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2.
BMJ Open Ophthalmol ; 8(1)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-37039095

RESUMO

BACKGROUND/AIMS: To characterise the baseline prevalence of subretinal fluid (SRF) and its effects on anatomical and visual acuity (VA) outcomes in diabetic macular oedema (DME) and retinal vein occlusion (RVO) following anti-vascular endothelial growth factor (VEGF). METHODS: This is a retrospective cohort study of 122 DME and 54 RVO patients who were initiated on anti-VEGF therapy with real-world variable dosing. The DME and RVO cohorts were subclassified based on the presence of SRF at presentation. Snellen VA was measured and converted to logarithm of the minimum angle of resolution (LogMAR). Changes in VA and central subfield thickness (CST) were assessed up to 24 months. RESULTS: SRF was present in 22% and 41% in DME and RVO patients, respectively. In the DME subcohort, eyes with SRF showed an improvement of 0.166 logMAR (1.7 Snellen chart lines) at 12 months and 0.251 logMAR (2.6 Snellen chart lines) at 24 months, which were significantly greater compared with those of the non-SRF group. A significantly greater reduction in CST was noted in the SRF eyes compared with the non-SRF eyes at 3 months and 1 month in the DME and RVO subcohorts, respectively. CONCLUSION: Baseline SRF is a good marker for a greater reduction in CST in both DME and RVO, but an improvement in VA associated with SRF may be only noted in DME.


Assuntos
Doenças Retinianas , Oclusão da Veia Retiniana , Líquido Sub-Retiniano , Humanos , Inibidores da Angiogênese/uso terapêutico , Estudos de Coortes , Injeções Intravítreas , Prevalência , Doenças Retinianas/epidemiologia , Oclusão da Veia Retiniana/complicações , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/uso terapêutico
3.
Ophthalmic Genet ; 44(3): 253-261, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36974392

RESUMO

PURPOSE: To report the genotype and phenotype of a cohort of unselected uveal melanoma (UM) patients who had germline multi-gene panel genetic testing, including the BAP1 gene, from a large multi-ethnic cancer centre. We describe the central role of the medical genetics clinic in collaboration with oncologists in a mainstreaming model to facilitate genetic testing, counselling and streamlining of patients with hereditary cancer predisposition. METHODS: A retrospective chart review of clinical and genetic findings of unselected UM patients who had germline genetic testing between December 2019 and October 2021 was conducted. Extracted DNA from peripheral blood samples were analyzed with a multi-gene panel that included at least six genes associated with hereditary melanoma. The correlation between the genotype and the phenotype of the cohort was evaluated. Statistical analysis comprised descriptive and comparative statistics with significance assigned at p < .05. The genetics clinic streamlined patients among the relevant oncology clinics for cancer screening in germline BAP1 positive individuals. RESULTS: In unselected UM patients, 3.5% (4/114) tested positive for a BAP1 pathogenic variant. Germline BAP1 status was associated with a family history of mesothelioma (p = .0015) and metastatic disease (p = .017). There were no other significant associations between the patient- or tumour-related characteristics and germline BAP1 results. CONCLUSION: A germline BAP1 mutation was detected in 3.5% of unselected UM patients. The oncologist-initiated and genetics-led mainstreaming model is a straightforward process and can be utilized for offering genetic testing to all UM patients.


Assuntos
Melanoma , Neoplasias Uveais , Humanos , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patologia , Testes Genéticos , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/genética , Neoplasias Uveais/patologia , Mutação em Linhagem Germinativa , Predisposição Genética para Doença , Ubiquitina Tiolesterase/genética
4.
Invest Ophthalmol Vis Sci ; 64(1): 15, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36656566

RESUMO

Purpose: Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Methods: Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Results: Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Conclusions: Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.


