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PURPOSE: To study image quality and artifacts seen on optical coherence tomography angiography (OCTA). METHODS: Sixty-five consecutive patients with unilateral posterior uveal melanoma treated with plaque radiotherapy had OCTA during follow-up. Optical coherence tomography angiography was performed on both the affected and fellow eye. Signal strength and frequency of image artifacts on en face images were compared between affected and fellow eyes. RESULTS: A total of 130 eyes in 65 patients were analyzed, the mean age at time of OCTA was 55 years (median: 56, range: 12-81 years), and 39 (39/65, 60%) were female. Majority of tumors were located in the choroid (62/65, 95%) and extramacular (55/65, 85%). The mean distance to the foveola was 4 mm (median: 3, range: 0-18 mm) and optic nerve was 4 mm (median: 4, range: 0-16 mm). Optical coherence tomography angiography was performed at a mean 46 months after plaque radiotherapy. Most patients had a history of radiation maculopathy or papillopathy in the treated eye at the time of OCTA (46/65, 71%). Overall, 95 eyes (95/130, 73%) had at least one significant artifact on OCTA. The most common major artifacts were loss of focus (71/130, 55%), broad (>5 pixels width and >4 lines) blink lines (48/130, 37%), motion artifact (34/130, 26%), specular dot (33/130, 25%), and edge duplication (10/130, 8%). Statistically, eyes treated with plaque radiotherapy (affected vs. fellow eye) were more likely to have at least one major OCTA artifact (92 vs. 54%, P < 0.001) and, specifically, loss of focus was more frequent (78 vs. 31%, P < 0.001). Multivariate analysis found decreased visual acuity significantly associated with higher incidence of broad blink lines (P = 0.0166) and loss of signal (P < 0.0001), whereas male sex was associated with increased loss of signal (P = 0.0015), and distance to the foveola was related to edge duplication (P = 0.0119). CONCLUSION: Image artifacts on OCTA are commonly encountered and appear to be more frequent in eyes with pathology and poor visual acuity. Recognition of these artifacts might help improve image interpretation and decision making.
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Neoplasias da Coroide/diagnóstico por imagem , Angiofluoresceinografia/normas , Melanoma/diagnóstico por imagem , Imagem Óptica/normas , Tomografia de Coerência Óptica/normas , Neoplasias Uveais/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Braquiterapia , Criança , Neoplasias da Coroide/patologia , Neoplasias da Coroide/radioterapia , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/radioterapia , Pessoa de Meia-Idade , Análise Multivariada , Imagem Óptica/métodos , Tomografia de Coerência Óptica/métodos , Neoplasias Uveais/patologia , Neoplasias Uveais/radioterapia , Adulto JovemRESUMO
PURPOSE: To study radiation retinopathy after plaque radiotherapy of choroidal melanoma using optical coherence tomography angiography. METHODS: Retrospective comparative analysis of 65 consecutive patients with choroidal melanoma, treated with standard dose I-125 plaque radiotherapy and imaged with optical coherence tomography angiography. A comparison of irradiated versus contralateral, nonirradiated (control) eyes was performed. RESULTS: The mean patient age was 55 years. Underlying medical diseases included diabetes mellitus (4/65, 4%) or hypertension (25/65, 38%), but no patient demonstrated disease-related retinopathy. The mean pretreatment melanoma diameter was 11 mm and mean thickness was 5 mm. The mean radiation dose to the foveola was 5663 centiGray. At mean follow-up of 46 months after plaque radiotherapy, the most frequent qualitative finding on optical coherence tomography angiography (irradiated eye) was nonperfusion in the superficial capillary plexus (19/65, 29%) and deep capillary plexus (20/65, 31%), followed by loss of choriocapillaris within tumor margins (11/65, 17%). The quantitative findings revealed foveal avascular zone with significantly larger mean area (irradiated vs. nonirradiated eye) in the superficial plexus (0.961 vs. 0.280 mm, P < 0.0001) and deep plexus (1.396 vs. 0.458 mm, P < 0.0001), even in eyes without clinical evidence of radiation maculopathy (superficial 0.278 mm, P = 0.03; deep 0.454 mm, P = 0.02). Parafoveal capillary density (superficial and deep) was decreased in all irradiated eyes (P < 0.001). This difference was maintained after subgroup analysis of eyes with (P < 0.001) or without (P < 0.001) clinical evidence of radiation maculopathy. Mean logMAR visual acuity was significantly reduced in irradiated eyes (0.7 vs. 0.1 [Snellen equivalent 20/100 vs. 20/25], P < 0.001) and the reduced vision was significant even in eyes without clinical evidence of radiation maculopathy (0.4 vs. 0.1 [Snellen equivalent 20/50 vs. 20/25], P < 0.001). CONCLUSION: Optical coherence tomography angiography demonstrated significant enlargement of the foveal avascular zone and decreased parafoveal capillary density of both superficial and deep capillary plexuses in eyes after plaque radiotherapy of choroidal melanoma, even in eyes with no clinical evidence of radiation maculopathy.
