean 1-month center point thickness (CPT), central subfield (CSF), and total macular volume were 265+/-107 microm, 288+/-94 microm, and 7.8+/-1.2 mm(3), respectively. Severity of postoperative inflammation predicted retinal thickness at 1 month (P<0.05). Intraoperative epinephrine use was associated with increased postoperative inflammation (P = 0.02). Eyes with greater reduction in CSF (or CPT) from baseline experienced more rapid visual recovery (r = -0.36; 95% CI, -0.61 to -0.06; P = 0.02). CONCLUSIONS: Postvitrectomy ME is common and delays visual recovery. Degree of postoperative inflammation is an important risk factor for ME and, in this series, was increased in the setting of intraocular epinephrine. Efforts to reduce or prevent inflammation after vitrectomy should be beneficial and therefore are encouraged.


Assuntos
Edema Macular/diagnóstico , Edema Macular/epidemiologia , Complicações Pós-Operatórias , Tomografia de Coerência Óptica , Vitrectomia , Feminino , Humanos , Incidência , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica/fisiologia , Retina/patologia , Doenças Retinianas/cirurgia , Fatores de Risco , Acuidade Visual/fisiologia , Hemorragia Vítrea/cirurgia
8.
Retina ; 29(7): 926-31, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19584650

RESUMO

PURPOSE: To evaluate the safety and effect of bevacizumab pretreatment on the incidence of recurrent vitreous hemorrhage and visual acuity after vitrectomy for proliferative diabetic retinopathy. METHODS: This was a consecutive, retrospective, and comparative cohort study. Patients undergoing vitrectomy from September 2006 through November 2007 at the Emory Eye Center for complications of proliferative diabetic retinopathy were identified and reviewed. A total of 33 eyes pretreated with bevacizumab and 104 untreated eyes were observed for postoperative vitreous hemorrhage and final visual acuity. RESULTS: Patients in the bevacizumab group were significantly younger than those in the untreated group (average age, 46.4 vs. 58.4 years) and were more likely to have 20-gauge instrumentation (58% vs. 36%). An average of 9.6 days passed between injection and surgery. Early (4-6 weeks) rebleed rates were 15% versus 13% in the bevacizumab and untreated groups, respectively, and not statistically different. Preoperative (7/200 vs. count finger at 4'), 1-month postoperative (20/200(-3) vs. 20/150), and 3-month postoperative visual acuity (20/100(-3) vs. 20/100(+2)) were not statistically different between groups. No statistical difference was found in rebleed rates regarding the gauge of vitrectomy. CONCLUSION: Bevacizumab pretreatment for diabetic vitrectomy was not associated with any observed complications but did not influence rates of postoperative vitreous hemorrhage or final visual acuity in this retrospective series. The overall incidence of postoperative early vitreous hemorrhage in this series was 13% and seems lower than historically reported rates.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Retinopatia Diabética/cirurgia , Cuidados Pré-Operatórios/efeitos adversos , Acuidade Visual , Vitrectomia/efeitos adversos , Hemorragia Vítrea/epidemiologia , Hemorragia Vítrea/etiologia , Adulto , Anticorpos Monoclonais Humanizados , Bevacizumab , Estudos de Coortes , Retinopatia Diabética/fisiopatologia , Humanos , Incidência , Pessoa de Meia-Idade , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
9.
Indian J Ophthalmol ; 55(5): 380-3, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17699951

RESUMO

We identified three eyes that had undergone enucleation after transscleral resection of uveal melanoma. Two enucleated eyes with microscopically positive margins of resection exhibited no evidence of residual melanoma and these patients were alive without metastasis with at least four years' follow-up. One eye with a transected melanoma contained residual melanoma and that patient died with metastatic melanoma to the liver three years after enucleation. There appear to be at least two general types of positive surgical margins of resection of uveal melanoma: microscopically positive margins and macroscopically positive (transected) margins of resection.


