**1. Introduction**

Leprosy is a chronic infectious disease, dermato neurological and incapacitating, which has *Mycobacterium leprae* as its causal agent [1]. Even with the worldwide effort to eliminate this disease as a public health problem [2], countries such as India and Brazil still present a higher number of cases than the World Health Organization (WHO) recommended [3]. In this sense, this organization defined as a global strategy the reduction in the incidence of new cases as a priority [4], highlighting the importance of early diagnosis, which aims to reduce the transmission of the disease in the community [5], which includes correctly diagnosing cases with suspicion of the disease and to identify subclinical infection.

**2.1. Dermato-neurological clinical exam, bacilloscopy, histopathology and**

For the diagnosis of leprosy, it is essential to perform clinical-dermatological exams that search for lesions in the epidermis, areas with changes in sensitivity (may be thermal, painful and tactile) and motor impairment-searching for thickened nerve trunks-which are classic signs of the disease [7]. In addition to clinical examination, there is a class of diagnostic exams and tests that are widely standardized and used in reference networks and centers [7, 15].

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Bacilloscopy is the most commonly used exam in clinical practice and, together with the dermato-neurological clinical test, is the most useful methodology for diagnosis [16]. The test presents advantages such as reduced cost and aid in the confirmation of new cases and patients with relapse [15]. The methodology used to perform the exam is a dermal smear of sites, these being: ear lobes (LO), elbows (C) and active lesions, where it is possible to analyze

As a result, a Bacilloscopy Index (BI), proposed by Ridley and Joplin, is provided, where there is a logarithmic scale ranging from 0 to 6 [19–21]. Thus, after an average of the fields analyzed, the result may vary from BI = 0, associated with patients of the tuberculoid (TT) pole and BI = 3+ to 6+, associated with lepromatous patients (LL). It is still possible to analyze the morphological index (MI) of the bacilli arranged on the slide, describing aspects of their morphological integrity [20]. Thus, bacilli may present three aspects related to their structure, classified as integral, fragmented or granular [21, 22]. Integral bacilli are considered viable, that is, they are related to host susceptibility to the parasite. These bacilli exhibit cell structure with preserved ends and uniform staining and are seen in smears of patients who are either non-treated or have relapse. Both fragmented and granular bacilli present flaws in the cell wall structure, being considered unviable or dead and more observed in post-

Bacilloscopy is effective when associated with the results of clinical exams [7, 15]. However, it is an exam that presents low sensitivity, since 50% of the smears of the sick individuals are negative. In addition, the exam requires adequate laboratory infrastructure and trained professional apparatus, factors that are not always a reality in hyperendemic regions and where

Histopathology is commonly performed for the diagnosis of diseases caused by obligate intracellular parasites and has good indices of sensitivity and specificity in the detection of leprosy [23]. However, the method encounters issues related to cost, time of analysis and false-negative results, besides of being an invasive exam [24]. Exactly for these reasons, histopathology is only recommended for individuals where it is impossible to assess degrees of cutaneous sensitivity, such as in children, elderly and mentally handicapped people; when it is not possible to classify the dimorphic clinical form; or when there is uncertainty whether the diagnosis is leprosy or other diseases that cause local hypoesthesia [23]. The diagnosis using this exam also depends on the association with the clinical aspects and bacilloscopy. In addition, biopsies of peripheral nerve branches are not recommended and should only be

the presence of the bacillus using a specific staining and optic microscopy [17, 18].

**Mitsuda test**

treatment patients [17–22].

medical and financial resources are reduced [7].

performed in the last instance [23, 24].

The clinical and epidemiological diagnosis of leprosy represents the gold standard for confirmation of the disease [6]. Bacilloscopy and Mitsuda's reaction are important tests to identify the etiological agent [7, 8], but there is a need to use complementary tests that allow a more accurate diagnosis with high sensitivity and specificity. In this context, stand out the standardization of serological and molecular tests, important for the understanding of the epidemiological profile of the disease.

The use of *M. leprae* specific antigens in serological tests has been the subject of research. The use of phenol-glycolipid-1 (PGL-1) [9], lipoarabinomannan (LAM) [1] and heat shock proteins (GroES and GroEL) [10] as antigens for the enzyme-linked immunosorbent assay (ELISA) and in immunosensors can be validated as methods for detecting new cases of the disease and for early diagnosis [11]. In addition, molecular tests aid in the identification of specific *M. leprae* sequences in clinical samples, which can be amplified through the polymerase chain reaction (PCR) technique, allowing DNA detection of the infectious agent [12] and/or through the use of real-time PCR technology that allows the evaluation of bacterial load [13] and also the monitoring of drug resistance [14].

Thus, this chapter will present an overview of the laboratory diagnosis of leprosy in the world. Initially, we will present a review of the main tests traditionally used in clinical routine and regulated by the WHO, in addition to the complementary tests that have been focus of research as a future perspective for the early diagnosis of the disease. These diagnostic approaches may contribute to a reduction in the number of cases of the disease, since they allow the monitoring of populations and endemic and hyperendemic areas.

## **2. Leprosy diagnosis: traditional exams**

The diagnosis of leprosy includes clinical observation of the patient, dermato-neurological clinical exams and complementary laboratory tests. Therefore, identify lesions and damaged nerves and analyze the life history of the patient are essential tools in the identification and detection of disease. These practices combined with other tools and methodologies are able to assist in epidemiological and disease control strategies, helping to map index cases and individuals who may develop leprosy, such as household contacts.

## **2.1. Dermato-neurological clinical exam, bacilloscopy, histopathology and Mitsuda test**

**1. Introduction**

64 Hansen's Disease - The Forgotten and Neglected Disease

miological profile of the disease.

monitoring of drug resistance [14].

**2. Leprosy diagnosis: traditional exams**

Leprosy is a chronic infectious disease, dermato neurological and incapacitating, which has *Mycobacterium leprae* as its causal agent [1]. Even with the worldwide effort to eliminate this disease as a public health problem [2], countries such as India and Brazil still present a higher number of cases than the World Health Organization (WHO) recommended [3]. In this sense, this organization defined as a global strategy the reduction in the incidence of new cases as a priority [4], highlighting the importance of early diagnosis, which aims to reduce the transmission of the disease in the community [5], which includes correctly diagnosing cases with

The clinical and epidemiological diagnosis of leprosy represents the gold standard for confirmation of the disease [6]. Bacilloscopy and Mitsuda's reaction are important tests to identify the etiological agent [7, 8], but there is a need to use complementary tests that allow a more accurate diagnosis with high sensitivity and specificity. In this context, stand out the standardization of serological and molecular tests, important for the understanding of the epide-

The use of *M. leprae* specific antigens in serological tests has been the subject of research. The use of phenol-glycolipid-1 (PGL-1) [9], lipoarabinomannan (LAM) [1] and heat shock proteins (GroES and GroEL) [10] as antigens for the enzyme-linked immunosorbent assay (ELISA) and in immunosensors can be validated as methods for detecting new cases of the disease and for early diagnosis [11]. In addition, molecular tests aid in the identification of specific *M. leprae* sequences in clinical samples, which can be amplified through the polymerase chain reaction (PCR) technique, allowing DNA detection of the infectious agent [12] and/or through the use of real-time PCR technology that allows the evaluation of bacterial load [13] and also the

Thus, this chapter will present an overview of the laboratory diagnosis of leprosy in the world. Initially, we will present a review of the main tests traditionally used in clinical routine and regulated by the WHO, in addition to the complementary tests that have been focus of research as a future perspective for the early diagnosis of the disease. These diagnostic approaches may contribute to a reduction in the number of cases of the disease, since they

The diagnosis of leprosy includes clinical observation of the patient, dermato-neurological clinical exams and complementary laboratory tests. Therefore, identify lesions and damaged nerves and analyze the life history of the patient are essential tools in the identification and detection of disease. These practices combined with other tools and methodologies are able to assist in epidemiological and disease control strategies, helping to map index cases and

allow the monitoring of populations and endemic and hyperendemic areas.

individuals who may develop leprosy, such as household contacts.

suspicion of the disease and to identify subclinical infection.

For the diagnosis of leprosy, it is essential to perform clinical-dermatological exams that search for lesions in the epidermis, areas with changes in sensitivity (may be thermal, painful and tactile) and motor impairment-searching for thickened nerve trunks-which are classic signs of the disease [7]. In addition to clinical examination, there is a class of diagnostic exams and tests that are widely standardized and used in reference networks and centers [7, 15].

