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Pantazopoulos D, Gouveri E, Papazoglou D, Papanas N. The Trigeminal Nerve in Diabetes Mellitus: A Brief Narrative Review. Exp Clin Endocrinol Diabetes 2025. [PMID: 40049604 DOI: 10.1055/a-2552-8692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
This brief narrative review discusses the clinical manifestations, diagnosis, and management of trigeminal nerve-related conditions, such as neuropathy and neuralgia, in patients with diabetes mellitus. Although these conditions are not very common, there is a solid connection between them in diabetes patients. Symptoms typically include facial pain, sensory disturbances, and muscle weakness for neuropathy and severe, stabbing pain for neuralgia. Diagnosis is based on characteristic clinical manifestations, along with laboratory investigation and magnetic resonance imaging to exclude other potential causes, such as tumours, multiple sclerosis, or vascular compression. Treatment focuses on strict glycaemic control, modification of vascular risk factors, pharmacological agents (carbamazepine and oxcarbazepine), and neurostimulation to improve symptoms and quality of life.
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Affiliation(s)
- Dimitrios Pantazopoulos
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100, Alexandroupolis, Greece
| | - Evanthia Gouveri
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100, Alexandroupolis, Greece
| | - Dimitrios Papazoglou
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100, Alexandroupolis, Greece
| | - Nikolaos Papanas
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100, Alexandroupolis, Greece
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Sun Y, Zhang Y, Shi F, Li Y, Wang C, Yu F, Chen T, Dong X, Xu Y, Zhao Y, Wan P. Characterization and Role of Glucagon-Like Peptide 1 Receptor in the Lacrimal Gland: Novel Insights into Diabetic Dry Eye Pathogenesis. THE AMERICAN JOURNAL OF PATHOLOGY 2025; 195:797-810. [PMID: 39725294 DOI: 10.1016/j.ajpath.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/20/2024] [Accepted: 12/11/2024] [Indexed: 12/28/2024]
Abstract
This study aimed to investigate the expression of glucagon-like peptide 1 receptor (GLP-1R) in the lacrimal gland and explore the effects of topical application of GLP-1R agonist on lacrimal gland function in a murine model of type 1 diabetes. Tear secretion was evaluated using phenol red threads, RNA sequencing was used to explore gene expression profiles associated with hyperglycemia-induced lacrimal gland injuries, and histologic analysis was conducted to evaluate the degree of damage. The expression of GLP-1R in the lacrimal gland was first identified, and a down-regulation trend associated with diabetes was observed. RNA-sequencing data from lacrimal gland tissues revealed that differentially expressed genes were enriched in inflammatory response pathways. Histologic analysis demonstrated persistent hyperglycemia-induced infiltration of inflammatory cells and progressive fibrosis in the lacrimal gland, resulting in atrophy and diminished tear secretion. Topical application of liraglutide effectively attenuated inflammation and alleviated fibrosis, thus promoting tear production in diabetic mice. Additionally, local intervention with liraglutide promoted autophagy degradation function in the lacrimal gland. This study represents the first validation of GLP-1R expression in the lacrimal gland and its down-regulation induced by diabetes. Additionally, these findings demonstrate that topical administration of liraglutide eye drops, a GLP-1R agonist, can effectively mitigate hyperglycemia-induced damage in the lacrimal gland while enhancing tear secretion.
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Affiliation(s)
- Yan Sun
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yue Zhang
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Fan Shi
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ye Li
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Congyao Wang
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Fenfen Yu
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tingting Chen
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xia Dong
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yuqi Xu
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Zhao
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pengxia Wan
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Shumye AF, Bekele MM, Tegegne MM, Eticha BL, Bayabil AZ, Birhan GS, Tegegn MT. Symptomatic dry eye disease and its associated factors among adult patients with diabetes attending comprehensive specialised hospitals in Amhara Region, Ethiopia: a multicentre institution-based cross-sectional study. BMJ Open 2025; 15:e090721. [PMID: 40081975 PMCID: PMC11907020 DOI: 10.1136/bmjopen-2024-090721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 02/27/2025] [Indexed: 03/16/2025] Open
Abstract
OBJECTIVE This study aimed to determine the prevalence and associated factors of symptomatic dry eye disease (SDED) among adult patients with diabetes visiting five comprehensive specialised hospitals in the Amhara Region, Ethiopia. DESIGN An institution-based cross-sectional study. SETTING This study was conducted at the University of Gondar, Debretabor, Tibebe Gion, Felege Hiwot and Debre Markos comprehensive specialised hospitals in the Amhara Region, Ethiopia, from 8 May 2023 to 8 June 2023. PARTICIPANTS The study included 1199 adult patients with diabetes aged >18 years who lived in the Amhara Region, Ethiopia, for more than 6 months and were selected using a systematic random sampling technique. PRIMARY AND SECONDARY OUTCOME MEASURES In this study, the primary outcome measure was the magnitude of SDED, and the secondary outcome measure was the associated factors of SDED. RESULTS A total of 1134 study subjects participated in this study with a response rate of 94.5%. The prevalence of symptomatic dry eye was 40.4% (95% CI 37.7 to 43.2). Factors such as poor glycaemic control (adjusted OR (AOR)=2.58, 95% CI 1.86 to 3.58), duration of diabetes ≥10 years (AOR=2.77, 95% CI 1.95 to 3.95), proliferative diabetic retinopathy (AOR=5.58, 95% CI 2.1 to 14.39), poor eye check-up practice (AOR=1.98, 95% CI 1.49 to 2.62) and peripheral diabetic neuropathy (AOR=3.76, 95% CI 2.58 to 5.48) were significant associated factors with SDED. CONCLUSION In this study, the prevalence of SDED among patients with diabetes was high. Poor glycaemic control, longer duration of diabetes, proliferative diabetic retinopathy, inadequate eye check-up practices and peripheral diabetic neuropathy were significantly associated with SDED. It is recommended that healthcare providers prioritise regular monitoring of eye health in patients with diabetes, emphasising the importance of maintaining optimal glycaemic control, and routine eye check-ups for early detection and management of SDED.
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Affiliation(s)
- Abebech Fikade Shumye
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Matiyas Mamo Bekele
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Mebratu Mulusew Tegegne
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Biruk Lelisa Eticha
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Abebizuhan Zigale Bayabil
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Getenet Shumet Birhan
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Melkamu Temeselew Tegegn
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
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Scarinci F, De Simone G, Ciancimino C, Caggiano C, Pocobelli G, Di Masi A. Enhancing Corneal Sensitivity in Diabetic Patients Through an Innovative Ophthalmic Solution: In Vivo and Vitro Results. J Clin Med 2025; 14:245. [PMID: 39797325 PMCID: PMC11721187 DOI: 10.3390/jcm14010245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 12/25/2024] [Accepted: 12/30/2024] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: Diabetes is a well-recognised factor inducing a plethora of corneal alterations ranging from dry eye to reduced corneal sensibility, epithelial defects, and reduced cicatrisation. This cohort study aimed to assess the efficacy of a novel ophthalmic solution combining cross-linked hyaluronic acid (CHA), chondroitin sulfate (CS), and inositol (INS) in managing diabetes-induced corneal alterations. Specifically, it evaluated the solution's impact on the tear breakup time (TBUT), the ocular surface disease index (OSDI), and corneal sensitivity after three months of treatment. Additionally, the solution's potential to promote wound healing was examined. Methods: Two different populations were retrieved from the database; the first one was composed of 20 diabetic subjects treated for three months with the ophthalmic CAH-CS (OPHTAGON srl, Rome, Italy), while the second group was composed of 20 diabetic subjects who did not want to use any eye lubricant or other treatment. The outcome measures were the TBUT, the OSDI score, and the corneal sensitivity measured using a Cochet-Bonnet aesthesiometer. To investigate the wound-healing properties, in vitro tests were conducted using two cell lines, comparing the results of scratch tests with and without the solution. Results: The results indicate that CHA-CS significantly improved the tear film stability, as evidenced by an increased TBUT and a reduction in dry eye symptoms reflected by lower OSDI scores. Moreover, the solution was associated with an enhanced corneal sensitivity in treated patients. In wound-healing assays, CHA-CS promoted cell motility, suggesting a supportive role in tissue repair compared to untreated cells. Conclusions: Collectively, the results suggest that CHA-CS could serve as an innovative tool for the treatment of diabetic patients with corneal alterations and delayed corneal sensitivity. Clinical trial registration number: Clinical Trial.gov NCT06573606.
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Affiliation(s)
- Fabio Scarinci
- Ophthalmology, San Giovanni-Addolorata Hospital, Via Santo Stefano Rotondo, 6, 00184 Rome, Italy
| | - Giovanna De Simone
- Department of Sciences, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy
| | - Chiara Ciancimino
- Ophthalmology Unit, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), St. Andrea Hospital, “Sapienza” University of Rome, Via di Grottarossa 1035/1039, 00189 Rome, Italy
| | | | - Giulio Pocobelli
- Department of Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT), University of Rome Tor Vergata, 00133 Rome, Italy
| | - Alessandra Di Masi
- Department of Sciences, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy
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Kalra S, Gokhale NS, Bantwal G, Matada R, Shaikh S, Pawar V, Khalse M, Patel K. Dry Eye in Diabetes: The Indian Diabetic and Endocrine Eye Diseases (INDEED) Review. TOUCHREVIEWS IN ENDOCRINOLOGY 2024; 20:30-41. [PMID: 39526056 PMCID: PMC11548426 DOI: 10.17925/ee.2024.20.2.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 07/05/2024] [Indexed: 11/16/2024]
Abstract
Dry eye disease (DED) is an inadequately addressed condition in the diabetes management process and can significantly impact the quality of life and self-care. Therefore, it was imperative to review DED in the diabetic population. The aim of this article was to obtain insights into the correlation between dry eye and diabetes, with a focus on data published in the Indian population. A comprehensive literature review was performed using MEDLINE and Google Scholar, along with an internet-based search of publicly available information and peer-reviewed publications that may not have been indexed in these databases. The recommendations from several important societies for patients with DED have also been reviewed. Major aspects commonly associated with DED and diabetes have been addressed, and specific suggestions for screening, diagnosis and treatment have been described. Therefore, this review could be an invaluable resource for doctors managing patients with both conditions.
