Ocular pharmacokinetics and toxicity of nanoparticular acetazolamide: In vivo distribution and safety of PHBV-ACZ nanoparticle.

Diabetic macular edema (DME) is defined as fluid accumulation in the macular region, between the retinal layers, due to many diseases, especially diabetes. DME is one of the major complications of diabetic retinopathy (DRP). Carbonic anhydrase inhibitors (CAI) are a pharmaceutical agent used in different fields, especially glaucoma treatment. Acetazolamide (ACZ), which is a CAI, is an active substance that has been used off-label for many years in the treatment of macular edema due to diabetes and many other diseases. The low solubility and bioavailability of ACZ limit its use in the treatment of DME. In this study, a nanoparticulate formulation was developed that would increase the solubility and bioavailability of ACZ and allow it to be administered intravitreally. ACZ was loaded on poly(3-hydroxybutyrate-co-3-Hydroxyvalerate) (PHBV) nanoparticles and the loading efficiency was 71.58 ± 1.22%. Toxicity of nanoparticles after intravitreal application was evaluated with anterior segment and posterior segment examination findings, intraocular pressure (IOP) measurements and electrophysiological tests. At the end of the 3-month follow-up, electroretinography (ERG) measurements demonstrated that ACZ loaded PHBV (PHBV-ACZ) nanoparticles did not cause loss of function in retinal cells. On histological examination, rare degenerative changes were observed in several cell groups. In addition, pharmacokinetic studies were performed to determine the tissue distribution of ACZ at various periods. ACZ was identified in vitreous humor and retina at the highest concentration. Based on our results, the prepared nanoparticle formulation can release long-term CAI for DRP therapy and accordingly can reduce the need for monthly intravitreal injections.

Tamoxifen related chorioretinal structural changes.

PURPOSE: To evaluate the vascular structure of the choroid and each retinal layer in patients with breast cancer on tamoxifen therapy and compare them with healthy subjects. MATERIALS AND METHODS: 124 eyes of 62 patients with breast cancer who were on tamoxifen therapy (group 1) and 80 eyes of 40 healthy controls (group 2) were included in this prospective cohort study. The structure of the choroid was evaluated using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) and choroidal binarisation. Spectral-domain OCT (SD-OCT) was performed to analyse the peripapillary nerve fibre layer thickness (pRNFL) and each retinal layer thickness. A subgroup analysis was performed based on chemotherapy history in Group 1. All parameters were compared between Group 1 and the healthy controls and between the subgroups of Group 1. RESULTS: The subfoveal choroidal thickness and temporal and nasal directions were increased in Group 1 when compared with Group 2 (p < 0.05, each comparison). Choroidal vascularity index was significantly decreased in Group 1 compared with Group 2 (63.15 ± 3.11% and 65.37 ± 4.63%, p < 0.001). There were no significant differences in each retinal layer, pRNFL thickness, and choroid structural parameters between the subgroups of Group 1. CONCLUSIONS: Increased choroidal thickness may be the initial finding of subclinical tamoxifen-induced retinopathy. Patients with breast cancer undergoing tamoxifen therapy may be screened prior to tamoxifen therapy and followed during treatment by SD-OCT.

The relation between serum inflammatory marker levels and serous retinal detachment in macular edema secondary to retinal vein occlusion.

PURPOSE: To assess blood-derived inflammatory markers in macular edema (ME) secondary to retinal vein occlusion (RVO) with and without serous retinal detachment (SRD). MATERIALS-METHODS: Treatment-naive patients with ME secondary to RVO were divided into two groups according to the existence of SRD in optical coherence tomography (OCT) images; group 1 consisted of 60 patients with SRD, and group 2 consisted of 60 patients without SRD. Age and gender-matched 60 patients formed group 3 as healthy controls. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII) were calculated from blood samples to assess the differences in the levels of blood-derived inflammatory markers and the presence of SRD. RESULTS: The PLR, NLR, and SII values were higher in groups 1 and 2 than in group 3 (p<0.05, each comparison). The NLR and SII values were also significantly elevated in group 1 compared to group 2 (p = 0.000 and p = 0.000, respectively). The optimal cutoff value to estimate SRD in patients with ME secondary to RVO for NLR was 2.08 with 66.7% sensitivity and 65% specificity; for SII was 530.93 with 68.3% sensitivity and specificity. CONCLUSION: SII is a reliable and cost-effective tool for predicting SRD, an inflammatory OCT biomarker in ME secondary to RVO.

