Management of Dry Eye Disease for Intraocular Lens Power Calculation in Cataract Surgery: A Systematic Review.

Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the tear film is lost. As the prevalence of both diseases increases with age, there is a high prevalence of DED among patients who are candidates for cataract surgery. In recent years, cataract surgery has evolved from vision restoration surgery to refractive surgery. To achieve good surgical outcomes, it is necessary to minimize postoperative refractive error in intraocular lens (IOL) power calculation, which requires accurate preoperative keratometry measurements. A stable tear film is important for the accuracy and reproducibility of keratometry measurements, and DED may have a deleterious effect. In this study, original articles that focused primarily on findings related to this topic were evaluated. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Although appropriate DED diagnoses were not presented in the articles evaluated in this review, it was confirmed that the clinical signs of DED, particularly the shortening of the tear film break-up time (TBUT), negatively impact IOL power calculations. Improvement in these clinical signs might mitigate the negative effects on these calculations.

Dry Eye Disease Symptoms Among Glaucoma Patients at a Portuguese Hospital.

INTRODUCTION: Glaucoma-related dry eye disease (DED) is often underestimated, but it is an important comorbidity affecting 40% to 59% of glaucoma patients. It may be an exacerbation of a pre-existing condition or a novel disease starting after the initiation of topical medication. The cumulative effect of medication, preservatives and excipients leads to an alteration in tear film composition and ocular surface stability. The main purpose of this investigation was to study a group of Portuguese glaucoma patients regarding the presence of DED symptoms and correlate the severity of the symptoms with the usage of different types of glaucoma topical medications. MATERIALS AND METHODS: This is a cross-sectional observational study of patients diagnosed with primary and secondary open-angle glaucoma. The questionnaire Standardized Patient Evaluation of Eye Dryness (SPEED) translated to Portuguese (SPEED-Vp) was taken by patients followed in the Glaucoma Department of Unidade Local de Saúde Entre Douro e Vouga, Santa Maria da Feira, Portugal. Data was collected regarding their age, gender, type of topical medication in use as well as frequency and duration of usage. A statistical analysis was performed. RESULTS: A total of 75 patients answered the SPEED-Vp questionnaire. The mean age was 72 ± 7 years old. Fifty-two percent (n=39) were male, and 48% (n=36) were female patients. About 49.33% (n=37) had been on intraocular pressure (IOP)-lowering eyedrops for more than five years. About 61.43% (n=43) of patients used IOP-lowering eyedrops with preservatives. Most of the patients used prostaglandin analogs (75.71%, n=53) and beta-blockers (72.86%, n=51). SPEED score average was 2.75. About 25.33% (n=19) had no DED symptoms, 58.67% (n=44) had mild symptoms, 8% (n=6) had moderate symptoms and 8% (n=6) had severe symptoms. No statistically significant correlation was found between SPEED score and age, gender, number of eyedrop containers, number of active principles, application frequency, presence of preservatives, number of eyedrop containers with preservatives, duration of eyedrops usage or any of the medication groups. CONCLUSION: Although a high percentage of patients were on eyedrops with preservatives, this low rate of symptoms might be because patients tended to devalue these symptoms; were already on treatment with artificial tears; or have an underestimation of the sensation of dry eye due to decreased neuronal corneal nerve responses and density. These results were surprisingly positive. This might also be the result of the healthcare provider's sensibilization to this issue (early diagnosis, early prescription of artificial tears and change from preservative to preservative-free medication).

TRPV1 in Dry Eye Disease.

Dry eye disease (DED) is a prevalent ophthalmic ailment with intricate pathogenesis and that occurs primarily due to various factors which affect the ocular surface. DED is characterized by the disruption of tear film homeostasis, inflammatory reaction, and neuroparesthesia. Transient receptor potential vanilloid 1 (TRPV1) is a versatile receptor that can be stimulated by heat, acid, capsaicin (CAP), hyperosmolarity, and numerous inflammatory agents. There is accumulating evidence that implicates TRPV1 in the initiation and progression of DED through its detection of hypertonic conditions and modulation of inflammatory pathways. In this article, we present a comprehensive review of the expression and function of the TRPV1 channel in tissues and cells associated with DED. In addition, we outline the potential mechanisms that implicate TRPV1 in the pathophysiology of DED. The aim of this review is to establish a theoretical basis for TRPV1 as a possible therapeutic target in DED, thereby encouraging further investigations into its role in DED.

