A summary of the early phases of the glaucoma surgical treatment.
\r\n\tThere will be a chapter on secondary causes of sexual dysfunction disorders related to diabetes, cardiovascular disease, and obesity. A chapter on remedial measures to enhance sexual activity and maintain human relationships will be discussed. As there is a growing number of cancer survivors a chapter on cancer-related sexual dysfunction will be welcomed for including it.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"b988fda30a4e2364ee9d47e417bd0ba9",bookSignature:"Dr. Dhastagir Sultan Sheriff",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11889.jpg",keywords:"Sex, Sexual Response Cycle, Erection, Premature Ejaculation, Libido, Orgasm, Painful Intercourse, Psychological, Female, Lack of Desire, Erectile Disorders, Pain Disorders",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dhastagir Sultan Sheriff is a life member of the European Society for Human Reproduction and Early Human Development, Association of Physiologists and Pharmacologists of India, member of the National Academy of Medical Sciences, New Delhi, and resource person for UNESCO for Medical and Bioethics. Dr. Sheriff has authored five books including a textbook on medical biochemistry with additional interest in human sexology. He has done extensive research in andrology, sex education, and counseling.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"167875",title:"Dr.",name:"Dhastagir Sultan",middleName:null,surname:"Sheriff",slug:"dhastagir-sultan-sheriff",fullName:"Dhastagir Sultan Sheriff",profilePictureURL:"https://mts.intechopen.com/storage/users/167875/images/system/167875.jpg",biography:"Dhastagir Sultan Sheriff is a life member of the European Society for Human Reproduction and Early Human Development, Association of Physiologists and Pharmacologists of India, member of the National Academy of Medical Sciences, New Delhi, and resource person for UNESCO for Medical and Bioethics. Dr. Sheriff has authored five books including a textbook on medical biochemistry with additional interest in human sexology. He had editorials written in the British Journal of Sexology, Journal of Royal Society of Medicine, Postgraduate Medicine, and Scientist. He was a former Rotarian, Citizen Ambassador, and was selected for the Ford Foundation Fellowship.",institutionString:"University of Benghazi",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Benghazi",institutionURL:null,country:{name:"Libya"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"6934",title:"Psycho-Social Aspects of Human Sexuality and Ethics",subtitle:null,isOpenForSubmission:!1,hash:"44731b106aa0d1ab5c64a7394483c7d5",slug:"psycho-social-aspects-of-human-sexuality-and-ethics",bookSignature:"Dhastagir Sultan Sheriff",coverURL:"https://cdn.intechopen.com/books/images_new/6934.jpg",editedByType:"Edited by",editors:[{id:"167875",title:"Dr.",name:"Dhastagir Sultan",surname:"Sheriff",slug:"dhastagir-sultan-sheriff",fullName:"Dhastagir Sultan Sheriff"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7163",title:"Infertility, Assisted Reproductive Technologies and Hormone Assays",subtitle:null,isOpenForSubmission:!1,hash:"6db6e4ccb7088f17f819121f7eb6424d",slug:"infertility-assisted-reproductive-technologies-and-hormone-assays",bookSignature:"Dhastagir Sultan Sheriff",coverURL:"https://cdn.intechopen.com/books/images_new/7163.jpg",editedByType:"Edited by",editors:[{id:"167875",title:"Dr.",name:"Dhastagir Sultan",surname:"Sheriff",slug:"dhastagir-sultan-sheriff",fullName:"Dhastagir Sultan Sheriff"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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This is possible thanks to modern devices and imaging techniques that allow much faster and better diagnosing. Even today, the single most important thing in this matter is to know the characteristics of the normal -healthy optic disc (Figure 1.). The appearance of the optic disc, as in the other biological variables varies widely among healthy individuals. This fact complicates the recognition of the pathological changes.
Today modern glaucoma diagnostic is unimaginable without technological support, when it comes to discovering as well as for following up glaucoma optic neuropathy.
With standard clinical exam aside, there is a number of imaging devices that we use in everyday practice, and to mention a couple i.e. CVF, HRT, GDX, OCT, PACHIMETRY, FUNDUS PHOTOS, CDI… and we agree that without the help of this wide technological spectrum of supporting diagnostic devices we could not be able to diagnose the disease or to track the glaucoma changes. Just stop for a second and remember how it was in the old days? Let’s take a glance of the old days and how it all started?
There was the time when ophthalmologist did not have those sophisticated imaging devices; they even did not have slit lamps… despite the fact that they were glaucomatologists!
This chapter is dedicated to the pioneers of ophthalmology and glaucomathology; their legacy for future glaucomatologists.
The term optic disc is frequently used to describe the portion of the optic nerve clinically visible on examination. This, however, may be slightly inaccurate as ‘disc’ implies a flat, 2 dimensional structure without depth, when in fact the ‘optic nerve head’ is very much a 3 dimensional structure which should ideally be viewed stereoscopically.
Healthy optic disc
Every disease has its history, as much in diagnosing-discovering it, as in quality and adequate treatment. History of the diseases categorized today under the term “glaucoma” may be divided into three major periods. First period is the earliest and it stretches from approximately 400 BC up until 1600 AD; during the course of this period the term “glaucoma” was used to refer to a general group of blinding ocular diseases without the distinctions that historians now can recognize. During the middle period from the beginning of the 17th century to the middle of the 19th century the cardinal signs of glaucoma, separately and in combination, were described in published texts. Finally, the third period starts with the introduction of the ophthalmoscope (Helmholtz, 1854) to the present.
First period (400 BC to 1600 AD)
Etymology of the term glaucoma is that it derives from the Greek word ‘‘glaukos’’, which appears in the Homer’s notes, where it is mentioned as -a sparkling silver glare, later used for colours such as sky-blue or green. As a diagnosis by physicians, glaucoma is first mentioned in Hippocrates\'
It is interesting that most authors, by the Roman era, used the term
However, Archigenes, who practised at Rome in the time of Trajan (98-117 AD), used the term “ophthalmosglaucos” for a curable blindness that was not caused by cataract.