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Braquiterapia/efeitos adversos , Neoplasias da Coroide/radioterapia , Macula Lutea/diagnóstico por imagem , Melanoma/radioterapia , Lesões por Radiação/diagnóstico por imagem , Retina/efeitos da radiação , Doenças Retinianas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Doenças Retinianas/etiologia , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To study the parafoveal capillary density using optical coherence tomography angiography (OCTA) in eyes treated with plaque radiotherapy. RESEARCH DESIGN: Retrospective comparative case series. PARTICIPANTS: Ten patients treated with plaque radiotherapy for choroidal melanoma without evident radiation maculopathy on ophthalmoscopy or optical coherence tomography were imaged with OCTA. MAIN OUTCOME MEASURE: Comparison of the parafoveal capillary density in the superficial and deep capillary plexuses in the irradiated versus fellow nonirradiated eye. RESULTS: Overall, mean patient age was 55 years (median: 57, range: 45-65 years), and majority were white (9/10, 90%) and female (9/10, 90%). No patient had diabetes mellitus, and 2 (2/10, 20%) had controlled systemic hypertension. The melanoma was located in the choroid in all patients (10/10, 100%), with 2 (2/10, 20%) in the macular region. The mean largest basal diameter was 11 mm (12, 6-16 mm), and mean thickness was 5 mm (5, 2-10 mm). Mean radiation dose to the tumor apex was 72 Gy (median: 70 Gy, range: 70-85 Gy). Mean foveolar radiation dose was 53 Gy (median: 35 Gy, range: 14-110 Gy). Mean follow-up duration after plaque radiotherapy was 17 months (median: 16 months, range: 5-39 months). There was no ophthalmoscopic evidence of radiation maculopathy throughout the follow-up in every case. Optical coherence tomography demonstrated normal foveal contour without edema or subretinal fluid in every case. On OCTA, there was no significant difference in signal strength (P = 0.1151), central macular thickness (P = 0.9316), and foveal avascular zone area in the superficial (P = 0.1595), and deep (P = 0.1534) capillary plexuses between the irradiated versus fellow eyes. However, there was a statistically significant decrease in capillary density in the parafoveal superficial (P = 0.0005) and deep (P = 0.0067) plexuses in the irradiated eye. In addition, mean logMAR visual acuity was 0.2 (0.1, 0.0-0.5) (Snellen equivalent 20/32) in the irradiated eye and 0.0 (0.0, range: 0.0-0.1) (Snellen equivalent 20/20) in the fellow eye (P = 0.0252). CONCLUSION: Optical coherence tomography angiography allows qualitative and quantitative analysis of parafoveal capillary density. After plaque radiotherapy for choroidal melanoma, in eyes with normal macular features on ophthalmoscopy and optical coherence tomography, there is a statistically significant decrease in parafoveal capillary density and logMAR visual acuity in irradiated eyes compared with fellow eyes. These subclinical ischemic findings represent the commencement of radiation maculopathy.
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Braquiterapia , Capilares/patologia , Neoplasias da Coroide/radioterapia , Fóvea Central/irrigação sanguínea , Melanoma/radioterapia , Lesões por Radiação/patologia , Retina/efeitos da radiação , Idoso , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/etiologia , Doenças Retinianas/patologia , Estudos Retrospectivos , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To report clinical features and treatment outcomes of ocular juvenile xanthogranuloma (JXG). DESIGN: Retrospective case series. PARTICIPANTS: There were 32 tumors in 31 eyes of 30 patients with ocular JXG. METHODS: Review of medical records. MAIN OUTCOME MEASURES: Tumor control, intraocular pressure (IOP), and visual acuity. RESULTS: The mean patient age at presentation was 51 months (median, 15 months; range, 1-443 months). Eye redness (12/30, 40%) and hyphema (4/30, 13%) were the most common presenting symptoms. Cutaneous JXG was concurrently present in 3 patients (3/30, 10%), and spinal JXG was present in 1 patient (1/30, 3%). The ocular tissue affected by JXG included the iris (21/31, 68%), conjunctiva (6/31, 19%), eyelid (2/31, 6%), choroid (2/31, 6%), and orbit (1/31, 3%). Those with iris JXG presented at a median age of 13 months compared with 30 months for those with conjunctival JXG. In the iris JXG group, mean IOP was 19 mmHg (median, 18 mmHg; range, 11-30 mmHg) and hyphema was noted in 8 eyes (8/21, 38%). The iris tumor was nodular (16/21, 76%) or diffuse (5/21, 24%). Fine-needle aspiration biopsy was used in 10 cases and confirmed JXG cytologically in all cases. The iris lesion was treated with topical (18/21, 86%) and/or periocular (4/21, 19%) corticosteroids. The eyelid, conjunctiva, and orbital JXG were treated with excisional biopsy in 5 patients (5/9, 56%), topical corticosteroids in 2 patients (2/9, 22%), and observation in 2 patients (2/9, 22%). Of 28 patients with a mean follow-up of 15 months (median, 6 months; range, 1-68 months), tumor regression was achieved in all cases, without recurrence. Two patients were lost to follow-up. Upon follow-up of the iris JXG group, visual acuity was stable or improved (18/19 patients, 95%) and IOP was controlled long-term without medication (14/21 patients, 74%). No eyes were managed with enucleation. CONCLUSIONS: Ocular JXG preferentially affects the iris and is often isolated without cutaneous involvement. Iris JXG responds to topical or periocular corticosteroids, often with stabilization or improvement of vision and IOP.
