Corneal Biomechanics and Other Factors Associated with Postoperative Astigmatism after Cataract Surgery.

This study aimed to investigate the impact of the cornea's biomechanical properties, corneal hysteresis (CH), and corneal resistance factor (CRF) on postoperative astigmatism after cataract surgery and determine the other factors that influence it. Forty eyes of 40 patients (13M/27F; the median age of 74) were included in this prospective study, underwent 2.75 mm incision cataract surgery, and were followed for 30 days. Visits were scheduled at baseline before surgery (V0), the 1st (V1), the 7th (V2), and the 30th (V3) postoperative days. The main parameters estimated and analyzed with Statistica® 14.0.1 were CH, CRF, astigmatism diopter, and axis. Following the cataract surgery, the CH did not significantly change during the study visits (p = 0.109). However, there was a significant change in the CRF from baseline during the study visits (per protocol set) (p = 0.002). After a slight but insignificant increase from V0 to V1, post hoc analysis found a significant decrease in the mean CRF from V1 to V2 (p = 0.049) with no substantial change from V2 to V3. According to the post hoc analysis, the median astigmatism diopter increased significantly only from V0 to V1 (p = 0.001) and slightly but not significantly decreased to the end of the study with the achievement of a near-baseline value. The main predictors for the final astigmatism diopter (R2 = 0.898) obtained by stepwise regression analysis were its values at V0, V1, and V2 (p < 0.001). The CRF at V1 was marginally significant, with a negative parameter estimate of -0.098303 (p = 0.0623). In conclusion, there was no correlation between preoperative CH and CRF and postoperative astigmatism using 2.75 mm incision cataract surgery. However, the final astigmatism diopter's main predictors were its baseline values before cataract surgery, the first, and the seventh postoperative days.

In Association with Other Risk Factors, Smoking Is the Main Predictor for Lower Transcutaneous Oxygen Pressure in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) significantly increases the risk of peripheral artery disease (PAD), and diabetes is the leading cause of nontraumatic amputations. This study investigated the risk factors for transcutaneous oxygen pressure (TcPO2) in T2DM, a noninvasive method to quantify skin oxygenation and the underlying microvascular circulation. The study included 119 T2DM patients (91 male/28 female). TcPO2 measurements were conducted with the Tina TCM4 Series transcutaneous monitor (Radiometer, Copenhagen, Sweden) and skin electrodes. Patients with TcPO2 < 40 mmHg were younger (p = 0.001), had significantly higher systolic blood pressure (SBP) (p = 0.023), glycated hemoglobin (HbA1c) (p = 0.013), fasting plasma glucose (fPG) (p = 0.038), total cholesterol (p = 0.006), LDL cholesterol (p = 0.004), and had more frequent smoking habits (p = 0.001) than those with TcPO2 ≥ 40 mmHg. The main predictors for the TcPO2 value (R2 = 0.211) obtained via stepwise regression analysis were age, smoking, SBP, HbA1c, fPG, and total and LDL cholesterol. Among all the listed predictors, smoking, HbA1c, and LDL cholesterol were found to be the most significant, with negative parameter estimates of -3.051310 (p = 0.0007), -2.032018 (p = 0.0003), and -2.560353 (p = 0.0046). The results of our study suggest that in association with other risk factors, smoking is the main predictor for lower TcPO2 in T2DM.

Risk Factors for Ankle Brachial Index and Carotid Artery Stenosis in Patients with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) significantly increases the risk of atherosclerotic cardiovascular disease. Ankle brachial index (ABI) and carotid artery stenosis are non-invasive indicators of generalized atherosclerosis. This study aimed to explore the risk factors for ABI and carotid artery stenosis and discover which factors simultaneously influence both conditions in T2DM. The study included a total of 101 patients with T2DM. ABI was performed via Doppler ultrasound, and both common carotid arteries were examined via ultrasound to obtain the percentage of carotid artery stenosis. A negative correlation was noted between the ABI and the percentage of carotid artery stenosis (p = 0.043). ABI correlated significantly negatively with waist circumference (p = 0.031), total cholesterol (p = 0.003), low-density lipoprotein (LDL) cholesterol (p = 0.003), and C-reactive protein (CRP) (p = 0.017), whereas the percentage of carotid artery stenosis correlated with the smoking habit (p = 0.017) and CRP (p = 0.042). The best model for predicting the ABI value (R2 = 0.195) obtained from stepwise regression analysis included waist circumference, LDL cholesterol, triglycerides, and CRP, while the best model for the percentage of the carotid artery stenosis (R2 = 0.112) included smoking and CRP. CRP influenced the ABI value with a negative parameter estimate of -0.008962 (p = 0.053) and the percentage of the carotid artery stenosis with a positive parameter estimate of 0.443655 (p = 0.006) relative to a one-unit change of it, presenting the negatively significant impact of CRP on the association between carotid artery stenosis and low ABI. Our results suggest that CRP is the most important risk factor that connects ABI and carotid artery stenosis, which are important non-invasive indicators of generalized atherosclerosis in T2DM.