Bacilloscopy is the most commonly used exam in clinical practice and, together with the dermato-neurological clinical test, is the most useful methodology for diagnosis [16]. The test presents advantages such as reduced cost and aid in the confirmation of new cases and patients with relapse [15]. The methodology used to perform the exam is a dermal smear of sites, these being: ear lobes (LO), elbows (C) and active lesions, where it is possible to analyze the presence of the bacillus using a specific staining and optic microscopy [17, 18].

As a result, a Bacilloscopy Index (BI), proposed by Ridley and Joplin, is provided, where there is a logarithmic scale ranging from 0 to 6 [19–21]. Thus, after an average of the fields analyzed, the result may vary from BI = 0, associated with patients of the tuberculoid (TT) pole and BI = 3+ to 6+, associated with lepromatous patients (LL). It is still possible to analyze the morphological index (MI) of the bacilli arranged on the slide, describing aspects of their morphological integrity [20]. Thus, bacilli may present three aspects related to their structure, classified as integral, fragmented or granular [21, 22]. Integral bacilli are considered viable, that is, they are related to host susceptibility to the parasite. These bacilli exhibit cell structure with preserved ends and uniform staining and are seen in smears of patients who are either non-treated or have relapse. Both fragmented and granular bacilli present flaws in the cell wall structure, being considered unviable or dead and more observed in posttreatment patients [17–22].

Bacilloscopy is effective when associated with the results of clinical exams [7, 15]. However, it is an exam that presents low sensitivity, since 50% of the smears of the sick individuals are negative. In addition, the exam requires adequate laboratory infrastructure and trained professional apparatus, factors that are not always a reality in hyperendemic regions and where medical and financial resources are reduced [7].

Histopathology is commonly performed for the diagnosis of diseases caused by obligate intracellular parasites and has good indices of sensitivity and specificity in the detection of leprosy [23]. However, the method encounters issues related to cost, time of analysis and false-negative results, besides of being an invasive exam [24]. Exactly for these reasons, histopathology is only recommended for individuals where it is impossible to assess degrees of cutaneous sensitivity, such as in children, elderly and mentally handicapped people; when it is not possible to classify the dimorphic clinical form; or when there is uncertainty whether the diagnosis is leprosy or other diseases that cause local hypoesthesia [23]. The diagnosis using this exam also depends on the association with the clinical aspects and bacilloscopy. In addition, biopsies of peripheral nerve branches are not recommended and should only be performed in the last instance [23, 24].

The Mitsuda test or Mitsuda reaction does not present diagnostic value, but it is an alternative prognostic tool that assists in assessing susceptibility to lepromatous forms [27]. It is an exam based on the use of heat-killed bacilli (lepromin), derived from extract of the inactivated "leprosy bacillus" under the skin of LL patients. The test consists of inoculating the Mitsuda antigen intradermally and reading them between days 21 and 28 after the challenge in order to analyze the late cellular response of patients [8, 25].

In addition, there's still a great limitation in obtaining the native molecule, restricted to the growth of *M. leprae* in armadillos. As an alternative, several synthetic analogous molecules associated with the tri or disaccharides of PGL-1 have been produced from the conjugation of these elements with BSA (Bovine serum albumin) and Phenol (P) or Octyl (O). The literature shows several semisynthetic analogues, among which the most well known are: monosaccharide-octyl-BSA (MO-BSA), disaccharide-BSA (D-BSA), natural disaccharide-octyl-BSA, natural octyl-HSA (ND-O -BSA and ND-O-HSA), natural trisaccharide-phenol-BSA (NT-P-BSA)

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A study carried out in the hyperendemic region of the Brazilian Amazon points to the potential of synthetic molecules to identify new cases of leprosy and, similar to glycolipid, they have good detection rates in multibacillary patients. In addition, research shows that the molecules exhibit behavior related to the spectral immunology of the disease, where the LL pole has a higher antibody titer that decays at the boderline and tuberculoid poles [35]. When comparing two molecules derived from PGL-1 in the region, it was possible to observe that NT-P-BSA was very effective in the monitoring of home contacts and MB patients, whereas ND-O-BSA

ELISA requires skilled labor and specific equipment which is not always available. Therefore, the use of serological tests of both the native molecule and synthetic derivatives is important to validate increasingly adequate methods for the seroepidemiology of both endemic and hyperendemic regions, besides helping to standardize the positivity indices of the clinical

If the characterization of PGL-1 was important for the synthesis of several derived molecules with similar immunological aspects, the decoding of the *M. leprae* genome was essential for the identification of proteins and peptides with applicability in the laboratory detection of the disease [38]. Several advantages are associated with the use of these molecules, especially for reducing the cost of the assays and reflecting the spectral character of leprosy immunology. Thus, assays using recombinant proteins indicate high levels of antibodies in LL patients that decay in patients of the boderline and tuberculoid poles [38–43].Currently, there are a large number of *M. leprae* recombinant proteins, normally identified as ML, and several studies have evaluated the potential of these proteins [44]. In 2007, a survey conducted in Brazil, the Philippines and Japan evaluated the cellular and humoral response to 33 recombinant proteins across a broad population spectrum and identified three proteins (ML0405, ML2055 and ML2331) capable of inducing the humoral response in multibacillary (MB), production of IgG, as well as the cellular response in PB. Comparison between sites identified differential response patterns between populations, however, in all locations ML0405 and ML2331

Due to the potential of these two proteins, the Leprosy IDRI Diagnostic protein (LID-1) was generated, resulting from the fusion between the two MLs. LID-1 was produced in order to maintain the reactivity profile of both proteins and was subsequently evaluated in several populations of Japan, Brazil, Venezuela, the Philippines and Nepal. The results pointed to the

obtained better sensitivity and specificity indices in paucibacillary individuals [37].

which are used as antigens in immunodiagnosis [30, 36].

forms that can vary intensely from one area to another.

showed similar results to PGL-1 serology in MB33 patients [40].

**3.2. ELISA with recombinant proteins**

Mitsuda's reaction has good agreement when related to bacilloscopy. Typically, individuals with a diameter reaction greater than 10 mm are considered resistant; they do not get sick or develop the TT shape, being Mitsuda positive [24]. While reactions with a diameter between 3 and 5 mm are indicative of dimorphic leprosy and, below this value, the test indicates anergy of the host's immune system to the bacillus, associated with patients in the LL pole, being Mitsuda negatives [8, 24, 26]


**2.1.8 Generations**

Beginning with the founders, 100 bouts of reproduction (101 generations or ages including the founding generation) were conducted for each set of trial conditions. Output results in Figures 1 to 3 are reported for the entire population at each age. For the pollen and offspring dispersal distance comparison trials (Figures 4 to 6) only the results at the terminal age 100 are given.

#### **2.1.9 Replicate runs**

The output values reported are mean values calculated from 40 replicate runs for each set of trial input conditions. When trials are said to differ, we mean that reported generation mean values differ significantly (p value < 0.05) unless otherwise stated. This convention is used rather than reporting each standard deviation and t-test results for all trial comparisons.


**1. Introduction**

In the past half-century, the Neurosurgery has been undergone tremendous technological innovation. The introduction of the operating microscope, stereotactic surgery, neuro endoscopy, modern neuroimaging, technologically demanding implants and image-guided surgery have enabled advancements while also challenging the limits of human dexterity [1]. Robot-assisted surgical systems can be beneficial for a variety of procedures chirurgical cranial and orthopedic due to their high precision, and ability to access and capacity to integrate various imaging and sensing modalities into the execution of the surgical task [2, 3].

The robot assisted surgical such Neuromate robots helps to ensure that the burr hole is accurately positioned and oriented cantered on the trajectory axis. The trajectory orientation is not restricted due to the variety of configurations to guide

#### **Figure 1.**

*System overview of the image-guided robot for skull base surgery [1].*

the surgery tools with a suitable orientation [4]. The current system (see **Figure 1**) consists of the following major components: a modified Neuromate robot.

Since the evolution of Micro-electro-mechanical systems (MEMS) many types of MEMS pressure sensors have been notified. They can be divided MEMS pressure sensors into, capacitive [5], piezoresistive [6], resonant [7]. Capacitive pressure sensing is considered as one of the most sensitive techniques in detecting low pressures [8]. Owing to the fact that the performance is solely a function of the mechanical properties and dimensions of the sensor structure [9]. Capacitive pressure sensors are preferred as they provide high sensitivity to pressure and their performance for most part remains invariant of temperature, this makes it suitable to be used for high pressure and temperature applications [10, 11].