Assuntos
Enucleação Ocular/métodos , Melanoma/patologia , Neoplasias Uveais/patologia , Idoso , Evolução Fatal , Seguimentos , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Neoplasias Uveais/cirurgia
10.
Retin Cases Brief Rep ; 11(4): 348-351, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27490976

RESUMO

PURPOSE: To describe the development of uveitis and retinal vasculitis in association with pembrolizumab treatment for metastatic uveal melanoma. METHODS: A case report and a brief review of the literature are presented. Information collected and reported include the patient's clinical course, physical examination findings, fluorescein angiogram images, retinal photographs, and her response to treatment. RESULTS: A 54-year-old woman was diagnosed with a large choroidal malignant melanoma and had the affected eye enucleated. Pathology confirmed a mixed cell choroidal melanoma, and gene expression profiling was Class 2. Seventeen months after enucleation, the patient was diagnosed with metastatic uveal melanoma to the liver. Disease progression was observed during ipilimumab treatment. Pembrolizumab treatment was initiated, and after four infusions, she presented to clinic complaining of floaters and blurred vision. Examination revealed a nongranulomatous panuveitis characterized by perivascular retinal pigment epithelium pigmentary changes, retinal venous sheathing, 1+ anterior chamber and vitreous cellular reaction, 2+ vitreous haze, and optic disk edema. A dexamethasone sustained-release implant was administered and the uveitis regressed. A relapse in symptoms occurred but quickly subsided with a repeat injection. CONCLUSION: Pembrolizumab may induce a uveitic reaction. There is mounting evidence that patients using prembrolizumab should be educated and monitored for signs of uveitis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Uveíte Posterior/induzido quimicamente , Neoplasias da Coroide/tratamento farmacológico , Feminino , Humanos , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Uveais/tratamento farmacológico
11.
Brachytherapy ; 16(3): 646-653, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28262517

RESUMO

PURPOSE: To evaluate outcomes of choroidal melanoma patients treated with 125I or 103Pd plaque brachytherapy. METHODS AND MATERIALS: From 1993 to 2012, our institution treated 160 patients with 103Pd (56.1%) and 125 patients with 125I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics. RESULTS: Median followup was longer for 125I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, 103Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3-T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both 103Pd and 125I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125I with 107 103Pd patients. 103Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103Pd than 125I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA. CONCLUSIONS: Both 125I and 103Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103Pd.


Assuntos
Braquiterapia , Neoplasias da Coroide/radioterapia , Radioisótopos do Iodo/uso terapêutico , Melanoma/radioterapia , Paládio/uso terapêutico , Radioisótopos/uso terapêutico , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias da Coroide/patologia , Neoplasias da Coroide/cirurgia , Enucleação Ocular , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/efeitos adversos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paládio/efeitos adversos , Lesões por Radiação/etiologia , Radioisótopos/efeitos adversos , Doenças Retinianas/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
12.
Am J Ophthalmol ; 142(2): 310-5, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16876514

RESUMO

PURPOSE: To report four cases of optic nerve neuropathy in three children treated with periocular carboplatin injections for unilateral or bilateral intraocular retinoblastoma. DESIGN: Retrospective, observational case series. SETTING: University-based Ophthalmology Practice. STUDY POPULATION: Four eyes of three children with retinoblastoma enucleated after nonsuccessful multimodality treatment including periocular carboplatin injections. OBSERVATION PROCEDURES: The enucleated eyes were routinely processed and evaluated by light microscopy. A retrospective chart review of all four cases was performed. RESULTS: Three enucleated eyes (Reese-Ellsworth groups III and VB) were obtained from two children with bilateral multifocal retinoblastoma, and one eye (Reese-Ellsworth group IIB) was harvested from a child with unilateral retinoblastoma. All affected eyes underwent three to seven periocular carboplatin injections before enucleation. Additional treatment modalities included systemic chemotherapy, transpupillary thermotherapy, transscleral cryotherapy, and external beam radiotherapy. Histopathologic evaluation of the enucleated eyes revealed focal areas of ischemic necrosis or atrophy of the optic nerve along with dystrophic calcification and mild inflammation in the surrounding fibrovascular adipose tissue. CONCLUSIONS: Periocular injections of carboplatin may be a useful treatment approach in the management of patients with advanced intraocular retinoblastoma and may minimize systemic side-effects. However, ophthalmologists and pediatric oncologists should be aware of potential marked local complications with periocular carboplatin delivery, including ischemic optic neuropathy. Modifying the injection site/location (for example, subtenon space) or adding other delivery routes adjuncts (for example, fibrin sealant) deserves further study.


Assuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Neuropatia Óptica Isquêmica/induzido quimicamente , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Atrofia/induzido quimicamente , Terapia Combinada , Enucleação Ocular , Feminino , Humanos , Lactente , Recém-Nascido , Injeções , Masculino , Necrose/induzido quimicamente , Nervo Óptico/patologia , Órbita , Estudos Retrospectivos
13.
J Oncol ; 2016: 5325762, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27446211

RESUMO

Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing. Thirty-seven patients in the prospective study were Class 1 and 33 were Class 2. Class 1 patients had 100% 3-year metastasis-free survival compared to 63% for Class 2 (log rank test p = 0.003) with 27.3 median follow-up months in this interim analysis. Class 2 patients received significantly higher-intensity monitoring and more oncology/clinical trial referrals compared to Class 1 patients (Fisher's exact test p = 2.1 × 10(-13) and p = 0.04, resp.). The results of this study provide additional, prospective evidence in an independent cohort of patients that Class 1 and Class 2 patients are managed according to the differential metastatic risk indicated by DecisionDx-UM. The trial is registered with Clinical Application of DecisionDx-UM Gene Expression Assay Results (NCT02376920).

14.
Ophthalmology ; 112(6): 1151-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15885791

RESUMO

PURPOSE: To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. DESIGN: Experimental study using LHbeta-Tag transgenic mice in a randomized controlled trial. PARTICIPANTS AND CONTROLS: Thirty-three 10-week-old LHbeta-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals. METHODS: Three groups of 11 mice were treated with a single, 30 microl injection of fibrin sealant in the subconjunctival space of 1 eye; the opposite eye was left untreated as an internal control. Group 1 (low-dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high-dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes. MAIN OUTCOME MEASURES: Main outcome measure was mean tumor burden per level per eye in each experimental group. RESULTS: The best therapeutic results were obtained in eyes treated with low-dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed, and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining 5 eyes in this group was minimal (4 eyes) or moderate (1 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although a similar reduction in mean tumor burden was observed in eyes treated with high-dose carboplatin in fibrin sealant, 5 of 10 eyes analyzed in this group also demonstrated histopathologic evidence of severe toxicity. CONCLUSIONS: Subconjunctival carboplatin in fibrin sealant is effective in the treatment of transgenic murine retinoblastoma. A single injection of low-dose carboplatin in fibrin sealant was sufficient to induce complete or near-complete intraocular tumor regression in 10 of 11 eyes (91%), with no associated histologic evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical use in the treatment of intraocular retinoblastoma.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Sistemas de Liberação de Medicamentos , Adesivo Tecidual de Fibrina , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Animais , Antígenos Transformantes de Poliomavirus/genética , Túnica Conjuntiva , Modelos Animais de Doenças , Injeções , Hormônio Luteinizante Subunidade beta/genética , Camundongos , Camundongos Transgênicos , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Retinoblastoma/genética , Retinoblastoma/patologia
15.
Arch Ophthalmol ; 123(3): 328-32, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15767474

RESUMO

OBJECTIVE: To investigate the efficacy of verteporfin and photodynamic therapy in the treatment of large retinal capillary hemangiomas. METHODS: Case reports of 3 patients with large retinal capillary hemangiomas treated with photodynamic therapy using verteporfin. Standard verteporfin dosages (6 mg/m(2) of body surface area) were given. Both standard and modified photodynamic protocols were followed. Modified protocols included shorter verteporfin infusion times and longer light exposure times. RESULTS: Pretreatment best-corrected Snellen visual acuity of the 3 affected eyes were 20/100, 20/50, and 2/200, respectively. All cases had associated exudative retinal detachments involving the macula. Cases 1 and 2 were classic endophytic retinal capillary hemangiomas. Case 3 was a reactive retinal capillary hemangioma. Case 1 had 2 photodynamic therapy treatments, and after 8 months, visual acuity improved to 20/40. Two years after initiating photodynamic therapy, the visual acuity was 20/30 and there was no reperfusion of the hemangioma. Case 2 had 3 photodynamic therapy treatments. The hemangioma was fibrotic, and 20 months after initiating photodynamic therapy visual acuity improved to 20/30. Case 3 had 1 treatment, 11 weeks later and visual acuity improved to 20/400. Four months after treatment, visual acuity returned to counting fingers because of tractional elevation of the macula as the capillary hemangioma fibrosed. Vitrectomy surgery was performed, and choroidal and retinal neovascularization was discovered. Three months after vitrectomy visual acuity was 20/400. In cases 1 and 2, the capillary hemangioma ultimately regressed, and the exudative detachment resolved. CONCLUSIONS: Verteporfin and photodynamic therapy were effective in achieving closure of large retinal capillary hemangiomas. In all cases, the hemangioma underwent fibrosis with consequent macular puckering due to retinal traction. In all cases, the visual acuity improved.


