Line Treatment For Patients Research Articles

Timing of Intervention for Aortic Intramural Hematoma

Intramural hematoma (IMH) is one of the acute aortic syndromes along with acute aortic dissection and penetrating aortic ulcer. The three conditions can occur alone or in combination with overlapping presentation. Medical, open surgical, and endovascular treatment is tailored depending on clinical presentation, timing, and location within the aorta. Among patients who present with acute IMH affecting the ascending aorta (Type A), urgent open surgical repair is considered the primary line of treatment in patients who are suitable candidates and unstable. The management of IMH in the descending aorta and aortic arch (Type B) is similar to that applied to treat acute dissections in the same segment. Medical treatment with sequential imaging is recommended in patients with uncomplicated course, and endovascular repair is indicated in patients with rupture, persistent pain, end-organ ischemia, or rapid aortic enlargement. This review discusses the ideal timing for treatment of IMH.

A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease.

Cardiovascular events caused by dyslipidemia are one of the leading causes of death in patients with Chronic Kidney Disease (CKD). Statins are the first line of treatment for patients with hyperlipidemia and in the treatment regimen for patients with CKD. Therefore, the introduction of Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9 inhibitors) is a viable and possibly effective treatment option for patients who, despite high doses of statins, struggle to lower their low-density lipoprotein cholesterol (LDL-C) levels. Our paper's objective is to explore the safety of these biological agents, particularly in patients with varying stages of impaired kidney function, and the correlating effectiveness in lowering their LDL-C levels, thereby reducing cardiovascular risks in these patients.We methodically retrieved relevant articles from PubMed, PubMed Central, Medline, and Google scholar in April 2022. We used the Medical Subject Heading (MeSH) Strategy and used the relevant keyword, then applied our inclusion and exclusion criteria; the initial search gave 10,542 results; with the removal of duplicates, irrelevant articles, and application of quality assessments done, we finally included 15 papers for our review with 37,188 patients.PCSK9 inhibitors are reliable, safe, and efficient therapy in lowering LDL-C levels in patients with CKD. However, its safety and efficacy in severe and end-stage kidney disease are grey, as other factors such as infections lead to morbidity and mortality. Future trials on chronic kidney disease and PCSK9 inhibitors should investigate the inhibitors' ability to improve kidney functions at all stages of kidney disease while lowering lipid levels and finally analyze the safety in patients with end-stage kidney disease.

835P Efficacy of checkpoint inhibitors and targeted therapy depending on the line of treatment in patients with advanced / metastatic melanoma

The use of targeted therapies (TT) and checkpoint inhibitors (IT) in patients with melanoma significantly prolonged survival, especially in the group of patients with BRAF-mutated melanoma. The aim of this study was to evaluate real-life outcomes of advanced melanoma second line therapy in TT-IT and IT-TT sequence with BRAFi/MEKi combination or anti-PD1 agent.

848P Second-line systemic treatment for patients with advanced melanoma: Results from the prospective real-world study GEM1801

Information regarding charatcteristics and outcomes of second line treatment for patients with advanced melanoma is scarce since no randomized clinical trials are published in the post-targeted and immunotherapy era. Real-world data studies are capital for benchmarking patients´ outcomes in order to design clinical trials in this scenario. GEM1801 is a prospective observational real-world study that currently has included 551 patients with advanced melanoma treated in 37 centers from the Spanish Melanoma Group (GEM). This is a descriptive analysis of basal characteristics, progression free survival (PFS) and overall survival (OS) from patients that received second line treatment in GEM1801. 186 (33.8%) patients received a second line (2L) treatment. For the 186 patients receiving 2L, with a median follow up of 6.4 months (m) (95% CI: 4.9-9.8), median PFS was 4.7 m (95% CI: 3.5-5.8) and median OS 11.3 m (95% CI: 8.6-13.4) from the beginning of 2L. Additionally, 63 (33.9%) patients received treatment beyond 2L. Table summarizes the patients characteristics and their outcomes according to BRAF status and treatments. For the 365 (66.2%) patients that did not receive 2L, the reasons were: 249 (68.2%) no progression with first line; 110 (30.1%) death before 2L; 6 (1.6%) loss of follow up.Table: 848PCHARACTERISTIC AT 2LBRAF Mutated N= 99BRAF wildtype N= 82SEX female N (%)47 (47.5)33 (40.2)age (median, Rank)59 (23-90)69 (29-93)ECOG 0-1 N (%)87 (87.9)78 (95.1)LDH >UNL N (%)34 (34.3)26 (31.7)M1C-D N (%)62 (62.6)40 (48.8)2L targeted therapy (TT): N, (%)44 (44.4)2 (2.4)TT mPFS, m (95% CI)12.4 (6.1-NR)2 (NA-NA)TT mOS, m (95% CI)20 (11.5-NR)2.7 (NA-NA)2L immunotherapy (IT): N (%)46 (46.5)34 (41.5)IT mPFS, m (95% CI)5.3 (2.9-10.8)3.1 (2.3-8.2)IT mOS, m (95% CI)10.9 (3.7-NR)12.5 (8.1-NR)2L Chemotherapy (CT): N, (%)4 (4)29 (35.4)CT mPFS, m (95% CI)0.4 (0-NR)3.2 (2.7-5.5)CT mOS, m (95% CI)0.6 (0.2-NR)5.6 (3.9-15.2)2L non specified: N (%)5 (5.1)13 (15.9)Treatment beyond 2L N (%)27 (27.8)33 (39.3)There are 5 patients with unknown BRAF status. Open table in a new tab There are 5 patients with unknown BRAF status. Second line treatment is still a difficult clinical scenario, especially for patients with BRAF wildtype melanoma and with BRAF mutated that progress after targeted therapy. The results, remarkably for PFS, need to be improved, thereby clinical trials participation is encouraged.

