1,720,988 research outputs found
LIQUID BIOPSY IN UVEAL MELANOMA: PROTEOMICS OF AQUEOUS HUMOR
Full text linkPosterior uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM occurs in a closed microenvironment characterized by a direct contact with ocular fluids. Therefore, the analysis of these fluids may allow to search and identify specific biomarkers providing information about the different pathways involved in UM pathogenesis and in the retinal complications related to its conservative treatment.
To evaluate, in vivo, the presence of specific AH biomarkers in eyes affected by UM before and after the conservative treatment.
Seventy-two eyes affected by primary UM underwent full ophthalmic examination. During brachytherapy (Iodine-125) surgical procedure, AH sample collection and 25-gauge transscleral fine needle aspiration biopsy of the primary tumor were performed. AH samples were analyzed to detect the concentration of selected proteins. Cytologic material underwent fluorescence in situ hybridization for chromosome 3. Tumor thickness and largest basal diameter (LBD) were quantified. The same seventy-two UM subjects underwent AH sampling at the time of a planned para surgical procedure 20 months after brachytherapy. The AH of thirty-six normal eyes, scheduled for cataract surgery, was used as control.
Compared with the control group, significantly higher levels of SSTR1 (p=0.028), HMB45 (p=0.018), IL-6 (p=0.047), IL-8 (p=0.008), RANTES (p=0.008), PEDF (p=0.048), Osteopontin (p=0.048), EGF (p=0.041), bFGF (p=0.019), MIF (p=0.009), MCP-1 (p=0.023). VEGF concentration between the two groups was statistically borderline (p=0.058). Comparison between clinical characteristics and cytokine concentrations showed a positive correlation between tumor thickness and IL-8 (p=0.032), and degree of serous retinal detachment and IL-6 (p=0.021). Monosomy 3 was detected in 20 cases (57%) and disomy 3 in the remaining 15 cases (43%). No correlation was found between chromosome 3 status and tumor dimensions (thickness: p=0.301; LBD: p=0.321), and between monosomy 3 and tumor location (ciliary body: p=0.871, choroid: p=0.931). Compared to UM with disomy 3, significant higher levels of IL-6 (p=0.022) IL-8 (p=0.003), RANTES (p=0.005), EGF (p=0.018), bFGF (p=0.012), VEGF (p=0.026), MIF (p=0.005) and MCP-1 (p=0.005) were detected in UM with monosomy 3. Comparison between clinical characteristics of UM with monosomy 3 and cytokine concentration showed a positive correlation between: tumor thickness and IL-8 (p=0.022), tumor thickness and VEGF (p=0.031), LBD and RANTES (p=0.015), and degree of retinal detachment and IL-6 (p=0.021). Compared with the control group, significantly higher protein levels of: GNAQ (p=0.022), BAP1 (p=0.013) and SF3B1 (p=0.023) were detected in eyes with UM. Cluster analysis of UM group revealed 2 clusters, one showing higher expression of GNAQ and BAP1 protein and one of EIF1AX protein. Moreover, the 2 clusters corresponded with the chromosome 3 status of UM. the AH of the UM group 20 months after the treatment showed that 22 subjects (30.5%) developed RME. All RME eyes at OCT analysis had significant increase in thickness of inner and middle retinal layers (p=0.002) mostly determined by intraretinal fluids, in number of hyperreflective retinal foci (p=0.003) and in areas of disrupted external limiting membrane (p=0.004). GFAP, Kir 4.1 and all inflammatory biomarkers were dramatically increased in RME eyes compared to those without RME (p=0.035, p=0.021 and p=0.032, respectively).