Archigenes revealed that he used the juice of the deadly nightshade, a mydriatic, in the treatment of this condition, adding, “the instilled juice of nightshade makes black the grey eyes.”
Galen (129-216 AD), (Figure 3.) defined glaucoma as a condition in which changes in fluids of the eye caused the pupil to become grey. He also refers to the mydriatic effect of nightshade.
Aetius, the physician of the emperor Justinian (482-565) AD, and a great Ophthalmologist, identified two forms of glaucoma, one a curable condition of the lens and the other an incurable condition that involved an effusion in which the pupil becomes thickly coagulated and dried.
Hippocrates (c.460 B.C.-c. 370 B.C.), a famous Greek physician, and the father ofMedicine, who first used the term \'glaucosis\' in his work \'Aphorisms\' to describe,conditions correlated with blindness and possibly glaucoma
Anatomy of the Eye, according to Galen as the Arabs transferred to the West
Second period (1600 TO 1854)
This period is marked by the rising awareness among ophthalmologists that technology is a key to a proper diagnostic.
Glaucoma became more distinct when it comes to adult or elderly patients with the emergence of four characteristics: (1) the consistent failure of cataract operations to improve vision, (2) the clinical appearance of eyes in terminal stages of the disease, (3) a specific history indicating self-limited forerunners of the severe disease, and (4) the elevated intraocular pressure.
Important breakthrough in ophthalmology is marked with the anatomic findings of Brisseau (1707) and the introduction of the process of lens extraction by Daviel (1752). This led to a search for the site of glaucoma in other structures of the eye and to concentration on clinical signs that could be helpful in distinguishing between cataract and glaucoma. Since a majority of the eyes in which the diagnosis of glaucoma was made in the 18th century were in an advanced stage of visual loss and iris atrophy after one or several acute attacks or after a prolonged chronic course, the clinical picture was dominated by congestion (varicosities) of the anterior ciliary veins, a dilated, poorly reacting pupil, and a varying degree of nuclear lens opacity. On examination with the light sources of that period, a greenish reflection could often be obtained; since this seemed to point to the real location of the disease, it became a prominent sign listed in the literature of the 181h and early 191h centuries.
The clinical features of advanced glaucoma, occasionally preceded by attacks of blurred vision that recurred with a high degree of uniformity, was first recorded in St. Yves\' “Treatise of the Diseases of the Eyes” (1741) and was described in more detail by Weller (1826).
It is a well known fact that elevation of the intraocular pressure as a distinct sign of ocular disease, recognizable by undue resistance of the eyeball to indentation by the physician\'s finger, was first clearly mentioned in the “Breviary” of the itinerant English oculist Banister (1626). In 1738 an equally clear reference to hardness of the eye appeared in the independent writings of Johann Platner, professor of anatomy, surgery, and therapeutics at the University of Leipzig. As a distinct clinical symptom, hardness of the eyeball was apparently generally known and accepted in the 1820s, as one may judge from the almost simultaneous but independent texts by Demours of France (1818), Guthrie of England (1823), and Weller of Germany (1826).
William Mackenzie[1] had a great influence on European and American ophthalmology through his personal teaching and through his textbook, between 1830. and 1854. He distinguished between acute and chronic glaucoma and gave a detailed description of the course of the latter from a stage 1 characterized just by a greenish hue reflected from the pupil to a stage 6 in which the eyeball, after perforation of a corneal ulcer in absolute glaucoma, has become atrophic. Mackenzie was well aware of the abnormal hardness of the glaucomatous eye from the second stage on; also, he apparently was the first to recommend a form of posterior sclerotomy to relieve the abnormal hardness.
Duke-Elder in his
Third period (1854. to the present day)
With Eduard Jaeger, the grandson and son of distinguished Austrian ophthalmologist, began modern ophthalmology and modern ophthalmic exam. He was the first investigator who described and documented with the picture, ophthalmoscopic appearance of the glaucomatous disc in the literature. It was a picture from the monocular indirect ophthalmoscope, on which was described the glaucomatous disc as a swelling of the papillary tissues with respect to the surrounding retina[3].
Just a few months later, Albrecht von Graefe also described a prominence of the papilla in glaucoma[4]. His description of the optic disc, specially his description of the pulsation of the arteries in the glaucomatous eyes, became reliable and, at time, reliable indicator of elevated intraocular pressure. The ring-shaped zone around the disc was officialy named -
Later, pathological findings confirmed ophthalmoscopic findings of the optic disc depression, what was interpreted as an effect of the elevated intraocular pressure, or-
Early classification of glaucoma was made at von Graefe’s clinic.
First type of glaucoma was acute or inflammatory, which characterized with self-limited prodromal attacks of misty vision (in 70 % of the cases), patient is seeing rainbows around the candle flame; attacks increased in severity, length and frequency until the real disease suddenly erupted in the form of an acute attack of inflammation and severe reduction of vision. Partial vision recovery with temporary remission mostly occurred spontaneously or responding on a treatment with large doses of opiates, antiphlogisthics and paracenthesis. Many penetrating exams were carried out during the remissions. After analysis of all phases of this type of glaucoma, von Graefe made a concept according which an acute glaucoma is:”achoroiditis or an iridochoroiditis, with diffuse impregnation of vitreous and aqueous with exudative material which caused the rise in pressure through an increase in volume.”
Second type was the chronic glaucoma. Prodromal attacks were without any sign of irritation, congestion or swelling; lengthen gradually and fused in a chronic form, characterized with the anterior ciliary veins dilatation, shallow anterior chamber, iris atrophy, glaucomatous cupping, arterial pulsation in the fundus; followed with reduction in vision.
The third type von Graefe simply named amaurosis with excavation of the optic nerve, and for him it was not in a group of glaucomatous diseases[6]. Normal anterior segment, with optic disc excavation, which lead to the vision impairment.
