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The nature of bile duct-like (oval) cells proliferating during chemical hepatocarcinogenesis has been controversial. To investigate this issue further, the authors compared the hepatic distribution of albumin (ALB) and alpha-fetoprotein (AFP) mRNAs in rats in which oval cell proliferation was induced by feeding a choline-devoid diet containing 0.1% ethionine (CDE, a hepatocarcinogenic diet) with that in normal rats and in rats in which biliary epithelial cell hyperplasia was induced by either bile duct ligation or feeding alpha-naphthylisothiocyanate (ANIT). Northern blot analysis in parenchymal and nonparenchymal liver cells isolated from these animals demonstrated that ALB mRNA was present in the hepatocytes of both control and experimental animals, whereas this transcript was detected in nonparenchymal epithelial cells only in CDE-fed rats. Alpha-fetoprotein mRNA was not seen in either parenchymal or nonparenchymal cells isolated from normal or hyperplastic livers induced by bile duct ligation or ANIT feeding. In CDE-fed rats, however, both parenchymal and nonparenchymal cell populations displayed AFP message. In situ hybridization directly demonstrated nonparenchymal cell expression of both ALB and AFP transcripts in CDE-fed rats. Most surprisingly, ALB and AFP mRNAs were also detected by in situ hybridization in occasional nonparenchymal cells located in portal tracts near the limiting plate in normal liver, as well as under conditions associated with bile duct hyperplasia. Immunohistochemical studies of intermediate filament proteins, cytokeratin 19 (a marker of glandular epithelia), vimentin (a marker of mesenchymal lineage), and desmin (a marker of muscle cell differentiation) demonstrated that oval cells, as well as normal and hyperplastic bile duct cells, were positive for cytokeratin 19 and negative for both vimentin and desmin. Cytokeratin-positive oval cells formed duct profiles and were connected to preexisting ductules and ducts. These results are construed to suggest that oval cells proliferating during CDE hepatocarcinogenesis are derived from epithelial cells within the biliary tree. The presence of cells with similar morphologic appearance, periportal location, and AFP and ALB expression in normal liver suggests that these cells may be the progenitors of oval cells induced by some carcinogenic regimens.

Optical coherence tomography angiography (OCTA) provides several data regarding the status of retinal capillaries. This information can be further enlarged by employing quantitative metrics, such as vessel density (VD). A mandatory preliminary step of OCTA quantification is image binarization, a procedure used to highlight retinal capillaries on empty background. Although several binarization thresholds exist, no consensus is reached about the thresholding technique to be used. In this study, we tested thirteen binarization thresholds on a dataset made by thirty volunteers. The aim was to assess the impact of binarization techniques on: (I) detection of retinal capillaries, assessed by the calculation of overlapping percentages between binarized and original images; (II) quantitative OCTA metrics, including VD, vessel tortuosity (VT) and vessel dispersion (Vdisp); (III) foveal avascular zone (FAZ) detection. Our findings showed Huang, Li, Mean and Percentile as highly reliable binarization thresholds (p

Background: To perform a quantitative optical coherence tomography (OCT) angiography (OCTA) analysis of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD), central serous chorioretinopathy (CSC) and best vitelliform macular dystrophy (BVMD), with the aim of highlighting quantitative features indicating different clinical entities. Methods: Study design: prospective, interventional. We recruited patients affected by AMD, CSC or BVMD, complicated by naive MNV. All patients underwent complete ophthalmologic examination and multimodal imaging. They were treated with anti-VEGF injections, following a pro-re-nata regimen. The ensuing follow-up lasted 1 year. Quantitative dye-based angiography, OCT, and OCTA parameters were analysed to obtain cutoff values able to distinguish two clinically different patient subgroups for each retinal disease. The main outcome measures were best-corrected visual acuity (BCVA), central macular thickness, vessel density of superficial, deep and choriocapillaris plexa, vessel tortuosity (VT) of MNV, vessel dispersion of MNV, number of injections, MNV/leakage ratio, MNV size, speckled fluorescence, and outer retinal atrophy. Results: Ninety-eight eyes affected by MNV (98 patients) were analysed. These included 66 eyes affected by AMD, 18 displaying CSC, and 14 eyes with BVMD. BCVA was alike in the three groups, both at baseline and after 1 year (p > 0.05). An MNV VT cutoff of 8.40 at baseline detected two patient subgroups differing significantly in terms of morpho-functional features, found both at baseline and at the end of the follow-up. Conclusions: Quantitative OCTA suggested that the MNV’s VT might be able to provide a better characterization of two different morpho-functional manifestations in AMD, CSC and BVMD.

