Non-Invasive Retinal Vessel Analysis as a Predictor for Cardiovascular Disease.

Cardiovascular disease (CVD) is the most frequent cause of death worldwide. The alterations in the microcirculation may predict the cardiovascular mortality. The retinal vasculature can be used as a model to study vascular alterations associated with cardiovascular disease. In order to quantify microvascular changes in a non-invasive way, fundus images can be taken and analysed. The central retinal arteriolar (CRAE), the venular (CRVE) diameter and the arteriolar-to-venular diameter ratio (AVR) can be used as biomarkers to predict the cardiovascular mortality. A narrower CRAE, wider CRVE and a lower AVR have been associated with increased cardiovascular events. Dynamic retinal vessel analysis (DRVA) allows the quantification of retinal changes using digital image sequences in response to visual stimulation with flicker light. This article is not just a review of the current literature, it also aims to discuss the methodological benefits and to identify research gaps. It highlights the potential use of microvascular biomarkers for screening and treatment monitoring of cardiovascular disease. Artificial intelligence (AI), such as Quantitative Analysis of Retinal vessel Topology and size (QUARTZ), and SIVA-deep learning system (SIVA-DLS), seems efficient in extracting information from fundus photographs and has the advantage of increasing diagnosis accuracy and improving patient care by complementing the role of physicians. Retinal vascular imaging using AI may help identify the cardiovascular risk, and is an important tool in primary cardiovascular disease prevention. Further research should explore the potential clinical application of retinal microvascular biomarkers, in order to assess systemic vascular health status, and to predict cardiovascular events.

A challenging differential diagnosis - Leber's Hereditary Optic Neuropathy.

Leber's hereditary optic neuropathy (LHON) is the most common maternally inherited disease linked to mitochondrial DNA (mtDNA). The patients present with subacute asymmetric bilateral vision loss. Approximately 95% of the LHON cases are caused by m.3460G>A (MTND1), m.11778G>A (MTND4), and m.14484T>C (MTND6) mutations. The hallmark of hereditary optic neuropathies determined by mitochondrial dysfunction is the vulnerability and degeneration of retinal ganglion cells (RGC). We present the case of a 28-year-old man who came to our clinic complaining of a subacute decrease in visual acuity of his left eye. From his medical history, we found out that one month before he had the same symptoms in the right eye. From the family history, we noted that an uncle has had vision problems since childhood. We carried out complete blood tests, including specific antibodies for autoimmune and infectious diseases. Laboratory tests and MRI were within normal limits. A blood test of the mtDNA showed the presence of 11778 G>A mutation on the mtND6 gene. The medical history, the fundus appearance, the OCT, and the paraclinical investigations, made us diagnose our patient with Leber's hereditary optic neuropathy. As soon as possible, we began the treatment with systemic idebenone, 900 mg/day. We examined the patient 2, 6, and 10 weeks after initiating the treatment. Abbreviations: LHON = Leber's Hereditary Optic Neuropathy, mtDNA = mitochondrial DNA, VA = visual acuity, RE = right eye, LE = left eye, OCT = Optical coherence tomography, pRNFL = peripapillary retinal nerve fiber layer, GCL = retinal ganglion cells layer, MRI = magnetic resonance imaging, VEP = visual evoked potentials, VEP IT = VEP implicit time, VEP A = VEP amplitude.

Current trends in targeting the oxidative stress in glaucoma (Review).

Glaucoma is a progressive optic neuropathy characterised by retinal ganglion cell degeneration and visual field loss. Glaucoma is considered to be the leading cause of blindness in the industrialised countries. Oxidative damage is an important pathogenic factor in glaucoma, which triggers trabecular meshwork (TM) degeneration, which then leads to intraocular hypertension. Neurodegenerative insults during glaucomatous neurodegeneration initiate an immune response to restore tissue homeostasis. However, the oxidative stress (OS) that develops during the pathogenic processes of glaucoma, along with the agerelated OS, plays a critical role in shifting the physiological equilibrium. In the TM from glaucoma donors, proinflammatory markers were found, which were induced by the activation of a stress response. Chronic changes in the composition of antioxidants found in aqueous humour may induce alterations in TM as well as in the optic nerve head cells. Highlighting the pathogenic role of reactive oxygen species (ROS) in glaucoma has implications in preventing this disease. Various clinical trials are available to test the efficacy of antioxidant drugs in glaucoma management. In this review, we discuss the OS as a therapeutic target, suggesting that the modulation of a pro-oxidant/antioxidant status might be a relevant target for glaucoma prevention and therapy.

The Diagnosis and Treatment of Fungal Endophthalmitis: An Update.