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Oftalmopatias/diagnóstico , Acuidade Visual/fisiologia , Xantogranuloma Juvenil/diagnóstico , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Oftalmopatias/terapia , Glucocorticoides/uso terapêutico , Humanos , Lactente , Pressão Intraocular/fisiologia , Estudos Retrospectivos , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Xantogranuloma Juvenil/terapia , Adulto JovemRESUMO
PURPOSE: To analyze the foveal avascular zone (FAZ) in normal eyes using optical coherence tomography angiography. METHODS: Prospective noncomparative case series. The parafoveal region of 70 eyes from 67 healthy subjects was imaged using optical coherence tomography angiography to visualize the superficial and deep capillary plexuses and correlated with standard macular volume scans using spectral domain optical coherence tomography to determine foveal morphology. RESULTS: In all 70 eyes imaged, 2 vascular plexuses could be detected within the retina: a superficial plexus within the ganglion cell layer and a deep plexus within the inner nuclear layer. A measurable FAZ was visualized in both plexuses in all imaged eyes. The FAZ area was variable in the study population with a mean of 0.266 mm² ± 0.097 mm² in the superficial plexus (range: 0.071 mm²-0.527 mm²) and a mean of 0.495 mm² ± 0.227 mm² in the deep plexus (range: 0.160 mm²-0.795 mm²). The FAZ area was significantly larger in the deep plexus (P < 0.0001) compared with superficial plexus. The FAZ area in both plexuses correlated inversely with central macular thickness and central macular volume (P < 0.0001). No significant correlation was found between superficial plexus FAZ area and age (P = 0.55) or sex (P = 0.34). In the same manner, no significant correlation was found between deep plexus FAZ area and age (P = 0.13) or sex (P = 0.13). CONCLUSION: Optical coherence tomography angiography provides a noninvasive method to visualize and measure the superficial and deep plexus FAZ in a normal population. The FAZ can vary in size and shape, with the FAZ area significantly larger in the deep compared with the superficial plexus. Both superficial and deep FAZ area correlate inversely with foveal thickness and volume.
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Angiofluoresceinografia , Fóvea Central/anatomia & histologia , Fóvea Central/irrigação sanguínea , Vasos Retinianos/anatomia & histologia , Tomografia de Coerência Óptica , Adolescente , Adulto , Idoso , Criança , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Anti-vascular endothelial growth factor (anti-VEGF) injections are the most effective treatment for exudative age-related macular degeneration (AMD). However, both bevacizumab and ranibizumab have been reported to cause submacular hemorrhage (SMH) in the treatment of exudative AMD. Aflibercept has also been reported to cause SMH but only in the treatment of polypoidal choroidal vasculopathy and not exudative AMD. This case series presents two patients with exudative AMD who developed SMH after treatment with aflibercept injections. The first patient is an 84-year-old female with exudative AMD in both eyes who presented with SMH four days after an aflibercept injection in her right eye. The second patient is a 77-year-old female who presented with exudative AMD in her left eye and SMH one month following an aflibercept injection. This case series shows that SMH in patients treated for exudative AMD is a rare yet possible complication of aflibercept injection that requires further research to establish its incidence and risk factors.