This work addresses the design and modeling of measurement system required the contact force for the effectiveness of the stimulation between the probe and the patient's head, thus ensuring the safety of the patient. However, capacitive pressure sensors are gaining market share over their piezoresistive counterparts since they consume less power, are usually less temperature sensitive and have a lower fundamental noise floor. This model performs an analysis of a capacitive pressure sensors as discussed below using the electro mechanics interface. The effect of a rather poor choice of packaging solution on the performance of the sensor is also considered. The results emphasize the importance of considering packaging in the MEMS (micro-electro mechanical system) design process (**Figure 1**).

#### **2. Neuromate robotic device and surgical procedure**

Stereotactic biopsy is a standard procedure in neurosurgery. In addition to or even replacing frame based stereotaxy, some centers also use frameless imagingbased techniques and more recently robotic systems. Here, Yasin et al. [12] report a retrospective analysis of experience with 102 consecutive biopsies performed in his institution using the Neuromate robotic device.

The Neuromate robotic device is a platform designed for robot assisted stereotactic neurosurgery. It consists of a robotic arm with 5 degrees of freedom and a planning station (**Figure 2A**) and can be used for frame-based surgery as well as in frameless mode. *Electromechanical Analysis (MEMS) of a Capacitive Pressure Sensor of a Neuromate Robot Probe DOI: http://dx.doi.org/10.5772/intechopen.88946*

#### **Figure 2.**

*Images of the Neuromate robot and surgical workflow [12]. (A) Robot and planning station. (B) Trajectory plan. (C) The base of the localizing device is mounted to the skull. (D) The preoperative magnetic resonance imaging including the trajectory is fused to the computed tomography reference scan. (E) Patient registration using the ultrasonic tracking system. (F) Positioning the biopsy needle through the instrument holder along the trajectory [12].*

The Neuromate device has been employed for a wide variety of stereotactic applications in neuro endoscopy, biopsy, epilepsy surgery, functional neurosurgery, and even convection-enhanced delivery.

All patients included in his study [12] had frameless biopsies. Biopsy trajectories were planned in advance using VoXim neuromata software (**Figure 2B**).

The localizing device consisted of a base mounted to the skull using a bone screw under local anesthesia and a helicopter-shaped ultrasonic localizing device and corresponding computed tomography (CT) localizers (**Figure 2C**). A CT reference scan was obtained and the data were uploaded on the planning station.

Next, the biopsy trajectory and the preoperative MR scan were fused to the reference scan (**Figure 2D**). Verifying trajectories were planned based on the reference scan data.

The second part of the procedure was performed in all patients under general anesthesia. Patients were placed in the supine, lateral, or prone position as required. The head was fixed in the head holder of the robot with 4–6 pins. Patient registration was performed using the ultrasound tracking system (**Figure 2E**).

Accuracy was tested using the verifying trajectory and a laser pointer mounted to the robot.

Next, the robotic arm with the instrument holder was moved into the planned biopsy position using a remote control. A Sedan side cutting aspiration needle (1.8 mm) was introduced manually through the instrument holder, and standard serial biopsies were taken as indicated (**Figure 2F**).

Biopsies through separate trajectories were obtained after simply repositioning the robotic arm.

#### **3. Configuration of the neuromate robot**

Nowadays, the use of robots in medicine becomes usual. One of the problems widely dealt in this area is the trajectory planning and contact force control.

**Figure 3.**

*The Neuromate robot [13]. (a) Representation of the robot. (b) Geometric configuration of the robot.*

In Menasria et al.'s (2015) works [13], a novel trajectory planning approach is proposed for redundant manipulators in the case of several obstacles. They use the property to find the best configuration that allows to avoid obstacles and singularities of the robot. The proposed method is based on a bi-level optimization formulation of the problem and bi-genetic algorithm to solve it.

The Neuromate robotic device is a platform designed for robot assisted stereotactic neurosurgery. It consists of a robotic arm with 5 degrees of freedom and a planning station (**Figure 3**) and can be used for frame-based surgery as well as in frameless mode. The Neuromate device has been employed for a wide variety of stereotactic applications in neuro endoscopy, biopsy, epilepsy surgery, functional neurosurgery, and even convection-enhanced delivery. Next, the assigned coordinate frames are followed to fill out the parameters as shown in **Tables 1** and **2** below.

Geometric and kinematic modeling was carried out under the symbolic software MapleSim (**Figure 4**) in order to simulate the trajectory of the probe.

#### **3.1 Neuromate inverse kinematics analysis**

Numerically, Inverse kinematic analysis is done by multiplying each inverse matrix of T matrices on the left side of above equation and then equalizing the corresponding elements of the equal matrices of both ends.

#### **Table 1.**

*Denavit Hartenberg table of the robot [13].*

#### **Table 2.**

*Angular rangers of the rotary articulations [13].*

*Electromechanical Analysis (MEMS) of a Capacitive Pressure Sensor of a Neuromate Robot Probe DOI: http://dx.doi.org/10.5772/intechopen.88946*

**Figure 4.** *Modelization of the Neuromate robot in MapleSim.*

**Figure 5.** *Inverse kinematics of the Neuromate robot in MapleSim.*

#### **Figure 6.**

*End effector positions of the Neuromate robot.*

With inverse kinematic solutions, the value of each joint can be determined in order to place the arm at a desired position and orientation. In our case, inverse kinematics is done under MapleSim software (**Figure 5**).

Based on relevant theories on robotic arms movement, a forward and an inverse kinematic model are successfully developed with the application of Neuromate with 5 dof in MapleSim software.

A simple trajectory is carried out in order to investigate the forward and inverse kinematics models of Neuromate. A movement flow planning is designed and further developed into the MapleSim programming.

A summary of the calculation is obtained for tree position of end effector (**Figure 6**).

### **4. Robotic pressure sensor control**

In robotic applications, position control of manipulators can only be effective if the task is precisely described. For this reason, there is a clear need to integrate force information to the control loop. The interaction control between the effector and the patient's head can be through the robot's position control algorithms in the direction of the task space while the environment imposes natural position constraints.

Pressure control has many advantages. It can provide the necessary Cartesian compliant behavior of a robot, enable robust and fast manipulation in contact with unknown surfaces, and provide safety and dependability in interaction with humans.

*Surgical robots with pressure control* the pressure information collected in one of the above described ways may be used to control the servos of the robot. In medical robotics, the fundamental methods of force control have been widely applied as usually there is interaction with patient, interaction with surgeon and the procedures mostly deal with soft and deformable tissues with variable stiffness. The realized control architecture can depend on the bandwidth of the force sensor (the frequency of sensor measurements) [14–16].

The following section presents an example of the field of surgical robotics performing pressure control by a force control MEMS probe described above.

#### **5. Geometry and material properties of pressure sensor**

Newly Micro electro mechanical system (MEMS) capacitive pressure sensor gains more advantage over micro machined piezo resistive pressure sensor due to high sensitivity, low power consumption, free from temperature effects, etc.

Geometry of Pressure sensor made of piezoelectric silicon layer and graphene substrate at 70°C, with high-pressure sensitivity of 120 pF/Pa.

Since the geometry is symmetric, only a single quadrant of the geometry needs to be included in the model, and it is possible to use symmetry boundary condition. **Figure 7** shows the total sensor geometry.

As extensively reported in Mechanics books and scientific papers, the governing differential equation for the deflection of a thin plate in Cartesian coordinates can be expressed as follows: \_*d*

$$
\Delta \mathbf{C} = \mathbf{C} - \mathbf{C}\_0 = \varepsilon A \frac{\Delta d}{d(d - \Delta d)} \tag{1}
$$

D is referred as the flexural rigidity of the plate and can be defined as follows:

$$
\Delta C = C - C\_0 = \varepsilon A \frac{\Delta d}{d(d - \Delta d)} \tag{1}
$$

$$
D \text{ is referred as the flexural rigidity of the plate and can be defined as follows:}
$$

$$
D = \frac{Et\_w^3}{12\{1 - \nu^2\}} \tag{2}
$$

*Electromechanical Analysis (MEMS) of a Capacitive Pressure Sensor of a Neuromate Robot Probe DOI: http://dx.doi.org/10.5772/intechopen.88946*

**Figure 7.** *The geometry of the total sensor.*

With E and v being the modulus of elasticity and Poisson's ratio of the plate material, respectively.

