Changes in Circulating Acylated Ghrelin and Neutrophil Elastase in Diabetic Retinopathy.

Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and proliferative (PDR). Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels was investigated. Materials and Methods: The serum markers were determined via enzyme-linked immunosorbent assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with NPDR, and 15 patients with PDR. Results: TG and AG serum levels were significantly decreased in Diabetic (respectively, p < 0.05 and p < 0.01 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and in PDR patients (p < 0.01 vs. NPDR). AG serum levels were inversely associated with DR abnormalities (microhemorrhages, microaneurysms, and exudates) progression (r = -0.83, p < 0.01), serum neutrophil percentage (r = -0.74, p < 0.01), and serum NE levels (r = -0.73, p < 0.01). The latter were significantly increased in the Diabetic (p < 0.05 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and PDR (p < 0.01 vs. PDR) groups. Conclusions: The two DR stages were characterized by decreased AG and increased NE levels. In particular, serum AG levels were lower in PDR compared to NPDR patients, and serum NE levels were higher in the PDR vs. the NPDR group. Together with the greater presence of retinal abnormalities, this could underline a distinctive role of AG in PDR compared to NPDR.

Three-dimensional printed models can reduce costs and surgical time for complex proximal humeral fractures: preoperative planning, patient satisfaction, and improved resident skills.

BACKGROUND: Proximal humeral fractures (PHFs) are still controversial with regards to treatment and are difficult to classify. The study's objective is to show that preoperative planning performed while handling a three-dimensional (3D) printed anatomical model of the fracture can ensure a better understanding of trauma for both surgeons and patients. MATERIALS AND METHODS: Twenty patients (group A, cases) with complex PHF were evaluated preoperatively by reproducing life-size, full-touch 3D anatomical models. Intraoperative blood loss, radiographic controls, duration of surgery, and clinical outcomes of patients in group A were compared with 20 patients (group B, controls) who underwent standard preoperative evaluation. Additionally, senior surgeons and residents, as well as group A patients, answered a questionnaire to evaluate innovative preoperative planning and patient compliance. Cost analysis was evaluated. RESULTS: Intraoperative radiography controls and length of operation were significantly shorter in group A. There were no differences in clinical outcomes or blood loss. Patients claim a better understanding of the trauma suffered and the proposed treatment. Surgeons assert that the planning of the definitive operation with 3D models has had a good impact. The development of this tool has been well received by the residents. The surgery was reduced in length by 15%, resulting in savings of about EUR 400 for each intervention. CONCLUSIONS: Fewer intraoperative radiography checks, shorter surgeries, and better patient compliance reduce radiation exposure for patients and healthcare staff, enhance surgical outcomes while reducing expenses, and lower the risk of medicolegal claims. LEVEL OF EVIDENCE: Level I, prospective randomized case-control study.

A Re-Purposing Strategy: Sub-Lethal Concentrations of an Eicosanoid Derived from the Omega-3-Polyunsaturated Fatty Acid Resolvin D1 Affect Dual Species Biofilms.

The fungal species Candida parapsilosis and the bacterial species Staphylococcus aureus may be responsible for hospital-acquired infections in patients undergoing invasive medical interventions or surgical procedures and often coinfect critically ill patients in complicating polymicrobial biofilms. The efficacy of the re-purposing therapy has recently been reported as an alternative to be used. PUFAs (polyunsaturated fatty acids) may be used alone or in combination with currently available traditional antimicrobials to prevent and manage various infections overcoming antimicrobial resistance. The objectives of the study were to evaluate the effects of Resolvin D1 (RvD1) as an antimicrobial on S. aureus and C. parapsilosis, as well as the activity against the mixed biofilm of the same two species. Microdilution assays and time-kill growth curves revealed bacterial and fungal inhibition at minimum concentration values between 5 and 10 µg mL-1. In single-species structures, an inhibition of 55% and 42% was reported for S. aureus and C. parapsilosis, respectively. Moreover, RvD1 demonstrated an eradication capacity of 60% and 80% for single- and mixed-species biofilms, respectively. In association with the inhibition activity, a downregulation of genes involved in biofilm formation as well as ROS accumulation was observed. Eradication capability was confirmed also on mature mixed biofilm grown on silicone platelets as shown by scanning electron microscopy (SEM). In conclusion, RvD1 was efficient against mono and polymicrobial biofilms in vitro, being a promising alternative for the treatment of mixed bacterial/fungal infections.

Inhibition of Galectins and the P2X7 Purinergic Receptor as a Therapeutic Approach in the Neurovascular Inflammation of Diabetic Retinopathy.