Assessment of the systemic immune-inflammation index in type 2 diabetic patients with and without dry eye disease: A case-control study.

Background: The inflammation plays a role in the pathophysiology of type-2 diabetes progression, and the mechanism remains unclear. The systemic immune-inflammation index (SII) is a novel inflammatory marker for type 2 diabetes patients and integrates multiple indicators in complete blood counts and routine blood tests. Aim: Since there is no international diagnostic standard for dry eye disease (DED), this study uses low-cost inflammatory blood biomarkers to investigate the correlation between SII and DM2-DED and determine the diagnosis indices of other biomarkers in DM2-DED. Methodology: A case-control retrospective analysis of totel patients n = 293 randomly selected and categorized into four groups: DED, DM2, DM2-DED, and healthy subjects. Demographic and blood biomarker variables were classified as categorical and continuous variables. The platelet-to-lymphocyte ratio (PLR), lymphocytes-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and SII were calculated platelet count multiply by NLR and analyzed for their correlation for all groups. Results: Focusing on DM2-DED patients was more common in females, 59.6%, than in males, 40.2%. The mean ages were 60.7 ± 11.85 years, a statistically significant difference with all groups. In the study group DM2-DED, there was an increase in all blood markers compared to all remaining groups except PLR. Only neutrophil, hemoglobin A1c (HbA1c), and fasting blood sugar levels were statistically significant differences in DM2-DED patients (p > 0.001, p < 0.001, and p < 0.001, respectively) compared to all groups. There was a positive correlation between HbA1c and PLR, HbA1c and NLR, and HbA1c and SII (r = 0.037, p = 0.705; r = 0.031, p = 0.754; and r = 0.066, p < 0.501, respectively) in the DM2-DED group. Conclusion: This study demonstrated that elevated SII values were linked to elevated HbA1c in DM2-DED patients. The potential of SII and HbA1c as early diagnostic indicators for ocular problems associated with diabetes mellitus is highlighted by their favorable connection in diagnosing DM2-DED.

Recent Advances in Nanotechnology for the Treatment of Dry Eye Disease.

Dry eye disease (DED) incidence is continuously growing, positioning it to become an emergent health issue over the next few years. Several topical treatments are commonly used to treat DED; however, reports indicate that only a minor proportion of drug bioavailability is achieved by the majority of eye drops available on the market. In this context, enhancing drug ability to overcome ocular barriers and prolonging its residence time on the ocular surface represent a new challenge in the field of ocular carrier systems. Therefore, research has focused on the development of multi-functional nanosystems, such as nanoemulsions, liposomes, dendrimers, hydrogels, and other nanosized carriers. These systems are designed to improve topical drug bioavailability and efficacy and, at the same time, require fewer daily administrations, with potentially reduced side effects. This review summarizes the different nanotechnologies developed, their role in DED, and the nanotechnology-based eyedrops currently approved for DED treatment.

Evaluation of the Use of Highly Concentrated Autologous Platelet-Rich Plasma and Platelet-Rich Fibrin Membrane to Improve the Outcome in the Management of Severe Dry Eye Disease, Corneal Neurotrophic Ulcer and Corneal Burn.

