Hyperreflective choroidal foci in diabetic eyes with and without macular edema: Novel insights on diabetic choroidopathy.

Histopathologic 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 < 0.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC >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.

A highly efficient catalytic method for the synthesis of phosphite diesters.

In contrast to conventional methods that rely on stoichiometric activation of phosphonylating reagents, we have developed a highly efficient catalytic method for the synthesis of phosphite diesters using a readily available phosphonylation reagent and alcohols with environmentally benign Zn(ii) catalysts. Two alcohols could be introduced consecutively on the P center with release of trifluoroethanol as the sole byproduct, without any additive, under mild conditions. The products could be oxidized smoothly to access phosphate triesters. A range of alcohols, including sterically demanding and highly functionalized alcohols such as carbohydrates and nucleosides, can be applied in this reaction.

Correlation between retinal sensitivity and retinal vascular perfusion after idiopathic epiretinal membrane peeling.

BACKGROUND: To evaluate the correlations between anatomical and functional changes after idiopathic epiretinal membrane (iERM) surgery. METHODS: In this prospective, observational, single-center study, consecutive patients who underwent iERM peeling were enrolled. Reported data were pre- and postoperative best-corrected visual acuity (BCVA), retinal sensitivity (RS) and fixation stability values on microperimetry, structural macular features on SD-OCT and OCTA. RS of foveal and parafoveal area was analysed and two sub-groups were identified whether RS improved or remained unchanged/worsened after surgery; consequently, vascular perfusion density (VPD) of the same area was studied. RESULTS: Twenty-nine eyes of 29 patients were examined. The post-operative improvement in terms of BCVA, RS and fixation within the central 4 degrees was significant (p < 0.001, p < 0.001, p = 0.001), as well as the foveal thickness and macular volume change/reduction (p < 0.001). The pre-operative superficial VPD, choriocapillaris VPD and capillary free zone (CFZ) area were significantly reduced compared to the fellow healthy eye (p = 0.001, p = 0.02, p < 0.001). Choriocapillaris VPD showed a statistically significant increase after surgery (p < 0.02). Superficial, deep and choriocapillaris VPD of the improved RS group showed a significant increase both in foveal (p = 0.03, p = 0.03, p = 0.01) and parafoveal areas (p = 0.01, p = 0.03, p = 0.001). CONCLUSIONS: We reported a higher VPD in the retinal area that experienced a retinal sensitivity improvement 6 months after ERM surgery. This result objectifies the tight bond between visual function and retinal perfusion in ERM patients.

The Disorganization of Retinal Inner Layers Is Correlated to Müller Cells Impairment in Diabetic Macular Edema: An Imaging and Omics Study.

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter.

Artificial intelligence in diabetic retinopathy screening: clinical assessment using handheld fundus camera in a real-life setting.

AIM: Diabetic retinopathy (DR) represents the main cause of vision loss among working age people. A prompt screening of this condition may prevent its worst complications. This study aims to validate the in-built artificial intelligence (AI) algorithm Selena+ of a handheld fundus camera (Optomed Aurora, Optomed, Oulu, Finland) in a first line screening of a real-world clinical setting. METHODS: It was an observational cross-sectional study including 256 eyes of 256 consecutive patients. The sample included both diabetic and non-diabetic patients. Each patient received a 50°, macula centered, non-mydriatic fundus photography and, after pupil dilation, a complete fundus examination by an experienced retina specialist. All images were after analyzed by a skilled operator and by the AI algorithm. The results of the three procedures were then compared. RESULTS: The agreement between the operator-based fundus analysis in bio-microscopy and the fundus photographs was of 100%. Among the DR patients the AI algorithm revealed signs of DR in 121 out of 125 subjects (96.8%) and no signs of DR 122 of the 126 non-diabetic patients (96.8%). The sensitivity of the AI algorithm was 96.8% and the specificity 96.8%. The overall concordance coefficient k (95% CI) between AI-based assessment and fundus biomicroscopy was 0.935 (0.891-0.979). CONCLUSIONS: The Aurora fundus camera is effective in a first line screening of DR. Its in-built AI software can be considered a reliable tool to automatically identify the presence of signs of DR and therefore employed as a promising resource in large screening campaigns.

