Efficacy of 100% autologous platelet-rich plasma and 100% autologous serum in dry eye disease: a randomised controlled trial.

OBJECTIVE: The 0bjective is to compare treatment effects between undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) in patients with moderate-to-severe dry eye disease (DED). METHODS AND ANALYSIS: A single-centre, randomised, double-masked, non-inferiority clinical trial was conducted. 96 adult DED patients with an Ocular Surface Disease Index (OSDI) Score of ≥23 and/or Oxford staining grade of ≥2 were randomised to receive either 100% APRP (n=48) or 100% AS (n=48) for 4 weeks. Primary outcomes included OSDI Score and ocular surface staining measured by Oxford grading scale at 4 weeks. Secondary outcomes included fluorescein tear break-up time, Schirmer's test, meibum quality and expressibility, and adverse events. The 95% CI for the mean difference in OSDI scores between groups was estimated to assess non-inferiority of the OSDI score at a prespecified margin of 4.18 points. RESULTS: At week 4, there was no significant difference in decreased OSDI scores between groups, with the mean difference (100% APRP-100% AS) of 1.41 (95% CI -1.26, 4.08, p=0.299). The upper limit was less than the prespecified margin, indicating non-inferiority of 100% APRP vs 100% AS. The probabilities of achieving an Oxford grade 0-1 after treatment were not significantly different between groups, with an OR of 0.61 (95% CI 0.25, 1.52, p=0.288). No significant differences in secondary outcomes were observed between groups. CONCLUSION: In the short-term, 100% APRP was not inferior to 100% AS in reducing dry eye symptoms and ocular surface staining in moderate-to-severe DED. TRIAL REGISTRATION NUMBER: NCT04683796.

Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease.

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers' recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device.

Nutrition and diet for dry eye disease: Insights toward holistic management.

Dry eye disease (DED) is one of the most common eye problems in the aging population. Hyperosmolarity triggers the immune response in DED and consequently activates the self-perpetuating immune cycle, leading to chronic damage of the ocular surface. This event causes symptoms such as a burning sensation, irritation, redness, photophobia, and blurred vision in DED patients. Subsequently, the quality of life gets significantly affected. The rising demand for DED management and treatment solutions, and the desirable outcomes from innovative therapies that draw global interest provide evidence to demonstrate the role of diet and nutrition in DED. Nutritional deficiency and a Westernized diet contribute to the chronic systemic progression of DED symptoms. It has been revealed in several published studies that the use of nutrients and dietary supplements improves the ocular surface and acts as a protective factor against DED. - We reviewed nutrition and dietary aspects in managing DED and its associated consequences, based on published studies, and reached an evidence-based conclusion.

Unveiling senescence-associated ocular pathogenesis via lacrimal gland organoid magnetic bioassembly platform and HMGB1-Box A gene therapy.

Dry eye disease (DED) is a multifactorial aging disorder leading to tear film insufficiency and instability. Yet, an important knowledge gap lingers in understanding senescence-associated ocular pathogenesis, due to limited in vitro translational lacrimal gland (LG) models. Consequently, this remains a major roadblock to discover effective therapies for the restoration of tear film secretion. Herein, the authors reported the magnetic bioassembly of two LG organoid platforms to recapitulate functional and aging states. Using a proof-of-concept approach, porcine primary LG cells were assembled into organoids via a magnetic 3D bioprinting (M3DB) platform. This platform could form reproducible LG organoids with epithelial hallmarks (AQP5+) and exhibit epithelial secretory functions (lysozyme activity). DNA damage-induced senescence and cell death was induced with etoposide, and LG organoid hypofunction and senescence-associated pathogenesis were observed. To confer DNA protection against aging, a novel gene therapy with Box A domain of high-mobility group box-1 (HMGB1-Box A) previously established by our group, was applied here to prevent LG cellular senescence for the first time. HMGB1-Box A transfection prevented LG organoids from senescence-associated pathogenesis at the transcriptomic, metabolomic and proteomic levels. Thus, M3DB platforms could generate functional and DNA damage-induced senescence LG organoids, and this latter damage could be prevented with HMGB1-Box A gene therapy.

