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Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: “(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)”. A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment.

To assess the potential additive effects of short-term display use and contact lens (CL) wear on the ocular surface and tear film.Thirty-four healthy volunteers (20.87 ± 2.33 years old) participated in this study. Participants' dry eye symptoms, ocular surface, tear film and pupil size were assessed before and after executing a 20-min reading task on a computer and a smartphone with and without CL wear, or with CL wear and artificial tear instillation. Measurements included the Ocular Surface Disease Index (OSDI) questionnaire; 5-item Dry Eye Questionnaire (DEQ-5); tear meniscus height (TMH); noninvasive keratograph break-up time (NIKBUT); bulbar conjunctival redness (BR) and pupil size.Higher symptoms were reported after reading on both displays with and without CLs (p ≤ 0.001) for short periods. BR was higher and NIKBUT shorter after reading on the computer regardless of wearing CLs (p ≤ 0.02 and p ≤ 0.02, respectively), while TMH increased for all conditions (p ≤ 0.02) except for CL computer reading (p = 0.23). Reading with CLs did not lead to greater signs of dry eye (BR, NIKBUT) and symptoms compared with reading unaided (p 0.05), although a smaller increase in TMH was observed when reading on the computer with CLs (p = 0.005). Artificial tear instillation during CL wear led to a smaller increase in symptoms (p ≤ 0.02), a smaller increase in BR (p ≤ 0.04) and a decrease in NIKBUT (p = 0.02) compared to reading without correction.Disposable CL wear had no additive effects on signs and symptoms of dry eye when using digital devices for short periods. The instillation of artificial tears is an effective strategy for reducing the impact of display use in CL wearers.

Background In clinical practice, fluctuating vision or decreased quality of vision is a common complaint in DED patients. Our study was designed to investigate the change in dynamic optical quality in dry eye patients after the use of artificial tears. Methods Fifty-nine patients with dry eye disease (DED) and 31 control subjects were included in this prospective case-control study. There was no significant difference in age and sex between these two groups (P = 0.342, P = 0.847, respectively). Clinical evaluation of the ocular surface included Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), lipid layer thickness (LLT), and Schirmer I test. DED patients were divided into two groups, mild (31 patients) and severe (28 patients). The optical quality of the tear film was measured with the Optical Quality Analysis System (OQAS) using the mean objective scatter index (mean OSI), standard deviation of objective scatter index (SD-OSI) and modulation transfer function cut-off (MTF cut-off). After baseline examinations, one drop of artificial tears (ATs, carboxymethylcellulose ophthalmic solution, 0.5%) was instilled in both eyes, and optical quality parameters were measured again at 5 and 30 min following application of ATs. Results At baseline, the mean OSI was higher in the DED group (0.95 ± 0.54) than in controls (0.54 ± 0.23, P P = 0.003). Five minutes after AT instillation, mean OSI and SD-OSI decreased significantly in severe DED patients (P = 0.044; P = 0.018), remained unchanged in mild DED patients, and increased in the control group (P = 0.019; P Conclusion The effect of ATs on optical quality in patients with DED may differ according to the severity of the disease. Measurement of optical quality might be a promising tool to evaluate the effects of various ATs and possibly individualize treatment in DED patients.

This is a randomized controlled study aiming to evaluate the safety and efficacy of two different concentrations of topical nalbuphine hydrochloride, when used to relieve pain in the first days following photorefractive keratectomy (PRK).This is a prospective double blinded randomized clinical trial that included 189 patients who had PRK for correction of low and moderate refractive errors. Patients were randomly assigned to three groups according to the eye drops given to relieve pain in the first three postoperative days; the first group received topical nalbuphine with a concentration of 2 mg/ml (Group A = 64 patients), the second group received topical nalbuphine in a concentration of 1 mg/ml (Group B = 69 patients) and the third group received topical artificial tears only (Group C = 56 patients).The patients were asked to rate their pain daily using a numeric rating scale and to record the number of drops instillation times/day. The time needed for complete epithelial healing, best-corrected visual acuity (BCVA) and spherical equivalent after three months were recorded in each group.In the first three days, there was a statistically significant difference in pain score among the three groups with lower values in the two topical nalbuphine groups when compared with the control group receiving artificial tears. Moreover, the higher concentration group showed significantly lower pain score and less number of drops used /day in comparison with the lower concentration group.There were no statistically significant differences in epithelial healing time, BCVA and spherical equivalent after three months among the three groups.The use of topical nalbuphine is effective in relieving pain in the first few days following PRK and this pain relief is not associated with any compromise regarding epithelial healing nor refractive outcome. The pain control with 2 mg/ml concentration is significantly higher than that with 1 mg/ml concentration of nalbuphine. Trial registration numberISRCTN21394752 https://doi.org/10.1186/ISRCTN21394752 The trial is retrospectively registered in ISRCTN registry at March 08, 2021.

