Dry eye disease caused by viral infection: review

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

Two-Year Outcome of Partial Lacrimal Punctal Occlusion in the Management of Dry Eye Related to Sjogren Syndrome

Purpose: To analyze the influence of thermal partial punctal occlusion on the ocular surface of dry eye related to Sjogren syndrome. Material and Methods: Thirty-seven eyes of 19 patients (3 male and 16 female; 49.11 +/- 14.33 years old) with keratoconjunctivitis sicca were enrolled in this study. Superior and inferior partial occlusion were performed in both eyes under topical anesthesia using thermal cautery with a sterile tip to obtain lacrimal punctum smaller than 0.5 mm. Schirmer I, break-up-time, diameter of lacrimal puncta, corneal fluorescein, and rose Bengal staining scores were analyzed before and after 24 weeks and after 24 months of the procedure. All measurements were performed under controlled climate. Results: The average lacrimal punctum diameter before the procedure was 0.65 +/- 0.134 mm. All lacrimal puncta were successfully reduced to less than 0.5 mm after 4 weeks of the procedure. The average Schirmer I test values improved statistically after 24 weeks and maintained stable after 24 months. Average break-up-time, rose Bengal, and fluorescein staining score values improved statistically after 24 weeks and improved even more after 24 months. Average Schirmer I test, break-up-time, rose Bengal, and fluorescein staining scores showed significant improvement (p < 0.0001) after 24 months of partial thermal punctal occlusion. Conclusion: Our study showed that reducing the punctum diameter to 0.5 mm can improve vital staining scores, break-up-time, and Schirmer I test in dry eye related to Sjogren syndrome.

Dry eye in childhood: Epidemiological and clinical aspects

Because dry eye disease is rare in children and its pathogenesis is less well known than in adults, its diagnosis is often overlooked. It can occur in association with a number of congenital, autoimmune, endocrine, and inflammatory disorders, or under certain environmental and nutritional conditions. In some cases, early detection allows the underlying cause of the dry eye to be successfully treated and eliminated. In other cases, the disease may represent a lifelong problem, whose proper management can prevent ulceration and scarring of the ocular surface. Because of the association of pediatric dry eye with other conditions, a multidisciplinary approach to diagnosis and treatment is usually required. The purpose of this review is to enhance physician awareness of dry eye in children, to describe the most frequently associated conditions, and to discuss the diagnostic and therapeutic options available.

Influence of climate on clinical diagnostic dry eye tests: pilot study

Purpose. To analyze dry eye disease (DED) tests and their consistency in similar nonsymptomatic population samples living in two geographic locations with different climates (Continental vs. Atlantic). Methods. This is a pilot study including 14 nonsymptomatic residents from Valladolid (Continental climate, Spain) and 14 sex-matched and similarly aged residents from Braga (Atlantic climate, Portugal); they were assessed during the same season (spring) of two consecutive years. Phenol red thread test, conjunctival hyperemia, fluorescein tear breakup time, corneal and conjunctival staining, and Schirmer test were evaluated on three different consecutive visits. Reliability was assessed using the intraclass correlation coefficient and weighted kappa (J) coefficient for quantitative and ordinal variables, respectively. Results. Fourteen subjects were recruited in each city with a mean (TSD) age of 63.0 (T1.7) and 59.1 (T0.9) years (p = 0.08) in Valladolid and Braga, respectively. Intraclass correlation coefficient and J values of the tests performed were below 0.69 and 0.61, respectively, for both samples, thus showing moderate to poor reliability. Subsequently, comparisons were made between the results corresponding to the middle and higher outdoor relative humidity (RH) visit in each location as there were no differences in mean temperature (p Q 0.75) despite RH values significantly differing (p e 0.005). Significant (p e 0.05) differences were observed between Valladolid and Braga samples on tear breakup time (middle RH visit, 2.76 T 0.60 vs. 5.26 T 0.64 seconds; higher RH visit, 2.61 T 0.32 vs. 5.78 T 0.88 seconds) and corneal (middle RH, 0.64 T 0.17 vs. 0.14 T 0.10; higher RH, 0.60 T 0.22 vs. 0.0 T 0.0) and conjunctival staining (middle RH, 0.61 T 0.17 vs. 0.14 T 0.08; higher RH, 0.57 T 0.15 vs. 0.18 T 0.09). Conclusions. This pilot study provides initial evidence to support that DED test outcomes assessing the ocular surface integrity and tear stability are climate dependent. Future large-sample studies should support these outcomes also in DED patients. This knowledge is fundamental for multicenter clinical trials. Lack of consistency in diagnostic clinical tests for DED was also corroborated. (Optom Vis Sci 2015;92:e284Ye289)

In vivo characterisation of a novel water-soluble Cyclosporine A prodrug for the treatment of dry eye disease.