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Affiliation(s)
- Sanjay Kalra
- Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India
| | | | - Ganapathi Bantwal
- Department of Endocrinology, St. Johns Medical College, Bangalore, Karnataka, India
| | - Roopashri Matada
- Department of Ophthalmology, JJM Medical College, Davangere, Karnataka, India
| | | | - Varsha Pawar
- Medical Affairs Division, Lupin Ltd., Mumbai, Maharashtra, India
| | - Maneesha Khalse
- Medical Affairs Division, Lupin Ltd., Mumbai, Maharashtra, India
| | - Kamlesh Patel
- Medical and Health Tech, Lupin Ltd., Mumbai, Maharashtra, India
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Bhandarkar NS, Shetty KB, Shetty N, Shetty K, Kiran A, Pindipapanahalli N, Shetty R, Ghosh A. Comprehensive analysis of systemic, metabolic, and molecular changes following prospective change to low-carbohydrate diet in adults with type 2 diabetes mellitus in India. Front Nutr 2024; 11:1394298. [PMID: 39279894 PMCID: PMC11397303 DOI: 10.3389/fnut.2024.1394298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/29/2024] [Indexed: 09/18/2024] Open
Abstract
Purpose South Asians, especially Indians, face higher diabetes-related risks despite lower body mass index (BMI) compared with the White population. Limited research connects low-carbohydrate high-fat (LCHF)/ketogenic diets to metabolic changes in this group. Systematic studies are needed to assess the long-term effects of the diet, such as ocular health. Method In this prospective, observational study, 465 candidates aged 25-75 years with type 2 diabetes included with institutional ethics approval. A total of 119 subjects were included in the final study assessment based on the availability of pathophysiological reports, tears, and blood samples collected at baseline, 3rd, and 6th months. Serum and tear samples were analyzed by an enzyme-linked lectinsorbent assay, to examine secreted soluble protein biomarkers, such as IL-1β (interleukin 1 Beta), IL-6 (interleukin 6), IL-10 (interleukin 10), IL-17A (interleukin 17A), MMP-9 (matrix metalloproteinase 9), ICAM-1 (intercellular adhesion molecule 1), VEGF-A (vascular endothelial growth factor A), and TNF-α (tumor necrosis factor-alpha). A Wilcoxon test was performed for paired samples. Spearman's correlation was applied to test the strength and direction of the association between tear biomarkers and HbA1c. p-value of < 0.05 was considered significant. Results After a 3- and 6-month LCHF intervention, fasting blood sugar decreased by 10% (Δ: -14 mg/dL; p < 0.0001) and 7% (Δ: -8 mg/dL; p < 0.0001), respectively. Glycated hemoglobin A1c levels decreased by 13% (Δ: -1%; p < 0.0001) and 9% (Δ: -0.6%; p < 0.0001). Triglycerides reduced by 22% (Δ: -27 mg/dL; p < 0.0001) and 14% (Δ: -19 mg/dL; p < 0.0001). Total cholesterol reduced by 5.4% (Δ: -10.5 mg/dL; p < 0.003) and 4% (Δ: -7 mg/dL; p < 0.03), while low-density lipoprotein decreased by 10% (Δ: -11.5 mg/dL; p < 0.003) and 9% (Δ: -11 mg/dL; p < 0.002). High-density lipoprotein increased by 11% (Δ: 5 mg/dL; p < 0.0001) and 17% (Δ: 8 mg/dL; p < 0.0001). At the first follow-up, tear proteins such as ICAM-1, IL-17A, and TNF-α decreased by 30% (Δ: -2,739 pg/mL; p < 0.01), 22% (Δ: -4.5 pg/mL; p < 0.02), and 34% (Δ: -0.9 pg/mL; p < 0.002), respectively. At the second follow-up, IL-1β and TNF-α reduced by 41% (Δ: -2.4 pg/mL; p < 0.05) and 34% (Δ: -0.67 pg/mL; p < 0.02). Spearman's correlation between HbA1c and tear analytes was not statistically significant. Conclusion The LCHF diet reduces the risk of hyperglycemia and dyslipidemia. Changes in tear fluid protein profiles were observed, but identifying promising candidate biomarkers requires validation in a larger cohort.
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Affiliation(s)
| | | | | | | | | | | | | | - Arkasubhra Ghosh
- GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
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Alhalwani AY, Baqar R, Algadaani R, Bamallem H, Alamoudi R, Jambi S, Abd El Razek Mady W, Sannan NS, Anwar Khan M. Investigating Neutrophil-to-Lymphocyte and C-Reactive Protein-to-Albumin Ratios in Type 2 Diabetic Patients with Dry Eye Disease. Ocul Immunol Inflamm 2024; 32:925-931. [PMID: 36637884 DOI: 10.1080/09273948.2022.2152698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/09/2022] [Accepted: 11/21/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND Patients with Diabetes mellitus (DM) are at risk of developing dry eye disease (DED). We investigated routine laboratory parameters in patients with type 2 DM (T2D) and T2D-DED to identify potential inflammatory markers. METHODS A retrospective study of 241 randomly selected patients (30 DED non-diabetic, 120 T2D, and 91 with T2D-DED). The neutrophil-to-lymphocyte ratios (NLR), CRP-to-albumin ratios (CAR), and the glycosylated haemoglobin A1c (HbA1c) results were correlated between groups. RESULTS The NLR and HbA1c were significantly higher in the T2D-DED group (p≤0.001 and 0.0001, respectively) when compared with T2D and DED non-diabetic groups. CAR was insignificantly high in the three groups (p=0.192). A positive correlation was identified between CAR and NLR in T2D-DED patients (p= 0.008). CONCLUSION In T2D-DED patients, NLR was significantly high and positively correlate with CAR. These results predicate diabetes with dry eye complications, and biomarker-mediated inflammation may have important roles in DED pathogenesis.
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Affiliation(s)
- Amani Y Alhalwani
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- Department of Biomedical Research, King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia
| | - Rawan Baqar
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Rawan Algadaani
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Hala Bamallem
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Rwzan Alamoudi
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Shatha Jambi
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Wessam Abd El Razek Mady
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Naif S Sannan
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- Department of Biomedical Research, King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia
| | - Muhammed Anwar Khan
- College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
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Jiang K, Zhang F, Chen Y, Li X, Zhao X, Jiang P, Li Y. Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway. Invest Ophthalmol Vis Sci 2024; 65:2. [PMID: 38829670 PMCID: PMC11156208 DOI: 10.1167/iovs.65.6.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 05/15/2024] [Indexed: 06/05/2024] Open
Abstract
Purpose The purpose of this study was to investigate the involvement of the TLR4/NF-κB/NLRP3 signaling pathway and its underlying mechanism in diabetic dry eye. Methods Two models of diabetic dry eye were established in high glucose-induced human corneal epithelial (HCE-T) cells and streptozotocin (STZ)-induced C57BL/6 mice, and the TLR4 inhibitor fosfenopril (FOS) was utilized to suppress the TLR4/NF-κB/NLRP3 signaling pathway. The expression changes in TLR4, NF-κB, NLRP3, and IL-1β, and other factors were detected by Western blot and RT‒qPCR, the wound healing rate was evaluated by cell scratch assay, and the symptoms of diabetic mice were evaluated by corneal sodium fluorescein staining and tear secretion assay. Results In the diabetic dry eye model, the transcript levels of TLR4, NF-κB, NLRP3, and IL-1β were raised, and further application of FOS, a TLR4 inhibitor, downregulated the levels of these pathway factors. In addition, FOS was found to be effective in increasing the wound healing rate of high glucose-induced HCE-T cells, increasing tear production, and decreasing corneal fluorescence staining scores in diabetic mice, as measured by cell scratch assay, corneal sodium fluorescein staining assay, and tear production. Conclusions The current study found that the TLR4/NF-κB/NLRP3 signaling pathway regulates diabetic dry eye in an in vitro and in vivo model, and that FOS reduces the signs of dry eye in diabetic mice, providing a new treatment option for diabetic dry eye.
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MESH Headings
- Animals
- Humans
- Male
- Mice
- Blotting, Western
- Cells, Cultured
- Diabetes Mellitus, Experimental/drug therapy
- Diabetes Mellitus, Experimental/metabolism
- Disease Models, Animal
- Dry Eye Syndromes/drug therapy
- Dry Eye Syndromes/metabolism
- Epithelium, Corneal/drug effects
- Epithelium, Corneal/metabolism
- Mice, Inbred C57BL
- NF-kappa B/metabolism
- NF-kappa B/antagonists & inhibitors
- NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors
- Real-Time Polymerase Chain Reaction
- Signal Transduction
- Tears/metabolism
- Toll-Like Receptor 4/metabolism
- Toll-Like Receptor 4/antagonists & inhibitors
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Affiliation(s)
- Kaiwen Jiang
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Fenglan Zhang
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Ying Chen
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Xiaojing Li
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Xinmei Zhao
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Pengfei Jiang
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Yuanbin Li
- Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
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Tran Tat T, Ngo Duc K, Pham Hong P, Nguyen Sa H, Nguyen Trung K, Nguyen Thi Thu H, Le Ha K, Nguyen Huu D, Thai Doan T, Le Viet T. Dry Eye and Some Related Factors in Patients with Type 2 Diabetic Nephropathy: A Cross-Sectional Study in Vietnam. Clin Ophthalmol 2024; 18:1217-1224. [PMID: 38737597 PMCID: PMC11088030 DOI: 10.2147/opth.s458633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 04/21/2024] [Indexed: 05/14/2024] Open
Abstract
Aim To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). Methods We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. Results The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Conclusion Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.
