Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis.

The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (>2 g/24 h) and/or impaired kidney function (serum creatinine > 1.5 mg/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09-4.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545-11.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN.

A normative blood velocity model in the exchange microvessels for discriminating health from disease: Healthy controls versus COVID-19 cases.

A usual practice in medicine is to search for "biomarkers" which are measurable quantities of a normal or abnormal biological process. Biomarkers can be biochemical or physical quantities of the body and although commonly used statistically in clinical settings, it is not usual for them to be connected to basic physiological models or equations. In this work, a normative blood velocity model framework for the exchange microvessels was introduced, combining the velocity-diffusion (V-J) equation and statistics, in order to define the normative range (NR) and normative area (NA) diagrams for discriminating normal (normemic) from abnormal (hyperemic or underemic) states, taking into account the microvessel diameter D. This is different from the usual statistical processing since there is a basis on the well-known physiological principle of the flow diffusion equation. The discriminative power of the average axial velocity model was successfully tested using a group of healthy individuals (Control Group) and a group of post COVID-19 patients (COVID-19 Group).

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.

Visual disorders and driving ability in persons with dementia: A mini review.

Background: Impaired driving ability in patients with Alzheimer's disease (AD) is associated with a decline in cognitive processes and a deterioration of their basic sensory visual functions. Although a variety of ocular abnormalities have been described in patients with AD, little is known about the impact of those visual disorders on their driving performance. Aim: Aim of this mini-review is to provide an update on the driving ability of patients with dementia and summarize the primary visual disorders affecting their driving behavior. Methods: Databases were screened for studies investigating dementia, associated visual abnormalities and driving ability. Results: There is consistent evidence that dementia affects driving ability. Patients with dementia present with a variety of visual disorders, such as visual acuity reduction, visual field defects, impaired contrast sensitivity, decline in color vision and age-related pathological changes, that may have a negative impact on their driving ability. However, there is a paucity in studies describing the impact of oculovisual decline on the driving ability of AD subjects. A bidirectional association between cognitive and visual impairment (VI) has been described. Conclusion: Given the bidirectional association between VI and dementia, vision screening and cognitive assessment of the older driver should aim to identify at-risk individuals and employ timely strategies for treatment of both cognitive and ocular problems. Future studies should characterize the basic visual sensory status of AD patients participating in driving studies, and investigate the impact of vision abnormalities on their driving performance.

COVID-19 hemodynamic and thrombotic effect on the eye microcirculation after hospitalization: A quantitative case-control study.

BACKGROUND & OBJECTIVE: To quantify the hemodynamic and thrombotic effect of COVID-19 on the eye microcirculation of patients with thromboprophylaxis, shortly after hospital discharge. METHODS: This case-control study included 17 COVID-19 survivors (named "COVID-19 Group") and 17 healthy volunteers (named "Control Group"). Axial blood velocity (Vax) and percentage of occluded vessels (POV) were quantified by Conjunctival Video Capillaroscopy (CVC). Microvessels were identified and classified as "capillaries" (CAP), "postcapillary venules of size 1" (PC1), and "postcapillary venules of size 2" (PC2). RESULTS: The COVID-19 Group did not differ significantly in basic demographics from the Control Group. In the COVID-19 Group, there was a statistically significant (p < 0.001) reduction of Vax (39%, 49% and 47%, for CAP, PC1, and PC2, respectively) in comparison to the Control Group and a sizeable (p < 0.001) increase of POV (600%) in comparison to the Control Group. CONCLUSIONS: COVID-19 not only reduces significantly axial blood velocity in the capillaries and postcapillary venules of the eye but has also a devastating effect on microthrombosis (POV) despite thromboprophylaxis treatment. This gives a possible explanation for long COVID and a hint about the existence of a possibly unknown coagulation factor.