Introduction: The fluocinolone acetonide (FAc) intravitreal drug-delivery system implant is a recent, second-line, intravitreal drug for the management of diabetic macular edema (DME). FAc acts against DME with a major anti-inflammatory effect. Despite the already proved efficacy, a number of patients still show persistent DME and require anti-VEGF retreatment. The main aim of the present study was to assess the relationship between quantitative biomarkers of inflammation and both DME recovery and the need for additional anti-VEGF in eyes treated by FAc implant. Methods: The study was designed as prospective and interventional with 1 year of follow-up. We analyzed structural optical coherence tomography (OCT) quantitative biomarkers of inflammation, namely choroidal hyperreflective foci (HF) and the choroidal vascularity index (CVI), and we assessed the relationship with other clinically relevant biomarkers and the outcome achieved after 1year. Moreover, we stratified DME eyes in good and poor responders to FAc implant to highlight clinically relevant differences. Results: Our study included 50 eyes (50 patients) treated by FAc implant. We found significant best-corrected visual acuity (BCVA) and central macular thickness (CMT) improvements after 1year. Good responders started with worse visual acuity and higher CMT than poor responders, but gained letters significantly at the end of the follow-up, whereas poor responders showed stable BCVA values. Good responders were characterized by significantly higher choroidal HF and lower CVI than poor responders. Poor responders required significantly higher additional anti-VEGF treatments. Conclusions: Quantitative structural OCT biomarkers of inflammation allowed distinguishing different inflammatory profiles of DME. The inflammatory component helped to categorize DME eyes in good and poor responders to FAc implant.

ObjectiveAim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome.MethodsThis is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries.ResultsA total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems.ConclusionsThe development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT 05200715.

ObjectiveThe aim of this paper is to present the AutoInflammatory Disease Alliance (AIDA) international Registry dedicated to Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome, describing its design, construction, and modalities of dissemination.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument designed for the retrospective and prospective collection of real-life data. Data gathering is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain real-world evidence for daily patients' management. The Registry may potentially communicate with other on-line tools dedicated to VEXAS syndrome, thus enhancing international collaboration and data sharing for research purposes. The Registry is practical enough to be easily modified to meet future needs regarding VEXAS syndrome.ResultsTo date (April 22nd, 2022), 113 Centers from 23 Countries in 4 continents have been involved; 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) are currently able to access the registry for data entry (or data sharing) and collection. The Registry includes 4,952 fields organized into 18 instruments designed to fully describe patient's details about demographics, clinical manifestations, symptoms, histologic details about skin and bone marrow biopsies and aspirate, laboratory features, complications, comorbidities, therapies, and healthcare access.ConclusionThis international Registry for patients with VEXAS syndrome will allow the achievement of a comprehensive knowledge about this new disease, with the final goal to obtain real-world evidence for daily clinical practice, especially in relation to the comprehension of this disease about the natural history and the possible therapeutic approaches. This Project can be found on https://clinicaltrials.gov NCT05200715.