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Affiliation(s)
- Thang Tran Tat
- Department of Cornea and Conjunctiva, Nghe An Eye Hospital, Nghe An, Vietnam
| | - Ky Ngo Duc
- Department of Endocrinology, Nghe An Friendship General Hospital, Nghe An, Vietnam
| | - Phuong Pham Hong
- Department of Cardiology, Nghe An Friendship General Hospital, Nghe An, Vietnam
| | - Huynh Nguyen Sa
- Department of Cornea and Conjunctiva, Nghe An Eye Hospital, Nghe An, Vietnam
| | - Kien Nguyen Trung
- Hematology and Blood Transfusion Center, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam
| | - Ha Nguyen Thi Thu
- Organ Transplantation Center, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam
| | - Khoa Le Ha
- Hanoi Medical University, Ha Noi, Vietnam
| | | | - Thang Thai Doan
- Department of Epidemiology, TTH Vinh General Hospital, Nghe An, Vietnam
| | - Thang Le Viet
- Organ Transplantation Center, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam
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Alhalwani AY, Jambi S, Borai A, Khan MA, Almarzouki H, Elsayid M, Aseri AF, Taher NO, Alghamdi A, Alshehri A. Assessment of the systemic immune-inflammation index in type 2 diabetic patients with and without dry eye disease: A case-control study. Health Sci Rep 2024; 7:e1954. [PMID: 38698793 PMCID: PMC11063262 DOI: 10.1002/hsr2.1954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 02/12/2024] [Accepted: 02/19/2024] [Indexed: 05/05/2024] Open
Abstract
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.
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Affiliation(s)
- Amani Y. Alhalwani
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | - Shatha Jambi
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | - Anwar Borai
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
- King Abdulaziz Medical CityJeddahSaudi Arabia
| | - Muhammad Anwar Khan
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | - Hashem Almarzouki
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
- King Abdulaziz Medical CityJeddahSaudi Arabia
| | - Mohieldin Elsayid
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | | | - Nada O. Taher
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
| | - Ali Alghamdi
- Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
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11
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Guo L, Xiao X. Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). Aging Med (Milton) 2024; 7:5-51. [PMID: 38571669 PMCID: PMC10985780 DOI: 10.1002/agm2.12294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/08/2024] [Accepted: 02/08/2024] [Indexed: 04/05/2024] Open
Abstract
With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de-intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full-cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence-based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes.
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Affiliation(s)
- Lixin Guo
- National Center of Gerontology, Chinese Society of Geriatrics, Diabetes Professional Committee of Chinese Aging Well AssociationBeijingChina
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina
| | - Xinhua Xiao
- National Center of Gerontology, Chinese Society of Geriatrics, Diabetes Professional Committee of Chinese Aging Well AssociationBeijingChina
- Department of EndocrinologyPeking Union Medical College Hospital, Chinese Academy of Medical SciencesBeijingChina
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12
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Zou XR, Zhang P, Zhou Y, Yin Y. Ocular surface microbiota in patients with varying degrees of dry eye severity. Int J Ophthalmol 2023; 16:1986-1995. [PMID: 38111925 PMCID: PMC10700088 DOI: 10.18240/ijo.2023.12.10] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 09/14/2023] [Indexed: 12/20/2023] Open
Abstract
AIM To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye (DE). METHODS The single-center, prospective, case-control, observational study categorized all participants into three distinct groups: 1) control group (n=61), 2) mild DE group (n=56), and 3) moderate-to-severe DE group (n=82). Schirmer's tear secretion strips were used, and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing. RESULTS The three groups had significant differences in alpha diversity: the control group had the highest richness (Chao1, Faith's phylogenetic diversity), the mild DE group showed the highest diversity (Shannon, Simpson), and the moderate-to-severe DE group had the lowest of the above-mentioned indices. DE severity was positively correlated with a reduction in beta diversity of the microbial community, with the moderate-to-severe DE group exhibiting the lowest beta diversity. Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each. Furthermore, the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria, as determined by random forest analysis. CONCLUSION As DE severity worsens, microbial community diversity tends to decrease. DE development corresponds with changes in microbial constituents, primarily characterized by reduced microbial diversity and a more homogenous species composition.
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Affiliation(s)
- Xin-Rong Zou
- Department of Ophthalmology, Fengcheng Hospital, Fengxian District, Shanghai 201411, China
- Fengcheng Branch, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201411, China
| | - Pei Zhang
- Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai 200040, China
- Department of Ophthalmology, Gonghui Hospital, Jing'an District, Shanghai 200436, China
| | - Yuan Zhou
- Department of Ophthalmology, Fengcheng Hospital, Fengxian District, Shanghai 201411, China
- Fengcheng Branch, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201411, China
| | - Yao Yin
- Department of Ophthalmology, Fengcheng Hospital, Fengxian District, Shanghai 201411, China
- Fengcheng Branch, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201411, China
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13
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Chen J, Chen Y, Qin G, Li L, Li M, Cheng Y, Zhuang S, Li Z, Zhang Q, Wu Y, Yang L, Moutari S, Moore JE, Xu L, He W, Yu S, Pazo EE, He X. A protocol for a single center, randomized, controlled trial comparing the clinical efficacy of 3% diquafosol and 0.1% hyaluronic acid in diabetic patients with dry eye disease. Trials 2023; 24:803. [PMID: 38087329 PMCID: PMC10714480 DOI: 10.1186/s13063-023-07818-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients. METHODS This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS (n = 101) and HA (n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8. DISCUSSION This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment. TRIAL REGISTRATION ClinicalTrials.govNCT05682547. Registered on December 05, 2022.
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Affiliation(s)
| | | | | | | | - Mingze Li
- Dalian Medical University, Shenyang, China
| | - Yuan Cheng
- Dalian Medical University, Shenyang, China
| | | | - Zhihui Li
- Dalian Medical University, Shenyang, China
| | - Qing Zhang
- Tianjin Medical University, Tianjin, China
| | - Yi Wu
- China Medical University, Shenyang, China
| | | | - Salissou Moutari
- Mathematical Sciences Research Centre, School of Mathematics and Physics, Queen's University Belfast, Belfast, UK
| | | | - Ling Xu
- He Eye Specialist Hospital, Shenyang, China
| | - Wei He
- He Eye Specialist Hospital, Shenyang, China
| | - Sile Yu
- He University, Shenyang, China
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14
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Zhang S, Wang Q, Qu M, Chen Q, Bai X, Zhang Z, Zhou Q, Xie L. Hyperglycemia Induces Tear Reduction and Dry Eye in Diabetic Mice through the Norepinephrine-α 1 Adrenergic Receptor-Mitochondrial Impairment Axis of Lacrimal Gland. THE AMERICAN JOURNAL OF PATHOLOGY 2023; 193:913-926. [PMID: 37088455 DOI: 10.1016/j.ajpath.2023.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/09/2023] [Accepted: 03/28/2023] [Indexed: 04/25/2023]
Abstract
Dry eye syndrome is a common complication in diabetic patients with a prevalence of up to 54.3%. However, the pathogenic mechanisms underlying hyperglycemia-induced tear reduction and dry eye remain less understood. The present study indicated that both norepinephrine (NE) and tyrosine hydroxylase levels were elevated in the lacrimal gland of diabetic mice, accompanied by increased Fos proto-oncogene (c-FOS)+ cells in the superior cervical ganglion. However, the elimination of NE accumulation by surgical and chemical sympathectomy significantly ameliorated the reduction in tear production, suppressed abnormal inflammation of the lacrimal gland, and improved the severity of dry eye symptoms in diabetic mice. Among various adrenergic receptors (ARs), the α1 subtype played a predominant role in the regulation of tear production, as treatments of α1AR antagonists improved tear secretion in diabetic mice compared with βAR antagonist propranolol. Moreover, the α1AR antagonist alfuzosin treatment also alleviated functional impairments of the meibomian gland and goblet cells in diabetic mice. Mechanically, the α1AR antagonist rescued the mitochondrial bioenergetic deficit, increased the mitochondrial DNA copy numbers, and elevated the glutathione levels of the diabetic lacrimal gland. Overall, these results deciphered a previously unrecognized involvement of the NE-α1AR-mitochondrial bioenergetics axis in the regulation of tear production in the lacrimal gland, which may provide a potential strategy to counteract diabetic dry eye by interfering with the α1AR activity.
