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1.
Am J Ophthalmol Case Rep ; 33: 101987, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38283770

RESUMO

Purpose: To report the successful treatment of persistent retinoblastoma vitreous seeding with 6 cycles of intra-arterial chemotherapy and 15 cycles of intravitreal chemotherapy injections. Observations: A three-year-old female presented to the ocular oncology clinic with Group D retinoblastoma with severe vitreous seeding. The patient received 3 cycles of intra-arterial chemotherapy (melphalan, topotecan, and carboplatin) and 15 cycles of intravitreal chemotherapy (melphalan and combined melphalan/topotecan). Complete tumor regression and resolution of vitreous seeding was achieved. The best corrected visual acuity in the affected eye was 20/50. Conclusions and Importance: Intravitreal chemotherapy for retinoblastoma vitreous seeding is often restricted to 8 treatment cycles. Patients who do not respond after 8 cycles face salvage therapy with radiation or enucleation. This is a case in which prolonged intravitreal chemotherapy delivery was well tolerated and resulted in sustained tumor remission, with useful visual acuity in the treated eye.

2.
Ophthalmol Sci ; 4(3): 100440, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38284098

RESUMO

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

3.
Am J Ophthalmol Case Rep ; 32: 101935, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37808082

RESUMO

Purpose: To report a case of a child with neovascular and ghost cell glaucoma in the setting of previously treated vitreous hemorrhage with unique fluorescein leakage from abnormal iris vessels ultimately preventing successful fluorescein angiography. Observations: A 3-year-9-month-old female with a medical history of very high-risk B-cell acute lymphoblastic leukemia presented with eye pain and was noted to have a complete vitreous hemorrhage and intraocular pressure elevation in the right eye which was refractory to maximum medical therapy and vitrectomy. Following vitreous hemorrhage resolution, an examination under anesthesia with fluorescein angiography was found to have diffuse leakage of fluorescein into the anterior chamber, presumably due to the active iris neovascularization. This anterior chamber fluorescein signal prevented visualization of the retinal vasculature. The patient was diagnosed with mixed mechanism glaucoma (neovascular and ghost cell) due to a resolved vitreous hemorrhage in the setting of a presumed prior ischemic event. Conclusions and Importance: We report a case of an unsuccessful fluorescein angiogram in the setting of anterior chamber fluorescein leakage due to active iris neovascularization, and review considerations for the differential diagnosis and useful diagnostic tests in this clinical scenario.

4.
Am J Ophthalmol Case Rep ; 31: 101863, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37351340

RESUMO

Purpose: Tumor metastases to the retina are a relatively rare occurrence. We report a unique case of retinal metastasis of a systemic malignancy with clinical and histopathologic correlations. Observations: A 62-year-old female with a history of stage IV small cell carcinoma of the lung (SCC, status post chemotherapy and maintenance immunotherapy) presented with hand motions vision and vitreous hemorrhage, status post prior vitrectomy and biopsy that was non-diagnostic. She was found to have unilateral retinal metastatic tumor and underwent a repeat vitrector-assisted biopsy which confirmed the diagnosis. The eye became blind and painful due to recurrent non-clearing vitreous hemorrhage and ghost cell glaucoma and was enucleated. Detailed histopathologic analysis of the globe confirmed small cell carcinoma metastatic to the retina and vitreous cavity and sparing the choroid. Conclusions and importance: This case demonstrates the importance of maintaining a high index of suspicion for metastasis in patients with a known history of malignancy who present with new vitreoretinal lesions.

5.
Am J Ophthalmol Case Rep ; 31: 101861, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37293395

RESUMO

Purpose: To report a large uveal melanoma with extra-scleral extension which underwent spontaneous infarction and its unique molecular signature profile. Observations: An 81-year-old female presented with a blind, painful eye. Intraocular pressure was 48 mm Hg. There was a large subconjunctival melanotic mass overlying a choroidal melanoma with anterior extension involving the ciliary body and the iridocorneal angle and iris. Ultrasonography confirmed a dome-shaped anterior cilio-choroidal mass with extra-scleral extension. The patient underwent enucleation and pathologic evaluation confirmed cilio-choroidal melanoma. The posterior half of the tumor involving the ciliary body and the extra-scleral component were spontaneously infarcted and were composed of large melanophages. Next-generation sequencing demonstrated a splice site mutation in PBRM1 and whole-genome doubling in addition to a GNAQ hotspot mutation, chromosome 3 loss and 8q gain. Conclusions and importance: This case of a large, auto-infarcted uveal melanoma demonstrates a PBRM1 mutation and whole-genome doubling.

