Comparison of ocular surface stainings.
\r\n\tWith this goal in mind, together with the US Prof. John M. Ballato and the InechOpen publishing house since 2011 we have published in 2011, 2013, 2015 and 2017 4 books of our serial “Optoelectronics” and the book “Excitons”, edited in 2018 by Prof. Sergei L. Pyshkin. Publishing the new book “Luminescence” we are pleased to note the growing number of countries participating in this undertaking as well as for a long time fruitfully cooperating scientists from the United States and the Republic of Moldova.
\r\n\tSpecialists from all over the world have published in edited by us books their works in the field of research of the luminescent properties of various materials suitable for use in optoelectronic devices, the development of new structures and the results of their application in practice.
In order to ensure a proper response to external stimuli, organisms have created complex and coordinated neural structures that allow the sophisticated analysis of information. As the central nervous system (CNS) evolved from a basic network structure to compacted ganglia and centralized brains, two types of connections emerged as specialized structures favoring the integration of neural networks [1]. In 1897, Sherrington proposed the point of functional contact between neurons as the specific area at which transfer of information takes place and named it “synapsis,” soon shortened to the “synapse,” from the Greek word
Basic structure of connexin-based channels. Connexins have four α-helical transmembrane domains connected by two extracellular loops and one cytoplasmic loop; both the amino- and carboxy-termini are intracellular. The relative positions of the extracellular loop cysteines (red balls) are also shown. Hemichannels (also known as connexons) are formed by the oligomerization of six subunit connexins around a central pore. Under resting conditions, hemichannels remain preferentially closed, but they may be activated by diverse physiological and pathological conditions and offer a diffuse transmembrane route between the intra- and extracellular milieu. Hemichannels dock each other to form functional cell-to-cell channels termed gap junction channels (right panel). Gap junction channels aggregate in well-known anatomical structures called gap junctions to facilitate the intercellular cytoplasmic exchange of metabolites, second messengers, and ions.
The traditional notion of neurons being the only functional elements in the synapse has been questioned with the finding that intracellular Ca2+ ([Ca2+]i) waves within and among astrocytes underlie the regenerative (nondissipative) transfer of biological signals [5, 6, 7]. Although astrocytes are not electrically silent cells [8], [Ca2+]i signals are their principal fast time-scale mechanism for allowing intra- and intercellular signaling [9]. These signals base their origin on the extracellular influx of Ca2+ via ion channels and through Ca2+ release from intracellular stores, resulting in [Ca2+]i transients that differ in frequency, kinetics, and spatial spread depending on the astroglial anatomical region [10]. Endowed with this machinery and along with pre- and postsynaptic neuronal elements, astrocytes embrace the “tripartite synapse”—the Rosetta stone of the chemical synaptic transmission—in where they sense neurotransmission and respond to it by releasing biomolecules that regulate neuronal activity called “gliotransmitters” (i.e., glutamate, D-serine, and ATP) [11]. Intracellular [Ca2+]i waves can spread among astrocytes to finally reach the terminal processes or “endfeet” of specialized astrocytes that contact the endothelium [12]. There, vasoactive molecules are released, permitting astrocytes to modulate the cerebral blood flow (CBF) and delivery of energy substances (i.e., glucose and lactate) with potentially significant consequences for neuronal firing and higher brain functions [13]. Indeed, a single astrocyte may contact over 100,000 synapses in rodents and up to 2,000,000 synapses in humans, revealing that they actually form a syncytium with multiple connections [14].
Nowadays, diverse mechanisms have been proposed to lead to gliotransmitter release (Figure 1), including Ca2+-dependent exocytosis [15, 16, 17], carrier membrane transport [18], and opening of a wide range of channels. Among the latter group, volume-regulated anion channels [19, 20, 21], P2X7 receptors [22, 23, 24], Ca2+-dependent Cl− channel bestrophin 1 [25, 26], and hemichannels [27, 28, 29, 30] are included. This chapter reviews and discusses recent data supporting a role for hemichannels as pathways for gliotransmission and relevant actors in that tuning of synaptic transmission and plasticity.
During the past decade, a growing body of evidence began to support a novel mechanism of autocrine/paracrine communication underlying gliotransmission and astrocyte-to-neuron communication: hemichannel-mediated signaling [31]. Each hemichannel is composed of the oligomerization of six protein subunits called connexins around a central pore (Figure 1). Connexins embrace a highly conserved protein family encoded by 21 genes in humans and 20 in mice, with orthologs in other vertebrate species [32]. These proteins are abundantly expressed in brain cells [33], including astrocytes [34], and they are named after their predicted molecular mass expressed in kDa, for instance, connexin 43 (Cx43) has a molecular mass of ~43 kDa [35]. For several years, the key function attributed to hemichannels was to constitute the building blocks of the gap junction channels, which are intercellular channels that allow the direct cytoplasmic exchange between contacting cells [35]. Nonetheless, in the 1990s, pioneering findings by Paul and colleagues revealed the presence of functional and solitary hemichannels in “nonjunctional” membranes [36]. Today, it is well accepted that these channels act like aqueous pores, providing a diffusional route of exchange for ions and molecules between the intra- and extracellular space [37]. Across the different tissues, hemichannels allow the cellular release of relevant quantities of autocrine and paracrine signaling molecules (e.g., ATP, glutamate, D-serine, NAD+, and PGE2), as well as the influx of other substances (i.e., Ca2+ and glucose) [37].