To prove the role of high-tech investigation in monitoring corneal morphological changes in patients with neurotrophic keratopathy (NK) using Keratograph 5M (K5M) and anterior segment OCT (AS-OCT), corneal healing was monitored with Keratograph 5M (Oculus, Wetzlar, Germany) and AS-OCT (DRI, Triton, Topcon, Tokyo, Japan) in 13 patients (8F and 5M), aged from 24 to 93 years (67.8 ± 19) with severe NK, who were treated with Cenegermin 0.002% (20 μg/mL) (Oxervate®, Dompè, Farmaceutici Spa, Milan, Italy). The surface defects were evaluated on Keratograph 5M with ImageJ software and the corneal thickness variations were measured using DRI-Triton OCT software. Instrumental procedures were performed at baseline, and after 4 and 8 weeks of the treatment, respectively. The main outcome measures were reduction of the ulcers’ area and corneal thickness recovery. The mean area of the corneal ulcers was reduced between baseline and 4 weeks examination in all patients, and at 8 weeks all ulcers were completely healed. An increase of the corneal thickness was evidenced between the baseline visit and after the 4- and 8-week follow-up, respectively. Additionally, only in collaborating subjects the In Vivo Confocal Microscopy (IVCM) was performed with HRT Rostock Cornea Module (Heidelberg Eng GmbH) to study the corneal nerves fibres. High-tech diagnostics with K5M, AS-OCT and IVCM proved useful in the assessment of corneal morphology and the healing process in patients with NK and could be extended to assess other corneal pathologies.

PURPOSE. The purpose of this study was to investigate the effects of the extension of collateral vessels on the outcomes of eyes affected by central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). METHODS. The study was designed as a cross-sectional case series. Patients affected by CRVO and BRVO were progressively recruited, along with an age- and sex-matched control group of healthy subjects. Structural optical coherence tomography (OCT) and OCT angiography (OCTA; 4.5 × 4.5 mm and 9.0 × 9.0 mm acquisitions) were performed on all participants in order to assess the relationship between the presence of collateral vessels and final anatomical outcomes - central macular thickness (CMT), foveal avascular zone - and functional outcomes - best corrected visual acuity (BCVA). RESULTS. Fifty-six eyes affected by CRVO and 47 eyes affected by BRVO were included. Baseline LogMAR BCVA was 0.41 ± 0.33 LogMAR in CRVO, and 0.39 ± 0.25 LogMAR in BRVO (P < 0.01), improving to 0.20 ± 0.26 LogMAR in CRVO (P < 0.01), and 0.19 ± 0.22 LogMAR in BRVO (P < 0.01). Baseline CMT was 511 ± 214 μm in CRVO and 482 ± 178 μm in BRVO (P > 0.05), decreasing to 328 ± 105 μm (P < 0.01) and 321 ± 78 μm in CRVO and BRVO, respectively (P < 0.01). Collateral vessels were detected in 16 of 56 eyes (29%) in CRVO and in 47 of 47 eyes (100%) in BRVO. Their extension was correlated with worse anatomic and visual outcomes. Remarkably, no correlation was found with peripheral capillary nonperfusion and vessel density impairment. CONCLUSIONS. The present study demonstrates that collateral vessel extension is associated with worse anatomic and functional outcomes in patients affected by CRVO and BRVO.

Background: Gene therapy cannot be yet considered a far perspective, but a tangible therapeutic option in the field of retinal diseases. Although still confined in experimental settings, the preliminary results are promising and provide an overall scenario suggesting that we are not so far from the application of gene therapy in clinical settings. The main aim of this review is to provide a complete and updated overview of the current state of the art and of the future perspectives of gene therapy applied on retinal diseases.Methods: We carefully revised the entire literature to report all the relevant findings related to the experimental procedures and the future scenarios of gene therapy applied in retinal diseases. A clinical background and a detailed description of the genetic features of each retinal disease included are also reported.Results: The current literature strongly support the hope of gene therapy options developed for retinal diseases. Although being considered in advanced stages of investigation for some retinal diseases, such as choroideremia (CHM), retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA), gene therapy is still quite far from a tangible application in clinical practice for other retinal diseases.Conclusions: Gene therapy is an extremely promising therapeutic tool for retinal diseases. The experimental data reported in this review offer a strong hope that gene therapy will be effectively available in clinical practice in the next years.

