Diabetic Dry Eye Research Articles

MUC1‑ND interacts with TRPV1 to promote corneal epithelial cell proliferation in diabetic dry eye mice by partly activating the AKT signaling pathway.

Although both mucin1 (MUC1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) have been reported to be associated with dry eye (DE) disease, whether they interact and their regulatory roles in diabetic DE disease are unknown. Diabetic DE model mice were generated by streptozotocin induction and assessed by corneal fluorescein staining, tear ferning (TF) tests, phenol red thread tests, hematoxylin and eosin staining of corneal sections and periodic acid Schiff staining of conjunctival sections. Cell proliferation was measured by CCK8 assay. Western blotting was performed to measure protein expression. Primary mouse corneal epithelial cells (MCECs) were cultured after enzymatic digestion. Immunofluorescence staining of MCECs and frozen corneal sections was conducted to assess protein expression and colocalization. Coimmunoprecipitation was performed to detect protein‑protein interactions. It was found that, compared with control mice, diabetic DE mice exhibited increased corneal epithelial defects, reduced tear production, poorer TF pattern grades and impaired corneal and conjunctival tissues. In vivo and in vitro experiments showed that hyperglycemia impaired cell proliferation, accompanied by decreased levels of the MUC1 extracellular domain (MUC1‑ND) and TRPV1. Additionally, it was found that capsazepine (a TRPV1 antagonist) inhibited the proliferation of MCECs. Notably, MUC1‑ND was shown to interact with the TRPV1 protein in the control group but not in the diabetic DE group. It was also found that the AKT signaling pathway was attenuated in the diabetic DE mice and downstream of TRPV1. MUC1‑ND interacted with TRPV1, partly activating the AKT signaling pathway to promote MCEC proliferation. The present study found that the interaction of MUC1‑ND with TRPV1 promotes MCEC proliferation by partly activating the AKT signaling pathway, providing new insight into the pathogenesis of corneal epithelial dysfunction in diabetic DE disease.

Efficacy of recombinant human epidermal growth factor plus sodium hyaluronate eye drops in diabetic dry eye post-cataract surgery

BACKGROUND Dry eye syndrome (DES) after diabetic cataract surgery can seriously affect the patient’s quality of life. Therefore, effective alleviation of symptoms in patients with this disease has important clinical significance. AIM To explore the clinical effect of recombinant human epidermal growth factor (rhEGF) plus sodium hyaluronate (SH) eye drops on DES after cataract surgery in patients with diabetes. METHODS We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital, Affiliated Hospital of Nankai University between April 2021 and April 2023. They were classified into an observation group (42 cases, rhEGF + SH eye drops) and a control group (40 cases, SH eye drops alone), depending on the different treatment schemes. The thera-peutic efficacy, dry eye symptom score, tear film breakup time (TFBUT), basic tear secretion score [assessed using Schirmer I test (SIt)], corneal fluorescein staining (FL) score, tear inflammatory markers, adverse reactions during treatment, and treatment satisfaction were compared between the two groups. RESULTS Therapeutic efficacy was higher in the observation group compared with the control group. Both groups showed improved TFBUT and dry eye, as well as improved SIt and FL scores after treatment, with a more pronounced improvement in the observation group. Although no marked differences in adverse reactions were observed between the two groups, treatment satisfaction was higher in the observation group. CONCLUSION rhEGF + SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy, fewer adverse reactions, and high safety levels. Thus, this treatment should be promoted in clinical practice.

Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

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. 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. 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. 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.