Since their discovery, hemichannels have been linked with cellular damage. This idea came from early studies suggesting that osmotic and ionic imbalances induced by the uncontrolled influx of Na2+ and Cl− through hemichannels could result in further cell swelling and plasma membrane breakdown [36]. In addition, it has been proposed that because hemichannels are permeable to Ca2+, their uncontrolled opening could lead to Ca2+ overload and the consequent production of free radicals, lipid peroxidation, and plasma membrane damage [38]. Alternatively, exacerbated hemichannel activity could also induce the release of molecules that at high concentration may be toxic for neighboring cells, such as glutamate, in the case of the CNS [39]. Despite the above, in the last decade, a substantial body of studies has proposed that hemichannels may underpin pivotal neurophysiological functions, such as synaptic efficacy, neural activity, signal processing, cognition, and behavior [27, 28, 40, 41, 42, 43, 44].
Although rat, mouse, and human astrocytes express abundantly Cx30 and Cx43, as well as Cx26 [45, 46, 47, 48, 49], at the moment, Cx43 is the only connexin probed to form functional hemichannels in astrocytes [50]. The opening of astroglial Cx43 hemichannels has been linked with the release of different gliotransmitters (e.g., glutamate, ATP, D-serine, lactate), as well as with the influx of extracellular Ca2+ and glucose. Seminal studies by Torres and colleagues demonstrated for the first time that astrocyte hemichannels may act as both sensors and modulators of synaptic activity [43]. Using UV-photolysis of caged MNI-glutamate in hippocampal slices, they found that specific deletion of Cx43 abrogates ATP-dependent spreading of slow Ca2+ waves among astrocytes. Furthermore, these slow Ca2+ waves were potentiated when authors used slices from transgenic mice with an astrocyte-targeted point mutation (Cx43G138R) that leads to an increased Cx43 hemichannel opening [51]. In addition, they observed that depolarization of inhibitory interneurons from the stratum radiatum reduced CA1 excitatory transmission via the astroglial Cx43 hemichannel-mediated release of ATP and subsequent stimulation of interneuronal P2Y1 receptors [43]. These data shed light for the first time about how astrocyte Cx43 hemichannels may underpin a negative feedback mechanism elicited during sustained excitation to prevent excitotoxicity (Figure 2).
Possible role of astroglial hemichannels in hippocampal synaptic transmission. During the basal firing of glutamatergic neurons in the hippocampus, Ca2+ influx into neurons results in a localized reduction in [Ca2+]e, which in turn opens Cx43 hemichannels (HCs) on astrocytes [
Although in normal astrocytes few Cx43 hemichannels are in the plasma membrane and most of them with a low open probability, recent findings have described that they facilitate the release of ATP under basal conditions [27, 41]. Chever and co-workers observed that basal release of ATP via astroglial Cx43 hemichannels is enough to boost the CA1 synaptic transmission triggered by stimulation of Schaffer collaterals, an effect mediated by purinergic receptors [27] (Figure 2). Likely the insertion of postsynaptic AMPA receptors as a result of the activation of P2X7 receptors could explain the ATP-dependent potentiation of glutamatergic transmission, as reported before in other brain areas [52]. Astroglial hemichannels also have been found to regulate neuronal activity in the olfactory bulb (OB) [41]. There, the group of Giaume demonstrated that pharmacological inhibition of Cx43 hemichannels decreased the firing and amplitude of depolarized states in mitral cells. Similar findings were observed in mitral cells of OB slices with specific astroglial deletion of Cx43 [41] or in slices treated with A1 adenosine receptor antagonists. These findings denote that likely astrocyte Cx43 hemichannels enhance the amplitude of depolarized states of mitral cells through the release of ATP and its further breakdown to adenosine (Figure 3). Usually, A1 receptors induce the presynaptic inhibition of glutamate release, reduced postsynaptic NMDAR activation, and decreased Ca2+ influx [53]. Therefore, it is possible that the adenosine-mediated enhancement of depolarized states is due to the suppression of inhibitory juxtaglomerular interneurons, as occurred in other brain areas [54] (Figure 3).