The mechanical deformation under compression for the pressure sensitivity of such a pressure sensor: \_*d*

$$
\Delta \mathbf{C} = \mathbf{C} - \mathbf{C}\_0 = \varepsilon A \frac{\Delta d}{d(d - \Delta d)} \tag{3}
$$

*C* is the charge of capacitance under compression, *C*0 is the initial capacitance value the sensor, A is the surface area of the overlapping plates, ε is the permittivity of dielectric medium between the two plates, d is the initial overall thickness of the medium and *d* is the amount compression.

The designed MEMS capacitive pressure sensors are composed of a square silicon diaphragm of 500 μm side length and 500 μm thickness that deflects because of pressure and acts as the movable plate of a differential capacitor, and a fixed Graphene substrate that acts as the other half of the pressure dependent capacitor.

#### **5.1 Mechanical properties**

The property material of graphene and Silicon is defined into the model is shown in **Table 3**.

#### **Table 3.**

*Material constants for silicon and graphene.*


**5. References**

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	- Wang, C., J.X. Liu, Z.P. Yuan, Y.M. Wu, S.W. Zhai and H.W. Ye, 2007. Effect of level of metabolizable protein on milk production and Nitrogen utilization in lactating dairy cows. J. Dairy Sci., 90: 2960-2965.
	- Wang, S., G.L. Roy, A.J. Lee, A.J. McAllister, T.R. Batra, C.Y. Lin, J.A. Vesely, J.M. Wauthy and K.A. Winter, 1992. Evaluation of various measures of and factors influencing feed efficiency of dairy cattle. J. Dairy Sci., 75: 1273–1280.
	- Zamani, P., 2005. Different measures of energetic efficiency of lactation and estimation of their genetic parameters in Holstein dairy cattle. PhD thesis, Department of Animal Science, University of Tehran.
	- Zamani, P., S.R. Miraei-Ashtiani and H. Mohammadi, 2008. Genetic parameters of residual energy intake and its correlations with other traits in Holstein dairy cattle. Turk. J. Vet. Anim. Sci., 32: 255-261.
	- Zamani, P., S.R. Miraei-Ashtiani, D. Alipour, H. Aliarabi and A.A. Saki. 2011a. Genetic parameters of protein efficiency and its relationships with yield traits in lactating dairy cows. Livest. Sci., 138: 272-277.
	- Zamani, P., S.R. Miraei-Ashtiani, D. Alipour, H. Aliarabi, A.A. Saki, M. Maleki and A Abdolmohammadi, 2011b. Statistical analysis of some factors affecting crude protein balance in lactating dairy cows. J. Agr. Sci. Tech., (In Press).
	- Zamani, P., S.R. Miraei-Ashtiani, D. Alipour, M.M. Tabatabaei, H. Aliarabi, A.A. Saki, A. Ahmadi and K. Zaboli, 2011c. Statistical evaluation of some environmental factors affecting gross efficiency of crude protein in high producing dairy cow. Turk. J. Vet. Anim. Sci., 35: 123-130.
	- Zamani, P., S.R. Miraei-Ashtiani, A.A. Naserian, A. Nikkhan, and M. Moradi Shahrbabak. 2004. Genetic variation in residual energy intake and its association with body weight, milk yield, fat corrected milk yield and economic merit in dairy cattle. J. Dairy Sci., 87 (Supple 1): M9, Page: 3. (Abstract).
	- Zamani. P., S.R. Miraei-Ashtiani, A.A. Naserian, A. Nikkhan, and M. Moradi Shahrbabak. 2005. Genetic variation of income over feed costs as an individual trait in Holstein cows. Proceedings of the British Society of Animal Science. Page: 130.

**Milk Production and Animal Management**

150 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

live weight and feed intake: a review. J. Dairy Sci., 81: 1109–1119.

residual feed intake in dairy cows. Livest. Prod. Sci., 41: 111–120.

mobilization in dairy cows. Livest. Prod. Sci., 39: 229–241.

efficiency of dairy cattle. J. Dairy Sci., 75: 1273–1280.

balance in lactating dairy cows. J. Agr. Sci. Tech., (In Press).

Proceedings of the British Society of Animal Science. Page: 130.

farms. J. Dairy Sci. 81: 272–282.

production. Wageningen, EAAP, No. 67.

cows. J. Dairy Sci., 90: 2960-2965.

Science, University of Tehran.

cows. Livest. Sci., 138: 272-277.

Anim. Sci., 32: 255-261.

Anim. Sci., 35: 123-130.

(Supple 1): M9, Page: 3. (Abstract).

VandeHaar, M.J., 1998. Efficiency of nutrient use and relationship to profitability on dairy

Veerkamp, R.F., 1998. Selection for economic efficiency of dairy cattle using information on

Veerkamp, R.F., G.C. Emmans, A.R. Cromie and G. Simm, 1995. Variance components for

Veerkamp, R.F., G.C. Emmans, J.D. Oldham and G. Simm, 1993. Energy and protein utilization of cows of high and low genetic merit for milk solids production on a high and low input diet. Proc. Zodiac Symp. Biological basis of sustainable animal

Veerkamp, R.F., G. Simm and J.D. Oldham, 1994. Effects of interaction between genotype and feeding system on milk production, feed intake, efficiency and body tissue

Wang, C., J.X. Liu, Z.P. Yuan, Y.M. Wu, S.W. Zhai and H.W. Ye, 2007. Effect of level of metabolizable protein on milk production and Nitrogen utilization in lactating dairy

Wang, S., G.L. Roy, A.J. Lee, A.J. McAllister, T.R. Batra, C.Y. Lin, J.A. Vesely, J.M. Wauthy and K.A. Winter, 1992. Evaluation of various measures of and factors influencing feed

Zamani, P., 2005. Different measures of energetic efficiency of lactation and estimation of their genetic parameters in Holstein dairy cattle. PhD thesis, Department of Animal

Zamani, P., S.R. Miraei-Ashtiani and H. Mohammadi, 2008. Genetic parameters of residual energy intake and its correlations with other traits in Holstein dairy cattle. Turk. J. Vet.

Zamani, P., S.R. Miraei-Ashtiani, D. Alipour, H. Aliarabi and A.A. Saki. 2011a. Genetic parameters of protein efficiency and its relationships with yield traits in lactating dairy

Zamani, P., S.R. Miraei-Ashtiani, D. Alipour, H. Aliarabi, A.A. Saki, M. Maleki and A Abdolmohammadi, 2011b. Statistical analysis of some factors affecting crude protein

Zamani, P., S.R. Miraei-Ashtiani, D. Alipour, M.M. Tabatabaei, H. Aliarabi, A.A. Saki, A. Ahmadi and K. Zaboli, 2011c. Statistical evaluation of some environmental factors affecting gross efficiency of crude protein in high producing dairy cow. Turk. J. Vet.

Zamani, P., S.R. Miraei-Ashtiani, A.A. Naserian, A. Nikkhan, and M. Moradi Shahrbabak. 2004. Genetic variation in residual energy intake and its association with body weight, milk yield, fat corrected milk yield and economic merit in dairy cattle. J. Dairy Sci., 87

Zamani. P., S.R. Miraei-Ashtiani, A.A. Naserian, A. Nikkhan, and M. Moradi Shahrbabak. 2005. Genetic variation of income over feed costs as an individual trait in Holstein cows.


