Tear Flow Rate Research Articles

Effect of the Jiedu Tongluo Shengjin formulation on plasma immunoglobulin G (IgG) levels in patients with primary Sjögren’s syndrome

This study assessed the effect of Jiedu Tongluo Shengjin formulation on plasma IgG levels in pSS patients. 89 pSS patients were randomized into treatment (45 cases; 1 drop-out) and control (44 cases) groups using the random number table method. The control group received hydroxychloroquine sulfate and a placebo dose of Jiedu Tongluo Shengjin. The treatment group received hydroxychloroquine sulfate and the original Jiedu Tongluo Shengjin formulation. The treatment group showed significant decreases in SS disease activity index, TCM syndrome score, plasma IgG, and ESR, and significant increases in tear film break-up time, tear flow rate, salivary flow rate, C3, and C4 levels (p<0.05). No significant changes were observed in the control group (p>0.05). Jiedu Tongluo Shengjin effectively reduced eye and mouth dryness in pSS patients by improving inflammation and immune status.

Applying Different Conditions in the OphthalMimic Device Using Polymeric and Hydrogel-Based Hybrid Membranes to Evaluate Gels and Nanostructured Ophthalmic Formulations.

The OphthalMimic is a 3D-printed device that simulates human ocular conditions with artificial lacrimal flow, cul-de-sac area, moving eyelid, and a surface to interact with ophthalmic formulations. All tests with such a device have used a continuous artificial tear flow rate of 1 mL/min for 5 min. Here, we implemented protocol variations regarding the application time and simulated tear flow to increase the test's discrimination and achieve reliable performance results. The new protocols incorporated the previously evaluated 0.2% fluconazole formulations containing or not chitosan as a mucoadhesive component (PLX16CS10 and PLX16, respectively) and novel moxifloxacin 5% formulations, either in a conventional formulation and a microemulsion (CONTROL and NEMOX, respectively). The flow rate was reduced by 50%, and a pre-flow application period was also included to allow formulation interaction with the membrane. The OphthalMimic model was used with both polymeric and hydrogel-based hybrid membranes, including a simulated eyelid. Lowering the flow made it feasible to prolong the testing duration, enhancing device discrimination potential. The hydrogel membrane was adequate for testing nanostructure formulations. The OphthalMimic device demonstrated once again to be a versatile method for evaluating the performance of ophthalmic drug formulations with the potential of reducing the use of animals for experimentation.

Investigation of Inter- and Intra-Day Variability of Tear Fluid Regarding Flow Rate, Protein Concentration as well as Protein Composition.

The purpose of this study was to present the determination of inter- and intra-day variations in tear flow rate, and tear fluid protein concentration, as well as protein composition regarding their impact for future biomarker studies. Tear fluid was collected noninvasively from 18 healthy subjects by performing Schirmer tests at 4 different time points repetitive in a period of 2days. The tear flow rate on the Schirmer test strips was measured. Proteins were extracted from strips and quantified using amino acid analysis. Protein composition was analyzed by the strips data-independent (DIA) based mass spectrometry. To exclude any impairments to health, volunteers underwent a detailed neurological as well as an ophthalmological examination. Whether tear fluid was collected from oculus sinister or oculus dexter did not affect the tear flow rate (P ≈ 0.63) or protein concentration (P ≈ 0.97) of individual subjects. Moreover, protein concentration was independent from the tear volume, so that a change in volume may only influence the total protein amount. When the examination days were compared, investigation of tear flow rate (P ≈ 0.001) and protein concentration (P ≈ 0.0003) indicated significant differences. Further, mass spectrometric analysis of tear fluid revealed 11 differentially regulated proteins when comparing both examination days. Our findings provide evidence of inter-day variation in tear flow rate, tear proteome concentration, and composition in healthy subjects, suggesting that inter-day variation needs to be taken into consideration in biomarker research of tear fluid. Identified proteins were assigned to functions in the immune response, oxidative and reducing processes, as well as mannose metabolism.

Lacrimal gland activity in lacrimal drainage obstruction: exploring the potential cross-talk between the tear secretion and outflow

PurposeTo investigate the effects of lacrimal drainage obstructions on the lacrimal gland activity and if there exists a potential link between the two.MethodsDirect assessment of the lacrimal gland activity from...