Assuntos
Neoplasias da Coroide , Melanoma , Neoplasias Uveais , Humanos , Corpo Ciliar/patologia , Neoplasias Uveais/genética , Neoplasias Uveais/patologia , Melanoma/genética , Melanoma/patologia , Neoplasias da Coroide/genética , Neoplasias da Coroide/patologia , Deleção Cromossômica , Monossomia , Fatores de Risco , Cromossomos Humanos Par 3/genética
5.
Clin Transl Radiat Oncol ; 38: 15-20, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36353653

RESUMO

Objective: To report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL). Methods: Retrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates. Results: This study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93-100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity. Conclusion: External Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20-30 Gy delivered over 10-20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities.

7.
Eur J Ophthalmol ; 32(1): NP1-NP4, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32700563

RESUMO

PURPOSE: Uveal melanoma extension to the central nervous system (CNS) is exceedingly rare, and can occur through optic nerve invasion. We report a rare clinical case that presented with cauda equina syndrome as the initial manifestation of metastasis of choroidal melanoma, and showed neurotropic extension by histopathology. Our patient did not demonstrate any evidence of systemic metastasis otherwise. OBSERVATIONS: A 60-year-old male patient with treated choroidal melanoma in his right eye, with presumed clinical control, developed radiation-induced neovascular glaucoma refractory to medical therapy. The eye required enucleation for pain control. One month post-enucleation, he presented to the emergency department with severe abdominal pain, urine retention, constipation, and leg weakness. Magnetic resonance imaging (MRI) of the spine showed extensive leptomeningeal involvement along the entire spinal cord and the cauda equina. On further inquisition, the patient noted prior visual field defect in the contralateral eye. Brain MRI revealed intracranial metastasis with chiasmal involvement. The patient underwent radiotherapy for the brain and spine to improve his symptoms, and was ultimately transferred to palliative care. CONCLUSION AND IMPORTANCE: Optic nerve invasion in uveal melanoma may lead to neurotropic spread of melanoma cells with risk of intracranial and spinal cord metastasis. Neurological symptoms should raise the suspicion of clinicians regarding this complication, which is associated with increased melanoma-related mortality.


Assuntos
Síndrome da Cauda Equina , Neoplasias da Coroide , Melanoma , Neoplasias Uveais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/radioterapia
9.
JAMA Ophthalmol ; 138(6): 652-659, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32324204

RESUMO

Importance: Retinal displacement following rhegmatogenous retinal detachment repair may have consequences for visual function. It is important to know whether surgical technique is associated with risk of displacement. Objective: To compare retinal displacement following rhegmatogenous retinal detachment repair with pneumatic retinopexy (PR) vs pars plana vitrectomy (PPV). Interventions or Exposures: Fundus autofluorescence images were assessed by graders masked to surgical technique. Design, Setting, and Participants: A multicenter retrospective consecutive case series in Canada and the UK. A total of 238 patients (238 eyes) with rhegmatogenous retinal detachments treated with PR or PPV who underwent fundus autofluorescence imaging from November 11, 2017, to March 22, 2019, were included. Main Outcomes and Measures: Proportion of patients with retinal displacement detected by retinal vessel printings on fundus autofluorescence imaging in PR vs PPV. Results: Of the 238 patients included in the study, 144 were men (60.5%) and 94 were women (39.5%); mean (SD) age was 62.0 (11.0) years. Of the 238 eyes included in this study, 114 underwent PR (47.9%) and 124 underwent PPV (52.1%) as the final procedure to achieve reattachment. Median time from surgical procedure to fundus autofluorescence imaging was 3 months (interquartile range, 1-5 months). Baseline characteristics in both groups were similar. The proportion of eyes with retinal vessel printing on fundus autofluorescence was 7.0% for PR (8 of 114) and 44.4% for PPV (55 of 124) (37.4% difference; 95% CI, 27.4%-47.3%; P < .001). Analysis based on the initial procedure found that 42.4% (42 of 99) of the eyes in the PPV group vs 15.1% (21 of 139) of the eyes in the PR group (including 13 PR failures with subsequent PPV) had displacement (27.3% difference; 95% CI, 15.9%-38.7%; P < .001). Among eyes with displacement in the macula, the mean (SD) displacement was 0.137 (0.086) mm (n = 6) for PR vs 0.297 (0.283) mm (n = 52) for PPV (0.160-mm difference; 95% CI, 0.057-0.263 mm; P = .006). Mean postoperative logMAR visual acuity was 0.31 (0.32) (n = 134) (Snellen equivalent 20/40) in eyes that initially underwent PR and 0.56 (0.42) (n = 84) (Snellen equivalent 20/72) in eyes that had PPV (-0.25 difference; 95% CI, -0.14 to -0.35; P < .001). Among eyes with displacement, mean postoperative logMAR visual acuity was 0.42 (0.42) (n = 20) (Snellen equivalent 20/52) in those that initially underwent PR and 0.66 (0.47) (n = 33) (Snellen equivalent 20/91) in those that initially underwent PPV (-0.24 difference; 95% CI, -0.48 to 0.01; P = .07). Conclusions and Relevance: These findings suggest that retinal displacement occurs more frequently and is more severe with PPV vs PR when considering the initial and final procedure used to achieve retinal reattachment. Recognizing the importance of anatomic integrity by assessing retinal displacement following reattachment may lead to refinements in vitreoretinal surgery techniques.