Quality-adjusted life years in macular oedema due to age-related macular degeneration, diabetes and central retinal vein occlusion: the impact of anti-VEGF agents in a tertiary centre in Greece.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), and macular oedema due to central retinal vein occlusion (CRVO) are leading causes of vision loss, currently managed with anti-vascular endothelial growth factor injections (anti-VEGF). The aim of this study was to calculate QALYs in patients with nAMD, DME, and CRVO treated with anti-VEGF agents (QALYs+) in a Greek tertiary hospital setting and compare them to theoretical QALYs that the patients would have without treatment (QALYs-). MATERIAL AND METHODS: The study included 143 treatment-naive patients with macular oedema due to nAMD (n = 79), DME (n = 57), and CRVO (n = 7), who received anti-VEGF injections as monotherapy according to the Treat-and-Extend (T&E) protocol. The anti-VEGF agents were ranibizumab and aflibercept in equivalent fractions. QALYs where calculated by the formula QALY = Utility Value × Time, where "Time" refers to the follow-up period of the study. For QALYs-, we assumed that visual acuity remained unchanged during this period. RESULTS: Mean follow-up time was 1.3 ± 1.2 years in the nAMD group, 1 ± 1.3 years in the DME group, and 0.5 ± 1 years in the CRVO group. There was no statistically significant difference between QALYs- and QALYs+ in all three ocular pathologies for the study period (p > 0.05 for each of the three statistical tests performed). DISCUSSION/CONCLUSION: Possible explanations for the lack of significant difference between QALYs - and QALYs + in nAMD, DME, and CRVO groups, may be the short time horizon used in this analysis, the inclusion of data from the better-seeing eye (BSE) and the specific socio-economic, geographical and health care characteristics of this rural Greek area.

Scleral buckling surgery for stage 4A and 4B retinopathy of prematurity in critically ill neonates.

PURPOSE: To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP). METHODS: Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. RESULTS: The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D. CONCLUSION: Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.

Spasm of the near reflex: a common diagnostic dilemma?

AIM: To report the clinical characteristics and diagnostic procedures used in patients with spasm of the near reflex (SNR), in order to present common investigation strategies and diagnostic pitfalls. METHODS: Retrospective case series of twenty-two patients, mainly children, with SNR or accommodation spasm (AS). AS was diagnosed on the basis of blurred vision and a difference of ≥2 dioptres between manifest and cycloplegic retinoscopy. If esotropia and miosis were present, the patients were diagnosed with SNR. All patients underwent visual acuity testing, orthoptic evaluation, assessment of refraction before and after cycloplegia, and dilated fundoscopy. Additional diagnostic investigations, such as neuroimaging, lumbar puncture (LP), electrophysiology and blood tests, were also recorded. Screen use among children was assessed in hours per day. RESULTS: There were 19 female and 3 male patients (age range 7-33y, median=10y). Seventeen patients had AS and 5 patients had SNR, with episodic blurry vision and headaches being the most common symptoms. Brain neuroimaging was performed in six patients (27%), although only one had a history of brain trauma. Two of those patients underwent visual evoked potentials and three also underwent LP and received intravenous steroid therapy. The majority of patients (90%) reported prolonged daily screen time (>2h/d), and in 55% of cases there were concurrent social problems or psychological triggers. Treatment consisted of careful explanation of the condition, atropine 1% eye drops and full cycloplegic correction by means of bifocal glasses. CONCLUSION: The diagnosis of SNR and AS may be challenging, because symptoms are usually intermittent and nonspecific, and a large number of patients are often subjected to redundant and potentially time-consuming examinations and treatment, that may exaggerate the underlying psychological disorder. Hence, detailed clinical testing and assessment of psychosocial profile is necessary, in order to avoid unnecessary investigations. Neuroimaging should be performed only in selected cases. Finally, due to prolonged screen use SNR and AS may become more frequent in the future.

Optical coherence tomography angiography reveals vascular alterations in pediatric commotio retinae.