Unique composition of ocular surface microbiome in the old patients with dry eye and diabetes mellitus in a community from Shanghai, China

BackgroundThis study investigates the variations in microbiome abundance and diversity on the ocular surfaces of diabetic patients suffering from dry eye within a community setting. The goal is to offer theoretical insights for the community-level prevention and treatment of dry eye in diabetic cohorts.MethodsDry eye screening was performed in the Shanghai Cohort Study of Diabetic Eye Disease (SCODE) from July 15, 2021, to August 15, 2021, in the Xingjing community; this study included both a population with diabetes and a normal population. The population with diabetes included a dry eye group (DM-DE, n = 40) and a non-dry eye group (DM-NoDE, n = 39). The normal population included a dry eye group (NoDM-DE, n = 40) and a control group (control, n = 39). High-throughput sequencing of the 16 S rRNA V3-V4 region was performed on conjunctival swab from both eyes of each subject, and the composition of microbiome on the ocular surface of each group was analyzed.ResultsSignificant statistical differences were observed in both α and β diversity of the ocular surface microbiome among the diabetic dry eye, diabetic non-dry eye, non-diabetic dry eye, and normal control groups (P < 0.05).ConclusionsThe study revealed distinct microecological compositions on the ocular surfaces between the diabetic dry eye group and other studied groups. Firmicutes and Anoxybacillus were unique bacterial phyla and genera in the dry eye with DM group, while Actinobacteria and Corynebacterium were unique bacterial phyla and genera in the normal control group.

Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

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

BackgroundThe 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.MethodsThis 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.DiscussionThis 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 registrationClinicalTrials.govNCT05682547. Registered on December 05, 2022.

Individuals with Diabetes Mellitus Have a Dry Eye Phenotype Driven by Low Symptom Burden and Anatomic Abnormalities.

Dry eye disease is an umbrella term that includes a variety of symptoms and signs. A link between diabetes mellitus and dry eye disease exists, but the associated phenotype needs further examination. Thus, our aim was to determine how diabetes mellitus relates to the dry eye disease phenotype. A prospective, cross-sectional study was conducted at the Miami Veteran Affairs Medical Center ophthalmology clinic between October 2013 and September 2019. Participants included a volunteer sample of 366 South Florida veterans with one or more symptoms or signs of dry eye disease [Dry Eye Questionnaire-5 ≥ 6 OR tear break-up time ≤ 5 OR Schirmer's test score ≤ 5 OR corneal fluorescein staining ≥ 2]. Participants were divided into three groups: (1) individuals without diabetes mellitus (controls); (2) individuals with diabetes mellitus but without end-organ complications; and (3) individuals with diabetes mellitus and end-organ complications. Dry eye metrics were compared across groups. The main outcome measures included ocular symptom questionnaires [e.g., 5-item Dry Eye Questionnaire, Ocular Surface Disease Index, and ocular pain assessment] and clinical parameters obtained from an ocular surface evaluation. A total of 366 individuals were included (mean age 59 ± 6 years; 89% males; 39% White; 11% diabetes mellitus and end-organ complications; 15% diabetes mellitus but without end-organ complications). Individuals with diabetes mellitus and end-organ complications had lower symptom scores on the dry eye disease and pain-specific questionnaires compared to individuals with diabetes mellitus but without end-organ complications and controls (Ocular Surface Disease Index: 42.1 ± 24.5 vs. 38.9 ± 25.1 vs. 23.6 ± 16.2; p < 0.001; numerical rating scale of ocular pain intensity: 4.9 ± 3.2 vs. 4.3 ± 2.7 vs. 3.5 ± 2.7; p = 0.02). Eyelid laxity was also more severe in the group with diabetes mellitus and end-organ complications (0.69 ± 0.64 vs. 0.73 ± 0.72 vs. 1.08 ± 0.77; p = 0.004) compared to the two other groups. The diabetic dry eye disease phenotype is driven by signs more so than by symptoms, with anatomic eyelid abnormalities being more frequent in individuals with diabetes mellitus and end-organ complications. Given this, ocular surface abnormalities in individuals with DM may be missed if screened by symptoms alone. As such, individuals with DM should undergo a slit lamp examination for signs of ocular surface disease, including anatomic abnormalities.

Hyperglycemia Induces Tear Reduction and Dry Eye in Diabetic Mice through the Norepinephrine–α1 Adrenergic Receptor–Mitochondrial Impairment Axis of Lacrimal Gland

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. In the present study, we found that both norepinephrine (NE) and tyrosine hydroxylase levels were elevated in the lacrimal gland of diabetic mice, accompanied by increased 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 adrenoceptors (ARs), the α1 subtype played the 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.

