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Stepwise approach for fundus imaging in the diagnosis and management of posterior uveitis.
Agarwal, A, Pichi, F, Invernizzi, A, Grewal, DS, Singh, RB, Upadhyay, A
Survey of ophthalmology. 2023;(3):446-480
Abstract
An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a 'multimodal' approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.
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Diabetic retinopathy in the pediatric population: Pathophysiology, screening, current and future treatments.
Invernizzi, A, Chhablani, J, Viola, F, Gabrielle, PH, Zarranz-Ventura, J, Staurenghi, G
Pharmacological research. 2023;:106670
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Abstract
Diabetic retinopathy (DR) is a sight threatening complication of diabetes mellitus (DM). The incidence of DR in the pediatric population has increased in the last two decades and it is expected to further rise in the future, following the increase in DM prevalence and obesity in youth. As early stages of the retinal disease are asymptomatic, screening programs are of extreme importance to guarantee a prompt diagnosis and avoid progression to more advanced, sight threatening stages. The management of DR comprises a wide range of actions starting from glycemic control, continuing with systemic and local medical treatments, up to para-surgical and surgical approaches to deal with the more aggressive complications. In this review we will describe the pathophysiology of DR trying to understand all the possible targets for currently available or future treatments. We will briefly consider the impact of screening techniques, screening strategies and their social and economic impact. Finally a large part of the review will be dedicated to medical and surgical treatments for DR including both currently available and under development therapies. Most of the available data in the literature on DR are focused on the adult population. The aim of our work is to provide clinicians and researchers with a comprehensive overview of the state of the art regarding DR in the pediatric population, considering the increasing numbers of this diseases in youth and the inevitable consequences that such a chronic disease could have if poorly managed in children.
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Nanoemulsions of Clove Oil Stabilized with Chitosan Oleate-Antioxidant and Wound-Healing Activity.
Perteghella, S, Garzoni, A, Invernizzi, A, Sorrenti, M, Boselli, C, Icaro Cornaglia, A, Dondi, D, Lazzaroni, S, Marrubini, G, Caramella, C, et al
Antioxidants (Basel, Switzerland). 2023;(2)
Abstract
Clove oil (CO) is a powerful antioxidant essential oil (EO) with anti-inflammatory, anesthetic, and anti-infective properties. It can be therefore considered a good candidate for wound-healing applications, especially for chronic or diabetic wounds or burns, where the balance of reactive oxygen species (ROS) production and detoxification is altered. However, EOs require suitable formulations to be efficiently administered in moist wound environments. Chitosan hydrophobically modified by an ionic interaction with oleic acid (chitosan oleate, CSO) was used in the present work to stabilize CO nanoemulsions (NEs). The dimensions of the NE were maintained at around 300 nm as the volume distribution for up to six months, and the CO content did not decrease to under 80% over 4 months, confirming the good stabilizing properties of CSO. The antioxidant properties of the CO NE were evaluated in vitro by a 2,2-diphenil-2-picrylhydrazyl hydrate (DPPH) assay, and in fibroblast cell lines by electron paramagnetic resonance (EPR) using α-phenyl-N-tert-butyl nitrone (PBN) as a spin trap; a protective effect was obtained comparable to that obtained with α-tocopherol treatment. In a murine burn model, the ability of CO formulations to favor macroscopic wound closure was evidenced, and a histological analysis revealed a positive effect of the CO NE on the reparation of the lesion after 18 days. Samples of wounds at 7 days were subjected to a histological analysis and parallel dosage of lipid peroxidation by means of a thiobarbituric acid-reactive substances (TBARS) assay, confirming the antioxidant and anti-inflammatory activity of the CO NE.
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Imaging-based Assessment of Choriocapillaris: A Comprehensive Review.
Singh, RB, Perepelkina, T, Testi, I, Young, BK, Mirza, T, Invernizzi, A, Biswas, J, Agarwal, A
Seminars in ophthalmology. 2023;(5):405-426
Abstract
PURPOSE Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.
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Local neuroplasticity in adult glaucomatous visual cortex.
Carvalho, J, Invernizzi, A, Martins, J, Renken, RJ, Cornelissen, FW
Scientific reports. 2022;(1):21981
Abstract
The degree to which the adult human visual cortex retains the ability to functionally adapt to damage at the level of the eye remains ill-understood. Previous studies on cortical neuroplasticity primarily focused on the consequences of foveal visual field defects (VFD), yet these findings may not generalize to peripheral defects such as occur in glaucoma. Moreover, recent findings on neuroplasticity are often based on population receptive field (pRF) mapping, but interpreting these results is complicated in the absence of appropriate control conditions. Here, we used fMRI-based neural modeling to assess putative changes in pRFs associated with glaucomatous VFD. We compared the fMRI-signals and pRF in glaucoma participants to those of controls with case-matched simulated VFD. We found that the amplitude of the fMRI-signal is reduced in glaucoma compared to control participants and correlated with disease severity. Furthermore, while coarse retinotopic structure is maintained in all participants with glaucoma, we observed local pRF shifts and enlargements in early visual areas, relative to control participants. These differences suggest that the adult brain retains some degree of local neuroplasticity. This finding has translational relevance, as it is consistent with VFD masking, which prevents glaucoma patients from noticing their VFD and seeking timely treatment.