INTRODUCTION: Aim of this study is to present the acute and long-term swept-source optical coherence tomography angiography findings in pediatric commotio retinae. MATERIALS AND METHODS: Two children presented with reduced visual acuity and Berlin edema after blunt trauma. RESULTS: Swept-source optical coherence tomography revealed hyperreflectivity of the retinal nerve fiber layer and disruption of the ellipsoid zone and the retinal pigment epithelium. Swept-source optical coherence tomography angiography showed enlarged superficial foveal avascular zone in both cases. In the more severe case, there was enlargement of both superficial and deep foveal avascular zone, and reduction of the superficial vascular plexus density. CONCLUSION: The present findings suggest that pediatric commotio retinae may be associated with retinal vascular changes, that is, foveal avascular zone enlargement and decreased vessel density. The extent of the microvascular alterations is possibly related to trauma severity.

CYP1A2 rs762551 and ADORA2A rs5760423 Polymorphisms in Patients with Blepharospasm.

Blepharospasm (BSP) is a neurological movement disorder. Coffee consumption has been found to have a protective effect against BSP. BSP and apraxia of eyelid opening are particularly common among patients with PD. The CYP1A2 rs762551 and ADORA2A rs5760423 variants have been previously marginally associated with the risk of PD and are also implicated in caffeine metabolism pathways. The aim of the present study was to evaluate the effect of the CYP1A2 rs762551 and ADORA2A rs5760423 variants on BSP. A Southeastern European Caucasian (SEC) cohort of 206 BSP patients and 206 healthy controls was genotyped for rs762551 and rs5760423. CYP1A2 rs762551 was associated with a decreased BSP risk in the dominant (OR (95% CI) 0.62 (0.41-0.92), p = 0.017), log-additive (OR (95% CI) 0.68 (0.51-0.92), p = 0.011), and co-dominant modes (for the CC genotype OR (95% CI) 0.49 (0.25-0.93), p = 0.038). We provide preliminary evidence that CYP1A2 rs762551 is associated with BSP. Further studies and replication of our results are needed.

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.

The treatment of amblyopia: current practice and emerging trends.

PURPOSE: The purpose of this review is to provide an update on current management and recent research for amblyopia treatment. Part I will review patching, atropine penalization, and pharmacological treatments. Part II will focus on perceptual learning, video gaming, and binocular dichoptic approaches. METHODS: A literature search was performed in PubMed, ClinicalTrials.gov , Google Scholar, and reference lists of retrieved articles until December 20, 2018, for all papers containing "amblyopia treatment" or "amblyopia therapy." We have included RCTs, prospective observational studies, prospective and retrospective cohort studies, pilot studies, and review articles. RESULTS: The mainstay of treatment for amblyopia has been based on increasing visual stimulation of the amblyopic eye by occlusion, atropine, or optical penalization of the dominant eye. It has been established that refractive adaptation alone can significantly enhance visual acuity. However, the duration of optical correction varies between studies and the effectiveness of spectacle wear over early beginning of patching is still under investigation. Additionally, by means of occlusion dose monitors, it was found that adherence to occlusion affects the outcome, as a dose-response relationship exists between adherence and visual acuity. Treatment efficiency declines with age; however, recent evidence indicates cortical plasticity beyond the "critical period" and recommends that an attempt at treatment should be offered to all amblyopic children regardless of age, including those in later childhood. Novel approaches targeted to the restoration of binocular functions, such as perceptual learning, video gaming, and dichoptic training, have shown small effects on visual acuity and have failed to demonstrate non-inferiority over standard treatments. CONCLUSIONS: On review, significant evidence for the successful management of amblyopia, with occlusion therapy and atropine, has been found. However, the management of amblyopia remains challenging, mainly due to compliance issues and suboptimal treatment outcomes during occlusion and atropine penalization. Recent studies have found evidence of new ways of treating amblyopia particularly in regard to binocular treatment although these remain under investigation. Further robust clinical trials on these new treatment modalities are still warranted in order to establish their role in treating amblyopia.