Using diabetic patients once daily fingerprick autologous blood eye drops for diabetic dry eye disease- A modified regimen to treat and prevent diabetic dry eye disease

Purpose: Diabetic patients tend to suffer from dry eye disease due to associated various reasons. Autologous blood is both safe and effective for treating Dry Eye Disease (DED) according to studies. Several papers demonstrated feasibility and effectiveness of four times Fingerprick Autologous Blood (FAB) eye drops to treat dry eye disease. As some diabetic patients perform daily finger pricking to monitor blood glucose level, the blood that remains can be used to apply to eyes to treat and prevent dry eye disease. This study intends to investigate if once daily fingerprick autologous blood eye drop in conjunction with blood glucose test is feasible and effective for diabetic patients who suffer from mild to moderate dry eye disease also to avoid four times fingerprick. This may be the first study on using diabetic patients once daily fingerprick autologous blood eye drops for mild to moderate diabetic’s dry eye disease. Design, setting and participants: This case series study enrolled 25 diabetics patients with mild to moderate DED who received ophthalmological care at a single clinic in Honolulu, Hawaii. All patients were performing once daily finger prick tests to monitor their blood glucose level. Participants were instructed to instill the remaining FAB after blood glucose tests into the medial inner canthus of each eye for one month. Patients remained on their daily dry eye treatment regimen throughout the study. Main outcomes and measures: The OSDI (Ocular Surface Disease Index) scores to categorize severity of DED were used for comparison before and after using FAB eye drop daily for one month. A questionnaire was used to evaluate the acceptability and compliance. Result: 52% of patients after one month of the trial demonstrated improvement in categorization of the severity in DED and willing to continue in the future. Conclusion and relevance: FAB that remained after routine once daily blood glucose testing applied to the eyes may be feasible to enhance prevention and treatment of mild to moderate Diabetic DED. It may be disseminated and used in conjunction with the general practice in diabetic’s patient care.

Mechanistic investigations of diabetic ocular surface diseases.

With the global prevalence of diabetes mellitus over recent decades, more patients suffered from various diabetic complications, including diabetic ocular surface diseases that may seriously affect the quality of life and even vision sight. The major diabetic ocular surface diseases include diabetic keratopathy and dry eye. Diabetic keratopathy is characterized with the delayed corneal epithelial wound healing, reduced corneal nerve density, decreased corneal sensation and feeling of burning or dryness. Diabetic dry eye is manifested as the reduction of tear secretion accompanied with the ocular discomfort. The early clinical symptoms include dry eye and corneal nerve degeneration, suggesting the early diagnosis should be focused on the examination of confocal microscopy and dry eye symptoms. The pathogenesis of diabetic keratopathy involves the accumulation of advanced glycation end-products, impaired neurotrophic innervations and limbal stem cell function, and dysregulated growth factor signaling, and inflammation alterations. Diabetic dry eye may be associated with the abnormal mitochondrial metabolism of lacrimal gland caused by the overactivation of sympathetic nervous system. Considering the important roles of the dense innervations in the homeostatic maintenance of cornea and lacrimal gland, further studies on the neuroepithelial and neuroimmune interactions will reveal the predominant pathogenic mechanisms and develop the targeting intervention strategies of diabetic ocular surface complications.

Effects of the Topical Use of the Natural Antioxidant Alpha-Lipoic Acid on the Ocular Surface of Diabetic Patients with Dry Eye Symptoms.