The purpose of this study was to assess short-term efficacy and safety of tear promotion eye drops (biological tear substitutes and topical secretagogues) for treating dry eye disease. Randomized controlled trials comparing short-term effects of biological tear substitutes or topical secretagogues versus placebo or other topical dry eye treatments in adults with dry eye disease were identified from the MEDLINE, Embase, Scopus, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases. Pairwise meta-analysis and network meta-analysis were performed. Outcomes were ocular symptoms, ocular surface staining, tear break-up time, Schirmer test, and adverse events. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Thirty-nine randomized controlled trials (3693 patients) were eligible. Using artificial tears as a reference, autologous platelet lysate was the most effective treatment for lowering ocular surface disease index (unstandardized mean difference [USMD] -31.85; 95% confidence interval [CI]: -43.19 to -20.51) and platelet rich plasma showed the most reduction in corneal fluorescein staining scores (standardized mean difference -2.52; 95% CI: -3.23 to -1.82). Cord blood serum was the most effective treatment for increasing tear break-up time (USMD 2.67; 95% CI: 0.53-4.82), and eledoisin was superior to others in improving Schirmer scores (USMD 2.28; 95% CI: 0.14-4.42). Most interventions did not significantly increase ocular adverse events compared with artificial tears. Biological tear substitutes, including autologous serum, autologous platelet lysate, platelet rich plasma, and cord blood serum, might be the most effective treatment among tear promotion eye drops in relieving dry eye symptoms without increasing adverse events. However, there remains uncertainty around these findings because of low/very low certainty of evidence.

Objective To confirm the feasibility of visualizing upper and lower proximal lacrimal canaliculi (LC) using spectral-domain optical coherence tomography (SD-OCT). Animals studied Eight eyes of four normal Beagle dogs. Procedures To obtain an upper proximal LC image, the head was turned in the opposite direction to the eye being imaged, and the medial part of the upper eyelid was everted to expose the LC. To obtain a lower LC image, the lower eyelid was everted just below the punctum. Using "angle mode", the scan line was placed parallel on the long axis of the LC. The inlet LC width (LCW) was measured. Artificial tears (AT) were instilled, and LCW was compared before and after AT instillation. Additionally, the return time to the initial LCW inlet width was recorded. Results Before AT instillation, there was a significant difference between the mean upper and lower LCW (91.8 ± 3.2 µm and 110.1 ± 8.4 µm, respectively). After AT instillation, the mean upper and lower LCW were 236.9 ± 27.7 µm and 238.4 ± 30.4 µm, respectively. Significant differences in the LCW before and after AT instillation in both the upper and lower LCWs were observed. The mean return time of the upper and lower LCW to their initial widths after AT instillation was within 4 min. Conclusions Spectral-domain optical coherence tomography was an effective method for providing high-resolution images of the upper and lower proximal LC. This method enables observation of LC changes after instillation of eyedrops in veterinary clinical practice.

Purpose: We aimed to investigate the efficacy and safety of single-dose autologous serum eye drops (ASEDs) for treatment of persistent corneal epithelial defects (PEDs). Methods: About 34 eyes of 26 patients treated from March 2016 to May 2020 with a single dose of ASEDs for PEDs that did not respond to conventional treatment were retrospectively evaluated. Patient demographics, predisposing factors, size, and duration of the PED, duration of treatment, and dosage of ASEDs, PED healing time, success rate of the ASED treatment, and follow-up time after the onset of ASED treatment were recorded. Autologous serum eye drops (20%) were prepared by diluting the serum with preservative-free artificial tears in single-dose vials. Vials were stored at −20°C and used daily after dissolving. Results: The mean patient age was 47.0 ± 18.5 years, and 13 (50%) of the patients were male. The most common indication for ASEDs was PED after keratoplasty. The mean duration of ASED treatment was 8.5 ± 6.3 months, and mean follow-up time was 22.8 ± 12.2 months. Autologous serum eye drop treatment was effective in 25 (73.5%) eyes and partially effective in 5 (14.7%) eyes. None of the eyes displayed complications related to the treatment. Conclusion: In patients with PED for whom conservative treatment is insufficient, ASEDs prepared by dilution with preservative-free artificial tears in single-dose vials and administered based on the daily use principle appear to be effective and safe.

Purpose: Evaluation of marketed eye drops with or without trehalose, a nonreducing natural osmoprotector disaccharide, in autophagy modulation and its role in cell survival during desiccation. Methods: Eye drops containing either sodium hyaluronate (SH) (Hyabak®, Thea, France) or a combination of SH with trehalose (Thealose Duo®, Thea, France) were compared with control conditions to evaluate the ability to modulate autophagy in human epithelial cells in vitro. Autophagy was monitored using LC3, a marker of the autophagic machinery, by fluorescence microscopy and immunoblot analysis. Control and autophagy-deficient cells treated with eye drops were exposed to desiccation to mimic dry eyes and cell survival was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Trehalose, a known autophagy inducer was used as a positive control. Results: Artificial tears containing SH with and without trehalose induce a complete autophagic flux, as indicated by an increase in the number of autophagosomes and autolysosomes, and the accumulation of the lipidated form of LC3 associated with complete autophagy. In addition, there was a synergistic effect of SH for autophagy induction when combined with trehalose, compared with each of the components alone. Survival of cells treated with both eye drops and exposed to desiccation was decreased in autophagy-deficient cells, demonstrating the essential role of autophagy on eye drop protection. Conclusions: Autophagic flux is induced by SH-containing eye drops, and this phenomenon is enhanced in combination with trehalose. We also demonstrated that autophagy induction is involved in the osmoprotective effects of both trehalose and SH-containing eye drops, to maintain epithelial cell homeostasis in dry conditions.

Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).We applied standard Cochrane methodology.We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.

Purpose: To systematically review and critically appraise clinical practice guidelines (CPGs) and summarise the recommendations for non-infectious and infectious conjunctivitis Methods: CPGs published on non-infectious and infectious conjunctivitis between 2010 and March 2020 were reviewed, evaluated, and selected using nine items from the Appraisal of Guidelines for Research and Evaluation II tool (4, 7, 8, 10, 12, 13, 15, 22 and 23). CPGs with an average score for items 4, 7, 8, 12, or 22 below 3 and/or a sum of the two researchers’ average score for all nine items less than 45 were excluded. Two authors independently extracted and validated the data using standardised forms. Results: Fifteen CPGs from five sources remained for data extraction. CPGs consistently recommended non-pharmacological interventions (artificial tears, cold compress, avoidance or removal of allergens) for non-infectious conjunctivitis and pharmacological interventions (topical anti-histamine, mast-cell stabiliser and dual-acting agent) for allergy types. Observation without treatment was strongly recommended for non-herpetic viral and bacterial infections. Systemic and topical anti-viral was consistently recommended for herpetic viral conjunctivitis, while systemic and topical antibiotics were recommended for chlamydial and gonorrhoeal conjunctivitis. The methods used to assess the level of evidence and the strength of recommendation varied among CPGs. Conclusions: There are a number of high-quality CPGs for non-infectious and infectious conjunctivitis. While there were a number of consistencies in the recommendations provided within these CPGs, several inconsistencies were also identified. Many of which related to the scope of practise of the targeted end-user of the particular guideline.

Purpose To evaluate the effect of brimonidine tartrate 0.025% ophthalmic solution on pupil size under scotopic conditions in healthy adults Methods Pupil size was measured in 56 eyes of 28 volunteer participants using a pupillometer under scotopic conditions. Age, gender, and iris color were recorded. Subjects using any ophthalmic medications other than artificial tears were excluded. The pupil size was subsequently measured again under scotopic conditions 60 min after instillation of brimonidine tartrate 0.025% ophthalmic solution. Results Statistically significant miosis was seen after instillation of brimonidine tartrate 0.025% (p = 0.04). Average pupil size prior to brimonidine 0.025% instillation was 7.28 ± 1.05 mm, and average pupil size after instillation of brimonidine 0.025% was 6.36 ± 1.68 mm, a reduction of − 23.7% in pupil area. Subjects with light irides demonstrated a greater miotic effect than subjects with dark irides (1.55 mm vs. 0.67 mm, p Conclusions Brimonidine tartrate 0.025% causes significant miosis in scotopic settings, although the effect is not as great in darker colored eyes. Further studies are needed to determine the latency and duration of the effect and whether the amount of miosis is clinically significant.

This study evaluates the effectiveness of objective techniques in assessing dry eye disease (DED) treatment compared with the subjective assessment commonly used in clinical practice. Thirty subjects were recruited for two visits separated by 28(± 3) days of treatment with artificial tears. A buttery of common subjective assessment methods were accompanied by a set of objective techniques including measurement of noninvasive tear film break-up time (NIBUT), lipid layer thickness (LLT), and quantitative evaluation of tear film surface quality and dynamics (TFD). Additionally, meibography was performed. Two commercially available videokeratoscopes and a prototype of a lateral shearing interferometer were used for the measurements. Both subjective and objective techniques showed a positive effect of artificial tears in DED treatment. Statistically significant improvements were observed in subjective symptoms (from P p = 0.019 for tearing), conjunctival redness (P = 0.022), ocular staining (P = 0.012), fluorescein tear film break-up time (P = 0.015), NIBUT (P = 0.037), LLT (P P = 0.048). In general, weak or statistically insignificant correlations were observed between subjective and objective assessment methods. The apparent lack of correlation between these methods might indicate the complementary character of objective techniques that likely assess other characteristics of ocular surface health than those assessed subjectively.