Cyclosporine A (CsA) has been demonstrated to be effective for the treatment of a variety of ophthalmological conditions, including ocular surface disorders such as the dry eye disease (DED). Since CsA is characterised by its low water solubility, the development of a topical ophthalmic formulation represents an interesting pharmaceutical question. In the present study, two different strategies to address this challenge were studied and compared: (i) a water-soluble CsA prodrug formulated within an aqueous solution and (ii) a CsA oil-in-water emulsion (Restasis, Allergan Inc., Irvine, CA). First, the prodrug formulation was shown to have an excellent ocular tolerance as well as no influence on the basal tear production; maintaining the ocular surface properties remained unchanged. Then, in order to allow in vivo investigations, a specific analytical method based on ultra high pressure liquid chromatography coupled with triple quadrupole mass spectrometer (UHPLC-MS/MS) was developed and optimised to quantify CsA in ocular tissues and fluids. The CsA ocular kinetics in lachrymal fluid for both formulations were found to be similar between 15 min and 48 h. The CsA ocular distribution study evidenced the ability of the prodrug formulation to penetrate into the eye, achieving therapeutically active CsA levels in tissues of both the anterior and posterior segments. In addition, the detailed analysis of the in vivo data using a bicompartmental model pointed out a higher bioavailability and lower elimination rate for CsA when it is generated from the prodrug than after direct application as an emulsion. The interesting in vivo properties displayed by the prodrug solution make it a safe and suitable option for the treatment of DED.

A novel cyclosporin a aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

PURPOSE: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporine A for dry eye treatment. METHODS: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labeled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labeled micelle formulation and analyzed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CyA kinetics in tears, and CyA ocular distribution after topical instillation. A 0.05% CyA micelle formulation was compared to a marketed emulsion (Restasis). RESULTS: The in vitro experiments showed the internalization of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CyA kinetics values: AUC = 2339 ± 1032 min*μg/mL and 2321 ± 881.63; Cmax = 478 ± 111 μg/mL and 451 ± 74; half-life = 36 ± 9 min and 28 ± 9 for the micelle formulation and Restasis, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CyA/g tissue to the cornea. CONCLUSIONS: The micelle formulation delivered active CyA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases.

Clinical Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

Purpose: To report the clinical outcome of the treatment of dry eyes using 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) (Ophthalmos, Sao Paulo, Brazil). Methods: Sixteen eyes of 8 patients with Sjogren syndrome dry eyes (age, 51.13 +/- 9.45 years) were enrolled in this study (prospective noncontrolled interventional case series). Patients were instructed to use topical 0.03% tacrolimus eye drops twice a day (every 12 hours) in the lower conjunctival sac. Schirmer I test, break-up time, corneal fluorescein, and rose bengal staining score were performed in all patients 1 day before, and 14, 28, and 90 days after treatment with 0.03% tacrolimus eye drops. Results: The average fluorescein staining and rose bengal staining scores improved statistically significantly after 14 days of treatment and improved even more after 28 and 90 days. The average Schirmer I test did not improve statistically significantly after 28 days of treatment, although we did observe a significant improvement after 90 days of treatment with 0.03% tacrolimus eye drops. The average break-up time did not improve statistically after 14 days of treatment, although we observed a significant improvement after 28 and 90 days of treatment with 0.03% tacrolimus eye drops. Conclusions: Topical 0.03% tacrolimus eye drops successfully improved tear stability and ocular surface status in patients with dry eyes.

Fluorophotometry is a sensitive method/technique to evaluate epithelial permeability in murine experimental dry eye

Purpose. Fluorophotometry is a well validated method for assessing corneal permeability in human subjects. However, with the growing importance of basic science animal research in ophthalmology, fluorophotometry’s use in animals must be further evaluated. The purpose of this study was to evaluate corneal epithelial permeability following desiccating stress using the modified Fluorotron Master™. ^ Methods. Corneal permeability was evaluated prior to and after subjecting 6-8 week old C57BL/6 mice to experimental dry eye (EDE) for 2 and 5 days (n=9/time point). Untreated mice served as controls. Ten microliters of 0.001% sodium fluorescein (NaF) were instilled topically into each mouse’s left eye to create an eye bath, and left to permeate for 3 minutes. The eye bath was followed by a generous wash with Buffered Saline Solution (BSS) and alignment with the Fluorotron Master™. Seven corneal scans using the Fluorotron Master were performed during 15 minutes (1 st post-wash scans), followed by a second wash using BSS and another set of five corneal scans (2nd post-wash scans) during the next 15 minutes. Corneal permeability was calculated using data calculated with the FM™ Mouse software. ^ Results. When comparing the difference between the Post wash #1 scans within the group and the Post wash #2 scans within the group using a repeated measurement design, there was a statistical difference in the corneal fluorescein permeability of the Post-wash #1 scans after 5 days (1160.21±108.26 vs. 1000.47±75.56 ng/mL, P<0.016 for UT-5 day comparison 8 [0.008]), but not after only 2 days of EDE compared to Untreated mice (1115.64±118.94 vs. 1000.47±75.56 ng/mL, P>0.016 for UT-2 day comparison [0.050]). There was no statistical difference between the 2 day and 5 day Post wash #1 scans (P=.299). The Post-wash #2 scans demonstrated that EDE caused a significant NaF retention at both 2 and 5 days of EDE compared to baseline, untreated controls (1017.92±116.25, 1015.40±120.68 vs. 528.22±127.85 ng/mL, P<0.05 [0.0001 for both]). There was no statistical difference between the 2 day and 5 day Post wash #2 scans (P=.503). The comparison between the Untreated post wash #1 with untreated post wash #2 scans using a Paired T-test showed a significant difference between the two sets of scans (P=0.000). There is also a significant difference between the 2 day comparison and the 5 day comparison (P values = 0.010 and 0.002, respectively). ^ Conclusion. Desiccating stress increases permeability of the corneal epithelium to NaF, and increases NaF retention in the corneal stroma. The Fluorotron Master is a useful and sensitive tool to evaluate corneal permeability in murine dry eye, and will be a useful tool to evaluate the effectiveness of dry eye treatments in animal-model drug trials.^