OA04.06 PEMbrolizumab Plus Lenvatinib In Second And Third Line Malignant Pleural MEsotheLiomA Patients: A Single Arm Phase II Study (PEMMELA)

There is a need for effective second line treatment in patients with recurrent malignant pleural mesothelioma (MPM). Pembrolizumab, a PD-1 receptor blocker, has shown a response rate up to 20% as monotherapy. Lenvatinib, a multiple tyrosine kinase inhibitor with mostly vascular endothelial growth factor receptor (VEGFR) blocking properties, has synergistic interactions with PD-1 blocking in other tumors. We aimed to evaluate clinical activity and toxicity of pembrolizumab plus lenvatinib in patients with recurrent MPM.

Synthesizing studies for comparing different treatment sequences in clinical trials.

With advances in cancer treatments and improved patient survival, more patients may go through multiple lines of treatment. It is of clinical importance to choose a sequence of effective treatments (eg, lines of treatment) for individual patients with the goal of optimizing their long-term clinical outcome (eg, survival). Several important issues arise in cancer studies. First, cancer clinical trials are usually conducted by each line of treatment. For a treatment sequence, we may have first line and second line treatment data from two different studies. Second, there is typically a treatment initiation period varying from patient to patient between progression of disease and the start of the second line treatment due to administrative reasons. Additionally, the choice of the second line treatment for patients with progression of disease may depend on their characteristics. We address all these issues and develop semiparametric methods under the potential outcome framework for the estimation of the overall survival probability for a treatment sequence and for comparing different treatment sequences. We establish the large sample properties of the proposed inferential procedures. Simulation studies and an application to a colorectal clinical trial are provided.

Statins in severe hypercholesterolemic patients: Gender and cardiovascular events gaps

Background and Aims : Statins are the first line of treatment in patients with severe hypercholesterolemia (SH) to prevent cardiovascular disease. Even though, it is well known that atherosclerosis is more prevalent in men than in women, there is a lack of information regarding their treatments in this population. Aim: to determine gender differences considering treatment and prognostic in a middle-age population with SH.

Budesonide in the first line treatment of patients with autoimmune hepatitis

Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug. La budesonida es un glucocorticoide que se caracteriza por su acción local, con una baja biodisponibilidad sistémica. Desde el ensayo original publicado en 2010, en el que se comparó la budesonida con prednisona, se recomienda como una alternativa eficaz en el tratamiento de los pacientes con hepatitis autoinmune aguda o crónica no grave. En este documento, revisamos las propiedades farmacológicas generales de los glucocorticoides, la evidencia disponible para el uso de budesonida como fármaco de primera línea en estos pacientes, así como el perfil de seguridad del fármaco.

Is there a place for chemotherapy in first line of treatment for metastatic NSCLC in era of immunotherapy?