5-Fluorouracil as a targeted lacrimal gland therapy for chronic Stevens-Johnson syndrome: A pilot study.

The surgical technique of periglandular 5-fluorouracil (5-FU) injection and its effects on the morphology and function of the main lacrimal gland of patients with severe dry eye disease due to Stevens-Johnson syndrome (SJS) are reported. 5-FU, as a potential antifibrotic agent, is given in the dose of 0.1 ml (50 mg/ml), subconjunctivally into the periglandular fibrosed area of the palpebral lobe of the main lacrimal gland. The injection is given using 30G needle into the subconjunctival plane and not into the substance of palpebral lobe. Eight eyes (eight lobes) of seven chronic SJS patients (mean age, 32.5 years, <5 mm Schirmer) received the injection. All eight lobes demonstrated a visible reduction in the conjunctival congestion and scarring over the lobar area. The mean OSDI scoring improved from 65.3 to 51.1. Three patients with mean pre-injection Schirmer I values of 4 mm showed a mean change of 1 mm at four weeks following a single injection. The tear flow rate per lobe for the above three patients improved from 0.22, 0.12, and 0.16 μl/min to 0.31, 0.12, and 0.21 μl/min, respectively. Another patient with pre-injection Schirmer of 4 mm showed no change in tear flow. Three eyes with zero baseline Schirmer values (no visible secretory opening) had no improvement in tearing or ocular surface staining. Local 5-FU injection alters morphology of the conjunctiva overlying the palpebral lobe in SJS patients, but fails to show any significant effect on tear secretion.

In vitro–in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model

There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studies.Graphical abstract

Current and Future Perspectives on Microfluidic Tear Analytic Devices.

Most current invasive analytic devices for disease diagnosis and monitoring require the collection of blood, which causes great discomfort for patients and may potentially cause infection. This explains the great need for noninvasive devices that utilize other bodily fluids like sweat, saliva, tears, or urine. Among them, eye tears are easily accessible, less complex in composition, and less susceptible to dilution. Tears also contain valuable clinical information for the diagnosis of ocular and systemic diseases as the tear analyte level shows great correlation with the blood analyte level. These unique advantages make tears a promising platform for use in clinical settings. As the volume of tear film and the rate of tear flow are only microliters in size, the use of microfluidic technology in analytic devices allows minimal sample consumption. Hence, more and more microfluidic tear analytic devices have been proposed, and their working mechanisms can be broadly categorized into four main types: (a) electrochemical, (b) photonic crystals, (c) fluorescence, and (d) colorimetry. These devices are being developed toward the application of point-of-care tests with rapid yet accurate results. This review aims to provide a general overview of the recent developmental trend of microfluidic devices for tear analysis. Moreover, the fundamental principle behind each type of device along with their strengths and weaknesses will be discussed, especially in terms of their abilities and potential in being used in point-of-care settings.

Physico-chemical properties of Artificial tear ducts from Fractionated Thai silk fibroin

Artificial tear ducts (ATD) or Jones tubes, have been used in patients with tear ducts obstruction for draining tears into the nose. Commercial ATDs are generally made of glass but they have slippery surfaces causing the ducts pushed out and easily broken. Polymer-based ATDs, are more flexible and adhesive to tissues. However, the users could encounter material-related problems due to allergic reactions, low tissue adhesion and complications. We designed artificial tear ducts from Thai silk fibroin (SF) solution. The SF was fractionated using freeze-thaw cycles (-4°C and 25°C for 5 cycles) into SF-P (precipitants, 63.53±4.58% yields) and SF-S (soluble, 34.05±5.76% yields (w/v)). The concentrated solutions (20%W/W) of SF, SF-P and SF-S were dip-coated into tubes. The leaking test was performed using simulated natural tear flow rate of 0.0022 mL/min for 6 h. SF-S duct lost its shape and leaked. Absorption of the balanced salt solution (BSS) of the SF and SF-P were at 5.67±0.76% and 8.05±1.28 wt.% respectively, giving their wet inner and outer diameters at 2 and 2.5 mm. and the thickness 500 microns. Crystallinities of SF and SF-P analyzed using ATR-FTIR, were at 42.27 and 44.51% respectively. The thermal decomposition temperature of SF and SF-P analyzed using TGA, were at 277 and 280°C. Degradability in BSS containing lysozyme 1.69 U/mg to mimic tears at 37°C in vitro showing that both ATDs are stabilized for at least 4 weeks. BSS height obtained capillary test that compared with glass ducts, SF and SF-P at 7.0±0.0, 6.9±0.4 and 7.1±0.4 mm, respectively, while glass ducts were 34.81±0.0. The SF and SF-P have flexural stress were 55.24±7.68 MPa and 81.42±2.71 MPa, %flexural strain at max stress was 5.43±0.46% and 2.54±0.17% and flexural Modulus was 1.82±0.29 GPa and 6.13±0.51GPa respectively. The results of all experiments indicate that SF-P had the highest potential for further development into natural polymer-based ATDs.