Completing this classification, von Graefe used the designation
In the late period of his research (1861.), von Graefe declared that an exclusion of amaurosis with the optic disc excavation from the group of glaucoma diseases was a mistake[7]. This correction he credited to Doners of Utrecht, his friend, who found a palpable tension among many eyes with so-called amaurosis with optic nerve excavation to be significantly above normal. Doners, after his research, prepositioned a term
It is interesting that von Graefe discovered also an ocular hypertension patients among his amaurosis with optic nerve excavation cases. He accepted Doner’s term glaucoma simplex. His posterity, first of all Schnabel[8], had verb his amaurosis with optic nerve excavation, implying that it was an optic nerve disease unrelated to elevated intraocular pressure.
Theory of inflammation, that von Graefe’s proposed as a cause of intraocular pressure rise and a name of that type of glaucoma held until the clinical discovery of the angle closure mechanism in the 20th century. Some of the alternative terms that were used are: “irritative” (de Wecker[9]), “congestive” (Hansen-Grut), and, much later, “uncompensated” (Elschnig).
The Anglo-Saxon literature preferred terms as acute, subacuteand chronic glaucoma
Finally, von Graefe in his last communication (1869), for the first time introduced a terms
In the late 1850s, German anatomist Heinrich Mueller[10] was the first who granted ophthalmoscopically observed depression of the optic disc. In his theory that was a result of an abnormally increased vitreous pressure acting upon the lamina and forcing it to recede. Mueller and his followers assumed that the receding lamina had taken the entire papilla with it, placing the nerve fibres on a steadily increasing stretch or pressing them against the sharp edge of the excavation. Consequence of that was optic nerve atrophy.
Considering that this concept was not uniform for all glaucomatous eyes (in some cases pathologists confirmed the lamina cribrosa displacement, in others not), the theory was add to the basic pressure hypothesis and was widely accepted but also a new ophthalmoscopic and pathologic facts of glaucoma were revealed.
Austrian ophthalmologist Isidor Schnabel (1842-1908)[8] was the first to describe in detail the nerve fibre breakdown with the formation of cavities as a characteristic of the glaucomatous process in the optic nerve. It was the earliest sign and for a long time the only glaucomatous change. In later stages the atrophy affected all portions of the optic nerve up to the entrance of the central vessels. In his opinion, cavernous atrophy was
Another perspective on the origin and nature of the glaucomatous optic neuropathy was introduced by Priestley Smith[11]. The glaucomatous cup is not a purely mechanical result of exalted pressure, but is in part at least, an atrophic condition which, though primarily due to pressure, includes vascular changes and impaired nutrition in the area of the disc and around its margin which require a considerable time for their full development.
This Priestley Smith\'s original notion that the rise in pressure may cause damage to the tissues of the disc through its influence on blood circulation is valid until the present day.
Previously mentioned essence of glaucoma, recognized in the mid-1850s, attributed to excessive formation of intraocular fluid or hyper secretion and assumed to eider a type of choroiditis (von Graefe) or a secretory neurosis (Donders).
The clear concept of the eye mechanisms that were involved in the intraocular pressure production, in that time, was not plain. German anatomist Schwalbe12 began in 1860s the experimental study of the fluid exchange of the eye, searching the lymphatics in the anterior segment. When the dye is injected into the anterior chamber of the eye, in aqueous solution or suspension, it appears promptly in veins on the surface of the globe! His conclusion was that the anterior chamber is a lymphatic space in open communication with anterior cilliary veins.
Theodor Leber13 also injected dyes into the anterior chamber of the eye of a rabbit, and discriminated certain border structures. This disclosure stimulated many investigators of that time, including Leber, to investigate a cannular system and Schwalbe, to investigate the anterior chamber angle in animals. Thus Leber discovered normal outflow (on a fresh enucleated mammalian eye), he presented it as a filtration through the trabecular meshwork and a flow through ciliary and vortex veins.His conclusion was that the rate of outflow was, in principle, proportional to the perfusion pressure, except during an initial period, when the perfusion fluid took up the space occupied in the living eye by blood. He actually determined filtration coefficients, the forerunners of today\'s coefficients of aqueous outflow.
Since this outflow was from fresh enucleated eyes at the pressures prevailing in the living eye, Leber reasoned that the same process of outflow must also take place in the normal living eye. To maintain a stable in vivo pressure, the steady loss of fluid must be compensated for by steady formation of an equal amount of fluid, which Leber believed could also take place through a process of filtration. Thus, the filtration theory of aqueous formation and elimination was born. In a few human eyes enucleated in far-advanced stages of glaucoma, Leber found very low filtration coefficients which indicated abnormal resistance to aqueous outflow[14]. This finding fitted in well with the first detailed pathologic report on the condition of the chamber angle in far-advanced glaucoma[15]: “The most important finding in genuine glaucoma is the circular adhesion of the iris periphery to the periphery of the cornea or the obliteration of the space of Fontana.”*
Considering that in either case glaucoma could result from an inflammatory or an obstructive process within the angle or from pressure from behind. It was realized almost immediately that the peripheral anterior synechiae could be either the cause or the effect of glaucoma. Pathologic specimens which supported these mechanisms were identified and reported. The theory that glaucoma was principally a disorder of aqueous outflow (referred to generally as the Leber-Knies theory) rapidly gained ground.
The essence of the Leber’s (Leber-Knies) filtration theory has stood the test of time. Leber’s best apprentice, Erich Seidel, in 1920’s, made some necessary additions to this theory, including the effects of the colloidosmotic pressure of the plasma proteins and of active transfer processes in the formation of aqueous[16].
Interesting appendage is that the essence of the Leber’s theory, the idea, admittedly without experimental proof, of a steady directional circulation of fluid through the chambers of the eye had been expressed by earlier observers, specifically William Porterfield, more than 100 years before Leber.