Nowadays we can see a significant improvement and changes in the treatment of the patients with lung cancer. The current recommendations for the treatment are constantly being changed. New schemes and medicines are coming to the clinical practice. However, there are a group of patients outside of guidelines: patients with ECOG‑2 status, clinically rapidly progressing, with severe anxiety. Such patients are not including in clinical trials. Apparently, it is not quite right to transfer the current standard recommendations for the treatment to this group of patients. This review discusses various aspects related to the choice of a first line treatment in patients with metastatic non-small cell lung cancer in the situation of time absence and luck of molecular status of the patient. Is there a place for the starting with chemotherapy or immunochemotherapy, switching to targeted therapy or immunotherapy in the process of treatment.

X-ray-endovascular interventions in the treatment of patients with liver metastases of colorectal cancer after the termination of systemic chemotherapy

Background: At present, the problem of treating common forms of colorectal cancer does not lose its relevance due to the increase in its incidence. Systemic chemotherapy is the main line of treatment for patients with unresectable liver metastases. However, a significant problem of modern oncology is the further treatment tactics for patients with chemoresistant metastases. Aims: to improve the treatment results for patients with chemoresistant liver metastases of colorectal cancer. Method: 36 patients with unresectable liver metastases of colorectal cancer were treated at the Granov Russian Research Center of Radiology and Surgical Technologies and the RZD-Medicine Central Clinical Hospital. For all the patients, systemic chemotherapy was considered unreasonable due to the development of chemoresistance or a high degree of toxicity. The patients underwent regional chemotherapy chemoinfusion and/or chemoembolization of the hepatic artery. Results: The treatment evaluation was performed using the RECIST 1.1 scale. After 6 months, a partial response was reached in 1 patient (2.8%), stabilization was observed in 29 (80.5%) patients, and 6 patients (16.7%) had the disease progression. In 2 (5.6%) cases, a lethal outcome was observed against the background of the systemic progression of the oncological disease. One year later, stabilization of the malignant process was detected in 21 (58.3%) cases, progression was detected in 15 (41.7%) cases. A one-year survival of patients was 83.3%, the overall survival 22 months. Conclusion: The use of interventional radiology methods has shown its effectiveness in patients with unresectable chemoresistant liver metastases of colorectal cancer.

Standardizing Optimal Medical Therapy in Heart Failure Patients to Improve NCDR Metrics for ICD Implantation

Purpose: The Heart Rhythm Society recommends two medications to be prescribed after an ICD (Implantable Cardioverter Defibrillator) implantation for patients with EF < 40%. The recommended medications are beta blockers and angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) These medications have been well established as front line treatment in patients with heart failure who often need ICD implantation in prevention of sudden cardiac death. Long term beta blocker therapy can improve symptoms of heart failure, improve patient clinical status, and reduce hospitalizations and mortality.

Recent Advances in Prostate Cancer (PCa) Diagnostics

Prostate cancer (PCa), which is among the most prevalent types of cancer in men, is a prominent topic in imaging research. The primary aim of PCa imaging is to acquire more accurate characterizations of the disease. More precise imaging of the local stage progression, early discovery of metastatic cancers, reliable diagnosis of oligometastatic cancer, and optimum treatment response evaluation are areas in which contemporary imaging is quickly improving and developing. Imaging techniques, such as magnetic resonance imaging (MRI) for the whole body and molecular imaging with combined positron emission tomography (PET), computed tomography (CT), and MRI, enable imaging to support and enhance treatment lines in patients with local and advanced PCa. With the availability of multiple imaging modalities for the management of PCa, we aim in this review to offer a multidisciplinary viewpoint on the appropriate function of contemporary imaging in the identification of PCa.

IMMUNIB trial (AIO-HEP-0218/ass): A single-arm, phase II study evaluating safety and efficacy of immunotherapy nivolumab in combination with lenvatinib in advanced-stage hepatocellular carcinoma (HCC).