Epidemiology and Risk Factors of Dry Eye Disease: Considerations for Clinical Management.

Dry eye disease is a multifactorial condition characterised by tear film instability, hyperosmolarity and ocular surface inflammation. Understanding the epidemiology of dry eye disease and recognising both modifiable and non-modifiable risk factors can assist eye care practitioners in assessing, treating, and managing patients with the condition. This review considers current knowledge surrounding its incidence and prevalence, as well as associated demographic, systemic, ocular, and iatrogenic, and lifestyle-related modifiable risk factors. Population-based prevalence estimates vary according to the diagnostic criteria used to define dry eye disease, as well as severity and demographic characteristics of the population. Considering recent data and variable population demographics, conservative prevalence estimates suggest that 10-20% of the population over 40 years of age report moderate to severe symptoms and/or seek treatment for dry eye disease. Individuals with specific non-modifiable demographic risk factors may be at increased risk of developing dry eye disease. Advanced age, female sex and East Asian ethnicity have been identified as key non-modifiable demographic features predisposing individuals to dry eye disease. Systemic conditions that have been associated with an increased risk of dry eye disease include migraine, Sjögren syndrome, connective tissue disorders, mental health disorders, diabetes mellitus and androgen deficiency. Medications that may contribute to this risk include antidepressants, antihistamines, and hormone replacement therapy. Ocular and iatrogenic risk factors of dry eye disease include blepharitis, Demodex infestation, ocular surgery, blink completeness, contact lens wear, and topical ophthalmic medications. A range of modifiable lifestyle factors that can increase the risk of dry eye disease have also been identified, including low humidity environments, digital screen use, quality of sleep, diet, and eye cosmetic wear. Dry eye is a common disease affecting millions globally. Increasing knowledge regarding its associated risk factors can better prepare the eye care practitioner to successfully manage patients with this ocular surface disease.

Complications and compliance in professionally-managed and self-managed contact lenses compared with non-contact lens wearers.

PURPOSE: To test the impact of professional management of soft contact lens wear on symptoms and ocular complications. METHODS: Subjective symptoms and ocular complications of soft CL users who did not seek professional follow-up care (self-managed, SM), were compared to users who were prescribed CLs and their care professionally managed in optometry practices (PM), and to a control group of non-CL wearers. Habitual visual acuity, subjective dry-eye symptoms, and corneal abnormalities were assessed in all participants. CL wearers filled-out a usage habits questionnaire, and their CL fit was assessed. Outcomes were compared using Kruskal-Wallis and Chi Squared tests. RESULTS: The SM, PM, and non-CL wearers cohorts included 127 (mean age:24.3±5.1, median:23, range:16-45 years,104 female), 132 (mean age:25.5±6.2, median:23, range:18-43 years,103 female), and 56 (mean age:22.3±3.5, median:21, range:18-39 years,36 female) participants, respectively. Meibomian gland dysfunction grade (p = 0.004, p<0.0001), limbal redness (both p = 0.04), corneal neovascularization (both p = 0.003), and papillary conjunctivitis (p<0.0001,p = 0.005) were significantly worse in SM CL wearers compared with both the non-CL wearers and PM CL wearers, respectively. Conjunctival staining was significantly worse in the SM cohort compared with the PM cohort (p = 0.01). 38.6% of the SM compared with 22.8% of the PM CL wearers, had an inappropriate refractive correction (p = 0.006). SM CL wearers wore CLs significantly more years (mean and median 1 year,p = 0.008), for more daily hours (mean and median of 2 hours,p<0.00001), and tended to nap or sleep with their CLs compared with the PM CL wearers (47 vs. 29,p = 0.02). The cohorts did not differ in their subjective symptoms. CONCLUSIONS: Complications are significantly more prevalent in SM CL wearers compared with PM CL wearers, and SM CL wearers tend to wear CLs with incorrect powers, and are less compliant with napping or sleeping with the CLs compared with PM CL wearers. These findings emphasize the importance of fitting, patient education and follow-ups in CL wearers.