Implications of astroglial hemichannel activity in neuronal oscillations of the olfactory bulb. Spontaneous neuronal activity in the glomerular layer of the olfactory bulb requires glutamatergic transmission. In this scenario, astrocytes display a basal release of ATP via Cx43 hemichannels (HCs) [
Astroglial Cx43 hemichannels have been involved not only in synaptic function and transmission but also in synaptic plasticity. High-frequency stimulation (HFS) of neuronal layer 2/3 (L2/3) triggers glutamatergic synaptic transmission in pyramidal cells at layer 5 (L5) of the prefrontal cortex (PFC) [55]. In this context and using PFC slices, Meunier and colleagues observed that genetic ablation of Cx43 or inhibition of Cx43 hemichannels strongly counteracts the NMDAR-dependent excitatory postsynaptic currents (EPSCs) and increases AMPA/NMDA current ratio induced by HSF in L5 [28]. Relevantly, the latter responses did not occur when D-serine was added at the recording media, revealing that the release of D-serine and astroglial hemichannel function are linked and modulate NMDAR-dependent synaptic transmission in PFC pyramidal cells. Furthermore, when [Ca2+]i was clamped or D-serine production was inhibited in the L5 astroglial network, HFS failed to potentiate the NMDAR-dependent synaptic currents [28] (Figure 4). Accordingly, the authors hypothesized that potentiation of glutamatergic transmission at the PFC relies on [Ca2+]i-mediated opening of astroglial Cx43 hemichannels and the further release of D-serine (Figure 4).
Astroglial hemichannels and their impact on synaptic plasticity in the prefrontal cortex. In the prefrontal cortex, continuous stimulation of layer 2/3 neurons induces long-term potentiation (LTP) of NMDA and AMPA receptor currents in layer 5 pyramidal neurons. In this context, [Ca2+]i is needed for the opening of Cx43 hemichannels (HCs) in astrocytes [
The impact of astroglial hemichannels on synaptic transmission and plasticity has a subsequent echo on higher brain function and behavior. Indeed, in vivo inhibition of Cx43 hemichannels at the basolateral amygdala causes transitory and specific amnesia for auditory fear conditioning [42]. Remarkably, learning capacity was restored by the co-administration of a cocktail of supposed gliotransmitters (lactate, glutamate, D-serine, glutamine, glycine, and ATP), evidencing for the first time a physiological involvement for astroglial Cx43 hemichannels in higher brain function. In the same line, a recent study found that intraventricular administration of Gap19, a specific Cx43 hemichannel blocker [56], significantly impairs the spatial short-term memory, as assayed with the delayed spontaneous alternation Y maze task [44].
The impact of functional astroglial hemichannels in synaptic transmission and plasticity may depend on the number of channels available in the plasma membrane, their open probability, and their conductance and/or selectivity. Of particular relevance is to disentangle how synaptic function is modulated by regulations in gating properties of astroglial hemichannels, as well as changes in their trafficking or de novo synthesis. Elucidating the latter will allow us to understand whether hemichannel opening in astrocytes tunes the temporal outcome for sculpting either short-term (milliseconds to a few minutes) or long-term (minutes to hours) plasticity in the nervous system. One point of concern is the urgent need of developing new molecular and pharmacological tools to specifically dissect the contribution of astroglial hemichannels to the function of neural networks without affecting other hemichannel-forming proteins in other brain cells (e.g., microglia, oligodendrocytes, and endothelial cells). Finally, although growing evidence in ex vivo preparations has extended our knowledge about the role of astroglial hemichannels in gliotransmission, additional data are necessary to demonstrate whether this truly occurs in vivo.
This work was supported by (i) the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) and Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) Grant 1160710 (to JAO) and (ii) the CONICYT and Programa de Investigación Asociativa (PIA) Grant Anillo de Ciencia y Tecnología ACT1411 (to JAO). The author did part of the schematics with support of the free online Servier Medical Art repository (https://smart.servier.com/).
The author declares no conflict of interest.
Dry eye disease is one of the most commonly encountered problem in daily practice. It is the reason why a patient visits the eye care professional. Dry eye—as it was defined by the National Eye Institute (NEI)/Industry Workshop on Clinical Trials in Dry Eyes—is a disorder of the tear film due to tear deficiency or excessive evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort [1]. In 2007, the International Dry Eye Workshop updated the original definition and classified dry eye as “multi-factorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” [2]. In 2017, the definition was revised, which centered on the clinical effects and associated signs as “multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” [3].
Based on those definitions, dry eye symptoms can change from day to day and they may vary in every patient, from mild to severe ocular discomfort and visual disturbance. Dry eye disease can affect patients’ quality of life. It is important for eye care professionals to recognize, diagnose, and treat DED; but, somehow DED can be puzzling since there is no consistent, well accepted, diagnostic test that is both readily available and reproducible [4]. When a patient comes in due to the symptoms that may suggest DED or for a routine examination, an eye care professional should do history taking comprehensively. Various diagnostic tests may be required to determine if the patient has DED due to aqueous deficient, evaporative, or both. In daily practice, tear-film and dry eye assessment are often performed in symptomatic patients. However, it must be kept in mind that dry eye symptoms and signs may be not well associated, as reported in previous studies [5, 6, 7].