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Affiliation(s)
- Sai Zhang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute of Shandong First Medical University, Qingdao, China
| | - Qun Wang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute of Shandong First Medical University, Qingdao, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China
| | - Mingli Qu
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute of Shandong First Medical University, Qingdao, China
| | - Qing Chen
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Xiaofei Bai
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute of Shandong First Medical University, Qingdao, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China
| | | | - Qingjun Zhou
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute of Shandong First Medical University, Qingdao, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
| | - Lixin Xie
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute of Shandong First Medical University, Qingdao, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
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15
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Zhmud T, Malachkova N, Redjak R, Costagliola C, Concilio M, Drozhzhyna G, Toro Mario D, Veretelnyk S. Dry eye disease severity and impact on quality of life in type II diabetes mellitus. Front Med (Lausanne) 2023; 10:1103400. [PMID: 36923012 PMCID: PMC10009182 DOI: 10.3389/fmed.2023.1103400] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 02/07/2023] [Indexed: 03/03/2023] Open
Abstract
Aim To assess the severity of dry eye disease (DED) in humans, its impact on quality of life (QoL) and to grade the damage incurred by the anterior ocular surface in patients diagnosed with type 2 diabetes mellitus (T2DM). Patients and methods Forty-six patients (mean age ± SD = 63.8 ± 6.7 years) diagnosed with T2DM were enrolled in the experimental group and 26 healthy individuals constituted the control group (67.9 ± 8.9 years). The diagnosis and gradation of DED were conducted in accordance with the International Task Force severity grading scheme. Disease-specific questionnaires were used to obtain the Ocular Surface Disease Index (OSDI) and assess the negative effects of the disease on the patient's QoL. The severity of conjunctival redness and corneal/conjunctival staining was assessed by Efron and Oxford scales, respectively. Results According to OSDI scores, the entire experimental group presented symptoms of DED: 54.4% were diagnosed with mild DED and 46.6% with moderately severe DED. No cases of severe DED were diagnosed in either the experimental or control group. In the control group, 57.7% of individuals did not have the disease. A significant difference between the experimental and control groups was recorded for both OSDI scores (p < 0.01) and health-related QoL (p < 0.01). It was observed that keratopathy influenced the mean OSDI values of patients. The mean OSDI value was 25.14 ± 3 in the experimental group diagnosed with keratopathy, 19.3 ± 3.5 in the subgroup with no indications of corneal injury (p = 0.000002), and 13.0 ± 3.0 in the control group (p < 0.000002). Based on the DEWS scheme, a grade I severity level was observed in 46% of control subjects and 33% of patients diagnosed with T2DM (p = 0.4915); grades II and III were detected in the bulk of the experimental group (p = 0.0051; p = 0.1707). None of the subjects in the control or experimental groups manifested grade IV severity of DED. Conclusion In comparison to healthy adults, DED adversely impacts the QoL of type 2 DM patients, regardless of the disease's association with keratopathy.
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Affiliation(s)
- Tetiana Zhmud
- Department of Ophthalmology, National Pirogov Memorial Medical University, Vinnytsia, Ukraine
| | - Natalia Malachkova
- Department of Ophthalmology, National Pirogov Memorial Medical University, Vinnytsia, Ukraine
| | - Robert Redjak
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, Lublin, Poland
| | - Ciro Costagliola
- Eye Clinic, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Marina Concilio
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
| | - Galyna Drozhzhyna
- Department of Corneal Pathology, SI "Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine", Odesa, Ukraine
| | - Damiano Toro Mario
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, Lublin, Poland.,Eye Clinic, Public Health Department, University of Naples Federico II, Naples, Italy
| | - Svitlana Veretelnyk
- Department of Ophthalmology, National Pirogov Memorial Medical University, Vinnytsia, Ukraine
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16
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Silva-Viguera MC, Pérez-Barea A, Bautista-Llamas MJ. Tear film layers and meibomian gland assessment in patients with type 1 diabetes mellitus using a noninvasive ocular surface analyzer: a cross-sectional case–control study. Graefes Arch Clin Exp Ophthalmol 2022; 261:1483-1492. [PMID: 36512089 PMCID: PMC10148784 DOI: 10.1007/s00417-022-05934-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/24/2022] [Accepted: 11/27/2022] [Indexed: 12/15/2022] Open
Abstract
Abstract
Purpose
To assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM).
Methods
Eighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer’s I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested.
Results
The T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups.
Conclusion
Patients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations.
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Affiliation(s)
- María-Carmen Silva-Viguera
- Department of Physics of Condensed Matter, Optics Area, Physics Faculty, University of Seville, Reina Mercedes St, Seville, Spain
- Vision Research Group (CIVIUS), University of Seville, Seville, Spain
| | - Alicia Pérez-Barea
- Department of Physics of Condensed Matter, Optics Area, Physics Faculty, University of Seville, Reina Mercedes St, Seville, Spain
| | - María-José Bautista-Llamas
- Department of Physics of Condensed Matter, Optics Area, Physics Faculty, University of Seville, Reina Mercedes St, Seville, Spain.
- Vision Research Group (CIVIUS), University of Seville, Seville, Spain.
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17
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Almohammed BA, Alnafeesah AA, Aldharman SS, Alenzi MH, Mahjari AA, Albalawi FA, Amer KA, Alkhathami GH, Al Taisan AA. Prevalence and Severity of Dry Eye Disease Symptoms Among Diabetics: A Nationwide Survey. Cureus 2022; 14:e30981. [DOI: 10.7759/cureus.30981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2022] [Indexed: 11/07/2022] Open
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18
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Pan LY, Kuo YK, Chen TH, Sun CC. Dry eye disease in patients with type II diabetes mellitus: A retrospective, population-based cohort study in Taiwan. Front Med (Lausanne) 2022; 9:980714. [PMID: 36082275 PMCID: PMC9445241 DOI: 10.3389/fmed.2022.980714] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 07/29/2022] [Indexed: 11/18/2022] Open
Abstract
Purpose To investigate the risk and protective factors of dry eye disease (DED) in patients with type II diabetes mellitus (DM). Design A retrospective cohort study using Chang- Gung research database collecting data from 2005 to 2020. Methods Patients with type II DM were included, and those with previous ocular diseases were excluded. Ten thousand twenty nine developed DED (DED group), and 142,491 didn't (non-DED group). The possible risk and protective factors were compared and analyzed using the logistic regression model. Results A majority of the DED group were female with significantly higher initial and average glycated hemoglobin levels, and higher incidence of diabetic neuropathy and retinopathy. In conditional logistic regression model, advanced age was a risk factor. After adjusting for sex, age, and DM duration; average glycated hemoglobin level, diabetic neuropathy, retinopathy, and nephropathy with eGFR 30 ~ 59 and intravitreal injection, vitrectomy, pan-retinal photocoagulation, and cataract surgery were contributing factors of DED. Considering antihyperglycemic agents, DPP4 inhibitor, SGLT2 inhibitor, GLP-1 agonist, and insulin monotherapy and dual medications combining any two of the aforementioned agents were protective factors against DED compared with metformin alone. In the monotherapy group, SLGT2 inhibitor had the lowest odds ratio, followed by GLP1 agonist, DPP4 inhibitor, and insulin. Conclusions DED in patients with DM is associated with female sex, advanced age, poor diabetic control, microvascular complications and receiving ocular procedures. GLP-1 agonist, SGLT-2 inhibitor, DPP4 inhibitor, and insulin are superior to metformin alone in preventing DM-related DED. A prospective randomized control trial is warranted to clarify our results.
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Affiliation(s)
- Li-Yen Pan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yu-Kai Kuo
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Tien-Hsing Chen
- Department of Cardiology, Chang Gung Memorial Hospital, Keelung, Taiwan
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
- Biostatistical Consultation Center of Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chi-Chin Sun
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- *Correspondence: Chi-Chin Sun
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Huang R, Su C, Fang L, Lu J, Chen J, Ding Y. Dry eye syndrome: comprehensive etiologies and recent clinical trials. Int Ophthalmol 2022; 42:3253-3272. [PMID: 35678897 PMCID: PMC9178318 DOI: 10.1007/s10792-022-02320-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 04/18/2022] [Indexed: 12/07/2023]
Abstract
Dry eye syndrome (DES) is multifactorial and likely to be a cause of concern more so than ever given the rapid pace of modernization, which is directly associated with many of the extrinsic causative factors. Additionally, recent studies have also postulated novel etiologies that may provide the basis for alternative treatment methods clinically. Such insights are especially important given that current approaches to tackle DES remains suboptimal. This review will primarily cover a comprehensive list of causes that lead to DES, summarize all the upcoming and ongoing clinical trials that focuses on treating this disease as well as discuss future potential treatments that can improve inclusivity.
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Affiliation(s)
- Ruojing Huang
- Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Huangpu Avenue West 613, Tianhe District, Guangzhou, 510630, China
| | - Caiying Su
- Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Huangpu Avenue West 613, Tianhe District, Guangzhou, 510630, China
| | - Lvjie Fang
- Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Huangpu Avenue West 613, Tianhe District, Guangzhou, 510630, China
| | - Jiaqi Lu
- Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Huangpu Avenue West 613, Tianhe District, Guangzhou, 510630, China
| | - Jiansu Chen
- Institute of Ophthalmology, Medical College, Jinan University, Huangpu Avenue West 601, Tianhe District, Guangzhou, 510632, China.
| | - Yong Ding
- Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Huangpu Avenue West 613, Tianhe District, Guangzhou, 510630, China.
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20
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Bu Y, Shih KC, Tong L. The ocular surface and diabetes, the other 21st Century epidemic. Exp Eye Res 2022; 220:109099. [DOI: 10.1016/j.exer.2022.109099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 04/25/2022] [Accepted: 04/26/2022] [Indexed: 11/25/2022]
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21
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Fang W, Lin ZX, Yang HQ, Zhao L, Liu DC, Pan ZQ. Changes in corneal nerve morphology and function in patients with dry eyes having type 2 diabetes. World J Clin Cases 2022; 10:3014-3026. [PMID: 35647133 PMCID: PMC9082719 DOI: 10.12998/wjcc.v10.i10.3014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/24/2021] [Accepted: 03/15/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dry eye syndrome (DES) is a common disease with various clinical manifestations. DES had a significant association with diabetes. Blink reflex (BR) is also known as trigeminal nerve facial reflex. The stimulation of corneal nerves is one of the origins of BR stimulation. The parasympathetic fibers sent out through the facial nerve are the outlet of tear reflexes. BR can be used to assess the function of the corneal nerve closed-loop; however, whether the BR changes in these patients is unclear. AIM To understand the morphology and function of the corneal nerve in patients with dry eyes having diabetes or not. METHODS This study enrolled 131 patients who visited the inpatient and outpatient services of ophthalmology and endocrinology departments between January 2019 to August 2020 with subjective symptoms of dry eyes and non-dry eye reasons, as well as volunteers such as colleagues. The patients were divided into four groups: DEwDM, with dry eyes having type 2 diabetes mellitus (T2DM); DMnDE, with T2DM not having dry eyes; DEnDM, with dry eyes not having diabetes; and nDMnDE, with neither dry eyes nor diabetes. The tear film break-up time, Schirmer I test, in vivo confocal microscopy, and BR were performed. RESULTS The DEwDM, DMnDE, DEnDM, and nDMnDE groups included 56, 22, 33, and 20 patients, respectively. Sex and age were not statistically different among the four groups. The nerve fiber length (NFL) of patients in the DEwDM, DEnDM, and DMnDE groups reduced (P < 0.001, P = 0.014, and P = 0.001, respectively). No significant difference in corneal nerve fiber density (NFD) (P = 0.083) and corneal nerve branch density (NBD) (P = 0.195) was found among the four groups. The R1 Latency of blink reflexes increased only in the DEwDM group (P = 0.008, P = 0.001, P < 0.001, compared with the DMnDE, DEnDM, and nDMnDE groups, respectively). The NBD and R1 Latency were different between DEwDM and DEnDM groups in patients with moderate and severe dry eyes. CONCLUSION The corneal nerve morphology changed in patients with dry eyes or diabetes, or with both, while the function of corneal nerve closed-loop reduced only in those with dry eyes and diabetes.