Efficacy and safety of the disposable eyelid warming masks in the treatment of dry eye disease due to Meibomian gland dysfunction.

BACKGROUND: Warm compresses are the routine treatment for Meibomian gland dysfunction (MGD) in daily life, but in order to achieve satisfactory efficacy, the treatment needs to be sustained over a long time, which can have an impact on the patient compliance. A more convenient warm compresses will help improve the patient compliance. Therefore, the purpose of the study is to investigate the efficacy and safety of the disposable eyelid warming masks for treatment of dry eye disease (DED) due to MGD. METHODS: This was a randomized, controlled, non-masked, two-center clinical trial. One hundred and forty-four patients were treated by the masks or the hot towel twice daily for 12 weeks. Patients were evaluated at baseline, 4-week and 12-week visits for subjective symptoms, objective signs and safety assessments, including ocular symptom scores, ocular surface disease index (OSDI), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), meibum quality, meibum expressibility, and adverse events (AEs). RESULTS: A totle of 134 patients were followed in the study. The mean age of the masks group (14 males and 52 females) and the hot towel group (20 males and 48 females) was 43.7 ± 13.5 years and 39.5 ± 13.9 years, respectively. At 4-week visit, there were significant statistical differences in ocular symptom scores, OSDI and CFS between two groups (P < 0.05). Except for SIT, the treatment group showed a greater improvement in subjective symptoms and objective signs than the control group at 12-week visit. (P < 0.05). In addition, 40 AEs occurred in 27 patients (37.5%) in the treatment group, and 34 AEs occurred in 21 patients (29.17%) in the control group. No serious AEs were reported. CONCLUSIONS: The masks had a good efficacy and safety in the treatment of DED due to MGD, and might offer an attractive treatment option for some patients. TRIAL REGISTRATION: The study was registered at Chinese Clinical Trial Registry (ChiCTR1900025443) on August 26, 2019.

Ocular surface disorders: office procedures for the allergist/clinical immunologist.

PURPOSE OF REVIEW: Ocular surface disorders (OSDs) are a prevalent and often debilitating condition encountered in clinical practice, particularly by allergists and clinical immunologists. RECENT FINDINGS: A comprehensive guide to office procedures for evaluating and managing OSDs, with a specific focus on ocular allergies, would assist in the evaluation process that begins with an initial patient assessment utilizing standardized forms to systematically gather detailed medical history, symptomatology, and environmental exposure data. This structured approach ensures a thorough understanding of the patient's condition and facilitates targeted interventions. In addition to allergy testing, the assessment of the tear film is essential for a comprehensive evaluation of OSDs. The Schirmer test is employed to quantify tear production, providing objective data on tear film adequacy and guiding interventions for tear film deficiencies. SUMMARY: This multifaceted diagnostic approach ensures that all contributing factors to OSDs are identified and appropriately managed. By integrating these office procedures, allergists and clinical immunologists can enhance their diagnostic accuracy and therapeutic efficacy, ultimately improving patient outcomes. This manuscript provides a practical resource, outlining some of the methodologies and clinical applications of each procedure, and highlighting their role in the holistic management of OSDs in allergic patients.

Integrative therapeutics for ocular surface disorders.

PURPOSE OF REVIEW: Integrative medicine techniques are increasingly accepted into the treatment paradigm for many chronic disorders including eye disease. Over 71% of patients, including 67% of those with eye disorders, use some form of Integrative therapy. Physicians should be well versed in evidence-based therapies to know how to refer patients for the best complimentary care. We highlight the most effective integrative therapeutics from different complementary treatment paradigms to offer a framework for approaching therapy in patients with ocular surface disorders (OSDs). RECENT FINDINGS: Lifestyle and behavioral modifications help a proportion of people with OSDs like dry eye disease and allergic conjunctivitis, which are interrelated disorders. Nutrition and supplementation can also play a role in addressing underlying inflammation and improving OSD symptoms. Acupuncture and traditional herbal medicine may also benefit some patients. New technologies offer innovative treatment pathways in the treatment of OSD but require referral to Ocular Surface Treatment Centers. SUMMARY: Integrative treatment approach for OSD incorporates allopathic medicine, traditional remedies and lifestyle behavioral interventions, Ayurveda and herbal medicine, Nutritional Supplements, Homeopathy, Acupuncture and Chinese Medicine. New cutting-edge technologies offer breakthroughs in difficult to treat ocular surface cases. Collaboration between allergy or otolaryngology offices, complementary practitioners, as well as optometrists and ophthalmologists in Ocular Surface Treatment Centers can offer patients new avenues of treatment.