A careful history taking is an important thing to perform in the first place to help the eye care professional in assessing dry eye correctly, including history of previous medication, long-term contact lens wear, ocular surface surgery, or systemic condition(s). Patients with dry eye often complain of eye discomfort or irritation, gritty or foreign body sensation, burning, tearing, stinging, intermittent sharp pain, redness, or/and photophobia. Visual disturbance may occur. Dry eye patients may have all, some, or none of these symptoms.
A clinician should also understand that dry eye symptoms increase with age, menopausal status, hormonal diseases, current smoking history, certain medications, and presence of pterygium are a few factors result in dry eye [4, 5, 8, 9, 10]. Noor et al. [7] found that there was a likelihood of shifting from preclinical dry eye towards DED and from normal towards predisposition to dry eye in older age.
There are many questionnaires available that can be used to utilize in assessing DED, such as National Eye Institute Visual Function Questionnaire-25 (NEV-VFQ-25) [11], Ocular Surface Disease Index (OSDI) [12], Standard Patient Evaluation of Dry Eye Questionnaire (DEQ-5) [13], and some others more. Every clinicians have their own preferences of questionniare.
Visual acuity assessment (including best-corrected acuity), thorough eyelid and slit-lamp of anterior segment examinations are mandatory. Patients with dry eye often complain of blurred vision which improves with blinking or instillation of artificial tear.
Whilst taking patient’s history, a clinician can examine the eyelids macroscopically. It can guide the clinician to evaluate if the patient has dry eye. Lagophthalmous, lid laxity, decreased frequency of blinking, and size of palpebral aperture. Malpositions of the eyelid have to be recognized (such as involutional or cicatrical ectropion, eversion of lacrimal punctum, dermatochalasis, full-thickness defects, inadequate lid closure due to previous eyelid surgical reconstruction) because these conditions can influence the tear turnover. Patient’s history can guide the clinician to perform identify certain ocular manifestations under careful and focused slit-lamp examination.
Under the slit-lamp biomicroscopy, a clinician should evaluate anatomical structures of the lid, including the alterations of lid margins and eyelashes. The alterations of the lid margins include hyperaemia, telangiectasia, thickening, scarring, keratinization, ulceration, tear debris, abnormalities of the meibomian orifices, metaplasia, character of expressed meibomian secretions; while for the eyelashes, the alterations include misdirection (trichiasis), malposition (dystichiasis), encrustations, collarettes [14, 15, 16]. Careful evaluation of meibomian gland is important since its dysfunction is the most frequent cause of evaportive DED and is often symtomatic [17, 18, 19]. Evaluate if the meibomian gland orifices are plugged or obstructed and/or change in its secretion.
Tear film should be evaluated for mucus, debris, or meibomian foam. Decreased tear meniscus is often a sign of dry eye. Normally, a patient with normal tear production has tear meniscus height of 0.2–0.5 mm; but in patient with dry eye, it is usually less than 0.25 mm or absent [4, 14, 15, 20, 21].
Ocular manifestations in mild to moderate dry eye may conjunctival hyperaermia, with or without corneal epithelial erosions; or these signs may not present in some mild cases. In severe forms of the disease, conjunctival scarring or conjunctivochalasis and/or corneal complications may occur. Filamentary keratitis, persistent epithelial defects, ulceration, and even corneal perforation can complicate the course [14, 15, 22]. Corneal staining may be required to evaluate the severity of its defects.
There are several tests that can be performed to confirm the diagnosis of dry eye and to evaluate the severity of the disease. The tests can measure the following parameters: (1) stability of the tear film as related to its break-up time (TBUT); (2) tear production (Schirmer, fluorescein clearance, and tear osmolarity); and (3) ocular surface disease (corneal stains and impression cytology). There is no clinical test to confirm the diagnosis of evaporative dry eye [21, 23].
Epithelial damage to the exposed ocular surface can be evaluated with vital stainings. Staining of the cornea occurs commonly in inferior part, often more in nasal and temporal areas. Corneal epithelial defect, erosions, filaments, or punctuates can be seen in dry eye. Staining of the bulbar conjunctiva occurs over a wedge-shaped zone nasally and temporally, and in advanced dry eye may become confluent; but in milder forms of dry eye, it may be present in the absence of corneal stain [23].
Fluorscein staining is a basic and standard method to evaluate ocular surface damage. Commonly, every clinician is able to perform this examination in daily practice. The orange-dyed fluorescein strip is wetted with a sterile drop of saline and then is applied to tarsal or bulbar conjunctiva. Excess fluid is shaken from the strip prior to application. The dye will distribute over ocular surface after blinking. Under slit-lamp examination using cobalt-blue filter, the orange dye will turn into fluoresces green in the damaged area. Common characteristic distribution of this test is confined to the exposed intrapalpebral area of the ocular surface, but the staining may extend to unexposed area in severe case.
