[Confocal microscopy of the corneal nerve fibers]. / Konfokal'naya mikroskopiya nervnykh volokon rogovitsy.

This article presents the results of confocal microscopy of the corneal nerve fibers (CNF). The transparency of the cornea provides a unique potential for in vivo visualization of thin unmyelinated nerve fibers at the level close to morphological study. Modern software eliminates the need for manual tracing of the confocal image fragments, allows objectifying the process of assessment of CNF structure based on quantitative indicators characterizing the length, density and tortuosity of the main nerve trunks. Clinical application of structural analysis of the CNF has two potential directions associated with immediate tasks of ophthalmology, as well as with interdisciplinary affairs. In terms of ophthalmology, this primarily concerns various surgical interventions potentially affecting the state of the cornea, and chronic pathological processes in the cornea of different nature. Such studies could analyze the degree of changes in the CNF, or the particularities of corneal reinnervation. The potential for interdisciplinary studies lies in using CNF as biomarkers of systemic polyneuropathies. Relative simplicity, high level of direct visualization of the thin nerve fibers, and the obtained results allow recommending corneal confocal microscopy as a tool for primary screening and consequent monitoring of neuropathies in addition to the conventional methods.

[Hybrid (femtolaser) phacoemulsification: technical aspects and functional results]. / Gibridnaya (femtolazernaya) fakoemul'sifikatsiya: tekhnologicheskie aspekty i funktsional'nye rezul'taty.

This article summarizes scientific and practical results of hybrid femtosecond laser-assisted phacoemulsification (HFE) including study of clinical and technical aspects of the intervention and evaluation of post-surgical functional state of the eye on the basis of clinical, morphological and biomechanical data. The HFE technology should be considered the method of choice for microinvasive phaco surgery, its main advantage being the possibility of controlled handling of such important surgical stages as anterior circular continuous capsulorhexis and nucleus fragmentation on a closed eyeball, which significantly reduces the risk of complications and decreases of effective ultrasound time.

In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma.

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

[Nerve fiber structure after different types of corneal transplantation]. / Struktura nervnykh volokon posle razlichnykh variantov peresadki rogovitsy.

This review presents basic information about the state of corneal nerve fibers and Langerhans cells before and after keratoplasty. Keratoplasty is a common corneal surgery that carries a risk of graft rejection. The state of corneal nerve fibers can vary after different types of keratoplasty. Corneal confocal microscopy allows in vivo evaluation of the cornea, which can help assess the condition of corneal nerve fibers, as well as reveal the presence of Langerhans cells. Further research in this direction would contribute to identifying the relationship between the state of corneal nerve fibers, the presence of Langerhans cells, and graft rejection.

[Methods and clinical significance of the condition of corneal nerve fibers]. / Metody i klinicheskoe znachenie otsenki sostoyaniya nervnykh volokon rogovitsy.

The review provides basic information about embryology, structural features, biochemical composition, functions and classification of corneal nerve fibers, and describes anatomical, histological and functional diagnostic techniques for corneal nerves. Each method for analyzing the structure of the nerve fiber, its advantages and disadvantages are described in detail, including the history of the development of confocal microscopy (laser and light) and esthesiometry (contact and non-contact). The article also presents the criteria according to which the structure of the nerve fiber is estimated using laser confocal microscopy, and the shortcomings of these criteria. Additionally, the article reports on the futility of the use of modern esthesiometry methods.

[State of corneal nerve fibers in systemic amyloidosis]. / Sostoyanie nervnykh volokon rogovitsy pri sistemnom amiloidoze.