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Affiliation(s)
- Wei Fang
- Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
- Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, Beijing, China
| | - Zhong-Xi Lin
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Hui-Qing Yang
- Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Lei Zhao
- Department of Endocrinology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Da-Chuan Liu
- Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Zhi-Qiang Pan
- Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, Beijing, China
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22
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Feldman-Billard S, Dupas B. Eye disorders other than diabetic retinopathy in patients with diabetes. DIABETES & METABOLISM 2021; 47:101279. [PMID: 34534696 DOI: 10.1016/j.diabet.2021.101279] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/18/2021] [Accepted: 08/29/2021] [Indexed: 10/20/2022]
Abstract
AIM While diabetic retinopathy is the most specific complication of chronic hyperglycaemia, numerous other ocular conditions also can involve the eyes of people with diabetes. Cataract, glaucoma, age-related macular degeneration, retinal vascular occlusion, and acute ischaemic optic neuropathy combine to impair vision in people with diabetes, especially when they are old. This report provides a critical analysis and an overview of the current knowledge of the main ocular disorders (excluding diabetic retinopathy) and their association in patients with diabetes. METHODS A literature search strategy was conducted for all English-language literature with a systematic review of key references until 2021. RESULTS Patients with diabetes have a high-to-moderate increased risk for most of the usual ocular disorders we reviewed with the exception of age-related macular degeneration. Exposure to chronic hyperglycaemia promotes the development of many eye disorders while acute glucose changes are involved in refractive disorders, diabetic papillopathy and acute cataract. CONCLUSION Diabetes, beyond diabetic retinopathy, increases the risk of numerous eye disorders leading to low vision with implications for daily diabetes management. Even in the absence of clearly demonstrated benefit from glucose control in all eye conditions, achieving good glycaemic control and adherence to diabetes treatment will likely help avoid an additional risk of visual impairment in people with diabetes. In perspective, interesting findings suggesting a preventive effect of metformin use on age-related macular degeneration occurrence justify further studies.
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Affiliation(s)
- Sylvie Feldman-Billard
- Service de Médecine Interne, CHNO des Quinze-Vingts, 28 rue de Charenton, 75571 Paris Cedex 12, France.
| | - Bénédicte Dupas
- Centre Ophtalmologique Sorbonne Saint-Michel, Paris, France; Service d'Ophtalmologie, Hôpital Lariboisière, Paris, France
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23
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Impact of Graves Disease on Ocular Surface and Corneal Epithelial Thickness in Patients With and Without Graves Orbitopathy. Cornea 2021; 41:443-449. [PMID: 34029245 DOI: 10.1097/ico.0000000000002753] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/14/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE Our aim was to assess ocular surface and tear film stability and corneal epithelial thickness (CET) in patients with Graves disease (GD) with and without Graves orbitopathy (GO). METHODS This study included healthy age-matched controls and patients with GD. Symptoms (Ocular Surface Disease Index questionnaire) and signs (schirmer test and tear breakup time test) of dry eye disease were determined, according to the International Dry Eye Workshop II criteria of DED. CET map was also assessed. RESULTS Twenty-four eyes were included in the control group, with a mean age of 41.00 ± 13.65 years, and 34 in the GD group, 18 with GO and 16 without GO, with a mean age of 44.44 ± 13.95 and 45.75 ± 10.59 years, respectively. All patients with GO had inactive disease (mean clinical activity score: 1.33 ± 0.69). Patients with GD had higher proportion of clinical diagnosis of dry eye disease (GO vs. GD without GO vs. controls: 77.77% vs. 75.00% vs. 4.17%), with higher Ocular Surface Disease Index (GO vs. GD without GO vs. controls: 15.44 vs. 15.06 vs. 9.88) and lower tear breakup time test (GO vs. GD without GO vs. controls: 6.33 s vs. 7.25 s vs. 11.63 s). Superior CET was lower in patients with GD (P < 0.05). No differences were found between patients with and without GO (P > 0.05). CONCLUSIONS GD negatively influenced ocular surface and CET, with a higher level of eye dryness and corneal thinning regardless of GO status, suggesting that subclinical chronic inflammation may play a role in the pathogenesis of tear film and ocular surface stability.
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24
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Qu M, Wan L, Dong M, Wang Y, Xie L, Zhou Q. Hyperglycemia-induced severe mitochondrial bioenergetic deficit of lacrimal gland contributes to the early onset of dry eye in diabetic mice. Free Radic Biol Med 2021; 166:313-323. [PMID: 33705960 DOI: 10.1016/j.freeradbiomed.2021.02.036] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 02/18/2021] [Accepted: 02/28/2021] [Indexed: 12/26/2022]
Abstract
Dry eye and diabetic keratopathy represent the major diabetic complications in ocular surface. Here we found that diabetic mice exhibited the early onset of reduced tear secretion and lacrimal gland weight compared to the symptoms of diabetic keratopathy. Considering to the high bioenergetic needs in lacrimal gland and cornea, we hypothesized that hyperglycemia may cause different severity of mitochondrial bioenergetic deficit between them. Through the measurement of oxygen consumption rate (OCR) and basal extracellular acidification rate (ECAR), we found the apparent alterations of mitochondrial bioenergetic profiles in diabetic lacrimal gland and cornea, accompanied with the mtDNA damage and copy number reduction, as well as the reduced glutathione content. Comparative analysis revealed that mouse lacrimal gland cells exhibited 2-3 folds higher of basal, ATP production, maximal OCR and basal ECAR than corneal epithelial cells in normoglycemia. However, the differences were slightly significant or even not detected in hyperglycemia. Accordingly, the mitochondrial bioenergetic metabolism of lacrimal gland was more compromised than that of corneal epithelium in diabetic mice. Through the administration of mitochondrial-targeted antioxidant SkQ1, the severity of dry eye and diabetic keratopathy was significantly attenuated with the improved mitochondrial function. These results indicate that the susceptibility of mitochondrial bioenergetic deficit in diabetic lacrimal gland may contribute to the early onset of dry eye, while mitochondria-targeted antioxidant possesses therapeutic potential for diabetic dry eye and keratopathy.
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Affiliation(s)
- Mingli Qu
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Lei Wan
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China
| | - Muchen Dong
- Eye Hospital of Shandong First Medical University, Jinan, China
| | - Yidi Wang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Lixin Xie
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
| | - Qingjun Zhou
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
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25
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De Freitas GR, Ferraz GAM, Gehlen M, Skare TL. Dry eyes in patients with diabetes mellitus. Prim Care Diabetes 2021; 15:184-186. [PMID: 32057723 DOI: 10.1016/j.pcd.2020.01.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 12/28/2019] [Accepted: 01/31/2020] [Indexed: 11/29/2022]
Abstract
Dry eyes may be caused by impairment in the tear production or excessive tear evaporation and are associated with photophobia, red eyes, vision impairment, local pain and pruritus. It has been described that patients with Diabetes Mellitus (DM) may have a higher prevalence of dry eyes than normal population. This is a case control study of 120 patients with Diabetes Mellitus (DM) and 120 paired controls aiming to compare their prevalence of dry eyes (by the Schirmer test) and its severity (measured by OSDI or Ocular Surface Disease Index) as well as their association with diseases' clinical variables. We found that 38.3% of DM patients had dry eyes, a prevalence that was higher than controls (p = 0.02). At univariate analysis, they were found to be more common in older individuals (p = 0.001) with type 2 diabetes (p = 0.001) and in those using metformin (p = 0.001). A multivariate linear regression showed that metformin use was the only independent variable associated with dry eyes. When patients with dry eyes with and without DM were compared, no differences in the symptom's intensity were found.
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26
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Chu EPF, Cho CHH, Lee WJ, Lee IT, Cheng IF, Kuo TC, Chen RY, Sheu WHH, Shen CN. Generation of three induced pluripotent stem cell lines from type 2 diabetic patients with ocular complications. Stem Cell Res 2020; 49:102109. [PMID: 33370876 DOI: 10.1016/j.scr.2020.102109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 11/28/2020] [Indexed: 12/01/2022] Open
Abstract
Retinopathy is a well-known ocular complication that occurs in patients with type 2 diabetes (T2D). Recent evidence also indicates that diabetic patients have an increased prevalence of dry eye syndrome. However, the etiologies of both diabetic retinopathy (DR) and dry eye disease are complex, and their associations with T2D remains to be fully understood. Patient-derived human induced pluripotent stem cells (hiPSCs) enable the generation of disease-specific retinal tissues such as retinal pigment epithelium and lacrimal gland to model disease pathogenesis. Here, we describe the establishment of three hiPSC lines from T2D patients with PDR or dry eye disease.