The purpose of this study is to investigate the effects of the treatment with eye-drops based on a combination of antioxidant and mucomimetic molecules, namely 0.1% alpha-lipoic acid (ALA) and 0.3% hydroxy-propyl-methylcellulose (HPMC) on the ocular surface of diabetic patients with dry eye symptoms. Seventy patients, 42 M and 28 F, aged from 50 to79 years (mean 62.1 ± 10.5), affected by type II diabetes mellitus, were enrolled and divided in two groups treated for 2 months as follows: Group 1 (35 patients), received topical ALA/HPMC three times a day, Group 2 (35 patients) received topical HPMC (0.3%) alone, three times a day. The main outcome measures were: Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), corneal fluorescein staining, Schirmer I test, corneal sensitivity. An examination of tear film morphology with confocal microscopy was carried out in a subset of patients of each group at baseline and after two months. Statistical analysis was performed with t-test for the parametric data and Mann-Whitney U-test or chi-squared test for the nonparametric data. Both treatments resulted in significant improvements of BUT, OSDI and tear film morphology, although the improvements observed in group 1 showed a higher trend than what observed for group 2. Moreover, only in group 1 a significant improvement was visible for corneal staining, and no significant improvements were observed in any group for Schirmer I and sensitivity. These results confirmed the efficacy of HPMC in the treatment of diabetic dry eye and indicated that the addition of a strong self-regenerating antioxidant like ALA may give a distinctive advantage for the healing of corneal defects (as evidenced by corneal staining), beside improving HPMC efficacy on three other parameters (BUT, OSDI score, tear morphology). Therefore, the addition of a strong antioxidant like ALA can be helpful in preventing or treating ocular surface defects in diabetic patients, in which the oxidative damage is predominant.

Novel glucagon-like peptide-1 analogue exhibits potency-driven G-protein biased agonism with promising effects on diabetes and diabetic dry eye syndrome

ABSTRACT Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered as effective treatments for type 2 diabetes. Here, we describe the in vitro characteristics and in vivo anti-diabetic efficacies of a novel GLP-1RA, termed SM102. The in vitro functions of SM102, including GLP-1R kinetic binding parameter, cAMP activation, endocytosis and recycling, were all evaluated using the INS-1 832/13 cells expressing human GLP-1R. Chronic efficacies study was performed to evaluate the effects of SM102 on the glycemic benefits, body weight loss and other diabetic complications in db/db mice. As a result, SM102 exhibited enhanced binding affinity and potency-driven bias in favor of cAMP over GLP-1R endocytosis and β-Arrestin 2 recruitment, as well as comparable insulin secretory response compared with Semaglutide. In addition, chronic treatment of SM102 led to more promising therapeutical effects on hyperglycemia, weight control and insulin resistance as well as dry eye syndrome (DES) than Semaglutide. Furthermore, SM102 could ameliorate diabetic DES via improving antioxidant properties, inflammatory factors and inhibiting MAPKs pathway in diabetic mice. In conclusion, SM102 is a G protein-biased agonist serving as a promising new GLP-1RA for treating diabetes and diabetic complications.

Impact of Diquafosol Ophthalmic Solution on Tear Film and Dry Eye Symptom in Type 2 Diabetic Dry Eye: A Pilot Study

Purpose: Diquafosol ophthalmic solution (DQS) stimulates P2Y2 receptors on the ocular surface, which enhances mucin secretion from goblet cells. Therefore, tear film stability and hydration of the ocular surface can be achieved independent from lacrimal gland function. Methods: This prospective, open-label pilot study included 60 eyes of 30 diabetic patients diagnosed with dry eye disease (DED) and were randomly assigned to either DQS (n = 30 eyes) or hyaluronate (HA) group (n = 30 eyes). Participants in the DQS group received 3% diquafosol ophthalmic solution, whereas HA group received 0.1% sodium HA preservative-free artificial tears. The dosage for both drugs was 1 drop, 6 times per day for 4 weeks. Tear film lipid layer (TFLL), noninvasive breakup time (NITBUT), corneoconjunctival staining (CS) score, meibomian gland (MG), conjunctival hyperemia [redness score (RS)], ocular surface disease index (OSDI) was assessed and compared at baseline, day 14, and day 28. Results: Comparing baseline and day 28 measurements revealed that both groups found significant improvements in NITBUT, CS, MG quality, MG expressibility, and OSDI scores significantly (P < 0.05), in addition TFLL improvements were only found in the DQS group. At day 28, the magnitude of change in mean NITBUT was 1.74 (DQS) versus 0.31 (HA), 1.16 (DQS) versus 0.37 (HA) point grade reduction in corneoconjunctival staining score and 9.80 (DQS) versus 4.80 (HA) point grade in mean OSDI score. Conclusion: Three percent diquafosol ophthalmic solution treatment demonstrated the ability to improve the tear film dry eye parameters and clinically reduced sign and symptoms of DED in diabetic dry eye patients. Clinical Trials.gov ID: NCT04980144.