The term systemic amyloidosis unites a group of diseases with a single pathogenetic mechanism involving diffuse deposition of a pathological fibrillar protein (amyloid) in the intercellular space of various organs. Among the systemic forms of amyloidosis, light chain amyloidosis (AL-amyloidosis) occurs most often in clinical practice, while transthyretin amyloidosis (TTR-amyloidosis) is its most common hereditary form. Laser corneal confocal microscopy (CCM) allows for in vivo and non-invasive assessment of the state of corneal nerve fibers (CNF). PURPOSE: To assess the state of CNF in systemic amyloidosis by confocal microscopy data obtained in vivo. MATERIAL AND METHODS: The main study group included 16 patients (6 men and 10 women, mean age 60.5±11.6 years) with morphologically confirmed primary AL-amyloidosis, and 14 patients (5 men and 9 women, mean age 59.4±11.3 years) with genetically and morphologically confirmed hereditary TTR-amyloidosis. The control group included 23 healthy volunteers of the same age range without any neurological pathologies. The state of CNF was assessed by in vivo CCM data recorded on the HRT III system and its consequently processing using authors' self-developed program Liner 1.2. The criteria for neuropathy intensity was the degree of CNF tortuosity characterized by coefficients of anisotropy (KΔL) and symmetry (Ksym) of CNF orientation. RESULTS: According to the NIS scale, the manifestations of neuropathy in the subgroup of patients with TTR-amyloidosis were significantly more pronounced compared to AL-amyloidosis patients. The severity of clinical manifestations of neuropathy did not depend on the duration of TTR-amyloidosis and AL-amyloidosis (Spearman R rs=0.21, p=0.58 and rs= -0.49, p=0.055, respectively). Changes in the quantitative indicators (a decrease in the anisotropy coefficient and an increase in the symmetry coefficient of the fibers orientation) confirm increased tortuosity of CNF in systemic amyloidosis. CONCLUSION: The clinical picture of systemic amyloidosis is characterized by polymorphism of neurological manifestations that include various symptoms of damage to the peripheral somatic and autonomic nervous system. In vivo CCM can be used to reveal qualitative and quantitative changes in CNF in patients with systemic amyloidosis. However, statistical unreliability of the identified quantitative changes allows considering the state of CNF in amyloidosis only as a component of the disease monitoring algorithm, but not as a biomarker of the disease.

[First results of clinical diagnostic analysis of post-COVID peripheral neuropathy]. / Pervye rezul'taty kliniko-diagnosticheskogo analiza postkovidnoi perifericheskoi nevropatii.

This analysis of ocular manifestations of the COVID-19 that can occur both in the acute and the post-COVID period focuses on pathological changes associated with hypercoagulation: thrombosis of the central retinal vein, occlusion of the central retinal artery, and decreased peripapillary perfusion. Potential changes in corneal nerve fibers (CNF) associated with coronavirus infection remain poorly understood. Meanwhile, previous studies have shown the possibility of using CNF as biomarkers of polyneuropathy (PNP). PURPOSE: To study clinical and diagnostic features of post-COVID PNP. MATERIAL AND METHODS: We examined 9 female patients aged 32 to 51 years who had suffered an infection caused by SARS-CoV-2 of varying severity. The patients were divided into two groups: the first consisted of 6 patients with clinical manifestations of PNP in the form of neuropathic pain, the second - 3 patients without clinical manifestations. Patients of group 1 underwent comprehensive examination including neurological examination, confocal microscopy of the cornea (in vivo CM), electroneuromyography (ENMG) of the nerves of the upper and lower extremities, quantitative sensory testing in the zone of painful sensations, while patients of group 2 only underwent in vivo CM. RESULTS: All patients of the first group, within 5-40 days after the onset of infection caused by SARS-CoV-2, exhibited symptoms of damage to various parts of the nervous system (peripheral nerves, thoracic spinal roots, trigeminal nerve). The main - and in most cases the only - symptom of the disease was neuropathic pain syndrome. In Guillain-Barré syndrome, for the first time using in vivo CM, the following changes were revealed: enlargement of in Langerhans cells, shortening of CNF and their processes, presence of neuromas. CONCLUSION: The standard neurological examination of patients with post-COVID neuropathy should be supplemented with special diagnostic methods for assessment of structural and functional state of the peripheral nerves. The in vivo CM method is capable of non-invasive assessment of changes in thin CNF and, with accumulation of empirical data, can be included in the algorithm for diagnosing post-COVID PNP.