6.
Mod Pathol ; 36(4): 100081, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36788079

RESUMO

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and despite excellent local control, more than 50% of patients develop and die from metastatic disease. Loss of BAP1 nuclear staining, a surrogate marker of BAP1 mutation, and preferentially expressed antigen in melanoma (PRAME) messenger RNA overexpression, as assessed using qPCR, have previously been shown to correlate with increased metastasis rate in UM. In this study, we demonstrated that UM could be successfully risk-stratified using a combination of BAP1 and PRAME immunohistochemical (IHC) stains. We retrospectively reviewed 318 UM cases with sufficient tissue and performed BAP1 and PRAME IHC to stratify them as BAP1+/PRAME- (group 1, n = 135), BAP1+/PRAME+ (group 2, n = 43), BAP1-/PRAME- (group 3, n = 94), and BAP1-/PRAME+ (group 4, n = 46). Increasing the study risk group on the basis of loss of BAP1 expression and positive PRAME staining was associated with a higher rate of metastasis and disease-specific death and lower metastasis-free survival (MFS) and disease-specific survival (DSS). Among tumors with loss of BAP1 staining, PRAME positivity was associated with shorter MFS (P = .018) and showed a trend toward shorter DSS (P = .061). Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs.


Assuntos
Melanoma , Neoplasias Uveais , Adulto , Humanos , Prognóstico , Imuno-Histoquímica , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética , Melanoma/patologia , Neoplasias Uveais/metabolismo , Ubiquitina Tiolesterase/genética , Antígenos de Neoplasias
8.
Ophthalmic Surg Lasers Imaging Retina ; 53(4): 234-238, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35417300

RESUMO

To describe a case of chronic granulomatous disease (CGD) with ocular lesions as the presenting findings. An ocular examination of a 4-month-old male infant with poor vision revealed punched-out macular and perivascular chorioretinal fibrosis and atrophy with peripheral retinal nonperfusion. Subsequently, he was hospitalized for recurrent infections and was diagnosed with CGD. Repeated examination demonstrated enlargement of the chorioretinal lesions without evidence of active inflammation or neovascularization. CGD causes recurrent, severe, life-threatening infections in children and should be considered in the differential diagnosis of chorioretinal lesions with peripheral retinal nonperfusion. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):234-238.].


Assuntos
Doença Granulomatosa Crônica , Atrofia , Criança , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico , Humanos , Lactente , Masculino , Retina/patologia
9.
Retin Cases Brief Rep ; 16(4): 523-527, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32541432

RESUMO

PURPOSE: To report a case of Coccidioides immitis endophthalmitis with severe vision loss and a return to excellent vision after aggressive intervention. METHODS: Case report. RESULTS: A 41-year-old man with a history of solid organ transplantation who complained of floaters and decreased vision in the setting of disseminated Coccidioides infection was found to have presumed coccidioidal endophthalmitis with visual acuities of 20/20 in the right eye and 20/200 in the left eye. The patient was managed with intravenous amphotericin B, oral voriconazole, and intravitreal injections of amphotericin B and voriconazole in the left eye every three days. Five weeks after presentation, his visual acuity remained 20/20 in the right eye and improved to 20/40 in the left eye. The patient was transitioned to twice weekly intravitreal injections and oral voriconazole on hospital discharge. One week later, vision in the left eye decreased to 20/500 with worsening vitritis, prompting vitrectomy. Vision in the left eye subsequently improved to 20/30. Five weeks later, the patient developed a macula-on inferior rhegmatogenous retinal detachment in the left eye and underwent a second vitrectomy, with scleral buckle, laser, and gas injection. Vision in the left eye returned to 20/25. In total, the patient received 22 amphotericin B and 17 voriconazole intravitreal injections in the left eye with two vitrectomies. Vision in the right eye remained 20/20 throughout his treatment course. At four months after presentation, the patient remained on oral voriconazole with no evidence of active intraocular infection on examination. CONCLUSION: Aggressive medical and surgical management can be successful in ocular conservation and restoration of vision in coccidioidal endophthalmitis. Very mild disease may be conservatively monitored and managed with systemic antifungal therapy alone. In severe disease, early diagnosis and prompt and aggressive use of systemic and intravitreal antifungals may spare panophthalmitis and preserve vision.