Assuntos
Angiofluoresceinografia/métodos , Complicações Pós-Operatórias , Retina/patologia , Descolamento Retiniano/cirurgia , Recurvamento da Esclera/efeitos adversos , Acuidade Visual , Vitrectomia/efeitos adversos , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Retina/cirurgia , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento
10.
Ophthalmologica ; 243(5): 323-333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126567

RESUMO

PURPOSE: To review visual outcomes in untreated premacular membrane (PMM) with macular pucker (MP) and evaluate novel predictors of progression. METHODS: In this retrospective observation study, we included 342 eyes with untreated PMM with MP between 2012 and 2015. PMMs were characterized by spectral-domain optical coherence tomography (SD-OCT) imaging based on foveal morphologies, number of retinal contraction centers, central subfield thickness (CST), inner segment ellipsoid band integrity, and photoreceptor deformation index. Additionally, the thickened retina portion was identified by en face OCT and processed digitally to calculate its area. Parameters were retrospectively analyzed using multiple regression analyses to identify associations with change in visual acuity (VA) between initial to final follow-up visit. RESULTS: In 468 eyes with untreated PMM, VA and CST did not change significantly during a mean observation period of 448 days (p = 0.52 and 0.35, respectively). Specifically, VA improved or stayed the same in 80% and worsened by 2 lines or more in 20% of eyes. The only consistent predictor of PMM progression was area of retinal thickening: for every 1 mm2 of retinal thickening at baseline, the odds of having worsened vision at follow-up increased by 6% (OR 1.0606, 95% CI 1.0031-1.1214, p = 0.0387). CONCLUSIONS: The majority of eyes with PMM and good visual function at baseline remain stable or spontaneously improve in VA and macular thickness. Area of retinal thickening as evaluated by en face OCT may be a novel predictor of vision loss in untreated PMM with MP.


Assuntos
Edema Macular/diagnóstico , Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
11.
Retina ; 40(5): 838-844, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30821730

RESUMO

PURPOSE: To describe and evaluate the efficacy of a novel technique, scleral needling (SN), for securing 23- and 25-gauge leaking sclerotomies in microincision vitrectomy surgery. METHODS: A retrospective comparative review of consecutive cases of 23- and 25-gauge pars plana vitrectomy performed by a single vitreoretinal surgeon before the introduction of the SN technique (pre-SN; November 2016 to January 2017) and after the introduction of the SN technique (post-SN; November 2017 to January 2018) was conducted. The SN technique was implemented as an alternative to suturing, using a 30-gauge needle inserted perpendicularly through the full thickness of the sclera adjacent to the scleral opening, with the needle then immediately removed and sclerotomy closure confirmed. RESULTS: A total of 203 eyes, 105 from pre-SN and 98 from post-SN, were included in the study. The number of eyes requiring suture closure was significantly reduced from 39% in the pre-SN group to 2% in the post-SN group (P < 0.001). The mean postoperative intraocular pressure and incidence of hypotony on Days 1 to 2, Days 3 to 20, and Days 21 to 50 was not significantly different between the pre-SN and post-SN groups. No major complications associated with the SN technique were noted during the study period. CONCLUSION: The SN technique is a safe and simple method for effectively securing leaking sclerotomies in microincision vitrectomy surgery.