The Role of Polymorphic Markers rs1478604, rs2292305, and rs2228262 in THBS1 Gene in the Development of Autoimmune Dry Eye Syndrome.

An association of polymorphic marker rs2228262 in the THBS1 gene with the risk of developing dry eye in Sjögren syndrome was revealed. Confocal microscopy data suggest that this polymorphic marker is responsible for the high probability of corneal nerve fiber lesion in Sjögren syndrome even in the absence of clinical and functional signs of dry eye syndrome. A significant correlation was established between polymorphic markers rs1478604, rs2228262 in THBS1 gene and the coefficients of anisotropy and orientation symmetry of corneal nerve fibers. These results allow considering these polymorphic markers as a genetic factor of predisposition to dry eye syndrome in patients with Sjögren syndrome.

[Changes in corneal nerve fibers after microinvasive cataract surgery (a preliminary report)]. / Izmeneniya nervnykh volokon rogovitsy posle mikroinvazivnoi fakokhirurgii (predvaritel'noe soobshchenie).

INTRODUCTION: Potential changes in corneal nerve fibers (CNF) induced by cataract phacoemulsification remain insufficiently studied. The need for research in this direction is dictated by a number of circumstances: introduction of corneal confocal microscopy into clinical practice, the need for phaco surgery in the presence of corneal changes of various genesis, the possible negative impact of laser radiation during hybrid (femtosecond laser-assisted) phacoemulsification. PURPOSE: To assess the changes in CNF after various methods of microinvasive cataract surgery. MATERIAL AND METHODS: The studies were conducted in patients aged 50 to 60 years who underwent standard ultrasound and hybrid phacoemulsification; the patients were respectively divided into two groups (30 surgeries each). The algorithm for assessing the state of CNF involved laser confocal microscopy using original software. To quantify the state of the nerves, two coefficients were used: CNF orientation anisotropy (KΔL) and CNF orientation symmetry (Ksym). RESULTS: Regardless of the surgery technique, tendencies were noted for the orientation anisotropy coefficient to decrease and the orientation symmetry coefficient to increase, which are conditionally comparable with previously identified age-related changes in CNF. After hybrid phacoemulsification, a decrease in the orientation anisotropy coefficient 2-2.5 months after the intervention turned out to be statistically less significant compared to the standard ultrasound technique. CONCLUSION: Further research should be aimed at analyzing the long-term results of both microinvasive phacosurgery techniques and the «classical¼ extracapsular cataract extraction, which remains the method of choice in a number of clinical situations.

[Changes in corneal nerves fibers in the early stages of Parkinson's disease according to in vivo confocal microscopy (preliminary report)]. / Izmeneniya nervnykh volokon rogovitsy na rannikh stadiyakh bolezni Parkinsona po dannym lazernoi konfokal'noi mikroskopii (predvaritel'noe soobshchenie).