Diabetic retinopathy (DR) is the most frequent microvascular retinal complication of diabetic patients, contributing to loss of vision. Recently, retinal neuroinflammation and neurodegeneration have emerged as key players in DR progression, and therefore, this review examines the neuroinflammatory molecular basis of DR. We focus on four important aspects of retinal neuroinflammation: (i) the exacerbation of endoplasmic reticulum (ER) stress; (ii) the activation of the NLRP3 inflammasome; (iii) the role of galectins; and (iv) the activation of purinergic 2X7 receptor (P2X7R). Moreover, this review proposes the selective inhibition of galectins and the P2X7R as a potential pharmacological approach to prevent the progression of DR.

Resolution of Inflammation in Retinal Disorders: Briefly the State.

The most frequent retinal diseases, such as diabetic retinopathy, age-related macular degeneration and posterior uveitis, are underlined by oxidative stress or aging-induced retinal inflammation, which contributes to vision impairing or loss. Resolution of inflammation is emerging as a critical phase able to counteract the inflammatory process leading to the progression of retinal damage. Particularly, pro-resolving mediators (PMs) play a key role in the modulation of inflammatory exudates and could be considered a new target to be investigated in different inflammatory-autoimmune pathologies. Here, we highlight the most recent studies concerning the role of the main PMs (lipoxins, resolvins, prtectins, maresins and annexins) in retinal inflammation, in order to collect the best evidence in the field of inflammatory retinal damage resolution and to propose novel pharmacological approaches in the management of the most common retinal diseases.

Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-ß/EMT Pathway.

Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5-5-10 µM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 µM and 10 µM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-ß/, NF-kB p65 levels, and ROS content. Moreover, epithelial-mesenchymal transition markers were reduced by OTX008 5 µM and 10 µM. The inhibition of galectin-1 by OTX008 in DR may preserve retinal pigment epithelial cell integrity and functionality by reducing their pro-fibrotic phenotype and epithelial-mesenchymal transition phenomenon induced by diabetes.

Sex and Age-Related Differences in Neuroinflammation and Apoptosis in Balb/c Mice Retina Involve Resolvin D1.

(1) Background: The pro-resolving lipid mediator Resolvin D1 (RvD1) has already shown protective effects in animal models of diabetic retinopathy. This study aimed to investigate the retinal levels of RvD1 in aged (24 months) and younger (3 months) Balb/c mice, along with the activation of macro- and microglia, apoptosis, and neuroinflammation. (2) Methods: Retinas from male and female mice were used for immunohistochemistry, immunofluorescence, transmission electron microscopy, Western blotting, and enzyme-linked immunosorbent assays. (3) Results: Endogenous retinal levels of RvD1 were reduced in aged mice. While RvD1 levels were similar in younger males and females, they were markedly decreased in aged males but less reduced in aged females. Both aged males and females showed a significant increase in retinal microglia activation compared to younger mice, with a more marked reactivity in aged males than in aged females. The same trend was shown by astrocyte activation, neuroinflammation, apoptosis, and nitrosative stress, in line with the microglia and Müller cell hypertrophy evidenced in aged retinas by electron microscopy. (4) Conclusions: Aged mice had sex-related differences in neuroinflammation and apoptosis and low retinal levels of endogenous RvD1.

Resolvin D1 attenuates the inflammatory process in mouse model of LPS-induced keratitis.

The aim of this study was to investigate the effects of the lipid mediator Resolvin D1 in experimental keratitis. C57BL/6J mice were injected with lipopolysaccharide (2 µg/eye), and after 24 hours, the corneal damage was assessed. Clinical score was quantified, and corneal inflammatory biomarkers were detected by immunohistochemistry. A robust accumulation of sub-epithelial macrophages and polymorphonuclear leucocytes, chemokine (C-X-C motif) ligand 1 (also known as keratinocyte-derived chemokine), interleukin-10 and promoters of apoptosis was also observed in lipopolysaccharide-treated mice. Formyl peptide receptor 2 corneal expression was also assessed. The corneal stroma treated with lipopolysaccharide was characterized by presence of macrophages of M1-like subtype and immature fibroblastic cells, marked with Ki67, not fully differentiated in fibroblasts. Indeed, the staining of the cornea with anti-vimentin antibodies, a marker of differentiated myofibroblasts, was very faint. Resolvin D1 attenuated all the inflammatory parameters assessed in the present study, except for IL-10. In conclusion, the data presented here seem to be consistent with the hypothesis that Resolvin D1 protected the cornea from the lipopolysaccharide-induced keratitis by acting on several inflammatory components of this damage, pivoted by Formyl peptide receptor 2 (FPR2) activation and macrophages-leucocytes activity.

