Effectiveness of acupuncture at acupoint BL1 (Jingming) in comparison with artificial tears for moderate to severe dry eye disease: a randomized controlled trial.

BACKGROUND: The global incidence of dry eye disease (DED) is very high. DED seriously affects the quality of life of patients; however, the current curative effect of medicine for moderate to severe DED is poor. This randomized clinical trial was planned to investigate the effect of acupuncture compared with artificial tears (AT) on moderate to severe DED. METHODS: A randomized clinical trial was performed at 2 hospitals in China. 120 DED patients were randomly equally divided into an acupuncture and an artificial tear group. Either acupuncture or artificial tears was performed for an 8-week period, and a 24-week follow-up was performed. The primary outcome measure was the Schirmer-I test (SIT) change from baseline. The secondary outcome measures included the numerical rating scale (NRS) change from baseline for improvement in ocular symptoms, the ocular surface disease index (OSDI), the tear-film break-up time (TBUT), corneal fluorescein staining (CFS), and acupuncture acceptability. Adverse events also were monitored and documented. RESULTS: For the primary outcome, the mean changes from baseline in the SIT values were significantly different between the acupuncture (5.75 [2.53-9.75]) and AT (0.52 [- 1.18-2.46]) groups at week 8 with a between difference of 5.23 (P < 0.05). Between-group differences of 8.49 in OSDI score change from baseline differed significantly at week 8 (P < 0.05). However, between-group differences of the changes in the average symptom NRS score, TBUT, and CFS did not differ significantly at week 8. Five cases experienced acupuncture-related adverse events. CONCLUSIONS: This randomized clinical trial found that acupuncture at BL1 significantly promoted tear secretion. Acupuncture showed greater benefits than AT for moderate to severe DED. However, the study findings warrant verification. TRIAL REGISTRATION: Registration number: ChiCTR1800015831. Name of trial registry: Efficacy and safety of acupuncture in the treatment of moderate to severe dry eye disease: a randomized controlled trial. Registered on 23 April 2018 ( https://clinicaltrials.gov/ ).

Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study.

BACKGROUND: Dry eye disease (DED) affects more than 14% of the elderly population causing decrease of quality of life, high costs and vision impairment. Current treatments for DED aim at lubricating and controlling inflammation of the ocular surface. Development of novel therapies targeting different pathogenic mechanisms is sought-after. The aim of this study is to evaluate safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops in patients with DED. METHODS: Forty consecutive patients with moderate to severe DED were included in a phase IIa, prospective, open label, multiple-dose, clinical trial to receive rhNGF eye drops at 20 µg/mL (Group 1: G1) or at 4 µg/mL (Group 2: G2) concentrations, two times a day in both eyes for 28 days (NCT02101281). The primary outcomes measures were treatment-emerged adverse events (AE), Symptoms Assessment in Dry Eye (SANDE) scale, ocular surface staining and Schirmer test. RESULTS: Of 40 included patients, 39 completed the trial. Both tested rhNGF eye drop concentrations were safe and well tolerated. Twenty-nine patients experienced at least one AE (14 in G1 and 15 in G2), of which 11 had at least 1 related AE (8 in G1 and 3 in G2). Both frequency and severity of DED symptoms and ocular surface damage showed significant improvement in both groups, while tear function improved only in G1. CONCLUSIONS: The data of this study indicate that rhNGF eye drops in both doses is safe and effective in improving symptoms and signs of DED. Randomised clinical trials are ongoing to confirm the therapeutic benefit of rhNGF in DED. TRIAL REGISTRATION NUMBER: NCT02101281.

A review of the efficacy, safety and tolerability of Lacrycon® eye drops for the treatment of dry eye syndrome.