Assuntos
Microcirurgia/métodos , Doenças Retinianas/cirurgia , Esclera/cirurgia , Esclerostomia/instrumentação , Procedimentos Cirúrgicos sem Sutura/métodos , Idoso , Desenho de Equipamento , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/fisiopatologia , Estudos Retrospectivos
13.
Ophthalmologica ; 242(1): 1-7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30928983

RESUMO

OBJECTIVE: To evaluate the outcomes and complications of bilateral same-day intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: This is a single-center, retrospective study that included 524 eyes of 262 patients who received concomitant bilateral intravitreal anti-VEGF injections in 2016 at St. Michael's Hospital, Toronto. If any of the patients were receiving simultaneous bilateral injections on a regular basis prior to 2016, data pertaining to previous injections were also reviewed. Everyone received bevacizumab, ranibizumab, or aflibercept in an office setting. RESULTS: A total of 9,798 intravitreal anti-VEGF injections (4,899 bilateral injection sessions) were performed in 524 eyes of 262 patients. The average number of bilateral injection sessions per patient was 18.7 ± 14.1. Ranibizumab was the most commonly used anti-VEGF drug (83.8%). The incidence of endophthalmitis was 0.01%, and there were 2 episodes of acute intraocular inflammation among the 9,798 injections (0.02%). All 3 cases occurred after treatment with ranibizumab. There were 2 deaths (0.76%) due to nonvascular causes but no vascular related systemic adverse events were reported. CONCLUSIONS: Same-day bilateral intravitreal anti-VEGF injections present a low rate of complications and are well tolerated by patients. This safe practice may reduce the burden on the health-care system and on the patients.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Assistência Ambulatorial , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Canadá , Endoftalmite/induzido quimicamente , Humanos , Inflamação/induzido quimicamente , Injeções Intravítreas , Ranibizumab/efeitos adversos , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Acuidade Visual/fisiologia
14.
Am J Ophthalmol ; 206: 176-183, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30959004

RESUMO

PURPOSE: To determine the association of aqueous humor cytokine concentrations with long-term treatment response to anti-vascular endothelial growth factor (VEGF) agents in diabetic macular edema (DME). DESIGN: Retrospective case series. METHODS: Pooled data of aqueous humor cytokine concentrations collected at baseline and 2-month follow-up (2 injections) for treatment-naïve eyes with center-involving DME previously enrolled in a prospective study were reviewed. Subjects receiving intravitreal anti-VEGF injections outside of study protocol as per standard of care were classified into Responders versus Nonresponders based on qualitative assessment of optical coherence tomography for persistence of DME at longitudinal follow-up visits. RESULTS: Of the 41 eyes, 85% were classified as Responders with a significant decline in baseline central subfield thickness and macular volume (P values < .001), and 15% were identified as Nonresponders to anti-VEGF therapy over 51.4 ± 18.7 months of follow-up. No significant difference in baseline aqueous humor VEGF concentration was noted, while at the 2-month follow-up the Nonresponder group had a significantly higher VEGF concentration compared with the Responder group (451.5 ± 690.9 pg/mL vs 113.7 ± 211.4 pg/mL; P = .02). The Responder group also demonstrated a significant decline from baseline to 2-month follow-up in concentration of intercellular adhesion molecule-1 (P < .001), interleukin-10 (P = .041), monocyte chemotactic protein-1 (P = .046), placental growth factor (P = .027), and transforming growth factor-ß2 (P = .017). CONCLUSIONS: Aqueous humor cytokine concentrations serve as an early biomarker for long-term response to anti-VEGF therapy and may enable more effective treatment regimens that improve anatomical outcomes in eyes with DME.