In recent, large case series of fungal endophthalmitis (FE) that were published by Asian authors, the most frequent etiologic agents for all types of FE are molds (usually Aspergillus species, while Fusarium is the prevalent etiology in keratitis-related FE). Candida was the organism found in most cases of endogenous FE. However, we must keep in mind that prevalence of fungal species varies with the geographical area. Lately, polymerase chain reaction (PCR) was increasingly used for the diagnosis of FE, allowing for very high diagnostic sensitivity, while the costs become more affordable with time. The most important shortcoming of PCR-the limited number of pathogens that can be simultaneously searched for-may be overcome by newer techniques, such as next-generation sequencing. There are even hopes of searching for genetic sequences that codify resistance to antifungals. We must not forget the potential of simpler tests (such as galactomannan and ß-d-glucan) in orienting towards a diagnosis of FE. There are few reports about the use of newer antifungals in FE. Echinocandins have low penetration in the vitreous cavity, and may be of use in cases of fungal chorioretinitis (without vitritis), or injected intravitreally as an off-label, salvage therapy.

Current trends in gene therapy for retinal diseases (Review).

The eye is considered an effective target for genetic therapy, as it has a privileged immune status, it is easily accessed for medication delivery and it is affected by a number of inherited disorders. In particular, the retina is considered for gene therapy due to the fact that it can be visualized with ease, it does not have lymphatic vessels, nor a direct blood network for the outer layers and its cells do not divide after birth, and thus transgene expression is not affected. As gene therapy is currently on a continuously progressive development trend, this emerging field of gene manipulation techniques has yielded promising results. This involves the development of treatments for a number of debilitating and blinding diseases, which were to date considered intractable. However, numerous unanswered questions remain as regards the long-term efficacy and safety profile of these treatments. The present review article discusses the current research status regarding genetic manipulation techniques aimed at addressing visual impairment related to retinal disorders, both inherited and degenerative.

Leber's hereditary optic neuropathy - Case report.

Leber's hereditary optic neuropathy is the most common mitochondrial condition and is characterized by bilateral, painless, subacute visual loss that develops during young adult life. LHON is a rare condition and this lack of knowledge can make doctors suspect and treat for other causes of vision loss. Typically, a series of tests are performed to confirm LHON diagnosis or exclude any other conditions. We presented the case of two brothers, HB, of 40 years old and HF, of 38 years old, who presented with a decrease in visual acuity in both eyes. The patients had been diagnosed with optic atrophy of unknown cause a long time ago, but no further investigations were made. They were treated with corticosteroids, antioxidants and vasodilators, but with no significant benefit. A blood test of the mitochondrial DNA, a magnetic resonance imaging and an optic coherence tomography of the optic nerve and macula were part of the following assessment of our patients. The mitochondrial DNA analyses revealed the 3460 G>A mutation on the mtND1 gene in both patients. Based on the medical history, the fundus aspect, the optic coherence tomography and the paraclinical investigations of the diagnosis of Leber's hereditary optic neuropathy were established in both patients. We started the treatment with idebenone and we evaluated the patients after three months. ABBREVIATIONS: LHON = Leber's hereditary optic neuropathy, mtDNA = mitochondrial DNA, VA = visual acuity, CF = count fingers, OCT = optical coherence tomography, RNFL = retinal nerve fiber layer, GCL = ganglion cells layer, MS = multiple sclerosis, MRI = magnetic resonance imaging, MTI = magnetization transfer imaging, MTR = magnetization transfer ratio.

The role of Optical Coherence Tomography in optic neuropathies.

Optical neuropathies are neuro-ophthalmologic disorders, the main symptoms of which are the decrease of visual acuity and the alteration of the color vision. Optical coherence tomography has been one of the most important innovations in ophthalmology, which offered the possibility to analyze specific structures of the retina. Optical coherence tomography performs in vivo, real-time, noncontact scanning and provides cross-sectional and volumetric images with a resolution approaching that of histology. Optical coherence tomography offers the opportunity to study neurological diseases in an objective and non-invasive manner. The measurements of retinal nerve fiber layer can be an objective measurement of nerve swelling or nerve atrophy. By analyzing the ganglion cell complex, optical coherence tomography can help detect early axonal damage and may predict the visual outcome. It can be useful for diagnosis and follow-up of optic nerve and chiasmal compressive diseases. Furthermore, optical coherence tomography is useful in patients with multiple sclerosis in distinguishing macular disease from optic neuritis and in monitoring the treatment. Multiple studies and clinical observations support the importance of optical coherence tomography in the diagnosis, treatment, and follow-up of optic neuropathies. ABBREVIATIONS: OCT = optical coherence tomography, VA = visual acuity, RNFL = retinal nerve fiber layer, GCL = ganglion cells layer, MS = multiple sclerosis, ON = optic neuropathy, NAION = non-arteritic ischemic anterior optic neuropathy, LHON = Leber hereditary optic neuropathy, RE = right eye, LE = left eye.