Lacrycon® is a preservative-free hypotonic artificial tear for the treatment of dry eye syndrome containing hyaluronic acid, carbomer, and glycerol. Lacrycon has been used for many years; this is the first comprehensive review of clinical efficacy and tolerability. Eight clinical studies (1992-2013) were reviewed. Comparators included phosphate-buffered saline (Phase I) and active controls (Phase II: Lacrisol™; Phase III: Gel-larmes™, Lacrisol, Hyalistil®, Vismed®, or the currently prescribed tear substitute). Administration schedules varied from 3 to 8 instillations per day for 7 to 84 days, and evaluation timepoints varied between studies. Pre-corneal retention of Lacrycon was 22% better than phosphate-buffered saline in terms of AUC (P=0.048). Patients' evaluation of efficacy was better for Lacrycon than Gel-larmes on Day 15 and 45 (P<0.05) and similar on Day 90 (P>0.05); there was no difference (P>0.05) versus Hyalistil (Day 30) or Vismed (Day 35 and 85). Functional tests were either in favor of Lacrycon (P<0.05) (fluorescein test [versus Gel-larmes/Lacrisol/Hyalistil], tear break-up time [TBUT] and rose Bengal test, Schirmer I test, and tear meniscus [versus Lacrisol]), or there was no difference between treatments (P>0.05) (fluorescein test [versus Vismed], TBUT and rose Bengal test [versus Gel-larmes], Schirmer I test [versus Gel-larmes/Lacrisol/Hyalistil/VisMed], tear meniscus [versus Lacrisol/Hyalistil], Oxford Grading Score, OSDI, van Bijsterveld score, and conjunctival hyperemia [versus Vismed]). Lacrycon was better tolerated than most comparators and had a similar safety profile to Vismed. No comparison showed favored the comparator over Lacrycon. These good efficacy, tolerability and safety data support the use of Lacrycon in dry eye syndrome.

The effect of ocular lubricants containing benzalkonium chloride on nasal mucosal flora.

PURPOSE: The effect of ocular artificial teardrop containing benzalkonium chloride (BAC) on nasal mucosa was investigated. MATERIALS AND METHODS: There were two different treatment trial groups. Each dry eye syndrome (DES) patient received the ocular lubricant treatment four times a day in both groups (one group containing BAC, the other group was not). Moistened sterile cotton-tipped applicators were placed in both nostrils and were immediately cultured prior to ocular lubricant treatment and at the end of treatment trial. The bacterial culture-positivity rate, species of bacteria, and drug sensitivity were recorded in the two groups during pre-treatment and post-treatment. RESULTS: There were 20 patients in each group with a mean age of 53.14 years (36 female, 4 male). At the beginning of the treatment trial, Staphylococcus epidermidis was the most frequently isolated organism from the nasal cavity accounting in 24/40 patients (60%). Of the 40 organisms isolated from the nares prior to treatment trial, 37 (92.5%) were sensitive to gentamycin. At the end of 1 month of treatment trial in patients who were treated with ocular lubricants containing BAC, none of the nasal cultures showed growth of any organisms. However, patients who were treated with ocular lubricants not containing BAC demonstrated persistent positive nasal cultures with the same species and the same antibiotic susceptibility profile at the end of the treatment trial period. CONCLUSION: Topically applied ocular lubricants including BAC has an anti-bacterial activity on nasal flora in DES patients.

[Prospective, monocentric, uncontrolled study of efficacy, tolerance and adherence of cyclosporin 0.1 % for severe dry eye syndrome]. / Étude prospective, monocentrique, non contrôlée de l'efficacité, de la tolérance et de l'adhésion au traitement par ciclosporine 0,1 % au cours des sécheresses oculaires sévères.

