Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

A novel osmoprotective liposomal formulation from synthetic phospholipids to reduce in vitro hyperosmolar stress in dry eye treatments.

Dry eye disease (DED) is a worldwide, multifactorial disease mainly caused by a deficit in tear production or increased tear evaporation with an increase in tear osmolarity and inflammation. This causes discomfort and there is a therapeutic need to restore the homeostasis of the ocular surface. The aim of the present work was to develop a biodegradable and biocompatible liposomal formulation from the synthetic phospholipids 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) that is able to reduce the effects of hypertonic stress by helping to restore the lipid layer of the tear film. Liposomes were made using the lipid film hydration method with synthetic phospholipids (10 mg/mL) with and without 0.2% HPMC. They were characterised in terms of size, osmolarity, pH, surface tension, and viscosity. Additionally, the in vitro toxicity of the formulation at 1 and 4 h in human corneal epithelial cells (hTERT-HCECs) and human conjunctival cells (IM-HConEpiC) was determined. Furthermore, osmoprotective activity was tested in a corneal model of hyperosmolar stress. In vivo acute tolerance testing was also carried out in albino New Zealand rabbits by topical application of the ophthalmic formulations every 30 min for 6 h. All the assayed formulations showed suitable physicochemical characteristics for ocular surface administration. The liposomal formulations were well-tolerated in cell cultures and showed osmoprotective activity in a hyperosmolar model. No alterations or discomfort were reported when they were topically administered in rabbits. According to the results, the osmoprotective liposomal formulations developed in this work are promising candidates for the treatment of DED.

Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease.

Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.

Quantification of a panel for dry-eye protein biomarkers in tears: A comparative pilot study using standard ELISA and customized microarrays.

Purpose: This paper examines the tear concentration of cystatin S (CST4), calcyclin (S100A6), calgranulin A (S100A8), and matrix metalloproteinase 9 (MMP9), and the correlation between biomarker expression, clinical parameters, and disease severity in patients suffering from dry eye (DE). A comparison of the results is obtained via ELISA tests and customized antibody microarrays for protein quantification. Methods: This single-center, observational study recruited 59 participants (45 DE and 14 controls). Clinical evaluation included an Ocular Surface Disease Index (OSDI) questionnaire, a tear osmolarity (OSM) test, the Schirmer test (SCH), tear breakup time (TBUT), fluorescein (FLUO) and lissamine green (LG) corneal staining, and meibomian gland evaluation (MGE). Tear concentrations of CST4, S100A6, S100A8, and MMP9 were measured using standard individual ELISA assays. The levels of CST4, S100A6, and MMP9 were also measured using customized multiplexed antibody microarrays. Correlations between variables were evaluated, and a significance level was p value <0.05. Results: The quantification of tear protein biomarkers with ELISA showed that the concentration of CST4 was significantly (2.14-fold) reduced in tears of DE patients in comparison with control (CT) subjects (p < 0.001). S100A6 and S100A8 concentrations were significantly higher in the tears of DE patients (1.36- and 2.29-fold; p < 0.001 and 0.025, respectively) in comparison with CT. The MMP9 level was also higher in DE patients (5.83-fold), but not significantly (p = 0.22). The changes in CST4 and S100A6 concentrations were significantly correlated with dry eye disease (DED) severity. Quantification of CST4, S100A6, and MMP9, using antibody microarrays, confirmed the ELISA results. Similar trends were observed: 1.83-fold reduction for CST4 (p value 0.01), 8.63-fold increase for S100A6 (p value <0.001) and 9.67-fold increase for MMP9 (p value 0.94), but with higher sensitivity. The biomarker concentrations were significantly associated with the signs and symptoms related with DED. Conclusions: S100A6, S100A8, and CST4 diagnostic biomarkers strongly correlate with DED clinical parameters. S100A6 and CST4 are also useful for grading DE severity. The multiplexed antibody microarray technique, used here for tear multi-marker quantification, appears more sensitive than standard ELISA tests.

Tear 1H Nuclear Magnetic Resonance-Based Metabolomics Application to the Molecular Diagnosis of Aqueous Tear Deficiency and Meibomian Gland Dysfunction.