Assuntos
Endoftalmite , Infecções Oculares Fúngicas , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Injeções Intravítreas , Masculino , Vitrectomia , Voriconazol/uso terapêutico
10.
Surv Ophthalmol ; 67(1): 288-292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33309950

RESUMO

A two-year-old full-term boy with a history of an intermittent exotropia presented to the pediatric ophthalmology clinic for routine follow-up. He was found to have a stable sensorimotor examination however dilated funduscopic examination of the right eye was significant for a dim foveal reflex with a new discrete, white, elevated retinal lesion superotemporal to the fovea with surrounding subretinal exudates. An examination under anesthesia (EUA) was performed two days later that revealed a subretinal posterior pole granuloma with hyperfluorescence and late leakage from the lesion without telangiectatic vessels on fluorescein angiography. A repeat EUA one month later demonstrated an increase in surrounding subretinal and overlying intraretinal fluid. The patient was started on topical 1% prednisolone with a presumed diagnosis of Toxocara granuloma. At EUA, three months later, the subretinal and intraretinal fluid had resolved. The topical steroids were tapered, and the patient continues to be followed closely.


Assuntos
Exotropia , Criança , Exotropia/diagnóstico , Angiofluoresceinografia , Humanos , Masculino , Tomografia de Coerência Óptica
11.
Am J Ophthalmol Case Rep ; 23: 101164, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34296045

RESUMO

PURPOSE: To describe acute and chronic retinal ischemic changes following an internal carotid artery pseudoaneurysm stenting procedure, and to review current evidence for risk factors and management of post-procedural retinal ischemic events. OBSERVATION: A 50-year-old man presented with a 3-month history of pulsatile tinnitus, headache, and intermittent blurry vision. A CT angiogram of head and neck showed bilateral cervicopetrous internal carotid artery (ICA) pseudoaneurysms. The patient underwent successful repair with angioplasty and stenting of the flow-limiting high-grade (>95%) stenosis of his left high cervical ICA. On post-operative day 1, the patient reported monocular vision loss with a large central scotoma. He was found to have a central macular area of retinal whitening and multiple areas of perivascular retinal whitening on exam, concerning for retinal artery occlusions secondary to peri-procedural emboli. Dual antiplatelet therapy was started and a stroke evaluation was performed. Two months later, his visual acuity in the affected eye was counting fingers and his left eye fundus examination was notable for multiple areas of scattered hemorrhages, microaneurysms, and retinal exudates in the distribution of prior retinal ischemia. OCT imaging revealed atrophic changes in the left macula. Subsequently, the patient completed stage-2 repair of the left ICA pseudoaneurysm followed by uncomplicated repair of the right ICA. Four months later, his left eye visual acuity and retinal findings remained stable. CONCLUSIONS AND IMPORTANCE: Post-procedure retinal emboli and ischemia are important, vision threatening possible ocular complications for patients undergoing carotid vascular and endovascular procedures.

12.
Am J Ophthalmol ; 229: 71-81, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33895151

RESUMO

PURPOSE: To examine associations between primary repair, patient characteristics, and rhegmatogenous retinal detachment (RRD) reoperation. DESIGN: Retrospective cohort study. METHODS: We used administrative claims to identify enrollees with incident RRD treatment by laser barricade, pneumatic retinopexy (PR), pars plana vitrectomy (PPV), or scleral buckle (SB) between 2003 and 2016. Analysis excluded patients with less than 3 years of continuous enrollment, previous RRD diagnosis, or repair. We determined reoperation frequency (PPV, PR, or SB) within 90 days postrepair and used multivariable logistic regression to identify associations between reoperation and patient and primary repair characteristics. RESULTS: Of 16,190 patients with documented primary RRD repair, 2,918 (18.0%) required reoperation within 90 days. Reoperation was significantly associated with male sex (odds ratio [OR] 1.24, P < .001), pseudophakia (OR 1.25, P < .001), vitreous hemorrhage (OR 1.22, P = .001), and worse systemic health (OR 1.19-1.25, P < .05, for Charlson Comorbidity Index ≥3). Pseudophakia had higher reoperation odds after all primary procedures except PPV. In addition, 28.7% of primary PR cases required reoperation, vs 19.1% of SB and 17.9% of PPV repairs. Adjusting for other patient characteristics, PR had highest odds of reoperation (OR 1.90, P < .001, vs primary PPV). Primary laser barricade had lowest odds of reoperation (OR 0.49, P < .001). PPV was the most frequent reoperation procedure. CONCLUSIONS: Nearly 1 in 5 patients require reoperation within 90 days after primary RRD repair. Cases requiring only primary laser barricade had lowest reoperation odds, likely representing less severe RRDs. Primary PR had highest reoperation odds; PPV and SB were similar to each other. These findings are important for patient education and surgical decision-making.


