Optical Coherence Tomography Angiography (OCTA) of the eye: A review on basic principles, advantages, disadvantages and device specifications.

Optical Coherence Tomography Angiography (OCTA) is a relatively new imaging technique in ophthalmology for the visualization of the retinal microcirculation and other tissues of the human eye. This review paper aims to describe the basic definitions and principles of OCT and OCTA in the most straightforward possible language without complex mathematical and engineering analysis. This is done to help health professionals of various disciplines improve their understanding of OCTA and design further clinical research more efficiently. First, the basic technical principles of OCT and OCTA and related terminology are described. Then, a list of OCTA advantages and disadvantages, with a special reference to blood flow quantification limitations. Finally, an updated list of the basic hardware and software specifications of some of the commercially available OCTA devices is presented.

Serpin Family E Member 1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetic Nephropathy: An Association Study and Meta-Analysis Using a Genetic Model-Free Approach.

BACKGROUND: Many lines of evidence highlight the genetic contribution on the development of diabetic nephropathy (DN). One of the studied genes is SERPINE1 whose the role in the risk of developing DN remains questionable. In order to elucidate the contribution of SERPINE1 in DN progression in the context of type 2 diabetes mellitus (T2DM), we conducted an association study and meta-analysis of SERPINE1 genetic variants. MATERIALS AND METHODS: A total of 190 patients with DN, 150 T2DM (type 2 diabetes mellitus) patients without DN and 238 healthy controls were recruited. We selected five tag single-nucleotide polymorphisms (SNPs) from the HapMap. The generalized odds ratio (ORG) was calculated to estimate the risk on DN development. Subgroup analyses based on ethnicity and type of diabetes were also performed. RESULTS: Both the present association study regarding SERPINE1 SNPs (rs2227667, rs2070682, rs1050813, rs2227690, rs2227692) did not found any significant association between SERPINE1 variants and DN and the meta-analysis of variant 4G>5G (rs1799889) did not also reveal a significant association between 4G>5G variant and DN in main and subgroup analyses. DISCUSSION: In conclusion, the present association study and meta-analysis provides strong evidence that SERPINE1 genetic variant 4G>5G is not implicated in the risk or development of DN in Caucasians. Further studies in other populations remain to further investigate the role of this variant in the course of DN.

Blood flow velocity comparison in the eye capillaries and postcapillary venules between normal pregnant and non-pregnant women.

BACKGROUND: There is no consensus on how much and at what diameters the blood flow velocity changes in the female microcirculation during normal pregnancy. METHODS: A non-contact, digital slit-lamp biomicroscopy system was used to measure axial blood velocity (Vax) and diameter (D) in the conjunctival microcirculation of 28 normal non-pregnant women (Control Group), 17 women in the first semester of their normal pregnancy (Group 1) and 16 women in the third trimester of their normal pregnancy (Group 2). Blood volume flow (Q) was estimated from Vax and D. Microvessels were classified as "capillaries" (CAP) with D < 9 µm, "postcapillary venules of size 1" (PC1) with 9 ≤ D < 14 µm and "postcapillary venules of size 2" (PC2) with 14 ≤ D ≤ 24 µm. RESULTS: The women groups did not differ significantly in age, diastolic and systolic pressure and diameter of each size. Taking as baseline the capillary Vax of 0.51 mm/s of the Control Group, there was a statistically significant (p < 0.001) increase to 0.74 mm/s (45%) in Group 1 and to 0.95 mm/s (86%) in Group 2. This significant Vax increase in capillaries (CAP) was a consistent finding irrespective of the exact vessel size cut-off value for discriminating CAP from PC1. There was no statistical difference in Vax among groups at postcapillary venules of size 2 (PC2). Statistical conclusions for blood volume flows were similar to velocities. CONCLUSIONS: Normal pregnancy increases significantly axial blood velocity (Vax) in capillaries (CAP) with diameter <9 µm.