Specific and selected proteins may be detected in the AH of eyes affected by UM. These novel findings confirm the possibilities provided by AH analysis in UM before and after its treatment
Hyperreflective choroidal foci in diabetic eyes with and without macular edema: Novel insights on diabetic choroidopathy
No full textHistopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p 0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm in vivo the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder
Small Hyperreflective Retinal Foci as in vivo imaging feature of resident microglia activation in geographic atrophy
No full textGeographic atrophy (GA), the atrophic late stage of age-related macular degeneration (AMD), is one of the leading causes of vision loss in developed countries. Based on genetic, histological and preclinical studies, the role of the innate immune system in the development and progression of GA is well established. Microglia, the principal resident immune cells, are recognized as key players in innate immunity and contributors to AMD development. Optical coherence tomography (OCT) allows to identify small hyperreflective retinal foci (HRF) with specific features known as aggregates of activated microglial cells as possible in vivo imaging feature of local neuroretinal inflammation. The purpose of this study was to evaluate the presence and amount of small HRF in the eyes of patients with different macular atrophic phenotypes. Patients with GA in both eyes (bilateral GA: B-GA group), patients with GA in one eye and macular new vessels (MNV) in the fellow-eye (unilateral GA: U-GA group) and patients with extensive macular atrophy with pseudodrusen (EMAP), a rare and aggressive variant of atrophic AMD, were retrospectively analyzed. HRF, defined as isolated punctiform elements of small dimensions (≤30 μm) with intermediate reflectivity (similar to that of the nerve fiber layer) and without a shadow cone, were manually identified and quantified. The amount of HRF was correlated to best corrected visual acuity (BCVA), GA lesion size, measured both at near infrared reflectance (NIR), and blue wavelength fundus autofluorescence (FAF) images, to some GA features (multifocal versus unifocal GA; presence versus absence of foveal sparing) and to central retinal thickness (CRT). Forty-six patients (26 in the B-GA group, 16 in the U-GA group and 4 in the EMAP group) were studied. Patients with EMAP were younger compared to patients with B-GA and to patients with U-GA (63.5 ± 6.8 years vs 80.4 ± 8.4 years B-GA, and vs 83.3 ± 6.1 years U-GA; p = 0.0004 and p= <0.0001, respectively). Mean BCVA, mean GA area at NIR and at FAF images, foveal sparing and multifocal versus unifocal GA distribution and mean CRT were not significantly different among groups. GA area was wider on NIR versus FAF in all groups, significantly in B-GA and U-GA groups (11.7 ± 7.6 mm2 vs 10.6 ± 7.1 mm2, p = 0.0087 in B-GA; 7.8 ± 9.2 mm2 vs 7.7 ± 9.4 mm2, p = 0.004 in U-GA). The number of HRF was significantly higher in U-GA compared to B-GA and to EMAP (47.4 ± 7.1 vs 31.6 ± 7.3 B-GA and 28.0 ± 4.9 EMAP, p < 0.0001 for both), while mean HRF number did not significantly differ between B-GA and EMAP (p = 0.1960). HRF count correlated only to CRT, positively in B-GA and negatively in U-GA group. The increase of small HRF, which mirrors retinal microglial activation, characterizes eyes with unilateral GA (and MNV in the fellow eye) but not eyes with bilateral GA or EMAP. The role of activated microglia in the retina of GA eyes needs to be better investigated, mainly considering the actual and new therapeutic strategies with which to reduce either the development or progression of the atrophic macular changes
Neuroinflammation in Radiation Maculopathy: A Pathophysiologic and Imaging Perspective
Full text linkBackground: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication
DICER1 Syndrome Discovered Through an Eye Tumor
No full textThis case report describes a patient with medulloepithelioma of the ciliary body that was subsequently diagnosed as DICER1 syndrome
Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report
No full textPurpose To report and investigate proptosis in a young girl with Noonan syndrome. Methods Observational case report. Results A 16-year-old girl affected by Noonan syndrome underwent a complete ophthalmological examination showing bilateral proptosis with hypofunction of lateral rectus and superior oblique muscles. Visual acuity, color discrimination and fundus examination were unremarkable. The orbital MRI showed bilateral proptosis and symmetrical enlargement of extraocular muscles, with bellies thickening and tendon sparing. The young patient also complained restrictive hypertrophic cardiomyopathy. Conclusions Proptosis is an uncommon ocular manifestation of Noonan syndrome and its pathophysiology has never been clarified. The MRI evidence of extraocular muscles enlargement associated with hypertrophic cardiomyopathy, led us to hypothesize a common altered pathway beneath these features, more specifically the MAP kinase pathway, since extraocular and cardiac muscles share a mesenchymal embryological origin