4. Instruments and tests for glare

#### 4.1. CSV-1000E

levels used during disability glare testing and how that relays to realistic encounters in

Contrast sensitivity performance in photopic conditions do not always correlate with mesopic conditions. Hertenstein et al. compared contrast sensitivity under both photopic and mesopic conditions [37]. Individuals recruited for the research comprised of normal, cataract patients, and glaucoma patients. The study utilized a glare testing device known as the Mesotest for the mesopic condition while using two different visual acuity test, Freiburg Acuity and Contrast Sensitivity Test (FrACT) and the Mars Letter Contrast Sensitivity Test for the photopic condition. Furthermore, the three testing methods were also retested to assure the reliability of the results. Overall, the study demonstrated that high mesopic contrast sensitivity score correlated with high photopic contrast sensitivity score. That correlation was also true when the subjects had low photopic contrast sensitivity score and low mesopic scores. However, high photopic contrast sensitivity score did not show the same predictability because individuals with those scores had various mesopic contrast sensitivity scores [37]. This suggest that to fully understand the visual impairments of disability glare, glare must be tested in different light conditions. Disability glare is present in everyday life at various light settings and so testing in many conditions provides more applicable knowledge of impairments patients face daily. As research has shown, visual performance differs depending on lighting and one condition cannot completely predict the results of another. However, testing under mesopic conditions may provide more information about visual function because a high score correlated to good

In patients with ocular pathologies and older drivers, concerns associated with disability glare often comes from difficulty driving at night. Realistic visual problems cannot always be accurately tested in clinical examination because visual acuity only tests visual function with high contrast and in photopics conditions. A study done by Kimlin and colleagues demonstrates this flaw by assessing the predictability of visual tests on the driving performance of its subjects [38]. These subjects had little to no ocular pathologies but had trouble night time driving. The subjects were put through driving obstacles to monitor their driving performance during night time. The subjects were also tested under photopic conditions for both visual acuity and contrast sensitivity. Then, they were tested under mesopic conditions for visual acuity and contrast sensitivity as well as glare testing. The study revealed that out of all the test results, high contrast visual acuity provided the least information about driving performance. In turn, glare and mesopic conditions were better predictors and accounted for more of the driving variations in the subjects [38]. Thus, a major visual problem like night time driving cannot be captured by typical clinical settings. Visual acuity and photopic conditions cannot provide information adequate in assessing all visual complaints. Thus, proper measurements of disability glare should be done in a lighting condition that most accurately addresses the

In addition, mesopic conditions mimic those of night time illuminance as well as fog. While it has been shown that visual acuity decreases during mesopic conditions, central vision is less important and the ability to discriminate contrast becomes more necessary [39]. Thus, the effects of disability glare on contrast sensitivity during mesopic conditions can be more clini-

everyday situations.

70 Causes and Coping with Visual Impairment and Blindness

vision in both light levels.

visual complaint of interest.

cally valuable and applicable to daily life.

One widely known clinical tool to measure disability glare is the CSV-1000E from Vector Vision. This device measures disability glare using contrast sensitivity at spatial frequencies ranging from low to high. The spatial frequencies are measured using sinusoidal gratings at varying levels of contrast. The CSV-1000E has a backlit illumination of 85 cd/m2 which can be used for glare testing under photopic conditions. The device can measure in mesopic conditions as well with the use of neutral density filters which lowers illuminance to 3 cd/m2 , the FDA recommended setting for mesopic measurements [40] (Figure 4).

The test consists of eight levels of contrast for each spatial frequency. There are eight columns consisting of two circles each, one which contains the sinusoidal gratings. The subject is tasked with identifying which of the two circles contain the grating for each of the columns. The responses are recorded and converted to a logarithmic scale.

Since the CSV-1000E can test in both photopic and mesopic conditions at various spatial frequencies, it has a variety of useful applications in a clinical setting. Shandiz et al. demonstrated the use of the CSV-1000E in individuals with different types of cataracts and different levels of severity. The CSV-1000E was sensitive enough to display a correlation between the subject's performance on contrast sensitivity and their level of lens opacity [41]. Since the CSV-1000E is a discriminative test that reflect ocular pathologies, it can be valuable in tracking the progression of a disease such as cataracts.

While the CSV-1000E has shown some discriminative ability, one report has shown the device is unreliable. Kelly et al. looked at the repeatability of the CSV-1000E in children and adults. The results indicated that the CSV-1000E has poor reliability. The reliability only improved in

Figure 4. CSV-1000E used for glare testing at varying luminance and contrast sensitivity at different spatial frequencies. Image courtesy of VectorVision [40].

the case of maintaining the same experimenter, but even so the reliability was still low [42]. Some issues with the study was it involved both children and adults and the groups were too small to perform a reliable sub-analysis.

Examining the reliability of the CSV-1000E with a subject of pool of glaucoma patients, the investigators found the device and testing to be reliable. The reliability was calculated as the coefficient of repeatability (COR) which was on average .191 which was lower when compared to another known glare test, the Miller-Nadler Glare Tester (COR = 0.36) [43]. The study tested the effectiveness of a beta-blocker therapy on the contrast sensitivity of open angle glaucoma and looked at the reliability of CSV-1000E. The CSV-1000E was able to detect the changes in visual function from the beta-blocker treatment which can suggest good discriminative sensitivity [43]. Furthermore, based on repeatability the results supported that CSV-1000E can be a clinically reliable tool.

The CSV-1000E is a clinically versatile device as it can measure disability glare in various conditions. The device has also shown discriminative ability in detecting the changes in state of those with cataracts and glaucoma. However, the repeatability of the test remains uncertain and so further assessment of the CSV-1000E with a large sample size will be necessary for understanding its suitability in glare testing.

The halometer showed significant correlation between the visual acuity and the digitized opacity measurements. The results indicate that this glare test can contribute additional knowledge to visual function in relation to cataracts. Furthermore, the repeatability of the halometer was also assessed. The halometer performed with high repeatability of about 0.998 with test and retest occurring 1 week apart [45]. The halometer being both discriminative and

Figure 5. Schematic of the Halometer glare device utilized by Babizhayev and colleagues to measure intraocular light

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Another modification of the halometer utilized an iPad application and an LED point light source. The halometer is known as the Aston Halometer [46] (Figure 6). The study subjects were tested monocularly with the use the Bangerter occlusion foil to induce disability glare. The target, presented at four different Weber contrast levels, was moved from the LED light source in eight different directions. The subject was to identify when the target was just visible from the light source and the distance, being the halo disk radius, was measured and analyzed. The performance of the Halometer was compared to the straylight meter which had been shown to be an accurate measurement of straylight and correlated to the amount of disability glare. The Halometer showed sensitivity to lower contrast letter and had high repeatability during testing which makes for a promising device [46]. However, the device was only tested on normal subjects without ocular pathologies. Therefore, while there is evidence in the Halometer's sensitivity to varying levels of contrast in normal subjects, the study did not provide insight to glare in ocular pathologies such cataract and glaucoma. Since the population of those living with ocular pathologies struggle with disability glare, a glare device needs to demonstrate discriminative ability in disease such as cataracts, glaucoma, and corneal

Another study also used the Aston halometer to measure disability. They did so to evaluate night time driving in older adults with minimal pathologies including cataracts, glaucoma, and corneal pathology [38]. The subjects recruited was put through a driving obstacle to monitor their driving performance. Then mesopic conditions as well as glare testing was measured to see whether the visual testing is an accurate predictor of the subject's driving. While the test showed that the Aston halometer was a better predictor than photopic high contrast visual acuity (HCVA) testing, it was not a better predictor than mesopic high contrast visual acuity testing [38]. This suggest that the Aston halometer may need other improvements to increase sensitivity

and further studies will be necessary to assess the validity of the halometer.

reliable can be a beneficial and useful addition to clinical evaluation of patients.

scatter in subjects with cataracts. Babizhayev et al. [45].

disease.

#### 4.2. Halometer

Disability glare while causing a veil of light over the visual object, can also create an illuminated ring in our viewpoint which is known as a halo. The halo can be quantified by its disk radius and be used as a mean to measure disability glare. In a study conducted by Palomo-Alvarez et al., it was demonstrated that in comparison to straylight and corrected visual distance acuity (CVDA), disk halo radius was more discriminatively sensitive at detecting differences between normal and cataract subjects under glare conditions [44]. Thus, disk halo radius can be a valuable diagnostic tool to measure disability glare in clinics. One of the current tools for measuring halos are halometers. There are several models of halometers which are adopted by researchers to fit their studies. However, the foundational principals of the different halometers for evaluating disability glare are very similar.

The halometer test mainly entails a point light source at the center of the testing screen which varies in intensity depending on the device and study. The optotype used can be illuminated with a green or red light to monitor the effects of wavelength on light scattering. The protocol usually comprises of the subject moving the optotype either away or to the light source until it is just no longer visible or just visible depending on the specific instructions. The distant from the light to the object is then measured and analyzed as the disk radius halo which correlates with the amount of disability glare experienced.