One of the research directions of the so-called non-motor manifestations of Parkinson's disease (PD) is associated with the assessment of structural and functional changes in the organ of vision. An assessment of the state of thin non-myelinated corneal nerve fibers (CNF) in Parkinson's disease seems to be promising considering the neurodegenerative nature of the disease, as well as the possibility of objective intravital assessment of both functional and structural changes in CNF. PURPOSE: To analyze the changes in the course and structure of corneal nerve fibers in the early stages of Parkinson's disease based on an objective algorithm of in vivo corneal confocal microscopy (CCM). MATERIAL AND METHODS: The study was conducted on a group of 16 patients aged 39 to 66 years with verified diagnosis of PD. In addition to standard neurological and ophthalmological examinations, all patients underwent IVCCM on a Heidelberg Retinal Tomograph device with special Rostock Cornea Module (HRT3 RCM), followed by processing of the obtained images using a uniquely designed analysis algorithm. RESULTS: A significant decrease in the directional anisotropy coefficient and an increase in the directional symmetry coefficient of the nerve fibers of the cornea were established (average values 3.15±1.08 and 0.92±0.04, respectively); in healthy individuals of the identical age range these indicators are 3.5±0.85 and 0.86±0.11, respectively. In addition, qualitative structural changes were noted, which consisted of an increase in the number of branches from the main nerve trunks, an increase in the tortuosity of CNF, multidirectionality, and "beaded" shape. In 9 cases, the presence of macrophages was revealed - dendritic Langerhans cells, which is an indirect sign of the inflammatory process. CONCLUSION: The preliminary nature of the results obtained in this study and the need for further research in this area are related, on the one hand, to a small sample of observations and, on the other hand, to the criterion used to assess the status of CNF based on a comparative analysis with conditionally normal indicators. In the future, in order to solve the problem of the uniqueness of changes in CNF and the possibility of using these changes as a marker for PD progression, longitudinal studies are required to reveal the presence or absence of a correlation between the stage of the disease, the results of known monitoring methods (e.g. electromyography) and quantitative indicators of the status of CNF.

[Phacosurgery effects on the condition of corneal nerve fibers]. / Vliyanie fakokhirurgii na sostoyanie nervnykh volokon rogovitsy.

The question of potential changes in the nerve fibers of the cornea induced by phacosurgery remains poorly investigated. This is a review of results of many individual studies aimed at assessing the condition of corneal nerve fibers following different techniques of cataract removal. The authors substantiate the necessity for structural analysis of fiber changes based on in vivo confocal microscopy of the cornea. Functional assessment of corneal sensitivity (esthesiometry) does not allow objective conclusions, for several reasons. Further studies on corneal nerve changes after phacosurgery could be directed at improving software products for objective quantitative assessment of corneal nerve fibers and analyzing long-term results of various phacosurgery techniques.

[Early diagnosis of diabetic polyneuropathy based on the results of corneal nerve fibers examination]. / Vozmozhnosti rannei diagnostiki diabeticheskoi polineiropatii na osnove issledovaniya nervnykh volokon rogovitsy.

Laser corneal confocal microscopy (CCM) is a method of objective visualization of thin corneal nerve fibers (CNF), the structure of which changes in patients with diabetes mellitus (DM). PURPOSE: To conduct comparative analysis of the results of CNF assessment using CCM and other known neurological instrumental techniques as well as evaluate their applicability to the early diagnosis of diabetic polyneuropathy (DPN). MATERIAL AND METHODS: We examined a total of 46 patients (85 eyes) with type 1 DM and either subclinical (24 patients), or clinical-stage DPN (22 patients) and 50 patients (87 eyes) with type 2 DM (subclinical DPN in 27 patients and clinical-stage DPN in 23 patients). The control group consisted of 34 healthy volunteers (68 eyes). All patients underwent standard ophthalmological examination, CCM with nerve tortuosity assessment (including calculation of coefficients of CNF orientation anisotropy, KΔL, and symmetry, Ksym) and interocular asymmetry, electroneuromyography (ENMG), and quantitative sensory testing (QST). RESULTS: Analysis of the CCM results revealed a reliable decrease in the average KΔL values in patients with type 1 and type 2 DM compared with the control group. In the group of patients with type 1 DM and subclinical DPN, correlations were revealed between the CNF tortuosity coefficients and a number of ENMG parameters, such as the M-response amplitude of the peroneal nerve (r=0.73, p≤0.02), M-response amplitude of the tibial nerve (r=0.58, p≤0.01), residual latency (r= -0.62, p≤0.05), and peroneal nerve conduction velocity (r=0.57, p≤0.01). Ksym values correlated with the warm sensitivity threshold (r=0.6, p≤0.008). Among patients with type 2 DM and subclinical DPN, the KΔL coefficient correlated with the peroneal nerve conduction velocity (r=0.46, p≤0.02), M-response amplitude of the tibial nerve (r=0.6, p≤0.04), and residual latency of the peroneal nerve (r=-0.56, p≤0.05). CONCLUSION: The state of thin corneal nerves correlates with functional changes in the peripheral nerves. Pathological changes in CNF in patients with DM can be detected at an early (subclinical) stage of DPN using laser CCM and a program for corneal nerve tortuosity analysis.