PURPOSE: Meibomian gland dysfunction (MGD) is a major cause of signs and symptoms related to dry eyes (DE) and eyelid inflammation. We investigated the composition of human tears by metabolomic approaches in patients with aqueous tear deficiency and MGD. METHODS: Participants in this prospective, case-control pilot study were split into patients with aqueous tear deficiency and MGD (DE-MGD [n = 15]) and healthy controls (CG; n = 20). Personal interviews, ocular surface disease index (OSDI), and ophthalmic examinations were performed. Reflex tears collected by capillarity were processed to 1H nuclear magnetic resonance (NMR) spectroscopy and quantitative data analysis to identify molecules by spectra comparison to library entries of purified standards and/or unknown entities. Statistical analyses were made by the SPSS 22.0 program. RESULTS: Chemometric analysis and 1H NMR spectra comparison revealed the presence of 60 metabolites in tears. Differentiating features were evident in the NMR spectra of the 2 clinical groups, characterized by significant upregulation of phenylalanine, glycerol, and isoleucine, and downregulation of glycoproteins, leucine, and -CH3 lipids, as compared to the CG. The 1H NMR metabolomic analyses of human tears confirmed the applicability of this platform with high predictive accuracy/reliability. CONCLUSIONS: Our key distinctive findings support that DE-MGD induces tear metabolomics profile changes. Metabolites contributing to a higher separation from the CG can presumably be used, in the foreseeable future, as DE-MGD biomarkers for better managing the diagnosis and therapy of this disease.

Conjunctivitis in COVID-19 patients: frequency and clinical presentation.

PURPOSE: The purpose of this study was to evaluate the frequency and clinical presentation of conjunctivitis in hospitalized patients with COVID-19. METHODS: A cross-sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. A total of 301 subjects from the COVID admission unit with laboratory-confirmed SARS-CoV-2 infection were included. The presence and clinical characteristics of conjunctivitis were evaluated. Laboratory, radiological, and clinical results in patients with and without conjunctivitis stratified by sex were analyzed. RESULTS: Of the 301 subjects included, 180 patients (59.8%) were male and the median age was 72 years (IQ 59-82). Overall, 35 patients (11.6%) were diagnosed with acute conjunctivitis. We found no relationship between the COVID-19 severity score and the presence of conjunctivitis (P = 0.17). However, conjunctivitis was more frequent in males with moderate clinical severity and in women classified as clinically mild. The natural history of the disease seems to be a rapid self-limited conjunctivitis that improves without treatment and does not affect visual acuity nor associate short-term complications. CONCLUSIONS: Approximately, 1 out of 10 hospitalized non-critical COVID-19 patients presents conjunctivitis during the disease. Compared with other viral conjunctivitis, we found distinctive clinical findings that could guide defining and differentiating conjunctivitis in COVID-19 patients. TRIAL REGISTRATION NUMBER: 20/336_E_COVID.

Correction to: Heredity and in vivo confocal microscopy of punctiform and polychromatic pre-Descemet dystrophy.

In the original publication, presentation of the following author names are incorrect in the HTML version.

Transforming growth factor beta-induced p.(L558P) variant is associated with autosomal dominant lattice corneal dystrophy type IV in a large cohort of Spanish patients.

IMPORTANCE: Rare transforming growth factor beta-induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features. BACKGROUND: The purpose of this study was to analyse TGFBI gene variants and genotype-phenotype correlations in a cohort affected by atypical stromal CD. DESIGN: Retrospective cohort study (from May 2014 to September 2017). PARTICIPANTS: Thirty-five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included. METHODS: Corneal phenotypes were assessed by slit-lamp examination and optical coherence tomography (OCT). Contrast sensitivity was measured under mesopic conditions. Genomic DNA was obtained from blood samples, and all 17 TGFBI exons were screened for variants by Sanger sequencing. MAIN OUTCOME MEASURES: p.(L558P) variant of TGFBI gene. RESULTS: The p.(L558P) variant was identified in 22 members of the 10 families diagnosed with atypical LCD, characterized by late-onset and absence of recurrent erosion syndrome. OCT revealed punctiform deposits in the deep-mid stroma and normal anterior stroma. This variant was demonstrated to be transmitted with the disease according to autosomal dominant inheritance in most families. CONCLUSIONS AND RELEVANCE: To the best of our knowledge, we describe a detailed clinical characterization of the largest CD cohort carrying the TGFBI p.(L558P) variant. We propose that the atypical phenotype of this recently reported alteration can be classified as a form of LCD type IV. The results show that OCT and anterior-posterior analysis of the stromal location of the opacities, along with a genetic analysis of TGFBI, are required to ensure accurate diagnosis and management of CDs.

Heredity and in vivo confocal microscopy of punctiform and polychromatic pre-Descemet dystrophy.