Real Life Multicenter Comparison of 24-Month Outcomes of Anti-VEGF Therapy in Diabetic Macular Edema in Turkey: Ranibizumab vs. Aflibercept vs. Ranibizumab-Aflibercept Switch.

The aim of this study was to compare the outcomes of diabetic macular edema (DME) treated with aflibercept (AFB) or ranibizumab (RNB) only, and after switching from RNB to AFB. This was a retrospective, real-world, multicenter (7 cities) 24 month study. Overall, 212 eyes in the AFB group, 461 in the RNB group, and 141 in the RNB to AFB group were included. The primary endpoints were differences in visual acuity (VA) and central macular thickness (CMT) from baseline to the final visit. The secondary outcomes were the percentage of eyes that achieved ≥10 letters gain and ≥10 letters loss in vision at month 12 and 24, and the percentage of eyes that achieved a thinning of ≥20% in CMT at month 3 and month 6. The results showed that VA did not significantly differ at baseline (AFB: 0.62 ± 0.38, RNB: 0.61 ± 0.36, RNB to AFB: 0.61 ± 0.38), at checkpoints, or at the final visit (AFB: 0.46 ± 0.38, RNB: 0.5 ± 0.37, RNB to AFB: 0.53 ± 0.36) (p > 0.05). Though the mean CMT at baseline was significantly thicker in the RNB to AFB group (479 ± 129.6 µm) when compared to the AFB (450.5 ± 122.6 µm) and RNB (442 ± 116 µm) groups (p < 0.01), similar measurements were obtained after 12 months. The percentages of eyes that gained or lost ≥10 letters in the AFB, RNB, and RNB to AFB groups at year 1 and 2 were similar, as was the percentages of eyes that demonstrated ≥20% CMT thinning at month 3 and 6. Our study showed similar visual improvements in non-switchers (AFB and RNB groups) and switchers (RNB to AFB group) through 2 years follow-up, however, AFB patients required fewer injections, visits, or need for additional treatments.

Effectiveness of carbonic anhydrase inhibitor loaded nanoparticles in the treatment of diabetic retinopathy.

Diabetic Retinopathy (DRP) is a disease consisting of all the structural and functional changes that develop in the retinal layer of the eye due to diabetes. DRP is the most important cause of blindness between the ages of 20-74 in the world, and the most successful standard treatment option in the treatment of DRP is intravitreal injections. To synthesize acetazolamide loaded nanoparticles to be applied intravitreal treatment of DRP and to examine thein vitroefficacy of the nanoparticles. ACZ loaded PHBV nanoparticles (PHBV-ACZ NPs) formulations were prepared. Nanoparticles with a particle size of 253.20 ± 0.55 nm. A DRP model was established and characterized in HRMEC cells. The effect of the nanoparticles on permeability has been investigated and carrier proteins in BRB due to the development of DRP has been investigated. To establish thein vitroDRP model, HRMEC was stimulated with Recombinant human 165 Vascular Endothelial Growth Factor (VEGF), thereby temporarily reducing the expression levels of endothelial junction proteins, increasing the number of intercellular spaces in the monolayers of HRMECs. It was determined that after the cells were exposed to Carbonic anhydrase inhibitors (CAI) loaded nanoparticles, permeability decreased and protein expression increased.

Choroidal vascularity index in adult patients with familial meditteranean fever.