Correlation between Nod-like Receptor Protein 3 Inflammasome and Diabetic Dry Eye

Correlation between Nod-like Receptor Protein 3 Inflammasome and Diabetic Dry Eye

Hyperglycemia-induced severe mitochondrial bioenergetic deficit of lacrimal gland contributes to the early onset of dry eye in diabetic mice

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.

Dynamic changes of ocular surface tissue of diabetic dry eye in mice

Objective To explore the occurring and developing characteristics of dry eye syndrome in type 1 diabetic mouse model induced with streptozotocin (STZ)-intraperitoneal injection. Methods Completely randomized design method was performed.Sixty SPF degree male C57BL/6 mice (6-8 weeks old) was randomly divided into diabetic group and control group, which were intraperitoneally injected with citrate buffer and STZ-citrate buffer (50 mg/kg per day), respectively.The average weight, blood glucose level and lacrimal gland weight were examined before injection and 1 month, 2 months, 4 months after the last injection; meanwhile, phenol cotton thread and rose bengal staining methods were used to check tear formation and ocular surface condition; corneal perception meter was used to test corneal sensitivity; periodic acid-schiff (PAS) staining method was used to test the density of conjunctival goblet cells; histopathological staining and Masson staining methods were used to test the tissue changes of lacrimal gland. Results Compared with before injections, the body weight and lacrimal gland weight in diabetic group were not significantly changed 1 month, 2 months and 4 months after injection (all at P>0.05), but these measurements in diabetic group 1 month, 2 months and 4 months after injection were significantly lower than those in control group at corresponding time points (all at P<0.05). Compared with before injections and control group at corresponding time points, the blood glucose level were dramatically higher and the tear formation were significantly decreased in diabetic group at 1 month, 2 months, 4 months after injection (all at P<0.05). The ocular surface of diabetic model mice showed positive rose bengal staining 2 months after STZ injections.The corneal sensitivities were significantly lower in diabetic model mice 2 months and 4 months after injection than those before injection and in control group at corresponding time points (all at P<0.05). The density of conjunctival goblet cells in diabetic group 4 months after injection was significantly decreased than those before injection in diabetic group and 4 months after injection in control group (all at P<0.05). The apparent collagen fibrosis and inflammatory cell infiltration were observed at lacrimal gland in diabetic model mice 4 months after injection. Conclusions The major early stage manifestations of STZ induced type 1 diabetes mice include retarded growth of lacrimal gland and decreased tear secretion volume, which gradually develop along the course of diabetes; in the later stage, the manifestations include decreased corneal sensitivity, ocular structural damage, structural changes of lacrimal gland and decreased conjunctival goblet cell density. Key words: Diabetes mellitus; Dry eye; Tear formation; Lacrimal gland; Corneal sensitivity

The long-term effects of platelet –rich plasma in diabetic dry eye: a series of cases