During 1880s and 1890s, it was observed that chronic inflammatory glaucomas composed two thirds of all glaucomas. Angle closure glaucomas were dominant. Priestley Smith measured the horizontal corneal meridian in normal eyes 11.6mm and in glaucomatous eyes 11.2mm[17], what expressed dominance of the angle closure glaucoma in that period. 1888. Priestley Smith also introduced the concept of a predisposition to glaucoma, which consists in progressive narrowing of the circumlental space with age, due to the steady growth of the lens in eyes with small corneas. Anatomicaly, the ciliary processes in states of hyperaemia are crowded forward, pressing the iris against the anterior angle wall. This based on a Smith\'s experiment on the animal that a small excess of pressure in the vitreous chamber (as little as 4 mm Hg) makes the lens and the suspensory ligament advance in such a manner as to close the angle of the anterior chamber.
Next step was the discovery of shallowness of the anterior chamber as an important role in the mechanism of the acute glaucoma (in the eyes with acute inflammatory glaucoma)[18]. The description of the mechanism: if the pupil dilates in an eye with shallow anterior chamber, the iris, particularly with its thicker portion, can occlude the filtration angle and, thereby, raise the intraocular pressure. If contraction of the sphincter frees the filtration space, the event remains a prodromal attack. At a certain level of intraocular pressure the ocular veins are compressed at their place of entry into the sclera; venous stasis develops with increased transudation; that, and not inflammation, is the true nature of glaucoma.[18]
The Revolution on this field came in 1920.when Curran [19](Kansas City) and Seidel [16](Heidelberg), on the basis of astute clinical observations, independently announced the concept of the relative pupillary block.
Curran\'s paper[19]: "normally the aqueous passes through the pupil from the posterior to the anterior chamber, but it is here contended that in glaucoma this passage is impeded on account of the iris hugging the lens over too great a surface extent. Some of the aqueous gets through while some passes back, forcing the lens and the iris still more forward. "
Ophthalmoscopy, the most important single invention in ophthalmology, that had shaped its evolution, was introduced by Hermann von Helmholtz in December of 1850.[20],[21]However, Jan Purkinje (known for the Purkinje images) had described the complete technique and published it in Latin in 1823,[22]but his audience apparently was not yet ready and his publication went unnoticed. A quarter of a century later, however, the situation changed.
The ophthalmoscope was not based on any radically new concepts. Rather, it combined the appropriate application of various known principles with recognition of its potential impact and presentation to an appropriate audience. Under the leadership of men like Bowman in London, Donders in Holland, and von Graefe and von Helmholtz in Germany, ophthalmology emerged as the first organ-based specialty in medicine.
Several workers had tried to visualize the inside of the eye but had fallen short of putting it all together. Kussmaul (known for “Kussmaul\'sairhunger”) described the imaging principles in a thesis in 1845[23]but failed to solve the illumination problem. Cumming[24](1846) in England and Brücke[25](1847) in Germany had shown that a reflection from the fundus could be obtained by bringing the light source in line with the observer, but they failed to solve the imaging problem. Babbage,[26]the English mathematician, reportedly constructed an ophthalmoscope in 1847, but his ophthalmologist friend did not recognize the importance and did not publish it until 1854, when von Helmholtz\' instrument was well known.
In the fall of 1850, von Helmholtz tried to demonstrate the inside of the eye to the students in his physiology class. On December 6, he presented his findings to the Berlin Physical Society[20]; on December 17, he wrote to his father[27]:
Helmholtz\' monograph on ophthalmoscopy was published in 1851 and soon was widely circulated. The next year there were several important improvements contributed by other workers. Rekoss,[28]von Helmholtz\' instrument maker, added two movable disks with lenses for easier focusing. Epkens, working with Donders in Holland,[27] introduced a perforated mirror for increased illumination. Ruete[29] in Germany did the same and also developed the indirect method of ophthalmoscopy. With these basic components in place, future generations provided technical improvements. In 1913, Landolt[30] listed 200 different types of ophthalmoscopes.
If the patient\'s fundus is properly illuminated, the field of view is limited by the most oblique pencil of light that can still pass from the patient\'s pupil to the observer\'s pupil (Figure 4.). In direct ophthalmoscopy the retinal point that corresponds to this beam can be found by constructing an auxiliary ray through the nodal point of the eye.[30] The point farthest from the centerline of view that can still be seen is determined by the angle α, that is, the angle between this oblique pencil and the common optical axis of the eyes.
Field limits in direct ophthalmoscopy. The maximum field of view is determined by the most oblique pencil of rays (shaded) that can still pass from one pupil to the other.
Angle α, and therefore the field of view, is increased when the patient\'s or the observer\'s pupil is dilated or when the eyes are brought more closely together.
The more peripheral pencils of light use ever-smaller parts of each pupil. This means that, even if the patient\'s fundus is uniformly illuminated, the luminosity of the fundus image gradually decreases toward the periphery, so that there is no sharp limitation to the field of vision. In practice, therefore, the effective field of vision is determined by the illuminating system not by the viewing system. Most ophthalmoscopes project a beam of light of about one disc diameter.
Even with appropriate illumination, direct ophthalmoscopy has a small field of view (Figure 5.) shows that of four points in the fundus, points one and four cannot be seen because pencils of light emanating from these points diverge beyond the observer\'s pupil. To bring these pencils to the observer\'s pupil, their direction must be changed (Figure 6). This requires a fairly large lens somewhere between the patient\'s and the observer\'s eye. This principle was introduced by Ruete[29]in 1852 and is called indirect ophthalmoscopy to differentiate it from the first method, in which the light traveled in a straight, direct path from the patient\'s eye to the observer.
Limited field of view in the direct method. Peripheral pencils of light do not reach the observer\'s pupil.
Extended field of view in the indirect method. The ophthalmoscopy lens redirects peripheral pencils of light toward the observer.
The use of the intermediate lens has several important implications that make indirect ophthalmoscopy more complicated than direct ophthalmoscopy.