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COVID-19-Related Retinal Micro-vasculopathy - A Review of Current Evidence.
Teo, KY, Invernizzi, A, Staurenghi, G, Cheung, CMG
American journal of ophthalmology. 2022;:98-110
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Abstract
PURPOSE To evaluate the occurrence of retinal microvasculopathy in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and who developed coronavirus disease (COVID-19). DESIGN Systematic review and meta-analysis. METHODS The Pubmed and Embase databases were comprehensively searched to identify studies that reported retina vascular changes in eyes with COVID-19. Two independent reviewers selected papers and extracted data for analysis. Data of interest were extracted and analyzed in RevMan Web versions 3.3. Quality of evidence was assessed using the National Institute of Health quality assessment tool for a case-control study. RESULTS Thirty-one studies reporting on 1373 subjects (972 COVID-19 and 401 controls) were included. Only case-control studies were included in the pooled analysis. There was a significantly higher likelihood of retinal microvasculopathy in subjects with COVID-19 compared to controls (odds ratio [95% confidence interval], 8.86 [2.54-27.53], P < .01). Optical coherence tomography angiography (OCTA) revealed reduced vessel density and enlarged foveal avascular zone in subjects with COVID-19 compared to controls. CONCLUSIONS The results suggested that COVID-19-related retinal microvasculopathy is a significant ocular manifestation of COVID-19 and may herald future retinal complications. These microvascular impairments might have occurred antecedent to clinically visible changes and could be detected earlier by OCTA. These findings are significant, due to the large numbers with COVID-19, and need to be recognized by ophthalmologists as a potential long-term sequalae of the disease.
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Outer Retinal Layer Thickening Predicts the Onset of Exudative Neovascular Age-Related Macular Degeneration.
Invernizzi, A, Parrulli, S, Monteduro, D, Cereda, MG, Nguyen, V, Staurenghi, G, Cheung, CMG, Gillies, M, Teo, KYC
American journal of ophthalmology. 2021;:19-27
Abstract
PURPOSE To assess changes in outer retinal layer (ORL) thickness before the development of exudative macular neovascularization (MNV) in eyes with age-related macular degeneration. DESIGN Retrospective observational case series. METHODS Eyes with age-related macular degeneration that eventually developed exudative MNV followed with sequential optical coherence tomography for ≥2 years before the exudation occurred were enrolled. The ORL thickness was automatically calculated by the optical coherence tomography software for each sector of the early treatment diabetic retinopathy study map at each follow-up visit. The ORL thickness change from baseline to the day when the exudative MNV developed was compared between sectors that eventually developed exudative MNV and those that did not. RESULTS Forty-seven eyes (47 patients) were included. At baseline (24 ± 3 months before exudative MNV), mean (standard deviation) ORL thickness of sectors that eventually developed exudative MNV was similar to that of sectors that did not (85.2 [8.2] µm vs 86.8 [5.7] µm, P = .08). ORL thickness significantly increased in sectors that developed exudative MNV compared with those that did not (+5.8 [10.4] µm vs -2.8 [3.6] µm, P < .01). The regression model based on these data predicted an increase in ORL thickness from baseline of +4.2% 55 days and +11.1% 30 days before exudative MNV was detected. The ORL thickness of areas that did not develop exudative MNV did not change. CONCLUSION Thickening of the ORL begins in the area where exudative MNV will develop long before the exudation, accelerating significantly in the last 2 months. The occurrence of exudative MNV could be predicted by 2 months using this simple analysis.
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The In Vivo Correlation between Retinal Pigment Epithelium Thickness and Quantitative Fundus Autofluorescence in a White Population.