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Affiliation(s)
| | | | - Wen-Jane Lee
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - I-Te Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - I-Fen Cheng
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Tzu-Chien Kuo
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ruei-Ying Chen
- Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wayne Huey-Herng Sheu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chia-Ning Shen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
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27
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Zou X, Wang S, Zhang P, Lu L, Zou H. Quantitative Proteomics and Weighted Correlation Network Analysis of Tear Samples in Adults and Children With Diabetes and Dry Eye. Transl Vis Sci Technol 2020; 9:8. [PMID: 33344052 PMCID: PMC7718812 DOI: 10.1167/tvst.9.13.8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 10/20/2020] [Indexed: 12/18/2022] Open
Abstract
Purpose Diabetics are more prone to suffer from dry eye (DE). The ages of diabetes are decreasing, so ocular surface status in younger generations is worthy of attention. We used tandem mass tag (TMT)–labeled proteomics and weighted correlation network analysis (WGCNA) to identify differentially expressed proteins in the tear proteome of adults and children with diabetic DE. Methods Study subjects were divided into six groups of 10, including three groups each for adults and children. The adult groups included diabetics with DE (A), diabetics without DE (B), and normal controls (C); the corresponding groups of children were identified as (D), (E), and (F). DE tests were performed on all subjects. We extracted total proteins and labeled them with TMTs for analysis. WGCNA was used to recognize hub genes. Results Tear film function was poorer in patients with diabetic DE. In adults, 1922 proteins were identified, and WGCNA analysis revealed three hub genes related to diabetic DE. For children, 2709 proteins were identified, and WGCNA analysis identified one hub gene related to diabetic DE. Kyoto Encyclopedia of Genes and Genomes analysis found similarities among metabolic pathways involved in differential expression of proteins in adult and child tear samples. Conclusions The pathogenesis of diabetic DE was highly similar in adults and children. The differentially expressed tear proteins in type 2 diabetes of adults and children was associated with inflammation, immune factors, and lipid metabolism. Translational Relevance Our findings found high similarities in the pathogenesis of diabetic DE in adults and children.
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Affiliation(s)
- Xinrong Zou
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, China.,Department of Ophthalmology, Fengcheng Hospital, Fengxian District, Shanghai, China
| | - Shanshan Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Pei Zhang
- Department of Ophthalmology, Gonghui Hospital, Jingan District, Shanghai, China
| | - Lina Lu
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, China
| | - Haidong Zou
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China
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28
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Manchikanti V, Kasturi N, Rajappa M, Gochhait D. Ocular surface disorder among adult patients with type II diabetes mellitus and its correlation with tear film markers: A pilot study. Taiwan J Ophthalmol 2020; 11:156-160. [PMID: 34295621 PMCID: PMC8259518 DOI: 10.4103/tjo.tjo_56_20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 07/26/2020] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The purpose is to study the ocular surface changes among patients with diabetes mellitus (DM) and to correlate them with tear film markers such as insulin-like growth factor (IGF)-1, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α levels. MATERIALS AND METHODS The study was carried out on diabetic patients (>5 years' duration) and healthy age- and gender-matched controls with 21 individuals in each group. Schirmer's test for basal and reflex tear secretion, tear film breakup time (TBUT) for tear stability, ocular staining score (OSS) for dryness severity, ocular surface disease index (OSDI) for symptomatic assessment of dryness and conjunctival impression cytology (IC) for epithelial cell integrity, keratinization, squamous metaplasia, and goblet cell density was studied. Thirty microliters of tears were collected to test IGF-1, IL-1β, and TNF-α levels. RESULTS Patients with DM showed significantly low Schirmer's, TBUT, and OSS values than controls. OSDI score showed moderate-severe dryness in patients with DM and only mild symptoms among controls. An abnormal IC score was seen among cases and controls. The level of TNF-α was significantly increased in patients with DM and positively correlated with Schirmer and TBUT values (P < 0.05). CONCLUSION Dry eye is more prevalent in patients with DM compared to controls as evidenced by poor OSDI score, Schirmer, TBUT, and OSS. TNF-α in the tears of patients with DM is a useful marker that showed a good correlation with Schirmer, TBUT, and dry eye symptoms. IC could not conclusively differentiate the dry eye status in patients with DM from controls.
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Affiliation(s)
- Vijayakumari Manchikanti
- Department of Ophthalmology, Jawaharlal Postgraduate Medical Education and Research, Puducherry, India
| | - Nirupama Kasturi
- Department of Ophthalmology, Jawaharlal Postgraduate Medical Education and Research, Puducherry, India
| | - Medha Rajappa
- Department of Biochemistry, Jawaharlal Postgraduate Medical Education and Research, Puducherry, India
| | - Debasis Gochhait
- Department of Pathology, Jawaharlal Postgraduate Medical Education and Research, Puducherry, India
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29
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Fogagnolo P, Melardi E, Tranchina L, Rossetti L. Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial. BMC Ophthalmol 2020; 20:315. [PMID: 32738875 PMCID: PMC7395393 DOI: 10.1186/s12886-020-01584-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 07/28/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy. METHODS This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups. RESULTS 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high. CONCLUSIONS Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect. TRIAL REGISTRATION Trial registration NCT03906513 , retrospectively registered on 08 April 2019.
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Affiliation(s)
- Paolo Fogagnolo
- Eye Clinic, Università degli Studi di Milano; ASST Santi Paolo e Carlo, San Paolo Hospital, Via di Rudini', 8, 20142, Milan, Italy.
| | - Ettore Melardi
- Eye Clinic, Università degli Studi di Milano; ASST Santi Paolo e Carlo, San Paolo Hospital, Via di Rudini', 8, 20142, Milan, Italy
| | - Laura Tranchina
- Eye Clinic, Università degli Studi di Milano; ASST Santi Paolo e Carlo, San Paolo Hospital, Via di Rudini', 8, 20142, Milan, Italy.,ASST Rhodense, Garbagnate Milanese Hospital, Milan, Italy
| | - Luca Rossetti
- Eye Clinic, Università degli Studi di Milano; ASST Santi Paolo e Carlo, San Paolo Hospital, Via di Rudini', 8, 20142, Milan, Italy
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30
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Mu PY, Chu CC, Yu D, Shao Y, Zhao SZ. PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland. Int J Ophthalmol 2020; 13:860-869. [PMID: 32566495 PMCID: PMC7270247 DOI: 10.18240/ijo.2020.06.02] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 04/10/2020] [Indexed: 12/12/2022] Open
Abstract
AIM To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor (PPAR) family in lacrimal gland dysfunction under conditions of desiccating stress or diabetes. METHODS Quantitative polymerase chain reaction (qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups: a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time (BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research, qPCR was used to examine the expression level of PPARγ, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), sirtuin 1 (Sirt1), myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β) in the lacrimal glands. RESULTS PPARα and PPARβ/δ were mainly expressed in the conjunctiva and the lacrimal gland, respectively. However, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARβ/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT, and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased (P<0.05), expression of Sirt1 also decreased (P<0.01), whereas expression of TNF-α, IL-1β, IL-6, MyD88, and TGF-β increased (P<0.05). CONCLUSION Among PPARs, PPARγ might play a dominant role in the regulation of metabolic- and inflammatory-signaling pathways on the ocular surfaces and in lacrimal glands. Down-regulation of PPARγ is highly relevant to lacrimal gland dysfunction under desiccating-stress and diabetic conditions. PPARγ, thus, is a potential therapeutic target in the treatment of environment- or diabetes-induced dry eye diseases.
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Affiliation(s)
- Peng-Yue Mu
- Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
| | - Chen-Chen Chu
- Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
| | - Di Yu
- Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
| | - Yan Shao
- Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
| | - Shao-Zhen Zhao
- Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
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31
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Li T, Xu Y, Shi Y, Chen J, Lin S, Zhu J, Xu X, Lu L, Zou H. Genome-wide analysis of DNA methylation identifies S100A13 as an epigenetic biomarker in individuals with chronic (≥ 30 years) type 2 diabetes without diabetic retinopathy. Clin Epigenetics 2020; 12:77. [PMID: 32493412 PMCID: PMC7268721 DOI: 10.1186/s13148-020-00871-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/21/2020] [Indexed: 01/13/2023] Open
Abstract
Background This study aimed to determine the epigenetic biomarkers of diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). This retrospective study is based on the Shanghai Xinjing community prevention and treatment administrative system of chronic diseases. The subjects enrolled herein were T2DM patients who had undergone long-term follow-up evaluation in the system. Two consecutive studies were conducted. In the discovery cohort, among 19 subjects who had developed DR with a DM duration < 3 years and 21 subjects without DR > 30 years after being diagnosed with DM, an Infinium Human Methylation 850 Beadchip was used to identify differential methylation regions (DMRs) and differential methylation sites (DMSs). The function of the genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis, and pathway network analysis. In the replication cohort, 87 DR patients with a short DM duration and 89 patients without DR over a DM duration > 20 years were compared to assess the association between DMSs and DR upon pyrosequencing. Results A total of 34 DMRs were identified. Genes containing DMSs with the top 5 highest beta value differences between DR and non-DR participants were located on chromosome 1 and were present in the S100A13 gene, which was associated with 71 GO terms. Two S100A13 gene sites, i.e., cg02873163 and cg11343894, displayed a good correlation with DR on pyrosequencing. Conclusions DMSs in the S100A13 gene may be potential biomarkers of DR.