The primary purpose of the ophthalmoscopy lens is to bend pencils of light toward the observer\'s pupil. Figure 3 also demonstrates one of the most characteristic side effects of this arrangement: Compared with the image in direct ophthalmoscopy, the orientation of the image on the observer\'s retina is inverted. For the novice, this often causes confusion in localization and orientation. Figure 3 further shows that in this arrangement the patient\'s pupil is imaged in the pupillary plane of the observer. In optical terms the pupils are in conjugate planes.
The most important changes are related to the change from candle light to gas light, to external electric light and, finally, to built-in electric light sources.[31]
Although the older generation found it difficult to adapt to the new instrument, the younger generation did so eagerly. One of them was Eduard von Jaeger (1828 to 1884) from Vienna, best known for his print samples that were based on the print catalogue of the Vienna State Printing House. He was the son of a well-known ophthalmologist and an artistically gifted mother. In 1855, at the age of 27, he published his first atlas; he continued to add to his collection of authoritative fundus paintings until his death in 1884.[32]
Although not generally considered as a method of ophthalmoscopy, fundus examination with the slit lamp offers an important addition to the traditional methods of direct and indirect ophthalmoscopy. It offers the advantage of high-power magnification through the microscope and flexible illumination with the slit-lamp beam. With appropriate contact lenses, it can offer higher magnification than direct ophthalmoscopy and a field several times wider than indirect ophthalmoscopy. These methods have become particularly important in combination with laser treatment.
Because the slit-lamp microscope has a fixed focus on a plane approximately 10 cm in front of the objective and because the image of the fundus of an emmetropic eye appears at infinity, the fundus cannot be visualized without the help of additional lenses. There are several options.
A negative lens placed in front of the objective of the microscope can move the microscope focus to infinity. The practical application of this principle was worked out by Hruby[33],[34]of Vienna (1942) with a lens known as the Hruby lens.
The optical principle is best understood if the lens is considered in conjunction with the eye, rather than as a part of the microscope. Parallel rays emerging from an emmetropic eye are made divergent by the Hruby lens and seem to arise from the posterior focal plane of that lens (Figure 7A.) For a -50-D lens, this would be 20 mm behind the lens (the usual Hruby lens is -55 D). The slit-lamp microscope is thus looking at a virtual image of the fundus in a plane somewhere in the anterior segment and must be moved a little closer to the patient than it would be for the regular external examination.
To estimate the field of view in this method, it may be assumed that only rays emerging parallel to the axis will reach the objective of the microscope and the observer\'s eye. When emerging from the eye, these rays must have been aimed at the anterior focal point of the Hruby lens. (Figure 7B), in which these rays are traced back to the retina, shows that the field of view (a) is proportional to the pupillary diameter as seen from the anterior focal point of the lens. This field is of the same order of magnitude as the field in direct ophthalmoscopy; it is largest when the lens is closest to the eye.
Hruby lens. A. The fundus image (F\') is formed in the posterior focal plane of the lens. B. The field of view is proportional to the size of the pupil as seen from the anterior focal point of the lens.
With the lens close to the cornea, the fundus image will be close to the fundus plane and approximately actual size. The magnification to the observer is thus largely determined by the magnification of the microscope. At 16×, the magnification is about equal to that of direct ophthalmoscopy; at higher settings, the magnification is greater. Binocular viewing and slit illumination are advantages over direct ophthalmoscopy, even at similar magnification. Limitation to the posterior pole is a disadvantage.
When the Hruby lens is moved progressively closer to the eye, it will eventually touch the cornea and become a contact lens. If the curvature of the posterior lens surface equals the curvature of the anterior corneal surface, the image formation will not change, but two reflecting surfaces will be eliminated, and image clarity will increase.
The use of a contact lens for fundus examination was perfected by Goldmann[35]of Berne, Switzerland (1938). His contact lens is known for the three mirrors incorporated in it. These mirrors positioned at different angles make it possible to examine the peripheral retina with little manipulation of the patient\'s eye or of the microscope axis (Figure 8).
Three mirror contact lens by Goldmann. Two of the three mirrors are shown. They allow visualization of different parts of the fundus.
The refractive power of the cornea is eliminated in the contact lens. The only effective refractive element left would seem to be the far less powerful crystalline lens. The retina is situated well within the focal length of this lens, and the crystalline lens will therefore form a virtual image of the fundus (F) in a plane (F\') behind the globe. How can the microscope focus on an image that far back? We overlooked one other refracting surface: the plano front surface of the contact lens. F\' is seen through plastic and vitreous. To the observer in air F\' appears at F", through the same effect that makes a swimming pool appear shallower than it is. Because of this, the microscope again must focus on a plane inside the globe. As with the Hruby lens, magnification is largely determined by the microscope.
Thus, contact lens fundus microscopy extends our range of examination methods to details beyond the reach of ordinary direct ophthalmoscopy.
The use of the Hruby lens and Goldmann contact lens is comparable to direct ophthalmoscopy, because no real intermediate image is formed. The equivalent of indirect ophthalmoscopy can be achieved by focusing the microscope on the real image formed by a high-power plus lens.
El Bayadi[36]introduced the use of a +60-D lens for this purpose. The inverted image formed by this lens is situated 16 mm (0.0167 m) in front of it. A practical problem with some older slit lamps is that they cannot be pulled back far enough to observe this image.
Compared with the Hruby (-55 D) lens, the El Bayadi (+60 D) lens offers the same major advantage as does indirect ophthalmoscopy: a larger field of view. With proper placement of the lens, the field is about six disc diameters (40 degrees), compared with the one- or two-disc diameter field of the Hruby lens.
With a 60-D lens the aerial image is as large as the fundus; thus the magnification is approximately equal to the microscope magnification (similar to that with the Hruby lens).
Can the field of view be widened even further? This is possible by using a contact lens of very high plus power with some additional optical tricks.Figure 9 illustrates the RodenstockPanfunduscope, based on a design by Schiegel.[37]
The unit contains a high plus contact lens, which forms an inverted fundus image (F\') located inside a second, spherical glass element.