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INTRODUCTION: Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown. METHODS: Patients with metastatic melanoma treated with chemotherapy after progression on immunotherapy with checkpoint inhibitors were identified retrospectively from 24 melanoma centres. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety were examined. RESULTS: In total, 463 patients were treated between 2007 and 2017. Fifty-six per cent had received PD-1-based therapy before chemotherapy. Chemotherapy regimens included carboplatin + paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes (9%, nab-paclitaxel 4%), fotemustine (6%) and others (13%). Median duration of therapy was 7.9 weeks (0-108). Responses included 0.4% complete response (CR), 12% partial response (PR), 21% stable disease (SD) and 67% progressive disease (PD). Median PFS was 2.6 months (2.2, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3), respectively. Twelve-month PFS was 12% (95% CI 2-15%). In patients who had received anti-PD-1 before chemotherapy, the ORR was 11%, and median PFS was 2.5 months (2.1, 2.8). The highest activity was achieved with single-agent taxanes (N = 40), with ORR 25% and median PFS 3.9 months (2.1, 6.2). Median OS from chemotherapy start was 7.1 months (6.5, 8.0). Subsequent treatment with checkpoint inhibitors achieved a response rate of 16% with a median PFS of 19.1 months (2.0-43.1 months). No unexpected toxicities were observed. CONCLUSION: Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between regimens. Chemotherapy has a limited role in the management of metastatic melanoma.
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Melanoma , Segunda Neoplasia Primária , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/patologia , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Taxoides/uso terapêutico , Microambiente TumoralAssuntos
Calcinose/patologia , Doenças Palpebrais/patologia , Dermatopatias/patologia , Adolescente , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Combination ipilimumab and nivolumab is approved for several malignancies. Toxicity most often occurs 6-10 weeks into treatment. Whether very early toxicity is harder to manage or influences efficacy is unknown. METHODS: Consecutive metastatic melanoma patients who developed hyperacute toxicity, defined as Grade 2+ irAE within 21 days of receiving ipilimumab + anti-PD-1 were retrospectively identified from nine centres. RESULTS: A total of 82 patients developed hyperacute toxicity (estimated incidence 9%), at a median 10 days (range 1-21). Toxicities included colitis (N = 23), rash (17), hepatitis (9), endocrine (9), pneumonitis (6) and neurotoxicity (4) and were G2 (38%), G3 (52%), G4 (6%) and G5 (2% myocarditis). Fifty-nine percent required treatment beyond oral steroids, including IV steroids (28%), infliximab and other immunosuppression (30%). A total of 29% patients developed an additional hyperacute toxicity and 26% another toxicity >21 days after treatment commencement but before further immunotherapy. The objective response rate (ORR) was 54%, and after a median 11.6 mo follow-up, median PFS was 7.4 mo. Increasing levels of immunosuppression was associated with a reduced PFS (12-month PFS 62% no immunosuppression versus 49% oral steroids versus 33% IV steroids versus 20% further immunosuppressants, p = 0.006). There was no significant difference in ORR or PFS by duration of immunosuppression. CONCLUSIONS: Hyperacute toxicities from combination immunotherapy have a wide spectrum and can be severe. Many patients require significant immunosuppression for prolonged durations and remain at risk of further severe toxicity. Melanoma outcomes in such patients appear similar to those of trial populations, although greater immunosuppression requirements may be associated with inferior outcomes.
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Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ipilimumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Ipilimumab/farmacologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Despite classic teaching that intracranial metastases typically arise at the gray-white matter junction, small intracranial melanoma metastases (IMM) are frequently observed at the interface between the cortex and leptomeninges (ie, "corticomeningeal interface"), suggesting possible leptomeningeal origin. METHODS: MRI brain examinations of melanoma patients treated at a specialist oncology center from July 2015 to June 2017 were retrospectively reviewed. The MRI examination on which IMM were first visible was identified, utilizing 1 mm volumetric postcontrast imaging prior to local therapy. Individual metastases (up to 10 per patient) were assessed for the presence of leptomeningeal contact, as well as their number, size, and morphology. Lesions ≥10 mm in long axis were excluded, in order to examine early metastatic disease. RESULTS: Seventy-five patients had evidence of IMM. Fifteen patients had only lesion(s) measuring ≥10 mm at diagnosis, leaving 60 patients. One hundred ninety-two individual metastases were examined (median 2 per patient; interquartile range, 1-4), 174 (91%) demonstrating leptomeningeal contact. A nodular morphology was observed in 154 of 192 (82%), 32 (17%) were ovoid but elongated along the cortex, and 6 (3%) were linear. Only 3 patients (5%) also exhibited a "classic" linear leptomeningeal disease appearance. CONCLUSIONS: Most IMM measuring between 2 and 9 mm in diameter are corticomeningeal nodules. These data raise the hypothesis that deeper parenchymal extension of IMM occurs secondarily. If the leptomeninges provide a preferential site for establishment of IMM, further investigation of the underlying biology of this phenomenon may provide opportunities for novel therapeutic strategies for patients with IMM.
