Macular Ischemia Changes in Patients with Diabetic Macular Edema Treated with Aflibercept and Ranibizumab.

Τhis study aims to assess changes in the fovea avascular zone (FAZ) in treatment naïve patients receiving aflibercept or ranibizumab injections for diabetic macular edema (DME). Best corrected visual acuity (BCVA) testing, OCT, and OCT-angiography imaging were performed at baseline and 1 month after each injection. Injections of either aflibercept or ranibizumab were administered monthly for 6 consecutive months. FAZ in the superficial (SCP) and the deep capillary plexus (DCP) using OCT angiography was recorded for each visit. Fifty eyes from fifty patients with a mean age of 67.0 ± 10.7 years were included in the study. Twenty-five patients received aflibercept and twenty-five received ranibizumab. BCVA was 40.8 ± 10.0 and increased to 52.1 ± 7.9 ETDRS letters at the last visit (p < 0.001). CRT was 295.6 ± 34.0 at baseline and 247.9 ± 29.7 at the last study visit (p < 0.001). SCP FAZ was 350.6 ± 79.5 µm2 at baseline and 339.0 ± 71.3 µm2 after sox monthly injections (p = 0.132). DCP FAZ was 558.6 ± 199.0 µm2 at baseline and 459.5 ± 156.1 µm2 after six monthly injections (p < 0.001). There was no effect of the choice of ranibizumab or aflibercept on DCP FAZ change (p = 0.277). In conclusion, treatment with 6 monthly injections of ranibizumab and aflibercept led to an increase in BCVA and a decrease in CRT and DCP FAZ area. Both drugs led to an improvement in DCP ischemia.

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.

Current Approaches to the Management of Patients with Endometrial Cancer.

The incidence of endometrial cancer (EC) is rising and healthcare professionals need to be informed about the latest data on the constant developments in the field of its management. With particular interest in the classification and management of EC, we surveyed current literature, national and international data, and guidelines, as well as the latest studies to present the most recent data regarding the management of EC. It became evident that despite the consensus on low-risk EC, there are still controversies surrounding the management of high-risk EC, especially regarding the role of sentinel lymph node biopsy (SLNB). Our aim is to present the old and new perspectives in the management of EC, the different available surgical routes, the possible desire for fertility preservation, the role of adjuvant therapies and the focus on the advantages and the limitations of the implementation of SLNB in therapeutic strategies. It became evident throughout our search and based on literature data that minimally invasive surgery (MIS) leads to satisfying outcomes, thus becoming gradually the preferred route of surgery, while SLNB could provide essential information and guidance about the overall management needed in cases of both low-risk and high-risk EC.

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.

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.

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.

Subperiosteal Orbital Hemorrhage: An Unusual Complication During Labor.

ABSTRACT: Subperiosteal orbital hemorrhage in the postpartum period has been rarely reported. The authors herein present a female patient who developed acute-onset vertical diplopia, proptosis, mild retro-orbital pain, and restriction of upgaze immediately after labor. Neuroimaging revealed a subperiosteal hematoma along the right orbital roof. Diplopia, motility limitation, and retro-orbital pain gradually resolved in the following weeks. Subperiosteal orbital hematomas are a rare complication of labor, with only 12 cases reported so far. They result from straining during labor, which increases central and orbital venous pressure by means of the Valsalva-maneuver. In order to evaluate ocular motility and exclude optic nerve compression, an urgent ophthalmological examination is required.

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.

The effect of carotid revascularization on the ophthalmic artery flow: systematic review and meta-analysis.

INTRODUCTION: High-grade internal carotid stenosis results in impaired flow dynamics in the ocular circulation that may lead to a rare clinical entity; ophthalmic ischemic syndrome (OIS). The aim of this study was to investigate hemodynamic changes in the ophthalmic circulation after carotid revascularization, assessed with duplex ultrasonography (DUS), and their potential impact on ocular function in patients suffering from OIS. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to the PRISMA guidelines. Medline, Embase and Central databases were searched. EVIDENCE SYNTHESIS: The analysis included fourteen cohort studies (589 patients) reporting on the hemodynamic effect of carotid revascularization on the ophthalmic circulation using DUS. Eighty-five per cent of patients were treated for symptomatic carotid stenosis. The pre- and postoperative ophthalmological evaluation was recorded in four studies (227 out of 358 patients [63%] diagnosed with OIS). Reversed ophthalmic artery (OA) flow prior to carotid revascularization was present in 86 cases (24%). Following carotid revascularization, a significant increase in peak systolic velocity (PSV) (mean difference [MD] 14.712 cm/s, 95% confidence interval [CI] 10.566-18.858, P<0.001, I2=96%) and a significant anterograde restoration of flow in the OA (OR: 2.047, 95% CI: 1.72-2.42, P<0.001, Ι2=0%) were recorded. Carotid revascularization resulted in regression of ischemic symptoms in 93.1% of patients (95% CI: 56.4-99.3%), P=0.001, I2=82%). CONCLUSIONS: Carotid revascularization may be associated with a significant flow restoration and PSV increase in the OA; as well as clinical improvement in ischemic ophthalmic symptoms in patients with OIS.

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.