In this arrangement, as in the previous example of a high myope (Figure 10), the image-forming and field-widening functions of the ophthalmoscopy lens are separated again. The contact lens forms the image; the spherical element serves to flatten the image and to redirect the diverging pencils of rays toward the observer. Because these elements are so close to the eye, the field of view can be very wide. Indeed, without moving the lens, the view reaches 200 degrees, that is, from equator to equator, 4 to 5 times the diameter (16 times the area) of regular indirect ophthalmoscopy or of the El Bayadi lens.
Contact lens arrangement for wide-angle indirect biomicroscopy. A high-power contact lens forms an inverted image (F\') inside a spherical element, which redirects the light toward the observer.
Indirect ophthalmoscopy of a high myope. The myopic eye forms its own aerial image (dotted lines) without the help of the ophthalmoscopy lens. Without the lens, only the central part of this image would be visible (dashed lines, limited by the patient\'s pupil). With lens (solid lines) the image is limited by the lens rim.
The size of the image inside the front lens is 70% of the retinal size; for detailed examination, therefore, 50% more microscope magnification is required than with the other slit-lamp methods. However, the principal use of this lens is not for its magnification but for its overview, an overview previously achievable only in fundus drawings or photocompositions.
Similar contact lens arrangements are used in specially designed fundus cameras that allow fundus photography of areas 100 degrees or more in diameter. With lenses such as these, the spectrum of our examining methods can be extended not only toward higher magnification than with direct ophthalmoscopy but also, at the other end, toward an overview of the fundus considerably beyond that obtainable with regular indirect ophthalmoscopy.
As the technology to calculate, design, and manufacture lenses with aspheric surfaces has improved, it has been possible to make lenses with higher powers and better light gathering abilities. The number and variety of lenses for indirect ophthalmoscopy and of contact lenses for slit-lamp microscopy has grown accordingly.
Fundus cameras have greatly improved the ability to document and follow fundus lesions. Eduard von Jaeger often spent countless hours drawing a single fundus, but today a photographic image is available in a fraction of a second. For reasons mentioned earlier, fundus cameras are built on the principle of indirect ophthalmoscopy. The observer\'s lens and retina are replaced by a camera lens and film. Because all components are enclosed in a rigid housing, more accessories can be built in. This includes a dual illumination system, which includes a constant light source for focusing and a flash for photography, and filters such as for fluorescein angiography. Rather than placing the viewing and illumination beams side by side, the illumination beam generally uses the periphery of the pupil and leaves the center for the observation beam.[38]
An angled glass plate that can be flipped to the right or to the left can be used to slightly deviate the observation beam to the right part or the left part of the patient\'s pupil to produce photo pairs that can be viewed stereoscopically.
Because newer lens designs have allowed the construction of wide-angle cameras, a special challenge has been to construct the optical system in such a way that the curved retina is imaged in a plane that can be captured on a flat film.
The optics of the eye are not perfect. Even if major errors are corrected with spherical and cylindrical lenses, small irregularities across the pupillary opening persist. The technique of adaptive optics was developed for astronomical telescopes to counteract image degradation by atmospheric irregularities. An adaptive optics system uses a grid to divide the pupillary opening into many small areas and determines a separate small correction for each area. The information is fed to a slightly deformable mirror with microactuators. Thus the image quality can be enhanced to the point at which the cone mosaic can be clearly visible. The setup is too laborious for use in routine photography. Because the corrective system has to be fixed in relation to the pupil, it cannot be implemented in glasses or contact lenses. However, the technique, also known as wavefront analysis, has found a place in the refractive sculpting of the cornea.[39]
Another important part of ophthalmic exam. First explored in by Trantas (1907.); then explored by Salzmann (1915-16.); Koeppe (1919-20.); and Troncoso (1925-30). Finally Otto Barkan (1887.-1958.) made gonioscopy a routine diagnostic method in the ophthalmologist\'s office, thereby bringing about the separation of the glaucomas due to the angle-closure mechanism from the open-angle glaucomas[40]that the elevation of the intraocular pressure depends of abnormal resistance to aqueous outflow caused by anatomic or functional changes within the outflow channels.
Not until the 1890s did open-angle glaucoma become well proved and accepted in theories.
Thanks to gonioscopy, started recognition of a type or types of glaucoma without obstruction of the angle by the iris.
In the first edition of the Graefe-SaemischHandbook of Ophthalmology (1877), Saemisch lists the following ocular diseases as frequently giving rise to secondary glaucoma: cicatricial ecstasies of the cornea, circular or total adhesions of the iris to the lens, iritis serosa, traumatic cataract, dislocations of the lens, intraocular tumours, hemorrhagic retinal processes (referring mainly, if not exclusively, to occlusions of the central retinal vein), and sclerectasia pastries (which probably referred to glaucoma in eyes with malignant myopia). Congenital hydrophthalmos was at the time also classified with the secondary glaucomas.
William Bowman introduced digital estimation of the ocular tension at the annual meeting of the British Medical Association in 1862. Estimation of the ocular tension by palpation became one of the ophthalmologist\'s special skills, and some ophthalmologists developed so much confidence in it that they viewed instrumental tonometry with suspicion.
The early beginning of instrumental tonometry, apparently made by von Graefe, who mentions preliminary trials of mechanical tonometers in a letter to Donders dated December 24, 1862. Unfortunately, none of these instruments, however, reached the drawing board stage.
The real beginning and the first tonometers actually produced and tested on human eyes were developed in Donders\' clinic in Utrecht between 1863 and 1868. They were instruments for use on the sclera. The scleral curvature at the site of tonometer application was determined first; it then served as a reference plane for the measurement of the depth of the indentation.
Impression tonometry had its drawbacks. The principal flaw was that the indentation, by displacing a significant amount of intraocular fluid, changes the pressure which is intended to measure; this was clearly expressed for the first time by AdoIf Weber in 1867. Weber was official inventor of the first applanation tonometer, which was intended to give a tension reading with only minimal fluid displacement. Despite its theoretic superiority, this instrument did not gain wide acceptance, because recognition of the point of perfect applanation without indentation proved to be difficult. Lately, the principles of applanation tonometry were explored by Maklakoff in 1885. andImbert and Fick, father and son, a few years later. It resulted a several new applanationtonometers, but only one of them, Maklakoff\'s model of 1892, has stood the test of time and has remained in use, mainly by groups in the USSR.