4107 Background: The field of systemic options in HCC therapy has significantly evolved in recent years, and first line options now include sorafenib, lenvatinib and bevacizumab plus atezolizumab. Nivolumab is a recombinant human IgG4 mAb targeting PD-1 with clinically meaningful activity in about 15-20% of HCC patients, but the confirmatory phase III trial Checkmate 459 failed to demonstrate superiority over sorafenib. VEGF signaling is not only a driver of tumor angiogenesis, but also contributes to the formation of an immunosuppressive microenvironment. Combinations of anti-angiogenic multikinase inhibitors, specifically lenvatinib, and PD-1/PD-L1 inhibitors have demonstrated remarkable antitumor activity and manageable toxicity in several tumor types, including HCC. We therefore aimed to evaluate the efficacy of nivolumab in combination with lenvatinib as first line treatment in patients with advanced HCC. Methods: This investigator-initiated single-armed phase II trial (NCT03841201) recruited 50 patients (pts) at 8 sites in Germany between 07/2019 and 05/2021. Primary endpoints were objective response rate (ORR) according to investigator assessed RECIST 1.1 and safety/tolerability. Secondary endpoints included ORR according to iRECIST, time to progression (TTP), progression free survival (PFS) and overall survival (OS). Recruitment of the trial was completed in 05/2021. At the time of analysis, 4 patients remained on treatment. Results: 50 pts (24 BCLC B, 24 BCLC C, 2 not evaluable) were enrolled and received at least one dose of the combination treatment. ORR by RECIST 1.1 was 28% (CR: 6.0%, PR: 22.0%, SD: 46.0%, PD: 12.0%). Median PFS was 9.0 mo (26 events). Median TTP was 11.5 mo (0.69 at 6 mo, 0.45 at 12 mo, 0.36 at 18 mo) and median OS was 27.1 mo (8 events). 45 (91.8%) pts experienced at least one TRAE, of which 29 pts (59.1%) encountered at least one TRAE ≥ grade 3. 17 (34.7%) pts had one or more SAE related to the study medication, whereof 15 pts (30.6%) experienced at least one treatment related SAE ≥ grade 3. Conclusions: No new safety signals were observed for the combination of nivolumab and lenvatinib. Although the study failed to reach its prespecified ORR of at least 40%, the high activity in all efficacy endpoints with a mOS of 27.1 mo supports the further investigation of the combination in HCC. Clinical trial information: NCT03841201.

A phase I trial to evaluate the biologic effect of CBM588 (Clostridium butyricum) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC).

TPS4606 Background: Combination therapy with the immune checkpoint inhibitor (ICI) nivolumab (nivo) and the tyrosine kinase inhibitor cabozantinib (cabo) is a new standard of care for first line treatment of patients with clear cell mRCC. However, despite the improved clinical benefit obtained with this regimen, a subgroup of patients still presents with progressive disease as best response (Choueiri et al NEJM 2021). There is now evidence supporting the role of the gut microbiome in mediating ICI activity (Routy et al Science 2018) and certain bacterial species, such as Bifidobacterium spp. in predisposing clinical response in patients with mRCC receiving ICIs (Salgia et al Eur Urol 2020). Moreover, recent evidence from a phase I clinical trial suggests that the addition of CBM588, a live probiotic comprised primarily of Clostridium butyricum, can enhance clinical response in patients with mRCC receiving nivolumab plus ipilimumab without incurring added toxicity (Meza et al ASCO, 2021). Herein we present the study design of an ongoing phase I study evaluating the biological effect of CBM588 in combination with cabozantinib plus nivolumab in patients with mRCC. Methods: This is an open label, randomized, single institution phase 1 trial for patients with confirmed mRCC with clear cell, papillary, or sarcomatoid components, who have not received prior systemic therapy for metastatic disease. A total of 30 eligible patient will be randomized 1:2 to receive either cabo/nivo at the standard dose/schedule (40mg PO QD and 480mg IV /4wks, respectively) alone or with CBM588 dosed at 80mg PO bid. The primary objective of the study is to determine the biologic effect of CBM588 with cabo/nivo in the modulation of the gut microbiome. This will be done by assessing the changes in Bifidobacterium spp. abundance and Shannon index (a measure of microbiome diversity) in stool specimens. Stool will be collected for bacteriomic profiling at baseline and after 12 weeks of treatment. Metagenomic sequencing will be performed using previously published methods (Dizman et al Cancer Med 2020). Secondary objectives include determining the effect of CBM588 on (1) clinical efficacy, through overall survival, response rate, and progression-free survival; (2) systemic immunomodulation, through assessment of changes in circulating Tregs, circulating cytokines/chemokines, etc; and (3) toxicities. A two-group t-test with a one-sided type I error of 0.05 will be used to assess the study primary endpoint. Clinical trial information: NCT05122546 .

