Circulating miR-146a predicts glucocorticoid response in thyroid eye disease

Objective: Thyroid eye disease (TED) is an immune-mediated disorder of the eye. Intravenous glucocorticoid (GC) is the first-line treatment for patients with active moderate-to-severe TED. However, the response rate is between 5 0% and 80%. There are still no simple and reliable markers of responsiveness to G C therapy. We aimed to explore the possible role of miR-146a and miR-21 as predictors of responsiveness to GC treatment in TED. Methods: We carried out a prospective longitudinal study on 30 consecutive adult patients with active moderate-to-severe TED and eligible for GC therapy. All patients received the standard GC treatment with methylprednisolone iv. In cases of progressive worsening of Gorman Score for diplopia or with duction restrict ion <30° in at least two consecutive controls, patients also underwent orbital radiotherapy. Response to GC treatment was defined as a decrease of two or more points in the clinical activity score (CAS) or CAS <4/10 at 24 weeks. Circulating miRNAs were extract ed from patients’ serum and quantified by real-time PCR. Results: Twenty-three (77%) patients responded to GC. Thyroid surgery, higher CAS, greater proptosis and higher pre-treatment circulating levels of miR-146a emerged as predictive factors of responsiveness to GC. A ROC analysis revealed that miR-146a could predict responsiveness to GC with a positive predictive value of 100%. Conclusion: This is the first study investigating the role of pre-treatment circulating miR-21 and miR-146a to predict responsiveness to GC in TED. miR-146a emerged as a simple, objective, new marker of GC sensitivity that could be used to avoid ineffective administration of GC therapy to TED patients

Radiation Maculopathy is Anticipated by OCT Hyperreflective Retinal Foci: a Large, Prospective Confirmation study

Purpose: 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

Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report

Purpose 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

Chorioretinal Side Effects of Therapeutic Ocular Irradiation: A Multimodal Imaging Approach

Radiation 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

Corneal Confocal Microscopy as a Quantitative Imaging Biomarker of Diabetic Peripheral Neuropathy: A Review

Distal symmetric polyneuropathy (DPN), particularly chronic sensorimotor DPN, represents one of the most frequent complications of diabetes, affecting 50% of diabetic patients and causing an enormous financial burden. Whilst diagnostic methods exist to detect and monitor this condition, they have significant limitations, mainly due to their high subjectivity, invasiveness, and non-repeatability. Corneal confocal microscopy (CCM) is an in vivo, non-invasive, and reproducible diagnostic technique for the study of all corneal layers including the sub-basal nerve plexus, which represents part of the peripheral nervous system. We reviewed the current literature on the use of CCM as an instrument in the assessment of diabetic patients, particularly focusing on its role in the study of sub-basal nerve plexus alterations as a marker of DPN. CCM has been demonstrated to be a valid in vivo tool to detect early sub-basal nerve plexus damage in adult and pediatric diabetic patients, correlating with the severity of DPN. Despite its great potential, CCM has still limited application in daily clinical practice, and more efforts still need to be made to allow the dissemination of this technique among doctors taking care of diabetic patients

Comparison of 50° handheld fundus camera versus ultra-widefield table-top fundus camera for diabetic retinopathy detection and grading

ObjectivesTo compare the performance of a handheld fundus camera with standard 50 degrees visual field to ultra-widefield (UWF) table-top fundus camera in diabetic retinopathy (DR) detection and grading.MethodsPatients affected by diabetes mellitus and referred to our diabetic retinopathy clinic were enroled and underwent fundus photography in mydriasis. All photos were taken using the ultra-widefield table-top fundus camera Zeiss Clarus (TM) 500 (four fields per eye) and the Optomed Aurora (R) handheld fundus camera (3 fields per eye). The following parameters were analysed: the gradability of the images, the grade of DR, and diabetic maculopathy (DM), the presence of hypertensive retinopathy (HR) and the presence of other ocular diseases.ResultsWe enroled 759 eyes of 384 diabetic patients and analysed 5313 fundus photos. The handheld fundus camera obtained a sensitivity of 84.2% and specificity of 95.4% for referable cases. Moreover, it obtained, compared to UWF, an almost perfect agreement with linear weighting for DR, DM and HR (k = 0.877, k = 0.854, and k = 0.961, respectively). The lowest sensitivity was achieved for proliferative DR (58.7% sensitivity, 100% specificity).ConclusionsOptomed Aurora (R) handheld fundus camera imaging showed a strong agreement compared to UWF in grading DR, considering all DR and DM grades, in mydriasis. However, the use of UWF imaging increases the detection of referable eyes