Lack of Association of the rs11655081 ARSG Gene with Blepharospasm.

Blepharospasm (BSP) is a sub-phenotype of focal dystonia. A few genetic risk factors are considered to be implicated in the risk of developing BSP. There is recent evidence, based on results from GWAS and meta-analyses, to suggest that arylsulfatase G (ARSG), and more specifically rs11655081, is implicated in focal dystonia. The aim of the present study was to evaluate the effect of rs11655081 ARSG on BSP. A Greek cohort, which consisted of 206 BSP patients and an equal number of healthy controls, was genotyped for rs11655081. Only a marginal trend for the association between rs11655081 and the risk of BSP was found in the over-dominant model of inheritance [odds ratio, OR (95% confidence interval, CI): 0.64 (0.38-1.07), p = 0.088]. It is rather unlikely that rs11655081 across ARSG is a major genetic risk contributor for BSP.

The Association Between Retinopathy of Prematurity and Ocular Growth.

Purpose: The purpose of this study was to prospectively investigate the association between retinopathy of prematurity (ROP) and ocular growth in premature infants during the earliest weeks of life. Methods: Premature infants in the national ROP screening program were recruited and examined at 1- or 2-week intervals between 30 and 38 weeks of postmenstrual age. One hundred infants with gestational age (GA) between 24 and 35 weeks (30.04 + 2.13), and birth weight (BW) between 550 and 2060 g (1251.45 + 317.19) were included in the study. At each examination, the presence, stage, and zone of ROP were recorded along with axial length (AL), central corneal thickness (CCT), and weight gain. Biometric parameters were measured by A-scan biometry. Study variables included GA, BW, AL, CCT, weight gain, relative weight (RW), and dif_AL, dif_CCT, and dif_weight, which are the differences between two consecutive recordings of the same infant. Multiple regression analysis models were used to determine the association between the study variables and ROP. Results: dif_AL, dif_CCT, and RW were the most appropriate variables to detect the optimal threshold points that discriminate ROP: weekly increase of AL < 0.095 mm, weekly reduction of CCT < 0.5 µm, or weekly weight gain < 7% is associated with ROP development. Conclusions: ROP is associated with delayed ocular development, as eyes of premature infants with ROP have shorter axial lengths and thicker corneas than eyes of premature infants without ROP. The association of AL, CCT, and weight gain with ROP could be of value for future development of predictive models for ROP.

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.

BDNF rs6265 (Val66Met) Polymorphism as a Risk Factor for Blepharospasm.

A few genetic variants are implicated in the development of blepharospasm (BSP). The precise role of the rs6265 on the brain-derived neurotrophic factor (BDNF) gene on BSP remains controversial. The effect of rs6265 on BSP was evaluated. 206 patients with BSP and 206 healthy controls were recruited and genotyped for the rs6265. We also performed a meta-analysis, by pooling our results with those from previous studies. A significant effect of rs6265 on the risk of BSP was found in the dominant model of inheritance [odds ratio (OR) (95% confidence interval (CI) 1.52 (1.01-2.29), p = 0.044]. Mutational load analysis of rs6265 in the risk of BSP using the ORG revealed that higher load of the "A" allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.48; 95% CI 1.00-2.19). Finally, pooled results from the meta-analysis revealed that the rs6265 is associated with an increased risk of BSP in the dominant model [OR 1.26; 95% CI 1.02-1.55, pz = 0.03]. Also, higher load of the "A" allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.26; 95% CI 1.04-1.53). The present study provides additional evidence to the existing knowledge concerning the contribution of the rs6265 BDNF on the risk of developing BSP. While the pathophysiology and genetic susceptibility in BSP and focal dystonia are only partially understood, it seems that BDNF and rs6265 may constitute one essential risk factor that is heavily involved.