Quantitative and Qualitative Assessments of Retinal Structure with Variable A-Scan Rate Spectralis OCT: Insights into IPL Multilaminarity.

The aim of this study was to evaluate the qualitative and quantitative differences between 20 and 85 kHz A-scan rate optical coherence tomography (OCT) images acquired by spectral domain OCT. The study included 60 healthy subjects analyzed with horizontal linear scans with a variable A-scan rate (SHIFT technology, Heidelberg Engineering, Heidelberg, Germany). The retinal thickness measurement of each retinal layer was performed in three different positions (subfoveal, nasal, and temporal). The qualitative assessment was performed by two independent observers who rated every image with a score ranging from 1 ("sufficient") to 3 ("excellent") on the basis of three parameters: visualization of the vitreo-retinal interface, characterization of the retinal layers, and visualization of the sclero-choroidal interface. No statistically significant differences in terms of retinal layer thickness between the two A-scan rate scans were observed (p > 0.05). The coefficient of variation of the retinal thickness values was lower in the 20 kHz group (25.8% versus 30.1% with the 85 kHz). The 20 kHz images showed a higher quality index for both observers. An inner plexiform layer (IPL) multilaminarity was detected in 78.3% of patients from the 20 kHz group and in 40% of patients from the 85 kHz group (p < 0.05).

Validation of an Automated Artificial Intelligence Algorithm for the Quantification of Major OCT Parameters in Diabetic Macular Edema.

Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738-0.924), 0.934 (0.886-0.982), and 0.936 (0.894-0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes.

Retinal obliterative vasculitis associated to contralateral retinal neovascularization in membranoproliferative glomerulonephritis.

PURPOSE: To report our experience with a peculiar case of asynchronous bilateral retinal vascular occlusion in a patient suffering from membranoproliferative glomerulonephritis. CASE REPORT: A 57-year-old dialysed male affected by membranoproliferative glomerulonephritis who underwent kidney transplantation complained of a sudden vision loss in his right eye (RE). His best-corrected visual acuity (BCVA) was 20/40 in RE and 20/20 in the left eye (LE); ophthalmological and fluorangiographic examinations revealed unilateral retinal obliterative vasculitis with panuveitis and apparent sparing of contralateral eye. About 6 months later the patient developed a branch retinal vein occlusion associated with a papillary neovascular membrane in LE. Corticosteroid therapy was administered and immunosuppressant dosage was increased with macular oedema reduction in both events. CONCLUSION: We report a case of unilateral retinal obliterative vasculitis and subsequent contralateral retinal neovascularization and branch retinal vein occlusion in a patient affected by membranoproliferative glomerulonephritis.

Sclerochoroidal calcification as an incidental finding during oncological staging of a patient with parotid malignancy: A case report.

INTRODUCTION: Incidental finding of mass lesion in the choroid represents a very challenging situation for the ophthalmologist. We describe a case of an incidental, computed tomography (CT)-hyperintense, choroidal lesion in a patient with parotid malignancy and renal failure, and how multimodal imaging helped us reaching the correct diagnosis. CASE DESCRIPTION: A 63-year-old man with parotid gland malignancy was brought to our attention because preoperative staging CT showed a hyperintense choroidal lesion of the right eye. Fundus examination showed a yellow elevated lesion near the superior temporal branch retinal artery. Enhanced depth imaging optical coherence tomography (EDI-OCT), A- and B-scan ultrasonography, and Indocyanine Green Angiography (ICGA) allowed us to exclude a malignant lesion and to diagnose a sclerochoroidal calcification. CONCLUSION: Multimodal imaging can guide the clinician to choose the appropriate therapeutic approach even in case of uncommon conditions like sclerochoroidal calcification.

Zinc-Catalyzed Phosphonylation of Alcohols with Alkyl Phosphites.

In the presence of a catalytic amount of either Zn(acac)2 or bis(2,2,6,6-tetramethyl-3,5-heptanedionato)zinc(II) (Zn(TMHD)2), primary, secondary, and tertiary alcohol substituents on a wide range of substrates, including acyclic and cyclic structures, carbohydrates, steroids, and amino acids, reacted with dimethyl phosphite to afford the corresponding H-phosphonate diesters in high to excellent yields.