Allogeneic serum-based eye drops may give better results than autologous drops in Sjögren's syndrome dry eye.

PURPOSE: Sjögren's syndrome (SS) may cause severe dry eye symptoms. One of the therapeutic option known for almost 40 years are autologous serum eye drops (ASEDs). Due to the presence of many pro-inflammatory factors in the autologous serum of SS patients, the use of allogeneic serum is often considered a better option. In our facility almost one-fifth of the patients using allogeneic serum-based eye drops (alloSEDs) suffered from autoimmune diseases, including SS. The study aim was to compare the effectiveness of both ASEDs and alloSEDs in SS patients. METHODS: From the group of SS patients using alloSEDs, five female SS patients aged 39-73 years were selected. They had the longest history of the use of the product. The analysis was based on OSDI forms and internal questionnaires which compared the effects of ASEDs and alloSEDs application. The patients used alloSEDs for a period of 5-28 months. All had previously used ASEDs for at least 2 years. RESULTS: For all five patients the mean OSDI after application of ASEDs and before introducing alloSEDs was 68.71, while the mean OSDI after the use of alloSEDs was 30.49. CONCLUSION: In SS the treatment results are better with alloSEDs than with ASEDs. Almost all SS patients who applied both autologous and allogeneic drops reported better effects with the latter as also confirmed by the study cases.

Effects of common eye diseases in children and their treatment measures on ocular surface homeostasis: A review.

Ocular surface homeostasis plays a vital role in maintaining of eye health. Dry eye disease is one of the prominent and typical manifestations of disruption of ocular surface homeostasis that leads to the worsening of ocular surface homeostasis that leads to the worsening of ocular surface disease when it interacts with other pathogenic factors. However, disruption in ocular surface homeostasis in children is often overlooked because of the current methods of assessing ocular surface homeostasis. This review summarizes the main factors affecting ocular surface homeostasis in children, with the aim of drawing the attention of clinicians to the disruption of ocular surface homeostasis in children when dealing with such diseases. Ocular surface homeostasis involves several interrelated components, each of which plays a nonnegligible role in ocular surface homeostasis. Unlike adults, children have a stronger lacrimal gland secretion capacity and milder symptoms when there is a slight disruption of the ocular surface homeostasis. In addition, children's expressive abilities were weaker. Therefore, dry eye in children is often ignored by doctors and parents, and clinicians should pay more attention to the protection of ocular surface homeostasis when treating children with these diseases. Therefore, there is a need for diagnostic criteria for dry eye disease specific to children.

SPARC overexpression in allogeneic adipose-derived mesenchymal stem cells in dog dry eye model induced by benzalkonium chloride.