Hyperreflective Intraretinal Spots in Diabetics without and with Nonproliferative Diabetic Retinopathy: An In Vivo Study Using Spectral Domain OCT

Purpose. To evaluate the presence of hyperreflective spots (HRS) in diabetic patients without clinically detectable retinopathy (no DR) or with nonproliferative mild to moderate retinopathy (DR) without macular edema, and compare the results to controls. Methods. 36 subjects were enrolled: 12 with no DR, 12 with DR, and 12 normal subjects who served as controls. All studied subjects underwent full ophthalmologic examination and spectral domain optical coherence tomography (SD-OCT). SD-OCT images were analyzed to measure and localize HRS. Each image was analyzed by two independent, masked examiners. Results. The number of HRS was significantly higher in both diabetics without and with retinopathy versus controls (P<0.05) and in diabetics with retinopathy versus diabetics without retinopathy (P<0.05). The HRS were mainly located in the inner retina layers (inner limiting membrane, ganglion cell layer, and inner nuclear layer). The intraobserver and interobserver agreement was almost perfect (κ> 0.9). Conclusions. SD-OCT hyperreflective spots are present in diabetic eyes even when clinical retinopathy is undetectable. Their number increases with progressing retinopathy. Initially, HRS are mainly located in the inner retina, where the resident microglia is present. With progressing retinopathy, HRS reach the outer retinal layer. HRS may represent a surrogate of microglial activation in diabetic retina

Early Microvascular and Oscillatory Potentials Changes in Human Diabetic Retina: Amacrine Cells and the Intraretinal Neurovascular Crosstalk

To analyze the early microvascular retinal changes and oscillatory potentials alterations secondary to diabetic retinal damage, 44 eyes of 22 diabetic patients without and with mild diabetic retinopathy (DR) and 18 eyes of 9 healthy controls were examined. All subjects underwent spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCTA), and electroretinography of oscillatory potentials (OPs). At OCTA, vessel area density (VAD), vessel length fraction (VLF), and fractal dimension (FD) were significantly reduced in the superficial vascular plexus (SVP), VLF and FD in the intermediate capillary plexus (ICP), and FD in the deep capillary plexus (DCP) in the diabetic group compared to the control group. The amplitude (A) of OP2, OP3, OP4 and the sum of OPs were significantly reduced in the diabetic group versus the controls, and the last two parameters were reduced also in patients without DR versus the controls. Moreover, in the diabetic group, a significant direct correlation was found between the A of OP1, OP2, OP3 and sOP and the VLF and FD in the SVP, while a statistically significant inverse correlation was found between the A of OP3 and OP4 and the VDI in the ICP and DCP. The reduced oscillatory potentials suggest a precocious involvement of amacrine cells in diabetic eyes, independently of DR presence, and their correlation with vascular parameters underlines the relevance of the crosstalk between these cells and vascular components in the pathophysiology of this chronic disease

Diabetic Macular Edema Treated with 577-nm Subthreshold Micropulse Laser: A Real-Life, Long-Term Study

The aim of this study was to evaluate the long-term efficacy and safety of 577-nm subthreshold micropulse laser (SMPL) treatment in a large population of patients affected by mild diabetic macular edema (DME) in a real-life setting. We retrospectively evaluated 134 eyes affected by previously untreated center-involving mild DME, and treated with 577-nm SMPL, using fixed parameters. Retreatment was performed at 3 months, in case of persistent retinal thickening. Optical coherence tomography (OCT), along with short and near-infrared fundus autofluorescence, were used to confirm long-term safety. At the end of at least one year follow-up, a significant improvement in visual acuity was documented, compared to baseline (77.3 +/- 4.5 and 79.4 +/- 4.4 ETDRS score at baseline and at final follow-up, respectively), as well as a reduction in the mean retinal thickness of the thickest ETDRS macular sector at baseline. A reduction in the central retinal thickness and the mean thickness of the nine ETDRS sectors was also found, without reaching statistical significance. No patients required intravitreal injections. No adverse effects were detected. This study suggests that 577-nm SMPL is a safe and repeatable treatment for mild DME that may be applied to real-life clinical settings using fixed parameters and protocols