Assuntos
Antineoplásicos/uso terapêutico , Hemangioma Capilar/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Neoplasias da Retina/tratamento farmacológico , Adolescente , Adulto , Criança , Feminino , Fibrose , Hemangioma Capilar/patologia , Humanos , Masculino , Neoplasias da Retina/patologia , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/patologia , Resultado do Tratamento , Verteporfina , Acuidade Visual , Vitrectomia
16.
Ophthalmology ; 111(9): 1725-33, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15350329

RESUMO

OBJECTIVE: To evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS). DESIGN: Open-label, 3-center, uncontrolled clinical study. PARTICIPANTS: Ocular histoplasmosis syndrome patients with subfoveal CNV (N = 26) with a greatest linear dimension no larger than 5400 microm with classic or occult CNV extending under the geometric center of the fovea, and best-corrected visual acuity letter score of approximately 20/40 to 20/200. METHODS: The methods were similar to those described in the 1-year results with follow-up examinations every 3 months continuing through the second year. During the second year, additional therapy was recommended if fluorescein angiography showed leakage at a scheduled visit. MAIN OUTCOME MEASUREMENTS: Visual function measurements included the changes from baseline in visual acuity and contrast sensitivity scores. Lesion size and leakage from classic and occult CNV were assessed at month 12 and month 24. Safety assessments also were made. RESULTS: A 24-month examination was completed in 22 of the 26 enrolled participants (85%). At the 24-month examination, median improvement from baseline in visual acuity of the 22 patients evaluated was 6 letters; median contrast sensitivity improved by 3.5 letters. At the 24-month examination, 10 patients (45%) gained 7 or more letters of visual acuity from baseline, whereas 4 patients (18%) lost 8 or more letters, including 2 patients (9%) who lost at least 15 letters. There was absence of fluorescein angiographic leakage from classic CNV in 17 of the 20 evaluable lesions (85%), and leakage from occult CNV was absent in all eyes. No serious ocular adverse events were reported, and no serious systemic event was considered to be associated with treatment. CONCLUSIONS: Median visual acuity improved and fluorescein angiographic leakage decreased after verteporfin therapy in this small, uncontrolled clinical study of patients with subfoveal CNV resulting from OHS. Verteporfin therapy seemed to be relatively safe in these patients. The selected cases feature fluorescein angiographic examples of CNV that are important in determining when to apply verteporfin therapy.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Histoplasmose/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Adulto , Idoso , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/fisiopatologia , Infecções Oculares Fúngicas/complicações , Infecções Oculares Fúngicas/fisiopatologia , Feminino , Angiofluoresceinografia , Histoplasmose/complicações , Histoplasmose/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Síndrome , Resultado do Tratamento , Verteporfina , Acuidade Visual/fisiologia
17.
Arch Ophthalmol ; 120(3): 320-4, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11879135