PURPOSE: This study aimed to evaluate choroidal vascular status by the choroidal vascularity index (CVI) in adult patients with familial Mediterranean fever (FMF) in remission period. MATERIALS-METHODS: 86 patients diagnosed with FMF and 54 healthy controls were recruited in this study. Retinal, ganglion cell complex and peripapillary retinal nerve fibre layer thicknesses were obtained using Spectralis domain-optical coherence (SD-OCT) tomography. Choroid images were obtained with the enhanced depth imaging mode of SD-OCT, and binarization was applied to the images using ImageJ software. CVI was described as the proportion of the luminal area to the total choroidal area. Blood-derived inflammation markers were calculated by the complete blood count. RESULTS: The subfoveal choroidal thickness and nasal and temporal directions from fovea centralis at 500 µm, 1000 µm and 1500 µm were reduced in patients with FMF in comparison to healthy controls (p<0.001, each comparison). CVI was significantly decreased in patients with FMF compared to controls (62.28±2.2 and 64.79±4.3, p<0.001). CONCLUSION: We concluded that the choroidal vasculature structure may be affected prior to retinal changes in patients with FMF.

Machine learning algorithms revealed distorted retinal vascular branching in individuals with bipolar disorder.

BACKGROUND: Converging evidence designate vascular vulnerability in bipolar disorder. The predisposition progresses into distortion in time, thus detection of the vascular susceptibility may help reducing morbidity and mortality. It was aimed to assess retinal fundus vasculature in cardiovascular risk-free patients with bipolar disorder. METHODS: Total of 68 individuals (38 patients with bipolar disorder, 30 healthy controls) were enrolled. In order to avoid from degenerative processes, participants were between 18 and 45 years of age, vascular risk factors were eliminated. Microscopic retinal fundus images were processed with machine learning algorithms (multilayer perceptron and support vector machine) and artificial neural network approaches. RESULTS: In comparison to the healthy control group, the bipolar disorder group had lower number of breaking points (P < 0.001), lower number of curved vessel segments (P < 0.001). Total length of smooth vessels was longer (P = 0.040), and total length of curved vessel segments was significantly shorter (P < 0.001) than the control group. Vascular endothelial growth factor levels and gender were the confounders. There were significant correlations between vascular measures and serum lipid levels. LIMITATIONS: Sample size was small and patients were on various medications. CONCLUSIONS: These results indicate distortion in retinal vascular branching in bipolar disorder. Disrupted branching may reflect disturbed prosperity of retinal vascular plexus in patients with bipolar disorder. Alterations in the retinal vessels might be indicators of disruption in cerebral vascular system efficiency and thus neurovascular unit dysfunction in bipolar disorder.

Anti-vascular endothelial growth factor therapy in diabetic macular edema: real-life outcomes from a multicenter study in Turkey over 36 months.

PURPOSE: This study aimed to report the visual and anatomical outcomes of intravitreal anti-VEGF treatment for diabetic macular edema (DME) in a real-world clinical setting from Turkey over 36 months. METHODS: This is a retrospective, multicenter (7 sites) study. The medical records of 1072 eyes (both previously treated and naive eyes) of 706 consecutive patients with visual impairment due to center-involving DME treated with intravitreal anti-VEGF injections between April 2007 and February 2017 were reviewed. The eyes were divided into mutually exclusive three groups based on the duration of follow-up (12, 24, or 36 months). Primary outcome measures were changes in visual acuity (VA) and central macular thickness (CMT) from baseline to final visit in each cohort, frequency of visits and intravitreal anti-VEGF injections. As secondary endpoints, VA outcomes were assessed in subgroups stratified by baseline VA [<70 ETDRS letters and ≥70 ETDRS letters] and loading dose status of anti-VEGF injections. RESULTS: VA increased by a mean of 8.2 letters (12-month cohort, p < 0.001), 5.3 letters (24-month cohort, p < 0.001), and 4.4 letters (36-month cohort, p = 0.017) at final visits. The eyes with <70 VA letters achieved more significant VA improvement at final visits in all cohorts compared with eyes with >70 VA letters (p < 0.001). The mean decreases in CMT from baseline to last visits at 12-, 24-, and 36- month cohorts were -100.5 µm, -107.7 µm, and -114.3 µm, respectively (p < 0.001). The mean number of injections given were 4.6, 2.3, and 1.8 during years 1 to 3, respectively. Patients who received loading dose showed greater VA gains than those who did not in all follow-up cohorts. CONCLUSION: Our study revealed that anti-VEGF treatment improved VA and CMT over a follow-up of 36 months. Although these real-life VA outcomes following anti-VEGF therapy for DME were similar to other real-life studies, they were inferior to those noted in randomized controlled trials, mainly due to undertreatment.