Resolvin D1 reduces mitochondrial damage to photoreceptors of primary retinal cells exposed to high glucose.

No study has investigated the interaction of Resolvin D1 (RvD1) with mitochondrial damage of retinal cells caused by diabetes. This study aims to investigate the effects of RvD1 (50 nM) on morphological and biochemical indicators of mitochondrial damage in primary retinal cells exposed to 30 mM d-glucose high glucose (HG). HG-cells exhibited photoreceptor damage characterized by short and small mitochondria with prevalent mitochondrial disruption, fragmentation, and aggregation. The cells had low mitochondrial transporters TIMM44 and TOMM40, Connexin 43, NAD/NADH ratio, and ATP levels, whereas increased cytosolic cytochrome c. Moreover, they expressed high cytosolic metalloproteinase matrix metallopeptidase 9 (MMP-9) and MMP-2 activity. HG-cells treated with RvD1 (50 nM) showed reduced reactive oxygen species levels, improved mitochondrial morphology and function, promoted mitochondrial DNA repair by OGG1, and reduced cell apoptosis and metalloproteinase activity. Therefore, RvD1 induces protection from high glucose-load to the retinal cell and promotes their survival by decreasing cytosolic MMP and mitochondrial damage.

Drug Delivery Systems for Glaucoma: A Narrative Review.

Glaucoma is one of the world's leading causes of blindness, and its management is challenging. The main objective is to lower intraocular pressure through medical, para-surgical, and surgical therapy. Medical therapy often represents the first line of treatment. Although effective in many cases, the eye drops are accompanied by significant problems. They require high patient compliance and can be associated with various side effects, limiting their efficacy. Consequently, the research for new drug delivery systems trying to overcome these limitations is ongoing: numerous devices are developing and gradually entering clinical practice. These new therapeutic options may offer better control of the intraocular pressure, with fewer side effects, and are less dependent on patients' compliance. Hence, the research in this field continues to flourish. This review summarizes the most recent findings in the scientific literature, underlines the role and possible limitations of the new glaucoma drug delivery systems in clinical practice, and recognizes their new horizons and perspectives.

Understanding Acanthamoeba Keratitis: An In-Depth Review of a Sight-Threatening Eye Infection.

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening corneal infection caused by the Acanthamoeba parasite. This microorganism is found ubiquitously in the environment, often in freshwater, soil, and other sources of moisture. Despite its low incidence, AK presents significant challenges due to delayed diagnosis and the complex nature of therapeutic management. Early recognition is crucial to prevent severe ocular complications, including corneal ulceration and vision loss. Diagnostic modalities and treatment strategies may vary greatly depending on the clinical manifestation and the available tools. With the growing reported cases of Acanthamoeba keratitis, it is essential for the ophthalmic community to thoroughly understand this condition for its effective management and improved outcomes. This review provides a comprehensive overview of AK, encompassing its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, and treatment.

Ocular pharmacological and biochemical profiles of 6-thioguanine: a drug repurposing study.

Introduction: The purine analog 6-thioguanine (6TG), an old drug approved in the 60s to treat acute myeloid leukemia (AML), was tested in the diabetic retinopathy (DR) experimental in vivo setting along with a molecular modeling approach. Methods: A computational analysis was performed to investigate the interaction of 6TG with MC1R and MC5R. This was confirmed in human umbilical vein endothelial cells (HUVECs) exposed to high glucose (25 mM) for 24 h. Cell viability in HUVECs exposed to high glucose and treated with 6TG (0.05-0.5-5 µM) was performed. To assess tube formation, HUVECs were treated for 24 h with 6TG 5 µM and AGRP (0.5-1-5 µM) or PG20N (0.5-1-5-10 µM), which are MC1R and MC5R antagonists, respectively. For the in vivo DR setting, diabetes was induced in C57BL/6J mice through a single streptozotocin (STZ) injection. After 2, 6, and 10 weeks, diabetic and control mice received 6TG intravitreally (0.5-1-2.5 mg/kg) alone or in combination with AGRP or PG20N. Fluorescein angiography (FA) was performed after 4 and 14 weeks after the onset of diabetes. After 14 weeks, mice were euthanized, and immunohistochemical analysis was performed to assess retinal levels of CD34, a marker of endothelial progenitor cell formation during neo-angiogenesis. Results: The computational analysis evidenced a more stable binding of 6TG binding at MC5R than MC1R. This was confirmed by the tube formation assay in HUVECs exposed to high glucose. Indeed, the anti-angiogenic activity of 6TG was eradicated by a higher dose of the MC5R antagonist PG20N (10 µM) compared to the MC1R antagonist AGRP (5 µM). The retinal anti-angiogenic effect of 6TG was evident also in diabetic mice, showing a reduction in retinal vascular alterations by FA analysis. This effect was not observed in diabetic mice receiving 6TG in combination with AGRP or PG20N. Accordingly, retinal CD34 staining was reduced in diabetic mice treated with 6TG. Conversely, it was not decreased in diabetic mice receiving 6TG combined with AGRP or PG20N. Conclusion: 6TG evidenced a marked anti-angiogenic activity in HUVECs exposed to high glucose and in mice with DR. This seems to be mediated by MC1R and MC5R retinal receptors.