PURPOSE: To evaluate the efficacy, tolerability and treatment adherence of Ikervis® (Santen, SAS) (ciclosporine 0.1 %) for first line therapy or following treatment with Restasis® (Allergan, Inc.) (ciclosporine 0.05 %) for severe dry eye syndrome. MATERIAL AND METHODS: A prospective, monocentric, uncontrolled study was conducted between January 2012 and March 2015 on 110 eyes of 55 patients with severe dry eye on first line therapy or previously treated with Restasis® who required the introduction of Ikervis®. Patients' quality of life was assessed before and after treatment was started using a standardized questionnaire (Ocular Surface Disease Index© [OSDI]), clinical efficacy was quantified at the slit lamp, by measurement of the Break Up time Test (BUT) and the Oxford classification. Tolerability and adherence to treatment were measured using a simple questionnaire. RESULTS: A total of 72 eyes of 37 patients were included. Etiologies of dry eye syndrome were dominated by Sjögren syndrome (32 %) and severe ocular surface conditions (48 %). The mean age was 57.7 years (±17.45) and mean follow-up was 458 days (±292). The mean BUT increased by 2.043seconds [1.522-2.563] (P<0.0001). Corneal/conjunctival involvement evaluated by the Oxford classification was also improved with a difference in level of 1.68 [1.290-2.071] (P<0.0001). Ocular Surface Disease Index© (OSDI) decreased by 21.7 [16.372-27.024] (P<0.0001). Treatment tolerability was moderate, with more than 50 % of patients experiencing pain on instillation. Overall satisfaction with treatment was good, with more than 60 % of patients feeling better after initiation of treatment. CONCLUSION: Ikervis® is an effective treatment of severe dry eye. Its indications tend to evolve towards less severe dry eye. However, the tolerability profile remains poor, and an improvement in this would be desirable.

Can artificial tears prevent Acanthamoeba keratitis? An in vitro approach.

BACKGROUND: The use of contact lenses has increased in recent years as has the incidence of Dry Eye Syndrome, partly due to their use. Artificial tears are the most common treatment option. Since these changes can facilitate Acanthamoeba infection, the present study has been designed to evaluate the effect of three artificial tears treatments in the viability of Acanthamoeba genotype T4 trophozoites. Optava Fusion™, Oculotect®, and Artelac® Splash were selected due to their formulation. METHODS: Viability was assessed using two staining methods, Trypan Blue stain and CTC stain at different time intervals (2, 4, 6, 8 and 24 h). Trypan Blue viability was obtained by manual count with light microscopy while the CTC stain was determined using flow cytometry. RESULTS: Trypan Blue staining results demonstrated a decrease in viability for Optava Fusion™ and Artelac® Splash during the first 4 h of incubation. After, this effect seems to lose strength. In the case of Oculotect®, complete cell death was observed after 2 h. Using flow cytometry analysis, Optava Fusion™ and Oculotect® exhibited the same effect observed with Trypan Blue staining. However, Artelac® Splash revealed decreasing cell respiratory activity after four hours, with no damage to the cell membrane. CONCLUSIONS: The present study uses, for the first time, CTC stain analyzed by flow cytometry to establish Acanthamoeba viability demonstrating its usefulness and complementarity with the traditional stain, Trypan Blue. Artelac® Splash, with no preservatives, and Optava Fusion TM, with Purite®, have not shown any useful amoebicidal activity. On the contrary, promising results presented by Ocultect®, with BAK, open up a new possibility for Acanthamoeba keratitis prophylaxis and treatment although in vivo studies should be carried out.

Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study.

Dry eye is defined by a tear film instability resulting in variable but systematic fluctuations in quality of vision. Variability in optical quality can be demonstrated using a double pass aberrometer such as the Optical Quality Analyzing System, Visiometrics (OQAS). The goal of this work is to compare fluctuations in objective quality of vision measured by OQAS between treatment with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye syndrome. Optical quality was measured by evaluating the variations in the Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria were dry eye syndrome with an ocular surface disease index (OSDI) score >23 treated only with artificial tears. The patients were their own controls: OF in one eye and normal saline in the fellow eye. The choice of the subject eye and control eye was determined in a randomized fashion. OSI variations were measured in each eye before instillation, 5minutes and 2hours after instillation. The primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary endpoints were the number of blinks and patient preference (preferred eye). Preliminary results were obtained on 19 patients. Average OSDI score was 36.8. Visual acuity was 10/10 with no significant difference between the two eyes. Prior to instillation, there was no significant difference between "normal saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In the normal saline eye, there were no significant variations in mean OSI, OSI variability, OSI slope, or number of blinks. However, in the "OF" eye, there was a significant variation between initial and 2-hour OSI variability (0.363 versus 0.204, P<0.05), the average slope of OSI (0.04 versus 0.01, P<0.05) and the number of blinks (4.2 versus 2.8, P<0.05). Among the patients, 65% preferred the OF eye, 24% did not have a preference, and 11% preferred the normal saline eye. Objective quality of vision measured by OQAS is an interesting parameter for evaluating the effectiveness of a lacrimal substitute. The purpose of artificial tears is, among other things, to provide comfort and a reduction of dry eye symptoms such as poor quality of vision. This study demonstrates that 0.5% carmellose and 0.1% hyaluronic acid allowed better stabilization of the tear film and thus a significant improvement in the quality of vision compared to normal saline.