In a study performed by Babizhayev et al., the halometer was used to assess individuals with cataracts [45] (Figure 5). Additionally, the performance of the Halometer was compared to other clinical tools such as visual acuity measurements and digitized opacity representations of the lens to determine the validity of the test. The digitized representations were done with retro-illumination photography that was digitally analyzed for light scattering and absorption.

the case of maintaining the same experimenter, but even so the reliability was still low [42]. Some issues with the study was it involved both children and adults and the groups were too

Examining the reliability of the CSV-1000E with a subject of pool of glaucoma patients, the investigators found the device and testing to be reliable. The reliability was calculated as the coefficient of repeatability (COR) which was on average .191 which was lower when compared to another known glare test, the Miller-Nadler Glare Tester (COR = 0.36) [43]. The study tested the effectiveness of a beta-blocker therapy on the contrast sensitivity of open angle glaucoma and looked at the reliability of CSV-1000E. The CSV-1000E was able to detect the changes in visual function from the beta-blocker treatment which can suggest good discriminative sensitivity [43]. Furthermore, based on repeatability the results supported that CSV-1000E can be a

The CSV-1000E is a clinically versatile device as it can measure disability glare in various conditions. The device has also shown discriminative ability in detecting the changes in state of those with cataracts and glaucoma. However, the repeatability of the test remains uncertain and so further assessment of the CSV-1000E with a large sample size will be necessary for

Disability glare while causing a veil of light over the visual object, can also create an illuminated ring in our viewpoint which is known as a halo. The halo can be quantified by its disk radius and be used as a mean to measure disability glare. In a study conducted by Palomo-Alvarez et al., it was demonstrated that in comparison to straylight and corrected visual distance acuity (CVDA), disk halo radius was more discriminatively sensitive at detecting differences between normal and cataract subjects under glare conditions [44]. Thus, disk halo radius can be a valuable diagnostic tool to measure disability glare in clinics. One of the current tools for measuring halos are halometers. There are several models of halometers which are adopted by researchers to fit their studies. However, the foundational principals of

The halometer test mainly entails a point light source at the center of the testing screen which varies in intensity depending on the device and study. The optotype used can be illuminated with a green or red light to monitor the effects of wavelength on light scattering. The protocol usually comprises of the subject moving the optotype either away or to the light source until it is just no longer visible or just visible depending on the specific instructions. The distant from the light to the object is then measured and analyzed as the disk radius halo which correlates

In a study performed by Babizhayev et al., the halometer was used to assess individuals with cataracts [45] (Figure 5). Additionally, the performance of the Halometer was compared to other clinical tools such as visual acuity measurements and digitized opacity representations of the lens to determine the validity of the test. The digitized representations were done with retro-illumination photography that was digitally analyzed for light scattering and absorption.

the different halometers for evaluating disability glare are very similar.

small to perform a reliable sub-analysis.

72 Causes and Coping with Visual Impairment and Blindness

understanding its suitability in glare testing.

with the amount of disability glare experienced.

clinically reliable tool.

4.2. Halometer

Figure 5. Schematic of the Halometer glare device utilized by Babizhayev and colleagues to measure intraocular light scatter in subjects with cataracts. Babizhayev et al. [45].

The halometer showed significant correlation between the visual acuity and the digitized opacity measurements. The results indicate that this glare test can contribute additional knowledge to visual function in relation to cataracts. Furthermore, the repeatability of the halometer was also assessed. The halometer performed with high repeatability of about 0.998 with test and retest occurring 1 week apart [45]. The halometer being both discriminative and reliable can be a beneficial and useful addition to clinical evaluation of patients.

Another modification of the halometer utilized an iPad application and an LED point light source. The halometer is known as the Aston Halometer [46] (Figure 6). The study subjects were tested monocularly with the use the Bangerter occlusion foil to induce disability glare. The target, presented at four different Weber contrast levels, was moved from the LED light source in eight different directions. The subject was to identify when the target was just visible from the light source and the distance, being the halo disk radius, was measured and analyzed. The performance of the Halometer was compared to the straylight meter which had been shown to be an accurate measurement of straylight and correlated to the amount of disability glare. The Halometer showed sensitivity to lower contrast letter and had high repeatability during testing which makes for a promising device [46]. However, the device was only tested on normal subjects without ocular pathologies. Therefore, while there is evidence in the Halometer's sensitivity to varying levels of contrast in normal subjects, the study did not provide insight to glare in ocular pathologies such cataract and glaucoma. Since the population of those living with ocular pathologies struggle with disability glare, a glare device needs to demonstrate discriminative ability in disease such as cataracts, glaucoma, and corneal disease.

Another study also used the Aston halometer to measure disability. They did so to evaluate night time driving in older adults with minimal pathologies including cataracts, glaucoma, and corneal pathology [38]. The subjects recruited was put through a driving obstacle to monitor their driving performance. Then mesopic conditions as well as glare testing was measured to see whether the visual testing is an accurate predictor of the subject's driving. While the test showed that the Aston halometer was a better predictor than photopic high contrast visual acuity (HCVA) testing, it was not a better predictor than mesopic high contrast visual acuity testing [38]. This suggest that the Aston halometer may need other improvements to increase sensitivity and further studies will be necessary to assess the validity of the halometer.

over visual acuity in the case of the Berkeley Glare Test to produce more sensitive and accurate results. Furthermore, the Berkeley Glare Test also presented versatility as a glare device because the charts can be changed to test a wider range of visual function. This is potentially helpful in ocular diseases such as cataracts to evaluate different visual impairments in various settings. The Berkeley Glare Test also presented good discriminative ability as it can differen-

Glare and Ocular Diseases

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http://dx.doi.org/10.5772/intechopen.74687

Further evaluation of the validity of the Berkeley Glare Test was done by Elliot and colleagues in a study where different glare tests were also observed [28]. The test was utilized with a low contrast (Weber 15%) Bailey-Lovie chart with a back illumination of 80 cd/m2 and the glare setting was set to 750 cd/m2 illumination. The Berkeley Glare Test displayed good repeatability but did not perform as well as the Regan chart and BAT (Brightness Acuity Test) as the glare source in reliability. The Berkeley Glare Test also exhibited good discriminative ability between normal and cataract patients. However, the study did disclaim that the subjects were referred to the ophthalmologist's office due to discrepancies in visual acuity. Since visual acuity in these subjects were already low, it can be expected that visual impairments were apparent enough to be easily detected by most tests. And so, these results did not further support the discriminative ability of the Berkeley Glare Test. The Berkeley Glare Test also fulfilled the three criteria of a vision test outlined by the American Academy of Ophthalmology (AAO). The criteria include: a force-choice protocol, test target follows a uniform logarithmic progression, multiple trials should be done at each level of acuity or contrast [28]. The Berkeley Glare Test's performance as outlined by the AAO criteria is both reliable and discriminative test. Therefore, the Berkeley Glare test can potentially be a strong

In another instance, a research study utilized the Berkley Glare Test to evaluate nighttime driving and disability glare. The study compared the Berkeley Glare Test to the Aston Glare Test in predicting night time driving performance. The Berkeley Glare Test did not show any significant correlation in driving performance while the Aston Glare Test displayed significant correlations [38]. This may suggest that while the Berkeley Glare Test can produce valid results, newer glare devices are surpassing it in sensitivity and leaves room for improvement

In another glare test, known as the EpiGlare tester, the inventors developed a glare testing device that has the validity and discriminative disability to detect vision loss caused by glare. Epitropoulos and colleagues assessed the changes in corrected distance visual acuity (CDVA) in cataract and normal subjects under glare conditions [48]. The EpiGlare tester is a LED light emitting device that can be attached to a phoropter. There are four LED lights placed evenly around the aperture of the device. Under induced glare conditions, the subjects are asked to read off an EDTRS chart to assess their CDVA. The study also incorporated a Functional Vision Questionnaire that assessed the subjects driving and glare experiences. An additional question was asked after glare testing on how closely the test resembled their glare problems while

tiate between those with early signs of nuclear sclerosis and normal subjects.

foundation as both a research and clinical tool.

in the test itself.

4.4. EpiGlare tester

nighttime driving (Figure 7).

Figure 6. Schematic of the Aston Halometer designed on the iPad with an LED light source and target optotype controlled by iPhone. Buckhurst et al. [46].