The beginning of the 20th century, digital tonometry was still a method of subjective assessment of the ocular pressure [41]. At that time neither applanation tonometer did not find widespread use in practice.Finally, in 1905.Schiøtz presented his impression tonometer and it did not take long for the instrument to acquire the epithet “the first clinically useful tonometer.” First major comprehensive reports of the clinical value of Schiotz tonometer began to appear in 1910. The essence of today\'s knowledge of the intraocular pressure in the normal and in the diseased human eye was acquired between 1910. and 1920. through the use of Schiøtztonometers.
Disadvantages of digital and instrumental tonometry, realized by the pioneers of these methods, addressed to the properties of the eyeball wall, especially elasticity, affected estimation of the intraocular pressure. Early experimental attempts in that time, to measure these properties and to eliminate them revealed new variables. Schiøtz wrote in 1920: “I can not imagine any method available for living eyes by which errors due to variations of the envelope could be eliminated.” [42]Thirty years later, the electronic form of his instrument came closest to yielding reasonable estimates of “ocular rigidity,” the term introduced by Friedenwald for the resistance that the in vivo eyeball offers to a change in intraocular volume [43].
Correcting readings taken with the Schiøtz tonometer for deviation of the particular eye from average ocular rigidity, the coefficient of ocular rigidity lost some of its clinical importance through the tremendous progress in applanation tonometry that occurred in the early 1950s through the work of Goldmann, Perkins, and Maurice.
The technology to estimate intraocular pressure (IOP) has evolved tremendously since Sir William Bowman emphasized the importance of ocular tension measurements in 1826. In an address delivered at the annual meeting of the British Medical Association, Sir William underscored the critical role that digital estimation of ocular tension played in his practice. In his address, Sir William stated that “it is now my constant practice, where defective vision is complained of, to ascertain almost at the first instant the state of tension in the eye...It is easy enough to estimate the tension of the eye, though there is a right and a wrong way of doing even so simple a thing... With medical men, the touch is already an educated sense, and a very little practice should suffice to apply it successfully to the eye.”[44]
Soon afterwards, digital tonometry became an essential clinical skill necessary to master by all ophthalmologists. When mechanical tonometry was first introduced in the late 1800s, many ophthalmologists felt so confident with their ability to estimate IOP by palpation that they viewed the new technology as inferior. Isador Schnabel, in an address to the Vienna Ophthalmological Society in 1908, was noted to state that although he did not object in principle to mechanical tonometry, he expected “…very little from this test since digital tonometry by an expert is a much more accurate test”.[45]
Although Grafe is credited with the first attempts to create instruments that mechanically measured IOP in the early 1860s, his proposed instruments were neither designed nor built. Rather, it was Donders who designed the first instrument capable of estimating IOP – albeit not accurately – with mechanical tonometry in the mid 1860s. The principle behind Donders’s instrument was to displace intraocular fluid by contact with the sclera. The ophthalmologist first measured the curvature of the sclera at the site of contact, and then used this measurement as a reference plane to measure the depth of indentation. Smith and Lazerat refined this technology in the 1880s, and the discovery of cocaine by Carl Koller in 1884 led the way to corneal impression tonometry soon thereafter. With the aid of a powerful corneal anesthetic agent, corneal tonometry became the definitive choice of IOP measurements because it offered a well – defined and uniform site of impression when compared with the sclera.
Impression tonometry’s major shortcoming was that it displaced so much fluid upon contact with the eye that the measured readings were highly variable and mostly inaccurate. What was needed was a way to displace a minimal amount of fluid to record IOP. This breakthrough came when Adolf Weber designed the first applanation tonometer in 1867, which gave a highly defined applanation point without indentation. After two decades of skepticism, the value of applanation tonometry was re-discovered when Alexei Maklakoff and others introduced new versions of applanationtonometers. In early 20th century, there were about 15 models of tonometers in use. In fact, Maklakoff’s 1892 model is the basis of applanation tonometry today. However, digital tonometry still remained the gold standard among most ophthalmologists in the early 1900s.
The first clinically useful mechanical tonometer was designed and introduced by HjalmarSchiotz in the early 1900s. The instrument was simple, easy to use, and highly precise. It was quickly accepted and became the new gold standard beginning the 1910s. Innovations in calibration led to its increased use, and a tremendous amount of knowledge about the normal and glaucomatous eye was quickly acquired. An adjustment for ocular rigidity was introduced by Goldmann in the 1950s, which led to the development of Goldmannapplanationtonometers. The Goldmanntonometers displace such little fluid that variations in ocular rigidity are mostly negligible. The electronic and non – contact tonometers used today rely heavily on the principles and instrumentation first introduced by Maklakoff, Schiotz and Goldmann.
Today, for the most part, digital tonometry has been replaced by sophisticated technologies to estimate IOP. Today’s instruments are incredibly accurate and easy to use. Yet, there is sometimes no good substitute for digital tonometry. For example, some ophthalmologists may prefer digital tonometry when estimating IOP in patients with keratoprostheses. In these situations, fingers that have mastered Sir William’s art are highly desirable. In fact, it is said that the famous Dr. Claus Dohlman, Harvard professor of Ophthalmology at the Massachusetts Eye and Ear Infirmary, remains as accurate in measuring IOP with his fingers as any ophthalmologist using the high-tech tonometers of today!
Modern diagnostic of glaucoma is unimaginable without perimetry. The merit for measurements of peripheral vision for the diagnosis and follow-up of ocular disease, as many other things in ophthalmology, is attributed to Albert von Graefe. With a primitive campimeter—a sheet of paper with radial rows of dots which served as stimuli—he was probably the first (1856) to plot paracentral field defects in chronic glaucoma and to use them in the evaluation of surgical results. Similar to von Graefe’s device, Haffmanns from Donder’s clinic discovered the greater frequency in glaucoma simplex of serious involvement of the upper half of the field, which gave rise to an easily detectable nasal step [46].