Cozzi, M, Viola, F, Belotti, M, Cigada, M, Cherepanoff, S, Staurenghi, G, Invernizzi, A
Ophthalmology. Retina. 2021;(4):365-373
Abstract
PURPOSE To investigate the influence of age on the thickness of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex and the quantitative autofluorescence (qAF) and to study the possible correlation existing between these 2 parameters in a healthy White population. DESIGN Cross-sectional, observational study. PARTICIPANTS Healthy White volunteers aged 18 to 65 years. METHODS All subjects underwent spectral domain OCT (SD-OCT) and qAF imaging with the Heidelberg HRA-Spectralis (Heidelberg Engineering, Heidelberg, Germany). Spectral domain OCT images were analyzed using the in-built graph-based automatic segmentation algorithm for single retinal layer identification to assess RPE/BM complex thickness in vivo. The thickness values of both inner and outer rings of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, generated by the software using the "RPE" segmentation, were averaged to obtain a single RPE/BM complex thickness value in each eye. Quantitative autofluorescence images were also evaluated using a dedicated software. The qAF values of 8 subfields forming a ring centered onto the fovea were collected and averaged to obtain a single qAF value (qAF8) in each eye. The correlation among the RPE/BM complex thickness, the qAF value, and the age of the subjects was investigated. MAIN OUTCOME MEASURES The in vivo correlation between RPE/BM complex thickness and qAF. RESULTS A total of 105 eyes from 105 subjects (mean age, 42.1 ± 13.9 years; range, 18-65) were included in the analysis. The mean RPE/BM complex thickness significantly increased with age (r = 0.33, P = 0.0006). The values of qAF also positively increased with age (P < 0.0001). A significant correlation was found between qAF and RPE/BM complex thickness (r = 0.27, P = 0.004). After adjusting for age, iris color, and gender, the correlation remained significant only for subjects aged less than 40 years (P = 0.009). CONCLUSIONS BM complex thickness was significantly co/BM complex thickness increased with age in a healthy White population. A similar increase was found for qAF values. After adjusting for age and iris color, qAF and RPE/BM complex thickness were still correlated in subjects aged less than 40 years. The RPE/BM complex thickness could reflect the lipofuscin/melanolipofuscin accumulation in normal subjects, adding great interest in RPE cell biology.
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Influence of electromagnetic radiation emitted by daily-use electronic devices on the Eyemate® system in-vitro: a feasibility study.
Invernizzi, A, Haykal, S, Lo Faro, V, Pennisi, V, Choritz, L
BMC ophthalmology. 2020;(1):357
Abstract
BACKGROUND Eyemate® is a system for the continual monitoring of intraocular pressure (IOP), composed of an intraocular sensor, and a hand-held reader device. As the eyemate®-IO sensor communicates with the hand-held reader telemetrically, some patients might fear that the electronic devices that they use on a daily basis might somehow interfere with this communication, leading to unreliable measurements of IOP. In this study, we investigated the effect of electromagnetic radiation produced by a number of everyday electronic devices on the measurements made by an eyemate®-IO sensor in-vitro, in an artificial and controlled environment. METHODS The eyemate®-IO sensor was suspended in a sterile 0.9% sodium chloride solution and placed in a water bath at 37 °C. The antenna, connected to a laptop for recording the data, was positioned at a fixed distance of 1 cm from the sensor. Approximately 2 hrs of "quasi-continuous" measurements were recorded for the baseline and for a cordless phone, a smart-phone and a laptop. Repeated measures ANOVA was used to compare any possible differences between the baseline and the tested devices. RESULTS For baseline measurements, the sensor maintained a steady-state, resulting in a flat profile at a mean pressure reading of 0.795 ± 0.45 hPa, with no apparent drift. No statistically significant difference (p = 0.332) was found between the fluctuations in the baseline and the tested devices (phone: 0.76 ± 0.41 hPa; cordless: 0.787 ± 0.26 hPa; laptop: 0.775 ± 0.39 hPa). CONCLUSION In our in-vitro environment, we found no evidence of signal drifts or fluctuations associated with the tested devices, thus showing a lack of electromagnetic interference with data transmission in the tested frequency ranges.
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Foveal pRF properties in the visual cortex depend on the extent of stimulated visual field.
Prabhakaran, GT, Carvalho, J, Invernizzi, A, Kanowski, M, Renken, RJ, Cornelissen, FW, Hoffmann, MB
NeuroImage. 2020;:117250
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Abstract
Previous studies demonstrated that alterations in functional MRI derived receptive field (pRF) properties in cortical projection zones of retinal lesions can erroneously be mistaken for cortical large-scale reorganization in response to visual system pathologies. We tested, whether such confounds are also evident in the normal cortical projection zone of the fovea for simulated peripheral visual field defects. We applied fMRI-based visual field mapping of the central visual field at 3 T in eight controls to compare the pRF properties of the central visual field of a reference condition (stimulus radius: 14°) and two conditions with simulated peripheral visual field defect, i.e., with a peripheral gray mask, stimulating only the central 7° or 4° radius. We quantified, for the cortical representation of the actually stimulated visual field, the changes in the position and size of the pRFs associated with reduced peripheral stimulation using conventional and advanced pRF modeling. We found foveal pRF-positions (≤3°) to be significantly shifted towards the periphery (p<0.05, corrected). These pRF-shifts were largest for the 4° condition [visual area (mean eccentricity shift): V1 (0.9°), V2 (0.9°), V3 (1.0°)], but also evident for the 7° condition [V1 (0.5°), V2 (0.5°), V3 (0.9°)]. Further, an overall enlargement of pRF-sizes was observed. These findings indicate the dependence of foveal pRF parameters on the spatial extent of the stimulated visual field and are likely associated with methodological biases and/or physiological mechanisms. Consequently, our results imply that, previously reported similar findings in patients with actual peripheral scotomas need to be interpreted with caution and indicate the need for adequate control conditions in investigations of visual cortex reorganization.