Preservative-free Drops Research Articles

What do we know about preservatives?

AbstractPreservatives have played an important role in traditional topical ophthalmic medications. However, problems associated with preserved eye drops include ocular surface disease, poor tolerability and adherence, reduced quality of life, and increased risk of failure of glaucoma surgery. This presentation explores the evidence for and against the use of preservatives in glaucoma medications and explores whether preservative free drops should be first line for all. The cytotoxic effects of preservatives will be examined and practical advice provided on the management of iatrogenic ocular surface disease.

A CLINICAL STUDY ON DRY EYE AFTER CATARACT SURGERY.

Introduction: Dry eye as dened by the International Dry eye workshop is a multifactorial disease of the tears and ocular surfaces. Cataract surgery can cause dry eye as surgery can damage ocular surface. To nd out various factors Aims: responsible for dry eye after cataract surgery in presenile patients and the incidence of dry eye cases after cataract surgery. It was a Methods: prospective study on 100 patients Complete ocular examination and dry eye tests were done preoperatively and postoperatively. patients Results: who had longest tunnel incison, longer period of microscopic light exposure, vigorous irrigation, and eyedrops with preservatives had developed dry eye disease. As dry eye may develop after cataract surgery, so by decrea Conclusion: sing incision size of tunnel, minimizing microscopic light exposure and vigorous irrigation, using preservative free drops can decrease dry eye symptoms post operatively

Комплексное лечение синдрома сухого глаза у пациентов с синдромом Шегрена путем применения препарата бесконсервантных капель, содержащих гиалуронат натрия 0,4 % и комплекса нутрицевтиков

The aim. To increase the effectiveness of treatment of dry eye syndrome in patients with Sjogren’s syndrome with preservative-free drops which contain 0.4 % sodium hyaluronate and nutraceutical complexes nutraceuticals. Materials and methods. The study was conducted on the basis of the Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine. The study included 64 patients aged 34 to 58 years (128 eyes) with dry eye syndrome accompanied by Sjogren’s syndrome. Examination of patients included: assessment of complaints, visometry, refractometry, bacterial culture of the conjunctiva and nasopharynx, biomicroscopy, ophthalmoscopy, Schirmer and Norn tests, assessment of "comfort of application of drops" on the questionnaire. This study is an extension of the study previously conducted at the premises of the Filatov Institute of Eye Diseases and Tissue Therapy of The National Academy of Medical Sciences of Ukraine on the effectiveness of preservative-free eye drops containing 0.4 % hyaluronic acid in the treatment of Sjogren’s syndrome. Results. Prior to the appointment of comprehensive treatment with instillations, the Norn test showed 6.55 s (SD 1.57) with a minimum of 3 s, a maximum of 9 s, and a median of 6.5 s. After 3 months of treatment the Norn test score in the 1st group averaged 14.66 (SD 1.07) vs. 13.86 (SD 1.07) in the 2nd group, but the difference was not statistically significant (p=1.0). The mean number of required instillations per day was 4.1 (SD 1.04) in the 1st group and 5.27 (SD 1.11) in the 2nd group. Conclusion. Instillations of preservative-free drops containing sodium hyaluronate 0.4 % (in a bottle with an innovative ophthalmic squeeze dispenser (OSD)) in combination with a nutraceutical complex in the treatment of dry eye syndrome in patients with Sjogren’s syndrome is effective and allows achieving a stable and long-term effect. Keywords: Sjogren’s syndrome, hyaluronic acid, nutraceuticals, artificial tear, Schirmer test, Norn test, dry eye syndrome, tear film.

Comparative efficacy and safety of preserved versus preservative-free beta-blockers in patients with glaucoma or ocular hypertension: a systematic review.

Preservative-free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of beta-blockers, or combination using beta-blockers, with and without preservatives. PubMed, EMBASE and Web of Science were examined. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews. The primary outcome was change in intraocular pressure (IOP) from baseline to final follow-up. Secondary outcomes included ocular and systemic side effects, and other clinical and quality of life outcomes. Of 242 records identified, seven RCTs (1125 patients) were included. The follow-up period ranged from one to 12 months. Timolol was used in five studies, and two studies used a combination (timolol with bimatoprost or dorzolamide). The difference in mean change (MD) in IOP between the preservative-free and the preserved drugs was statistically significant but not clinically relevant: (MD 0.29 mmHg, 95% confidence interval 0.07-0.51 mmHg, p = 0.010; moderate-certainty evidence). Regarding adverse events: Level of evidence for all ocular surface outcome was low or very low and reported in few studies. No significant difference was observed on ocular surface symptoms. Tear break-up time (TBUT) was better with preservative-free drops (p < 0.001). Schirmer's test was better in the preservative-free group (p < 0.001). Level of evidence for all ocular surface outcomes was low or very low. There was no difference in other secondary outcomes. We found no clinically relevant difference in mean change in IOP between the preserved and the preservative-free treatments. Data on adverse events used different methods and were incompletely reported. Although some measures of ocular surface health favoured preservative-free medications, more evidence is needed. The increasing use of preservative-free drops may be associated with better ocular surface and tolerability, but strong evidence from RCTs would be welcome.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Preservative-free versus preserved glaucoma eye drops and occurrence of glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008-2016.

Preservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. We aimed to assess the association between preservative exposure and the occurrence of further glaucoma surgery among patients with glaucoma or ocular hypertension in France. The study concerned all patients who first received glaucoma eye drop treatments in a French medical-administrative database (EGB) between 2008 and 2015. Three groups were created according to the level of preservative exposure during the whole follow-up: '0% preservatives', 'mixed' and '100% preservatives'. The occurrence of glaucoma surgery was estimated according to preservative exposure indicators in Cox multivariate models adjusted on age, sex, number of glaucoma eye drops simultaneously used, systemic antihypertensive treatment and duration of treatment. The sample consisted of 12454 patients. The median (interquartile range) follow-up was 4.1 (1.7-6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow-up. On multivariable analysis, the risk of glaucoma surgery was increased for the 'mixed' group (hazard ratio [HR]=3.94 [95% CI, 1.54-10.05]) and for the '100% preservative' group (HR=7.97 [95% CI, 3.07-20.67]) when compared with the 0% preservative group. We found an association between exposure to glaucoma eye drop preservatives and the prevalence of further glaucoma surgery. While these data might be used to support the consideration of routine use of preservative-free drops, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between preservative-free glaucoma eye drops and further glaucoma surgery.

Changes in ocular signs and symptoms in patients switching from bimatoprost–timolol to tafluprost–timolol eye drops: an open-label phase IV study

ObjectivesBimatoprost–timolol (bimatoprost 0.03%–timolol 0.5% fixed-dose combination [FDC]) and tafluprost–timolol (tafluprost 0.0015%–timolol 0.5% FDC) eye drops are currently the only topical intraocular pressure (IOP)-reducing therapies available as preservative-free (PF) prostaglandin and...

Effect of changing from preserved prostaglandins to preservative-free tafluprost in patients with glaucoma on tear film thickness

Long-term glaucoma therapy with preservative-containing eye drops may impact ocular surface health. This study was performed to investigate whether a switch from preserved topical prostaglandin therapy to preservative-free tafluprost therapy improves precorneal tear film thickness in patients with glaucoma or ocular hypertension. A total of 30 patients who were under topical preservative-containing prostaglandin monotherapy for at least 6 months were included. Patients were then switched from preserved prostaglandin therapy to unpreserved tafluprost drops once daily. Tear film thickness was measured at baseline and 4 and 12 weeks after therapy change with an ultrahigh-resolution optical coherence tomography system. Furthermore, clinical measures of ocular surface disease were determined and symptoms were assessed using the Dry Eye-Related Quality-of-Life Score. After switching to unpreserved tafluprost, tear film thickness significantly increased from 4.7 ± 0.5 to 5.0 ± 0.6 µm 4 weeks after therapy change and still tended to be increased after 12 weeks (4.8 ± 0.7 µm). Breakup time significantly increased from 5.1 ± 2.3 to 7.2 ± 3.4 s and to 10.1 ± 3.6 s after therapy change. In addition, a significant decrease in corneal staining score from 1.8 ± 0.7 to 1.4 ± 0.8 after 4 weeks and to 0.7 ± 0.7 after 12 weeks treatment was observed. Switching to preservative-free drops reduced Dry Eye-Related Quality-of-Life Score from 11.4 ± 11.0 to 5.7 ± 6.4 and to 4.7 ± 7.5. Our data show that switching to preservative-free tafluprost leads to an increase in tear film thickness, breakup time, and an improvement of Dry Eye-Related Quality-of-Life Score. Our results therefore indicate that a switch to unpreserved tafluprost is beneficial for ocular surface health in patients under long-term preserved prostaglandin eye drops.

Effectiveness of a Preservative-Free Eye Drop, Cyclosporine 0.05% Emulsion, and Omega-3 Supplementation as a Fixed Combination in Dry Eye Disease – a Pilot Study

Purpose: We aim to evaluate the impact of combining a preservative-free drop, cyclosporine 0.05% emulsion, and omega-3 oral supplementation on the signs and symptoms of dry eye in a typical ophthalmic practice.Design: A retrospective case series conducted on patients with dry eye disease.Methods: Patients diagnosed with dry eye in a typical ophthalmology practice were initiated on a fixed combination regimen which included a preservative-free eye drop (I-DROP ® PUR GEL, I-MED pharma), cyclosporine 0.05% ophthalmic emulsion, and oral omega-3 supplement(Dry Eye Omega Benefits®, PRN)for 3 monthsconsecutively. The primary outcome measured was a symptom score using the Canadian Dry Eye Assessment Tool (CDEA). Secondary outcome measure was Non-invasive Keratograph Break-up Time (NIKBUT). Primary and secondary outcomes measured at baseline and 3 months following intervention were compared.Results: Thirty-six patients were included with a female male ratio of 2.6:1 and average age of 64.Patient symptoms improved significantly following the intervention as demonstrated by a lower CDEA score during the second visit compared to the first visit (16.11 vs. 19.50, respectively) (p&lt; .05). NIKBUT scores were also significantly improved as demonstrated by a higher score during the second visit compared to the first in both the right (13.18 vs. 11.44) (p&lt; .05) and left (14.62 vs. 12.78) (p&lt; .01) eyes, respectively.Conclusion: A fixed combination of preservative-free eye drops, cyclosporine 0.05% and omega-3 supplementation may be an effective first line treatment option in alleviating symptoms and improving signs of patients suffering from dry eye.

A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface

Background: Preserved anti-glaucoma drops cause ocular surface disease (OSD), which is increasingly being recognized as a likely cause of trabeculectomy failure. Aim: To determine the routine pre-trabeculectomy management of the ocular surface by glaucoma specialists. Methods: A questionnaire consisting of 11 questions was posted to 146 UK glaucoma specialists. Results: The first-time response rate was 43.8%. Regarding routine pre-operative management, 40.6% of specialists use preservative-free drops, 29.7% commence a drop holiday, and 53% advise lid hygiene. 42.1% prescribe lubricants, 50% prescribe topical steroids, 7.8% topical NSAIDs, and 34.4% systemic tetracyclines. 84.4% of specialists change their routine management if OSD is present. Pre-operative optimization of the ocular surface is viewed “necessary” by 48.4% and “beneficial” by 85.9%. Conclusion: A wide variation exists in the routine pre-operative management of the ocular surface. Research to determine the impact of different pre-operative interventions upon trabeculectomy outcomes is required.

The effects of ocular hypotensive drugs on the cornea: An in vivo analysis with confocal microscopy

PurposeTo evaluate the effects of anti-glaucoma treatments containing benzalconium chloride (BAC) on the human cornea. MethodsA prospective single masked cohort study was conducted on the 50 eyes of 50 patients. The inclusion criteria were recently diagnosed glaucoma or ocular hypertension with previous treatment, or ophthalmologist-prescribed anti-glaucoma therapy, and oral consent to participate in the study. The patients were not randomized, as the ophthalmologist decided the best therapy according to clinical criteria. The patients were divided in 2 cohorts: those exposed to BAC (23 patients), and those not exposed (27 patients). The mean follow-up period was 22 weeks (range 18–30). The change in cell density before and after therapy was measured in basal layer epithelium, basal layer of limbal epithelium and endothelium. The change in stromal reflectivity and the number of nerve branches in sub-basal nerve plexus was also measured. BAC exposure was blinded to the main researcher. ResultsA greater increase in basal layer epithelium cell density was observed in BAC exposed cohort (p<0.05). No significant differences were detected in the endothelium, limbal cell density, stromal reflectivity, or sub-basal nerve plexus. Age, sex, IOP, active ingredient or BAC concentration did not affect the direction or magnitude of the ocular surface alterations found. ConclusionChronic anti-glaucoma therapy induces changes in the corneal epithelium. Preservative free drops showed less disruption of the ocular surface by confocal microscopy analysis. Further studies should be conducted to evaluate the clinical impact of these histological findings.

Efectos corneales de hipotensores oculares que contienen cloruro de benzalconio: análisis in vivo con microscopia confocal

PurposeTo evaluate the effects of anti-glaucoma treatments containing benzalconium chloride (BAC) on the human cornea. MethodsA prospective single masked cohort study was conducted on the 50 eyes of 50 patients. The inclusion criteria were: recently diagnosed glaucoma or ocular hypertension with previous treatment, or ophthalmologist-prescribed anti-glaucoma therapy, and oral consent to participate in the study. The patients were not randomised, as the ophthalmologist decided the best therapy according to clinical criteria. The patients were divided in 2 cohorts: one exposed to BAC (23 patients), and not exposed (27patients). The mean follow-up period was 22 weeks (range 18-30). The change in cell density before and after therapy was measured in: basal layer epithelium, basal layer of limbal epithelium and endothelium. The change in stromal reflectivity and the number of nerve branches in sub-basal nerve plexus was also measured. BAC exposure was blinded to the main researcher. ResultsA greater increase in basal layer epithelium cell density was observed in BAC exposed cohort (P<.05). No significant differences were detected in the endothelium, limbal cell density, stromal reflectivity, or sub-basal nerve plexus. Age, sex, IOP, active ingredient or BAC concentration did not affect the direction or magnitude of the ocular surface alterations found. ConclusionChronic anti-glaucoma therapy induces changes in the corneal epithelium. Preservative free drops showed less disruption of the ocular surface by confocal microscopy analysis. Further studies should be conducted to evaluate the clinical impact of these histological findings.

Surgical Modifications Required for Planned Extracapsular Cataract Extraction under Topical Anaesthesia with Van Lint Block

Objective: To assess the intensity of pain after applying some modifications in the surgical steps undertaken during the course of planned extracapsular cataract extraction under topical anaesthesia with Van Lint block. Study Design and Patients: This is a prospective study of 20 patients divided into 2 groups. Fifteen patients had previous extracapsular cataract extraction in 1 eye under retrobulbar anaesthesia (group 1). Those were chosen to compare the difference in their perception of pain under retrobulbar anaesthesia vs topical anaesthesia using these surgical modifications. Group 2 was initially made of 15 patients who had no previous ocular surgery and had no preference for the type of anaesthesia. They were chosen to outline their response to topical anaesthesia. This would have made the total of 30 patients, however, it was felt that the first 10 patients of this group did not have the benefit of all the surgical modifications and their responses would distort the results. Therefore, only the responses of the last 5 who benefited from the modifications were included. Setting: The Eye Department, Pilgrim Hospital, Boston, Lincolnshire, UK. Main Outcome Measures: Single dose of 0.5 ml preservative free Xylocaine 4% drops in the conjunctival sac with the lids maintained open for up to 1 min immediately preoperatively gives complete anaesthesia of the cornea and conjunctiva. A ‘clear corneal incision’, a wide ‘can-opener capsulotomy’, and ‘equatorial flush’ are surgical modifications required to abolish any feeling of pain in planned extracapsular cataract extraction under topical anaesthesia. Results: The severity of the pain was graded from 0–4. Eight patients had no pain, 5 patients had grade 1 and 7 patients had grade 2 pain. No patients graded 3 or 4. Conclusions: Xylocaine 4% preservative-free drops produce complete corneal anaesthesia and decrease the palpebral reflex when applied immediately before the start of surgery for 30–60 s while the lids are held apart—allowing complete immersion of the ocular surface under a layer of drops. Corneal section and wide capsulotomy are surgical steps that prevented pain during nucleus delivery. Equatorial flush speeds aspiration/irrigation. Pain was caused during suturing the posterior lip of the incision involving the conjunctiva if the surgery took longer than expected.

Slow-release artificial tear inserts in the treatment of dry eyes resulting from the oculomucocutaneous syndrome.

Patients with dry eyes resulting from the practolol syndrome present a therapeutic challenge. Very frequent instillation of preservative-free drops are the only therapy in most cases. Using an entirely new agent--a hydrophilic polymer in insert form--we have provided in this open study an alternative therapy which shows some subjective and objective advantages. Few patients experienced problems, and none left the study because of failure of retention of the insert. Some patients preferred the cooling, soothing effects of frequent drops. The problems in mounting a clinical trial of this sort are discussed.