Anaphylaxis to polyvinylpyrrolidone in eye drops administered to an adolescent

No disponible

Efficacy and Safety of 0.2% Hyaluronic Acid in the Management of Dry Eye Disease.

OBJECTIVES: To evaluate the safety and efficacy of a new artificial tear containing 0.2% hyaluronic acid, as compared with 0.9% saline solution, in mild dry eye patients after 1-month use in a crossover study design with washout periods. METHODS: Overall, 16 mild dry eye patients were included. After a week of washout, every patient used the experimental product (Visaid 0.2%) and the control product (0.9% saline solution), each for a month (3-8 drops daily). Both products were preservative free. The percentage change for the following variables were calculated and analyzed: Ocular Surface Disease Index (OSDI) questionnaire, visual acuity, intraocular pressure, ophthalmoscopy evaluation, biomicroscopy findings, fluorescein corneal staining and lissamine green conjunctival staining, tear breakup time, contrast sensitivity, Schirmer's test, and subject satisfaction. RESULTS: Patients reported an improvement (a significant decrease of -19.5%±27.5%) in OSDI scores after using Visaid 0.2% and a worsening (a significant increase of 19.2%±32.4%) after using 0.9% saline solution; the difference was significant (P=0.0087, Student's t test). Significant changes (P≤0.04, Wilcoxon's test) were found comparing Visaid 0.2% with saline solution for bulbar hyperemia (-39.1%±50.8% vs. 7.8%±12.0%, respectively), corneal staining (-26.0%±53.0% vs. 36.5%±73.3%), conjunctival staining (-54.7%±53.4% vs. -7.8%±47.2%), and subjective satisfaction (26.8%±28.5% vs. -13.3%±22.5%). There were no significant differences in the safety parameters for either solution. CONCLUSION: This clinical trial demonstrates the safety of Visaid 0.2% and its clear benefit over 0.9% saline solution.

Safety and Efficacy of an Artificial Tear Containing 0.3% Hyaluronic Acid in the Management of Moderate-to-Severe Dry Eye Disease.

PURPOSE: To evaluate the safety and efficacy of a new 0.3% hyaluronic acid artificial tear compared with 0.9% saline solution (0.9% NaCl) in moderate-to-severe dry eye patients after 1 month's use. METHODS: A total of 16 patients with moderate-to-severe dry eye were included in this crossover study. After a 1-week washout period, patients used the experimental (Visaid 0.3%) or control solution (0.9% NaCl), selected randomly, applying three to eight drops daily for a month. After another washout period, patients used the other solution in the same way. Percentage of change (ΔY) was calculated and analyzed for (1) safety variables: visual acuity, intraocular pressure, and ophthalmoscopy evaluation; (2) efficacy variable: Ocular Surface Disease Index (OSDI) questionnaire; and (3) secondary variables: biomicroscopy findings, fluorescein corneal staining, lissamine green conjunctival staining, tear breakup time (TBUT), contrast sensitivity, Schirmer test, and subject satisfaction. RESULTS: There were no significant differences in the safety parameters for either solution. After using Visaid 0.3%, patients showed significant improvements in OSDI score (ΔY: -9.66%±10.90), tarsal hyperemia (ΔY: -16.67%±27.89), corneal staining extension (ΔY: -34.90%±42.41), TBUT (ΔY: 13.98%±26.19), and subjective satisfaction (ΔY: 38.06%±47.06). When using 0.9% NaCl, Schirmer test results were significantly worse (ΔY: -11.47%±19.27). A significant difference between the 2 solutions was found in TBUT (ΔY: 13.98%±26.19 vs. 10.15%±42.34, respectively; P=0.0214). CONCLUSION: Visaid 0.3% is a safe product with some benefits over 0.9% NaCl in reducing ocular symptoms and improving some ocular signs in patients with moderate-to-severe dry eye.