PURPOSE: To describe and analyze the biomicroscopic features and in vivo confocal microscopy of the crystalline form of pre-Descemet corneal dystrophy (PDCD). METHODS: We examined two non-related families using biomicroscopy, in vivo confocal microscopy, and a genetic study using a gene panel test, looking for mutations in the PIKFYVE gene. RESULTS: A slit-lamp examination of the first family revealed polychromatic crystalline punctiform opacities distributed all over the stroma in 8 of 11 family members in three generations with an autosomal dominant inheritance. The second family showed in three of four members in two generations the same opacities located in the pre-Descemet region. It was also a hint for autosomal dominant inheritance. The in vivo confocal microscopy identified numerous rounded and hyperreflective stromal particles measuring 10-15 µm in diameter, with the highest density in the posterior stroma and with normal keratocytes. No systemic disease was diagnosed. No variants or mutations were identified in PIKFYVE gene. CONCLUSIONS: Polychromatic deposits in patients with Punctiform and Polychromatic Pre-Descemet corneal dystrophy can be located not only in the deep stroma but also in the anterior and middle stroma. Our presentation reveals the possibility of considering this characteristic corneal disorder as a corneal dystrophy of its own and not as a subtype of pre-Descemet corneal dystrophy.

Tonometry after Intrastromal Corneal Ring Segments for Keratoconus.

SIGNIFICANCE: Reliable intraocular pressure (IOP) measurement after intrastromal corneal ring segments (ICRS) implantation is a challenge because of altered corneal morphology. In this study, IOP is measured with four tonometers, compared with Goldmann applanation tonometry (GAT) values and the influence of corneal parameters is established. PURPOSE: This study compares IOP measurements made using different tonometers in patients implanted with ICRS and assesses the effects of central corneal thickness (CCT), corneal curvature, and corneal astigmatism on the IOP measurements obtained. METHODS: In this cross-sectional study, IOP was measured using three different tonometers in 91 eyes of 91 patients with corneal ectasia implanted at least 6 months previously with ICRS. The tonometers tested were the TonoPen XL, Pascal dynamic contour tonometer (DCT), and iCare Pro rebound tonometer. GAT measurements were used as reference. Agreement among the IOPs provided by the different tonometers and the influence of corneal variables on the IOP measurements obtained were assessed using the Bland-Altman method, intraclass correlation coefficients, and multiple linear regression analysis. RESULTS: Mean IOP differences were GAT versus TonoPen XL -0.8 ± 3.07 mm Hg, GAT versus DCT -1.0 ± 3.26 mm Hg, and GAT versus iCare Pro 0.8 ± 2.92 mm Hg. Our multiple linear regression analysis identified CCT as a confounding factor affecting all the tonometer readings but DCT-IOP. CONCLUSIONS: In patients fitted with ICRS, IOP measurements made using the iCare Pro and TonoPen XL showed most agreement with GAT. Intraocular pressure measurements made by DCT were unaffected by corneal topographic factors though this procedure slightly overestimated GAT readings.

Topical Insulin Eye Drops: Stability and Safety of Two Compounded Formulations for Treating Persistent Corneal Epithelial Defects.

Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280-300 mOsm/L), had a pH close to neutral (7-8), medium surface-tension values (<56 MN/m-1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90-110% range in the compounded formulations containing normal saline solution when stored at 2-8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.

Long-Term Effects of Adipose-Derived Stem Cells for the Treatment of Bilateral Limbal Stem Cell Deficiency.

PURPOSE: To determine the safety and feasibility of human autologous adipose tissue-derived adult mesenchymal stem cells (ASCs) for ocular surface regeneration in patients with bilateral limbal stem-cell deficiency (LSCD). METHODS: A phase IIa clinical trial was designed (https://Clinicaltrials.gov, NCT01808378) with 8 patients, 3 of whom had aniridia, 2 meibomian glands diseases, 2 multiple surgeries and 1 chronic chemical injury. The therapeutic protocol was as follows: 6-mm of central corneal epithelium was removed, 400,000 ASCs were injected into each limboconjunctival quadrant, 400,000 ASCs were suspended over the cornea for 20 min, and finally the cornea was covered with an amniotic membrane patch. RESULTS: No adverse events were detected after a mean of 86,5 months of follow-up. One year after surgery, 6 of the 8 transplants were scored as successful, five patients had improved uncorrected visual acuity (mean of 12 letters), two patients presented epithelial defects (also present at baseline) and the mean percentage of corneal neovascularization was of 28.75% (36.98%, at baseline). Re-examination 24 months after treatment disclosed preserved efficacy in 4 patients. At the last visit (after a mean of 86,5 months of follow up) epithelial defects were absent in all patients although improvement in all of the variables was only maintained in patient 3 (meibomian glands agenesia). CONCLUSION: ASCs are a feasible and conservative therapy for treating bilateral LSCD. The therapeutic effect differs between etiologies and diminishes over time.

