The Effect of Interlayer Delay on the Heat Accumulation, Microstructures, and Properties in Laser Hot Wire Directed Energy Deposition of Ti-6Al-4V Single-Wall.

Laser hot wire directed energy deposition (LHW-DED) is a layer-by-layer additive manufacturing technique that permits the fabrication of large-scale Ti-6Al-4V (Ti64) components with a high deposition rate and has gained traction in the aerospace sector in recent years. However, one of the major challenges in LHW-DED Ti64 is heat accumulation, which affects the part quality, microstructure, and properties of as-built specimens. These issues require a comprehensive understanding of the layerwise heat-accumulation-driven process-structure-property relationship in as-deposited samples. In this study, a systematic investigation was performed by fabricating three Ti-6Al-4V single-wall specimens with distinct interlayer delays, i.e., 0, 120, and 300 s. The real-time acquisition of high-fidelity thermal data and high-resolution melt pool images were utilized to demonstrate a direct correlation between layerwise heat accumulation and melt pool dimensions. The results revealed that the maximum heat buildup temperature of the topmost layer decreased from 660 °C to 263 °C with an increase to a 300 s interlayer delay, allowing for better control of the melt pool dimensions, which then resulted in improved part accuracy. Furthermore, the investigation of the location-specific composition, microstructure, and mechanical properties demonstrated that heat buildup resulted in the coarsening of microstructures and, consequently, the reduction of micro-hardness with increasing height. Extending the delay by 120 s resulted in a 5% improvement in the mechanical properties, including an increase in the yield strength from 817 MPa to 859 MPa and the ultimate tensile strength from 914 MPa to 959 MPa. Cooling rates estimated at 900 °C using a one-dimensional thermal model based on a numerical method allowed us to establish the process-structure-property relationship for the wall specimens. The study provides deeper insight into the effect of heat buildup in LHW-DED and serves as a guide for tailoring the properties of as-deposited specimens by regulating interlayer delay.

Targeting type I DED interactions at the DED filament serves as a sensitive switch for cell fate decisions.

Activation of procaspase-8 in the death effector domain (DED) filaments of the death-inducing signaling complex (DISC) is a key step in apoptosis. In this study, a rationally designed cell-penetrating peptide, DEDid, was engineered to mimic the h2b helical region of procaspase-8-DED2 containing a highly conservative FL motif. Furthermore, mutations were introduced into the DEDid binding site of the procaspase-8 type I interface. Additionally, our data suggest that DEDid targets other type I DED interactions such as those of FADD. Both approaches of blocking type I DED interactions inhibited CD95L-induced DISC assembly, caspase activation and apoptosis. We showed that inhibition of procaspase-8 type I interactions by mutations not only diminished procaspase-8 recruitment to the DISC but also destabilized the FADD core of DED filaments. Taken together, this study offers insights to develop strategies to target DED proteins, which may be considered in diseases associated with cell death and inflammation.

The RNA Helicase Ded1 from Yeast Is Associated with the Signal Recognition Particle and Is Regulated by SRP21.

The DEAD-box RNA helicase Ded1 is an essential yeast protein involved in translation initiation that belongs to the DDX3 subfamily. The purified Ded1 protein is an ATP-dependent RNA-binding protein and an RNA-dependent ATPase, but it was previously found to lack substrate specificity and enzymatic regulation. Here we demonstrate through yeast genetics, yeast extract pull-down experiments, in situ localization, and in vitro biochemical approaches that Ded1 is associated with, and regulated by, the signal recognition particle (SRP), which is a universally conserved ribonucleoprotein complex required for the co-translational translocation of polypeptides into the endoplasmic reticulum lumen and membrane. Ded1 is physically associated with SRP components in vivo and in vitro. Ded1 is genetically linked with SRP proteins. Finally, the enzymatic activity of Ded1 is inhibited by SRP21 in the presence of SCR1 RNA. We propose a model where Ded1 actively participates in the translocation of proteins during translation. Our results provide a new understanding of the role of Ded1 during translation.

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.

3D Nanocrystallography and the Imperfect Molecular Lattice.

Crystallographic analysis relies on the scattering of quanta from arrays of atoms that populate a repeating lattice. While large crystals built of lattices that appear ideal are sought after by crystallographers, imperfections are the norm for molecular crystals. Additionally, advanced X-ray and electron diffraction techniques, used for crystallography, have opened the possibility of interrogating micro- and nanoscale crystals, with edges only millions or even thousands of molecules long. These crystals exist in a size regime that approximates the lower bounds for traditional models of crystal nonuniformity and imperfection. Accordingly, data generated by diffraction from both X-rays and electrons show increased complexity and are more challenging to conventionally model. New approaches in serial crystallography and spatially resolved electron diffraction mapping are changing this paradigm by better accounting for variability within and between crystals. The intersection of these methods presents an opportunity for a more comprehensive understanding of the structure and properties of nanocrystalline materials.