Assuntos
Descolamento Retiniano , Humanos , Masculino , Reoperação , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Recurvamento da Esclera , Resultado do Tratamento , Acuidade Visual , Vitrectomia
13.
Ophthalmology ; 128(1): 121-129, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619546

RESUMO

PURPOSE: To analyze the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy (CSC) diagnosis. DESIGN: Retrospective claims-based analysis. PARTICIPANTS: A nationally representative sample of commercial insurance beneficiaries who received care between 2007 and 2015. METHODS: We limited the study population to beneficiaries with incident CSC diagnosed by an eye care provider, excluding those with other major ophthalmologic comorbidities. We developed a non-CSC comparison cohort matched to CSC patients by age, sex, general health (Charlson Comorbidity Index), and geographic region. We compared systemic corticosteroid prescriptions before and after CSC diagnosis and by diagnosing provider (optometrist vs. ophthalmologist) and evaluated likelihood of steroids treatment among CSC versus matched control patients using logistic and Cox proportional hazard regression models. MAIN OUTCOME MEASURES: Systemic corticosteroid prescription frequency among CSC patients within 12 months pre-diagnosis and at 6, 12, and 24 months post-diagnosis, median time to steroid initiation and discontinuation, and odds of receiving steroids post-diagnosis among CSC and control patients. RESULTS: We identified 3418 CSC patients. Nearly 39% (n = 1326) were prescribed systemic steroids at some point during the analysis period, versus 23% of controls (4033 of 17 178 patients). Over 12% of CSC patients (n = 430) within 1 year pre-diagnosis, and nearly 12% (n = 404) within 1 year post-diagnosis. Most patients who received steroids after diagnosis were steroid naive (n = 231). Among those receiving steroids, CSC patients demonstrated longer median time to first post-diagnosis steroid prescription (1.82 years vs. 0.50 years for non-CSC patients) and longer time to last steroid prescription (1.62 years vs. 0.35 years for non-CSC patients). Although CSC patients were significantly less likely to receive steroids within 6 months post-diagnosis compared with non-CSC patients (odds ratio, 0.72; 95% confidence interval, 0.59-0.89), they were significantly more likely to receive steroids by 2 years post-diagnosis. Prescribing patterns were similar for patients diagnosed by an ophthalmologist versus optometrist. CONCLUSIONS: Despite evidence showing that steroids contribute to CSC development, many patients continue to be prescribed systemic corticosteroids after CSC diagnosis. Our results suggest a need for greater communication and collaboration among providers to ensure that clinical practice reflects evidence-based recommendations.


Assuntos
Coriorretinopatia Serosa Central/diagnóstico , Glucocorticoides/uso terapêutico , Coriorretinopatia Serosa Central/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
15.
Am J Ophthalmol Case Rep ; 19: 100787, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32760850

RESUMO

PURPOSE: To describe the first series of six young uveal melanoma (UM) patients with oral isotretinoin and/or topical retinoid therapy prior to diagnosis. OBSERVATIONS: The case series is based on clinical observations at our UM quaternary referral center. Six UM patient cases are reported, ages 16-44 years old. All had been using either oral (isotretinoin) and/or topical (tretinoin or tazarotene) retinoid treatment (3 months-~10 years) prior to or at the time of diagnosis (3 of 6 cases). All patients had ocular complaints on presentation, and the onset of certain symptoms corresponded with the course of retinoids. Other potential risk factors or relevant history included Caucasian background, cone-rod dystrophy and active smoker status (Case 2), family history of UM and pregnancy at time of diagnosis (Case 3), past smoking and possible secondary Chernobyl exposure as a baby (Case 5). All patients were treated with proton beam radiotherapy and currently have no sign of recurrent or metastatic disease. CONCLUSIONS AND IMPORTANCE: Retinoid therapy has been linked to various benign and/or reversible effects on the anterior and posterior eye, though pathophysiology remains not well understood. Uveal melanoma (UM) is a rare cancer diagnosis in young adults. We report here the first case series of young UM patients with a history of retinoid use and ocular complaints. No causal link is claimed and further systematic epidemiologic and biologic study of retinoid therapy and ocular impact may provide additional relevant data, particularly in young ocular melanoma patients.

