Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress.

Acknowledged as a significant pathogenetic driver for numerous diseases, aging has become a focal point in addressing the profound changes associated with increasing human life expectancy, posing a critical concern for global public health. Emerging evidence suggests that factors influencing vascular aging extend their impact to choroidal and retinal blood vessels. The objective of this work is to provide a comprehensive overview of the impact of vascular aging on ocular blood vessels and related diseases. Additionally, this study aims to illuminate molecular insights contributing to vascular cell aging, with a particular emphasis on the choroid and retina. Moreover, innovative molecular targets operating within the domain of ocular vascular aging are presented and discussed.

Redox mechanisms in autoimmune thyroid eye disease.

Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1ß, IL-6, and transforming growth factor (TGF)-ß. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Retinopathy of Prematurity-Targeting Hypoxic and Redox Signaling Pathways.

Retinopathy of prematurity (ROP) is a proliferative vascular ailment affecting the retina. It is the main risk factor for visual impairment and blindness in infants and young children worldwide. If left undiagnosed and untreated, it can progress to retinal detachment and severe visual impairment. Geographical variations in ROP epidemiology have emerged over recent decades, attributable to differing levels of care provided to preterm infants across countries and regions. Our understanding of the causes of ROP, screening, diagnosis, treatment, and associated risk factors continues to advance. This review article aims to present the pathophysiological mechanisms of ROP, including its treatment. Specifically, it delves into the latest cutting-edge treatment approaches targeting hypoxia and redox signaling pathways for this condition.

Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System.

Age-related macular degeneration (AMD) is a prevalent degenerative disorder of the central retina, which holds global significance as the fourth leading cause of blindness. The condition is characterized by a multifaceted pathophysiology that involves aging, oxidative stress, inflammation, vascular dysfunction, and complement activation. The complex interplay of these factors contributes to the initiation and progression of AMD. Current treatments primarily address choroidal neovascularization (CNV) in neovascular AMD. However, the approval of novel drug therapies for the atrophic and more gradual variant, known as geographic atrophy (GA), has recently occurred. In light of the substantial impact of AMD on affected individuals' quality of life and the strain it places on healthcare systems, there is a pressing need for innovative medications. This paper aims to provide an updated and comprehensive overview of advancements in our understanding of the etiopathogenesis of AMD. Special attention will be given to the influence of aging and altered redox status on mitochondrial dynamics, cell death pathways, and the intricate interplay between oxidative stress and the complement system, specifically in the context of GA. Additionally, this review will shed light on newly approved therapies and explore emerging alternative treatment strategies in the field. The objective is to contribute to the ongoing dialogue surrounding AMD, offering insights into the latest developments that may pave the way for more effective management and intervention approaches.

Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects.

Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions.

High-fat diet causes endothelial dysfunction in the mouse ophthalmic artery.

Obesity is a significant health concern that leads to impaired vascular function and subsequent abnormalities in various organs. The impact of obesity on ocular blood vessels, however, remains largely unclear. In this study, we examined the hypothesis that obesity induced by high-fat diet produces vascular endothelial dysfunction in the ophthalmic artery. Mice were subjected to a high-fat diet for 20 weeks, while age-matched controls were maintained on a standard diet. Reactivity of isolated ophthalmic artery segments was assessed in vitro. Reactive oxygen species (ROS) were quantified in cryosections by dihydroethidium (DHE) staining. Redox gene expression was determined in ophthalmic artery explants by real-time PCR. Furthermore, the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), the receptor for advanced glycation end products (RAGE), and of the lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) was determined in cryosections using immunofluorescence microscopy. Ophthalmic artery segments from mice on a high-fat diet exhibited impaired vasodilation responses to the endothelium-dependent vasodilator acetylcholine, while endothelium-independent responses to nitroprusside remained preserved. DHE staining intensity in the vascular wall was notably stronger in mice on a high-fat diet. Messenger RNA expression for NOX2 was elevated in the ophthalmic artery of mice subjected to high fat diet. Likewise, immunostainings revealed increased expression of NOX2 and of RAGE, but not of LOX-1. These findings suggest that a high-fat diet triggers endothelial dysfunction by inducing oxidative stress in the ophthalmic artery via involvement of RAGE and NOX2.

Measurement of Retrobulbar Blood Flow and Vascular Reactivity-Relevance for Ocular and Cardiovascular Diseases.