Quantitative Assessment of Age and Gender Related Changes in Human Lacrimal Fluid Composition in Subjects

Purpose: The frequency of eyelids blink rate has effect on the integrity of the tear fluid and replacement of old of tears on the ocular surface. Comprehension of the effect of advancing age and gender on tears fluid stability and quality is contentious. Basal tears continuously bathe the ocular facet lubricating and providing protection from viral and bacterial infections, cooling the surface as warmth encourages pathogen. Basal tear dysfunction basically results in conjunctival and corneal conditions which exposes the ocular facet to dryness, ulceration, opacity and even blindness. This study determined the quantitative assessment of age and gender related changes in human lacrimal fluid composition in subjects&#x0D; Methods: The design involved 400 (192 males and 208 females) human subjects aged 6 years and above who do not wear contact lenses, not on topical medication and having healthy eyes grouped into twelve groups based on age and gender. Maximum blink interval (for tear break-up time) and phenol red thread procedure (for tear volume) were carried out monocularly for each subject.&#x0D; Results: Findings from this study have established that tear fluid stability among different age groups; are often higher for group 6-12years and lower for 60years and above; therefore, study established that tear fluid stability is age dependent. In addition, tear fluid stability (average MBI. Tear volume and flow rate) are gender independent.&#x0D; Conclusion: The present study revealed that tears fluid breakup time increases with decrease in tears fluid flow rate, volume and flow.

Diagnostic biomarkers in tear fluid: from sampling to preanalytical processing

Tear fluid is receiving growing attention as a source for novel diagnostic biomarkers. Multiple techniques are available for its collection and impact the composition of acquired samples. We sought to provide a direct comparison of two collection methods with regard to implementation, acceptance, and impact on sample composition. Tear fluid was collected from fifteen healthy volunteers with capillary tubes and Schirmer strips and analyzed for total protein and IgG concentrations. Sampling parameters and perception by test persons were compared. The use of capillary tubes was more convenient for the participants while causing more effort for the collector. Tear flow rates as well as the relative and absolute amount of IgG were higher when Schirmer strips were used. Consecutive collections with Schirmer strips significantly influenced tear flow rates, IgG, and protein concentrations. A moderate correlation was observed between tear flow rates and IgG concentrations for both methods. Samples collected with both methods can be analyzed by isoelectric focusing, a potential diagnostic application in the field of neurology. The specific advantages and limitations of tear fluid sampling with either capillary tubes or Schirmer strips demonstrate the need for a thorough investigation of collection methods with regard to the application of interest.

Lysozyme Deposition on Contact Lenses in an In Vitro Blink-Simulation Eye Model Versus a Static Vial Deposition Model.

To evaluate active lysozyme deposition on daily disposable (DD) contact lenses (CL) using a novel in vitro blink model. Three conventional hydrogel DD CL materials (etafilcon A, omafilcon A, nelfilcon A) and three silicone hydrogel DD CL materials (delefilcon A, senofilcon A, somofilcon A) were tested. The device blink rate was set to 6 blinks/min with a tear flow rate of 1 μL/min using an artificial tear solution (ATS) containing lysozyme and other typical tear film components. After incubation at 2, 4, or 8 hr, lenses were removed, and lysozyme activity was measured. A separate experiment was conducted with lenses incubated in a static vial containing 480 μL of ATS. Etafilcon A deposited significantly higher amounts of active lysozyme (402±102 μg/lens) than other lens materials after 8 hr (P<0.0001). Etafilcon A had a higher amount of active lysozyme using the blink model compared with the static vial (P=0.0435), whereas somofilcon A (P=0.0076) and senofilcon A (P=0.0019) had a higher amount of lysozyme activity in the vial compared with the blink model. The blink model can be tuned to provide quantitative data that closely mimics ex vivo studies and can be used to model deposition of lysozyme on CL materials.