BACKGROUND: Nowadays, companion and working dogs hold significant social and economic importance. Dry eye, also known as dry keratoconjunctivitis (KCS), a common disease in ophthalmology, can readily impact a dog's working capacity and lead to economic losses. Although there are several medications available for this disease, all of them only improve the symptoms on the surface of the eye, and they are irritating and not easy to use for long periods of time. Adipose-derived mesenchymal stem cells (ADMSC) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of ADMSC. Here, we aimed to use ADMSC overexpressing Secreted Protein Acidic and Rich in Cysteine (SPARC) to treat 0.25% benzalkonium chloride-treated dogs with dry eye to verify its efficacy. For in vitro validation, we induced corneal epithelial cell (HCECs) damage using 1 µg/mL benzalkonium chloride. METHODS: Fifteen male crossbred dogs were randomly divided into five groups: normal, dry eye self-healing control, cyclosporine-treated, ADMSC-CMV-treated and ADMSC-OESPARC-treated. HCECs were divided into four groups: normal control group, untreated model group, ADMSC-CMV supernatant culture group and ADMSC-OESRARC supernatant culture group. RESULTS: SPARC-modified ADMSC had the most significant effect on canine ocular surface inflammation, corneal injury, and tear recovery, and the addition of ADMSC-OESPARC cell supernatant also had a salvage effect on HCECs cellular damage, such as cell viability and cell proliferation ability. Moreover, analysis of the co-transcriptome sequencing data showed that SPARC could promote corneal epithelial cell repair by enhancing the in vitro viability, migration and proliferation and immunosuppression of ADMSC. CONCLUSION: The in vitro cell test and in vivo model totally suggest that the combination of SPARC and ADMSC has a promising future in novel dry eye therapy.

Bridging the gap in managing dry eye disease: a consensus report by the Taiwan society of cataract and refractive surgeons.

BACKGROUND: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. METHODS: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. RESULTS: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. CONCLUSION: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively.

Efficiency of Combining Heated Eye Mask with Intense Pulsed Light Therapy as a Treatment Option for Evaporative Dry Eye Disease.

Background and objectives: The study aimed to establish the efficiency of combining the Posiforlid heated eye mask with intense pulsed light therapy (IPL), as a treatment strategy for evaporative dry eye disease. Materials and methods: This study included 110 patients, respectively 220 eyes, diagnosed with evaporative dry eye disease, patients between 18 and 86 years old, divided into two study groups. The first one, the control group, consisted of 73 patients treated with IPL therapy, and the second of 37 patients, who underwent IPL therapy associated with Posiforlid heated eye mask. Subjective evolution was assessed using an eye fitness test (EFT) regarding symptomatology. Objective assessment of the ocular surface was performed by tear film stability evaluation (TFSE), non-invasive first break-up time (NIFBUT), non-invasive average breakup time (NIABUT), ocular surface inflammatory evaluation (OSIE), measuring of the central tear meniscus height (CTMH) and thinnest tear meniscus height (TTMH). The assessment was performed at the beginning of the IPL treatment, during the IPL sessions, at the end of the IPL treatment, and afterward, at 3, 6, and 12 months. Results: Tear film stability has increased in both study cases, but no statistically significant difference was observed between the two groups studied. For the control group, tear film stability evaluation (TFSE) started from 310.56 ± 389.54 at baseline (time 1 presentation) to 114.40 ± 122.90 after 12 months, and for the heated mask group, from 391.11 ± 456.45 (time 1 presentation) to 97.38 ± 105.98 after 12 months. NIABUT increased from 10.72 ± 4.90 seconds to 14.79 ± 3.72 seconds in the control group, and from 11.11 ± 5.08 seconds to 15.84 ± 2.26 seconds in the second group. OSIE decreased, as expected, from 7.18 ± 7.93 percent in the control group to 2.24 ± 2.38 percent after 12 months and from 7.42 ± 7.77 percent to 2.47 ± 2.50 percent in the Posiforlid group. Although significantly lower, there was no significant difference between the two studied groups. No statistically significant changes were registered in the studied quantitative parameters. Using the EFT test, great improvements were registered regarding symptomatology, with a score increasing from 29.99 ± 8.60 to 39.10 ± 5.08 in the control group and from 27.35 ± 9.24 to 38.35 ± 4.62 in the other group. Again, the same statistical result was registered on this variable. Conclusions: The improvement of tear film stability, ocular surface inflammatory condition, and subjective symptoms during IPL therapy sessions and the first year of observation after the completion of the treatment was not necessarily increased by the additional use of a heated eye mask. Abbreviations: IPL = intense pulsed light therapy, EFT = eye fitness test, NIFBUT = non-invasive first break-up time, NIABUT = non-invasive average break-up time, OSIE = ocular surface inflammatory evaluation, TFSE = tear film stability evaluation, CTMH = central tear meniscus height, TTMH = thinnest tear meniscus height, DED = dry eye disease, MGD = meibomian gland dysfunction, SD = standard deviation.