Thicknesses of the retinal layers in patients with Graves' disease with or without orbitopathy.

PURPOSE: Graves' orbitopathy (GO) is an inflammatory process that may involve the ocular surface, orbital fat, extraocular muscles, and optic nerves in patients with Graves' disease (GD). We aimed to compare thicknesses of retinal layers in patients with GD with and without GO. METHODS: One hundred seven patients with GD [23 with GO (Group 1), 84 without GO (Group 2)] and eighteen volunteers (Group 3) were enrolled. The spectral-domain optical coherence tomography (SD-OCT) was used for ophthalmologic evaluation. Seven retinal layers including retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE) were assessed. The thicknesses of layers were compared in groups. RESULTS: The median GCL thickness values in groups 1, 2, and 3 were 14 µm, 15 µm, and 17.5 µm, respectively (p = 0.02). The median IPL thickness was 20 µm in group 1, 21 µm in group 2, and 22 µm in group 3 (p = 0.038). The median RPE thickness values in groups 1, 2, and 3 were 16 µm, 17 µm, and 18.5 µm, respectively (p = 0.001). GCL in group 1 was thinner than in group 3 (p = 0.02), while similar in groups 2 and 3 (p = 0.06). IPL in group 1 was thinner than in group 3 (p = 0.035), while similar in groups 2 and 3 (p = 0.13). RPE in groups 1 and 2 was thinner than in group 3 (p = 0.009, p = 0.001, respectively), while it was similar in groups 1 and 2 (p = 0.93). RNLF, INL, OPL, ONL were similar in all three (p > 0.05 for each). CONCLUSION: Ganglion cell layer and IPL were thinner in patients with GO than in healthy controls, while both were similar in patients without GO and healthy controls. RPE was thinner in all Graves patients than in healthy controls. Early detection of changes in retinal layers of GD may guide the physician to prevent significant vision problems.

Evaluation of sphingolipid metabolism on diabetic retinopathy.

PURPOSE: To evaluate the aqueous and serum levels of sphingolipid metabolism mediators such as sphingosine 1 phosphate (S1P), sphingosine kinase 1 (SK1), sphingosine kinase 2 (SK2), ceramide kinase (CK), and acid sphingomyelinase (ASM) which are thought to take part in diabetic retinopathy (DR) pathogenesis, and development and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: A prospective cross-sectional study was conducted on type 2 diabetic and control patients who underwent cataract surgery. Three different subgroups, namely, non-diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR), were allocated and the S1P, SK1, SK2, CK, and ASM levels in the serum and aqueous humor samples of diabetic and control patients were evaluated. Kolmogorov-Smirnov test, Student's t-test, and Mann-Whitney U test were used for the statistical analysis of the study. RESULTS: Among a total of 45 patients, including diabetic and control patients, the mean aqueous levels of SK1 (P < 0.001), SK2 (P = 0.012), ASM (P = 0.006), and CK (P = 0.002) were higher in all diabetic patients. The mean aqueous level of S1P was significantly higher in the PDR group than in other groups (P = 0.003). The mean aqueous levels of SK2 and ASM also increased in the NDR, NPDR, and PDR subgroups, respectively (P < 0.001). In addition, the mean serum levels of S1P, SK1, and ASM were higher in the diabetic patients (P = 0.015, P = 0.034, and P = 0.006, respectively). CONCLUSION: According to our findings, both aqueous and serum levels of S1P, SK1, and ASM and only the aqueous levels of SK2 and CK were higher in diabetic patients. This study suggested that sphingolipid metabolism may play an important role in DR pathogenesis.

Retinal layers in prolactinoma patients: a spectral-domain optical coherence tomography study.