Allergic Contact Dermatitis to Ophthalmic Medications: Relevant Allergens and Alternative Testing Methods.

Allergic contact dermatitis is an important cause of periorbital dermatitis. Topical ophthalmic agents are relevant sensitizers. Contact dermatitis to ophthalmic medications can be challenging to diagnose and manage given the numerous possible offending agents, including both active and inactive ingredients. Furthermore, a substantial body of literature reports false-negative patch test results to ophthalmic agents. Subsequently, numerous alternative testing methods have been described. This review outlines the periorbital manifestations, causative agents, and alternative testing methods of allergic contact dermatitis to ophthalmic medications.

Efficacy and Safety of Carbomer-Based Lipid-Containing Artificial Tear Formulations in Patients With Dry Eye Syndrome.

PURPOSE: To evaluate the efficacy and safety profile of carbomer-based lipid-containing artificial tear formulations (CBLAT) in patients with dry eye syndrome. METHODS: A multicenter parallel-group study was conducted in 412 patients with dry eye syndrome. Of these patients, 221 switched from using artificial tears to CBLAT (switching group) and 191 added CBLAT to their current treatment (add-on group). Ocular symptom scores, ocular staining grades, tear film breakup time (tBUT), Schirmer I test value, and Korean dry eye level (as defined by the Korean Corneal Disease Study Group guidelines) were evaluated at baseline and after 4 weeks of treatment. RESULTS: After 4 weeks of treatment, ocular surface staining grade, tBUT, Schirmer I value, ocular irritation symptom scores, and the positive rate of visual symptom improved significantly in both groups. Mean reductions in ocular surface staining grades (-0.8 ± 0.9) and ocular irritation symptom scores (-0.8 ± 0.8) in the add-on group were significantly higher than those (-0.5 ± 0.8 and -0.6 ± 0.8) in the switching group (P < 0.01 and P < 0.05). The positive rate of visual symptoms (44.2%) in the add-on group was significantly higher than that (26.4%) in the switching group (P < 0.01). The decrease of Korean dry eye level was 30.1% in the switching group and 51.6% in the add-on group. More patients in the add-on group had decreased dry eye levels than those in the switching group (P < 0.0001). CONCLUSIONS: CBLAT improves ocular surface staining grades, tBUT, Schirmer I values, and ocular symptoms in patients with dry eye syndrome.

Dendritiform Keratopathy Associated with Exposure to Polyquarternium-1, a Common Ophthalmic Preservative.

PURPOSE: To describe dendritiform keratopathy associated with exposure to polyquaternium-1, a common preservative found in contact lens solutions and tear replacement products. DESIGN: Case series. PARTICIPANTS: Sixteen patients who demonstrated dendritiform keratopathy during topical ophthalmic exposure to polyquaternium-1. METHODS: Records were reviewed of all patients diagnosed with dendritiform keratopathy between 1999 and 2014 who had documented exposure to contact lens care disinfecting solutions or artificial tear solutions containing polyquaternium-1. Patients were excluded who had coexisting potential causes for dendritiform keratopathy, such as prior herpes simplex keratitis, varicella-zoster viral keratitis, the linear form of Thygeson's superficial keratitis, epithelial regeneration line, Acanthamoeba keratitis, mucus plaque keratopathy, medication-related keratopathy, or limbal stem cell deficiency characterized by conjunctivalization of the corneal epithelium. MAIN OUTCOME MEASURES: Effect of discontinuation of exposure to polyquaternium-1 on the dendritiform keratopathy. RESULTS: Sixteen patients demonstrated dendritiform keratopathy after exposure to the preservative polyquaternium-1. Thirteen patients had a history of recent exposure to contact lens disinfecting solutions (Opti-Free, Equate) containing polyquaternium-1. Three patients used a tear replacement product (Systane) containing a polyquaternium-1 preservative. Four patients were treated with antiviral medications for presumed herpes simplex keratitis; 4 patients underwent diagnostic testing for Acanthamoeba keratitis. Two additional patients were diagnosed sequentially with herpes simplex keratitis, then Acanthamoeba keratitis before referral. All dendritiform lesions resolved within 2 to 6 weeks after elimination of exposure to polyquaternium-1. CONCLUSIONS: Ophthalmic products containing polyquaternium-1 may cause dendritiform keratopathy that may be confused with infections of the superficial cornea, such as herpes simplex virus keratitis or Acanthamoeba keratitis.