Resumo Objetivo: Avaliar a eficacia a longo prazo apos 6 meses de uso do colirio de concentrado de plaquetas (CCP) autologo no olho seco sintomatico de pacientes diabeticos. Metodos: Um estudo de intervencao com unico grupo prospectivo tipo serie de casos; dez pacientes diabeticos com doenca do olho seco refratario que usaram o CCP e foram reavaliados 6 meses apos suspensao do tratamento. Na etapa inicial 221 pacientes diabeticos foram avaliados quanto a olho seco, destes 12 foram submetidos ao CCP, e avaliados para sintomas, escore de OSDI (Ocular Surface Disease Index), TFBUT (Tear Film Break Up Time) e Teste de Schirmer. Nesta etapa do estudo os pacientes foram reconvocados apos 6 meses de suspensao do CCP, e o escore de OSDI, TFBUT e teste de Schirmer foram revistos. Resultados: Houve diferenca estatisticamente significante nos escores de OSDI e TFBUT entre o basal (antes do tratamento com CCP) e apos 1 mes do uso do CCP ; entre o basal e apos 6 meses de suspensao do uso do CCP, e entre os valores apos 1 mes de uso e apos 6 meses sem uso (p= 0,005, p=0,010 e p= 0,028, p=0,04, p= 0,03 e p=0,02 respectivamente). Nos resultados do Teste de Schirmer nao houve diferenca significativa em nenhuma das comparacoes (p=0,09, p= 0,26, p=0,47 respectivamente). Conclusoes: O CCP apos 6 meses de uso apresenta evidencias de que ainda seria eficaz mesmo com a suspensao do colirio.

Interleukin-1β and tumour necrosis factor-α levels in conjunctiva of diabetic patients with symptomatic moderate dry eye: case–control study

ObjectivesTo compare expression of interleukin (IL)-1β and tumour necrosis factor (TNF)-α in the conjunctiva of diabetic and non-diabetic patients with symptomatic moderate dry eye.Setting and participantsNineteen diabetic patients with dry...

Platelet-rich plasma in diabetic dry eye disease

Objetivo: Avaliar a eficacia do colirio de concentrado de plaquetas (CCP) autologo no olho seco sintomatico de pacientes diabeticos. Projeto Um estudo de intervencao unico grupo prospectivo. Participantes Doze pacientes diabeticos com doenca do olho seco refratario. Metodos Os pacientes foram tratados com colirio de PRP autologo quatro vezes por dia durante um mes. Sintomas de olho seco e sua frequencia, seguindo os criterios de DEWS, tempo de ruptura do filme lacrimal, a melhoria das linhas de acuidade visual e teste de Schirmer. Resultados Todos os pacientes tiveram alguma melhora dos sintomas de ressecamento, coceira, ardor e vermelhidao (p = 0,002). Destes, 41,66% (5/12) tiveram melhora de uma ou mais linhas de acuidade visual em ambos os olhos; 50% e 58,33% nao tinham alteracao no olho direito e esquerdo, respectivamente (p = 0,14) . Considerando o teste de Schirmer, 66,66% (8/12) tiveram melhora no valor do teste, 25% (3/12) nao apresentaram alteracao neste valor de teste e de 8,33% (1/12) tiveram um valor reduzido no teste apos tratamento. (p = 0,04). Considerando o valor de teste BUT 58,33% (7/12) apresentaram melhora no valor de teste e 41,66% (12/05) nao apresentaram alteracao neste valor de teste (p = 0,018). Conclusoes O CCP e seguro e uma terapia alternativa interessante no olho seco diabetico sintomatico. Mais ensaios clinicos sao necessarios para criar protocolos especificos para este tratamento.

Influence of insulin treatment on the lacrimal gland and ocular surface of diabetic rats

Previous studies have observed changes in the lacrimal gland and ocular surface related to diabetes mellitus and related it to insulin resistance or insufficiency and oxidative damage. The aim of this study was to evaluate whether insulin treatment inhibits those changes. Diabetes was induced in male Wistar rats with a single intravenous injection of streptozotocin and a subgroup was treated with insulin. After 5 and 10 weeks, the three groups (n = 5-10/group/experimental procedure) were compared for biochemical, functional, and histological parameters. After 5 weeks, changes in morphology and increased numbers of lipofucsin-like inclusions were observed in lacrimal glands of diabetic but not insulin-treated rats. After 5 weeks, malonaldehyde and total peroxidase activity were significantly higher in diabetic rats, but similar to control in insulin-treated diabetic rats (P = 0.03, P = 0.02, respectively). Our data indicate that diabetes induces histological alterations in lacrimal gland and suggests that hyperglycemia-related oxidative stress may participate in diabetic dry eye syndrome. Prevention by insulin replacement suggests direct hormone action and/or benefit by early sub optimal metabolic control.