INTRODUCTION: The aim of this study was to evaluate the use of highly concentrated platelet-rich plasma (PRP) subconjunctival injections, in combination with eye drops (eye PRP, or E-PRP), in treating dry eye disease (DED) and the use of platelet-rich fibrin (PRF) membrane in treating corneal burns and neurotrophic ulcers for the restoration of the homeostasis of the tear film and the morphology and function of the cornea. METHODS: We studied 16 patients (n=32 eyes) with severe DED. The disease was graded as severe according to the Oxford Grading Scale. There were 12 males (75%) and four females (25%) with a mean age of 56 years; these patients were treated with monotherapy, which involved a single subconjunctival injection of 0.2-0.3 mL of PRP prepared from autologous blood, followed by application of autologous PRP eye drops four times a day for 15 days between September 2019 and December 2020 in the same geographic area. All patients gave written informed consent before undergoing the outlined treatment protocol. We evaluated best corrected visual acuity (BCVA), Schirmer test score, tear film breakup time (TBUT) and corneal staining with fluorescein (Oxford Grading Scale) before and after six to eight weeks of treatment. Subjective normalization was defined by a decrease in the Ocular Surface Disease Index (OSDI) score to 10 or less, an objective normalization of the TBUT to five to six seconds, improvement in the Schirmer test score and Oxford grading and the BCVA gain of at least one line in the vision chart (Snellen chart). Furthermore, we report on the results from different variants of platelet concentrate-based treatments in five cases of corneal diseases: neurotrophic ulcers and corneal burns due to different causes (e.g., chemical burns) using E-PRP and PRF membrane with regard to normalization of morphology and function. RESULTS: The OSDI score decreased to normalization in 75% of the patients (p=6.545 × 10-15). TBUT was restored significantly in 20 of 32 eyes from 2.78±0.55 to 5.43±0.71 (p=1.612 × 10-24). The Schirmer test score showed an improvement from 4.46±0.67 to 10.28±1.18 (p=3.411 × 10-29), and BCVA improved by 43.75%, from 0.15±0.19 to 0.09±0.16 (logMAR, p=0.2331). Oxford grading changed to Scale I in 75% and Scale 0 in 25% of the patients. No complications or adverse reactions occurred in the five cases of corneal injuries. We observed a restoration of the morphology and function of the cornea with PRP injections or PRF+PRP application in 7-12 days, depending on the severity of the initial finding. CONCLUSION:  PRP treatment is a new approach in ophthalmology with impressive results. Although patients show good compliance and acceptance of the treatment protocol, studies with larger sample sizes are needed to confirm and optimize its use.

Preventing and Managing Iatrogenic Dry Eye Disease during the Entire Surgical Pathway: A Study Focusing on Patients Undergoing Cataract Surgery.

Patient expectations for cataract surgery are continuously increasing, and dry eye disease (DED) represents a major cause of patient dissatisfaction in eye surgery. The present opinion paper aims to provide useful insights to improve the entire pathway of a patient undergoing cataract surgery, from the preoperative setting to the postoperative one. The available evidence from main clinical trials published on this topic is presented in association with experience-based points of view by the authors. Ocular surface disease (OSD) is common in patients presenting for cataract surgery, and more than half of these patients have DED and meibomian gland dysfunction (MGD), even in the absence of symptoms. Therefore, there is a need to encourage preoperative assessments for the risk of DED development or worsening in all patients as a routine approach to cataract surgery. New all-in-one diagnostic machines allow for fast and noninvasive screening of the ocular surface status. Once a preoperative diagnosis of DED/OSD is reached, ocular surface optimization should be obtained before surgery. In the case of unresolved OSD, the decision to delay surgery should be considered. The surgical procedure can be optimized by avoiding large incisions, limiting microscope light intensity and exposure, and avoiding an aspirating speculum or preserved eye drops. Postoperatively, the continued avoidance of preserved agents is advisable, as well as a limited exposure to epitheliotoxic antibiotics and nonsteroidal anti-inflammatory drugs. Short-term, preservative-free, soft corticosteroids may be useful for patients with extensive or persistent inflammation.

Characterizing the Robustness of Distinct Clinical Assessments in Identifying Dry Eye Condition of Animal Models.

PURPOSE: The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells. METHODS: Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination. RESULTS: Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED. CONCLUSION: The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.

Association of Systemic Markers of Inflammation with Signs and Symptoms of Dry Eye Disease and Sjogren's Syndrome in the Dry Eye Assessment and Management (DREAM©) Study.