SLC2A1 Tag SNPs in Greek Patients with Diabetic Retinopathy and Nephropathy.

Backround: Genetic variants are implicated in the development of diabetic retinopathy (DR) and nephropathy (DN). The role of solute carrier family 2-facilitated glucose transporter member 1 (SLC2A1), also known as glucose transporter (GLUT1), on DR and DN remain controversial. OBJECTIVE: Examination of the influence of tag SLC2A1 single-nucleotide polymorphisms (SNPs) on the development of DR and DN during the course of type 2 diabetes mellitus (T2DM). METHODS: A total of 169 patients with DR or DN, 107 uncomplicated T2DM patients, and 315 controls were recruited and genotyped for 14 SLC2A1 tag SNPs. SNPs and haplotypes were tested for associations with microvascular diabetes' complications. RESULTS: rs3768029 TT genotype was associated with a lower risk of DR + DN, compared to the CC wild-type (p = 0.0024). Moreover, CT and TT rs841847 genotypes were associated with a higher risk of DR + DN compared to the CC genotype (p = 0.0028). A common haplotype (GGCCCGCATCAAT) was associated with an increased risk of DR, DN, DR ± DN, and DR + DN phenotypes. Mutational loads of rs3768029, rs3729548, rs841853, and rs841847 were found to influence the development of microvascular complications during the T2DM course. CONCLUSIONS: This study provides evidence that SLC2A1 gene variants might be implicated in the development of T2DM microvascular complications.

Plasminogen Activator Inhibitor Type-1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetes Mellitus Type 2 and Diabetic Retinopathy.

BACKGROUND: There is accumulating evidence for genetic susceptibility to the development of diabetic retinopathy (DR). The role of plasminogen activator inhibitor-1 (PAI-1) in DR risk remains controversial. OBJECTIVE: The present study was designed to investigate possible influence of PAI-1 gene region polymorphisms on the risk of DR and on the risk of developing DR early vs late in the course of type 2 diabetes mellitus (T2DM). METHODS: A total of 138 patients with DR, 107 patients with T2DM without DR, and 315 healthy controls were recruited. To cover the majority of the genetic variability across the extended region of PAI-1 gene, five tag single-nucleotide polymorphisms (SNPs) from the HapMap using a pairwise approach and an r2 ≥ 0.8 and a minor allele frequency (MAF) of >0.05 were identified. Using logistic regression analyses, tag SNPs and haplotypes were tested for associations with DR risk and risk of DR development early or late in the course of T2DM. The generalized odds ratio (ORG) was calculated to estimate the mutational load effect on DR development among all participants. Corrections for multiple comparisons were carried out (p-value < 0.01). RESULTS: A significant effect of rs2070682 on the risk of early DR onset was found in the codominant model of inheritance [odds ratio, OR (95% confidence interval, CI): 5.04 (1.47-17.28), p = 0.018]. However, this association marginally did not survive multiple testing corrections. No other significant association between PAI-1 tag-SNPs and haplotypes was revealed. Furthermore, no significant mutational load effect of PAI-1 tag SNPs on the risk of DR development in T2DM course was found. CONCLUSIONS: In conclusion, the present study does not provide any strong evidence that PAI-1 gene variants are implicated in the risk of DR or the development of DR during T2DM course.

Wall shear stress quantification in the human conjunctival pre-capillary arterioles in vivo.

Blood volume flow (Q), wall shear rate (WSR) and wall shear stress (WSS) were quantified, for the first time, in the conjunctival pre-capillary arterioles of normal human volunteers with diameters (D) between 6 and 12 µm. The variation of the blood velocity throughout the cardiac cycle was taken into account using high speed video microcinematography. The dual effect of arteriolar diameter, firstly on the WSR and secondly on the dynamic viscosity of blood, was taken into account in the estimation of WSS. The average Q, WSR and WSS, throughout the cardiac cycle ranged from 13 to 202 pl/s, 587 to 3515 s(-1) and 1.7 to 21.1 N/m(2) respectively. The best fit power law equations, giving the increase of Q and the decrease of WSR and WSS with diameter, are presented for the systolic and diastolic phase as well as for the averages throughout the cardiac cycle. According to the WSS best fit equation, the average WSS decreases from 10.5 N/m(2) at D=6 µm down to 2.1 N/m(2) at D=12 µm.

