Wearable, Biocompatible, and Dual-Emission Ocular Multisensor Patch for Continuous Profiling of Fluoroquinolone Antibiotics in Tears.

The abuse or misuse of antibiotics in clinical and agricultural settings severely endangers human health and ecosystems, which has raised profound concerns for public health worldwide. Trace detection and reliable discrimination of commonly used fluoroquinolone (FQ) antibiotics and their analogues have consequently become urgent to guide the rational use of antibiotic medicines and deliver efficient treatments for associated diseases. Herein, we report a wearable eye patch integrated with a quadruplex nanosensor chip for noninvasive detection and discrimination of primary FQ antibiotics in tears during routine eyedrop treatment. A set of dual-mode fluorescent nanoprobes of red- or green-emitting CdTe quantum dots integrated with lanthanide ions and a sensitizer, adenosine monophosphate, were constructed to provide an enhanced fluorescence up to 45-fold and nanomolar sensitivity toward major FQs owing to the aggregation-regulated antenna effect. The aggregation-driven, CdTe-Ln(III)-based microfluidic sensor chip is highly specific to FQ antibiotics against other non-FQ counterparts or biomolecular interfering species and is able to accurately discriminate nine types of FQ or non-FQ eyedrop suspensions using linear discriminant analysis. The prototyped wearable sensing detector has proven to be biocompatible and nontoxic to human tissues, which integrates the entire optical imaging modules into a miniaturized, smartphone-based platform for field use and reduces the overall assay time to ∼5 min. The practicability of the wearable eye patch was demonstrated through accurate quantification of antibiotics in a bactericidal event and the continuous profiling of FQ residues in tears after using a typical prescription antibiotic eyedrop. This technology provides a useful supplement to the toolbox for on-site and real-time examination and regulation of inappropriate daily drug use that might potentially lead to long-term antibiotic abuse and has great implications in advancing personal healthcare techniques for the regulation of daily medication therapy.

Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

OphthalMimic: A new alternative apparatus without animal tissue for the evaluation of topical ophthalmic drug products.

The necessity of animal-free performance tests for novel ophthalmic formulation screening is challenging. For this, we developed and validated a new device to simulate the dynamics and physical-chemical barriers of the eye for in vitro performance tests of topic ophthalmic formulations. The OphthalMimic is a 3D-printed device with an artificial lacrimal flow, a cul-de-sac area, a support base, and a simulated cornea comprised of a polymeric membrane containing poly-vinyl alcohol 10 % (w/v), gelatin 2.5 % (w/v), and different proportions of mucin and poloxamer, i.e., 1:1 (M1), 1:2 (M2), and 2:1 (M3) w/v, respectively. The support base is designed to move between 0° and 50° to replicate the movement of an eyelid. We challenged the model by testing the residence performance of poloxamer®407 16 % and poloxamer®407 16 % + chitosan 1 % (PLX16CS10) gels containing fluconazole. The test was conducted with a simulated tear flow of 1.0 mL.min-1 for 5 min. The OphthalMimic successfully distinguished PLX16 and PLX16C10 formulations based on their fluconazole drainage (M1: 65 ± 14 % and 27 ± 10 %; M2: 58 ± 6 % and 38 ± 9 %; M3: 56 ± 5 % and 38 ± 18 %). In conclusion, the OphthalMimic is a promising tool for comparing the animal-free performance of ophthalmic formulations.

Tear biomarkers.

An extensive exploration of lacrimal fluid molecular biomarkers in understanding and diagnosing a spectrum of ocular and systemic diseases is presented. The chapter provides an overview of lacrimal fluid composition, elucidating the roles of proteins, lipids, metabolites, and nucleic acids within the tear film. Pooled versus single-tear analysis is discussed to underline the benefits and challenges associated with both approaches, offering insights into optimal strategies for tear sample analysis. Subsequently, an in-depth analysis of tear collection methods is presented, with a focus on Schirmer's test strips and microcapillary tubes methods. Alternative tear collection techniques are also explored, shedding light on their applicability and advantages. Variability factors, including age, sex, and diurnal fluctuations, are examined in the context of their impact on tear biomarker analysis. The main body of the chapter is dedicated to discussing specific biomarkers associated with ocular discomfort and a wide array of ocular diseases. From dry eye disease and thyroid-associated ophthalmopathy to keratoconus, age-related macular degeneration, diabetic retinopathy, and glaucoma, the intricate relationship between molecular biomarkers and these conditions is thoroughly dissected. Expanding beyond ocular pathologies, the chapter explores the applicability of tear biomarkers in diagnosing systemic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This broader perspective underscores the potential of lacrimal fluid analysis in offering non-invasive diagnostic tools for conditions with far-reaching implications.