In the case of perforation, aqueous from the anterior chamber will leak out of the eye and mix with the tear film. The fluorescein dye around the perforated area will be diluted by this leak and the leak will appear bright green (Seidel test).
Rose bengal is a synthetic fluorescein derivative, also perhaps referred to as bengal rose and also known as a Chemical Index (C.I.) Acid Red 94 [24]. It has the ability to bind to epithelial cells that are uncoated by certain proteins (mainly mucin) and presents high cell toxicity [25]. The instillation of this dye causes stinging or pain, particularly in DED patients, and it may be disliked by some patients; thus topical anesthesia is best instilled first to limit stinging sensation. Although rose bengal had been thought to be a vital dye, staining dead or degenerating cells, it is known that rose bengal normally stains healthy cells [26, 27].
Under slit-lamp with a white light, rose bengal staining can revealed discrete or confluent punctuate in damaged area of cornea and visible bulbar conjunctiva which can be seen as red dots (Figure 1). But there are disadvantages in using rose bengal in addition to pain on instillation. Although bulbar conjunctival staining is demonstrated well against the white background provided by the sclera, the dye is difficult to see on the cornea against the background of a dark iris [23]. Another disadvantage of rose bengal is its toxicity, including decreasing the chance to recover herpes viruses in human cell cultures [25].
Left: Fluorescein staining shows large defect in central cornea with discrete punctate staining all over cornea; right: Rose bengal staining in the same patient.
Lissamine green is a synthetically produced organic acid dye with two amino-phenyl group and it has been used as a substitute for rose bengal since it has similar laboratory and clinical staining properties, also it is a less toxic stain and less stinging upon instillation [25, 28].
Lissamine green is a vital dye that stains ocular surface epithelial cells that are unprotected by mucin or glycocalyx, as well as cells that have been damaged, and it does not stain healthy cells or damage them [28, 29, 30]. In patient with red eyes, lissamine green could provide better staining visualization than rose bengal.
The use of ocular staining mentioned above is helpful in assessing the integrity of the ocular surface epithelium. These tests are easy to perform in daily clinical practice in-office setting. The clinician can choose one of these staining to assess dry eye based on the availability of the equipment in the clinic. Fluorescein impregnated strips are preferred due to their availability and simplicity of use; while rose bengal and/or lissamine may not always be available in some eye care facilities. Table 1 helps the clinician to compare these three stainings. Significant staining of the conjunctiva with rose bengal or lissamine green is most common in severe dry eye to Sjögren’s syndrome [29].
Fluorescein | Rose Bengal | Lissamine Green | |
---|---|---|---|
Discomfort (pain/stinging) | No | Yes | No |
Staining normal/healthy cells | No | Yes | No |
Staining dead or degenerated cells | No | Yes | Yes |
Clinical means | Disruption of cellular junctions and increased membrane permeability | Loss of insufficient protection by ocular surface mucin | Cell degeneration and death (unprotected by ocular mucin or glyco-calyx) |
Slit-lamp filter | Cobalt-blue | White light or green barrier filter | Red barrier filter |
Staining grading systems remain an essential element of ocular examination and allow the clinician to record the level of ocular surface staining and evaluate the severity of dry eye. The three most common grading systems are: (1) the van Bijsterveld grading system (uses rose bengal staining of the conjunctiva and cornea); (2) the Oxford grading scheme (uses fluorescein, rose bengal, or lissamine green of the conjunctiva and cornea); and (3) and the NEI Workshop system (uses fluorescein staining to grade the cornea and rose bengal to grade the conjunctiva) [29].
The van Bijstervel grading system is the first proposed system to grade three areas in each eye: the nasal and temporal bulbar conjunctiva and the cornea (Figure 2). The intensity of the staining is graded on scale 0 (no staining), 1 (sparsely scattered staining), 2 (densely scattered), and 3 (confluent staining). The maximum score for each eye is 9. Staining score of 3 or higher is considered abnormal.
The van Bijsterveld grading system. The exposed nasal and temporal conjunctiva (NC and NT, respectively) and cornea (C) are graded on scale: 0 (no staining) to 3 (confluent staining), with maximum score is 9.
The Oxford grading scheme uses a chart consisting of a series of panels labeled A to E in order of increasing severity of staining (Figure 3). Staining is represented by punctate dots and increases by 1 log unit between panel A and B and by ½ log unit between each subsequent panel (B to E).
The Oxford grading scheme. Staining is represented by punctate dots. (adapted from Bron AJ, Evan VE, smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003;22(7):640–650).