Assuntos
Humor Aquoso/metabolismo , Bevacizumab/administração & dosagem , Citocinas/metabolismo , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Acuidade Visual , Inibidores da Angiogênese/administração & dosagem , Biomarcadores/metabolismo , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Macula Lutea/patologia , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
15.
Ophthalmology ; 126(4): 531-539, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30468761

RESUMO

PURPOSE: The optimal surgery to repair rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for the management of primary RRD. DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: Patients with RRD demonstrating a single retinal break or a group of breaks in detached retina within 1 clock hour above the 8- and 4-o'clock meridians, with any number, location and size of retinal breaks or lattice degeneration in attached retina. METHODS: Patients were randomized to undergo either PnR or PPV. Macula-on and macula-off patients were assigned to intervention group by stratified randomization and were treated within 24 and 72 hours, respectively. MAIN OUTCOME MEASURES: The primary outcome was 1-year Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA). Important secondary outcomes were subjective visual function (25-item National Eye Institute Visual Function Questionnaire), metamorphopsia score (M-CHARTS), and primary anatomic success. RESULTS: One hundred seventy-six patients were recruited between August 2012 and May 2016. ETDRS VA after PnR exceeded that after PPV by 4.9 letters at 12 months (79.9±10.4 letters vs. 75.0±15.2 letters; P = 0.024). Mean ETDRS VA also was superior for the PnR group compared with the PPV group at 3 months (78.4±12.3 letters vs. 68.5±17.8 letters) and 6 months (79.2±11.1 letters vs. 68.6±17.2 letters). Composite 25-item National Eye Institute Visual Function Questionnaire scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs. 0.28±0.42; P = 0.026). Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P = 0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success. Sixty-five percent of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months versus 16% in the PnR group (P < 0.001). CONCLUSIONS: Pneumatic retinopexy should be considered the first line treatment for RRD in patients fulfilling Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) recruitment criteria. Pneumatic retinopexy offers superior VA, less vertical metamorphopsia, and reduced morbidity when compared with PPV.


Assuntos
Terapia a Laser/métodos , Descolamento Retiniano/cirurgia , Vitrectomia/métodos , Idoso , Tamponamento Interno/métodos , Feminino , Fluorocarbonos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/fisiopatologia , Perfurações Retinianas/cirurgia , Perfil de Impacto da Doença , Hexafluoreto de Enxofre/administração & dosagem , Inquéritos e Questionários , Resultado do Tratamento , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia
16.
JAMA Ophthalmol ; 136(4): 382-388, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29522144

RESUMO

Importance: Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. Objectives: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. Design, Setting, and Participants: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 µm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. Interventions: Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. Main Outcomes and Measures: Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. Results: Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). Conclusions and Relevance: Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.


Assuntos
Humor Aquoso/metabolismo , Citocinas/metabolismo , Retinopatia Diabética/tratamento farmacológico , Macula Lutea/patologia , Edema Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Acuidade Visual , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Biomarcadores/metabolismo , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
17.
Retina ; 37(1): 76-79, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28005718

RESUMO

PURPOSE: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients. METHODS: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined "favorable" ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ≤400 µm. The authors further categorized "optimal" candidates as age ≤65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ≤400 µm. RESULTS: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ≤400 µm in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates. CONCLUSION: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.


Assuntos
Fibrinolisina/uso terapêutico , Fibrinolíticos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Perfurações Retinianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Epirretiniana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pseudofacia/patologia , Perfurações Retinianas/tratamento farmacológico , Perfurações Retinianas/patologia , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia/métodos
18.
Retina ; 37(4): 761-769, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27471825

RESUMO

PURPOSE: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema. METHODS: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 µm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone. RESULTS: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03). CONCLUSION: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.