Introduction Triple A syndrome is a very uncommon disease marked by a triad of adrenocorticotrophic hormone (ACTH)—resistant features: adrenal insufficiency, alacrimia, and achalasia. It presents in several clinical forms with undetermined incidence and shows an autosomal pattern of inheritance. It is caused by a variety of mutations in the AAAS genes which encode a protein of unknown function called ALADIN. Diagnosis depends on clinical manifestations, laboratory test results, imaging and endoscopic findings, and Schirmer’s test. The treatment includes artificial tears, glucocorticoid replacement therapy, and treatment of achalasia. Case presentation A 12-year-old Syrian girl was referred to Damascus University’s Children’s Hospital for recurrent pulmonary infection. Her mother had noted an absence of tears when crying since birth, diffused pigmentations since birth, especially on the cheeks and genitals, recurrent vomiting of both solid and liquid foods, and recurrent exacerbations of bronchitis and recurrent pneumonia. ACTH and blood cortisol levels indicated an adrenal insufficiency, chest computed tomography and barium swallow test results indicated achalasia, tear break-up time as well as eye examination indicated alacrimia, which led to the diagnosis of triple A syndrome. Treatment included Heller cardiomyotomy, artificial tears, and hydrocortisone (15–30 mg/m2), as well as continuous observation of ACTH levels. Discussion Triple A syndrome (which is characterized by the triad of achalasia, alacrima, adrenal insufficiency) is a rare multisystem disease. It has a genetic background and is potentially fatal. This syndrome is often misdiagnosed, especially in regions where it is expected to have a high prevalence rate (regions with documented cases and high rate of consanguinous marriage), This study is the first documentation of triple A syndrome in Syria, a country where consanguineous marriage is common. This syndrome should be kept in mind when a child presents with one or more of its characteristic features.

Our purpose is to demonstrate the changes in cornea nerve parameters and symptoms and signs in dry eye disease (DED) patients after oral vitamin B1 and mecobalamin treatment. In this randomized double-blind controlled trial, DED patients were randomly assigned to either the treatment group (oral vitamin B1 and mecobalamin, artificial tears) or the control group (artificial tears). Corneal nerve parameters via in vivo confocal microscopy (IVCM), DED symptoms, and signs were assessed at baseline and 1 and 3 months post-treatment. In total, 398 eyes from 199 patients were included. In the treatment group, there were significant improvements in corneal nerve length, width, and neuromas, the sign of conjunctival congestion score (CCS), symptoms of dryness, pain, photophobia, blurred vision, total symptom score, and OSDI (OSDI) at 1/3 months post-treatment (all p < 0.05). Patients who received vitamin B1 and mecobalamin showed greater improvement in CCS, dryness scores at 1 month (p < 0.05), corneal fluorescein staining (CFS) (p = 0.012), photophobia (p = 0.032), total symptom scores (p = 0.041), and OSDI (p = 0.029) at 3 months. Greater continuous improvement in CFS (p = 0.045), dryness (p = 0.033), blurred vision (p = 0.031) and total symptom scores (p = 0.023) was demonstrated at 3 months than at 1 month post-treatment in the treatment group. We found that oral vitamin B1 and mecobalamin can improve corneal nerve length, width, reflectivity and the number of neuromas in IVCM, thereby repairing epithelial cells and alleviating some ocular symptoms. Thus, vitamin B1 and mecobalamin are potential treatment options for patients with DED.