Chemotherapy Induced Corneal Changes Assessed by Corneal Confocal Microscopy: A Review
Full text linkThe eye, and the cornea in particular, is a common site of chemotherapy induced toxicity, and ocular side effects of both traditional and novel agents have been reported. Corneal confocal microscopy (CCM) is an in vivo technique that allows for the study of all the corneal layers in an easy, non-invasive and reproducible way via the direct visualization of corneal cell morphologies as well as of sub-basal nerve plexus. Thus, it represents a useful way to identify and monitor chemotherapy induced corneal alterations. This work aims to review the use of CCM in identifying corneal toxicity secondary to chemotherapy treatment, as regards both corneal nerves alterations in the setting of chemotherapy induced peripheral neuropathy (CIPN) and other corneal structure changes, particularly involving the corneal epithelium
Chorioretinal Side Effects of Therapeutic Ocular Irradiation: A Multimodal Imaging Approach
Full text linkRadiation chorioretinopathy, radiation maculopathy, and radiation optic neuropathy are the major complications of ophthalmic radiotherapy. Optical coherence tomography (OCT) and OCT angiography (OCTA) are revolutionary imaging methods, allowing the visualization of the retinal cellular architecture and the retinal vascular system, respectively. In recent years this multimodal imaging approach has been applied to several retinal disease, but its role in the clinical characterization of retinal complications secondary to ophthalmic radiotherapy has not yet been defined. The purpose of this review is to critically evaluate the role of OCT and OCTA in the clinical assessment of radiation-induced chorioretinopathy, maculopathy, and optic neuropathy
RADIATION MACULOPATHY IS ANTICIPATED BY OCT HYPERREFLECTIVE RETINAL FOCI
No full textPurpose: To investigate, by means of spectral domain optical coherence tomography (SD-OCT), retinal reflectivity changes as an early biomarker anticipating radiation induced macular edema (ME) in patients treated by Iodine-125 (I-125) brachytherapy. Methods: Thirty patients planned for I-125 brachytherapy because of uveal melanoma (UM) were prospectively included and followed every 4 months for 5 years. Reflectivity alterations, namely hyperreflective retinal foci (HRF) were characterized and counted by two independent masked examiners by means of SD-OCT imaging. HRF were defined as discrete intraretinal reflectivity changes ≤30μm, with reflectivity similar to nerve fiber layer and without back shadowing. Results: ME occurred in seventeen patients 24.2 ±15.1 months (group 1) after irradiation. Thirteen patients showed no signs of ME at 5-year follow-up (group 2). The number of HRF was statistically higher in sequential visits until the evidence of ME in group 1 vs group 2 (p<0.0001). In group 1, HRF at the follow-up before the evidence of ME were significantly related to the OCT central subfield thickness at ME appearance (P=0.0002, r2=0.6129). The intergrader agreement was almost perfect (ICC=0.80). Conclusions: HRF may be considered as an early in vivo imaging biomarker of retinal inflammatory response to ocular irradiation, anticipating the development of radiation maculopathy
Expression of GNAQ, BAP1, SF3B1, and EIF1AX Proteins in the Aqueous Humor of Eyes Affected by Uveal Melanoma
Full text linkPurpose: The purpose of this study was to quantify specific aqueous humor (AH) proteins in eyes affected by posterior uveal melanoma (UM). Methods: Thirty-six eyes affected by primary UM were included. Tumor thickness and largest basal diameter were specific clinical characteristics. Tumors were staged with the American Joint Commission on Cancer Eighth Edition (AJCC) classification. During the brachytherapy (Iodine-125) surgical procedure, both the AH sample collection and the 25-gauge transscleral fine needle aspiration biopsy (FNAB) were performed. AH samples were analyzed by immunoprecipitation and SDS PAGE techniques to quantify GNAQ, BAP1, SF3B1, and EIF1AX proteins. Cytologic material underwent fluorescence in situ hybridization for chromosome 3. The AH of 36 healthy eyes was used as the control group. Cluster analysis of groups was also performed. Results: Compared with the control group, significantly higher protein levels of: GNAQ (P = 0.02), BAP1 (P = 0.01), and SF3B1 (P = 0.02) were detected in eyes with UM. Cluster analysis of UM group revealed 2 clusters, one showing higher expression of GNAQ and BAP1 protein and one of EIF1AX protein. Moreover, the 2 clusters corresponded with the chromosome 3 status of UM. Conclusions: Specific and selected proteins may be detected in the AH of eyes affected by UM. These findings confirm the possibilities provided by AH analysis in UM
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