[Condition of corneal nerve fibers after laser keratorefractive surgery]. / Sostoianie nervnykh volokon rogovitsy posle lazernykh keratorefraktsionnykh operatsii.

The article reviews studies dedicated to evaluation of corneal nerve fibers (CNF) after various laser keratorefractive methods of correcting refractive error based on confocal microscopy. The matter of studying the dynamics of the condition of CNF after laser keratorefractive techniques continues to be relevant and requires further research with regard to the prevalence of refractive errors on the one hand, and the future life of patients who undergo these procedures, on the other. Certain heterogeneity of the research results presented in this review can be partially explained by the subjective nature of the study algorithm (in particular, the need for manual tracing of nerve fibers) and the lack of objective quantitative indicators of CNF condition suitable for statistical processing.

[Morphological changes in the cornea of patients with recurrent corneal erosion after diamond burr polishing of Bowman's membrane]. / Morfologicheskie izmeneniia rogovitsy pri sindrome retsidiviruiushchei érozii posle shlifovki boumenovoi membrany almaznym borom.

PURPOSE: To evaluate morphological changes in the cornea of patients with recurrent corneal erosion (RCE) using laser confocal microscopy before and after abrasive polishing of Bowman's membrane with a diamond burr (APBMDB). MATERIAL AND METHODS: The study included 17 patients (20 eyes) with established RCE diagnosis; they underwent laser confocal microscopy on HRT III device with Rostock Cornea module (Heidelberg Engineering GmbH, Germany). Morphological analysis of epithelial cells, nerve fibers, stroma and corneal endothelium was conducted. After that, all patients underwent APBMDB. Patient examination was repeated after 1, 3, 6, and 12 months. RESULTS: Superficial epithelium was intact before treatment in almost all cases. Islets of hyper-reflective cells, drop-shaped arrangements and stripes characterizing abnormal basal membrane were found in basal epithelium layer. Activated keratocytes and anomalous extracellular matrix were observed in the anterior stroma. No changes could be found in the posterior stroma or endothelium. Subbasal nerve plexus had changes in the form of short and atypically formed corneal nerve fiber funiculi, reduced amount of long corneal nerve fiber funiculi, as well as their tendency for forming closed round shapes. Increase in the amount of Langerhans cells was observed. One month after the procedure, pathological changes in the epithelium and basal membrane were absent, reduction in the amount of Langerhans cells and activated keratocytes was observed. Three months after the polishing, continued reduction of the amount of Langerhans cells was noted. Regeneration of nerves partially restored after 6 months; after 12 months, confocal microscopy results were comparable to healthy volunteers. CONCLUSION: Confocal laser microscopy of the cornea of patients with RCE showed presence of changes in basal epitheliocytes, basal membrane, anterior stroma and corneal nerve fibers, as well as positive dynamics of these changes after abrasive polishing of Bowman's membrane with a diamond burr.

[Clinical and morphological changes in the eye in Fabry's disease (a clinical case study)]. / Kliniko-morfologicheskie aspekty izmeneniia glaza pri bolezni Fabri (klinicheskii sluchai).

The article presents a clinical case of Fabry's disease accompanied by changes in the eye and gives detailed description of standard ophthalmological examination and results of some modern methods of assessing macro- and micro-structure of certain ocular tissues. Fabry's disease (also known as Anderson-Fabry disease, diffuse angiokeratoma of the body, hereditary dystonic lipidosis) is a progressive hereditary multi-systemic disease; more specifically, it is a progressive congenital defect in the metabolism of tissues of the human body. It is included in the list of orphan diseases. One of its local manifestations is development of dystrophic changes in the structure of the cornea with tendency to progress. Early diagnosis of Fabry's disease is crucial, but its extensive and 'mixed' symptoms often mask the true causes of pathological changes, which leads to late diagnosis.