16.
Adv Radiat Oncol ; 5(4): 682-686, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32337386

RESUMO

Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the coronavirus disease (COVID-19) pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group is the largest international community of particle/proton therapy providers. Participating experts have current or former affiliation with the member institutions of the Particle Therapy Co-Operative Group Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of health care providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears, and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment.

17.
Am J Ophthalmol Case Rep ; 18: 100688, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32309677

RESUMO

PURPOSE: to present a case of a choroidal melanoma located along a scleral buckle contour and was successfully treated with proton beam radiotherapy, without disturbing the scleral buckle. OBSERVATIONS: A 60-year-old woman presented with photopsias and history of retinal detachment repair with scleral buckle 36 years prior. She had annual dilated exams with her ophthalmologist over the last several years. While initially diagnosis of choroidal detachment, hemorrhage and intraocular buckle intrusion were suspected, the patient was referred to an ophthalmic oncology center and choroidal melanoma was confirmed. The patient underwent tantalum marker placement, trans-retinal biopsy and proton beam radiotherapy. Despite no evidence of metastatic disease on systemic imaging, prognostic genetic testing of the tumor revealed high-risk alterations for future metastasis, and the patient enrolled in an adjuvant clinical trial. CONCLUSIONS: The location of this choroidal melanoma along a scleral buckle contour presented a unique therapeutic challenge. We successfuly treated the tumor with proton beam radiotherapy without disturbing the scleral buckle. IMPORTANCE: chorioretinal elevations adjacent a scleral buckle may be presumed to be due to the buckle element; ultrasound can be helpful in distinguishing an intraocular tumor. Proton beam radiotherapy has the advantage over plaque brachytherapy in this setting as removing the scleral buckle is not needed and placing a plaque over the scleral buckle risks altering the effective radiotherapy dose.

18.
Cancer Cytopathol ; 128(7): 499-505, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32196967

RESUMO

BACKGROUND: Uveal melanoma is highly aggressive, and overall prognosis depends on mutation status. Fine-needle aspiration biopsies (FNABs) play an important role in obtaining fresh tissue for cytologic diagnosis and molecular studies. It has been suggested that, although FNAB usually provides high diagnostic accuracy, there may be limited cellularity, which may compromise diagnostic potential for molecular studies. FNABs of uveal melanocytic lesions were evaluated to assess sample adequacy for both cytologic evaluation and next-generation sequencing (NGS). METHODS: The authors retrospectively evaluated 36 cases of melanocytic uveal lesions from 2015 to 2018. Samples were obtained by ophthalmologist-performed FNAB and aliquoted for cytology and NGS. Various combinations of direct smears, liquid-based cytology slides, cell blocks, and immunohistochemical stains for melanocytic markers were performed. All samples were tested for molecular alterations using hybrid-capture-based NGS. RESULTS: There was sufficient material for cytologic diagnosis in 33 of 36 cases (92%), for NGS testing in 30 of 36 cases (83%), and for both cytologic diagnosis and NGS testing in 28 of 36 cases (78%). Of 7 cases that were cytologically categorized as indeterminate or diagnosed as "atypical" or "nondiagnostic," NGS testing was sufficient and diagnostic for melanoma in 5 cases. Of the cases diagnosed as melanoma on pathology, 20 cases (87%) had concordant NGS testing results, 2 lacked molecular alterations, and 1 was insufficient for testing. CONCLUSIONS: FNA sampling of melanocytic uveal lesions is adequate for both cytologic diagnosis and NGS testing. In a subset of cases in which pathologic findings were indeterminate, NGS testing results were clarifying for diagnosis. In addition, specific molecular alterations identified can aid in evaluating prognosis and guide further management.


Assuntos
Biomarcadores Tumorais/genética , Citodiagnóstico/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Melanoma/diagnóstico , Mutação , Neoplasias Uveais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Uveais/genética
19.
Ophthalmology ; 127(6): 804-813, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139107

RESUMO

PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN: Cohort study. PARTICIPANTS: Thirty-two children with retinoblastoma. METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.


Assuntos
Inativação Gênica , Mutação em Linhagem Germinativa , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Retinoblastoma/patologia , Ubiquitina-Proteína Ligases/genética , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , DNA de Neoplasias/genética , Enucleação Ocular , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Inclusão em Parafina , Neoplasias da Retina/cirurgia , Retinoblastoma/cirurgia , Fixação de Tecidos
20.
Cancers (Basel) ; 12(2)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085617

RESUMO

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3's performance using discrimination and calibration methods. LUMPO3's ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers.

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