RESUMO

OBJECTIVE: To report the visual outcome in patients with a neovascular membrane (NVM) associated with idiopathic juxtafoveolar telangiectasis (IJFT). METHODS: We performed a retrospective, noncomparative analysis of 26 eyes of 16 patients with an NVM associated with bilateral IJFT (Gass classification group 2A). Eyes were divided into 2 groups: group WO (n = 11) included eyes with IJFT without evidence of an NVM on initial examination; eyes in group W (n = 15) had an NVM at the initial diagnosis of IJFT. In group WO, the initial visual acuity and the time between the initial examination to the diagnosis of an NVM were evaluated. Characteristic fundus findings, including the presence or absence of a chorioretinal anastomosis, intraretinal pigmentary plaques, and crystalline deposits, as well as the final visual acuity were reviewed for both groups. RESULTS: The initial visual acuity for eyes in group WO ranged from 20/20 to 20/70 (median, 20/30); in group W, from 20/20 to 4/200 (median, 20/70). The average time from initial diagnosis of IJFT to the development of an NVM was 73 months (range, 5-142 months). In group WO, chorioretinal anastomosis and concurrent perivascular retinal pigment epithelial hyperplasia were observed before the development of an NVM. The final visual acuity for all eyes ranged from 20/40 to 2/200 (median, 20/200). Eighty-one percent of eyes (21/26) had a final visual acuity of 20/200 or worse. CONCLUSIONS: The stable final visual acuity in patients with an NVM associated with IJFT is generally poor, with 80% of eyes in this series having a final visual acuity of l20/200 or worse. In patients with IJFT, the presence of a chorioretinal anastomosis and retinal pigment epithelial hyperplastic plaques always preceded the development of an NVM.


Assuntos
Fóvea Central/irrigação sanguínea , Neovascularização Retiniana/etiologia , Vasos Retinianos/patologia , Telangiectasia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Membranas , Pessoa de Meia-Idade , Neovascularização Retiniana/diagnóstico , Estudos Retrospectivos , Telangiectasia/diagnóstico , Acuidade Visual
18.
Arch Ophthalmol ; 120(8): 1069-74, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12149061

RESUMO

OBJECTIVES: To compare the in vitro scleral permeability of carboplatin using either a fibrin sealant or a balanced salt solution (BSS) vehicle and to measure in vivo ocular tissue levels following subconjunctival injection of carboplatin in fibrin sealant or BSS. METHODS: The permeability of carboplatin in fibrin sealant or BSS through human eye bank sclera was tested using an in vitro perfusion apparatus. Levels of carboplatin permeating the sclera were measured every hour for 24 hours using atomic absorption spectrometry. In vivo studies were performed in Dutch Belted rabbits injected subconjunctivally with carboplatin in either fibrin sealant or BSS; eyes were enucleated at 1(1/2) hours, 48 hours, and 2 weeks after injection, and levels of carboplatin were measured in various tissues. RESULTS: In vitro carboplatin in fibrin sealant had a peak permeability constant of 13.7 +/- 2.3 x 10(-6) cm/s; carboplatin in BSS, 27.0 +/- 1.7 x 10(-6) cm/s. After 24 hours, 33.2% +/- 1.8% of the carboplatin was retained in the fibrin sealant, while 5.5% +/- 1.0% was retained in the BSS. In vivo subconjunctival injection of carboplatin in fibrin sealant vehicle achieved 11.83 +/- 5.16 microg/mL in the vitreous at 1(1/2) hours and 0.03 +/- 0.06 microg/mL in the vitreous at 2 weeks. The fibrin sealant also attained 396.59 +/- 177.84 microg/mg in the choroid and retina at 1(1/2) hours and 3.38 +/- 1.97 microg/mg in the choroid and retina at 2 weeks. (Data are given as mean +/- SEM.) CONCLUSION: Fibrin sealant provided a more controlled and localized release of carboplatin and delivered carboplatin to the ocular tissues for up to 2 weeks. CLINICAL RELEVANCE: This study reports the use of fibrin sealant as a subconjunctival delivery vehicle for carboplatin, and quantifies ocular drug levels achieved in an animal model.


Assuntos
Antineoplásicos/farmacocinética , Carboplatina/farmacocinética , Sistemas de Liberação de Medicamentos , Esclera/metabolismo , Acetatos , Animais , Disponibilidade Biológica , Túnica Conjuntiva , Difusão , Combinação de Medicamentos , Adesivo Tecidual de Fibrina , Humanos , Injeções , Minerais , Permeabilidade , Coelhos , Cloreto de Sódio , Espectrofotometria Atômica
19.
J Control Release ; 89(3): 409-17, 2003 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-12737843