Comparative analysis of human tear fluid and aqueous humor proteomes.

PURPOSE: Technological advancements allowing for the analysis of low-volume samples have led to the investigation of human tear fluid and aqueous humor (AH) as potential biomarker sources. However, acquiring AH samples poses significant challenges, making human tear fluid a more accessible alternative. This study aims to compare the protein compositions of these two biofluids to evaluate their suitability for biomarker discovery. METHODS: Paired tear and AH samples were collected from 20 patients undergoing cataract surgery. Tear samples were collected using Schirmer strips prior to surgery, and AH samples were collected from the anterior chamber immediately after corneal incision. Proteins were extracted and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 481 proteins were identified in greater than 50% of the tear samples, and 191 proteins were detected in greater than 50% of the AH samples. Of these proteins, 82 were found to be common between the two biofluids, with ALB, LTF, TF, LCN1, and IGKC being the most abundant. CONCLUSION: Although tear fluid and the AH are functionally independent and physically separated, many of the proteins detected in AH were also detected in tears. This direct comparison of the proteomic content of tear fluid and AH may aid in further investigation of tear fluid as a source of readily accessible biomarkers for various human diseases.

Discovery and Verification of Sjögren's Syndrome Protein Biomarkers in Tears by Targeted LC-MRM.

Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by exocrine gland dysfunction, mainly from the lacrimal and salivary glands. The disease causes severe aqueous dry eye syndrome (DED) and is associated with high rates of complications, including corneal ulceration, scaring, and perforation. Systemic complications may occur as well as a higher risk of developing lymphoma. Diagnosis of SS-DED is often delayed and difficult to establish. With the aim of discovering biomarkers to help discriminate SS-DED patients, a combination of untargeted and targeted LC-MS/MS analyses were performed on tear samples collected on Schirmer strips and subjected to tryptic digestion. Following the analysis of three cohorts and the development of two targeted LC-sMRM methods for the verification of putative biomarkers found in the first cohort of samples, 64 proteins could be linked to Sjögren's syndrome, in the hopes of helping to confirm diagnoses as well as potentially stratifying the severity of disease in these patients. Proteins that were increased in SS-DED showed activation of the immune system and alterations in homeostasis. Several proteases and protease inhibitors were found to be significantly changing in SS-DED, as well as a consistent decrease in specific proteins known to be secreted by the lacrimal gland.

Immediate Impact on Tear Osmolarity Following the Application of Different Ocular Lubricants in Patients Experiencing Moderate Dry Eye Symptoms.

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy. METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface's tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED. RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance. CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Effects of elevated serum estrogen on dry eye in women undergoing in vitro fertilisation.

PURPOSE: Sex hormones impact inflammatory and immune-mediated diseases. During IVF (in vitro fertilisation) treatment, circulating estrogen levels increase dramatically (10-50x) alongside changes in other hormones. This study examined changes in dry eye with IVF and its relationship with sex hormones. METHODS: A two visit study was conducted on first day of menstruation when estrogen levels are lowest (baseline visit), and on day 9-11 (peak estrogen visit (PO)) of IVF. Symptoms of dry eye and ocular pain and signs of dry eye were examined. Serum hormone levels were assessed using mass spectrometry and immunoassay. Changes in signs and symptoms and associations were explored. Hierarchical multiple regression analysis assessed factors contributing to signs and symptoms. RESULTS: 40 women (36.2 ± 4.0 years) completed the study. Baseline and PO oestradiol (E2) levels were 28.9 pg/ml (20) (median (IQR)); 1360 pg/ml (1276) respectively. Ocular pain and dry eye symptoms worsened (p = 0.02 and p < 0.01) and tear break up and tear secretion values decreased (p = 0.005 and 0.01) at PO. Higher E2 and lower luteinizing hormone (LH) were associated with worsening of dry eye symptoms (ρ = 0.34 p = 0.03, ρ = -0.49 p = 0.001). Reduction in LH and increase in progesterone (P4) were associated with increased ocular pain (ρ = 0.45, p = 0.004 and ρ = 0.39, p = 0.01). Dry eye symptoms were predicted by LH and tear break up (p = 0.02; R2 = 0.18). CONCLUSIONS: IVF treatment resulted in significantly increased ocular symptoms and tear film alterations although these changes were not clinically significant. Dry eye signs and symptoms were poorly predicted by hormone levels.