The NEI Workshop grading system divides cornea into five areas and conjunctiva into six areas for each eye (Figure 4). The scale of 0 to 3 is used for the grading, according to the intensity of fluorescein staining. The maximum staining score for the cornea is 15, and for conjunctiva, the maximum score is 18. The values above 3 is considered abnormal for cornea or conjunctiva in each eye.
The NEI scale system for grading fluorescein staining which divides the corneal and conjunctival surfaces. The conjunctival surface is divided into 6 areas and the corneal surface is divided into 5 areas. A standardized grading system of 0 to 3 is used for each of areas on cornea and conjunctiva.
Lack of stability in the tear film can be seen in aqueous deficient, evaporative, or both type of dry eye. It may also occur in the setting of a poor blink rate or epithelial irregularity [30]. There are several numbers of tools designed to evaluate tear film stability to help clinician or researcher to assess and support the diagnosis of DED.
Tear break-up time was first introduced by Norn in 1969 and remains the most frequently used diagnostic test to evaluate tear film stability [31]. It measures the time between a complete blink and the first appearance of a dry spot on the ocular surface using fluorscein. Right after applying the fluorescein strip on to the ocular surface, and under cobalt blue filter in slit-lamp biomicroscopy, patient is asked to blink completely and hold the eye open (avoid blinking). The clinician should observe the first dry spots appear on his/her ocular surface. Normally, dry spot(s) will appear after 10 seconds.
The TBUT less than 10 seconds is considered as a cut-off score for the diagnosis of dry eye, with values of 5–10 seconds are considered marginal and less than 5 seconds indicate the dry eye symptoms [31, 32, 33, 34]. But, the threshold for Asian patients may be set much lower as many Asians with TBUT between about 7–10 seconds do not have dry eye symptoms [35]. Some studies suggest that healthy Asian subjects have an 11–24% shorter TBUT than non-Asians [35, 36]. It hypothesized that the tear lipid layer is not able to efficiently perform its usual expansion and compression during a blink in an eye with a small palpebral aperture size (Asian), resulting in a less stable tear film [37].
This technique was first introduced by Mengher et al. in 1983 and is defined as ‘the time taken in seconds between the last complete blink and the appearance of the first random disturbance of a grid’ [38, 39]. The NIBUT test can be performed using several device options, such as topography, keratography, or Placido disc video-keratography. Tear break-up time is considered when the reflected mires become distorted.
Mengher et al. [38] reported a NIBUT value of 47.9 seconds (range of four to 214 seconds), but Mohidin et al [36] reported lower NIBUT value (15.8 ± 9.4 seconds, range of 4.2 to 48.6 seconds). Sharanjeet-Kaur et al. [40] reported that NIBUT values for normal Malays and Chinese were 7.74 ± 3.34 seconds and 7.15 ± 3.38 seconds respectively. Generally, in normal population, NIBUT is longer than TBUT, with range of four to 214 seconds (median 4–19 seconds); and in patients with DED, NIBUT and TBUT values are almost the same (the cut-off values for positive finding can be as low as 2.7 seconds for automated algorithms and up to 10 seconds for subjective observation techniques) [41].
The aim of tear volume assessment is to measure the quantity of tear film produced by lacrimal gland and conjunctiva.
The Schirmer’s test is the most common examination performed whenever there is a suspicion of inadequate tear secretion. The test was named after Schirmer who brought the test forward for the first time in 1903 [42]. Basically, without anesthesia, the test measures total (basic and reflex) tear secretion, as with anesthesia it measures basic tear secretion devoid of reflex component [43, 44]. This test remains as the most common test used for tear quantity assessment [45]. It can be divided into Schirmer I and Schirmer II test.
The Schirmer I test is performed using strip that is folded from one end and inserted into the lower conjunctival sac at the junction of lateral and middle thirds, avoiding touching the cornea. After five minutes, the length of wetted strip is recorded. Fifteen minutes later, after instillation of topical anesthesia, the strip is placed again over the same point in the same patient for five minutes. The Schirmer II test measure reflex secretion of lacrimal gland. The procedure of this test is as the same as Schirmer I test with topical anesthesia and nasal mucosa is irritated with a cotton-tiped applicator prior to measuring tear production. The result is recorded after 5 minutes. Normally, the length of wetted strip is around 10 mm or greater and if the length is less than 5 mm, it indicates symptomatic tear deficient; but Schirmer’s test values less or equal to 10 mm have greater diagnostic value and indicate hyposecretion [22, 46, 47, 48, 49, 50].
The phenol red thread (PRT) test was invented by Hamano in 1982 and developed to overcome the disadvantage of Schirmer’s test including variable results, poor repeatibility, and low sensitivity in detecting dry eyes [44, 51, 52, 53]. The test uses a special cotton thread impregnated with phenol red (a pH-sensitive indicator). The procedure is performed in the similar manners to Schirmer test, which the thread is folded at the end and inserted into the lower conjunctival sac and it will absorb the tears that contact with it. The color of this thread will change from yellow to red over the pH range of normal tears. The result is recorded after 15 seconds, much shorter than Schirmer’s test. The PRT is almost comparable with Schirmer’s test and it has advantages including simpler and more comfortable to the patient and can also be performed in children [54].
