The Severity of Diabetic Retinopathy Corresponds with Corneal Nerve Alterations and Ocular Discomfort of the Patient.

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35-+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = -0.26, 95% CI: -0.44--0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-ß, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM.

VEGFR and DPP-IV as Markers of Severe COVID-19 and Predictors of ICU Admission.

The pathophysiology of the severe course of COVID-19 is multifactorial and not entirely elucidated. However, it is well known that the hyperinflammatory response and cytokine storm are paramount events leading to further complications. In this paper, we investigated the vascular response in the pathophysiology of severe COVID-19 and aimed to identify novel biomarkers predictive of ICU admission. The study group consisted of 210 patients diagnosed with COVID-19 (age range: 18-93; mean ± SD: 57.78 ± 14.16), while the control group consisted of 80 healthy individuals. We assessed the plasma concentrations of various vascular factors using the Luminex technique. Then, we isolated RNA from blood mononuclear cells and performed a bioinformatics analysis investigating various processes related to vascular response, inflammation and angiogenesis. Our results confirmed that severe COVID-19 is associated with vWF/ADAMTS 13 imbalance. High plasma concentrations of VEGFR and low DPP-IV may be potential predictors of ICU admission. SARS-CoV-2 infection impairs angiogenesis, hinders the generation of nitric oxide, and thus impedes vasodilation. The hypercoagulable state develops mainly in the early stages of the disease, which may contribute to the well-established complications of COVID-19.

Association between Light-Induced Dynamic Dilation of Retinal Vessels and Echocardiographic Parameters of the Left Ventricular Function in Hypertensive Patients.

BACKGROUND AND OBJECTIVES: The goal was to evaluate the association of dynamic retinal vessel analysis (DVA) with echocardiographic parameters assessing systolic and diastolic function of the left ventricle in hypertension (HT) patients with preserved left ventricle ejection fraction. MATERIALS AND METHODS: This observational retrospective study recruited 36 patients with HT and 28 healthy controls. Retinal vessel diameter and reactions to flicker light were examined. Each patient was examined with echocardiography to assess left ventricular systolic and diastolic function. RESULTS: Multivariate analysis revealed that hypertension was an independent factor associated with lower flicker-induced arterial vasodilatation (ß = -0.31, p = 0.029). In the HT group, there was a significant positive association between left ventricular ejection fraction and flicker-induced arterial vasodilation (Rs = +0.31, p = 0.007). Additionally, end-diastolic left ventricular diameter negatively correlated with both arterial (Rs = -0.26, p = 0.02) and venous (Rs = -0.27, p = 0.02) flicker responses. Additionally, the echocardiographic characteristics of the left atrium (LA) remodeling in the course of HT, including the area of the LA and its antero-posterior dimension, were both negatively correlated with the arterial flicker response (Rs = -0.34, p = 0.003; Rs = -0.33, p = 0.004, respectively). From tissue Doppler parameters, the left ventricular filling index E/e' negatively correlated with AVR (arteriovenous ratio) values (Rs = -0.36, p = 0.002). CONCLUSIONS: We revealed that systolic and diastolic function of the left ventricle in hypertensive patients is associated with retinal microvascular function.

Evaluation of choroidal parameters in eyes at the first onset of acute anterior uveitis.

BACKGROUND: Little is known about choroidal involvement in anterior uveitis. The aim of our study was to evaluate changes in choroidal thickness and volume in eyes with acute anterior uveitis (AAU) using enhanced depth imaging-optical coherence tomography (EDI-OCT) at baseline and after treatment, which were compared with healthy fellow eyes. METHODS: For the study, 35 individuals with unilateral acute AAU at the first onset were enrolled. Subfoveal thickness and choroidal volume were measured with EDI-OCT in nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields before and after the completion of treatment. Moreover, axial length measurements of both eye bulbs were determined by optical biometry. RESULTS: No statistically significant differences in choroidal thickness or choroidal volume were detected between AAU eyes at baseline and after treatment and fellow eyes. Positive correlations between the values of anterior chamber flare and absolute CT changes in both temporal and inferior ETDRS fields, as well as in superior outer ring were detected. Negative correlations between age and both choroidal thickness and choroidal volume were detected in AAU eyes at baseline and after treatment, as well as in fellow eyes. CONCLUSIONS: Evaluation of the choroid with EDI-OCT does not appear to be a reliable tool for the treatment monitoring of eyes with anterior uveitis.