Experimental Analysis of Tear Fluid and Its Processing for the Diagnosis of Multiple Sclerosis.

A pilot analysis of the tear fluid of patients with multiple sclerosis (MS) collected by glass microcapillary was performed using various experimental methods: liquid chromatography-mass spectrometry, Raman spectroscopy, infrared spectroscopy, and atomic-force microscopy. Infrared spectroscopy found no significant difference between the tear fluid of MS patients and the control spectra; all three significant peaks were located at around the same positions. Raman analysis showed differences between the spectra of the tear fluid of MS patients and the spectra of healthy subjects, which indicated a decrease in tryptophan and phenylalanine content and changes in the relative contributions of the secondary structures of the polypeptide chains of tear proteins. Atomic-force microscopy exhibited a surface fern-shaped dendrite morphology of the tear fluid of patients with MS, with less roughness on both oriented silicon (100) and glass substrates compared to the tear fluid of control subjects. The results of liquid chromatography-mass spectrometry showed downregulation of glycosphingolipid metabolism, sphingolipid metabolism, and lipid metabolism. Proteomic analysis identified upregulated proteins in the tear fluid of patients with MS such as cystatine, phospholipid transfer protein, transcobalamin-1, immunoglobulin lambda variable 1-47, lactoperoxidase, and ferroptosis suppressor protein 1; and downregulated proteins such as haptoglobin, prosaposin, cytoskeletal keratin type I pre-mRNA-processing factor 17, neutrophil gelatinase-associated lipocalin, and phospholipase A2. This study showed that the tear proteome in patients with MS is modified and can reflect inflammation. Tear fluid is not a commonly used biological material in clinico-biochemical laboratories. Experimental proteomics has the potential to become a promising contemporary tool for personalized medicine, and it might be applied in clinical practice by providing a detailed analysis of the tear-fluid proteomic profile of patients with MS.

Meibomian Gland Dysfunction in Primary Acquired Nasolacrimal Duct Obstruction.

This study was designed to investigate the influence of primary nasolacrimal duct obstruction (PANDO) on the structure and function of the Meibomian gland and to examine whether it is related to functional failure after dacryocystorhinostomy surgery. Medical records of patients diagnosed as PANDO from August 2021 to February 2022 were retrospectively studied. Results of slit lamp examination, lacrimal drainage test, tear break-up time, anterior segment optical coherence tomography, and meibography were collected. Tear meniscus height, tear break-up time, meiboscore, and lipid layer thickness of tear membrane were parameters compared between the eyes with complete PANDO and the control group. Medical records of 44 patients, therefore 88 eyes were collected, and there were 28 eyes with complete PANDO (total obstruction group), while normal eyes (control group) were 30. Mean tear meniscus height was significantly higher than that of the control group ( P value<0.001), but tear break-up time ( P value=0.322), lipid layer thickness ( P value=0.755), and meiboscore ( P value=0.268) were not significantly different. However, in the cases with moderate and severe meibomian gland destruction, the lipid layer thickness of the total obstruction group was significantly thinner than the control group. Lipid secretion of meibomian glands was less in eyes with PANDO than in eyes without PANDO, under moderate to severe meibomian gland destruction. It can lead to persistent epiphora after dacryocystorhinostomy due to a compensatory response against evaporative dry eye disease. Patients should be educated before the decision to undergo surgeries about the possibilities of persistent epiphora. Further studies are needed to prove the mechanism of meibomian gland function disturbance in PANDO.

Vitamin D and eye: Current evidence and practice guidelines.