ilustraciones, gráficas, tablas Introducción: Este es un estudio farmacoepidemiológico acerca de patrones de prescripción de lubricantes oculares en pacientes sometidos a cirugía refractiva en un centro oftalmológico de la ciudad de Bogotá durante el año 2019. Objetivos: Describir la terapia farmacológica y los patrones de prescripción de lubricantes oculares en pacientes post quirúrgicos de cirugía refractiva. Objetivos Específicos: Caracterizar clínica y demográficamente a la población de estudio, evaluar la frecuencia de prescripción de lubricantes oculares y contrastarlo con las guías de práctica clínica. Metodología: Se realizó un estudio observacional descriptivo de corte transversal con recolección retrospectiva de la información. Este estudio describió 3 grupos de variables: Demográficas, clínicas y farmacológicas. Resultados: Demográficamente el 61,2% de la población de estudio correspondió al género femenino, mientras 38,70% correspondió al género masculino. En cuanto a la pirámide poblacional, el mayor porcentaje de pacientes intervenidos se ubicó en el grupo etáreo de 24 a 36 años para género femenino y 30 a 32 años para el masculino; el menor porcentaje para ambos géneros se ubicó entre 18 a 20 años. Para el análisis ocupacional de la población se plantearon categorías, donde las actividades laborales fueron similares, un 45% de la población describió la categoría “otros”, seguido de un 30% de la categoría de “Estudiantes” y un 12% en la categoría “Oficina”. En cuanto a las variables clínicas se encontró que en el 93% de la población se practicó el procedimiento refractivo conocido como Lasik y el diagnóstico refractivo preoperatorio más frecuente en ambos géneros fue astigmatismo Miópico compuesto. En cuanto a las variables farmacológicas, se encontró que el 12% de la población de estudio tenía antecedentes farmacológicos previos a la cirugía refractiva, y algunos de estos principios activos estaban asociados con sintomatología de ojo seco. Así mismo, se encontró mayor frecuencia de prescripción de lubricantes oculares derivados de celulosa tales como carboximetilcelulosa sódica en combinación con hialuronato de sodio y glicerina en el manejo de ojo seco post quirúrgico. No obstante, se encontraron prescritos otros principios activos como antiinflamatorios, antibióticos y antihistamínicos oftálmicos, así como diferentes formas farmacéuticas, lo cual estuvo en relación con la guía de práctica clínica analizada. Conclusiones: Existen elementos como ocupación, género, edad e incluso el tipo de procedimiento refractivo influyentes en el diagnóstico de ojo seco post quirúrgico. El mayor porcentaje de individuos que cursaron sintomatología de ojo seco y que fue tratado, correspondió al género femenino, lo que se correlaciona con la literatura consultada. Sobresalen los derivados de celulosa como los principios activos de lubricantes oculares más prescritos tanto en post operatorio como fase evolución. No obstante, en la práctica profesional se tiende a subestimar el diagnóstico de ojo seco en población joven. Existe diversidad en los patrones de prescripción de lubricantes a nivel oftálmico, los cuales pueden fundamentarse en las recomendaciones de escalonamiento de las guías de práctica clínica; aunque en la práctica los manejos no suelen llevarse de manera rigurosa. (Texto tomado de la fuente). This is a pharmacoepidemiological study about ocular lubricant prescription patterns in patients undergoing refractive surgery in an ophthalmologic center in the city of Bogota during 2019. Objectives: To describe the pharmacological therapy and prescription patterns of ocular lubricants in post refractive surgery patients. Specific Objectives: To clinically and demographically characterize the study population, evaluate the frequency of prescription of ocular lubricants and contrast it with clinical practice guidelines. Methodology: A cross-sectional descriptive observational study with retrospective data collection was performed. This study described 3 groups of variables: demographic, clinical and pharmacological. Results: Demographically, 61.2% of the study population was female, while 38.70% was male. Regarding the population pyramid, the highest percentage of patients undergoing surgery was in the age group 24 to 36 years for females and 30 to 32 years for males; the lowest percentage for both genders was between 18 and 20 years. For the occupational analysis of the population, categories were proposed, where the work activities were similar, 45% of the population described the category "others", followed by 30% in the category "Students" and 12% in the category "Office". Regarding the clinical variables, it was found that 93% of the population underwent the refractive procedure known as Lasik and the most frequent preoperative refractive diagnosis in both genders was compound myopic astigmatism. Regarding pharmacological variables, it was found that 12% of the study population had a pharmacological history prior to refractive surgery, and some of these active ingredients were associated with dry eye symptoms. Likewise, a higher frequency of prescription of ocular lubricants derived from cellulose such as sodium carboxymethyl cellulose in combination with sodium hyaluronate and glycerin was found in the management of post-surgical dry eye. However, other active ingredients such as anti-inflammatories, antibiotics and ophthalmic antihistamines were found to be prescribed, as well as different pharmaceutical forms, which was in relation to the clinical practice guideline analyzed. Conclusions: There are elements such as occupation, gender, age and even the type of refractive procedure influential in the diagnosis of post-surgical dry eye. The highest percentage of individuals who presented dry eye symptoms and were treated corresponded to the female gender, which correlates with the literature consulted. Cellulose derivatives stand out as the most prescribed active principles of ocular lubricants both in postoperative and evolution phase. However, in professional practice, dry eye diagnosis tends to be underestimated in young people. There is diversity in the prescription patterns of lubricants at ophthalmic level, which can be based on the recommendations of clinical practice guidelines; although in practice, management is not usually carried out in a rigorous manner. Maestría Magíster en Ciencias - Farmacología

This study aimed to systematically evaluate the effect of intense pulsed light (IPL) therapy in patients harboring dry eye disease caused by meibomian gland dysfunction (MGD) based on qualified studies.The electronic databases, including PubMed, Cochrane, and Embase, were searched using keywords to identify available publications updated to November 2021. Relative risk or weighted mean difference combined with 95% confidence interval was used to synthesize the outcomes of included studies. The meta-analysis included 15 randomized controlled trials with 1,142 patients (2,284 eyes).The results revealed that IPL could significantly decrease the ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED), artificial tear usage, tear film lipid layer, meibomian gland quality (MGQ), meibomian gland expression (MGX), and corneal fluorescein staining (CFS) while increase tear break-up time (TBUT) and noninvasive tear break-up time (NIBUT) compared with sham. Compared with MGX, IPL+MGX markedly decreased the SPEED, CFS, and tear meniscus height (TMH), but with increased TBUT. Compared with MGX, IPL showed significant effect in increasing the OSDI and TBUT, but decreasing the TMH and NIBUT. However, no significant differences were seen between IP+MGX and MGX in OSDI, MGQ, and MGX, nor between IPL and MGX in OSDI, SPEED, and TBUT.We identified that the application of IPL alone or IPL combined with MGX elicited superior clinical effect for improving the eye function and symptoms in the treatment of MGD-related dry eye disease, which is considered available for wide clinical application.

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer’s test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 (p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.