Preclinical Evaluation of Long-Term Neuroprotective Effects of BDNF-Engineered Mesenchymal Stromal Cells as Intravitreal Therapy for Chronic Retinal Degeneration in Rd6 Mutant Mice.

This study aimed to investigate whether the transplantation of genetically engineered bone marrow-derived mesenchymal stromal cells (MSCs) to overexpress brain-derived neurotrophic factor (BDNF) could rescue the chronic degenerative process of slow retinal degeneration in the rd6 (retinal degeneration 6) mouse model and sought to identify the potential underlying mechanisms. Rd6 mice were subjected to the intravitreal injection of lentivirally modified MSC-BDNF or unmodified MSC or saline. In vivo morphology, electrophysiological retinal function (ERG), and the expression of apoptosis-related genes, as well as BDNF and its receptor (TrkB), were assessed in retinas collected at 28 days and three months after transplantation. We observed that cells survived for at least three months after transplantation. MSC-BDNF preferentially integrated into the outer retinal layers and considerably rescued damaged retinal cells, as evaluated by ERG and immunofluorescence staining. Additionally, compared with controls, the therapy with MSC-BDNF was associated with the induction of molecular changes related to anti-apoptotic signaling. In conclusion, BDNF overexpression observed in retinas after MSC-BDNF treatment could enhance the neuroprotective properties of transplanted autologous MSCs alone in the chronically degenerated retina. This research provides evidence for the long-term efficacy of genetically-modified MSC and may represent a strategy for treating various forms of degenerative retinopathies in the future.

Associations of microRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism-An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in AMD patients. We also focused on possible correlations of their expression with the presence of CFH Y402H or ARMS A69S risk variants. A total of 354 AMD patients and 121 controls were enrolled in this study. The levels of angiogenesis-regulating factors were analyzed in plasma samples using Luminex technology. The expression of selected miRNAs was analyzed in peripheral blood plasma using real-time qPCR. The genetic analysis was performed with an Illumina NextSeq500 system. AMD was an independent factor associated with lower levels of angiogenin (ß = -0.29, p < 0.001), endostatin (ß = -0.18, p < 0.001), FGF-basic (ß = -0.18, p < 0.001), PlGF (ß = -0.24, p < 0.001), miRNA-21-3p (ß = -0.13, p = 0.01) and miRNA-155-5p (ß = -0.16, p = 0.002); and with higher levels of FGF-acidic (ß = 0.11, p = 0.03), miRNA-23a-3p (ß = 0.17, p < 0.001), miRNA-126-5p (ß = 0.13, p = 0.009), miRNA-16-5p (ß = 0.40, p < 0.001), miRNA-17-3p (ß = 0.13, p = 0.01), miRNA-17-5p (ß = 0.17, p < 0.001), miRNA-223-3p (ß = 0.15, p = 0.004), and miRNA-93 (ß = 0.11, p = 0.04). The expression of analyzed miRNA molecules significantly correlated with the levels of tested angiogenesis-regulating factors and clinical parameters in AMD patients, whereas such correlations were not observed in controls. We also found an association between the CFH Y402H polymorphism and miRNA profiles, whereby TT homozygotes showed evidently higher expression of miRNA-16-5p than CC homozygotes or TC heterozygotes (p = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis.

The effect of intravitreal ranibizumab on apoptosis induction in rat retinal tissue.