PURPOSE: Prolactinoma is a type of pituitary tumour that produces an excessive amount of the hormone prolactin. It is the most common type of hormonally-active pituitary tumour. These tumours can cause ocular complications such as vision loss and visual fields (VF) defect. In this study, we aimed to evaluate the thickness of chorioretinal layers in patients with prolactinoma. METHODS: We enrolled 63 eyes of 32 prolactinoma patients and 36 eyes of 18 age and gender-matched healthy controls. All participants underwent complete hormonal and ophthalmological examination, including spectral-domain optical coherence tomography (SD-OCT) and VF test.The complete biochemical response was defined as serum PRL concentration ≤ 20 ng/mL at the time of evaluation.The seven layers were retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE). The results of prolactinoma patients were compared with the control group. RESULTS: The mean RNFL, GCL, IPL, INL, ONL, and RPE were thinner in prolactinoma patients than the control group (p < 0.05) while OPL was similar between groups (p > 0.05).None of the patients had VF defect.The thickness of retinal layers was similar in patients with and without complete biochemical response (p > 0.05). CONCLUSION: To our knowledge, this is the first study that evaluates the thickness of chorioretinal layers in patients with prolactinoma.Most of the layers were thinner than the control group.Therefore, detailed eye assessment should be a routine component of the follow-up visits of prolactinoma patients and further studies related to this condition are required.

Effect of Transcatheter Aortic Valve Replacement on Retinal Layer Thickness Measured by Optical Coherence Tomography.

Transcatheter aortic valve replacement (TAVR) is associated with clinically significant cerebral microembolism and cognitive status changes. There are no data on the impact of TAVR on retinal layers. We assessed the influence of TAVR on the retinal nerve fiber layer, ganglion cell complex (GCC), and macular thickness (MT) measured by spectral domain optical coherence tomography (SD-OCT). Elderly patients (n = 50) with severe aortic stenosis undergoing TAVR were included in this study (mean age: 78.5 ± 6.9 years). Retinal nerve fiber layer, GCC, and MT were measured with SD-OCT by an ophthalmologist before and on the first day and in the first month after TAVR. The average MT was significantly increased on the first day after TAVR compared with the basal value (P = .04). Ganglion cell complex thickness was significantly thinner on the first day after TAVR than the basal value in the inner inferior quadrant and outer temporal quadrant of the left eye (P = .03 and .04, respectively). Postoperative changes observed on the first day compared with the preoperative period returned to basal values in the first month. In conclusion, TAVR did not cause permanent changes in retinal layers.

RELATIONSHIP BETWEEN STAGES OF DIABETIC RETINOPATHY AND LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN AQUEOUS HUMOR AND SERUM.

PURPOSE: The aim of the study was to determine aqueous humor and serum levels of brain-derived neurotrophic factor (BDNF) in diabetic patients with and without retinopathy. METHODS: The study included diabetic patients with or without retinopathy, who had an indication for cataract surgery. The study groups were diabetic patients without retinopathy (Group 2), with nonproliferative diabetic retinopathy (Group 3), and with proliferative retinopathy (Group 4). To quantitatively determine the amount of BDNF in samples, the RayBio Human BDNF ELISA kit (Norcross, GA), based on an enzyme-labeled immunosorbent assay was used. RESULTS: The median serum BDNF levels were significantly lower in all the study groups than in the control group (P values: 0.038 Group 2, 0.02 Group 3, and 0.002 Group 4). Serum BDNF was lower in Group 4 than in Group 3 (P = 0.030), and in Group 3 than in Group 2 (P = 0.04). The median aqueous humor BDNF levels were significantly decreased in all groups (P values: 0.047 Group 2, 0.021 Group 3, and 0.007 Group 4). There was no significant difference between Groups 2, 3, and 4 (P = 0.214). CONCLUSION: The serum and aqueous humor BDNF levels decreased in patients with diabetes mellitus (DM) before the emergence of clinical signs of retinopathy.