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Affiliation(s)
- Tao Li
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yi Xu
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yongyong Shi
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), the Collaborative Innovation Center for Brain Science, Shanghai Jiaotong University, Shanghai, China
| | - Jianhua Chen
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Senlin Lin
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jianfeng Zhu
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xian Xu
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Lina Lu
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Haidong Zou
- Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China. .,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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Tear Levels of IGFBP-3: A Potential Biomarker for Diabetic Nerve Changes in the Cornea. Eye Contact Lens 2020; 46:319-325. [DOI: 10.1097/icl.0000000000000700] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Li B, Tian Y, Wang S. The correlation of cytokines and sensory hypersensitivity in mild dry eye patients characterized by symptoms outweighing signs. Mol Vis 2020; 26:359-369. [PMID: 32476816 PMCID: PMC7245605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 05/07/2020] [Indexed: 11/25/2022] Open
Abstract
PURPOSE To explore the correlation of tear and conjunctival cytokines and sensory hypersensitivity in mild dry eye (MDE) patients characterized by symptoms outweighing signs (DESOS). METHODS The subjects comprised 39 patients with MDE characterized by DESOS, 18 patients with common MDE (CMDE), and 15 healthy controls. The patients with DESOS were randomly subdivided into two groups; the C-DESOS group received artificial tears only, and the G-DESOS group received artificial tears and 0.1% fluorometholone eye drops three times a day. Symptoms were assessed using the Ocular Surface Disease Index (OSDI) and the Neuropathic Pain Symptoms Inventory modified for Eye (NPSI-E) questionnaire. Ocular examinations and in vivo confocal microscopy (IVCM) were also employed. Tear and conjunctival cytokines were measured using Multiplex or RT-PCR on Days 0, 7, and 30. The correlation between the expression of cytokines and hypersensitivity status was analyzed. RESULTS Compared with the CMDE and control groups, the DESOS groups showed a significant increase in symptom scores and in the ratio of symptoms versus signs. IL-1 β, IL-2, IL-6, and TNF-α in tears and conjunctiva increased in the DESOS groups compared to the CMDE and control groups, indicating a high correlation with hypersensitivity status in the DESOS groups. Glucocorticoid treatment significantly decreased the level of cytokines in tears and conjunctiva in the G-DESOS group and subsequently ameliorated the symptoms. CONCLUSIONS Tear and conjunctival cytokines, including IL-1 β, IL-2, IL-6, and TNF-α, were correlated with sensory hypersensitivity status in the DESOS groups, suggesting they play an important role in the discordance of symptoms outweighing signs.
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Zou X, Zhang P, Xu Y, Lu L, Zou H. Quantitative Proteomics and Weighted Correlation Network Analysis of Tear Samples in Type 2 Diabetes Patients Complicated with Dry Eye. Proteomics Clin Appl 2020; 14:e1900083. [PMID: 31951085 DOI: 10.1002/prca.201900083] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 12/30/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE Diabetic patients are more likely to experience dry eye (DE). TMT-based proteomics and WGCNA are used to identify the differentially expressed proteins in tear proteome of type 2 diabetes with DE. The aim is to provide a molecular basis for exploring possible mechanisms underlying the pathogenesis of diabetic DE. EXPERIMENTAL DESIGN Subjects are divided into four groups (ten in each): type 2 diabetes with DE; type 2 diabetes without DE; non-diabetes with DE and normal controls. All subjects undergo DE tests. Total proteins are extracted and quantitatively labeled with TMT, then analyzed using liquid chromatography-mass spectrometry. WGCNA is used to identify the hub genes. Finally, differentially expressed proteins are validated by ELISA. RESULTS A total of 1922 proteins are identified, of which 1814 contain quantitative information. Ultimately, 650 of these proteins yield quantitative values. WGCNA performed on these 650 proteins reveal four distinct hub genes of diabetic DE. CONCLUSIONS AND CLINICAL RELEVANCE DE is associated with the differential expression of tear proteins in type 2 diabetes. Inflammation, immune factors, and lipid metabolism may play a role in the development of diabetic DE. LTF, LYZ, ZAG, and DNAJC3 have the potential to be the biomarkers of DE in diabetes.
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Affiliation(s)
- Xinrong Zou
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, 200040, China.,Department of Ophthalmology, Fengcheng Hospital, Fengxian District, Shanghai, 201411, China
| | - Pei Zhang
- Department of Ophthalmology, Gonghui Hospital, Jingan District, Shanghai, 200041, China
| | - Yi Xu
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China
| | - Lina Lu
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China
| | - Haidong Zou
- Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, 200040, China.,Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China
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Liu R, Zhao Y, Wu Y, Guo M, Duan Y, Ye J, Lu X. Individualized Chinese medicine for the treatment of diabetic patients with dry eye disease: A single-case randomized controlled protocol. Medicine (Baltimore) 2020; 99:e18459. [PMID: 31895776 PMCID: PMC6946556 DOI: 10.1097/md.0000000000018459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The high incidence of Diabetes mellitus (DM) has become a serious challenge for the global epidemic. Increased blood glucose leads to abnormal ocular surface structure and metabolic disorder in patients. DM is a high-risk factor for dry eye disease (DED), with high incidence and increased difficulty in treatment. The disease can cause discomfort, visual impairment, tear film instability and ocular surface damage, and even cause corneal erosion in severe cases, which has a serious impact on people's daily life. Traditional Chinese Medicine (TCM) plays an important role in the evaluation and treatment of DM and its complications. However, whether TCM treatment could improve the treatment efficacy of DM suffering from DED remains poorly understood. OBJECTIVE To investigate the curative effect of TCM for the alleviation of clinical symptoms in Diabetic patients with DED, and to evaluate its long-term efficacy. METHODS This trial is a single-case randomized, single-blind, placebo-controlled study. A total of 12 subjects will be recruited in this trial. The trial is divided into three cycles, and one cycle has 2 treatment periods. There is a washout period at each adjacent treatment stage. TCM individualized treatment and placebo will be randomized during the treatment period. The test period will last for 29 weeks, with 4 weeks for each treatment period and 1 week for each washout period to minimize carryover effects. Subjects will be selected by the researcher strictly in accordance with the inclusion and exclusion criteria. The outcomes will evaluate the efficacy of treatment by changes in the various observation indicators. DISCUSSION This study will realize a patient-centered outcome approach necessary to provide clinical researchers with the evidence that TCM treatment can effectively improve the objective indicators of the eye and systemic symptoms in Diabetic patients with DED. TRIAL REGISTRATION This study has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, No. ChiCTR1900024481), (October, 2019).
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Affiliation(s)
- Ruibao Liu
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
| | - Ying Zhao
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
| | - Yanxia Wu
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
| | - Minglu Guo
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
| | - Yu Duan
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
| | - Jianbin Ye
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
| | - Xuejing Lu
- Chengdu University of Traditional Chinese Medicine, Academy of Ophthalmology
- Yinhai Eye Hospital affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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Two-Year Incidence and Associated Factors of Dry Eye Among Residents in Shanghai Communities With Type 2 Diabetes Mellitus. Eye Contact Lens 2020; 46 Suppl 1:S42-S49. [DOI: 10.1097/icl.0000000000000626] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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PPARG Polymorphisms Are Associated with Unexplained Mild Vision Loss in Patients with Type 2 Diabetes Mellitus. J Ophthalmol 2019; 2019:5284867. [PMID: 31915541 PMCID: PMC6930731 DOI: 10.1155/2019/5284867] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 11/11/2019] [Accepted: 11/20/2019] [Indexed: 01/17/2023] Open
Abstract
Objectives To investigate whether the presence of peroxisome proliferator-activated receptor gamma (PPARG) gene polymorphisms is associated with unexplained mild visual impairment (UMVI) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 135 T2DM residents with UMVI and 133 with normal vision (NV; best-corrected visual acuity ≥ 20/25 in both eyes) were enrolled. UMVI was defined as best-corrected visual acuity (BCVA) < 20/25 and ≥ 20/63 in both eyes, with no visual impairment-causing diseases found. Four PPARG gene single-nucleotide polymorphisms (SNPs) (rs3856806, rs1801282, rs709158, and rs10865710) were assessed with the HAPLOVIEW 4.0 software to examine the statistical association of PPARG polymorphisms and UMVI in patients with T2DM. Results Four SNPs qualified the Hardy-Weinberg equilibrium (p > 0.05). The frequency of genotype GC at SNP rs10865710 was significantly higher in the UMVI group than in the NV group (p < 0.001; GG + GC versus CC) (OR = 8.94, 95% CI: 4.90-16.31), whereas genotype CC decreased the risk (OR = 0.07, 95% CI: 0.03-0.14). Genotype TT at SNP rs3856806 was strongly associated with UMVI (p < 0.0001, TT + TC versus CC) (OR = 4.74, 95% CI: 2.68-8.54), whereas genotype CC appeared to be protective for UMVI (OR = 0.55, 95% CI: 0.37-0.82). Conclusions Susceptibilities of PPARG variants may lead to differences in PPARG transcription, result in early function loss of retinal photoreceptor cells, and eventually cause UMVI.