Purpose: Despite the rapidly accumulating knowledge on pharmacokinetic properties and dosage of ranibizumab, the influence of this vascular endothelial growth factor inhibitor on retinal cell survival/apoptosis homeostasis remains unclear. The aim of this study was to investigate the biological effects of a single intravitreal injection of ranibizumab on retinal tissue with a focus on apoptosis-related signaling pathways in the rat retina. Material and methods: Male Wistar rats were treated with an intravitreal injection of ranibizumab or anti-rat vascular endothelial growth factor antibody in the right eye. The left eyes were injected with the same volume of physiological saline. On the 3rd and 7th day post-injection, the eyes were enucleated, and the retinas were isolated for further molecular analysis of the expression of selected apoptosis-related molecules at mRNA (BAX, BCL-2) and protein (caspase-3) levels using quantitative RT-PCR and western blot techniques, respectively. Results: Following a 3-day-exposure to ranibizumab at the established concentration, the BAX/BCL-2 mRNA expression ratio was significantly increased compared to the saline-treated controls and the healthy control eyes. Furthermore, on day 3. post ranibizumab injection, caspase-3 cleavage, detected qualitatively using western blotting, confirmed potential activation of the ir­reversible phase of apoptosis. In contrast, on day 7. post-injection, there were no significant differences in the BAX/BCL-2 mRNA expression ratios or caspase-3 cleavage between different groups. Conclusions: Intravitreal administration of ranibizumab leads to a transient induction of apoptosis in retinal cells, with an onset directly after the vascular endothelial growth factor inhibitor administration and apparent down-regulation shortly afterwards. These results must be considered when intravitreal injections of ranibizumab are administered to treat retinal diseases.

Aqueous levels of VEGF correlate with retinal non-perfusion areas in patients with diabetic macular edema and macular edema secondary to central retinal vein occlusion.

AIM: To evaluate the association between the level of vascular endothelial growth factor in the aqueous humor and the size of capillary non-perfusion areas in patients with macular edema secondary to retinal vein occlusion and diabetic retinopathy. MATERIAL AND METHODS: The study group consisted of 24 patients (24 eyes) at the age of 55-78 years, with diffuse macular edema secondary to retinal vein occlusion and diabetic retinopathy. The control group consisted of 26 subjects aged 55-87 years who were admitted for scheduled cataract surgery. The VEGF aqueous humor levels, retinal thickness using optical coherence tomography, as well as the size of non-perfusion areas measured on fluorescein angiography images were evaluated in each enrolled subject. RESULTS: The vascular endothelial growth factor aqueous humor levels were found to be significantly higher in patients with macular edema as compared to controls (p = 0.0002). In the diabetic macular edema and retinal vein occlusion group, the con- centration of vascular endothelial growth factor in aqueous humor positively correlated with the extent of non-perfusion areas measured on fluorescein angiograms (Rs = + 0.45, p = 0.02;). Multivariate analysis of patients and controls performed using the general linear model, adjusted for age, sex, intraocular pressure and the presence of diabetes, revealed that macular edema was an independent factor associated with higher aqueous VEGF concentrations (ß = +0.74, p = 0.0012). CONCLUSIONS: Macular edema secondary to either retinal vein occlusion or diabetic retinopathy is associated with the increased levels of vascular endothelial growth factor in the aqueous humor. Therefore, the management of patients with macular edema secondary to retinal vein occlusion or diabetic retinopathy should aim at reducing the ocular vascular endothelial growth factor concentrations, especially in the presence of capillary non-perfusion areas.

Retinal degeneration following lead exposure - functional aspects.

Due to the prevalence of lead (Pb) in the environment, the neurotoxic effects on the human body have become an important clinical problem. Despite that Pb concentration in the environment decreased after banning its use in petrol, it is still a significant issue which can affect child development and vision. This paper focuses on the degeneration of the retina under exposure to lead. We present the most frequent sources of exposure to lead in the environment and the influence on vision, mechanisms leading to the apoptosis of photoreceptor cells, as well as strategies for blocking rod apoptosis. We also present Pb-induced disorders in the calcium metabolism of photoreceptor cells and Ca2+-dependent enzymes.

[The interpretation of normal and pathological optical coherence tomography retinal image as compared to their histological cross-sections]. / Prawidlowe i patologiczne obrazy badania optycznej koherentnej tomografii siatkówki--interpretacja w korelacji z obrazem histologicznym.

Due to technological advances that have taken place in recent years, optical coherence tomography retinal imaging provides qualitative data of informational value similar to the one of data obtained with conventional histological techniques. Correlation of optical coherence tomography images with histological retinal cross-sections enables the identification of the major retinal layers and anatomical structures. If the retina is pathologically altered, it is possible to visualize pathophysiological processes responsible for reflectivity changes, such as: activation of apoptosis and necrosis, phagocytic cell infiltration and dye accumulation in glial cells.

[Increased expression of endothelin-1-- a novel diagnostic marker for early AMD detection?]. / Wzrost ekspresji endoteliny-1--nowy marker wczesnej diagnostyki AMD?