PURPOSE: To evaluate the possible role of systemic inflammation in dry eye disease (DED) via systemic inflammatory marker associations with DED signs and symptoms, and an analysis of a subgroup with Sjogren's Syndrome (SS). METHODS: Participant serums were analyzed using line immunoassays (LIAs) for the presence of antibodies against 34 systemic inflammatory markers. Using the 2012 American College of Rheumatology definition, the 481 participants were categorized into group 1 (SS; n = 52), group 2 (autoimmune disease not including SS; n = 66), or group 3 (control, i.e. no autoimmune disease; n = 363). RESULTS: 3 markers were positive in ≥10% of participants: Ro52 (19.3%), Scl-70 (15.0%), CN-1A (14.2%). 2 markers were positively associated with symptoms: PM-Scl100 (p = 0.02), Sm (p = 0.009). 5 markers were positively associated with signs: U2SnRNP A', Ro52, La, DNA, Ro60. SS participants showed significantly higher positivity for 4 markers compared to participants with no autoimmune disease: PL-7 (p = 0.02), Ro52 (p < 0.0001), La (p < 0.0001), Ro60 (p < 0.0001). SS participants showed significantly higher positivity for 3 markers compared to participants with another autoimmune disease: Ro52 (p < 0.0001), La (p = 0.002), Ro60 (p < 0.0001). CONCLUSIONS: This study did not show evidence of significant systemic inflammation in participants with moderate-to-severe DED, based on the markers tested. PM-Scl100 and Sm may be associated with more severe DED symptoms. U2SnRNP A', Ro52, La, DNA, and Ro60 may be associated with more severe ocular surface disease. Ro52 and PL-7 may be diagnostic markers for SS. Future research evaluating these relationships and their clinical significance is needed.

Modified Danzhi Xiaoyao Powder (MDXP) improves the corneal damage in dry eye disease (DED) mice through phagocytosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao Powder (MDXP) is a traditional Chinese medicine formula remedy for treating Dry Eye Disease (DED). It showed the function of dispersing stagnated liver Qi for relieving Qi stagnation and clearing heat, which can be effective in treating conditions such as Dry Eye Disease (DED) and irregular menstruation due to liver depression and fire transformation. AIM OF THE STUDY: This study investigated the mechanism of the effect of MDXP in mice with DED. MATERIALS AND METHODS: A DED model was induced in mice using chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops administered in a dry box for 28 days. After modeling, the MDXP groups were given Chinese medicine with different dosages by gavage for 14 days. The following parameters were recorded in each group: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. Behavioral changes were evaluated by elevating cross-maze and open-field experiments. The levels of inflammatory factors serum tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), fcγR-mediated phagocytosis pathway cell division control protein 42 homolog (CDC42), actin-related protein 2/3 complex subunit 2 (ARPC2), and actin-related protein 3 (ACTR3) were measured by using Enzyme-linked immunoassay (ELISA), immunohistochemical staining, and real-time fluorescent qualitative polymerase chain reaction (RT-qPCR). RESULTS: MDXP increased body mass and lowered body temperature, prolonged tear film break-up time, promoted tear secretion, repaired corneal damage, decreased horizontal and vertical scores, elevated percentage of open arm times and boom opening time percentage, and reduced the expression levels of inflammatory factors of TNF-α, IL-1ß and pathway-related proteins CDC42, ARPC2, and ACTR3 in mice. MDXP also reduced the expression levels of inflammatory factors of TNF-α and IL-1ß in human corneal endothelial cells (HCECs), mouse mononuclear macrophage cells (RAW264.7), and human myeloid leukemia mononuclear cells (THP-1). CONCLUSIONS: MDXP can relieve tension and anxiety, inhibit apoptosis, reduce phagocytosis, reduce the expression of pro-inflammatory factors, repair corneal damage, and improve the symptoms in DED mice. The mechanism of action may be through the fcγR-mediated phagocytosis pathway.

Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy.

PURPOSE: Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear. METHODS: In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production. RESULTS: The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines. CONCLUSION: The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.

Dry eye disease caused by viral infection: Past, present and future.

Following viral infection, the innate immune system senses viral products, such as viral nucleic acids, to activate innate defence pathways, leading to inflammation and apoptosis, control of cell proliferation, and consequently, threat to the whole body. The ocular surface is exposed to the external environment and extremely vulnerable to viral infection. Several studies have revealed that viral infection can induce inflammation of the ocular surface and reduce tear secretion of the lacrimal gland (LG), consequently triggering ocular morphological and functional changes and resulting in dry eye disease (DED). Understanding the mechanisms of DED caused by viral infection and its potential therapeutic strategies are crucial for clinical interventional advances in DED. This review summarizes the roles of viral infection in the pathogenesis of DED, applicable diagnostic and therapeutic strategies, and potential regions of future studies.