Conjunctival biopsy may be one of the best methods to investigate and evaluate the ocular surface condition, which offers specimens of epithelial layers and conjunctival stroma to be examined under light or electron microscopy, cytology, and immunohistochemical analyses. These techniques may allow identification and counting of inflammatory cells and analysis of cell membrane markers, intracyto-plasmic cells, or extracellular matrix components [55]. But, of all methods mentioned above, conjunctival biopsy is an invasive technique that may cause discomfort to the patient.
Impression cytology (IC) refers to the application of cellulose acetate filter to the ocular surface to remove the superficial layers of the ocular surface epithelium [56]. The analysis techniques used in this method vary, depend on the purpose and the equipment availability in eye care facility. The simplest analysis technique remains light microscopy, in which epithelial and goblet cells can be well visualized through hemtoxylin and periodic acid Schiff (PAS) staining. Other techniques include electron microscopy, immunohistochemistry, flow cytometry, and RT-PCR/PCR.
The RT-PCR was used in IC specimens as early as 1994 and identified inflammatory cytokins in conjunctival specimens from Sjögren’s syndrome eyes [57].
Tear osmolarity is the most accurate method to diagnose DED. Tear hyper-osmolarity is considered as pathogenic factor causing ocular surface inflammation, symptoms, and tissue damage which can lead to DED. This condition can occur in many situations including insufficient tear production, meibomian gland dysfunction, and exposure. There is a commercially available objective point of care test (TearLab Osmolarity System; TearLab, San Diego, California) that can measure the osmolarity of a 50-nL tear sample and is easier to use [30, 58, 59]. A reading of 308 mOsms/L or greater indicates tear osmolarity disruption. This test must be completed quickly to avoid any evaporation of tear sample. Although reproducible, this test is difficult to perform in clinic setting.
Tear ferning test is a simple test for tear film quality. This test requires capillary tubes, spatula, or glass rods to collect tear from the lower tear meniscus (about 5–20 μl). The collected tear is applied to a glass slide and evaluated under light or digital microscope with various magnifications (40-100x). In DED, the delicate fronded pattern becomes fragmented or broken up and irregular and the appearances can be graded into type I and II (healthy tear film) and type III and IV (increasing degrees of dry eye) [14, 60].
The diagnosis of dry eye depends on the results of several of tests mentioned above, which ideally could be performed at a single clinic visit. It is important to keep in mind that a clinician should carry out the test in an appropriate order. Table 2 suggests a suitable order for diagnostic test, although there are various and informal data to justify a particular sequence of the tests. Some of the standard tests are specific for subgroup of the disease (Table 3). Table 4 helps the clinician to grade the severity of the DED.
|
Practical sequence of dry eye tests.
|
Practical applications of several test for assessing DED.
Adapted from Módis and Szalai [22].
Dry Eye Severity Level | ||||
---|---|---|---|---|
1 | 2 | 3 | 4 | |
Discomfort, severity, and frequency | Mild and/or episodic; occurs under enviromental stress | Moderate episodic or chronic, strees or no stress | Severe frequent or constant without stress | Severe and/or disabling and constant |
Visual symptoms | None or episodic mild fatigue | Annoying and/or activity-limiting episodic | Annoying, chronic and/or constant, limiting activity | Constant and/or possibly dissabling |
Conjunctival injection | None to mild | None to mild | Mild or not present | Mild to moderate |
Corneal staining (severity/location) | None to mild | Variable | Marked central | N/A |
Cornea/tear signs | None to mild | Mild debris, decreased meniscus | Filamentary keratitis, mucus clumping, increased tear debris | Filamentary keratitis, mucus clumping, increased tear debris, ulceration |
Lid/meibomian glands | MGD variably present | MGD variably present | MGD frequent | Trichiasis, keratinization, symblepharon |
TBUT (seconds) | Variable | ≤ 10 | ≤ 5 | Immediate |
Schirmer score (mm/5 minutes) | Variable | ≤ 10 | ≤ 5 | ≤ 2 |
The severity grading scheme for dry eye disease.
Despite the wide use in clinical practice, standard tests for assessing DED and ocular surface disorders (including history taking and symptoms recording, TBUT, meibomian gland testing, ocular surface saining, and Schirmer’s testing) have shown poor repeatability and lack of efficacy [22, 57]. Moreover, it is well know that subjective symptoms often do not correlate with objective signs. Additional exploratory technique may be required to assess DED and evaluate the severity of the disease. The laboratory test may be required in patient who have subjective complaint that is not identified as dry eye (such as fluctuating vision) but do not show a lot of ocular finding such as corneal staining or any other marked conditions.