Analysis of COF-300 synthesis: probing degradation processes and 3D electron diffraction structure.

Although COF-300 is often used as an example to study the synthesis and structure of (3D) covalent organic frameworks (COFs), knowledge of the underlying synthetic processes is still fragmented. Here, an optimized synthetic procedure based on a combination of linker protection and modulation was applied. Using this approach, the influence of time and temperature on the synthesis of COF-300 was studied. Synthesis times that were too short produced materials with limited crystallinity and porosity, lacking the typical pore flexibility associated with COF-300. On the other hand, synthesis times that were too long could be characterized by loss of crystallinity and pore order by degradation of the tetrakis(4-aminophenyl)methane (TAM) linker used. The presence of the degradation product was confirmed by visual inspection, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). As TAM is by far the most popular linker for the synthesis of 3D COFs, this degradation process might be one of the reasons why the development of 3D COFs is still lagging compared with 2D COFs. However, COF crystals obtained via an optimized procedure could be structurally probed using 3D electron diffraction (3DED). The 3DED analysis resulted in a full structure determination of COF-300 at atomic resolution with satisfying data parameters. Comparison of our 3DED-derived structural model with previously reported single-crystal X-ray diffraction data for this material, as well as parameters derived from the Cambridge Structural Database, demonstrates the high accuracy of the 3DED method for structure determination. This validation might accelerate the exploitation of 3DED as a structure determination technique for COFs and other porous materials.

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.

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.

Progress and Challenges of Additive Manufacturing of Tungsten and Alloys as Plasma-Facing Materials.

Tungsten (W) and W alloys are considered as primary candidates for plasma-facing components (PFCs) that must perform in severe environments in terms of temperature, neutron fluxes, plasma effects, and irradiation bombardment. These materials are notoriously difficult to produce using additive manufacturing (AM) methods due to issues inherent to these techniques. The progress on applying AM techniques to W-based PFC applications is reviewed and the technical issues in selected manufacturing methods are discussed in this review. Specifically, we focus on the recent development and applications of laser powder bed fusion (LPBF), electron beam melting (EBM), and direct energy deposition (DED) in W materials due to their abilities to preserve the properties of W as potential PFCs. Additionally, the existing literature on irradiation effects on W and W alloys is surveyed, with possible solutions to those issues therein addressed. Finally, the gaps in possible future research on additively manufactured W are identified and outlined.

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).

Efficacy and Safety of Plasma Rich in Growth Factor in Patients with Congenital Aniridia and Dry Eye Disease.

Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms. METHODS: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed. RESULTS: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss. CONCLUSION: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF.

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.

Celiac Disease-Related Enamel Defects: A Systematic Review.

INTRODUCTION: This systematic review aims to elucidate the intricate correlation between celiac disease (CD) and dental enamel defects (DED), exploring pathophysiological mechanisms, oral health implications, and a dentist's role in early diagnosis. MATERIALS AND METHODS: Following PRISMA guidelines, a comprehensive search from 1 January 2013 to 1 January 2024 across PubMed, Cochrane Library, Scopus, and Web of Science identified 153 publications. After exclusions, 18 studies met the inclusion criteria for qualitative analysis. Inclusion criteria involved study types (RCTs, RCCTs, case series), human participants, English language, and full-text available. RESULTS: The search yielded 153 publications, with 18 studies meeting the inclusion criteria for qualitative analysis. Notable findings include a high prevalence of DED in CD patients, ranging from 50 to 94.1%. Symmetrical and chronological defects, according to Aine's classification, were predominant, and significant associations were observed between CD severity and enamel defect extent. CONCLUSIONS: The early recognition of oral lesions, particularly through Aine's classification, may signal potential CD even in the absence of gastrointestinal symptoms. Correlations between CD and dental health conditions like molar incisor hypomineralization (MIH) emphasize the dentist's crucial role in early diagnosis. Collaboration between dentists and gastroenterologists is essential for effective monitoring and management. This review consolidates current knowledge, laying the groundwork for future research and promoting interdisciplinary collaboration for improved CD-related oral health outcomes. Further large-scale prospective research is recommended to deepen our understanding of these issues.