Assessing the Effects of 0.3% Carboxymethylcellulose Tear Substitute Treatment on Symptoms and Signs of Dry Eye Disease in Elderly Population: A Prospective Longitudinal Study.

BACKGROUND: We aimed to evaluate the effects of 0.3% carboxymethylcellulose (CMC) tear substitute treatment in dry eye disease (DED), as well as treatment compliance and adverse events (AEs). METHODS: In this prospective, longitudinal study, a total of 30 eyes receiving 0.3% CMC tear substitute four times daily for DED were evaluated. Clinical endpoints included an ocular surface disease index (OSDI) questionnaire, average non-invasive tear film break-up time (A-NIBUT), lipid layer thickness (LLT), and a Schirmer test with anesthesia (ST). Treatment compliance and AEs were also assessed. All evaluations were performed at 2, 4, and 12 weeks of follow-up. RESULTS: At the end of the follow-up, significant improvement was observed in all clinical endpoints with the following mean values: ΔOSDI questionnaire of -22.53 ± 14.68 points, ΔA-NIBUT of 4.81 ± 2.88 s, ΔLLT of 5.63 ± 6.53 nm, and ΔST of 2.8 ± 2.1 mm (p < 0.001 for all comparisons). Although repeated measures analysis showed that all clinical endpoints presented statistically significant differences (p < 0.001 for all comparisons LLTBaseline-LLT2-weeks (p = 0.460) and LLT4-weeks-LLT12-weeks (p = 0.071) were the only pairs of measures that reported non-statistically significant differences). In addition, treatment compliance was 94.3 ± 5.2% and transient AEs related to the use of 0.3% CMC tear substitute were reported. CONCLUSIONS: 0.3% CMC tear substitute treatment seems to achieve beneficial effects on the OSDI questionnaire, A-NIBUT, LLT, and ST. However, further studies at this concentration are needed to confirm these results.

Treatment of Dry Eye Disease (DED) in Asia: Strategies for Short Tear Film Breakup Time-Type DED.

Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time-type DED, which has become a global problem in recent years, is common. While the mainstay of DED treatment in the West is the suppression of inflammation, the first goal of treatment is the stabilization of the tear film in Asia. To date, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side-effects (cataracts, increased intraocular pressure). This review evaluates the new generation therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on considerations, it is proposed that the optimal treatment for the short tear film breakup time-type DED is the initial application of mucin-secretion-enhancing eye drops (long-acting diquafosol) and oral supplements; and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

Allogeneic Serum Eye Drops: A Randomized Clinical Trial to Evaluate the Clinical Effectiveness of Two Drop Sizes.

INTRODUCTION: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs). METHODS: In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments. RESULTS: Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher. CONCLUSIONS: For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03539159).

Immunoglobulin A levels and its correlation with neutrophil-to-lymphocyte ratio as inflammatory biomarkers for dry eye disease in type 2 diabetes: a retrospective study.

Background: The neutrophil-to-lymphocyte ratio (NLR) and immunoglobulin A (IgA) level are commonly used as biomarkers for inflammation. Patients with type 2 diabetes (T2D) may experience an imbalance of tear film and inflammation, which can result in dry eye disease (DED). This study aimed to assess the levels of IgA and explore its correlation with the NLR as potential inflammatory biomarkers for dry eye disease in patients with T2D. Methods: A retrospective study was conducted at the cornea clinic and diabetes centre of King Abdulaziz Medical City (Jeddah, Saudi Arabia). The study included patients with DED and the number of available T2D-DED patients determined the sample size. Neutrophil, lymphocyte, IgA and CRP (C-reactive protein) laboratory values were obtained from medical records and correlational analyses were performed. Results: The study included 85 patients with an average age of 54 ± 14.4 years for the DED group (n=32) and 62 ± 13.9 years for the T2D-DED group (n=53). The age difference between the two groups was statistically significant (p 0.0001). The NLR values of the T2D-DED and DED groups were 3.203 ± 0.66 and 2.406 ± 0.46, respectively, with no significant difference (p<0.285). Similarly, there were no significant differences in neutrophil and lymphocyte values between the two groups. The IgA levels showed no significant variation between T2D-DED and DED groups (p<0.364). Spearman's correlation analysis in the DED group showed a significant negative correlation between IgA and lymphocyte (p=0.011; r= - 0.471) values and significant positive correlations between IgA and neutrophil (p=0.014; r=0.309) and NLR (p=0.052; r= - 0.283) values. In the T2D-DED group, a significant correlation was found between IgA and CRP values (p=0.032; r=0.33). Conclusion: Although diabetic patients may exhibit higher levels of NLR and IgA that correlate with disease severity, our study did not find significant differences in NLR and IgA values between the two groups. These findings may guide future research and enhance understanding of the disease's underlying mechanisms.