Short-Term Effect of Conventional Versus Accelerated Corneal Cross-Linking Protocol on Corneal Geography and Stability.

Purpose: To determine the 6-month effect of conventional (CXL30) and accelerated cross-linking with a UVA intensity of 9 mW/cm2 (CXL10) on corneal stability and to investigate whether there was a difference in ABCD grading system parameters regarding the two different procedures. Methods: Twenty-eight eyes of 28 patients with a documented keratoconus (KN) progression were included. Patients were selected to undergo either epi off CXL30 or CXL10. At the baseline and the follow-up visits after one (V1), three (V2), and six months (V3), the patients underwent complete ophthalmic examination and corneal tomography. Results: In the CXL30 group, all the parameters from the ABCD grading system significantly changed from baseline to V3; parameter A decreased (p = 0.048), B and C increased (p = 0.010, p < 0.001), and D decreased (p < 0.001). In the CXL10 group, there were no changes in parameters A (p = 0.247) and B (p = 0.933), though parameter C increased (p = 0.001) and D decreased (p < 0.001). After an initial decline after one month, visual acuity (VA) recovered on V2 and V3 (p < 0.001), and median maximal keratometry (Kmax) decreased in both groups (p = 0.001, p = 0.035). In the CXL30 group, there were significant changes in other parameters; average pachymetric progression index (p < 0.001), Ambrósio relational thickness maximum (ARTmax) (p = 0.008), front and back mean keratometry (p < 0.001), pachymetry apex (PA) (p < 0.001), and front elevation (p = 0.042). However, in the CXL10 group, there were significant changes only in ARTmax (p = 0.019) and PA (p < 0.001). Conclusion: Both epi-off CXL protocols showed similar short-term efficacy in improving VA and Kmax, halting the progression of KN, and both similarly changed tomographic parameters. However, the conventional protocol modified the cornea more significantly.

Human complement component C3 N-glycome changes in type 1 diabetes complications.

Aim: Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors. Research design and methods: Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling. Results: Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration. Conclusion: This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity.

N-glycosylation of serum proteins in adult type 1 diabetes mellitus exposes further changes compared to children at the disease onset.

OBJECTIVE: Previously we have shown that plasma protein N-glycosylation is changed in children at the onset of type 1 diabetes. In this study, we aim to identify N-glycan changes in adults with T1DM, compare them to those in children, and investigate their associations with disease duration, complications, glycaemic status, and smoking. METHODS: Serum protein N-glycans from 200 adults with type 1 diabetes and 298 healthy controls were analysed using ultra-high performance liquid chromatography and divided into 39 directly measured glycan groups from which 16 derived traits were calculated. RESULTS: Compared to healthy controls, subjects with type 1 diabetes showed differences in 19 glycan groups and a decrease in monogalactosylated, an increase in digalactosylated, monosialylated, and antennary fucosylated derived traits, from which changes in monogalactosylation and seven directly measured traits overlapped with previously reported in children. Changes in four directly measured and two derived traits previously seen in children were not detected in adults. HbA1c was positively associated with sialylated and highly branched structures, whereas N-glycome was not influenced by disease duration or diabetic complications. CONCLUSIONS: Our results suggest potential N-glycome involvement in different stages of type 1 diabetes, including processes underlying its development, the disease itself, as well as those occurring after disease establishment.

ORAL CHANGES IN PEDIATRIC PATIENTS WITH EATING DISORDERS.