AIM: The relationship between ischemic vascular disease and age-related macular degeneration may indicate the role of vascular injury as the primary insult causing functional deficits in age-related macular degeneration. The vasoactive factors produced by endothelial cells include endothelin-1 (ET-1), which is one of the most potent vasoconstricting peptides. In this study we sought to explore the potential role of endothelial dysfunction in the pathogenesis of age-related macular degeneration by measuring the concentration of ET-1 in peripheral blood of individuals diagnosed with age-related macular degeneration and evaluating its intracellular expression in peripheral blood cells, on mRNA level. MATERIAL AND METHODS: Peripheral blood samples from 31 patients with diagnosed dry age-related macular degeneration and 46 patients with neovascular age-related macular degeneration were collected. Forty six age- and sex-matched volunteers without age-related macular degeneration were enrolled as a control group. ET-1 plasma levels were analyzed by ELISA and intracellular expression of ET-1 in peripheral blood cells was studied by using qRT-PCR. RESULTS: The expression of intracellular ET-1 was significantly elevated in peripheral blood cells of both dry and wet age-related macular degeneration patients compared with the control subjects. Immunofluorescence staining revealed that ET-1 was specifically expressed in the circulating endothelial cells. CONCLUSIONS: We assume that damaged endothelial cells may release a variety of vasoconstricting molecules, including ET-1, leading to derangement between the endothelium-derived relaxing and contracting factors. Local retinal ischemia consequently develops which may promote the development of retinal degeneration in patients with age-related macular degeneration,

In vivo imaging of the mouse retina using high-resolution optical coherence tomography.

PURPOSE: In this study, we demonstrate the advantages of high-resolution optical coherence tomography for the non-invasive, in vivo, three-dimensional imaging of the mouse retina. METHODS: High-resolution optical coherence tomography images of the mouse retina were acquired using the Bioptigen Envisu R2200-HR SD-OCT system. We measured the retinal thickness and compared the measurements to those obtained using conventional histology techniques. RESULTS: High-resolution spectral-domain optical coherence tomography enables high-quality in vivo visualization of retinal structures in mice, providing an accurate quantitative description of retinal layers. Additionally, the ultra-high-speed system offers many advantages over histology, e.g., it permits the visualization of retinal microvasculature and pulsatile flow dynamics. CONCLUSIONS: Spectral domain optical coherence tomography is a new important tool for the in vivo analysis of mouse eyes.

In vitro and in vivo characterization of human serum albumin-based PEGylated nanoparticles for BDNF and NT3 codelivery.

The utilization of neurotrophins in medicine shows significant potential for addressing neurodegenerative conditions, such as age-related macular degeneration (AMD). However, the therapeutic use of neurotrophins has been restricted due to their short half-life. Here, we aimed to synthesize PEGylated nanoparticles based on electrostatic-driven interactions between human serum albumin (HSA), a carrier for adsorption; neurotrophin-3 (NT3); and brain-derived neurotrophic factor (BDNF). Electrophoretic (ELS) and multi-angle dynamic light scattering (MADLS) revealed that the PEGylated HSA-NT3-BDNF nanoparticles ranged from 10 to 430 nm in diameter and exhibited a low polydispersity index (<0.4) and a zeta potential of -8 mV. Based on microscale thermophoresis (MST), the estimated dissociation constant (Kd) from the HSA molecule of BDNF was 1.6 µM, and the Kd of NT3 was 732 µM. The nanoparticles were nontoxic toward ARPE-19 and L-929 cells in vitro and efficiently delivered BDNF and NT3. Based on the biodistribution of neurotrophins after intravitreal injection into BALB/c mice, both nanoparticles were gradually released in the mouse vitreous body within 28 days. PEGylated HSA-NT3-BDNF nanoparticles stabilize neurotrophins and maintain this characteristic in vivo. Thus, given the simplicity of the system, the nanoparticles may enhance the treatment of a variety of neurological disorders in the future.

Whole-Exome Analysis for Polish Caucasian Patients with Retinal Dystrophies and the Creation of a Reference Genomic Database for the Polish Population.