#### 4.3. Berkeley glare test

The Berkeley Glare Test has long been used for glare testing in clinic and research. The Berkeley Glare test measures visual acuity optotypes and different contrast levels under glare conditions [47]. A chart of varying levels of contrast is placed in the device, behind the opal Plexiglas screen which has a back illumination of 85 cd/m2 . The device has three levels of glare, being 300, 800, and 3000 cd/m2 . The creators of the Berkeley Glare test, Bailey and Bullimore, tested the technique on young and older ocular healthy adults [47]. Older adults were categorized as healthy if no ocular pathologies were present and their nuclear sclerosis score was grade 1 and under. The subjects were tested under four conditions which were no glare, and the three glare illuminations mentioned earlier. The chart used in the Berkeley Glare Test can vary and be chosen to meet specific needs. Visual function at high contrast was measured using the Bailey-Lovie Chart, a letter chart that assessed visual acuity. Low contrast visual function was also measured by using a letter chart that was at a Michaelson 10% contrast. The subjects were scored on a basis of a disability glare index (DGI) which was the difference in the number of letters the subject can see in the no glare versus glare conditions. Bailey and Bullimore's testing results showed that subjects with early nuclear sclerosis had a higher reduction in disability glare in comparison to visual acuity. The data also reflected subtle changes in lens opacity in the subject's DGI score before those changes could be detected by visual acuity testing [47]. The significant difference between DGI scores suggested that the Berkeley Glare test was more sensitive to physiological changes when assessing for contrast sensitivity than visual acuity [47]. This also noted the importance of using contrast sensitivity over visual acuity in the case of the Berkeley Glare Test to produce more sensitive and accurate results. Furthermore, the Berkeley Glare Test also presented versatility as a glare device because the charts can be changed to test a wider range of visual function. This is potentially helpful in ocular diseases such as cataracts to evaluate different visual impairments in various settings. The Berkeley Glare Test also presented good discriminative ability as it can differentiate between those with early signs of nuclear sclerosis and normal subjects.

Further evaluation of the validity of the Berkeley Glare Test was done by Elliot and colleagues in a study where different glare tests were also observed [28]. The test was utilized with a low contrast (Weber 15%) Bailey-Lovie chart with a back illumination of 80 cd/m2 and the glare setting was set to 750 cd/m2 illumination. The Berkeley Glare Test displayed good repeatability but did not perform as well as the Regan chart and BAT (Brightness Acuity Test) as the glare source in reliability. The Berkeley Glare Test also exhibited good discriminative ability between normal and cataract patients. However, the study did disclaim that the subjects were referred to the ophthalmologist's office due to discrepancies in visual acuity. Since visual acuity in these subjects were already low, it can be expected that visual impairments were apparent enough to be easily detected by most tests. And so, these results did not further support the discriminative ability of the Berkeley Glare Test. The Berkeley Glare Test also fulfilled the three criteria of a vision test outlined by the American Academy of Ophthalmology (AAO). The criteria include: a force-choice protocol, test target follows a uniform logarithmic progression, multiple trials should be done at each level of acuity or contrast [28]. The Berkeley Glare Test's performance as outlined by the AAO criteria is both reliable and discriminative test. Therefore, the Berkeley Glare test can potentially be a strong foundation as both a research and clinical tool.

In another instance, a research study utilized the Berkley Glare Test to evaluate nighttime driving and disability glare. The study compared the Berkeley Glare Test to the Aston Glare Test in predicting night time driving performance. The Berkeley Glare Test did not show any significant correlation in driving performance while the Aston Glare Test displayed significant correlations [38]. This may suggest that while the Berkeley Glare Test can produce valid results, newer glare devices are surpassing it in sensitivity and leaves room for improvement in the test itself.

#### 4.4. EpiGlare tester

4.3. Berkeley glare test

being 300, 800, and 3000 cd/m2

controlled by iPhone. Buckhurst et al. [46].

74 Causes and Coping with Visual Impairment and Blindness

The Berkeley Glare Test has long been used for glare testing in clinic and research. The Berkeley Glare test measures visual acuity optotypes and different contrast levels under glare conditions [47]. A chart of varying levels of contrast is placed in the device, behind the opal

Figure 6. Schematic of the Aston Halometer designed on the iPad with an LED light source and target optotype

tested the technique on young and older ocular healthy adults [47]. Older adults were categorized as healthy if no ocular pathologies were present and their nuclear sclerosis score was grade 1 and under. The subjects were tested under four conditions which were no glare, and the three glare illuminations mentioned earlier. The chart used in the Berkeley Glare Test can vary and be chosen to meet specific needs. Visual function at high contrast was measured using the Bailey-Lovie Chart, a letter chart that assessed visual acuity. Low contrast visual function was also measured by using a letter chart that was at a Michaelson 10% contrast. The subjects were scored on a basis of a disability glare index (DGI) which was the difference in the number of letters the subject can see in the no glare versus glare conditions. Bailey and Bullimore's testing results showed that subjects with early nuclear sclerosis had a higher reduction in disability glare in comparison to visual acuity. The data also reflected subtle changes in lens opacity in the subject's DGI score before those changes could be detected by visual acuity testing [47]. The significant difference between DGI scores suggested that the Berkeley Glare test was more sensitive to physiological changes when assessing for contrast sensitivity than visual acuity [47]. This also noted the importance of using contrast sensitivity

. The device has three levels of glare,

. The creators of the Berkeley Glare test, Bailey and Bullimore,

Plexiglas screen which has a back illumination of 85 cd/m2

In another glare test, known as the EpiGlare tester, the inventors developed a glare testing device that has the validity and discriminative disability to detect vision loss caused by glare. Epitropoulos and colleagues assessed the changes in corrected distance visual acuity (CDVA) in cataract and normal subjects under glare conditions [48]. The EpiGlare tester is a LED light emitting device that can be attached to a phoropter. There are four LED lights placed evenly around the aperture of the device. Under induced glare conditions, the subjects are asked to read off an EDTRS chart to assess their CDVA. The study also incorporated a Functional Vision Questionnaire that assessed the subjects driving and glare experiences. An additional question was asked after glare testing on how closely the test resembled their glare problems while nighttime driving (Figure 7).

Figure 7. EpiGlare tester designed by Dr. Alice Epitropoulos can be easily attached to phoropter for clinical use. Image courtesy of good-Lite. Epitropoulos et al. [48].

From the data of 40 subjects with cataracts and 49 ocular healthy subjects, EpiGlare tester demonstrated that cataract subjects are more impaired by disability glare than normal subjects [43]. These findings support the discriminative ability of the EpiGlare tester to distinguish the visual loss between pathology and healthy vision. Furthermore, the questions asked during the testing provides additional evidence to the validity of the device. From all the subjects, 83% of the cataract subjects reported the device accurately simulated their difficulties nighttime driving [48]. The device was easy to utilize and incorporate in clinical settings. The attachment to phoropter increases repeatability of the glare tester because the device setup will be consistent. The study did not directly examine its reliability and thus further evaluation of the device is still necessary. However, the EpiGlare tester simple use can be advantageous in clinical settings with its discriminative sensitivity and convenience.

#### 4.5. Ophthimus glare tester versus contrast sensitivity function glare test

While there can be many variations among glare devices, the core of what is required in glare testing is the same. Therefore, there are several present methods and devices that share similar set ups. Two of which are the Ophthimus Glare Tester (Hightech Vision) and the contrast sensitivity function (CSF) glare tester created by Abrahamsson and his colleagues [21, 49]. Both these models examine cataract and normal subjects as well as monitoring their visual performance with contrast sensitivity under glare conditions (Figures 8 and 9).

These devices employed similar setups by using a ring fluorescent tube as the glare source with the optotype presented in the middle. Both assessed contrast sensitivity; however, the Ophthimus Glare Test utilized the Landolt C with varying levels of contrast as its optotype [21]. The CSF Glare Tester, on the other hand, used sinusoidal gratings to measure contrast sensitivity with different contrast levels and spatial frequencies [49]. Furthermore, the type of glare sources differed, and the intensity of both glare sources were not disclosed. Hence, there is no basis to compare the two on illuminance.

When using the Landolt C, the protocol normally ensued a force choice answer. In the case of Ophthimus Glare Tester, the subjects were asked to report which direction the gap of the Landolt C was facing. This was done until the subject reached the lowest contrast in which the direction of the Landolt C could still be answered correctly [21]. This resembled the procedure of the CSF tester as the sinusoidal gratings were gradually increased to the contrast that was

Figure 9. Schematic of Abrahamsson and Sjostrand glare device with a ring light as the glare source and sine wave

contrast sensitivity in the center. Abrahamsson and Sjostrond [21].