Assuntos
Humor Aquoso/metabolismo , Citocinas/metabolismo , Retinopatia Diabética/metabolismo , Edema Macular/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Estudos Transversais , Retinopatia Diabética/diagnóstico , Feminino , Humanos , Macula Lutea/patologia , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Acuidade Visual
19.
Ophthalmologica ; 234(1): 6-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26088287

RESUMO

BACKGROUND: The availability of new therapeutic approaches, particularly intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies, has prompted significant changes to the established treatment paradigms for retinal vein occlusion (RVO). Better visual outcomes and significantly lower rates of adverse events have been noted in multiple large randomized clinical trials and have led to a new standard of care for this sight-threatening condition. OBJECTIVE: To develop an expert consensus for the management of RVO and associated complications in the context of recent clinical evidence. METHODS: The development of a Canadian expert consensus for optimal treatment began with a review of clinical evidence, daily practice, and existing treatment guidelines and algorithms. The expert clinicians (11 Canadian retina specialists) met on February 1, 2014, in Toronto to discuss their findings and to propose strategies for consensus. RESULTS: The result of this expert panel is a consensus proposal for Canadian ophthalmologists and retina specialists treating patients presenting with RVO. Treatment algorithms specific to branch and central RVO (BRVO and CRVO) were also developed. CONCLUSIONS: The consensus provides guidelines to aid clinicians in managing RVO and associated complications in their daily practice. In summary, laser remains the therapy of choice when neovascularization secondary to RVO is detected. Adjunctive anti-VEGF could be considered in managing neovascularization secondary to RVO in cases of vitreous hemorrhage. Intravitreal anti-VEGF should be considered for symptomatic visual loss associated with center-involving macular edema on optical coherence tomography. Patients with BRVO and a suboptimal response to anti-VEGF could be treated with grid laser, and those with CRVO and an inadequate response to anti-VEGF may be candidates for intravitreal steroids.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Consenso , Fotocoagulação a Laser/métodos , Oclusão da Veia Retiniana/terapia , Canadá , Humanos , Oclusão da Veia Retiniana/fisiopatologia , Acuidade Visual
20.
Am J Ophthalmol ; 153(5): 890-895.e3, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22265155

RESUMO

PURPOSE: To describe the morphologic features of calcified and decalcified choroidal osteomas using multimodal imaging and correlate these findings with a previous histopathologic study. DESIGN: Retrospective observational case series. METHODS: Three patients with choroidal osteoma underwent complete ophthalmologic examination, fundus photography, and multimodal fundus imaging, including Fourier-domain optical coherence tomography (FD-OCT) and blue-light fundus autofluorescence (bAF). RESULTS: FD-OCT imaging of calcified tumors revealed a distinctive latticework pattern of reflectivity resembling the spongy bone structure seen histopathologically. On bAF the fluorescence was relatively well preserved overlying calcified tumors. In decalcified areas 2 patterns of reflectivity were identified: the first consisted of areas of relative hyperreflectivity with a lamellar appearance while the second was characterized by heterogeneous, hyperreflective, mound-like irregular areas associated with some posterior optical shadowing. Decalcified tumor areas had reduced overall fluorescence on bAF. CONCLUSION: FD-OCT demonstrated different reflectivity patterns in both calcified and decalcified portions of the choroidal osteoma, which may correspond to different stages of tumor evolution. A distinctive latticework pattern of reflectivity similar to spongy bone was seen in calcified tumors. These observations improve our knowledge of the in vivo structure of choroidal osteomas and may have implications for the diagnosis and management of this tumor.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias da Coroide/patologia , Osteoma/patologia , Adolescente , Adulto , Calcinose/patologia , Descalcificação Patológica/patologia , Feminino , Angiofluoresceinografia , Análise de Fourier , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual
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