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Imageamento por Ressonância Magnética/métodos , Melanoma/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Masculino , Neoplasias Meníngeas/secundário , Meningioma/secundário , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To determine outcomes after photodynamic therapy (PDT) for choroidal metastasis. DESIGN: Retrospective interventional case series. PARTICIPANTS: Forty-three patients with 40 eyes harboring 58 choroidal metastases. METHODS: Treatment with standard fluence PDT using verteporfin. MAIN OUTCOME MEASURES: Tumor control and visual outcomes. RESULTS: The primary cancer originated in the lung (n = 17 [39%]), breast (n = 16 [37%]), kidney (n = 3 [8%]), thyroid (n = 2 [6%]), and other sites (n = 5 [10%]). The mean patient age at entry was 61 years. Ocular symptoms included decreased visual acuity (n = 23 [53%]), visual field defect (n = 2 [5%]), floaters (n = 7 [16%]), flashes (n = 3 [7%]), and asymptomatic (n = 8 [19%]). The median entering visual acuity (Snellen equivalent) was 20/40. The median tumor diameter was 5.0 mm, and median thickness by ultrasonography was 2.0 mm. The median distance to the optic disc was 3.0 mm, and that to the foveola was 2.0 mm. Of the 43 patients, 35 maintained follow-up (40 eyes, 45 tumors), and PDT achieved tumor control with 1 session (n = 32 tumors [71%]) or 2 sessions (n = 3 tumors [7%]) and failed to achieve regression (n = 10 tumors [22%]). The 10 metastases for which treatment failed were managed further with plaque radiotherapy (n = 3), proton beam radiotherapy (n = 1), external beam radiotherapy (n = 1), systemic chemotherapy (n = 4), and observation (patient preference; n = 1). A comparison of clinical features for tumor control (PDT alone vs. PDT plus additional therapy) revealed those controlled with PDT alone were more likely to be adenocarcinoma (73% vs. 30%; P = 0.02) and those eyes were more like to achieve final visual acuity of 20/20 to 20/40 (66% vs. 30%; P = 0.03), with better median final Snellen visual acuity (20/30 vs. 20/70; not significant). Primary cancer site or ocular tumor features (size, location, color, shape, related subretinal fluid) did not impact tumor control. In the entire group of 40 eyes, visual acuity improved or remained stable in 28 (70%) and decreased in 12 (30%), related to subfoveal scar, persistent subretinal fluid, reactive exudation, radiation maculopathy, and brain metastasis. At last follow-up (mean, 20 months), of the entering 43 patients, 9 (21%) were alive and 34 (79%) had died of systemic metastasis. CONCLUSIONS: Photodynamic therapy with verteporfin is an effective outpatient method for small to medium choroidal metastatic tumors, providing tumor control in 78% of eyes and visual outcome of 20/20 to 20/40 in 66% of eyes.
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Neoplasias da Coroide/tratamento farmacológico , Corioide/diagnóstico por imagem , Fotoquimioterapia/métodos , Verteporfina/uso terapêutico , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/secundário , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmologia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Sociedades Médicas , Resultado do Tratamento , UltrassonografiaRESUMO
Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have transformed the management of many malignancies. Although rare, immune-mediated myocarditis presents unique clinical challenges due to heterogenous presentation, potential life-threatening consequences, and the time-critical need to differentiate it from other causes of cardiac dysfunction. Increasingly, TKI are being combined with ICI to promote immune modulation and improve efficacy. However, these combinations are associated with more toxicities. This series describes six patients with advanced melanoma who developed immune-mediated myocarditis while receiving an anti-PD-1 antibody or an anti-PD-L1 antibody plus a mitogen-activated protein kinase inhibitor. It provides a review of their heterogenous clinical presentations, investigational findings and treatment outcomes. Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool for the early detection and subsequent monitoring of myocardial inflammation. Five of the six patients exhibited CMRI changes characteristic of myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiogram. Of the five patients who received immunosuppression, four recovered from myocarditis and one died of cardiac failure. The sixth patient improved with cardiac failure management alone. Three of the four patients responding to ICI derived long-term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis.
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Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Imageamento por Ressonância Magnética , Miocardite/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Creatina Quinase/sangue , Diagnóstico Diferencial , Ecocardiografia , Feminino , Coração/diagnóstico por imagem , Coração/efeitos dos fármacos , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/imunologia , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , Miocardite/sangue , Miocardite/induzido quimicamente , Miocardite/imunologia , Miocárdio/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Troponina T/sangueRESUMO
PURPOSE: To assess visual outcomes of Coats disease by classification stage. METHODS: A retrospective review was conducted on consecutive patients with Coats disease, classified according to Shields classification and with available Snellen visual acuity before and after treatment. RESULTS: There were 160 eyes with Coats disease (stage 1 (n=2) vs stage 2A (n=17) vs stage 2B (n=22) vs stage 3A1 (n=26) vs stage 3A2 (n=40) vs stage 3B (n=42) vs stage 4 (n=9) vs stage 5 (n=2)). By comparison, more advanced stage showed greater frequency of poor presenting visual acuity (<20/200) (0% vs 0% vs 50% vs 35% vs 38% vs 83% vs 100% vs 100%, p<0.001) and higher mean intraocular pressure (17 vs 15 vs 15 vs 15 vs 15 vs 15 vs 37 vs 26, p<0.001). More advanced stage was less likely managed with laser photocoagulation (100% vs 87% vs 48% vs 62% vs 74% vs 35% vs 0% vs 0%, p<0.001) and more likely with cryotherapy (0% vs 47% vs 81% vs 81% vs 82% vs 88% vs 50% vs 100%, p=0.001). More advanced stage was associated with lower frequency of visual acuity ≥20/40 (100% vs 71% vs 5% vs 42% vs 23% vs 5% vs 0% vs 0%, p<0.001) and greater frequency of visual acuity <20/200 (0% vs 12% vs 36% vs31 % vs 45% vs 88% vs 0% vs 100%, p<0.001). CONCLUSION: Visual acuity in eyes with Coats disease parallels staging with more advanced stage demonstrating poorer visual acuity at presentation and final visit.