Liposomal ozonated oil effectiveness in the signs and symptoms of blepharitis in usual clinical practice.

PURPOSE: To analyze the efficacy of liposomal ozonated oil (Ozonest®) treatment, in patients with blepharitis or blepharoconjunctivitis, in improving the signs and symptoms of the pathology. METHODS: Exploratory, open-label, prospective, single-arm, pre-post comparative pilot study in usual clinical practice, in 20 patients with blepharitis/blepharoconjunctivitis, receiving treatment with liposomal ozonated oil, one drop in each eye, 4 times a day, for 28 days. Main purpose was to assess whether there was a clinically improvement in the blepharitis specific BLISS questionnaire score. Changes in the 12-item OSDI, in eyelid signs of blepharitis assessed by the physicians were also evaluated among other tests, and there was also a subjective evaluation of the treatment by patients. RESULTS: The BLISS score significantly improved from 16.4 before treatment to 11.8 after treatment (p < 0.05). The OSDI score was also significantly improved from 27.5 before treatment to 20.5 after treatment (p < 0.05). All tests conducted before and after treatment showed significant improvement (p < 0.05), except for NIBUT. The treatment received a score of 7 out of 10 by the patients. There were no adverse events in any patient. CONCLUSION: Liposomal ozonated oil treatment showed good efficacy in improving the signs and symptoms of blepharitis/blepharoconjunctivitis, satisfaction of patients, and good safety and tolerability.

Face mask use and effects on the ocular surface health: A comprehensive review.

In the COVID-19 period, face masks increased exponentially. Several studies suggest that the rise in ocular discomfort symptoms during the pandemic is mostly part of dry eye disease and that these are due to the effect of face masks, resulting in the newly described term MADE, for "mask-associated dry eye". The most commonly proposed mechanism states that wearing a face mask creates an unnatural upward airflow towards the ocular surface during expiration, although the increased temperature, humidity and levels of carbon dioxide of the exhaled air, stress, increased use of video display terminals, as well as changes in the ocular microbiota may contribute. Evidence supports that the use of face masks causes an increase in dry eye disease symptoms, a decreased tear break-up time, corneal epithelial trauma, periocular temperature changes and inflammatory markers secretion. Given that the use of masks may be frequent in some settings in the near future, it is important to establish its effects and consequences on the ocular surface.

NOVATIVE: A Phase II/III, Multicenter, Double-masked, Randomized Study of Cyclosporine A 0.05% and 0.1% Ophthalmic Cationic Emulsion Versus Vehicle in Patients with Vernal Keratoconjunctivitis.

PURPOSE: This study evaluates the efficacy and tolerability of cyclosporine A cationic emulsion (CsA-CE) in patients ≥4 years of age with moderate-to-severe vernal keratoconjunctivitis (VKC). METHODS: This Phase II/III, multicenter, double-masked, dose-ranging study had 2 treatment periods: a 4-week, randomized, vehicle-controlled period in which patients received 0.05% CsA-CE, 0.1% CsA-CE, or vehicle eye drops 4 times daily (period 1) and a 3-month period in which patients received 0.05% CsA-CE or 0.1% CsA-CE 2 or 4 times daily (period 2). The primary efficacy end point was rating of subjective symptoms at day 28 in period 1 per the BenEzra scale. FINDINGS: All groups showed improvement in subjective VKC symptoms at day 28, without a statistically significant difference between 0.05% or 0.1% CsA-CE vs vehicle. Both CsA-CE doses produced statistically significant improvements in corneal fluorescein staining scores vs vehicle at day 28; improvements were evident as early as week 1 and continued through month 1. Progressive reduction in subjective itching was evident after week 1 and continued through month 1. Treatment for an additional 3 months further improved subjective symptoms and objective signs of VKC in both CsA-CE groups. Improvement was most notable with 0.1% CsA-CE in patients with severe keratitis. The safety and tolerability profile is favorable. IMPLICATIONS: Although treatment with 0.05% and 0.1% CsA-CE showed clinical efficacy in alleviating keratitis and itching as early as week 1, with sustained benefit through 1 month, the primary efficacy end point was not met. These findings informed the design of the Phase III trial of 0.1% CsA-CE (Vernal Keratoconjunctivitis Study). CLINICALTRIALS: gov identifier: NCT00328653.

Topical insulin, a novel corneal epithelial regeneration agent in dry eye disease.