Development of an In Vitro Blink Model for Ophthalmic Drug Delivery.

Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model.

Tear secretion from the lacrimal gland: variations in normal versus dry eyes

PurposeTo investigate the secretory status of the main lacrimal gland in healthy and dry eye disease (DED) via fluorescein-assisted direct assessment of tear secretion from the palpebral lobes.MethodsIncluded were 25...

Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren’s Syndrome-Like Disease

Sjogren’s syndrome (SS) is an autoimmune disease that manifests primarily in salivary and lacrimal glands leading to dry mouth and eyes. Unfortunately, there is no cure for SS due to its complex etiopathogenesis. Mesenchymal stem cells (MSCs) were successfully tested for SS, but some risks and limitations remained for their clinical use. This study combined cell- and biologic-based therapies by utilizing the MSCs extract (MSCsE) to treat SS-like disease in NOD mice. We found that MSCsE and MSCs therapies were successful and comparable in preserving salivary and lacrimal glands function in NOD mice when compared to control group. Cells positive for AQP5, AQP4, α-SMA, CK5, and c-Kit were preserved. Gene expression of AQP5, EGF, FGF2, BMP7, LYZ1 and IL-10 were upregulated, and downregulated for TNF-α, TGF-β1, MMP2, CASP3, and IL-1β. The proliferation rate of the glands and serum levels of EGF were also higher. Cornea integrity and epithelial thickness were maintained due to tear flow rate preservation. Peripheral tolerance was re-established, as indicated by lower lymphocytic infiltration and anti-SS-A antibodies, less BAFF secretion, higher serum IL-10 levels and FoxP3+ Treg cells, and selective inhibition of B220+ B cells. These promising results opened new venues for a safer and more convenient combined biologic- and cell-based therapy.

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis.

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at selected times. Prednisone and prednisolone were quantified in tears by liquid chromatography-mass spectrometry.Results: Lacrimal prednisone and prednisolone concentrations ranged from 2 to 523 ng/mL and 5 to 191 ng/mL, respectively. Drug concentrations were overall greater in dogs receiving higher doses of prednisone, but were not correlated with tear flow rate. Eyes with conjunctivitis often had larger amounts of prednisone and prednisolone in tear fluid compared to control eyes (up to +64%), but differences were not statistically significant. Significantly greater, but clinically insignificant, levels of prednisolone were found in eyes with severe versus mild conjunctivitis for oral prednisone doses ≥1.0 mg/kg.Conclusions: Disruption of the blood–tear barrier with conjunctivitis did not significantly affect drug levels in tears. Based on drug PK in tears, oral prednisone is likely safe for the management of reflex uveitis and ocular surface diseases. However, further prospective trials using systemic corticotherapy in diseased animals are warranted to confirm findings from this preclinical study.

Impact of Flow Rate, Collection Devices, and Extraction Methods on Tear Concentrations Following Oral Administration of Doxycycline in Dogs and Cats.

Purpose: Compare the precision of doxycycline quantification in tear fluid collected with either Schirmer strips or polyvinyl acetal (PVA) sponges following oral drug administration.Methods: Three dogs and 3 cats were administered doxycycline orally at a dose of 4.2–5 mg/kg every 12 h for 6 consecutive days. At day 5 and 6, blood and tear fluid were sampled to capture doxycycline trough and maximal concentrations. Tear fluid was collected 3 times (spaced 10 min apart) at each session with the absorbent material placed in the lower conjunctival fornix until the 20-mm mark was reached (Schirmer strip, one eye) or for 1 min (PVA sponge, other eye). Tear extraction was performed with either centrifugation or elution in methanol. Doxycycline concentrations were measured with liquid chromatography–mass spectrometry. Low (100 ng/mL) and high (1,000 ng/mL) tear concentrations measured in vivo were spiked into each absorbent material in vitro to evaluate percentage drug recovery.Results: After oral administration of doxycycline, the drug reached the tear compartment at concentrations of 45.1–900.7 ng/mL in cats and 45.4–632.0 ng/mL in dogs, representing a tear-to-serum ratio of 12% and 16%, respectively. Doxycycline tear concentrations were significantly more precise when tear collection was performed with Schirmer strips rather than PVA sponges (P = 0.007), but were not correlated with tear flow rate. In vitro doxycycline recovery was poor to moderate (<75%).Conclusions: Schirmer strips represent a good option for lacrimal doxycycline quantification, although the collection and subsequent extraction have to be optimized to improve drug recovery.