Evaluation of the correlation between quantitative measurement of the foveal avascular zone and retinal vessel density and outer retinal disruptions in diabetic patients

Background/aim: The aim of the current study was to evaluate the correlation between the integrity of the outer retinal layers on optical coherence tomography (OCT) and objective parameters of retinal microvascular perfusion on optical coherence tomography angiography (OCTA). Materials and methods: A total of 105 eyes of 54 diabetic patients were included in the study. Integrity of the outer retinal layers including the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) was assessed by spectral-domain optical coherence tomography. The foveal avascular zone (FAZ) area and vessel density (VD) measurements in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in all the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were evaluated by OCTA. Associations between the quantitative measurement of the FAZ and retinal VD measurements and outer retinal disruptions were evaluated. Results: The FAZ area was correlated with outer retinal layer disruption both in the superficial plexus (r = 0.244, 0.228, 0.212, P = 0.013, 0.02, 0.031 for the ELM, EZ, and IZ, respectively) and the deep capillary plexus (r = 0.298, 0.234, 0.197, P = 0.002, 0.019, 0.048 for the ELM, EZ, and IZ, respectively). A significant relationship was also found between the VD measurements in the SCP and DCP in ETDRS sectors and the outer retinal layers disruption. Conclusion: The results of the current study show a significant relationship between the quantitative OCTA parameters and the integrity of the outer retinal layers. This finding reveals a correlation between retinal capillary nonperfusion and outer retinal disruption in eyes with diabetic retinopathy.

Blood coagulation parameters after intravitreal injection of aflibercept in patients with neovascular age-related macular degeneration.

PURPOSE: The aim of this study was to evaluate the effect of intravitreal injection of aflibercept (IVA) on blood coagulation tests in neovascular age-related macular degeneration (AMD) patients. METHODS: Thirty-four patients with neovascular AMD (study group) and 32 healthy individuals (control group) were enrolled. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured at different times in patients with neovascular AMD. RESULTS: The levels of PT and aPTT after IVA were decreased at 1 month after the first injection and 1 month after the second injection compared to the baseline measurement in the study group. CONCLUSIONS: IVA may cause a decrease in the levels of PT and aPTT at 1 month after the first injection and 1 month after the second injection although these results are not statistically significant in our study.

Molecular identification of viral agents associated with acute conjunctivitis: a prospective controlled study.

BACKGROUND: Viral conjunctivitis are the most frequent infections in ophthalmology clinics. The diagnosis is usually relying on clinical findings and medical history. However, topical antibiotics are often used unnecessarily addition to symptomatic treatment because of unsure agents. We aimed to detect the Adenovirus, Coxsackievirus and Enterovirus from conjunctiva and pharyngeal samples of patients. METHODS: The conjunctiva and pharyngeal samples of the patients with conjunctivitis were taken by Virocult transport media and kept at -80̊C up to study day. Adenovirus spp, Enterovirus 70 and Enterovirus 71, Coxsackie A24 and Coxsackie A16 were detected by real-time PCR. Samples from healthy health care workers of ophthalmology clinic were used for control group. RESULTS: A total of 176 samples (conjunctival and pharyngeal samples of 62 patient and 26 healthy subjects) were included. The mean age of 34 (55.7%) male and 27 (44.3%) female patients was 34±17. Twenty five (40.3%) of the patients were receiving antibiotic drops at first visit. The main etiologic agent in conjunctival samples was found to be Adenovirus (46/62, 74.2%) followed by Enterovirus 70 (4/62, 6.4%) and Enterovirus 71 (4/62, 6.4%). Coxsackievirus 16 and 24 were also found in 2 patients (1/62 each, 1.6%). Pharyngeal samples were also positive for Adenovirus (20/62, 32.3%), Enterovirus 70 and 71 (7/62, 11.3% and 5/62, 8.1% respectively), Coxsackievirus 16 and 24 (2/62, 3.2% and 1/61, 1.6%). CONCLUSIONS: It is very difficult in viral conjunctivitis to make clinical differentiation caused by different agents because of common clinical signs and symptoms. In routine clinical work, the viral conjunctivitis usually related with Adenovirus. But almost one fourth of the patients' conjunctivitis were not related to Adenovirus, which shows the importance of the laboratory diagnostics. True diagnosis plays an important role on prevention of contamination and unnecessary use of antibiotics in viral conjunctivitis.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.