Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received much attention as potential tools for managing chronic-degenerative ocular diseases. A systematic search of PubMed, Web of Science, hand-searched publications and historical archives were performed by the professionals involved in this study, to include peer-reviewed articles in which natural food, nutrient content, and its potential relationship with ocular health. Five ophthalmologists and two researchers collected the characteristics, quality and suitability of the above studies. Finally, 177 publications from 1983 to 2021 were enclosed, mainly related to natural food, Mediterranean diet (MedDiet) and nutraceutic supplementation. For the first time, original studies with broccoli and tigernut (chufa de Valencia) regarding the ocular surface dysfunction, macular degeneration, diabetic retinopathy and glaucoma were enclosed. These can add value to the diet, counteract nutritional defects, and help in the early stages, as well as in the course of ophthalmic pathologies. The main purpose of this review, enclosed in the Special Issue “Health Benefits and Nutritional Quality of Fruits, Nuts and Vegetables,” is to identify directions for further research on the role of diet and nutrition in the eyes and vision, and the potential antioxidant, anti-inflammatory and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts), the Mediterranean Diet, and nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss. This review work was designed and carried out by a multidisciplinary group involved in ophthalmology and ophthalmic research and especially in nutritional ophthalmology.

Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND.

Purpose: To evaluate the clinical efficacy and safety of propylene glycol/hydroxypropyl-guar (PG-HPG)-based nanoemulsion (Systane^® Complete) lubricant eye drops in participants with dry eye disease (DED). Participants and Methods: In this phase IV, open-label, single-arm, interventional, multicenter study, adult participants with DED – subtyped into aqueous deficient, evaporative, and mixed dry eye – were instructed to instill one drop of PG-HPG in each eye twice a day for 28 days. Endpoints included change from baseline in tear film break-up time (TFBUT) (primary) and ocular discomfort visual analog scale (VAS) score at Day 14 and TFBUT at Day 28 (secondary). Safety was assessed throughout the study. Data were analyzed for overall patient cohort and by DED subtypes. Results: A total of 134 participants received treatment (mean age: 56.6 years; female: 75.4%). At Day 14, the mean (standard deviation [SD]) TFBUT increased from 2.6 (1.00) seconds at baseline to 4.2 (2.92) seconds (mean change: 1.5 [2.80] seconds); median change was 0.8 seconds (95% CI: 0.52, 1.19) for the overall cohort; the change was maintained at Day 28 (mean change: 1.4 (2.80) seconds, median change: 0.8 seconds (95% CI: 0.49, 1.17). Subgroup analysis showed a mean change (SD) from baseline in TFBUT of 1.1 (2.41) seconds for aqueous deficient, 2.4 (3.17) seconds for evaporative, and 1.2 (2.63) seconds for mixed dry eye at Day 14, respectively. The ocular discomfort VAS score improved (decreased) from baseline at Day 14 (mean [SD] change: − 17.3 [24.80]) for the overall cohort, − 22.0 [21.73] for aqueous deficient, − 17.6 [24.17] for evaporative and − 13.1 [27.49] for mixed dry eye subgroups). Adverse events (AEs) were reported in 9 (6.7%) participants. No serious AEs were reported during the study. Conclusion: Our study findings demonstrated that PG-HPG-based nanoemulsion lubricant eye drops were effective and well tolerated in participants with DED and all of its subtypes.

Reactive oxygen species (ROS) overproduction and ROS-signaling pathways activation attack the eyes. We evaluated the oxidative stress (OS) and the effects of a daily, core nutritional supplement regimen containing antioxidants and omega 3 fatty acids (A/ω3) in type 2 diabetics (T2DM). A case-control study was carried out in 480 participants [287 T2DM patients with (+)/without (−) diabetic retinopathy (DR) and 193 healthy controls (CG)], randomly assigned to a daily pill of A/ω3. Periodic evaluation through 38 months allowed to outline patient characteristics, DR features, and classic/OS blood parameters. Statistics were performed by the SPSS 24.0 program. Diabetics displayed significantly higher circulating pro-oxidants (p = 0.001) and lower antioxidants (p = 0.0001) than the controls. Significantly higher plasma malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS; p = 0.006) and lower plasma total antioxidant capacity (TAC; p = 0.042) and vitamin C (0.020) was found in T2DM + DR versus T2DM-DR. The differential expression profile of solute carrier family 23 member 2 (SLC23A2) gene was seen in diabetics versus the CG (p = 0.001), and in T2DM + DR versus T2DM − DR (p < 0.05). The A/ω3 regime significantly reduced the pro-oxidants (p < 0.05) and augmented the antioxidants (p < 0.05). This follow-up study supports that a regular A/ω3 supplementation reduces the oxidative load and may serve as a dietary prophylaxis/adjunctive intervention for patients at risk of diabetic blindness.