Light Therapy for Facial Rejuvenation and Dry Eyes, Blepharitis, and Styes.

Intense pulsed light has a growing body of research supporting its use in skin rejuvenation, dermatologic conditions, as well as ocular rosacea, dry eyes and meibomian gland dysfunction. This paper will start with the conception of one protocol for treating dry eyes, blepharitis and styes using broad band light, a version of intense pulsed light, and its evolution into a life-changing in-office procedure for many patients. The approach for optimizing the settings, considerations during the consultation, the procedure in detail, after treatment care, and potential complications to avoid are all explained. Periocular and facial rejuvenation treatment protocols are discussed as well. This should be a useful guide for clinicians looking to add intense pulsed light to their in-office treatment armamentarium to significantly improve the lives of their patients.

Sutureless Dehydrated Amniotic Membrane (Omnigen) Application Using a Specialised Bandage Contact Lens (OmniLenz) for the Treatment of Dry Eye Disease: A 6-Month Randomised Control Trial.

Background and Objectives: Dry Eye Disease (DED) is a chronic condition characterised by tear film instability and ocular surface disruption, significantly impacting patients' quality of life. This study aimed to provide top-level clinical evidence for the long-term efficacy of dehydrated amniotic membrane (dAM, Omnigen®) delivered via a specialised bandage contact lens (sBCL, OmniLenz) for managing moderate-to-severe DED. Materials and Methods: This randomised controlled trial (NCT04553432) involved 93 participants with moderate-to-severe DED, randomised to receive a 1-week bilateral treatment of either dAM (17 mm diameter with 6 mm central 'window') applied under a sBCL or sBCL alone. Participants were assessed at baseline and followed up at 1, 3, and 6 months post-treatment. Outcomes included changes in symptomatology, tear film and ocular surface measurements, and in vivo confocal microscopy imaging of corneal nerve parameters and corneal dendritic cell (CDC) counts. Results: The dAM-sBCL group demonstrated a 65% reduction in OSDI scores at 6 months (p < 0.001), with 88% of participants showing improvement at 1 month. Corneal staining was significantly reduced in both groups. dAM-sBCL provided significant improvements in corneal nerve parameters at 1 month, with sustained positive trends at 3 months. Additionally, dAM-sBCL significantly reduced mature CDC counts, suggesting an anti-inflammatory effect. Conclusions: Treatment with dAM-sBCL for just 1 week significantly and rapidly improved dry eye symptoms as well as ocular surface signs for at least 3 months. It also enhanced corneal nerve health while reducing activated/mature corneal inflammatory cell numbers, presenting a safe and promising new treatment for moderate-to-severe DED.

Application of a practical amniotic membrane ring made on-site for restoration of ocular surface health in dry eye disease.