Evaluation of Therapeutic Capability of Emustil Drops against Tear Film Complications under Dry Environmental Conditions in Healthy Individuals.

Background and Objectives: Dry eye disease (DED) is a multifactorial ailment of the tears and ocular surface. The purpose of this study was to assess the tear film physiology under controlled dry environmental conditions and compare the efficacy of oil-in-water emulsion drops on tear film parameters in protection and relief treatment modalities under low-humidity conditions. Emustil eye drops were used after exposure to a low-humidity environment in the relief method, whereas, in the protection method, the drops were applied before exposure to low humidity. Materials and Methods: 12 normal male subjects (mean age 34.0 ± 7.0 years) were exposed to ultra-dry environmental conditions. A number of tear film measurements were carried out under desiccating environmental conditions in a controlled environment chamber (CEC), where the chamber temperature sat at 21 °C with a relative humidity (RH) of 5%. Keeler's TearScope Plus and an HIRCAL grid were used to assess the tear break-up time and lipid layer thickness (LLT), and the evaporation rate was evaluated using a Servomed EP3 Evaporimeter. Results: LLT measurements showed that the dry environment affected LLT significantly (p = 0.031). The median grade of LLT dropped from grade 3 (50-70 nm) at 40% RH to grade 2 (13-50 nm) at 5% RH. A significant increase in LLT was seen after both modes of treatment, with a median LLT grade of 3 when the Emustil was used for both protection (p = 0.004) and relief (p = 0.016). The mean tear evaporation rate in normal environmental conditions (40%) was 40.46 ± 11.80 g/m2/h (0.11 µL/min) and increased sharply to 83.77 ± 20.37 g/m2/h (0.25 µL/min) after exposure to the dry environment. A minimal decrease in tear film evaporation rate was seen in relief; however, statistical tests showed that the decrease in tear film evaporation rate was not significant. Mean NITBUT dropped from 13.6 s at 40% RH to 6.6 s at 5% RH (p = 0.002). All NITBUT measurements at 5% RH (with or without the instillation of Emustil) were significantly lower than those at 40%. The instillation of Emustil at 5% RH resulted in a significant improvement in NITBUT for protection (p = 0.016) but this was not the case for relief (p = 0.0.56). Conclusions: A control environmental chamber (CEC) enables the analysis of tear film parameters comparable to those found in dry eye patients. This enables us to examine the capability of oil in emulsion drops to manage tear film disruption in healthy individuals. This study suggests that using Emustil oil-in-water emulsion before exposure to a dry environment should be advocated for people who work in dry environments.

Binocular dynamic visual acuity in dry eye disease patients.

Purpose: To investigate binocular dynamic visual acuity (DVA) for patients with dry eye disease (DED). Methods: The prospective study included DED patients. The binocular DVA at 40 and 80 degrees per second (dps), Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear film break-up time first (TBUTF), corneal fluorescein staining (CFS), eyelid margin abnormalities and meibomian gland (MG) abnormalities morphology and function were evaluated. A deep learning model was applied to quantify the MG area proportion. The correlation between DVA and DED parameters was analyzed. Results: A total of 73 DED patients were enrolled. The age, OSDI, CFS, MG expressibility, secretion quality, and eyelid margin abnormalities were significantly positively correlated with the DVA for 40 and 80 dps (all P < 0.05). The MG area proportion in the upper eyelid was negatively correlated with DVA at 40 dps (R = -0.293, P < 0.001) and at 80 dps (R = -0.304, P < 0.001). Subgroup analysis by MG grade demonstrated that the DVA of patients with severe MG dropout (<25% of the total area) was significantly worse than other mild and moderate groups, both in 40 and 80 dps (all P < 0.05). The patients with CFS showed worse 40 (P < 0.001) and 80 dps (P < 0.001) DVA than the patients without CFS. Conclusion: Binocular DVA is significantly associated with DED symptoms and signs. The DED patients with CFS and severe MG dropout and dysfunction have worse DVA.