Label-free biosensing for dry eye by Means of BICELLS

The use of Biophotonic Sensing Cells (BICELLs) based on micro-nano pattemed photonic architectures has been recently proven as an efficient methodology for label-free biosensing by using Optical Interrogation [1]. According to this, we have studied the different optical response for a specific typology of BICELL, consisting of structures of SU -8. This material is biocompatible with different types of biomolecules and can be immobilized on its sensing surface. In particular, we have measured the optical response for a biomarker in clinic diagnostic of dry eye. Although different proteins can be enstudied such as: PRDX5, ANXA 1, ANXA 11, CST 4, PLAA Y S 1 OOA6 related with ocular surface (dry eye), for this work PLAA (phospholipase A2) is studied by means of label free biosensing based on BICELLs for analyzing the performance and specificity according with means values of concentration in ROC curves.

Clinical Characterization of Asymptomatic or Minimally Symptomatic Young Patients Showing Signs Compatible With Dry Eye: A Pilot Study

Purpose: To evaluate and characterize the clinical profile of young asymptomatic or minimally symptomatic patients without diagnosis of dry eye but showing signs compatible with dry eye syndrome (DES). Methods: Prospective study including a total of 50 consecutive subjects with ages ranging from 18 to 40 years that were identified as asymptomatic or minimally symptomatic by means of the Ocular Surface Disease Index (OSDI) (score of <22). In all patients, a complete battery of tests for the diagnosis of DES was performed including the evaluation of the tear film break-up time (TFBUT), the level of corneal and conjunctival staining, and the eyelid and Meibomian morphology. Results: The OSDI score was significantly higher in women than in men (median: 12.5 vs. 5.3, P=0.01). Low grades of ocular surface staining, dysfunction of Meibomian gland expression, and alteration of quality of Meibomian secretions were observed in 56%, 58%, and 84% of eyes, respectively. More eyes with some dysfunction of Meibomian gland expressibility had a TFBUT less than 5 sec (P=0.033). A statistically significant difference in the OSDI score was found between patients with and without systemic allergies (P=0.036) and between male and female (P=0.01). Likewise, the OSDI score was significantly higher in those women wearing contact lenses compared with those not wearing them (P=0.012). Conclusions: Asymptomatic or minimally symptomatic young subjects may present low grades of clinical signs compatible with DES, with a trend to more symptomatology in women and allergic patients. These outcomes should be confirmed in future studies with larger samples.

Essential fatty acids for dry eye:a review

Purpose Dry eye is a common complaint often encountered in optometric practice. However, it is a difficult condition to treat as clinical signs do not always correlate with patient symptoms. Essential fatty acids (EFA), particularly omega-3 EFA, may be effective in dealing with the underlying causes. Methods A literature review was carried out on the PubMed, ScienceDirect and Ovid databases. Searches included keywords such as ‘dry eye’, ‘essential fatty acids’ and ‘nutrition’ to find articles relating to the treatment of dry eye syndrome (DES) with omega-3 EFAs. Results Omega-3 and -6 EFAs need to be consumed together within a reasonable ratio to be effective. Currently, typical diets in developed countries lack omega-3 EFA and this results in an overexposure to omega-6. Omega-3 supplementation has an anti-inflammatory effect, inhibiting creation of omega-6 prostaglandin precursors. Omega-3 EFAs also demonstrate anti-inflammatory action in the lacrimal gland preventing apoptosis of the secretory epithelial cells. Supplementation clears meibomitis, allowing a thinner, more elastic lipid layer to protect the tear film and cornea. Conclusion Dietary supplementation of omega-3 EFA has already proven to be effective in coronary heart disease and arthritis. Safety is not a concern as it works synergistically with omega-6 in the body. Evidence suggests that supplementation with omega-3 EFA may be beneficial in the treatment and prevention of DES.

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.