Abnormal retrobulbar hemodynamics have been linked to the development of various ocular diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy. Additionally, altered retrobulbar blood flow has been observed in patients with severe cardiovascular diseases, including carotid artery occlusion, stroke, heart failure, and acute coronary syndrome. Due to the complex and intricate anatomy of retrobulbar blood vessels and their location behind the eyeball, measurement of retrobulbar blood flow and vascular reactivity, as well as the interpretation of the findings, are challenging. Various methods, such as color Doppler imaging, computed tomography angiography or magnetic resonance imaging, have been employed to assess retrobulbar blood flow velocities in vivo. Color Doppler imaging represents a fast and non-invasive method to measure retrobulbar blood flow velocities in vivo. While no information about vessel diameter can be gained performing this method, computed tomography angiography and magnetic resonance imaging provide information about vessel diameter and detailed information on the anatomical course. Additionally, ex vivo studies, such as myography, utilizing genetically modified animal models may provide high optical resolution for functional vascular investigations in these small vessels. To our best knowledge, this is the first review, presenting a detailed overview of methods aiming to evaluate retrobulbar blood flow and vascular reactivity in both humans and laboratory animals. Furthermore, we will summarize the disturbances observed in retrobulbar blood flow in retinal, optic nerve, and cardiovascular diseases.

Adrenoceptors in the Eye - Physiological and Pathophysiological Relevance.

The autonomic nervous system plays a crucial role in the innervation of the eye. Consequently, it comes as no surprise that catecholamines and their corresponding receptors have been extensively studied and characterized in numerous ocular structures, including the cornea, conjunctiva, lacrimal gland, trabecular meshwork, uvea, and retina. These investigations have unveiled substantial clinical implications, particularly in the context of treating glaucoma, a progressive neurodegenerative disorder responsible for irreversible vision loss on a global scale. The primary therapeutic approaches for glaucoma frequently involve the modulation of α1-, α2-, and ß-adrenoceptors, making them pivotal targets. In this chapter, we offer a comprehensive overview of the expression, distribution, and functional roles of adrenoceptors within various components of the eye and its associated structures. Additionally, we delve into the pivotal role of adrenoceptors in the pathophysiology of glaucoma. Furthermore, we provide a concise historical perspective on adrenoceptor research, examine the distinct contributions of individual adrenoceptor subtypes to the treatment of various ocular conditions, and propose potential future avenues of exploration in this field.

Oxidative stress in the eye and its role in the pathophysiology of ocular diseases.

Oxidative stress occurs through an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense mechanisms of cells. The eye is particularly exposed to oxidative stress because of its permanent exposure to light and due to several structures having high metabolic activities. The anterior part of the eye is highly exposed to ultraviolet (UV) radiation and possesses a complex antioxidant defense system to protect the retina from UV radiation. The posterior part of the eye exhibits high metabolic rates and oxygen consumption leading subsequently to a high production rate of ROS. Furthermore, inflammation, aging, genetic factors, and environmental pollution, are all elements promoting ROS generation and impairing antioxidant defense mechanisms and thereby representing risk factors leading to oxidative stress. An abnormal redox status was shown to be involved in the pathophysiology of various ocular diseases in the anterior and posterior segment of the eye. In this review, we aim to summarize the mechanisms of oxidative stress in ocular diseases to provide an updated understanding on the pathogenesis of common diseases affecting the ocular surface, the lens, the retina, and the optic nerve. Moreover, we discuss potential therapeutic approaches aimed at reducing oxidative stress in this context.

Studies on the Effects of Hypercholesterolemia on Mouse Ophthalmic Artery Reactivity.

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, the vascular mechanics, lipid content, levels of reactive oxygen species (ROS), and expression of pro-oxidant redox enzymes and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, the levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via the involvement of LOX-1, NOX1, and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. A lack of LOX-1 expression/overexpression in response to increased oxidized low-density lipoprotein levels may be a possible mechanism of action.

Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment.

Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc, and a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading risk factor for glaucoma development. However, glaucoma can also develop at normal pressure levels. An increased susceptibility of retinal ganglion cells to IOP, systemic vascular dysregulation, endothelial dysfunction, and autoimmune imbalances have been suggested as playing a role in the pathophysiology of normal-tension glaucoma. Since inflammation and oxidative stress play a role in all forms of glaucoma, the goal of this review article is to present an overview of the inflammatory and pro-oxidant mechanisms in the pathophysiology of glaucoma and to discuss immunomodulatory and antioxidant treatment approaches.

Effects of aircraft noise cessation on blood pressure, cardio- and cerebrovascular endothelial function, oxidative stress, and inflammation in an experimental animal model.