Osmolarity of prevalent eye drops, side effects, and therapeutic approaches.

PURPOSE: Little is known about how the osmolarity of ophthalmic formulations affects the ocular surface. Because hyperosmolar eye drops could be therapeutic for treating corneal edema, this article presents an ex vivo model of corneal edema for testing ophthalmic drugs based on their osmolarity. The respective osmolarity of common eye drops found in the German market is also analyzed here. METHODS: For modeling corneal edema, an Ex Vivo Eye Irritation Test was used to simulate an ocular anterior chamber with a physiological corneal barrier. To induce corneal edema, the anterior chamber was supplied with a hypoosmolar medium (148 mOsm/L) for 24 hours. Preserved and preservative-free 5% sodium chloride (hyperosmolar Omnisorb and Ocusalin 5% UD) were used for 1 hour, on 5 corneas each, to test their efficiency to reduce corneal edema in this model. Corneal thickness was determined by optical coherence tomography. Osmolarity of 87 common eye drops was measured by freezing point osmometry. RESULTS: Ex vivo, the tested hypoosmolar condition induced corneal edema from 450 µm (±50 µm) at baseline to 851 µm (±94 µm, P < 0.0001). Omnisorb and Ocusalin 5% UD significantly reduced the corneal thickness by 279 µm (±28 µm, P < 0.001) for Omnisorb and 258 µm (±29 µm, P < 0.001) for Ocusalin 5% UD. Forty-three (49%) of the tested products had an osmolarity below and 44 (51%) above the physiological tear osmolarity of 289 mOsm/L. Osmolarity values of less than 200 mOsm/L were found in lubricant drops. The highest osmolarity was detected in Omnisorb (1955 mOsm/L). CONCLUSIONS: The Ex Vivo Eye Irritation Test has proven to be a reliable novel model of corneal edema for evaluating osmotic eye drops. Osmolarity measurements revealed a wide range from hypotonic to hypertonic formulations for commonly marketed ophthalmic drugs.

Comparison of the lubricant eyedrops Optive®, Vismed Multi®, and Cationorm® on the corneal healing process in an ex vivo model.

PURPOSE: To evaluate the impact of lubricant eyedrops on the corneal healing process and corneal toxicity. METHODS: Optive® and Cationorm® were tested regarding corneal irritability against Vismed Multi® and 0.01% benzalkonium chloride as negative and positive control, respectively. Formulas were applied on rabbit corneas (n = 5) cultured on artificial anterior chambers (EVEIT system) hourly over 3 days. Initially, 4 corneal abrasions (2-5.4 mm²) were induced. All defects were monitored during drug application by fluorescein stains and photographs. To ensure corneal vitality, glucose and lactate concentrations were determined photometrically in artificial anterior chamber fluids. Corneal fluorescein sodium permeability was tested as an indicator of the corneal barrier function. RESULTS: Optive® and Vismed Multi® showed a complete corneal healing on day 2. In one cornea (Optive®), erosion reoccurred on day 3. Erosion sizes of Cationorm®-treated corneas increased significantly from 12.20 mm² to a subtotal erosion of 51.89 mm² on day 3. Histology revealed epithelial loss and severe alterations of the superficial stroma for Cationorm®. Glucose and lactate concentrations did not change after application of Optive® and Vismed Multi®. In contrast, Cationorm®- and BAC-treated corneas showed a significant increase in lactate concentrations. CONCLUSIONS: Vismed Multi® application resulted in rapid corneal healing. Whether the toxicity seen for Optive® in one cornea is a valid result should be examined further. Cationorm® showed considerable corneal toxicity that could be caused by its additive, cetalkonium chloride. Otherwise, the electrostatic properties of Cationorm® led to a drug film on the area of epithelial loss that could hinder epithelial cell migration and adhesion in order to heal the lesion.