We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016-2019. Moreover, to facilitate such diagnostic analyses and enable future application of gene therapy and genome editing for IRD patients, a Polish genomic reference database (POLGENOM) was created based on whole-genome sequences of healthy Polish Caucasian nonagenarians and centenarians. The newly constructed database served as a control, providing a comparison for variant frequencies in the Polish population. The diagnostic yield for the selected group of IRD patients reached 64.9%. The study uncovered the most common pathogenic variants in ABCA4 and USH2A in the European population, along with several novel causative variants. A significant frequency of the ABCA4 complex haplotype p.(Leu541Pro; Ala1038Val) was observed, as well as that of the p.Gly1961Glu variant. The first VCAN causative variant NM_004385.5:c.4004-2A>G in Poland was found and described. Moreover, one of the first patients with the RPE65 causative variants was identified, and, in consequence, could receive the dedicated gene therapy. The availability of the reference POLGENOM database enabled comprehensive variant characterisation during the NGS data analysis, confirming the utility of a population-specific genomic database for enhancing diagnostic accuracy. Study findings suggest the significance of genetic testing in elder patients with unclear aetiology of eye diseases. The combined approach of NGS and the reference genomic database can improve the diagnosis, management, and future treatment of IRDs.

Endogenous regeneration of damaged retinal pigment epithelium following low dose sodium iodate administration: an insight into the role of glial cells in retinal repair.

The retinal pigment epithelium (RPE) has been reported to demonstrate feasible self-regenerative potential under specific conditions. However, the precise underlying mechanisms involved in this process are still elusive. Here, we performed a sequential morphological, molecular, and functional analysis of retinal injury and subsequent tissue regeneration after intravenous administration of a low dose of sodium iodate (15 mg/kg) in mice over long-term observation, up to 3 months post-injury. To assess the kinetics of the injury/recovery process, the electroretinography (ERG) responses were correlated with ongoing alterations in retinal structure and the global gene expression profile of injured retinas using genome-wide RNA microarray technology, western blotting and immunohistochemical analyses. We observed considerable improvement in the rod cell-mediated ERG response, which was accompanied by the regeneration of RPE within the injury site by the 3rd month post-injury. Our results confirm that the repairing mechanisms within injured retinas involve a significant glial cell reaction marked by glial cell proliferation, migration from their original location toward the injury site, followed by a significant overproduction of NTs such as BDNF, GDNF and NT-3. The global gene expression analysis revealed that initially up-regulated genes associated with cell death, apoptosis, acute response to stress pathways underwent considerable down-regulation in the late post-injury period. Accordingly, the genes implicated in nervous tissue remodeling and neuron development, the regulation of synaptic transmission and the establishment of localization were substantially induced by the 3rd month. Collectively, our observations support the view that Müller glial cells might well play an active role not only in retinal cell reorganization following injury but potentially also in RPE regeneration, which appears to be the key event in retinal reparative process. Furthermore, we provided novel compelling evidence of the crucial role of neurotrophins in the pathophysiology of retinal repair and identified the signaling pathways that are activated during this process.

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis]. / Zwyrodnienie plamki zwiazane z wiekiem jako lokalna manifestacja miazdzycy - nowe spojrzenie na patogeneze.

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

[The role of circulating endothelial progenitor cells in the development of vascular retinal diseases]. / Rola krazacych komórek progenitorowych sródblonka w rozwoju chorób naczyniowych siatkówki.

Based on the recent reports, circulating endothelial progenitor cells play an important role in the pathogenesis of vascular-related disorders. It is suggested that ischemia triggers endothelial progenitor cells to proceed from bone marrow into peripheral blood. Consequently, the mobilized endothelial progenitor cells may contribute to neovasculogenesis within injured retina and/or choroid tissue. Hence, in the present review the potential relationship between development of vascular retinal diseases and systemic endothelial progenitor cells migration has been discussed. Understanding of all pathophysiological mechanisms underlying progressive neovascularization may lead to development of effective prevention and treatment of these disorders. Further investigations are required to elucidate precisely the role of endothelial progenitor cells in this process and to create background for therapeutic applications.

Potential contribution of mobilized circulating endothelial progenitor cells to development of retinal neovascularization in preterm infants with ROP.