Tear film instability is associated with weakened colocalization between occludin and MUC5AC in scopolamine-induced dry eye disease (DED) rats.

PURPOSE: Dry eye disease (DED) is a disease with tear film instability because of multiple factors. This study was conducted to explore roles of occludin and MUC5AC in tear film instability in DED rat model. METHODS: A total of 20 SD rats were divided into DED group (n = 10) and normal control (NC) group (n = 10). DED rat model was established by subcutaneously injecting with scopolamine hydrobromide. Clinical examinations, including tear breakup time (tBUT), Schirmer's test and corneal fluorescein staining, were conducted to determine corneal functions. Transmission electron microscopy was used to measure the ultrastructures of corneal epithelial cells. Western blotting assay was used to identify occludin expression in corneal tissues of DED rats. Real-time PCR (RT-PCR) was performed to verify gene transcription of occludin and MUC5AC. Colocalization between occludin and MUC5AC was identified with confocal fluorescence microscopy. RESULTS: Tear breakup time was significantly shorter, and corneal fluorescein staining score was predominantly higher in DED rats compared to those in normal rats (P < 0.05). Normal rats showed a steady tear secretion throughout the whole experiments, while DED rats showed a dramatic reduction on day 14. DED rats demonstrated ultrastructural damage of Golgi apparatus and endoplasmic reticulum in corneal epithelial cells. Occludin and MUC5AC expressions were significantly downregulated in corneal tissue of DED rats compared with those of normal rats (P < 0.05). Percentage of occludin-MUC5AC-colocalized corneal epithelial cells in DED rats was significantly less compared with those in normal rats (P < 0.01). CONCLUSIONS: Tear film stability was damaged in scopolamine-induced DED rats because of the weakened colocalization between occludin and MUC5AC molecule. This study would provide a potential clue for the pathogenesis and a promising theoretical basis for clinical work of DED.

Understanding and Optimizing Ocular Biometry for Cataract Surgery in Dry Eye Disease: A Review.

PURPOSE: To understand the impact of dry eye disease (DED) on the components of ocular biometry and ways to optimize the visual outcomes of cataract surgery in eyes with DED. METHODOLOGY: A thorough literature review of the components pertaining to this review was undertaken using the databases, PubMed (from the year 2000), MEDLINE, CENTRAL (including Cochrane Eyes and Vision Trials Register; Cochrane Library: Issue 12 of 12 December 2019), metaRegister of Controlled Trials (mRCT) (www.controlled-trials. com), ClinicalTrials.gov (www.clinicaltrial.gov) and WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en). The keywords used for the search included "cataract surgery" or "phacoemulsification" combined with "dry eye", "dry eye disease","biometry", "keratometry". RESULTS: Publications considered for this review included meta-analysis, systematic reviews, case-control and cohort studies, case series, and laboratory-based studies. Published articles reporting tear film alteration in DED, its impact on the quality of vision and optical aberrations, the effect of topical medications on keratometry variations, and reports on optimizing the ocular surface before cataract surgery were included. CONCLUSIONS: DED is a common entity seen in patients presenting to routine cataract clinics and is known to impact the accuracy, reliability, and repeatability of ocular biometry and IOL power calculations in them. This review intends to emphasize the preoperative screening for the presence of DED, initiation of appropriate medical management for optimization of the ocular surface before cataract surgery, and recommendations for performing biometry. The algorithmic approach proposed will help the general ophthalmologists in routine practice to provide quality care and acceptable visual outcomes in patients with pre-existing DED.