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Angiofluoresceinografia/métodos , Telangiectasia Retiniana/fisiopatologia , Acuidade Visual , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Telangiectasia Retiniana/classificação , Telangiectasia Retiniana/diagnóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
A 70-year-old woman underwent adjuvant chemotherapy with dose-dense doxorubicin and cyclophosphamide for early breast cancer. After her fourth cycle of chemotherapy, she developed severe fatigue and cough with rapid-onset hypoxic respiratory failure. Investigations demonstrated extensive bilateral consolidation with positive bronchial washings for Pneumocystis jirovecii by polymerase chain reaction (PCR). Despite high-dose trimethoprim-sulfamethoxazole, she progressed to multi-organ failure and succumbed. Pneumocystis jirovecii pneumonia (PJP) has traditionally rarely occurred in women on adjuvant breast cancer chemotherapy but may pose a more serious risk in dose-dense regimes due to higher concurrent exposure to anti-emetic corticosteroids. Clinicians are alerted to the need for vigilance of this rare complication and for rationalization of dexamethasone dosage to mitigate this risk, particularly in the era of modern triple-agent anti-emetic regimens.
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PURPOSE: To evaluate the effects of clinical features associated with enucleation in eyes with Coats disease. METHODS: The medical records of all patients with Coats disease at the Ocular Oncology, Wills Eye Hospital from November 1, 1973, to July 31, 2018, were reviewed retrospectively. The clinical features pertaining to need for ultimate enucleation and time to enucleation were compared. RESULTS: The records of 351 eyes were reviewed, of which 259 had follow-up at our center and 32 (12%) were managed with enucleation. Reasons for enucleation included neovascular glaucoma (n = 24 [75%]), possible tumor (6 [19%]), and phthisis bulbi (2 [6%]). Compared to nonenucleated eyes, enucleated eyes had more extensive clock hour involvement of telangiectasia (P < 0.001), light bulb aneurysms (P < 0.001), exudation (P < 0.001), and subretinal fluid (P < 0.001). On adjusted analysis by binomial logistic regression, variables predictive of enucleation included presence of iris neovascularization (P = 0.01), ultrasonographic retinal detachment (P = 0.004), open-funnel retinal detachment (P = 0.04), closed-funnel retinal detachment (P = 0.01), ultrasonographic elevation of subretinal fluid by millimeters (P = 0.001), and angiographic extent of light bulb aneurysms by clock hours (P = 0.02). By Kaplan-Meier analysis of 4-year cumulative risk of enucleation, risk factors for enucleation included presence of iris neovascularization (hazard ratio [HR] 31.0; P < 0.001), ultrasonographic retinal detachment (HR 56.2; P < 0.001), open-funnel retinal detachment (HR 2.7; P = 0.01), and closed-funnel retinal detachment (HR 4.5; P < 0.001). CONCLUSIONS: Clinical features that predict risk of and time to enucleation in eyes with Coats disease include iris neovascularization, ultrasonographic presence and millimeter-elevation of retinal detachment, and angiographic extent of light bulb aneurysms.