Efficacy and safety of dual-polymer hydroxypropyl guar- and hyaluronic acid-containing lubricant eyedrops for the management of dry-eye disease: a randomized double-masked clinical study Marc Labetoulle,1 Stefanie Schmickler,2 David Galarreta,3 Daniel Böhringer,4 Abayomi Ogundele,5 Michel Guillon,6 Christophe Baudouin7,8 1Ophtalmologie, Hôpital Bicêtre, APHP, South Paris Université, Kremlin-Bicêtre, Paris, France; 2Augen-Zentrum-Nordwest Augenpraxis, Ahaus, Germany; 3Hospital Clinico Universitario de Valladolid, Valladolid, Spain; 4Eye Center, University Hospital Freiburg, Freiburg, Germany; 5Novartis Pharmaceutical Corporation, Fort Worth, TX, USA; 6Ocular Technology Group, London, UK; 7Quinze-Vingts Hospital, DHU Sight Restore, University Versailles Saint Quentin en Yvelines, INSERM-DHOS CIC, Paris, France; 8Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France Background: An artificial-tear formulation containing the dual polymers hydroxypropyl guar (HPG) and hyaluronic acid (HA) is approved for the treatment of dry-eye disease (DED). The present study compared the efficacy and safety of the HPG-HA dual-polymer formulation vs a sodium hyaluronate (SH)-containing artificial-tear formulation in patients with DED.Methods: In a prospective, 6-week, multicenter, double-masked, parallel-group study, patients with DED aged ≥18 years and total ocular surface staining (TOSS) score ≥4 and ≤9 were randomized (1:1) to receive either HPG-HA or SH four times a day for 42 days. Changes from baseline in TOSS (primary end point), impact of dry eye on everyday life (IDEEL) treatment-satisfaction scores (effectiveness and inconvenience), and tear-film breakup time (TFBUT) at day 42 were assessed using a fixed-sequence testing strategy. Noninferiority was assessed on the primary end point based on the upper limit of two-sided 95% CIs for mean treatment difference (HPG-HA or SH) <2 units.Results: In total, 99 patients were randomized (HPG-HA, n= 50; SH, n= 49). At day 42, the least square (LS) mean ± SE change from baseline in TOSS was -1.16±0.24 and -0.92±0.23 in the HPG-HA and SH groups, respectively, and the treatment difference was -0.24±0.33 (95% CI -0.90 to 0.42). Noninferiority was demonstrated as the upper limit of the 95% CI was <2 units. LS mean change from baseline at day 42 for HPG-HA vs SH was -3.18 (P=0.4817) in IDEEL treatment-effectiveness scores, -12.56 (P=0.0001) in treatment-inconvenience scores, and 0.30 seconds (P=0.5789) in TFBUT.Conclusion: The HPG-HA dual-polymer formulation was noninferior to the SH lubricant eyedrops for improvement in ocular surface staining in DED. HPG-HA did not show improvement over SH in IDEEL treatment-satisfaction scores. No new safety findings were reported. Keywords: dry-eye disease, dual polymer, artificial tears, hydroxypropyl guar, hyaluronic acid

Purpose: To evaluate symptom relief in patients with dry eye disease (DED) following a single drop of propylene glycol-hydroxypropyl guar (PG-HPG) nanoemulsion (Systane^® Complete) lubricant eye drops. Methods: This was a Phase IV, multicenter, open-label, interventional study in adult patients with DED of aqueous-deficient, evaporative, and mixed subtypes. Patients instilled one drop of PG-HPG in each eye at Day 1. Endpoints included change from baseline in dry eye symptom and soothing sensation scores on Day 1 at 0, 4, and 8 hours post-dose. Symptom scores were assessed on a 0– 10 scale (0=no symptoms; 10=worst imaginable symptom). Tolerability of the drop was assessed based on assessment score on Day 1 following instillation for overall cohort and by DED subtype. Results: A total of 134 patients received treatment (mean age: 56.6 years; female: 75.4%). Median changes from baseline at Day 1 in dry eye symptom scores were − 1.0 (95% confidence interval [CI]:-3.0,-1.0), − 2.0 (95% CI:-3.0,-2.0), and − 2.0 (95% CI:-2.0,-1.0) at 0, 4, and 8 hours respectively. Subgroup analysis showed a median change from baseline in dry eye symptom score of − 2 (95% CI:-3.0,-1.0) for aqueous-deficient and evaporative subtypes and − 1 (95% CI:-3.0,-1.0) for mixed subtype at 8 hours. Median soothing sensation scores were 3 at 0 and 4 hours and 3.5 at 8 hours, with a range of 0– 10. Median (range) tolerability assessment scores were 0 (0– 8) for burning sensation, stinging sensation, blurring, and 0 (0– 10) for foreign body sensation. Tolerability assessment scores by DED subtype confirmed that the majority of patients reported scores in the range of 0– 5 for all components and in all subgroups analyzed. Conclusion: Our study demonstrated that PG-HPG nanoemulsion provided instant/immediate and sustained symptom relief for 8 hours post-single application and was well tolerated in patients with DED, demonstrated by their responses on each of the assessment scales.