Significance The effectiveness of masking is rarely evaluated or reported in single- or double-masked clinical trials. Knowledge of treatment assignment by participants and clinicians can bias the assessment of treatment efficacy. Purpose This study aimed to evaluate the effectiveness of masking in a double-masked trial of 5% povidone-iodine for the treatment of adenoviral conjunctivitis. Methods The Reducing Adenoviral Patient Infected Days study is a double-masked, randomized trial comparing a one-time, in-office administration of 5% povidone-iodine with artificial tears for the treatment of adenoviral conjunctivitis. Masking was assessed by asking participants and masked clinicians at designated time points if they believed the treatment administered was povidone-iodine or artificial tears, or if they were unsure. Adequacy of masking was quantified using a modified Bang Blinding Index. Results Immediately after treatment, 34% of participants who received povidone-iodine and 69% of those who received artificial tears guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.31 and -0.38, respectively). On day 4, 38% of the povidone-iodine participants and 52% of the artificial tear participants guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.24 and -0.05, respectively), indicating adequate and ideal masking. On days 1, 4, 7, 14, and 21, masked clinicians guessed incorrectly or were unsure of treatment in 53%, 50%, 40%, 39%, and 42% among povidone-iodine participants compared with 44%, 35%, 38%, 35%, and 39% among artificial tears participants, respectively. The modified Bang Indices for clinician masking in the povidone-iodine group ranged from -0.05 to 0.25 and from 0.13 to 0.29 in the artificial tears group. Conclusions Masking of participants and clinicians was adequate. Successful masking increases confidence that subjective measurements are not biased. We recommend quantitative assessment and reporting the effectiveness of masking in ophthalmic clinical trials.

To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180.Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED.Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.

Significance The prevalence of dry eye disease and low vision increases with age; they share risk factors and can be the result of underlying common causes. They are generally studied separately; however, combining these perspectives is relevant for research on assistive technology given that sustained focus affects the tear film because of decreased blinking rates. Purpose The objective of this study was to elucidate to which extent dry eye disease risk factors, signs, and symptoms are assessed in low vision patients who receive an eye examination as part of their vision rehabilitation services. Methods Using a retrospective chart review, dry eye disease risk factors, signs, or symptoms were extracted from 201 randomly selected files that contained an eye examination in the past 5 years from two vision rehabilitation centers. Results Demographic variables of charts from the two sites did not differ (mean visual acuity, 0.85 logMAR [standard deviation, 0.53; range, 0 to 2.3]; mean age, 71.2 years [standard deviation, 19 years; range, 24 to 101 years]). Fifty charts (25%) mentioned at least one dry eye disease symptom. Sixty-one charts (30.3%) reported systemic medications that can exacerbate dry eye disease, whereas 99 (49.2%) contained at least one systemic disease thought to contribute to dry eye disease symptoms; 145 (72.1%) mentioned at least one type of ocular surgery. Artificial tears were documented in 74 charts (36.8%). Few specific dry eye tests were performed, with the exception of corneal integrity assessment reported in 18 charts (8.95%). Conclusions Low vision patients have multiple risk factors for dry eye disease; however, dry eye disease tests were not frequently performed in comprehensive low vision eye examinations in this sample. More efforts should be made to assess dry eye disease to enhance comfort and functional vision, especially with the increasing demands of digital devices as visual aids.

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.

Purpose The purpose of this study was to compare the efficacy of artificial tears and warm compress with an eyelid warming mask (EWM) in alleviating dry eye syndrome (DES) in contact lens wearers Methods This study was a prospective, randomized, active-controlled trial. Participants included 81 university students aged 19 or over, who had been wearing contact lenses for more than 1 year; they were randomly categorized into three groups. In the artificial tear group, one single-use artificial tear was administered every day as needed over a period of 4 weeks. In the EWM group, participants were instructed to apply a warm compress using a disposable EWM for 30 min before bedtime daily. Participants in the control group maintained their normal lifestyle without any treatment regimen. Ocular Surface Disease Index (OSDI) and Schirmer test scores for all participants were checked before the experiment and after 4 weeks. Results After treatment, the EWM and artificial tears group had significantly decreased OSDI scores compared with the control group. However, there was no significant difference between the former two groups. The post-treatment Schirmer test scores for the right eye did not differ between three groups, whereas those for the left eye were significantly higher in the two treatment groups than in the control group. However, there was no significant difference between the EWN and artificial tears groups. Conclusion Contact lens wearers who were instructed to apply a warm compress using EWM had significantly increased OSDI and Schirmer test scores, indicating that it has a positive effect on DES. In conclusion, applying a warm compress with EWM can be recommended as a treatment for DES in contact lens wearers who use lenses for an extended period.

Purpose Dry eye disease (DED) is often managed with over-the-counter eye drops. This study evaluated the diurnal effects of a single drop of two ocular lubricants (nanoemulsion vs. non-emollient) on tear film lipid layer thickness (LLT) and symptoms of ocular dryness. Subjects were also assessed after 1 month of nanoemulsion eye drop use. Methods Part 1 was a cross-over comparison of a nanoemulsion and a non-emollient eye drop. LLT and dry eye symptoms were measured at baseline and at 15 min, 1 h, 2 h, 4 h and 6 h after instillation of each drop. Part 2 was a 1-month observational study assessing LLT and symptoms after 30-day use of the nanoemulsion drop four times daily (qid). Results Total of 20 subjects completed the study (mean age = 45.6 ± 7.9, 15 female). Part 1 found a significant increase in average LLT 15 min after nanoemulsion drop instillation in the overall and inferior third of the tear film for subjects with baseline LLT values