[Anatomical and functional features of corneal nerve fibers and methods of their evaluation]. / Anatomo-funktsional'nye osobennosti i metody issledovaniia nervnykh volokon rogovitsy.

Condition of the ocular surface greatly depends on functional integrity of corneal nerve fibers. Improving the methods used to study corneal nerve fibers allows their condition to be timely evaluated and adequately interpreted. The article reviews the structure, function, chemical composition of corneal nerve fibers, specifics of their innervation, as well as application of modern methods of their evaluation in diagnostics of various pathological conditions.

[Clinical features and diagnosis of diabetic polyneuropathy]. / Klinicheskie osobennosti i diagnostika diabeticheskoi polineiropatii.

Diabetic polyneuropathy (DPN) is a serious complication of diabetes that leads to early disability in patients if late diagnosed. There has been a lot of research into pathophysiological mechanisms of nerve fiber damage and risk factors for neurological complications of diabetes. Early diagnosis of the latter is quite a challenge and, thus, the problem of finding more reliable diagnostic modalities is rather pressing. In this review, an interdisciplinary approach to the said problem, high-end diagnostic methods, and clinical features of DPN are described.

Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.

The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes.

The purpose of this study was to determine the effect of supplementing the diet of a mouse model of type 2 diabetes with menhaden (fish) oil or daily treatment with resolvin D1 on diabetic neuropathy. The end points evaluated included motor and sensory nerve conduction velocity, thermal sensitivity, innervation of sensory nerves in the cornea and skin, and the retinal ganglion cell complex thickness. Menhaden oil is a natural source for n-3 polyunsaturated fatty acids, which have been shown to have beneficial effects in other diseases. Resolvin D1 is a metabolite of docosahexaenoic acid and is known to have anti-inflammatory and neuroprotective properties. To model type 2 diabetes, mice were fed a high-fat diet for 8 wk followed by a low dosage of streptozotocin. After 8 wk of hyperglycemia, mice in experimental groups were treated for 6 wk with menhaden oil in the diet or daily injections of 1 ng/g body wt resolvin D1. Our findings show that menhaden oil or resolvin D1 did not improve elevated blood glucose, HbA1C, or glucose utilization. Untreated diabetic mice were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities, had decreased innervation of the cornea and skin, and had thinner retinal ganglion cell complex. These end points were significantly improved with menhaden oil or resolvin D1 treatment. Exogenously, resolvin D1 stimulated neurite outgrowth from primary cultures of dorsal root ganglion neurons from normal mice. These studies suggest that n-3 polyunsaturated fatty acids derived from fish oil could be an effective treatment for diabetic neuropathy.

Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia.

INTRODUCTION: This study assessed the association of cerebral ischemia with neurodegeneration in mild cognitive impairment (MCI) and dementia. METHODS: Subjects with MCI, dementia and controls underwent assessment of cognitive function, severity of brain ischemia, MRI brain volumetry and corneal confocal microscopy. RESULTS: Of 63 subjects with MCI (n = 44) and dementia (n = 19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both subcortical and cortical ischemia. Brain volume and corneal nerve measures were comparable between subjects with subcortical ischemia and no ischemia. However, subjects with subcortical and cortical ischemia had a lower hippocampal volume (P < 0.01), corneal nerve fiber length (P < 0.05) and larger ventricular volume (P < 0.05) compared to those with subcortical ischemia and lower corneal nerve fiber density (P < 0.05) compared to those without ischemia. DISCUSSION: Cerebral ischemia was associated with cognitive impairment, brain atrophy and corneal nerve loss in MCI and dementia.