Numerous oral changes develop as a result of dysfunctional eating behavior in patients with eating disorders (ED). The aim of this study was to evaluate the correlation among oral manifestations, age, disease duration and nutritional status in pediatric patients with ED. The study included 50 female ED patients, median age 14 (range 10-18) years and median disease duration 9 (range 1-42) months. Nutritional status was expressed as z-score for body mass index (BMI). Mean BMI z-score was -2.10±1.64. The most commonly observed oral findings were dental plaque, marginal gingivitis, morsicatio, dental calculus, caries, pharyngeal erythema, exfoliative cheilitis and angular cheilitis. Dental plaque and pharyngeal erythema were correlated with shorter disease duration (p=0.048; p=0.040), while frictional keratosis of tongue was correlated with longer disease duration (0.011). Linea alba and pain in the temporomandibular joint were associated with younger age (p=0.012; p=0.024), and tooth impression on tongue with lower degree of nutrition (p=0.030). This study showed that there was a link among oral manifestations, age, disease duration and degree of nutritional disorder, although further investigations comparing the groups of ED patients with different age, disease duration and nutritional status would give better, concrete and precise conclusions.

Serum adipocytokines are associated with microalbuminuria in patients with type 1 diabetes and incipient chronic complications.

AIMS: Recent studies have implicated possible contribution of adipocytokines in development and progression of microvascular complications in patients with type 1 diabetes (T1DM). The aim of our study was to investigate relationship between adipocytokines, namely leptin, resistin, adiponectin and dipeptidyl peptidase-4 (DPP-4) activity, with albuminuria in T1DM. METHODS: This study included 202 T1DM without or with incipient microvascular complications. Urinary albumin excretion rate (UAE) was measured from at least two 24-h urine samples. Serum DPP-4 activity was measured by a colorimetric assay, and the level of adiponectin, leptin, and resistin was determined by the ELISA method. RESULTS: Serum DPP-4 activity and adiponectin were significantly higher in patients with normoalbuminuria compared to patients with microalbuminuria (47 vs 36 U/L, and 10.9 vs 7.3 µg/mL, respectively, p ≤ 0.02). In multivariate logistic regression analysis adiponectin and serum DPP-4 activity were significantly associated with risk of microalbuminuria in our subjects (p ≤ 0.04), with odds ratios of 0.72-0.99. However, after adjustment for age, sex, HbA1c, duration of diabetes and BMI, only serum DPP-4 activity was significantly associated with risk of microalbuminuria (p = 0.008). CONCLUSION: The results of our study suggest that serum DPP-4 activity is lower in T1DM with microalbuminuria. Prospective studies are warranted to evaluate the relationship between serum DPP-4 activity and progression and development of albuminuria and nephropathy in T1DM.

Total Serum Cholesterol Increases Risk for Development and Progression of Nonproliferative Retinopathy in Patients with Type 1 Diabetes Without Therapeutic Intervention: Prospective, Observational Study.

INTRODUCTION: Results from studies investigating relationship between serum lipids and risk of development and progression of diabetic retinopathy (DR) in patients with type 1 diabetes (T1DM) are not consistent. The objective of this study was to explore the relationship between serum lipids and risk of development and progression of nonproliferative diabetic retinopathy (NPDR) in T1DM with normal renal function and with no therapeutic intervention that might influence on retinopathy and serum lipids status. METHODS: A total of 103 T1DM with normal renal function (urinary albumin excretion rate <30 mg/24 h, estimated glomerular filtration rate (eGFR) >60 mL min‒11.73m‒2), and before any interventions with lipid-lowering therapy, ACE inhibitors or angiotensin II receptor blockers were included in this study and followed for 41 months. Photodocumented retinopathy status was made according to the EURODIAB protocol. RESULTS: Patients who developed NPDR or progressed to proliferative retinopathy were older (44 vs. 33 years, p <0.001), had longer duration of diabetes (21.1 vs. 13.3 years, p <0.001), and higher serum total cholesterol level (5.1 vs. 4.5 mM/L, p = 0.02) compared to patients without retinopathy. In a backward stepwise Cox's multiple regression analysis serum total cholesterol was significantly associated with risk of development or progression of NPDR in our subjects (p = 0.04), with odds ratios of 1.27-1.91. CONCLUSION: These data suggest that serum total cholesterol levels are associated with risk of development and progression of NPDR in T1DM and normal renal function. The study was conducted in patients with no therapeutic interventions.