Direct visualization of aqueous tear secretion from lacrimal gland.

To introduce a new method for direct observation of tear secretion from the palpebral lobes of the main lacrimal glands and Wolfring glands using fluorescein dye. Twenty-six patients with dry eye and 26 healthy subjects were included in the study. Fluorescein was applied to the conjunctiva overlaying the palpebral lobe of the main lacrimal glands. Under cobalt blue light, we captured tear secretion from the glands in movies. We compared the number of excretory openings, the location and tear flow rate between the dry eye and healthy-subject groups. To observe tear secretion from the Wolfring glands, we everted the upper lids and applied fluorescein dye to the upper margin of the tarsus. Mean number of excretory openings on the palpebral lobe was 2.5 in the dry eye group and 3.4 in the healthy-subject group (p=0.031). Most of the openings were observed at the ridge, the most protruding portion of the palpebral lobe. Mean flow rate from the palpebral lobe was 0.45μl/min in the dry eye group and 0.91μl/min in the healthy-subject group (p=0.046). Mean flow ratefrom the Wolfring glands was 0.007μl/min in the dry eye group and 0.009μl/min in the healthy-subject group (p=0.615). This visualization method allowed us to directly observe tear secretion from the palpebral lobe of the main lacrimal glands and Wolfring glands, and to quantitatively measure the tear flow rate from the lacrimal glands.

Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling.

Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.

Changes in the Chemical Barrier Composition of Tears in Alzheimer's Disease Reveal Potential Tear Diagnostic Biomarkers.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, with increasing prevalence affecting millions of people worldwide. Currently, only autopsy is able to confirm the diagnosis with a 100% certainty, therefore, biomarkers from body fluids obtained by non-invasive means provide an attractive alternative for the diagnosis of Alzheimer`s disease. Global changes of the protein profile were examined by quantitative proteomics; firstly, electrophoresis and LC-MS/MS were used, thereafter, SRM-based targeted proteomics method was developed and applied to examine quantitative changes of tear proteins. Alterations in the tear flow rate, total tear protein concentration and composition of the chemical barrier specific to AD were demonstrated, and the combination of lipocalin-1, dermcidin, lysozyme-C and lacritin was shown to be a potential biomarker, with an 81% sensitivity and 77% specificity.

Dry eye in LASIK patients.

BackgroundIncreasing age is a known risk factor for developing dry eye. The specific aims of the present study were to determine the prevalence of dry eye syndrome (DES) and use of post-operative dry eye medications in a relatively young population presenting for LASIK surgery at an academic ophthalmology clinic.FindingsA retrospective, analysis of 948 de-identified patient charts (median age 39 years, not age stratified) was performed to extract pre-LASIK diagnoses and post-LASIK medication lists. Clinical evaluation for DES and the results of Schirmer’s reflex tear flow test were used to assign LASIK patients into Normal, Pre-dry eye (Pre-DES), and Dry Eye Syndrome (DES) groups; which were then compared for use of dry eye medications.Based on pre-operative diagnoses, only 2% (CI: 1.3 – 3.1) of LASIK patients presented with overt DES. Unexpectantly, 25% (CI: 22.2 – 27.6) of LASIK patients labeled Pre-DES were not classified by the clinician as having overt DES, yet they showed poor reflex tear flow rates ≤ 5 mm before surgery, and frequently used post-operative lubricant dry eye medications.ConclusionsAlthough the number of patients with pre-existing eye conditions was unknown, a sizable portion of relatively young LASIK patients displays poor reflex tear flow without overt DES. Such patients could go on to develop more serious consequences of poor tear flow, such as corneal abrasion and erosion. More specific, dry eye medications may be needed for ideal treatment.