Patient with xerostomia in addition to dry eye must be investigated for the possible presence of Sjögren’s syndrome. The revised criteria of the European-American Consensus Group for the diagnosis of Sjögren’s syndrome are summarized in Table 5. The diagnosis of Sjögren’s syndrome is made if four of the six criteria are fulfilled. If SSA/SSB diagnostic testing is negative, a positive ANA (antinuclear antibody) test or positive rheumatoid factors may be indicative [15].
|
Diagnosis criteria for Sjögren’s syndrome.
Careful and thorough examinations help the clinician to assess and evaluate dry eye disease. Various examinations are available, but the clinicians must adjust the examination to the available tools or equipments in their facilities. Ocular surface staining is the simplest test that can be performed in every clinic. If the case is complicated with or without underlying disease and needs further examniations, a clinician should refer to higher facility or dry eye specialist.
Author would like to acknowledge Susi Heryati, Angga Fajriansyah, Arief Mustaram, Patriotika Muslima, and Elfa Ali Idrus as supervisors in Infection and Immunology Division, Department of Ophthalmology, Cicendo National Eye Hospital, Bandung, Indonesia.
The author declares that there is no conflict of interest in this work.
antinuclear antibody best-corrected visual acuity chemical index dry eye disease Standard Patient Evaluation for Dry Eye Questionnaire impression cytology meibomian gland dysfunction milliosmole National Eye Institute National Eye Institute Function Questionnaire-25 non-invasive break-up time Ocular Surface Disease Index periodic acid Schiff polymerase chain reaction power of hydrogen phenol red thread reverse transcription polymerase chain reaction anti-Sjögren’s syndrome type A anti-Sjögren’s syndrome type B tear break-up time uncorrected visual acuity
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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As a reinforcement agent, calcium carbonate from avian eggshell waste was used, at 10 ph of micro particles, 125 μm. Admixtures were further processed in a single-screw extruder, using CO2 as physical blowing agent (PBA). Property investigations were performed by DSC, TGA, XRD, SEM, FTIR, and mechanical essays.",book:{id:"8352",slug:"use-of-gamma-radiation-techniques-in-peaceful-applications",title:"Use of Gamma Radiation Techniques in Peaceful Applications",fullTitle:"Use of Gamma Radiation Techniques in Peaceful Applications"},signatures:"Elizabeth C.L. Cardoso, Duclerc F. Parra, Sandra R. Scagliusi, Ricardo M. Sales, Fernando Caviquioli and Ademar B. 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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{paginationCount:7,paginationItems:[{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",hash:"8d41fa5f3a5da07469bbc121594bfd3e",secondStepPassed:!0,currentStepOfPublishingProcess:4,submissionDeadline:"March 24th 2022",isOpenForSubmission:!0,editors:[{id:"335401",title:"Prof.",name:"Margherita",surname:"Mori",slug:"margherita-mori",fullName:"Margherita Mori"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11460",title:"Pluralistic Approaches for Conservation and Sustainability in Biodiversity",coverURL:"https://cdn.intechopen.com/books/images_new/11460.jpg",hash:"ab014f8ed1669757335225786833e9a9",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"April 22nd 2022",isOpenForSubmission:!0,editors:[{id:"101105",title:"Dr.",name:"Gopal",surname:"Shukla",slug:"gopal-shukla",fullName:"Gopal Shukla"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11475",title:"Food Security Challenges and Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11475.jpg",hash:"090302a30e461cee643ec49675c811ec",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 5th 2022",isOpenForSubmission:!0,editors:[{id:"292145",title:"Dr.",name:"Muhammad",surname:"Haseeb Ahmad",slug:"muhammad-haseeb-ahmad",fullName:"Muhammad Haseeb Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11450",title:"Environmental Impacts of COVID-19 Pandemic on the World",coverURL:"https://cdn.intechopen.com/books/images_new/11450.jpg",hash:"a58c7b02d07903004be70f744f2e1835",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 10th 2022",isOpenForSubmission:!0,editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11477",title:"Public Economics - 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Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"80546",title:"Streptococcal Skin and Skin-Structure Infections",doi:"10.5772/intechopen.102894",signatures:"Alwyn Rapose",slug:"streptococcal-skin-and-skin-structure-infections",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Streptococcal Infections",coverURL:"https://cdn.intechopen.com/books/images_new/10828.jpg",subseries:{id:"3",title:"Bacterial Infectious Diseases"}}}]},subseriesFiltersForOFChapters:[{caption:"Parasitic Infectious Diseases",value:5,count:1,group:"subseries"},{caption:"Viral Infectious Diseases",value:6,count:1,group:"subseries"},{caption:"Bacterial Infectious Diseases",value:3,count:2,group:"subseries"}],publishedBooks:{paginationCount:0,paginationItems:[]},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:249,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"26",type:"subseries",title:"Machine Learning and Data Mining",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11422,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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