OBJECTIVE: To evaluate the efficacy of insulin eye drops for dry eye disease in reducing corneal staining and improving symptoms. METHODS: In this retrospective case series, patients with dry eye disease treated with off-label use of insulin eye drops were collected. The main inclusion criterion was diagnosis of dry eye disease with epithelial damage and acceptance of the off-label use of topical insulin. Age, sex, type of dry eye disease, time since diagnosis, previous ocular surgeries, concomitant treatment, best corrected visual acuity, symptoms, conjunctival hyperemia and corneal staining were recorded. Data from the 1 and 3-month visit were included. RESULTS: 16 patients (32 eyes) were treated with insulin (14 females and 2 males; mean age 61.3 ± 16.8 years). 12 patients (71%) were also on autologous serum and 10 patients (63%) on cyclosporine. Symptoms were 3.4 ± 1.3 (range 2-5) when scaled from 0 to 5. Mean hyperemia was 1.0 ± 0.9 (range 0-3) and corneal staining was 2.5 ± 1.3 (range 0-5). After 3 months, 5 patients (31%) referred to be much better, 6 (38%) better, 3 (19%) slightly better and 2 patients (13%) were subjectively similar, mean symptoms being 2.3 ± 1.0 (range 1-4; p = 0.001). Hyperemia was 0.3 ± 0.4 (range 0-1) and corneal staining was 1.1 ± 1.0 (range 0-3; both p < 0.001). Topical insulin was well tolerated with no adverse events. CONCLUSIONS: The excellent results presented in these case series illustrate topical insulin as a promising treatment in dry eye disease with refractory epithelial damage.

Efficacy and safety of intense pulsed light of upper and lower eyelids in Meibomian gland dysfunction: A prospective multicentric study.

PURPOSE: To demonstrate that intense pulsed light therapy (IPL) of the upper and lower eyelids with meibomian gland expression (MGX) is effective in improving dry eye disease due to meibomian gland dysfunction (MGD). METHODS: Patients with ocular discomfort (Ocular Surface Disease Index -OSDI- above 13) and signs of MGD were recruited. All patients underwent OSDI, visual acuity (VA), intraocular pressure, Schirmer test, meibography, non-invasive tear breakup time (NITBUT), slit-lamp examination (corneal and conjunctival staining, hyperemia, gland expressibility, and meibum quality), tear osmolarity and lipid layer thickness. IPL was performed with Optima IPL (Lumenis Ltd.) following a standardized protocol on upper and lower eyelids of both eyes, with inferior eyelid MGX. Patients received four sessions separated by two weeks each. Four weeks after, examinations were repeated. RESULTS: 160 patients (320 eyes) were included, of which 108 (67.5%) were women and mean age was 59.2 ± 15.08 (range 20-89). After four sessions, VA, OSDI, tear osmolarity, lipid layer thickness, NITBUT, hyperemia, corneal and conjunctival staining, gland expressibility, meibum quality, inferior eyelid Meiboscore and Schirmer test improved (all, p < 0.027). Changes in OSDI, initial and average NITBUT increased with dry eye disease severity (according to OSDI). Increased pre-treatment OSDI, hyperemia, corneal and conjunctival staining and Schirmer test were associated with an improvement in OSDI (all, p < 0.040). No adverse events were noted. CONCLUSIONS: The combination of IPL on upper and lower eyelids with MGX is safe and effective for the treatment of MGD. Patients with severe dry eye disease present greater improvements.

Liposomal Ozonated Oil in Ocular Infections: A Review of Preclinical and Clinical Studies, Focusing on Its Antiseptic and Regenerative Properties.

Ozonated oil has shown antimicrobial, anti-inflammatory and regenerative properties that make it useful in the prevention of infectious diseases and also as an adjuvant in wound-healing management. This review brings together most aspects of the use of liposomal ozonated oil for ocular infections and regeneration of the ocular surface. A search was performed in PubMed, Medline, Web of Science and Cochrane Library for studies published by June 2021. Search terms were combined to sort out papers on the properties and use of ozonated oil in ocular infections. A total of 25 publications were selected for this review on the composition, mechanism of action, restorative action, and preclinical and clinical studies of liposomal ozonated oil focused on ocular infections. In patients with complicated corneal pathology, liposomal ozonated oil has been found to restore corneal ulcers and improve keratitis. In patients with ocular pathologies involving inflammation and infections, liposomal ozonated oil has been found to improve and almost completely restore the signs of vernal, granulomatous and even adenoviral conjunctivitis. Liposomal ozonated oil has also been found to be effective in reducing ocular microbial flora. In conclusion, liposomal ozonated oil has an antiseptic and regenerative effect on corneoconjunctival tissues. It has demonstrated efficacy and safety profile for its use in ocular infections and can be considered as a suitable supportive strategy both alone and combined with other antimicrobial agents.

Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment.

Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface.