Artificial Tear Supplements Research Articles

Formulation Considerations for the Management of Dry Eye Disease.

Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.

Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial

PurposeTo assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED). MethodsNinety-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. ResultsSustained 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. ConclusionsOver 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.

Sleep apnea and dry eye: how sleep apnea affects the eye surface

Purpose: The purpose of this study was to determine the presence of dry eye disease and possible treatment options in patients with obstructive sleep apnea and continuous positive airway pressure.&#x0D; Materials and methods: A total of 72 patients (midlife age) with obstructive sleep apnea and continuous positive airway pressure therapy underwent a comprehensive eye examination. Fluorescein staining of the anterior ocular surface and tear break-up test were performed. All of the patients who were diagnosed with dry eye disease received personalized therapy. One month later, re-examination was performed using the same methodology and clinical settings.&#x0D; Results: On the first examination, 48 of 72 patients (66.67%) were diagnosed with dry eye disease. Floppy eyelid syndrome was reported in 26 patients (54.17%) with dry eye disease. The treatment of 40 patients included artificial tear supplements during the day in combination with high-viscosity topical gels before bedtime. In more severe cases (10.42% of all participants), the application of bandage contact lenses for 3 months was necessary. Because of excessive lid laxity, surgical reconstruction of the eyelids was performed in three patients (6.25%).&#x0D; Conclusions: A multidisciplinary approach is essential for obstructive sleep apnea. Practitioners from different specialties must be well acquainted with risk factors, signs, and symptoms. The early detection of dry eye disease in patients with obstructive sleep apnea and appropriate treatments are important for improving the quality of life in this patient group.

English

Two group of 50 patients each of DES were taken for study with schirmer's test - 1 value of <7 mm/ 5min .Group A received artificial tear & nutritional supplements of EFAs for 8 weeks and Group B received artificial tears only for 8 week . Study reveals that dietary intervention with omega- 3 fatty acid not only causes symptomatic improvement but also betters clinical markers of dry eye as seen by a positive drift in primary and secondary outcome measures. There is a likely improvement in inherent stability of the tear film as seen by the larger TBUT drift and CIC scores. This paper will discuss the results in detail. INTRODUCTION: Dry eye syndrome (DES) is a multifactorial disease, affecting tears and the ocular surface. It is accompanied by increased osmolarity of tear film, and inflammation of the ocular surface.(1)-(3) Despite recent advances in understanding the etiopathogenesis of DES, there remain a lacuna in diagnosis, prevention and definitive treatment. DES is a common problem worldwide and can reduce the working efficiency of an individual. Dry eye is therefore a frequent reason that patient present to eye care clinics. Common patient's complaints related to dry eye include reduced vision, difficulty reading, difficulty driving at night and difficulty doing computer work.(5) Most diagnostic tests for dry eye are poorly standardized, making compare between studies tenuous at best. A generally agreed upon 'gold standard' still does not exist. Additionally, some of these tests are poorly associated with subjective symptoms. (6)-(7)

Corneal and Conjunctival Sensitivity in Patients With Dry Eye: The Effect of Topical Cyclosporine Therapy

: To evaluate changes in mechanical sensitivity of cornea and conjunctiva in patients with dry eye disease unresponsive to artificial tears therapy and to investigate the effect of topical cyclosporine therapy on sensitivity of the ocular surface. : Thirty-seven patients with dry eye disease and 35 healthy control subjects were enrolled to this prospective study. All patients included in the study completed a 3-month run-in period of using nonpreserved artificial tear supplements, but all failed to achieve adequate subjective or objective improvement. Patients were then instructed to use topical cyclosporine A 0.05% twice a day. Pre- and posttreatment (1, 3, and 6 months) evaluations included, corneal and conjunctival sensitivity testing with the Cochet-Bonnet esthesiometer, subjective symptom scoring, fluorescein and lissamine green staining, Schirmer test, and tear breakup time (BUT). : Conjunctival and corneal sensitivities were significantly lower in patients with dry eye compared with controls (P < 0.0001). In patients with dry eye, corneal sensitivity correlated positively with conjunctival sensitivity and negatively with ocular surface staining scores. Conjunctival sensitivity correlated negatively with the duration of dry eye disease, the total symptom severity score, and the severity of dryness symptom and positively with Schirmer test and tear BUT. Corneal and conjunctival sensitivities did not change significantly after artificial tear therapy (P > 0.05). After topical cyclosporine, statistically significant improvements from baseline were observed in corneal sensitivity at 3- and 6-month visits (P < 0.001). For conjunctival sensitivity, statistically significant improvements from baseline were seen at all follow-up visits (P < 0.0001). Topical cyclosporine treatment also led to significant improvements in symptom scores, Schirmer test, tear BUT, and ocular surface staining scores (P < 0.0001). : The mechanical sensitivity of cornea and conjunctiva to tactile stimulus is reduced in patients with dry eye. Our findings suggest that topical cyclosporine may be effective in improving this reduced mechanical sensitivity of the ocular surface.

Attitudes towards Diagnostic Tests and Therapies for Dry Eye Disease

Aim: The purpose of this study was to survey the attitudes of optometrists and ophthalmologists, located in a number of different countries, towards diagnostic tests and therapies for dry eye disease. Methods: A web-based questionnaire was used to survey attitudes using forced-choice questions and Likert scales. Results: Sixty-one respondents (23 ophthalmologists and 38 optometrists) reported a wide range of patient dry eye symptoms. A large variation in use of diagnostic tests was noted. Patient symptoms and fluorescein staining were reported to be significantly more valuable and more frequently performed than any other test. Artificial tear supplements and improved lid hygiene were the preferred therapeutic options selected by the entire group. The results demonstrated a wide variation in attitudes in relation to satisfaction with the range of available diagnostic and therapeutic options. Conclusions: This study indicates that the interest for the issue of dry eye is relatively limited amongst eye professionals, as demonstrated by the poor participation in the questionnaire.

SmartPlug Versus Silicone Punctal Plug Therapy for Dry Eye

To evaluate the clinical efficacy, retention rates, and complications of SmartPlug insertion compared with silicone punctal plugs in patients with dry eye. Thirty-six eyes with subjective symptoms of dry eye in addition to a tear film breakup time (TBUT) <5 seconds and evidence of ocular surface damage on rose Bengal or fluorescein staining were included. Treated eyes were randomized to either a silicone plug or SmartPlug inferior punctal occlusion. Pre- and posttreatment evaluations included subjective symptom scoring, tear meniscus height, TBUT, Schirmer test, fluorescein and rose Bengal staining, and artificial tear use. After a mean follow-up period of 11.2 weeks, both the silicone plug- and SmartPlug-treated eyes showed significant improvement in symptom scoring (P = 0.002 and P = 0.005, respectively), TBUT (P = 0.035 and P = 0.009, respectively), and fluorescein (P = 0.024 and P = 0.016, respectively) and rose Bengal (P = 0.008 and P = 0.046, respectively) staining. There was no significant difference in these parameters between the 2 plugs. SmartPlug-, but not the silicone plug-treated eyes showed significant improvement in mean tear meniscus height (P = 0.037). The use of artificial tear supplements was reduced in 10 (55.6%) silicone- and 11 (61.1%) SmartPlug-treated eyes. Minor complications related to plug insertion were experienced in 4 (22%) silicone- and 2 (11%) SmartPlug-treated eyes. Spontaneous plug loss occurred with 6 (33%) silicone plugs. This prospective randomized trial shows that SmartPlug insertion has equivalent clinical efficacy to the use of conventional silicone plugs. Both SmartPlug and silicone plug use can reduce dependency on tear supplements in >55% of patients with dry eye.

Effect of Artificial Tears on Visual Performance in Subjects With Dry Eye

Disruption of the anterior refracting surface of the eye (i.e., the tear layer) reduces visual performance. Tear layer breakup occurs soon after a blink in contact lens wearers and patients with dry eye. This study determined whether artificial tears stabilize the tear film and improve visual performance in contact lens wearers who also exhibit a dry eye. Five subjects with mild to moderate dry eye (probably as a result of an evaporative dry eye) during spectacle and contact lens wear were fitted with a Focus Night & Day hydrogel lens for this study. A temporal, two-alternative, forced-choice paradigm was used to measure contrast sensitivity. The stimuli were vertically oriented sine wave gratings (between 0.5 and 14 cpd) presented for 16.67 msec. The stimuli were presented at two different times after blink detection: 2 sec after blink detection (i.e., before tear layer breakup) or 4 sec after tear film breakup. Four conditions were investigated at 4 sec after tear layer breakup: 1) without artificial tears added, 2) with Clerz2 (Alcon, Fort Worth, TX) instilled, 3) with Sensitive Eyes (Bausch & Lomb, Rochester, NY), and 4) with GenTeal (Novartis, Basel, Switzerland) applied. The artificial tears were instilled at 10-min intervals during the data collection. The short-term visual effects of drop instillation were also investigated by continually monitoring contrast sensitivity for a 14-cpd grating after a single-drop administration. High spatial frequency contrast sensitivity and visual acuity were found to be reduced after tear film breakup in the absence of supplementation with artificial tears. For the group data (and four of five subjects), the instillation of Sensitive Eyes improved the contrast sensitivity and visual acuity to the level attained before tear breakup, thus prolonging visual performance. Clerz2 and GenTeal did not produce any enhancement in visual performance. A short-term decrease in contrast sensitivity was also observed with a single administration of Clerz2 and GenTeal. This study indicates that there was a benefit of Bausch & Lomb Sensitive Eyes tear supplementation on visual performance in subjects with an evaporative dry eye. This may be the result of 1) aqueous supplementation in these subjects and/or 2) the minimal tear layer disruption found with Sensitive Eyes drop administration. The results suggest that practitioners need to identify those patients who can benefit from the use of appropriate artificial tear supplements.

Comparison of Artificial Tear Supplements on the Ocular Surface Health and Tear Film in Patients with Dry Eye

Purpose. To compare the effects of four commonly used, non-preserved, ‘over the counter’ artificial tear supplements on the ocular surface health and tear film of patients with moderate-to-severe dry eye. Methods. A prospective, controlled, investigator-masked, parallel, randomised study design was used to compare three months’ treatment with: (1) carboxymethyl cellulose 0.5% (Cellufresh, Allergan) (2) hydroxy propylmethyl cellulose 0.3% with bicarbonate (Bion Tears, Alcon) (3) carbomer 980 gel 0.2% (Viscotears Gel, Ciba Vision) or (4) hydroxy propylmethyl cellulose 0.3% (Polytears Free, Alcon) (Study: AKX/01/02/004). The cornea, conjunctiva and tear film of one eye of each eligible randomised patient were assessed at baseline (after a 14-day washout), then 1, 2, 4, 8 and 12 weeks after treatment. Results Treatment differences were observed in the sample studied (N = 73). Conjunctival fluorescein staining was significantly different (P = 0.0002) between treatments, with Cellufresh significantly better than each of the three comparators. Tear film contamination was significantly different (P = 0.003) between treatments, with Cellufresh significantly better than Bion Tears and Polytears. For tear film debris, there was a trend (P = 0.053) for a difference between treatments, with the Cellufresh group having the least amount of debris. Frequency of supplement instillation was also significantly different (P = 0.047) between treatments, with Cellufresh requiring the least frequent instillation. There were no detrimental effects on visual acuity or the lipid layer of the tear film detected for any supplement. Conclusions. Commonly used, artificial tear supplements can improve the ocular surface health and tear film in patients with moderate-to-severe dry eye. In this study, the most consistent and favourable results were achieved with the use of carboxymethyl cellulose 0.5% (Cellufresh). Support: Allergan Australia Pty Ltd

Coefficient of Friction of Ocular Surface Lubricants for Laser in situ Keratomileusis

The coefficient of friction was empirically derived for a series of commercially available ophthalmic lubricants having potential use during laser in situ keratomileusis (LASIK). Measurements were obtained using a modified tensile testing machine. Solutions tested included the artificial tear supplements Polytears-free, Bion Tears, Genteal, Refresh, Cellufresh, Celluvisc, Theratears, and Viscotears gel; and balanced salt solution (BSS). Viscotears carbomer gel had a significantly lower mean coefficient of friction compared to other ophthalmic lubricants tested (P=.002) and the dry plate (P=.005). Addition of 0.1 ml of BSS to 0.025 ml of Celluvisc significantly reduced the coefficent of friction of Celluvisc (P=.01). Polytears, Bion Tears, Genteal, Refresh, Celluvisc, Theratears, and BSS had coefficients of friction significantly higher than that of the dry plate. A range of values were obtained for the coefficient of the ophthalmic lubricants tested. Viscotears gel (0.1 ml), and Celluvisc (0.025 ml) + BSS (0.1 ml) had coefficients of friction significantly lower than that of the dry plate.

The conjunctival epithelium in dry eye subtypes: Effect of preserved and non-preserved topical treatments

Purpose. To determine the effect of topical treatments on the conjunctiva in dry eye. Methods. N = 134 dry eye subjects were diagnosed using a protocol of McMonnies dry eye symptom survey score > 14, fluorescein break up time (FBUT) < 10s and presence of rose Bengal staining. Differential diagnosis of dry eye subtypes was based on biomicroscopic signs and ocular/medical history. Superficial perilimbal bulbar conjunctival epithelial samples were collected using impression cytology. The nucleo-cytoplasmic ratio (N/C), goblet cell density (GCD) and expression of monoclonal antibodies HLA DR and CD23 were determined. The ocular surface characteristics of untreated subjects, those receiving preserved dry eye treatments and those receiving non-preserved treatments were compared with each other and with controls. Ocular surface characteristics of dry eye subtypes were also examined. Results. An increase in N/C (p = 0.011), reduction in GCD (p = 0.0001) and increase in expression of HLA DR (p = 0.0001) and CD23 (p = 0.0001) were detected in the untreated group compared to controls. No significant differences were found between the group receiving non-preserved dry eye treatments and untreated dry eye group. The group receiving preserved treatments had a reduced GCD (p = 0.0003) and increased expression of HLA DR (p = 0.0003) and CD23 (p = 0.0001) compared to the group receiving non-preserved treatments. Dry eye subtype specific differences in HLA DR and CD23 expression were noted. Conclusions. The conjunctival inflammation and reduced goblet cell density of dry eye is exacerbated by use of preserved topical agents, and is not significantly improved by use of non-preserved artificial tear supplements alone. Therapeutic strategies for dry eye should aim to increase goblet cell density and control ocular surface inflammation.

Importance of the lipid layer in providing tear stability

Previous tear film investigations on patients with rheumatoid arthritis (Craig et al., 1995) suggested that a poor meibomian lipid layer on the surface of the tears resulted in tear film instability and could allow increased evaporation of the tears. This, in turn, could raise the osmolality of the tears, causing ocular surface, damage which is visible with rose bengal staining. The study was conducted to determine the importance of this lipid layer in providing stability for the tears. Tear film appearance and stability were assessed in a masked fashion on 20 control subjects and compared to 40 test subjects in whom forced meibomian gland expression was carried out unilaterally, 10 min prior to tear film assessment. The appearance of the tear film was assessed by thin film interferometry (Keeler Tearscope®) and the time of the break‐up of this image (non‐invasive break‐up time) measured to ±0.1 s. The modal tear film lipid layer pattern changed from a marble‐like appearance to a coloured fringe pattern with meibomian gland expression (P &lt; 0.001). Concurrently, tear film stability improved from a mean of 21.6 ± 11.5 s to 42.2 ± 21.2 (P &lt; 0.001). Surprisingly, there were subtle changes in the contralateral eye of the test subjects. No change in modal lipid layer appearance was observed (P &gt; 0.05) but stability had improved slightly to a mean of 30.8 ± 14.5 s (P = 0.011). Improvement of tear stability in normal eyes by addition of lipid to the tear film suggests that incorporation of lipomimetics in artificial tear supplements should help improve tear stability. This could perhaps prevent development of ocular surface damage, and consequently symptoms, in patients with rheumatoid arthritis and in other dry‐eye patients.

Importance of the lipid layer in providing tear stability

Previous tear film investigations on patients with rheumatoid arthritis (Craig et al., 1995) suggested that a poor meibomian lipid layer on the surface of the tears resulted in tear film instability and could allow increased evaporation of the tears. This, in turn, could raise the osmolality of the tears, causing ocular surface, damage which is visible with rose bengal staining. The study was conducted to determine the importance of this lipid layer in providing stability for the tears. Tear film appearance and stability were assessed in a masked fashion on 20 control subjects and compared to 40 test subjects in whom forced meibomian gland expression was carried out unilaterally, 10 min prior to tear film assessment. The appearance of the tear film was assessed by thin film interferometry (Keeler Tearscope®) and the time of the break-up of this image (non-invasive break-up time) measured to ±0.1 s. The modal tear film lipid layer pattern changed from a marble-like appearance to a coloured fringe pattern with meibomian gland expression (P < 0.001). Concurrently, tear film stability improved from a mean of 21.6 ± 11.5 s to 42.2 ± 21.2 (P < 0.001). Surprisingly, there were subtle changes in the contralateral eye of the test subjects. No change in modal lipid layer appearance was observed (P > 0.05) but stability had improved slightly to a mean of 30.8 ± 14.5 s (P = 0.011). Improvement of tear stability in normal eyes by addition of lipid to the tear film suggests that incorporation of lipomimetics in artificial tear supplements should help improve tear stability. This could perhaps prevent development of ocular surface damage, and consequently symptoms, in patients with rheumatoid arthritis and in other dry-eye patients.