Figure 8. Schematic of the Ophthimus glare test with the ring light as the glare source and Landolt C at the center. Martin

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[49].

Figure 8. Schematic of the Ophthimus glare test with the ring light as the glare source and Landolt C at the center. Martin [49].

From the data of 40 subjects with cataracts and 49 ocular healthy subjects, EpiGlare tester demonstrated that cataract subjects are more impaired by disability glare than normal subjects [43]. These findings support the discriminative ability of the EpiGlare tester to distinguish the visual loss between pathology and healthy vision. Furthermore, the questions asked during the testing provides additional evidence to the validity of the device. From all the subjects, 83% of the cataract subjects reported the device accurately simulated their difficulties nighttime driving [48]. The device was easy to utilize and incorporate in clinical settings. The attachment to phoropter increases repeatability of the glare tester because the device setup will be consistent. The study did not directly examine its reliability and thus further evaluation of the device is still necessary. However, the EpiGlare tester simple use can be advantageous in clinical

Figure 7. EpiGlare tester designed by Dr. Alice Epitropoulos can be easily attached to phoropter for clinical use. Image

While there can be many variations among glare devices, the core of what is required in glare testing is the same. Therefore, there are several present methods and devices that share similar set ups. Two of which are the Ophthimus Glare Tester (Hightech Vision) and the contrast sensitivity function (CSF) glare tester created by Abrahamsson and his colleagues [21, 49]. Both these models examine cataract and normal subjects as well as monitoring their visual

These devices employed similar setups by using a ring fluorescent tube as the glare source with the optotype presented in the middle. Both assessed contrast sensitivity; however, the Ophthimus Glare Test utilized the Landolt C with varying levels of contrast as its optotype [21]. The CSF Glare Tester, on the other hand, used sinusoidal gratings to measure contrast sensitivity with different contrast levels and spatial frequencies [49]. Furthermore, the type of glare sources differed, and the intensity of both glare sources were not disclosed. Hence, there

settings with its discriminative sensitivity and convenience.

courtesy of good-Lite. Epitropoulos et al. [48].

76 Causes and Coping with Visual Impairment and Blindness

is no basis to compare the two on illuminance.

4.5. Ophthimus glare tester versus contrast sensitivity function glare test

performance with contrast sensitivity under glare conditions (Figures 8 and 9).

Figure 9. Schematic of Abrahamsson and Sjostrand glare device with a ring light as the glare source and sine wave contrast sensitivity in the center. Abrahamsson and Sjostrond [21].

When using the Landolt C, the protocol normally ensued a force choice answer. In the case of Ophthimus Glare Tester, the subjects were asked to report which direction the gap of the Landolt C was facing. This was done until the subject reached the lowest contrast in which the direction of the Landolt C could still be answered correctly [21]. This resembled the procedure of the CSF tester as the sinusoidal gratings were gradually increased to the contrast that was barely visible to the subject under glare conditions. The task was done at all spatial frequencies [49]. Both glare test measured the lowest contrast level visible by the subject to determine their contrast sensitivity. These results were both used to calculate a glare score which was used to understand the visual function of the cataract subjects and ocular healthy subjects.

Author details

Pomona CA, USA

References

My Diep1 and Pinakin Gunvant Davey2

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gov/health/cornealdisease

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\*Address all correspondence to<EMAIL_ADDRESS>
\*

1 Western University of Health Sciences, College of Osteopathic Medicine of the Pacific,

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[1] Mainster MA, Turner PL. Glare's causes, consequences, and clinical challenges after a century of ophthalmic study. American Journal of Ophthalmology. 2012;153(4):587-593 [2] Aslam TM, Haider D, Murray IJ. Principles of disability glare measurement: An ophthalmological perspective. Acta Ophthalmologica Scandinavica. 2007;85(4):354-360

[3] Van Rijn LJ. Measurement of stray light and glare: Comparison of Nyktotest, Mesotest, stray light meter, and computer implemented stray light meter. British Journal of Oph-

[4] Spadea L, Maraone G, Verboschi F, Vingolo EM, Tognetto D. Effect of corneal light scatter on vision: A review of the literature. International Journal of Ophthalmology. 2016;9(3):459-464

[5] Davey P. Fabry disease: A survey of visual and ocular symptoms. Clinical Ophthalmol-

[6] Facts about the Cornea and Corneal Disease. 2016, May. Retrieved from https://nei.nih.

[7] Swartz TS, Wang M. Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment.

[8] Fan-Paul NI, Li J, Miller JS, Florakis GJ. Night vision disturbances after corneal refractive

[9] Wang A, Cheng H. Amiodarone-associated optic neuropathy: Clinical review. Neuro-Ophthalmology (Aeolus Press). 2016;41(2):55-58. DOI: 10.1080/01658107.2016.1247461 [10] Jinabhai A, O'Donnell C, Radhakrishnan H, Nourrit V. Forward light scatter and contrast sensitivity in Keratoconic patients. Contact Lens & Anterior Eye. 2012;35(1):22-27

[11] Mäntyjärvi M, Laitinen T. Normal values for the Pelli-Robson contrast sensitivity test. Journal of Cataract & Refractive Surgery. 2001;27(2):261-266. DOI: 10.1016/s0886-3350(00)

2 Western University of Health Sciences, College of Optometry, Pomona CA, USA

Their shared similarities in testing methods also yielded the same results where both glare tests displayed discriminative ability between cataract subjects and age-matched ocular healthy subjects. However, each study correlated their glare score with different measurements and so each drew their own specific inferences from their results. The Ophthimus Glare Tester study looked at cataract patients in preparation for cataract surgery. These individuals had normal visual acuity, but the results of the study showed their disability glare score to be significantly lower and they also reported visual complaints associated with glare. After the surgery, 24 out of 25 subjects had no self-reported glare problems but some of the subjects still displayed elevated glare sensitivity [21]. This supported the discriminative ability of the Ophthimus Glare Tester that the glare test could still distinguish between cataracts and ocular healthy individuals even after surgery when visual function improved. The validity of the Ophthimus Glare Tester's performance was supported by being relevant to the subjective visual complaints of the subjects as well as with the results of preoperative and postoperative surgery. The CSF glare tester, on the other hand, measured their scores against opacity levels of the cataract subjects. They demonstrated a correlation between the glare scores and the current pathology of each subject [49]. Hence, the validity that the CSF glare tester was based more so on physiological progress of the disease rather than subjective experiences. Both these glare tests exhibited strong discriminative findings but because the studies that utilized the tests based their results on different foundations, the information yielded by each glare testing device was distinctive. This also applied to the information each study provided about the effects of glare on cataracts even though the glare tests shared a number of similarities. And so more testing should be conducted to assess the comparative validity of these glare tests.


**8. Prophylaxis**

Currently, even if the food manufacturing is done according to the standards proposed by the WHO, an important part of the fight against zoonoses must be borne by the consumer, who can be considered an integral link in the chain. We must therefore inform about the risks that may result from errors in food handling. Unfortunately, at present, few initiatives have been undertaken in Africa, unlike the situation in Europe and the United States, where politics at this level is a little more proactive. The operation FightBac ® bases its message on a logo simple and easy to understand for educators, children and operators of processing lines and distribution. CSCC logo are constantly reminded that people must wash their food ("Clean"), separate ("Separate"), Cook ("Cook") and cool ("Chill"). Advice is provided for hand washing, cooking food. The FDA in collaboration with the Center for food Safety and Applied Nutrition (CFSAN) has published a brochure about the risk of salmonellosis associated with eggs (FDA 2002). The CDC ("Centers for Disease Control") has published a leaflet on Salmonella Enteritidis, available on the Internet (Center for Disease Control, 2003). Finally, the educated consumers will, no doubt, more likely to seek medical attention, which will encourage feedback and help to reduce the phenomenon of under-reporting of cases.


**2.2 Obstruction**

Tube blockage is one more reason for the infertility in men. Obstruction in the tubes that pave way to the passage of sperm from the testicle to penis can have underlying causes like previous infections, pelvic surgeries, and cystic fibrosis associated with it. In case a severe duct obstruction is found, patients are advised to undergo the invasive procedure like transurethral resection to pave way for the normal course of ejaculate besides proving very important for the maintenance of sperm parameters [10].