RESUMO

This study determined the in vitro permeability of cisplatin through isolated human sclera as delivered by a collagen matrix vehicle. Short-term and long-term intraocular levels of cisplatin were also measured in the rabbit eye after a subconjunctival injection. Cisplatin in either a collagen matrix vehicle or a control balanced salt solution (BSS) vehicle was applied to human sclera mounted in a specially designed in vitro perfusion chamber. The amount of cisplatin that diffused across the sclera was measured in hourly samples for 24 h using atomic absorption spectrometry. In vivo studies were also performed in Dutch Belted rabbits given subconjunctival injections of cisplatin in collagen matrix or in BSS. Eyes were enucleated at 1.5 h and 2 weeks after injection, frozen, and dissected to determine the intraocular cisplatin concentrations. Cisplatin had a peak in vitro scleral permeability constant of 8.3+/-1.2 x 10(-6) and 20.1+/-1.8 x 10(-6) cm/s, delivered in collagen matrix and in BSS, respectively (mean+/-S.D.). At the end of the in vitro experiments, 35.9+/-4.6% of the cisplatin remained in the collagen matrix, while 0.8+/-0.2% remained in the BSS vehicle. Subconjunctival injection of cisplatin in the collagen matrix vehicle achieved 3.3+/-0.1 microg/ml in the vitreous humor at 1.5 h and 0.1+/-0.1 microg/ml at 2 weeks. This vehicle also achieved a cisplatin concentration of 73.5+/-23.9 microg/mg in the choroid and retina at 1.5 h and 3.2+/-1.3 microg/mg at 2 weeks. Compared to BSS, the collagen matrix vehicle provided a more controlled release of cisplatin, and after subconjunctival injection into rabbits, attained higher drug levels in several ocular tissues.


Assuntos
Humor Aquoso/metabolismo , Cisplatino/farmacocinética , Colágeno/farmacocinética , Esclera/metabolismo , Animais , Humor Aquoso/efeitos dos fármacos , Cisplatino/administração & dosagem , Colágeno/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Humanos , Técnicas In Vitro , Permeabilidade/efeitos dos fármacos , Coelhos , Esclera/efeitos dos fármacos
20.
Am J Ophthalmol ; 133(1): 89-94, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11755843

RESUMO

PURPOSE: To report the results of macular hole surgery using indocyanine green to improve visualization and facilitate peeling of the internal limiting membrane. METHODS: A retrospective noncomparative review of a consecutive series of 22 patients (22 eyes) who underwent macular hole repair using indocyanine green to facilitate visualization of the internal limiting membrane was performed. One patient was excluded because of a history of a rhegmatogenous retinal detachment. All patients underwent a three-port pars plana vitrectomy with internal limiting membrane peeling. Indocyanine green (0.1% solution) was used to assist in the visualization of the internal limiting membrane. The main outcome measures were postoperative visual acuity, macular hole status, and postoperative retinal pigment epithelial changes. RESULTS: In 21 eyes, the median preoperative best-corrected visual acuity was 20/200 (range, 20/60 to counting fingers at 5 feet). The median postoperative visual acuity was 20/400 (range, 20/60-1/200) with an average follow-up of 13 weeks. The macular hole was closed in 18 eyes (86%) at the most recent follow-up. Ten eyes were found to have atrophic retinal pigment epithelium changes in the area of the previous macular hole. CONCLUSIONS: Indocyanine green assists in visualization of the internal limiting membrane in macular hole surgery. In our series, 10 eyes had unusual atrophic changes in the retinal pigment epithelium at the site of the previous macular hole, or in the area where the indocyanine green solution would have had direct access to the bare retinal pigment epithelium cells. Although the use of indocyanine green improves visualization and assists with peeling of the internal limiting membrane, the safety and potential toxicity of indocyanine green to the retinal pigment epithelium require further investigation.


Assuntos
Membrana Epirretiniana/cirurgia , Corantes Fluorescentes , Verde de Indocianina , Epitélio Pigmentado Ocular/patologia , Complicações Pós-Operatórias/patologia , Perfurações Retinianas/cirurgia , Vitrectomia , Idoso , Idoso de 80 Anos ou mais , Atrofia , Membrana Epirretiniana/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfurações Retinianas/diagnóstico , Estudos Retrospectivos , Acuidade Visual
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