PURPOSE: Dry eye disease (DED) is one of the most common ocular surface disorders worldwide. Despite different underlying pathogenic processes, DED is characterized by ocular surface inflammation, which in turn induces further damage to the corneal epithelium and its underlying structures. Amniotic membrane transplants are known to have potent anti-inflammatory effects and also have the ability to enhance epithelial healing. In this study, we aimed to evaluate the clinical efficacy of amniotic membrane ring (AMR) application in treating refractory dry eye disease. METHODS: A retrospective analysis of 22 patients treated with contact lens-like amniotic membrane rings was performed. This amniotic membrane ring was formed using an aspiration catheter covered by a large piece of amniotic membrane graft. The amniotic membrane was sutured to the catheter using eight sutures. In this way, a customized amniotic membrane ring was prepared for each patient. Patients' demographics, symptoms, use of medications, conjunctival inflammation, corneal staining, and visual acuity were compared before and after treatment. In addition, the amniotic membrane retention duration, the amniotic membrane's effect on ocular surface healing, follow-up time, and complications were evaluated. RESULTS: Twenty-eight eyes of 22 patients (18 females and 4 males) aged 53.32±13.36 (6-73) years were included. The AMR retention duration ranged from 5 to 16 days, with a mean of 11±3.09 days, at which time the amniotic membrane had dissolved or been removed inadvertently by the patient. Discomfort with the ring was seen in 1 of 28 eyes (3.6%). The patients reported symptomatic relief for a period of 3.64±1.25 months. Symptomatic relief was accompanied by a reduction of OSDI scores (from 63.39±17.24 to 33.19±12.45) (P<0.001), use of topical medications (from 4.21±1.03 to 2.42±0.50) (P<0.001), conjunctival hyperemia (from 1.57±1.19 to 0.35±0.48) (P<0.001), corneal staining (from 2.89±1.16 to 0.57±0.74) (P<0.001), and improvement in visual acuity (from 0.23±0.16 to 0.16±0.25 logMAR) (P=0.001). CONCLUSIONS: Amniotic membrane ring treatment might be used to treat refractory dry eye disease. This technique has an economic advantage over other commercially available amniotic bandage tissues and can be easily removed and replaced during a follow-up examination.

Membrane Fusion-Mediated Loading of Therapeutic siRNA into Exosome for Tissue-Specific Application.

Tissue-specific delivery of oligonucleotide therapeutics beyond the liver remains a key challenge in nucleic acid drug development. To address this issue, exploiting exosomes as a novel carrier has emerged as a promising approach for efficient nucleic acid drug delivery. However, current exosome-based delivery systems still face multiple hurdles in their clinical applications. Herein, this work presents a strategy for constructing a hybrid exosome vehicle (HEV) through a DNA zipper-mediated membrane fusion approach for tissue-specific siRNA delivery. As a proof-of-concept, this work successfully fuses a liposome encapsulating anti-NFKBIZ siRNAs with corneal epithelium cell (CEC)-derived exosomes to form a HEV construct for the treatment of dry eye disease (DED). With homing characteristics inherited from exosomes, the siRNA-bearing HEV can target its parent cells and efficiently deliver the siRNA payloads to the cornea. Subsequently, the NFKBIZ gene silencing significantly reduces pro-inflammatory cytokine secretions from the ocular surface, reshapes its inflammatory microenvironment, and ultimately achieves an excellent therapeutic outcome in a DED mouse model. As a versatile platform, this hybrid exosome with targeting capability and designed therapeutic siRNAs may hold great potential in various disease treatments.

Effect of Acupuncture on Tear Proteomics in Patients with Video Display Terminal-Related Dry Eye.

Acupuncture is widely used to treat dry eye disease (DED), but its effect has not been reported in treating video display terminal (VDT)-related dry eye, and the mechanism of acupuncture on VDT-related dry eye is also unknown. In our study, the tear proteome was compared with identifying possible mechanisms and biomarkers for predicting acupuncture effectiveness in VDT-related dry eye. The results showed that the ocular surface disease index scores were significantly different between the acupuncture group (AC group) and artificial tears group (AT group) at the end of the study, whereas tear film breakup time (TFBUT) and Schirmer I test (SIT) were not significantly different between the groups. Proteome changes pre- and post-treatment in the AC group were associated with B cell-related immune processes, inflammation, glycolysis, and actin cytoskeleton. Furthermore, the proteins hexosaminidase A and mannose-binding lectin 1 could prospectively predict whether acupuncture treatment was effective. Therefore, we believe that acupuncture can provide greater improvement in the clinical symptoms of VDT-related dry eye than artificial tears. The mechanism of acupuncture in VDT-related dry eye treatment may be associated with glycolysis- and actin cytoskeleton remodeling-mediated inflammatory and immune processes. Additionally, hexosaminidase A and mannose-binding lectin 1 are biomarkers for predicting the efficacy of acupuncture for VDT-related dry eye.

Electroacupuncture modulates the TLR4-NF-κB inflammatory signaling pathway to attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats.

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.