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Aneurisma/diagnóstico , Enucleação Ocular , Iris/irrigação sanguínea , Neovascularização Patológica/diagnóstico , Descolamento Retiniano/diagnóstico , Telangiectasia Retiniana/diagnóstico , Vasos Retinianos/patologia , Adolescente , Adulto , Idoso , Aneurisma/cirurgia , Criança , Pré-Escolar , Feminino , Angiofluoresceinografia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/cirurgia , Descolamento Retiniano/cirurgia , Telangiectasia Retiniana/cirurgia , Estudos Retrospectivos , Líquido Sub-Retiniano , Fatores de Tempo , UltrassonografiaRESUMO
PURPOSE: The aim of this study was to investigate factors predictive of subretinal fluid (SRF) resolution in Coats disease. DESIGN: Retrospective cohort study. METHODS: Institutional review board-approved review of patients diagnosed with Coats disease demonstrating SRF (stage 3-5) at a single center from November 1973 to July 2018 with comparison of eyes that had resolution of SRF to those in which SRF persisted. RESULTS: There were 177 cases (154 males, 87%) of Coats disease diagnosed at a mean age of 8 years. After a mean follow-up of 62 months, SRF resolved in 110 (62%) and persisted in 67 (38%) eyes. Comparison (resolved SRF vs persistent SRF) revealed classification as stage 3A [63 (57%) vs 20 (29%)], stage 3B [47 (43%) vs 40 (60%)], or stage 4 [0 (0%) vs 7 (11%)] (Pâ<â0.001). Eyes with resolved SRF presented with fewer clock hours of telangiectasia (mean: 5 vs 7 clock hours, Pâ<â0.001), light bulb aneurysms (mean: 5 vs 7 clock hours, Pâ<â0.001), exudation (mean: 7 vs 10 clock hours, Pâ<â0.001), and extent of SRF (mean: 7 vs 10 clock hours, Pâ<â0.001). Factors predictive of SRF resolution included absence of iris neovascularization on fluorescein angiography [odds ratio 0.05 (95% confidence interval 0.01-0.60), Pâ=â0.02], and less elevated SRF by ultrasonography [odds ratio 0.84 (95% confidence interval 0.76-0.95), Pâ=â0.004). For every 1-mm decrease in SRF, likelihood of SRF resolution increased by 16%. CONCLUSIONS: Resolution of SRF was achieved in the majority of eyes (62%) with stage 3 to 5 Coats disease. Predictors of SRF resolution included lack of neovascularization on fluorescein angiography and less elevation of SRF by ultrasonography.
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Angiofluoresceinografia/métodos , Retina/patologia , Telangiectasia Retiniana/diagnóstico , Líquido Sub-Retiniano/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Fundo de Olho , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/patologia , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Purpose: To assess features and outcomes of Coats disease over 5-decades. Methods: Retrospective review of Coats disease patients at a single center. Features and outcomes were compared based on decade of presentation. Results: There were 351 patients with Coats disease. The presenting median age (6 years), male sex (84%), and unilaterality (100%) did not change per decade. Coats disease classification did not change per decade with Stage 1 (1%), Stage 2 (21%), Stage 3 (68%), Stage 4 (6%), and Stage 5 (1%). Clinical features that changed per decade (1970s vs. 1980s vs. 1990s vs. 2000s vs. 2010s) included 1980s features of more eyes with exudation in all 4 quadrants (22% vs. 58% vs. 44% vs. 33% vs. 27, P = 0.01) and total exudative retinal detachment (33% vs. 53% vs. 39% vs. 27% vs. 21%, P < 0.001). Imaging features that changed per decade included 2010s greater fluorescein angiographic extent of retinal non-perfusion in mean clock hours (4 vs. 4 vs. 3 vs. 5 vs. 6, P = 0.003), and 1980s greater mean height of retinal detachment ultrasonographically (5 vs. 12 vs. 5 vs. 5 vs. 4 mm, P < 0.001). Treatment features that changed per decade included 1980s greater primary enucleation (11% vs. 16% vs. 3% vs. 4% vs. 1%, P = 0.001), and 2010s greater use of laser photocoagulation (55% vs. 33% vs. 38% vs. 40% vs. 72%, P < 0.001), sub-Tenon corticosteroid (0% vs. 4% vs. 5% vs. 8% vs. 29%, P < 0.001), and intravitreal anti-VEGF) (0% vs. 4% vs. 2% vs. 13% vs. 18%, P = 0.003). Outcomes that changed per decade included 2010s findings of more complete resolution of subretinal fluid (64% vs. 59% vs. 38% vs. 58% vs. 72%, P = 0.01) and less need for primary/secondary enucleation (17% vs. 27% vs. 14% vs. 13% vs. 6%, P = 0.04). Conclusion: Eyes with Coats disease in the 1980s demonstrated more advanced findings, often requiring enucleation. Over the decades, greater use of laser photocoagulation and injections has led to improved disease resolution with greater globe salvage.