P280 USE OF SYSTEMIC THROMBOLYSIS IN HEMODYNAMICALLY UNSTABLE PULMONARY EMBOLISM PATIENTS WITH AND WITHOUT CARDIAC ARREST: DATA FROM THE IPER REGISTRY

Abstract Background Systemic thrombolysis (ST) remains the treatment of choice in haemodynamically unstable patients with acute pulmonary embolism (PE). However, it remains frequently underused in clinical practice. The purpose of the study is to evaluate the use of ST in hemodynamically unstable PE patients with aand without acute cardiac arrest using the IPER registry. Materials and Methods IPER is a multicentre, national, prospective, web–based registry based on 47 Italian hospitals. In this study, the population was divided into two groups: patients with (ACC) and without (No ACC) cardio–circulatory arrest at admission. Results Of 1716 patients enrolled between September 2006 and August 2010, 201 (11.7%) [mean age 74 ± 14 years 127 females] were defined as high risk (i.e. haemodynamically unstable). Of these 59 (29.4%, mean age 76.4 ± 13.3 years, 40 females) were admitted with ACC while the remaining 142 (70.6, mean age 73.5 ± 13.7 years, 87 females) without. No differences were observed for venous thromboembolism risk factors, such as immobilization for more than three days, trauma, surgery within the previous 4 weeks, previous venous thromboembolism, history of heart failure, cancer and ischemic heart disease, among the two gropus. Mortality from all causes (62.7% vs 19.0, p &amp;lt; 0.001) and for acute PE (55.9% vs 9.9%, p &amp;lt; 0.001) was higher in ACC patients. Thrombolysis was administered in 82 (40.7%) of haemodynamically unstable patients and more frequently in ACC subjects (55.9% VSA 34.5%, p = 0.005) (Figure 1, panel A). The administration of systemic thrombolysis increased with aging in the No ACC group but showed a significant reduction in over–octogenarian patients (Figure 1, panel B). Major bleeding complications following reperfusive treatment were observed in 8 patients (3.9%); among these, intracranial hemorrhage was registered in 2.4% of cases. Conclusions Although systemic thrombolysis remains the first–line treatment in patients with hemodynamically unstable acute PE and is capable of improving both the mortality and morbidity, it continues to be underused in daily clinical practice, often for fear of major bleeding complications.

Osimertinib 80 mg EOD? Does this work?

Osimertinib is a third-generation thyroxine kinase inhibitor (TKI) used in treating advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. Osimertinib is used as a second line treatment for patients who develop EGFR T790 M resistance mutation rather than first line due to financial constraints. We present a case of a 60-year-old Chinese gentleman who diagnosed as stage 4 adenocarcinoma with EGFR Exon 19 deletion. His disease progressed after a year of treatment with afatinib. His plasma T790 M was negative and due to delay in tissue biopsy, he was empirically started on osimertinib. However, in view of financial concerns, he opted a dose reduction of 80 mg every alternate day rather than the conventional dose of 80 mg daily. Serial CT Thorax showed partial response based on RECIST 1.1 criteria and he has 9 months of progression free survival. This case report shows that Osimertinib in reduced dose may achieve good partial response and progression free survival in patients.

β-blocker adherence among patients with congenital long QT syndrome: a nationwide study.

β-blockers are the first line of treatment in patients with congenital long QT syndrome (cLQTS) (class I or II recommendation) in order to prevent malignant arrhythmias. Hence, we examined long-term β-blocker adherence and associated risk factors among patients with cLQTS. Danish patients with cLQTS claiming a prescription for any β-blocker after their cLQTS diagnosis were identified using data from nationwide registries and specialized inherited cardiac disease clinics (1995-2017). Patients were followed for up to 5 years. Treatment breaks >60days were assessed (i.e. proxy for reduced adherence). Multivariable Cox regression was used to identify risk factors associated with breaks of >60 days in β-blocker treatment. Overall, 500 out of 633 (79%) patients with cLQTS claimed at least one prescription for any β-blocker after cLQTS diagnosis. During follow-up, 38.4% had a treatment break. Risk factors significantly associated with treatment breaks were implantable cardioverter defibrillator (ICD) [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.08-2.53], β-blocker side effects (HR=2.69, 95% CI: 1.75-4.13), and psychiatric disease (HR=1.63, 95% CI: 1.04-2.57). In contrast, patients presenting with ventricular tachycardia/syncope as cLQTS disease manifestation were less likely to have a treatment break compared with asymptomatic patients (HR=0.55, 95% CI: 0.33-0.92). Reduced β-blocker adherence was common with more than a third of patients having a treatment break >60days after cLQTS diagnosis. Patients with psychiatric disease, self-reported β-blocker side effects, and an ICD were more likely to display reduced adherence, whereas a severe cLQTS disease manifestation was associated with optimal β-blocker adherence.

Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial

ObjectiveTo evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell...

Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma

BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC.Patients and methodsPatients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months.ResultsFrom March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%).ConclusionsCabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.

Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease.

Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.