Large epidemiological studies have shown that traffic noise promotes the development of cardiometabolic diseases. It remains to be established how long these adverse effects of noise may persist in response to a noise-off period. We investigated the effects of acute aircraft noise exposure (mean sound level of 72 dB(A) applied for 4d) on oxidative stress and inflammation mediating vascular dysfunction and increased blood pressure in male C57BL/6 J mice. 1, 2 or 4d of noise cessation after a 4d continuous noise exposure period completely normalized noise-induced endothelial dysfunction of the aorta (measured by acetylcholine-dependent relaxation) already after a 1d noise pause. Vascular oxidative stress and the increased blood pressure were partially corrected, while markers of inflammation (VCAM-1, IL-6 and leukocyte oxidative burst) showed a normalization within 4d of noise cessation. In contrast, endothelial dysfunction, oxidative stress, and inflammation of the cerebral microvessels of noise-exposed mice did not improve at all. These data demonstrate that the recovery from noise-induced damage is more complex than expected demonstrating a complete restoration of large conductance vessel function but persistent endothelial dysfunction of the microcirculation. These findings also imply that longer noise pauses are required to completely reverse noise-induced vascular dysfunction including the resistance vessels.

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.

Ectrodactyly-Ectodermal Dysplasia-Cleft Syndrome: Ocular Findings and Surgical Treatment.

PURPOSE: Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome is a rare genetic disorder. We present ocular findings and their treatment in patients with EEC. METHODS AND RESULTS: We report on 3 female patients (aged 59, 45, and 11 years) suffering from EEC with varying extraocular and ocular severity of phenotypic expression of the disease. Slit-lamp biomicroscopy, visual acuity, and medical treatment were evaluated over 4 months to 4 years. All patients experienced visual impairment and foreign body sensation. Examination revealed bilateral chronic blepharitis, dry eye syndrome, and corneal vascularization and clouding due to limbal stem cell deficiency (LSCD). Patient #1 presented a corneal ulcer with severe stromal thinning on the right eye. Allogeneic simple limbal epithelial transplantation (allo SLET), penetrating keratoplasty combined with allo SLET, and in total 5 amniotic membrane transplantation were performed to preserve the integrity of the eye. In patients #2 and #3, conservative therapy with lubricant eye drops, topical steroids, and antibiotics was sufficient to stabilize LSCD. In all cases, corneal epithelialization and improvement of visual acuity were achieved. CONCLUSIONS AND IMPORTANCE: To the best of our knowledge, this is the first report of surgical treatment in a patient with EEC. Allo SLET may be a surgical option to treat LSCD associated with EEC.

Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting, and pharmacological α1AMPK activation: molecular proof of a protective key role of endothelial α1AMPK against environmental noise exposure.

AIMS: Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting, and pharmacological treatment. METHODS AND RESULTS: Wild-type (B6.Cg-Tg(Cdh5-cre)7Mlia/J) mice were exposed to aircraft noise [maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)] for the last 4 days. The α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure produced significant endothelial dysfunction in wild-type mice aorta, mesenteric arteries, and retinal arterioles. This was associated with increased vascular oxidative stress and asymmetric dimethylarginine formation. The α1AMPK activation with all three approaches prevented endothelial dysfunction and vascular oxidative stress development, which was supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting. CONCLUSION: Our results demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise, and intermittent fasting effectively mitigates noise-induced cardiovascular damage. Future population-based studies need to clinically prove the concept of exercise/fasting-mediated mitigation of transportation noise-associated disease.

Traffic noise, e.g. from aircraft, significantly contributes to an increased risk of cardiovascular or metabolic diseases in the general population by brain-dependent stress reactions leading to higher levels of circulating stress hormones and vasoconstrictors, all of which cause hypertension, oxidative stress, and inflammation. With the present experimental studies, we provide for the first time molecular mechanisms responsible for successful noise mitigation: Physical exercise, intermittent fasting, and pharmacological activation of the adenosine monophosphate-activated protein kinase (AMPK), a metabolic master regulator protein, prevent cardiovascular damage caused by noise exposure, such as hypertension, endothelial dysfunction, and reactive oxygen species formation (e.g. free radicals) and inflammation.These beneficial mitigation manoeuvers are secondary to an activation of the endothelial AMPK, thereby mimicking the antidiabetic drug metformin.

Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) events are involved in the development of various ocular pathologies, e.g., retinal artery or vein occlusion. We tested the hypothesis that resveratrol is protective against I/R injury in the murine retina. Intraocular pressure (IOP) was elevated in anaesthetized mice to 110 mm Hg for 45 min via a micropipette placed in the anterior chamber to induce ocular ischemia. In the fellow eye, which served as control, IOP was kept at a physiological level. One group received resveratrol (30 mg/kg/day p.o. once daily) starting one day before the I/R event, whereas the other group of mice received vehicle solution only. On day eight after the I/R event, mice were sacrificed and retinal wholemounts were prepared and immuno-stained using a Brn3a antibody to quantify retinal ganglion cells. Reactivity of retinal arterioles was measured in retinal vascular preparations using video microscopy. Reactive oxygen species (ROS) and nitrogen species (RNS) were quantified in ocular cryosections by dihydroethidium and anti-3-nitrotyrosine staining, respectively. Moreover, hypoxic, redox and nitric oxide synthase gene expression was quantified in retinal explants by PCR. I/R significantly diminished retinal ganglion cell number in vehicle-treated mice. Conversely, only a negligible reduction in retinal ganglion cell number was observed in resveratrol-treated mice following I/R. Endothelial function and autoregulation were markedly reduced, which was accompanied by increased ROS and RNS in retinal blood vessels of vehicle-exposed mice following I/R, whereas resveratrol preserved vascular endothelial function and autoregulation and blunted ROS and RNS formation. Moreover, resveratrol reduced I/R-induced mRNA expression for the prooxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2). Our data provide evidence that resveratrol protects from I/R-induced retinal ganglion cell loss and endothelial dysfunction in the murine retina by reducing nitro-oxidative stress possibly via suppression of NOX2 upregulation.