PURPOSE: To investigate the role of endothelial progenitor cells in the pathogenesis of abnormal blood vessel formation in preterm infants with retinopathy of prematurity. MATERIAL AND METHODS: A total of 29 preterm infants with proliferative stage of retinopathy of prematurity and neovascularizatio (grade 3 or higher) were involved in this study. The CD133+/CD34+/CD144+ EPC count in peripheral blood was measured b flow cytometry. Plasma levels of stromal derived factor-1 (SDF-1), vascular endothelial growth factor, and insulin-like growth factor-1 (IGF-1) were quantified by enzyme-linked immunosorbent assay (ELISA). All cellular and biochemical measurements were performed twice in the same neonate: i) initially, during the proliferative phase of ROP, and ii) subsequently, during the remission after a successful retinal photocoagulation and regression of pathological blood vessels. RESULTS: The endothelial progenitor cells count significantly decreased during the remission phase, compared to the proliferative phase of retinopathy of prematurity in the same neonates. The SDF-1 plasma level was found to be markedly lower during the remission stage and positively correlated with the endothelial progenitor cell count in peripheral blood. CONCLUSIONS: The endothelial progenitor cell count in peripheral blood of preterm infants significantly decreased with the regression of abnormal vasculature in the neonate retina. This may indicate that pathological blood vessel formation during the proliferative phase of retinopathy of prematurity results not only from local endothelial proliferation but also from the systemic endothelial progenitor cell mobilization.

Does the Presence of the Cilioretinal Artery Affect the Incidence, Clinical Picture and Progression of Age-Related Macular Degeneration?

The aims of this study were to analyze the relationship between the presence of the cilioretinal artery (CRA) and the incidence, severity and progression of age-related macular degeneration (AMD) and to estimate the influence of the CRA on choroidal and retinal parameters. A total of 287 patients with AMD and 110 healthy controls were enrolled in the study. CRA occurrence was determined using color fundus images. AMD progression was assessed after 3 years. There was no difference in the incidence of CRA between the AMD and control groups (23.34% vs. 24.55%; p = 0.8). Lower-stage AMD was more frequently observed in eyes with the CRA than in eyes without the artery (p = 0.016). The CRA did not influence disease progression (p = 0.79). The CRA did not influence retinal and choroidal thickness and volume parameters or the retinal vessel caliber and functionality in either the AMD or control groups. There was no relationship between CRA presence and CFH Y402H and ARMS2 A69S risk variants. The results did not show a protective effect of the CRA on the incidence and progression of AMD. The CRA may affect the severity of AMD; however, the mechanism of this phenomenon is unclear.

The Effect of Oral Isotretinoin Therapy on Meibomian Gland Characteristics in Patients with Acne Vulgaris.

INTRODUCTION: The aim of the study was to determine the effect of oral isotretinoin therapy on the functional and morphological condition of the anterior segment of the eye, with particular emphasis on the meibomian glands. METHODS: Twenty-four patients (48 eyes) with a diagnosis of acne vulgaris were involved in the survey. All patients underwent a thorough ophthalmological examination at three time points: before therapy, 3 months after the start of therapy, and 1 month after the completion of isotretinoin therapy. The physical examination included the following elements: blink rate, analysis of the lid margin abnormality score (LAS), tear film break-up time (TFBUT) and Schirmer's test, meibomian gland loss (MGL), and the evaluation of the meibum quality score (MQS) and meibum expressibility score (MES). Additionally, the total score of an ocular surface disease index (OSDI) questionnaire was analysed. RESULTS: In comparison with pretreatment values, significant increases in OSDI during and after the treatment (p = 0.003 and p = 0.004, respectively) were observed. Substantial deterioration during the treatment was observed for MGL (p < 0.0001), MQS (p < 0.001) and LAS (p < 0.0001), while an improvement in those parameters after isotretinoin cessation was observed (p = 0.006, p = 0.02 and p = 0.0003, respectively). The frequency of using artificial eye drops was positively associated with MGL during (Spearman's rank correlation coefficient (Rs) = + 0.31; p = 0.03) and after the cessation of the therapy (Rs = + 0.28; p = 0.04). Meibomian gland atrophy correlated significantly with MQS during (Rs = + 0.29; p = 0.04) and after treatment (Rs = + 0.38; p = 0.008). The decrease in TFBUT values correlated with increased LAS (Rs = - 0.31; p = 0.03) during the course of isotretinoin usage. We found no changes in Schirmer's test or blink rates. CONCLUSION: Isotretinoin therapy leads to increased ocular complaints related to lipid tear film component dysfunction. This is due to reversible changes in meibomian gland morphology and function observed during drug usage.