Vitamin D is a steroid hormone that has widespread role in human physiology, not only in the maintenance of calcium homeostasis but also in immunomodulation, cellular differentiation, and proliferation. The immunomodulatory effects of vitamin D are well known and are applicable to the ocular surface immune cells and structural cells. The role of vitamin D in ocular surface conditions such as dry eye disease (DED), keratoconus (KC), and post-surgical outcomes has received widespread and well-deserved attention. Vitamin D supplementation is shown to improve DED clinically as well as in experimental models. The anti-inflammatory properties may be crucial in the treatment of ocular surface conditions such as DED and KC. Vitamin D plays a multifaceted role in corneal wound healing with its anti-inflammatory and extracellular matrix remodeling properties. In this review, we discuss how to approach patients with DED and those undergoing refractive surgery with the available basic and clinical knowledge on the role of vitamin D in these conditions. We aim to highlight the importance of clinically harnessing vitamin D-mediated natural immuno-inflammatory modulation in combination with currently available standard of care strategies to reduce the morbidity and disease duration associated with ocular surface diseases.

Tear biomarkers in dry eye disease: Progress in the last decade.

Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to discomfort and visual compromise. DED is driven by chronic inflammation and its pathogenesis involves multiple ocular surface structures such as the cornea, conjunctiva, lacrimal glands, and meibomian glands. The tear film secretion and its composition are regulated by the ocular surface in orchestration with the environment and bodily cues. Thus, any dysregulation in ocular surface homeostasis causes an increase in tear break-up time (TBUT), osmolarity changes, and reduction in tear film volume, all of which are indicators of DED. Tear film abnormalities are perpetuated by underlying inflammatory signaling and secretion of inflammatory factors, leading to the recruitment of immune cells and clinical pathology. Tear-soluble factors such as cytokines and chemokines are the best surrogate markers of disease severity and can also drive the altered profile of ocular surface cells contributing to the disease. Soluble factors can thus help in disease classification and planning treatment strategies. Our analysis suggests increased levels of cytokines namely interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-9, IL-12, IL-17A, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α); chemokines (CCL2, CCL3, CCL4, CXCL8); MMP-9, FGF, VEGF-A; soluble receptors (sICAM-1, sTNFR1), neurotrophic factors (NGF, substance P, serotonin) and IL1RA and reduced levels of IL-7, IL-17F, CXCL1, CXCL10, EGF and lactoferrin in DED. Due to the non-invasive sample collection and ease of quantitively measuring soluble factors, tears are one of the best-studied biological samples to molecularly stratify DED patients and monitor their response to therapy. In this review, we evaluate and summarize the soluble factors profiles in DED patients from the studies conducted over the past decade and across various patient groups and etiologies. The use of biomarker testing in clinical settings will aid in the advancement of personalized medicine and represents the next step in managing DED.

Dry eye disease in head and neck cancer patients undergoing radiotherapy.

Purpose: To study the incidence of dry eye disease (DED) in head and neck cancer (HNC) patients undergoing external beam radiotherapy (EBRT), to find a correlation between tumor location and total radiation dose with DED, and to report various radiotherapy (RT) induced acute toxic effects on ocular and adnexal structures. Methods: A prospective cohort study was conducted at a tertiary eye-care center on 90 patients of HNC undergoing EBRT from March 2021 to May 2022. All underwent a thorough clinical history and complete ophthalmological examination including an ocular surface disease index (OSDI) questionnaire, visual acuity, anterior segment, angle and posterior segment examination, dry eye workup including the Schirmer test, tear meniscus height, tear break-up time, corneal fluorescein staining and grading, and meibography by auto-refractometer and its scoring at each visit. Patients were evaluated before the start of RT and then at 1 week, 4 weeks, and 12 weeks post-RT. Radiation records of all patients were noted. Data were analyzed using percentage and Microsoft Excel. Results: Of the 90 patients, 66 were male and 24 female (M: F ratio of 2.75) with a median age of 52.5 years (range 24 to 80 years). The most common HNC was the carcinoma oral cavity and lip. Most patients received a total radiation dose between 46 to 55 Gy. DED developed in 48 (53.3%) patients. The incidence of DED increased with the increase in total radiation dose (r = 0.987). DED was also found to be correlated with tumor location (r = 0.983). Conclusion: The incidence of DED positively correlated with the total radiation dose and tumor location.