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Bevacizumab/administração & dosagem , Crioterapia/métodos , Previsões , Fotocoagulação a Laser/métodos , Retina/diagnóstico por imagem , Telangiectasia Retiniana/diagnóstico , Adolescente , Adulto , Inibidores da Angiogênese/administração & dosagem , Criança , Pré-Escolar , Progressão da Doença , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Lactente , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Telangiectasia Retiniana/terapia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Adulto JovemRESUMO
PURPOSE: Immune checkpoint inhibitors (ICI) and BRAF and MEK inhibitors (BMi) have improved survival in metastatic melanoma (MM). However, the experience of long-term responders remains undescribed. This study characterised survivorship issues faced by long-term responders to ICI or BMi. METHODS: Patients with MM, aged ≥ 18 years old, ≥ 6 months post-ICI or BMi initiation with an objective response or stable disease. A 72-question survey assessed physical and psychological effects, impact on lifestyle, access to information, satisfaction with care, and availability of supports. RESULTS: One hundred and five of 120 (88%) patients completed the survey (ICI 69/BMI 36). For the ICI cohort, 39 (57%) were receiving ongoing treatment, 17 ceased due to toxicity and 13 due to a sustained response. For the BMi cohort, 31 (85%) were receiving ongoing treatment, 4 ceased due to toxicity and 1 due to a sustained complete response. At data cut-off on 18 December 2018, median PFS (range) was 2.5 years (1.3-8.5) for ICI and 3.1 years (0.6-7.3) for BMi. Long-term toxicities included dry/itchy skin (ICI 51, 74%/ BMi 25, 69%), arthralgias (ICI 30, 58%/ BMi 23, 64%) and fatigue (ICI 62, 90%/ BMi 33, 92%). Psychological morbidity was common, including anxiety awaiting results (ICI 50, 72%/ BMi 29, 81%), fear of melanoma recurring or progressing (ICI 56, 81%/ BMi 31, 86%) or death (ICI 44, 64%/ BMi 26, 72%). CONCLUSION: MM survivors experience chronic treatment toxicities and frequently report psychological concerns. IMPLICATIONS FOR CANCER SURVIVORS: Survivors may benefit from discussions regarding long-term toxicities and tailored psychological supports.
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Sobreviventes de Câncer , Melanoma/tratamento farmacológico , Melanoma/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Sobrevivência , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Feminino , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Avaliação das Necessidades , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/mortalidade , Inquéritos e Questionários , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
PURPOSE: To investigate features and outcomes of Coats disease by patient age. METHODS: Patients with Coats disease from 1973 to 2018 were evaluated based on age category at presentation (3 years or younger vs older than 3 to 10 years vs older than 10 years). RESULTS: There were 351 eyes of 351 patients with Coats disease diagnosed (2 vs 6 vs 27 years, P < .001). The youngest age group had more referral diagnoses of retinoblastoma (29% vs 15% vs 0%, P < .001), worse presenting visual acuity (< 20/200: 80% vs 67% vs 31%, P < .001), more advanced Coats disease stage (stage 3B: 65% vs 38% vs 10%, P < .001), and greater clock-hour extent of telangiectasia (7 vs 5 vs 4, P < .001), light bulb aneurysms (7 vs 4 vs 3, P < .001), exudation (10 vs 7 vs 5, P < .001), and subretinal fluid (10 vs 7 vs 4, P < .001). The oldest patients received a greater total number of treatments (3.3 vs 3.1 vs 4.4, P = .04), with more argon laser photocoagulation (37% vs 52% vs 73%, P < .001) and intravitreal anti-vascular endothelial growth factor (6% vs 9% vs 23%, P < .002) and less cryotherapy (74% vs 84% vs 58%, P < .001). At mean follow-up (70 vs 65 vs 38 months, P = .02), the youngest patients had poorer visual acuity outcome (< 20/200: 83% vs 64% vs 39%, P < .001), had less disease resolution (43% vs 65% vs 62%, P = .01), and were more likely to ultimately require enucleation (22% vs 10% vs 6%, P = .01). CONCLUSIONS: Younger patients (3 years or younger) with Coats disease present with worse visual acuity and more advanced disease stage, and are more likely to require ultimate enucleation. [J Pediatr Ophthalmol Strabismus. 2019;56(5):288-296.].
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Inibidores da Angiogênese/administração & dosagem , Crioterapia/métodos , Angiofluoresceinografia/métodos , Fotocoagulação a Laser/métodos , Acuidade Visual , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Prognóstico , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/terapia , Estudos Retrospectivos , Adulto JovemRESUMO
BRAF and CRAF are critical components of the MAPK signaling pathway which is activated in many cancer types. In approximately 1% of melanomas, BRAF or CRAF are activated through structural arrangements. We describe here a metastatic melanoma with a GOLGA4-RAF1 fusion and pathogenic variants in CTNNB1 and CDKN2A. Anti-CTLA4/anti-PD1 combination immunotherapy failed to control tumor progression. In the absence of other actionable variants the patient was administered MEK inhibitor therapy on the basis of its potential action against RAF1 fusions. This resulted in a profound and clinically significant response. We demonstrated that GOLGA4-RAF1 expression was associated with ERK activation, elevated expression of the RAS/RAF downstream co-effector ETV5, and a high Ki67 index. These findings provide a rationale for the dramatic response to targeted therapy. This study shows that thorough molecular characterization of treatment-resistant cancers can identify therapeutic targets and personalize management, leading to improved patient outcomes.