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Ai X, Hou Y, Wang X, Wang X, Liang Y, Zhu Z, Wang P, Zeng Y, Li X, Lai X, Meng X, Li Q. Amelioration of dry eye syndrome in db/db mice with diabetes mellitus by treatment with Tibetan Medicine Formula Jikan Mingmu Drops. JOURNAL OF ETHNOPHARMACOLOGY 2019; 241:111992. [PMID: 31150794 DOI: 10.1016/j.jep.2019.111992] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 05/22/2019] [Accepted: 05/27/2019] [Indexed: 05/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Jikan Mingmu Drops (JMD), a traditional Tibetan medicine containing six herbs, has been used to treat dry eye syndrome (DES) in individuals with diabetes mellitus. AIM OF STUDY However, the activity of JMD ameliorates DES with diabetes mellitus has not been previously examined. The aim of the study is to investigate the molecular mechanism of JMD on db/db mice. MATERIALS AND METHODS The main chemical constituents of JMD were analyzed by high-performance liquid chromatography and gas chromatography-mass spectrometry. DES was then induced in db/db mice by applying 0.2% benzalkonium chloride to the ocular surface for 7 days. Eye drops containing JMD (0.25, 0.5, or 1 g/mL) or vehicle subsequently were administered three times daily for another 7 days, and the therapeutic effects were evaluated by phenol red thread tear and sodium fluorescein tests. Conjunctival specimens were subjected to hematoxylin and eosin staining and periodic acid-Schiff staining to examine pathological changes and number of goblet cells. ELISA was performed to assess the levels of various inflammatory cytokines. RESULTS JMD contains hydroxysafflor yellow A, magnoflorine, jatrorrhizine hydrochloride, palmatine hydrochloride, berberine hydrochloride, gallic acid, ellagic acid, tauroursodeoxycholic acid, camphor, isoborneol, borneol, trans-cinnamic acid, and muscone. JMD treatment significantly increased the tear volume, decreased the corneal fluorescein staining score, restored the morphology and structure of conjunctival epithelial cells, and markedly downregulated the levels of interleukin (IL)-6, IL-17α, IL-1β, tumor necrosis factor-α, and vascular endothelial growth factor in the conjunctiva. Further data showed that these protective effects were accompanied by inhibition of inflammation in a dose-dependent manner. CONCLUSIONS Amelioration of DES in db/db mice with diabetes mellitus by treatment with Tibetan medicine formula JMD maybe related to its anti-inflammatory effects.
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Affiliation(s)
- Xiaopeng Ai
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Ya Hou
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xiaobo Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xiaoyan Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yusheng Liang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Zhengwen Zhu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Ping Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yong Zeng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xianjia Li
- Tibetan Medical College, Qinghai University, Xining, 810001, China
| | - Xianrong Lai
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Xianli Meng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Qi'en Li
- Tibetan Medical College, Qinghai University, Xining, 810001, China.
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Wang S, Jia Y, Li T, Wang A, Gao L, Yang C, Zou H. Dry Eye Disease Is More Prevalent in Children with Diabetes than in Those without Diabetes. Curr Eye Res 2019; 44:1299-1305. [PMID: 31294638 DOI: 10.1080/02713683.2019.1641827] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Purpose: To compare the prevalence of dry eye disease between children with and without diabetes, and analyze the factors associated with dry eye disease in children with diabetes.Materials and methods: 38 children with diabetes were selected as cases, and 40 children without diabetes constituted the control group. The prevalence of dry eye disease in both groups was statistically analyzed. Related factors of dry eye disease were analyzed in children with diabetes.Results: The prevalence of dry eye disease in the case group was significantly higher than that in the control group (P < .01), with the attributable proportion among the exposed (0.827) and the population attributable fraction (0.700). Univariate analysis showed that the diabetes duration, best-corrected visual acuity, corneal sensation, and levels of glycosylated hemoglobin were associated with dry eye disease in children with diabetes. Logistic regression analysis revealed that only diabetes duration and corneal sensation were independent factors associated with dry eye disease. The diabetes duration was significantly higher and the level of corneal sensation was significantly lower in subjects with dry eye disease than in those without dry eye disease.Conclusions: Early screening and close follow-up of dry eye disease in children with diabetes should be strictly implemented, especially in children with a long duration of diabetes and those with peripheral neuropathy.
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Affiliation(s)
- Shanshan Wang
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
| | - Yan Jia
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Tao Li
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
| | - Anken Wang
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Lu Gao
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Chenhao Yang
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Haidong Zou
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
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Dutra BDAL, Carneiro CLB, Gomes MSM, Nagashima RD, Machado AJ, Crispim J. Clinical Evaluation of Dry Eye Syndrome in Patients with Proliferative Diabetic Retinopathy and Laser Therapy Indication. Open Ophthalmol J 2019. [DOI: 10.2174/1874364101913010001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background:
Studies have shown a higher incidence of dry eye among patients with diabetes compared to patients without diabetes. However, information regarding dry eye in patients with proliferative diabetic retinopathy and laser therapy indication is not sufficient.
Objective:
To estimate the clinical manifestation of dry eye syndrome in patients with proliferative diabetic retinopathy and laser therapy indication.
Method:
A cross-sectional study was performed during a local evaluation campaign of diabetic patients with vision disabilities at the Instituto Cearense de Oftalmologia in Fortaleza, CE, Brazil. Patients with proliferative diabetic retinopathy and laser therapy indication were included in the study. An anamnesis directly to dry eye complaints was performed, and eligible participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The slit lamp examination was performed with fluorescein staining; the tear break-up time (TBUT) was measured, and conjunctiva and corneal was evaluated using Rose Bengal (RB) staining. Finally, the Schirmer I test was performed.
Results:
Twenty-five patients were included in the study with a diagnostic time of Diabetes Mellitus ranged from 1 to 35 years, with an average of 17.2 ± 8.7 years. In our sample, 14 patients (56%) reported glycemic control with insulin, while 11 patients (44%) had oral hypoglycemic agents. The most prevalent complaint was blurred vision (96% of patients) followed by low visual acuity (92%). A less prevalent complaint was pain (44%). The mean OSDI score was 49.4 ± 24.2. TBUT was less than 10 seconds in 21 patients (84%), and RB staining grade was more than 3 in 13 patients (52%). The results of the Schirmer I test ranged from 2 to 35 mm, with a mean of 13.57 ± 9.78 mm. It was smaller than 10 mm in 15 patients (60%).
Conclusion:
The frequency of manifestation of dry eye syndrome was very common in patients with proliferative diabetic retinopathy and laser therapy indication. Ocular surface care should be provided for those patients with significant ocular morbidity.
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Yazdani-Ibn-Taz MK, Han MM, Jonuscheit S, Collier A, Nally JE, Hagan S. Patient-reported severity of dry eye and quality of life in diabetes. Clin Ophthalmol 2019; 13:217-224. [PMID: 30774302 PMCID: PMC6354694 DOI: 10.2147/opth.s184173] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE The purpose of the study was to assess the relationship between patient-reported severity of dry eye disease (DED), quality of life (QoL), presence of diabetic retinopathy (DR) and length of disease duration in people with type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2). PATIENTS AND METHODS A survey of 152 people (110 with and 42 without diabetes). All participants completed the Ocular Surface Disease Index (OSDI) and Dry Eye-related Quality of Life Score (DEQS) questionnaires. RESULTS Forty-four percent of all diabetic subjects reported dry eye symptoms, compared to 29% in the control group. Patients with DM2 reported dry eye symptoms more frequently than those with DM1 (55% and 27% respectively, P=0.001). Dry eye severity was linked to a significant deterioration in QoL in both types of diabetes (DM1, r=0.609 and P=0.036; DM2, r=0.417 and P=0.011). Irrespective of DR, the presence of DED was significantly higher in DM2 compared to DM1 (with DR, P=0.011; without DR, P=0.018). CONCLUSION Dry eye symptoms are associated with reduced QoL and are more common in people with DM2 than in DM1, irrespective of DR status. Routine clinical screening for severe DED could potentially allow for a timely and more effective treatment and could contribute to mitigating the dry eye-associated reduction in QoL in those with DM2.
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Affiliation(s)
| | - Myint Myint Han
- School of Health and Life Sciences, Glasgow Caledonian University (GCU), Glasgow G4 0BA, UK,
| | - Sven Jonuscheit
- School of Health and Life Sciences, Glasgow Caledonian University (GCU), Glasgow G4 0BA, UK,
| | - Andrew Collier
- School of Health and Life Sciences, Glasgow Caledonian University (GCU), Glasgow G4 0BA, UK,
- Diabetes Day Centre, University Hospital Ayr, Ayr KA6 6DX, UK
| | - Jane E Nally
- School of Health and Life Sciences, Glasgow Caledonian University (GCU), Glasgow G4 0BA, UK,
| | - Suzanne Hagan
- School of Health and Life Sciences, Glasgow Caledonian University (GCU), Glasgow G4 0BA, UK,
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Bussan KA, Robertson DM. Contact lens wear and the diabetic corneal epithelium: A happy or disastrous marriage? J Diabetes Complications 2019; 33:75-83. [PMID: 30391097 PMCID: PMC7364814 DOI: 10.1016/j.jdiacomp.2018.09.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 09/10/2018] [Accepted: 09/23/2018] [Indexed: 12/11/2022]
Abstract
Diabetes mellitus is an epidemic in the US and abroad. With the advent of new contact lens technology, the use of contact lenses as glucose sensors in lieu of the traditional finger stick is quickly becoming realized. This has the potential to rapidly expand the contact lens market into this growing patient population. The independent cellular and physiological effects of contact lens wear and diabetes on the corneal epithelium have been described. However, little evidence exists to date to support whether there is increased risk associated with contact lens wear in diabetes. The focus of this review is to discuss what is known about the cellular effects of contact lenses on the corneal epithelium, the pathophysiological changes in the corneal epithelium that occur in diabetes, and whether an increased risk for corneal epithelial damage and/or infection may negatively impact safety in diabetic contact lens wearers. Available data indicates that there are inherent risks associated with contact lens wear in diabetics. Importantly, eye care practitioners fitting contact lenses in the diabetic patient need to carefully consider the duration of disease, the level of glycemic control, the presence of retinopathy, and the patient's overall health.
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Affiliation(s)
- Katherine A Bussan
- The Department of Ophthalmology, The University of Texas Southwestern Medical Center, United States of America
| | - Danielle M Robertson
- The Department of Ophthalmology, The University of Texas Southwestern Medical Center, United States of America.
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Dry Eye Syndrome Preferred Practice Pattern®. Ophthalmology 2019; 126:P286-P334. [DOI: 10.1016/j.ophtha.2018.10.023] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 10/09/2018] [Indexed: 01/04/2023] Open
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