To evaluate the short-term effect of 0.15% sodium hyaluronate (SH), 0.20% SH, and Trehalose + 0.15% SH on anterior corneal aberrations in dry eye patients.76 eyes of 76 dry eye patients were divided into three groups. Non-preserved 1.5 mg/mL SH was administered in group 1, non-preserved 2.0 mg/mL SH was administered in group 2, and non-preserved trehalose 30 mg/mL and 1.5 mg/mL SH was administered in group 3. Aberrometry measurements were performed before and 10 min after application of the artificial tear drop. Using the Pentacam Scheimpflug imaging system, total root mean square (RMS), lower-order aberration (LOA), higher-order aberrations (HOAs), spherical aberration (SA), trefoil, and coma aberrations were investigated.In each group; the RMS of total, LOA, HOAs, and spherical aberration were significantly decreased after the artificial drop instillation, compared with those of them at baseline; and in groups 1 and 2, vertical trefoil term was also significantly increased, compared with those of them at baseline. According to intergroup analyzes, there was no significant outcome.It was observed that three artificial tears reduced the anterior corneal aberrations, in a 10-min period. The short-term effect of three artificial tears on the anterior corneal aberration was similar.

Purpose: High-frequency applied cetalkonium chloride (CAC) and benzalkonium chloride (BAC) 0.02% did not hamper corneal healing in a living rabbit model of induced corneal erosion. In contrast, the...

Purpose: To compare the 3-month results of treatment with 20% autologous serum or combination treatment with preservative-free artificial tears and 0.05% cyclosporine in patients with dry eye disease due to primary Sjögren’s syndrome. Methods: A total of 130 eyes of 65 patients with newly diagnosed dry eye disease due to primary Sjögren’s syndrome were included in the study. The patients were divided into two treatment groups: 66 eyes of 33 patients were assigned to the autologous serum treatment group, and 64 eyes of 32 patients were assigned to the combination treatment group. Schirmer test, tear break-up time and Ocular Surface Disease Index (OSDI) scores were recorded at pretreatment and at 3 months of treatment. Results: At 3 months of treatment, the mean Schirmer value and the mean tear break-up time were significantly higher in the combination treatment group (p

To assess and compare the effectiveness of four main management strategies for preventing short-term effects of digital display use on dry eye signs and symptoms.The ocular surface, tear film, and visual fatigue of 47 healthy individuals were assessed before and after reading on a laptop computer for 20 min under five different experimental conditions: control, instillation of artificial tears, taking a brief break, using a blue light screen filter, and blink control. Measurements included the Ocular Surface Disease Index (OSDI) Questionnaire, 5-item Dry Eye Questionnaire (DEQ-5), tear meniscus height (TMH), noninvasive keratograph break-up time (NIKBUT), bulbar conjunctival redness, and pupil size.Worse results were obtained after the control and blue light filter conditions in all variables (P≤0.037). A higher post-task DEQ-5 score (P=0.013) and TMH (P0.0005) were obtained when taking a brief break compared with pretask, although the increase in symptoms was significantly smaller than that observed in the nonmanagement control condition (P≤0.036). Similarly, a smaller increase in OSDI and DEQ-5 was obtained with the use of artificial tears and blink control in comparison with the control condition (P≤0.008), whereas a greater increase in DEQ-5 and decrease in NIKBUT was obtained for the blue light filter condition in comparison with the instillation of artificial tears (P=0.017) or blink control (P=0.008), respectively. Finally, a significantly lower post-task pupil size was obtained for all the conditions (P≤0.027).The instillation of artificial tears and blink control were the best management strategies for preventing short-term effects of digital display use on dry eyes. Conversely, using a blue light filter did not offer any benefits.

Dry eye disease (DED) is a common disorder that remains challenging from a clinical perspective. Unstable or deficient tear film is a major factor contributing to DED and the inability to resolve the loss of tear film homeostasis that accompanies DED can result in a vicious circle of inflammation and treatment-refractory disease. Recently recognized as a multifactorial disease, the main etiological subtypes of DED are aqueous-deficient and evaporative which exist on a continuum, although evaporative dry eye (EDE) is the more frequent classification. Although attaining greater recognition in recent years, there is currently no consensus and no clear recommendation on how to manage EDE. Clarity on the early diagnosis and treatment of EDE may facilitate the avoidance of progression to chronic inflammation, permanent damage to the ocular surface, and treatment-refractory disease. The purpose of this review was to identify current best practice for management of EDE in order to help clinicians in providing accurate diagnosis and optimized treatment. We summarize recent literature considering the role of the lipid layer on tear film stability, the importance of its composition and of its dynamic behavior, and the link between its malfunction and the insurgence and maintenance of tear film-related diseases. We have provided an assessment of the best management of lipid-deficient EDE based upon an understanding of disease pathophysiology, while indicating the flow of current treatments and possible future evolution of treatment approaches. Lipid containing eye drops may be considered as a step closer to natural tears from artificial aqueous tears because they more closely mimic the aqueous and lipid layers and may be used in combination with other management approaches. As a next step, we recommend working with a wider expert group to develop full guidelines to enable patient-centered management of EDE. Key pointsDry eye is a multifactorial disease of variable presentation with the tendency to become a chronic disease for which it is essential to identify and treat the main pathogenic mechanisms involved and tailor the treatment to the individual patient.Early intervention is needed to prevent the vicious cycle of DED and may require a multi-faceted management approach.EDE is not just a problem of MGD but can be the result of anything affecting blinking, mucin spreading, aqueous layer volume and content.Lipid-containing eye drops may provide significant relief of symptoms by improving the lipid layer and its spreading ability and, as such, are an appropriate component of the overall management of lipid-deficient EDE; natural lipid-containing eye drops should be the preferred treatment.

Rheological patterns were objectively calculated considering the first and last viscosity, besides the difference of viscosity with a specific shear rate. Shear thinning, shear thickening, thixotropic, and Newtonian behavior patterns were found.This study aimed to describe, in an objective way, the rheological behavior of several artificial tears.Seventy-eight artificial tears were included in this experimental analytical study. Its viscous behavior was measured using a cone-plate rheometer. An ascending and descending measurement range was defined for the shear rate from 1 to 1000 s-1 and vice versa. Hysteresis was calculated with the initial and final difference of viscosity. The rheological behavior pattern was calculated as the viscosity difference for the shear rate between 100 and 1000 s-1.Four rheological patterns with different magnitudes were found: shear thinning, shear thickening, thixotropic, and Newtonian.The viscosity of artificial tears always depends on the shear rate. It is possible to find two patterns simultaneously depending on the shear rate. These rheological patterns could serve to optimize the treatment with lubricants for different conditions of the ocular surface. In vivo studies are necessary to evaluate the clinical significance of these findings.

The current study is the first report to describe the improvement of ferning patterns of human tears using electrolyte solutions. The results can help in the production of new artificial tears to improve the quality of tears.This study aimed to investigate the effect of the addition of different volumes of various electrolyte solutions on ferning patterns of human tears.Tear samples (20 μL) were collected from the right eye of 13 subjects (5 men and 5 women) aged 19 to 36 years (27.1 ± 5.1 years) with normal eyes. Then, 1 μL of each tear sample was dried on a microscopic glass slide, and obtained ferns were observed using light microscopy and graded using the 5-point tear ferning (TF) grading scale. Homogenous mixtures of each tear sample (0.5 μL) and different volumes (0.5 to 5 μL) of each electrolyte were prepared. A sample (1 μL) of each mixture was dried, and the ferns obtained were graded and compared with those of the corresponding tears collected from subjects before the addition of electrolyte solutions.After the addition of electrolyte solutions, the TF grades of tears collected from healthy humans were generally improved. Significant (Wilcoxon test) improvements have been seen in the TF grades of the tear samples after the addition of a solution of potassium chloride (P = .03), calcium chloride (P = .01), magnesium chloride hexahydrate (P = .002), and sodium dihydrogen phosphate (P = .002). No significant improvements in the TF grades were seen after the addition of sodium chloride solution (P = .33).Ferning grades of human tears improved with most of the electrolytes used.

BACKGROUND: Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care. OBJECTIVES: To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021. SELECTION CRITERIA: We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune‐modulating therapy was compared with placebo, an active control, or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid‐containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone‐iodine [PVP‐I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP‐I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP‐I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP‐I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA‐I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP‐I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP‐I or PVA‐I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty. AUTHORS' CONCLUSIONS: The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP‐I alone resolves signs and symptoms by seven days relative to artificial tears. PVP‐I or PVA‐I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high‐level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short‐ and long‐term outcomes.

PURPOSE: To clarify the short-term effect of topical anesthetics on 16S ribosomal ribonucleic acid amplicon sequencing results in ocular surface microbiome research. METHODS: Both eyes of 24 eligible volunteers undergoing general anesthesia were sampled. Before sampling, a drop of artificial tears or a drop of topical anesthetic was applied in a randomized way. By using artificial tears as a control, we assured blinding of the executer and took a potential diluting effect into account. Bacterial DNA was extracted using the QIAGEN RNeasy PowerMicrobiome Kit with specific adaptations. Amplified DNA was sequenced with the Illumina MiSeq sequencing platform. RESULTS: Four sample pairs were excluded due to low yield of bacterial DNA. In the remaining 20 sample pairs, no differences were observed with topical anesthetics at the levels of amplicon sequence variants (ASVs), phylum, genera, or alpha and beta diversity. Weighted UniFrac distance confirmed that the intraindividual distance between the right and left eye was smaller than the effect of the topical anesthetic. Interestingly, however, we identified Cutibacterium as a potential discriminative biomarker for topical anesthetic use. Overall, a significantly higher number of observed reads were assigned to genera with Gram-positive characteristics. CONCLUSIONS: Based on our targeted, double-blinded, within-subject study, topical anesthetics do not affect the overall sequencing results but display a specific effect on Cutibacterium. When comparing research results, the impact of topical anesthetics on prevalence and abundance of Cutibacterium should be considered. TRANSLATIONAL RELEVANCE: Understanding and standardization of sampling techniques are indispensable to properly execute clinical microbiome research. ispartof: TRANSLATIONAL VISION SCIENCE & TECHNOLOGY vol:11 issue:3 ispartof: location:United States status: published