Efficacy, safety, and acceptability of a lipid-based artificial tear formulation: a randomized, controlled, multicenter clinical trial.

PURPOSE: Dry eye disease is highly prevalent worldwide, causing discomfort and visual disturbances that can limit basic activities such as reading and driving. Although artificial tears represent first-line therapy, there is a paucity of published controlled clinical trials. The present study compared the efficacy, clinical safety, and acceptability of 2 multicomponent, lipid-based tear formulations (ADV1 and ADV2) to those of an existing lipid-based tear formulation (DET) in patients with signs and symptoms of dry eye disease. METHODS: This 3-month, multicenter, double-masked study was conducted in patients with dry eye symptoms, reduced tear break-up time (TBUT), and ocular surface damage. Patients were randomized to receive 1 of 2 lipid-based tear formulations containing carboxymethylcellulose, glycerin, polysorbate 80, and emulsified lipid (ADV1 or ADV2) or DET, and instilled 1 to 2 drops per eye at least twice daily. The primary end point was the mean change from baseline in Subjective Evaluation of Symptom of Dryness score at day 90 to determine noninferiority of the 2 ADV formulations versus DET. Secondary end points included Ocular Surface Disease Index (OSDI) score, TBUT, ocular surface staining, and tolerability. FINDINGS: Of 288 randomized patients, 256 completed the study. All 3 groups showed improvement in symptoms, and the 2 lipid-based formulations were noninferior to DET in reducing the severity of symptoms of dryness at 90 days. Of the 3 treatment groups, the ADV2 group had the greatest improvements in TBUT and OSDI. Significant improvements in mean tolerability scores for comfort, soothing, burning/stinging, and discomfort were observed in the ADV2 group versus the DET group at 90 days. Treatment-related adverse events were reported in 13 patients (13.4%) receiving ADV1, 8 (8.4%) receiving ADV2, and 21 (21.9%) receiving DET. Four patients (4.1%) in the ADV1 group and 2 (2.1%) in the ADV2 group discontinued owing to an adverse event compared with 14 (14.6%) receiving DET. IMPLICATIONS: In these patients with dry eye symptoms, ADV2 was an effective and relatively well-tolerated artificial tear for first-line therapy and should be considered as a treatment option for dry eye, especially in those patients who would benefit from a lipid-based formulation in addition to lubrication. https://clinicaltrials.gov/ct2/show/NCT01010282.

Effects of benzalkonium chloride on the blood-aqueous and blood-retinal barriers of pseudophakic eyes.

PURPOSE: To evaluate the effects of benzalkonium chloride (BAK) on the blood-aqueous (BAB) and blood-retinal barriers (BRB) of pseudophakic eyes. METHODS: Prospective, randomized, investigator-masked, comparative study. Patients were randomly assigned to preservative-free artificial tears or BAK-preserved artificial tears. One drop of artificial tears was instilled 4 times a day in the study eye, starting the day after randomization for 30 days. Anterior chamber flare was assessed by a laser flare meter (LFM) and macular thickness measurements were obtained with optical coherence tomography, before, 15, and 30 days after randomization. RESULTS: A total of 44 healthy eyes of 44 pseudophakic volunteers were recruited. There were no significant differences regarding demographics (age, gender, and race distributions) and clinical characteristics (eye, mean intraocular pressure, and mean best-corrected visual acuity) between the 2 groups (P>0.05). No significant differences in baseline mean LFM values were observed (P=0.262). However, we detected a statistically significant increase in mean LFM measurements in the BAK-preserved group (11.4 ± 5.1 ph/ms) (P=0.017) after 15 days. After 30 days, the BAK-preserved group maintained significantly higher flare values (11.9 ± 5.9 ph/ms) compared with baseline (P=0.043). On the other hand, the preservative-free group showed mean flare values of 8.4 ± 2.5 ph/ms, not significantly different from those obtained at baseline (P=1.00). We observed no statistically significant change in macular thickness measurements at days 15 and 30 in either group (P>0.05). Cystoid macular edema was not detected in this series. CONCLUSIONS: Our results suggest that a short-term exposure to BAK can cause disruption of the BAB, without altering the BRB in pseudophakic eyes.