Background: Glaucoma is a chronic, vision-threatening disease, and a major cause of legal blindness. The current view is no longer limited to the progressive optic nerve injury, since growing evidence strongly support the interpretation of glaucoma as a complex neurodegenerative disease. However, the precise pathogenic mechanisms leading to the onset and progression of central nervous system (CNS) impairment, and the functional consequences of this damage, are still partially understood. The main aim of this review is to provide a complete and updated overview of the current knowledge regarding the CNS involvement in glaucoma, and the possible therapeutic perspectives.Methods: We made a careful survey of the current literature reporting all the relevant findings related to the cognitive dysfunctions occurring in glaucoma, with specific remarks dedicated on the higher-order visual function impairment and the possible employment of neuroprotective agents.Results: The current literature strongly support the interpretation of glaucoma as a multifaceted chronic neurodegenerative disease, widely affecting the CNS. The cognitive impairment may vary in terms of higher-order functions involvement and in the severity of the degeneration. Although several neuroprotective agents are currently available, the development of new molecules represents a major topic of investigation for future clinical trials.Conclusions: Glaucoma earned the right to be fully considered a neurodegenerative disease. Glaucomatous patients may experience a heterogeneous set of visual and cognitive symptoms, progressively deteriorating the quality of life. Neuroprotection is nowadays a necessary therapeutic goal and a future promising way to preserve visual and cognitive functions, thus improving patients’ quality of life.

Background: The aim was to study the relationship between quantitative information provided by optical coherence tomography (OCT) angiography (OCTA) and conventional angiography in macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).Methods: The research was designed as an interventional, prospective study. We included 66 eyes (66 patients) affected by naïve MNV. Multimodal imaging included structural OCT, OCTA, fluorescein angiography (FA), and indocyanine green angiography (ICGA). The follow-up lasted 1 year. Patients were treated by PRN anti-VEGF injections. Based on FA/ICGA examinations, we divided the patients into two categories: low vessel tortuosity (VT) (8.40), correlating VT with the MNV area, leakage area, speckled fluorescence (SF) quadrants and MNV area/leakage area ratio.Results: Mean baseline BCVA was 0.50 ± 0.61 LogMAR, improved to 0.31 ± 0.29 LogMAR after 1 year (p < 0.01), with a mean number of 7 ± 2 anti-VEGF injections. The patients revealed type-1 MNV in 36 eyes (55%), mixed type 1 and 2 MNV in 18 eyes (27%), and type-2 MNV in 12 eyes (18%). MNV eyes in high-VT MNV featured poorer BCVA, CMT, and OCTA parameters, higher SF quadrants, and less exudation, compared with low-VT MNV (p < 0.01). Moreover, 30% of high-VT MNV eyes developed outer retinal atrophy.Conclusions: Low VT MNV turned out to be more exudative at the baseline but less damaging to the outer retinal structures, whereas high VT MNV proved to be less exudative but more prone to lead to atrophic changes and visual function deterioration. VT may be usefully applied to artificial intelligence-based models designed to characterize MNV secondary to AMD.

Background: In this study, we aimed to discriminate high reflectivity and low reflectivity macular neovascularization (MNV) lesions secondary to age-related macular degeneration (AMD)and to assess the influence of blood flow features on the amount of MNV detected by optical coherence tomography angiography (OCTA).Methods: The study was designed as observational, cross-sectional. Type 1 and type 2 MNV lesions were included. All the patients underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and OCTA. MNV size was calculated on early FA for type 2 MNV and on both early and late phases of ICGA for type 1 lesions. From OCTA, we calculated both MNV size and MNV reflectivity. We assessed the agreement between FA/ICGA and OCTA MNV sizes. Moreover, we studied the relationship between MNV reflectivity properties and MNV OCTA detection.Results: Fifty eyes (50 patients) were included. MNV was identified as follows: 35 /70%) type 1 and 15 (30%) type 2. We found a good agreement between early ICGA size and OCTA size for type 1 MNV (2.10 ± 1.91 mm2 vs 2.09 ± 1.87 mm2; p > 0.05), whereas MNV lesions turned out to be remarkably bigger on late ICGA phase (3.41 ± 2.87 mm2; p < 0.01). Interestingly, OCTA well-matched with FA in terms of MNV size for type 2 lesions (2.36 ± 2.15 mm2 vs 2.37 ± 2.25 mm2). MNV reflectivity was higher in type 2 MNV and it was strongly associated with the OCTA ability to reconstruct the neovascular network.Conclusion: Our study quantitatively showed that MNV filling pattern and MNV blood flow reflectivity features influence the OCTA detection of the MNV in its entirety.

Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal.

Retinal vein occlusion is the second most common retinal vascular pathology after diabetic retinopathy and a major cause of vision impairment. Nowadays, both central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) can be well-managed by intravitreal treatments. However, considering the long-life expectance of the patients, few data are present in the literature about the very long-term outcome of CRVO and BRVO. The present study was an interventional, retrospective analysis of the morphological and functional long-term outcome of CRVO and BRVO patients, followed in an Italian referral center. We collected data from 313 eyes (178 CRVO eyes and 135 BRVO eyes). Mean follow-up was 45 ± 25 months (range 12–84 months). Both CRVO and BRVO eyes experience a significant visual acuity improvement secondary to anti-vascular endothelial growth factor/dexamethasone treatments (from 0.57 ± 0.25 to 0.41 ± 0.24 LogMAR in CRVO and from 0.53 ± 0.42 to 0.30 ± 0.41 LogMAR in BRVO, respectively) (p

Purpose. To evaluate the effects of anti-VEGF treatment of neovascular age-related macular degeneration (nAMD) in a real-life clinical setting. Methods. Study design is a retrospective case series. Naïve nAMD patients treated with intravitreal injection of aflibercept or ranibizumab were analyzed over a 24-month follow-up. Each patient received the loading dose, followed by a PRN regimen. Patients were further subdivided into subgroups according to macular neovascularization type, best corrected visual acuity (BCVA) at baseline ( BCVA > 0.3 LogMAR and BCVA ≤ 0.3 LogMAR ), and different anti-VEGF drugs. Primary outcome was the changes in BCVA and central macular thickness (CMT) over 24 months. Secondary outcomes included the influence of the selected drug and of the baseline BCVA on the final outcomes. Results. 439 patients (224 males; 51%) with naïve AMD-related macular neovascularization were included in the analyses. Mean age was 78 ± 8 years old. Compared to baseline evaluations, not significant BCVA changes were found at 1-year and 2-year examinations. CMT was significantly reduced at both 1-year and 2-year follow-ups ( p < 0.01 ). Classic, polypoidal choroidal vasculopathy and mixed subtypes significantly correlated with worse visual outcome ( p < 0.01 ). Overall, baseline BCVA significantly correlated with both 1-year and 2-year follow-up changes ( p < 0.01 ). Moreover, BCVA at 1-year significantly correlated with BCVA changes at 2-year follow-up ( p < 0.01 ). Furthermore, CMT changes from baseline significantly correlated with both 1-year and 2-year follow-up measurements ( p < 0.01 ). Conclusion. Anti-VEGF approach is generally effective in stopping nAMD progression in our real-life analysis. No difference was found comparing patients treated with ranibizumab and aflibercept, nor in patients with drug switching.

Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p p p p

Introduction This study aimed to assess quantitative factors associated with treatment response and macular neovascularization (MNV) onset in central serous chorioretinopathy (CSC) through an artificial intelligence-based approach. Methods The study was designed as an interventional, prospective case series with a planned follow-up of 36 months. We included only eyes demonstrating the first episode of CSC. All the patients underwent eplerenone or photodynamic therapy (PDT) treatment. Eyes developing MNV underwent anti-VEGF injections. We developed an artificial intelligence-based model to assess predictive quantitative structural optical coherence tomography (OCT) factors related to treatment response and onset of MNV. Main outcome measures were best-correct visual acuity (BCVA), central macular thickness (CMT), retinal thickness (RT), retinal pigment epithelium (RPE) thickness, choroidal thickness, Sattler’s layer thickness (SLT), Haller’s layer thickness, retinal and choroidal hyperreflective foci (HF), and MNV. Results We included 96 naïve CSC eyes (96 patients). Baseline BCVA was 0.18 ± 0.25 logMAR, which increased to 0.16 ± 0.27 logMAR after 3 years (p > 0.05). Baseline CMT was 337 ± 126 µm, which improved to 229 ± 40 µm after 3 years (p

BACKGROUND: Retinal microaneurysms (MAs) are among the earliest signs of diabetic retinopathy (DR) and are typically detected by fluorescein angiography (FA). Confocal MultiColor is a noninvasive-imaging technique able to analyze different retinal features by capturing three simultaneous reflectance images. The main aim of the present study was to characterize morphological features of MAs by means of MultiColor images and to compare these with spectral domain optical coherence tomography (SD-OCT) and FA findings. METHODS: A cross-sectional, observational study setting was chosen. Multimodal imaging included MultiColor, SD-OCT and FA images. We performed a qualitative analysis in order to assess the relationship between MultiColor and its green- and red-reflectance components, SD-OCT (hyperreflective, hyporeflective and mixed reflectivity) and FA findings. MAs detected on our MultiColor images were then categorized in accordance with a previously published histological classification. RESULTS: In our study FA images were used to detect 153 MAs in 30 eyes displaying DR. MultiColor was able to distinguish 122 MAs (80%). We identified green (16%), red (19%), and mixed (65%) MAs, corresponding to different reflectivity features detected by SD-OCT. MAs not visualized on MultiColor images corresponded to tiny hyperreflective lesions on SD-OCT. We compared our imaging findings with a histological MA classification reported in the literature. Our findings showed a strict relationship between MA subtypes and SD-OCT, suggesting that the composition of MAs (cells + endothelium + fibrosis) may influence the signal detected in MultiColor images. CONCLUSIONS: MultiColor appears to be a useful technique for investigating MA features in patients with DR.

Purpose: To evaluate safety and tolerability on the ocular surface of an anti-septic formulation containing 0.6% povidone-iodine (0.6% PVI) for a 4 week period.Methods: An observational, prospective study included 20 mild-moderate dry eye disease (DED) patients who enrolled at the Ocular Surface Disease Unit of the University of Messina, receiving 0.6% PVI eye drops for 28 days, 2 drops twice daily (BID). The assessment included the Ocular Surface Disease Index questionnaire; symptoms score (0 = absent to 3 = severe) for burning, ocular dryness, foreign body sensation, watery eyes, tearing, photophobia, and ocular pain; fluorescein tear break-up time (TBUT); and corneal-conjunctival staining, performed at baseline (T0), after 7 (T7) and 28 (T28). Schirmer I-test, corneal endothelial cell count, intraocular pressure, and fundus examination were performed at T0 and T28. The main outcome measures were TBUT and corneal-conjunctival staining as markers of ocular surface homeostasis. For statistical analysis, Student's T-test and Wilcoxon test were used as appropriate.Results: No significant alterations of the safety parameters were found throughout the study. Further, at T28 a significant improvement of burning, ocular dryness, foreign body sensation, and watery eyes (T0 vs. T28 P < 0.03) were observed; corneal-conjunctival staining improved at T28 (T0 vs. T28 P < 0.0001), and TBUT improved already at T7 (T0 vs. T7 P = 0.0008) lasting so till the end of the study. The only adverse event was mild burning at instillation for the first 3 days of treatment in most of the patients.Conclusions: The treatment with 0.6% PVI was safe and well tolerated in a group of patients with a damaged ocular surface.