Tear Cytokines Associated With Therapeutic Effects in Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: The local application of antiinflammatory and immunosuppressive agents is an effective method for the treatment of ocular graft-versus-host disease (oGVHD); however, we noticed that some patients with oGVHD did not respond to topical therapy as well as many others. This study aimed to determine whether tear cytokines were associated with therapeutic effects in oGVHD. METHODS: Forty patients with chronic oGVHD were enrolled and grouped as responders (n = 24) and nonresponders (n = 16) based on the clinical response to 1 month of topical treatment. Tear samples were collected from each participant before and after treatment, and the tear concentrations of 7 cytokines (IL-2, IL-6, IL-8, IL-10, IL-17A, TNF-α, and ICAM-1) were measured using microsphere-based immunoassay analysis. Differences between pretreatment and posttreatment tear samples were analyzed using the Wilcoxon test. RESULTS: No significant differences in ophthalmic symptoms or cytokine levels were observed between responders and nonresponders at baseline. After 1 month of topical treatment, ocular surface parameters (including Ocular Surface Disease Index, National Institutes of Health eye score, best-corrected visual acuity, corneal fluorescein staining score, and fluorescein tear film break-up time) were significantly ameliorated in responders, but not in nonresponders. Moreover, none of the cytokines exhibited significant alteration in nonresponders, whereas the tear levels of IL-6 (P = 0.031) and IL-8 (P = 0.037) exhibited significant decreases in responding patients. CONCLUSIONS: Our results revealed that tear IL-6 and IL-8 levels were significantly altered in response to topical oGVHD treatment.

The effect of sodium hyaluronate on tear film stability in patients with dry eye syndrome after cataract surgery.

BACKGROUND: This study aimed to observe the changes in the ocular surface after phacoemulsification in patients with age-related cataracts with respect to the addition of varying concentrations of hyaluronate. METHODS: Patients with dry eye syndrome were treated with 0.3% and 0.1% sodium hyaluronate eye drops to evaluate the clinical improvement in each treatment group. A total of 73 patients (91 eyes) with age-related cataracts suffering from dry eye syndrome after phacoemulsification were divided into treatment group A (30 eyes), undergoing conventional therapy and treatment with 0.3% sodium hyaluronate; treatment group B (31 eyes), undergoing conventional therapy and treatment with 0.1% sodium hyaluronate; and the control group (group C; 30 eyes), undergoing conventional therapy only. Two groups were given different concentrations of sodium hyaluronate eye drops four times a day (should be completed between 8 AM and 8 PM), one drop at a time. RESULTS: Seven days, 2 weeks, 1 month, and 2 months postoperatively, there were significant differences in the Schirmer I test (SIt), first noninvasive tear film break-up time (NIBUTf), average noninvasive tear film break-up time (NIBUTav), tear meniscus height (TMH), and irregularity (when the refractive force of different parts of different meridians on the same meridian is different. The main manifestation is that the two meridians on the anterior surface of the cornea do not show a 90-degree vertical distribution, which cannot be corrected by conventional astigmatism lenses) between the three groups (p < 0.05). When compared with group C, there were significant differences in the SIt, NIBUTf, NIBUTav, TMH, and irregularity of group A and group B (p < 0.05). When compared with group B, there were significant improvements in the SIt, NIBUTf, NIBUTav, and TMH in group A (p < 0.05). CONCLUSIONS: In the early stage after phacoemulsification, the stability of the tear film is reduced. Adding sodium hyaluronate eye drops can restore tear film structure and improve corneal surface regularity, and a 0.3% solution of sodium hyaluronate eye drops is more effective than a 0.1% solution.

Corneal subbasal nerve analysis in patients with primary Sjogren's syndrome: a novel objective grading method and clinical correlations.

PURPOSE: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. METHODS: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. RESULTS: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 µm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [ß = 0.284 (0.187-0.455)], MG score [ß = 0.185 (0.109-0.300)] and OSS [ß = 0.163 (0.020-0.345)], but decreased NIBUT [ß = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [ß = 0.418 (0.157-0.793)] and OSS [ß = 0.287 (0.027-0.547)], but decreased ST [ß = - 0.410 (-0.857 ~ - 0.138)]. CONCLUSIONS: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.

Tear film substance P in patients treated with neurotoxic chemotherapy.