Diabetic Macular Edema: Traditional and Novel Treatment

Diabetes is one of the leading public health problems worldwide. Diabetic macular edema (DME) is the main cause of vision loss in patients with diabetes. Ideal metabolic control of diabetes is the primary goal of treatment and the basic way of preventing and stopping the progression of DME. Although laser photocoagulation has been the standard treatment of DME for nearly three decades, superior outcomes can be achieved with novel, intravitreal anti-VEGF and steroid therapy. Novel treatment option for DME depends on visual acuity and location/extent of macular thickening based on optical coherence tomography scans. According to the International Clinical Classification Scale, DME is divided into no center-involving DME and center-involving DME (CI-DME). New guidelines recommend intravitreal treatment as the treatment of choice for patients with CI-DME and moderate visual impairment. Patients with no CI-DME and mild visual impairment should be treated with modified ETDRS laser photocoagulation and closely observed. Vitrectomy is the treatment of choice for patients with a tractional component of DME. Nowadays, traditional treatment goal of preventing blindness in patients with DME has been changed by the new goal aiming to restore impaired vision, prevent further vision loss and improve visual function. Therefore, many trials addressing this new concept have been underway worldwide.

Inflammation and pharmacological treatment in diabetic retinopathy.

Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer.

Maternal immune system adaptation to pregnancy--a potential influence on the course of diabetic retinopathy.

BACKGROUND: Progression of diabetic retinopathy occurs at least temporarily during pregnancy. Although the cause of this progression is not entirely understood, the immune phenomenon and chronic inflammation may play a significant role. During pregnancy in order to avoid fetus rejection, certain components of the immune system that are knowingly implicated in the pathogenesis of diabetic retinopathy are activated including generalized leukocyte activation and an increase in certain cytokine plasma levels. Activated leukocytes with up regulated adhesion molecules have an increased potential to bind to the endothelium cells of blood vessels. Leukocyte-endothelial interaction and the consequent leukostasis with capillary occlusion, ischemia and vascular leakage have a substantial role in the development of diabetic retinopathy. Furthermore, certain increased cytokines are known to cause blood-retinal-barrier breakdown whilst others promote angiogenic and fibrovascular proliferation and thereby can also be implicated in the pathogenesis of this diabetic complication. PRESENTATION OF THE HYPOTHESIS: We hypothesized that the activation of the immune system during gestation may have an influence on the course of retinopathy in pregnant diabetic women. TESTING THE HYPOTHESIS: We suggest two prospective follow up studies conducted on women with type 1 diabetes mellitus. The first study would include a group of non-pregnant women and a group of diabetic women undergoing normal pregnancy matched for age and duration of diabetes. In the second study pregnant women would be divided into two groups: one with normal pregnancy and the other with preeclampsia. The procedure and data collection in both studies will be identical: a complete ophthalmological examination, glycaemic control, blood pressure measurement and venous blood samples for the determination of plasma levels of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8) and adhesion molecules (ICAM-1, VCAM-1). IMPLICATIONS OF THE HYPOTHESIS: Considering the present assumption, the gestational immune activation could be suggested as a potential risk factor for the development and progression of retinopathy in diabetic women. A better understanding of immunomodulatory effects of pregnancy on diabetic retinopathy pave the way for further investigations of the mechanism of its pathogenesis and could be essential for novel approaches to the treatment of this serious sight threatening complication of diabetes mellitus.

Endonasal endoscopic orbital decompression in patients with Graves' ophthalmopathy.

AIM: To present the results of endonasal endoscopic orbital decompression in patients with Graves' ophthalmopathy. METHODS: Endonasal endoscopic orbital decompression was performed in 32 orbits of 21 patients with Graves' ophthalmopathy. In 17 patients the surgery was performed because of active ophthalmopathy non-responsive to conservative treatment, and in 4 patients for esthetic reasons. Preoperative and postoperative examination included visual acuity, examination of the eyelids and cornea, ocular motility, cover testing, Hertel exophthalmometry, and applanation tonometry. RESULTS: Visual acuity improved from preoperative 0.81+/-0.28 (mean +/- standard deviation) to postoperative 0.92+/-0.21 (p=0.0032, Student t-test). Retraction of upper and lower eyelids, as well as exposure keratitis, was reduced after operation (p<0.001). Mean proptosis reduction in all orbits was 4.6+/-1.7 mm (p<0.001). An average reduction of intraocular pressure was 3.4+/-3.0 mmHg (p<0.001). New-onset diplopia developed in 8 patients. Diplopia persisted in 9 out of 11 patients who had preoperative diplopia. Two patients experienced postoperative relief of diplopia. Ocular motility was subsequently corrected by eye muscle surgery in 13 eyes, whereas prisms were used in other 5 manifestly strabic eyes. CONCLUSIONS: Endonasal endoscopic orbital decompression procedure improved visual acuity, decreased proptosis and intraocular pressure, and also had favorable cosmetic results in most patients. Post decompression diplopia and strabismus were successfully managed by either eye muscle surgery or application of prisms.