Normospermic Patients Infected With Ureaplasma parvum: Role of Dysregulated miR-122-5p, miR-34c-5, and miR-141-3p.

Background: Ureaplasma parvum (UP) is a causative agent of non-gonococcal urethritis, involved in the pathogenesis of prostatitis and epididymitis, and it could impair human fertility. Although UP infection is a frequent cause of male infertility the study evidence assessing their prevalence and the association in patients with infertility is still scarce. The molecular processes leading to defects in spermatozoa quality are not completely investigated. MicroRNAs (miRNAs) have been extensively reported as gene regulatory molecules on post-transcriptional levels involved in various biological processes such as gametogenesis, embryogenesis, and the quality of sperm, oocyte, and embryos. Methods: Therefore, the study design was to demonstrate that miRNAs in body fluids like sperm could be utilized as non-invasive diagnostic biomarkers for pathological and physiological conditions such as infertility. A post-hoc bioinformatics analysis was carried out to predict the pathways modulated by the miRNAs dysregulated in the differently motile spermatozoa. Results: Here it is shown that normospermic patients infected by UP had spermatozoa with increased quantity of superoxide anions, reduced expression of miR-122-5p, miR-34c-5, and increased miR-141-3p compared with non-infected normospermic patients. This corresponded to a reduction of sperm motility in normospermic infected patients compared with normospermic non-infected ones. A target gene prediction presumed that an essential role of these miRNAs resided in the regulation of lipid kinase activity, accounting for the changes in the constitution of spermatozoa membrane lipids caused by UP. Conclusions: Altogether, the data underline the influence of UP on epigenetic mechanisms regulating spermatozoa motility.

Candida Biofilm Eye Infection: Main Aspects and Advance in Novel Agents as Potential Source of Treatment.

Fungi represent a very important cause of microbial eye infections, especially in tropical and developing countries, as they could cause sight-threating disease, such as keratitis and ocular candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent microorganisms associated with fungal infection. Although Candida albicans is still the most frequently detected organism among Candida subspecies, an important increase in non-albicans species has been reported. Mycotic infections often represent an important diagnostic-clinical problem due to the difficulties in performing the diagnosis and a therapeutic problem due to the limited availability of commercial drugs and the difficult penetration of antifungals into ocular tissues. The ability to form biofilms is another feature that makes Candida a dangerous pathogen. In this review, a summary of the state-of-the-art panorama about candida ocular pathology, diagnosis, and treatment has been conducted. Moreover, we also focused on new prospective natural compounds, including nanoparticles, micelles, and nanocarriers, as promising drug delivery systems to better cure ocular fungal and biofilm-related infections. The effect of the drug combination has also been examined from the perspective of increasing efficacy and improving the course of infections caused by Candida which are difficult to fight.

Intravitreal DEX Implant for the Treatment of Diabetic Macular Edema: A Review of National Consensus.

Diabetic macular edema (DME)'s therapeutic approach can frequently be challenging. The purpose of the review is to propose evidence-based recommendations on the employment of intravitreal dexamethasone implants (DEX) when approaching patients suffering from DME. Seven national consensuses redacted by different groups of retina specialists from Europe and Asia were examined and confronted. Each consensus was redacted utilizing a Delphi approach, in person meetings, or by reviewing the literature. DEX can be studied as a first-line strategy in individuals suffering from DME with inflammatory OCT biomarkers, in vitrectomized eyes, in patients with recent cardiovascular events, in pregnant women, in patients scheduled to undergo cataract surgery or with poor compliance. The other parameters considered were the indications to the DME treatment, when to switch to DEX, the definition of non-responder to anti-VEGFs agents and to the DEX implant, whether to combine DEX with laser photocoagulation, the association between glaucoma and DEX, and the management of DEX and the cataract. Although several years have passed since the introduction of DEX implants in the DME treatment, there is still not a unified agreement among retina specialists. This paper compares the approach in the DME treatment between countries from different continents and provides a broader and worldwide perspective of the topic.

Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren's Syndrome.

BACKGROUND: Vitamin D deficiency has been associated with dry eye development during Sjögren's syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. METHODS: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C-) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). RESULTS: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C-), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. CONCLUSIONS: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

Viral Infection and Antiviral Treatments in Ocular Pathologies.

Ocular viral infections are common and widespread globally. These infectious diseases are a major cause of acute red eyes and vision loss. The eye and its nearby tissues can be infected by several viral agents, causing infections with a short course and limited ocular implications or a long clinical progression and serious consequences for the function and structure of the ocular region. Several surveillance studies underline the increased emergence of drug resistance among pathogenic viral strains, limiting treatment options for these infections. Currently, in the event of resistant infections, topical or systemic corticosteroids are useful in the management of associated immune reactions in the eye, which contribute to ocular dysfunction. Many cases of viral eye infections are misdiagnosed as being of bacterial origin. In these cases, therapy begins late and is not targeted at the actual cause of the infection, often leading to severe ocular compromises, such as corneal infiltrates, conjunctival scarring, and reduced visual acuity. The present study aims at a better understanding of the viral pathogens that cause eye infections, along with the treatment options available.

Reduction in the Duration of Postoperative Fever during the COVID-19 Pandemic in Orthopedic and Traumatic Surgery Due to PPE and Cautions.

The Italian government on the 8th of march in response to the increased global prevalenceof severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stated a national quarantine. In this period the absence of rapid and sure screening tests for COVID-19 made necessary more attention for presence of fever in hospitalized patients, like continuous use of surgical, FFP2, and FFP3 masks (PPE) by nurses, physicians, and patients; moreover, patients visits were restricted. In this period, during the daily activities in our orthopedic department we observed an empirical decreased incidence of post-operative fever in patients admitted for trauma surgery. The aim of this study is to compare the prevalence of post-operative fever in this period with the same period in 2019. We analyzed the presence of post-operative fever in 110 patients admitted in 2020 and 129 admitted in 2019. The results show a significant decrease of the prevalence and duration of post-operative fever in patients admitted in 2020. This study evidenced that the use of PPE and limitation in external access to the hospital decrease postoperative fever in hospitalized patients undergone surgery for fracture.

Ophthalmic Solutions with a Broad Antiviral Action: Evaluation of Their Potential against Ocular Herpetic Infections.

HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection.

Serum Iba-1, GLUT5, and TSPO in Patients With Diabetic Retinopathy: New Biomarkers for Early Retinal Neurovascular Alterations? A Pilot Study.

Purpose: This study explored the possibility of highlighting early retinal neurovascular alterations of diabetic retinopathy (DR) by monitoring in DR patients the serum levels of microglial biomarkers ionized calcium-binding adapter molecule 1 (Iba-1), glucose transporter 5 (GLUT5), and translocator protein (TSPO), along with serum changes of the endothelial dysfunction marker arginase-1. Methods: Serum markers were determined by enzyme-linked immunosorbent assay in 50 patients: 12 non-diabetic subjects, 14 diabetic patients without DR, 13 patients with non-proliferative DR (NPDR), and 11 patients with proliferative DR (PDR). The results were correlated with hyperreflective retinal spots (HRS), observed with optical coherence tomography (OCT). Results: Although HRS were absent in diabetic patients without DR, NPDR patients showed an average of 4 ± 1 HRS, whereas the highest presence was detected in PDR patients, with 8 ± 1 HRS (P < 0.01 vs. NPDR). HRS were positively correlated (P < 0.01) with serum levels of arginase-1 (r = 0.91), Iba-1 (r = 0.96), GLUT5 (r = 0.94), and TSPO (r = 0.88). Moreover, serum proinflammatory cytokines and chemokines showed a positive correlation (P < 0.01) with HRS number and the serum markers analyzed. Conclusions: Serum markers of microglial activation positively correlate with retinal HRS in NPDR and PDR patients. Translational Relevance: These data corroborate the possibility of highlighting early retinal neurovascular changes due to diabetes by monitoring circulating microglial markers.