Neurotoxic chemotherapy has been shown to be associated with reduced corneal nerves and ocular surface discomfort. Substance P is a neuropeptide expressed by sensory nerves including those in the densely innervated cornea. It is involved in both pain signaling and the regulation of epithelial and neural health. While its levels in tear fluids have been used as a neuropathic biomarker in diabetes, investigations of tear concentrations of substance P in chemotherapy-induced peripheral neuropathy have not been explored. The current cross-sectional study assessed substance P expression in tears of patients following neurotoxic chemotherapy treatment. Patients treated with paclitaxel (n = 35) or oxaliplatin (n = 30) 3-24 months prior to assessment were recruited along with healthy controls (n = 25). Flush tear collection, in-vivo corneal confocal microscopy and neurotoxicity assessments were also conducted. Enzyme-linked immunosorbent assays were used to measure substance P concentrations in collected tears, while total protein content (TPC) was measured with the bicinchoninic acid method (BCA). General linear models were used for statistical analysis. Substance P concentration was reduced in paclitaxel-treated patients [Median (Interquartile range, IQR): 1.11 (0.20-2.24) ng/ml)] compared to the oxaliplatin group [4.28 (1.01-10.73) ng/ml, p = 0.02]. Substance P expressed as a proportion of TPC was also lower in the paclitaxel group [0.00006 (0.00001-0.00010) %] compared to the oxaliplatin group [0.00018 (0.00008-0.00040) %, p = 0.005]. Substance P concentration and its percentage in TPC were also reduced in the paclitaxel group when compared to healthy controls [4.61 (1.35-18.51) ng/ml, p = 0.02; 0.00020 (0.00006-0.00060) %, p = 0.04, respectively]. Higher cumulative dose of paclitaxel was correlated with a reduction in substance P concentrations (r = -0.40, p = 0.037), however no associations were found with corneal nerve parameters or neuropathy severity (p > 0.05). While these findings show evidence for the dysregulation of tear film substance P following paclitaxel treatment, longitudinal studies should be conducted to investigate how substance P levels in tears change during treatment.

Assessment of tear inflammatory cytokines concentration in patients with diabetes with varying severity of involvement.

Diabetic retinopathy (DR), as one of the most important causes of blindness in Western societies, is a common micro-vasculopathy associated with diabetes. There is growing evidence of the role of inflammation in its development. This study was designed to measure cytokines in patients with diabetes with different stages of retinopathy .In this study, tear concentrations of three types of cytokines with different angiogenic properties including IL-1RA, IL-8, and TNF-α were measured in patients with diabetes without retinopathy, with non-proliferative retinopathy, with proliferative retinopathy, and in a healthy control group. The results showed that concentrations of TNF-α and IL-8 were higher in the tear sample of diabetics than in the control group and the concentrations of these cytokines were higher in patients with more advanced stages of diabetes, while the tear level of IL-1RA was significantly lower in diabetics. Based on these findings, it can be concluded that diabetes and its progression of severity affects the tear levels of IL-1RA, IL-8, and TNF-α inflammatory cytokines.

Choroidal thickness and granulocyte colony-stimulating factor in tears improve the prediction model for coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) detection in asymptomatic patients still remains controversial. The aim of our study was to evaluate the usefulness of ophthalmologic findings as predictors of the presence of CAD when added to cardiovascular classic risk factors (CRF) in patients with acute coronary cardiopathy suspicion. METHODS: After clinical stabilization, 96 patients with acute coronary cardiopathy suspicion were selected and divided in two groups: 69 patients with coronary lesions and 27 patients without coronary lesions. Their 192 eyes were subjected to a complete routine ophthalmologic examination. Samples of tear fluid were also collected to be used in the detection of cytokines and inflammatory mediators. Logistic regression models, receiver operating characteristic curves and their area under the curve (AUC) were analysed. RESULTS: Suggestive predictors were choroidal thickness (CT) (OR: 1.02, 95% CI 1.01-1.03) and tear granulocyte colony-stimulating factor (G-CSF) (OR: 0.97, 95% CI 0.95-0.99). We obtained an AUC of 0.9646 (95% CI 0.928-0.999) when CT and tear G-CSF were added as independent variables to the logistic regression model with cardiovascular CRF: sex, age, diabetes, high blood pressure, hypercholesterolemia, smoking habit and obesity. This AUC was significantly higher (p = 0.003) than the prediction derived from the same logistic regression model without CT and tear G-CSF (AUC = 0.828, 95% CI 0.729-0.927). CONCLUSIONS: CT and tear G-CSF improved the predictive model for CAD when added to cardiovascular CRF in our sample of symptomatic patients. Subsequent studies are needed for validation of these findings in asymptomatic patients.