ß-Adrenoreceptors as Therapeutic Targets for Ocular Tumors and Other Eye Diseases-Historical Aspects and Nowadays Understanding.

ß-adrenoreceptors (ARs) are members of the superfamily of G-protein-coupled receptors (GPCRs), and are activated by catecholamines, such as epinephrine and norepinephrine. Three subtypes of ß-ARs (ß1, ß2, and ß3) have been identified with different distributions among ocular tissues. Importantly, ß-ARs are an established target in the treatment of glaucoma. Moreover, ß-adrenergic signaling has been associated with the development and progression of various tumor types. Hence, ß-ARs are a potential therapeutic target for ocular neoplasms, such as ocular hemangioma and uveal melanoma. This review aims to discuss the expression and function of individual ß-AR subtypes in ocular structures, as well as their role in the treatment of ocular diseases, including ocular tumors.

Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles.

Diabetes mellitus may cause severe damage to retinal blood vessels. The central aim of this study was to test the hypothesis that sulodexide, a mixture of glycosaminoglycans, has a protective effect against hyperglycemia-induced endothelial dysfunction in the retina. Functional studies were performed in isolated porcine retinal arterioles. Vessels were cannulated and incubated with highly concentrated glucose solution (HG, 25 mM D-glucose) +/- sulodexide (50/5/0.5 µg/mL) or normally concentrated glucose solution (NG, 5.5 mM D-glucose) +/- sulodexide for two hours. Endothelium-dependent and endothelium-independent vasodilatation were measured by videomicroscopy. Reactive oxygen species (ROS) were quantified by dihydroethidium (DHE) fluorescence. Using high-pressure liquid chromatography (HPLC), the intrinsic antioxidant properties of sulodexide were investigated. Quantitative PCR was used to determine mRNA expression of regulatory, inflammatory, and redox genes in retinal arterioles, some of which were subsequently quantified at the protein level by immunofluorescence microscopy. Incubation of retinal arterioles with HG caused significant impairment of endothelium-dependent vasodilation, whereas endothelium-independent responses were not affected. In the HG group, ROS formation was markedly increased in the vascular wall. Strikingly, sulodexide had a protective effect against hyperglycemia-induced ROS formation in the vascular wall and had a concentration-dependent protective effect against endothelial dysfunction. Although sulodexide itself had only negligible antioxidant properties, it prevented hyperglycemia-induced overexpression of the pro-oxidant redox enzymes, NOX4 and NOX5. The data of the present study provide evidence that sulodexide has a protective effect against hyperglycemia-induced oxidative stress and endothelial dysfunction in porcine retinal arterioles, possibly by modulation of redox enzyme expression.

Risk factors for peripheral hypertrophic subepithelial corneal opacification.

BACKGROUND: To evaluate the phenotype, tear secretion and refractive changes of patients diagnosed with peripheral hypertrophic subepithelial corneal opacification (PHSCO). METHODS: This is a retrospective, interventional case series conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. Medical records of patients diagnosed with PHSCO were analysed. Sex, age, fluorescein tear film breakup time (FTBUT), Schirmer Test II, iris colour and hair colour were assessed. Objective refraction was evaluated at different time points and, in case of surgery, 1 month and 1 year postoperatively. RESULTS: One hundred ninety-five eyes of 112 patients (78.6% female, 21.4% male; mean age 56.2 ± 14.3) were included. The median FTBUT was 6 sec. (Q1: 4/Q3: 8.75; range 1-20 s) (measured in 70 eyes of 36 patients), the median Schirmer Test II was 8 mm (Q1: 5/ Q3:15; range 1-35 mm). In 83 patients (74.1%) both eyes were involved. In 86 eyes of 64 patients (55.3%) superficial keratectomy was performed. Sphere and cylinder changed significantly 1 month and 1 year postoperative compared to the pre-operative objective refraction, while there was no significant change between 1 month and 1 year postoperatively. CONCLUSION: We found that PHSCO occurs mostly bilaterally in middle-aged women and appears to be associated with decreased tear production and reduced tear film stability.