European ST80 community-associated methicillin-resistant Staphylococcus aureus orbital cellulitis in a neonate.

BACKGROUND: Methicillin-resistant Staphylococcus aureus is a serious cause of morbidity and mortality in hospital environment, but also, lately, in the community. This case report is, to our knowledge, the first detailed description of a community-associated methicillin-resistant S. aureus ST80 orbital cellulitis in a previously healthy neonate. Possible predisposing factors of microbial acquisition and treatment selection are also discussed. CASE PRESENTATION: A 28-day-old Caucasian boy was referred to our hospital with the diagnosis of right orbital cellulitis. His symptoms included right eye proptosis, periocular edema and redness. Empirical therapy of intravenous daptomycin, rifampin and ceftriaxone was initiated. The culture of pus yielded a methicillin-resistant S. aureus isolate and the molecular analysis revealed that it was a Panton-Valentine leukocidine-positive ST80 strain. The combination antimicrobial therapy was continued for 42 days and the infection was successfully controlled. CONCLUSIONS: Clinicians should be aware that young infants, even without any predisposing condition, are susceptible to orbital cellulitis caused by community-associated methicillin-resistant S. aureus. Prompt initiation of the appropriate empirical therapy, according to the local epidemiology, should successfully address the infection, preventing ocular and systemic complications.

Blood velocity pulse quantification in the human conjunctival pre-capillary arterioles.

Axial red blood cell velocity pulse was quantified throughout its period by high speed video microcinematography in the human eye. In 30 conjunctival precapillary arterioles (6 to 12 microm in diameter) from 15 healthy humans, axial velocities ranged from 0.4 (the minimum of all the end diastolic values) to 5.84 mm/s (the maximum of all the peak systolic values). With the velocity pulse properly quantified, two parameters can be estimated: (1) the average velocity of the pulse during a cardiac cycle AVV (average velocity value) and (2) the magnitude of the pulsation using Pourcelot's resistive index RI. These parameters are important for the estimation of other hemodynamic parameters such as the average volume flow and the average shear stress. The results of this study revealed that the AVV in the human precapillary arterioles ranged between 0.52 and 3.26 mm/s with a mean value for all microvessels of 1.66 mm/s+/-0.11(SE). The RI ranged between 35.5% and 81.8% with a mean value of 53.1%+/-2.2. Quantitative information was obtained for the first time on the velocity pulse characteristics just before the human capillary bed.

Volume flow and wall shear stress quantification in the human conjunctival capillaries and post-capillary venules in vivo.

Understanding the mathematical relationships of volume blood flow and wall shear stress with respect to microvessel diameter is necessary for the study of vascular design. Here, for the first time, volume flow and wall shear stress were quantified from axial red blood cell velocity measurements in 104 conjunctival microvessels of 17 normal human volunteers. Measurements were taken with a slit lamp based imaging system from the post capillary side of the bulbar conjunctiva in microvessel diameters ranging from 4 to 24 micrometers. The variation of the velocity profile with diameter was taken into account by using a profile factor function. Volume flow ranged from 5 to 462 pl/s with a mean value of 102 pl/s and gave a second power law best fitting line (r=0.97) deviating significantly from the third power law relation with diameter. The estimated wall shear stress declined hyperbolically (r=0.93) from a maximum of 9.55 N/m(2) at the smallest capillaries, down to a minimum of 0.28 N/m(2) at the higher diameter post capillary venules. The mean wall shear stress value for all microvessels was 1.54 N/m(2).