Structure solution and refinement of beam-sensitive nano-crystals.

Radiation sensitive materials are among the most difficult materials to study, even more so if they exist only as nanometer-sized particles, where their size is either intentional because of enhanced properties at the nano-scale or it is unintentional because it is impossible to obtain bigger particles of the same structure. In both cases characterization methods need to be optimized to get the most information out of these particles before the radiation damages them to a point where their structure is altered. When the particles are crystallized, both characteristics, the small size and the beam sensitivity, call for electron diffraction as a privileged investigation tool. The strong interaction of electrons (as compared to X-rays) with matter allows single crystal diffraction experiments on nanometer-sized crystals and for the same amount of beam damage, electron diffraction yields more information than X-rays. These inherent advantages of electron diffraction are optimized in the recently developed low-dose electron diffraction tomography (LD-EDT) by minimizing the necessary dose for a complete data collection. In this contribution we show that in some cases even doses as low as 2 e-/Ų can induce damage in crystal structures that inhibit a correct structure refinement. However, by LD-EDT we can obtain data using extremely low doses that don't alter the structure which make it then possible not only to solve crystal structures but also to refine them using dynamical diffraction theory. Here a synthetic oxide containing volatile Na and a metal-organic framework are given as examples. A dynamical refinement of the structures is possible with data sets requiring a dose of less than 0.15 e-/Ų.

Local administration of myeloid-derived suppressor cells prevents progression of immune-mediated dry eye disease.

Myeloid derived suppressor cells (MDSCs) are a heterogenous population of immature hematopoietic precursors with known immunoregulatory functions. The immunosuppressive role of MDSCs has been highlighted in several inflammatory ophthalmic disorders; however, their therapeutic application in suppressing the immune-mediated changes in dry eye disease (DED) has not been studied. We observed significant reduction in antigen presenting cell (APC) frequencies and their maturation in the presence of MDSCs. Moreover, co-culturing MDSCs with T helper 17 cells (Th17) resulted in reduced Th17 frequencies and their IL-17 expression. On the contrary, MDSCs maintained regulatory T cell frequencies and enhanced their function in-vitro. Furthermore, we delineated the role of interleukin-10 (IL-10) secreted by MDSCs in their immunoregulatory functions. We confirmed these results by flow cytometry analysis and observed that treatment with MDSCs in DED mice effectively suppressed the maturation of APCs, pathogenic Th17 response, and maintained Treg function and significantly ameliorated the disease. The results in this study highlight the potential therapeutic application of MDSCs in treating refractory DED.

Characterization of Complexes and Supramolecular Structures by Electron Microscopy.

Recent advancements in cryo-electron microscopy (cryo-TEM) have enabled the determination of structures of macromolecular complexes at near-atomic resolution, establishing it as a pivotal tool in Structural Biology. This high resolution allows for the detection of ligands and substrates under physiological conditions. Enhancements in detectors and imaging devices, like phase plates, improve signal quality, facilitating the reconstruction of even smaller macromolecular complexes. The 100-kDa barrier has been surpassed, presenting new opportunities for pharmacological research and expanding the scope of crystallographic analyses in the pharmaceutical industry. Cryo-TEM produces vast data sets from minimal samples, and refined classification methods can identify different conformational states of macromolecular complexes, offering deeper insights into the functional characteristics of macromolecular systems. Additionally, cryo-TEM is paving the way for time-resolved microscopy, with rapid freezing techniques capturing snapshots of vital structural changes in biological complexes. Finally, in Structural Cell Biology, advanced cryo-TEM, through tomographic procedures, is revealing conformational changes related to the specific subcellular localization of macromolecular systems and their interactions within cells.

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.

Repression of MRP51 in cis does not contribute to the synthetic growth defect conferred by an hphMX4-marked deletion of DBP1 in a ded1-ts mutant.

Powers et al. recently demonstrated that the hphMX6 cassette used to delete DPB1 in dbp1Δ::hphMX6 yeast mutants leads to reduced expression in cis of the adjacent gene MRP51, encoding the mitochondrial small subunit (SSU) ribosomal protein Mrp51. Here we provide evidence that elimination of Dbp1, not reduced MRP51 expression, underlies the synthetic growth defect of a dbp1Δ::hphMX6 ded1-ts mutant on glucose-containing medium, where respiration is dispensable, consistent with our previous conclusion that Dbp1 and Ded1 perform overlapping functions in stimulating translation initiation on mRNAs burdened with long or structured 5'UTRs in cells cultured with glucose.

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.

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.