In 1857.Förster introduced the first perimeter, which placed accent on large targets, such as the 10/330, which permitted only very gross measurements. The observations of that time did suggest partial reversibility of field defects if the pressure was lowered substantially by an iridectomy or sclerotomy. 1889. was a very important year for a development of techniques most appropriate for glaucoma. Bjerrum presented 2-meter screen, the 2-meter test distance, and the 2- to 5-ram white test objects. He discovered the relative or absolute scotomas, circling the point of fixation and including the blind spot, which became the hallmark of chronic glaucoma. Conceptually, it means the beginning of the nerve fibre bundle theory of the glaucomatous optic nerve disease.
Further major step was the occurrence of small scotomas in the zone from 12° to 20° from the point of fixation, in early glaucomas, presented by Peter [47]. These scotomas, in the beginning were not connected with the blind spot, but they reached it later via expansion.
The construction of smaller isopters, another early glaucoma characteristic, presented in 1920s, was clearly established with Bjerrum’s technique. Bjerrum’s technique also confirmed the regression of early glaucomatous defects following normalization of pressure documented by instrumental tonometry. The close relationship between pressure and field of vision was demonstrated further by Samojloff\'s observations [48]of temporary enlargement of the blind spot concurrent with osmotically induced pressure elevations. By stereocampimetry with minute targets, Evans was able to detect a gross form of parallelism between diurnal pressure fluctuations and the size of paracentralscotomas[49].
Also in 1920s was noticed that among patients with glaucomatous defects close to the point of fixation (late stages of glaucoma optic neuropathy), a surgical procedure, particularly iridectomy, could have an untoward effect and lead to further rapid shrinkage of the visual field. The incrimination of the iridectomy referred originally to the period when the alternative, the sclerotomy, had proved relatively free of unfavourable effects on the visual field. Subsequent experience with filtering operations temporarily led to the distinction between two classes of glaucoma operations: 1) the less risky: cyclodialysis and sclerotomy and 2) the riskier: iridectomy, sclerectomy, and trephination.
The early treatment of glaucoma has its course of history (Table 1. and Table 2.).
Main discoveries where:
A curative action of the iridectomy in certain glaucomas7,[44],
The development of the filtering operations [50], and
The discovery of the first three ocular hypotensive drugs: eserine, pilocarpine, and epinephrine [51].
\n\t\t\t\t | \n\t\t|
1830 | \n\t\t\tMackenzie1 recommends scleral punctures to release vitreous and to relieve the pressure on the retina. | \n\t\t
1857 | \n\t\t\tvon Graefe\'s iridectomy6 almost overnight gains the position of | \n\t\t
1882 | \n\t\t\tde Wecker, in a paper on the “filtering cicatrix”9, expresses the concept that in the presence of elevated intraocular pressure, a properly executed corneoscleral incision can heal in a manner allowing intraocular fluid to “filter,” ie, be driven by a pressure gradient through the loose scar tissue into subconjunctival spaces. | \n\t\t
1891 | \n\t\t\tBader [52] finds the occurrence of an iris prolapse during or shortly after an iridectomy a favourable sign, auguring success of the operation. | \n\t\t
1903 | \n\t\t\tHerbert reports on a series of subconjunctival fistula operations in which he purposely leaves the iris in the operative incision. The report includes the first detailed description of the transformation of the epibulbar tissues that become exposed to the steady flow of aqueous [53]. | \n\t\t
1905 | \n\t\t\tHeine first reports on the operation of cyclodialysis[54], based on Fuchs\' [55] and Axenfeld\'s[56] observation of the association between postoperative choroidal detachment, a tear or tears in the insertion of the ciliary muscle at the scleral spur, and hypotony. | \n\t\t
1906 | \n\t\t\tLagrange first reports on his iridosclerectomy[50]. | \n\t\t
1909 | \n\t\t\tFreeland and Elliot independently substitute the trephine for Lagrange\'s scissors. | \n\t\t
1913 | \n\t\t\tAt the first international review of glaucoma surgery the pronouncement is made that chronic glaucoma can only be arrested by establishing a filtering cicatrix in connection with the anterior chamber. The iridectomy loses its status of | \n\t\t
1915 | \n\t\t\tThe abexterno incision is introduced by Foroni[58]. | \n\t\t
1920 | \n\t\t\tSeidel demonstrates the transconjunctival passage of aqueous after trephining procedures[16]. | \n\t\t
A summary of the early phases of the glaucoma surgical treatment.
\n\t\t\t\t | \n\t\t|
1863 | \n\t\t\tArgyll Robertson and von Graefe study the effect of extracts of the calabar bean on pupil and accommodation. Von Graefe finds the miotic effect useful in that it facilitates the iridectomy. | \n\t\t
1876 | \n\t\t\tLaqueur[59] reports “a definite drop of the elevated tension after repeated installations of physostigmine in five cases of glaucoma simplex and in one case of secondary glaucoma.” | \n\t\t
1876 | \n\t\t\tWeber studies the mechanisms underlying the hypotensive effect of physostigmine in rabbits and in man and advises caution in its use because of the marked swelling and engorgement of the ciliary processes caused by the drug [60]. | \n\t\t
1877 | \n\t\t\tLaqueur gives the first clear-cut account of the successful termination by use of physostigmine of attacks of acute glaucoma and of the prevention of recurrences [61]. | \n\t\t
1877 | \n\t\t\tWeber introduces pilocarpine with the hope that it will replace the iridectomy in some of the chronic and simple glaucomas and that it will serve to make up for the insufficient effect of the latter in many other cases [62]. | \n\t\t
1898 | \n\t\t\tThe hypotensive effect of topically administered adrenal extracts is discovered. | \n\t\t
1902 | \n\t\t\tDarier reports significant lowering of pressure in some glaucomas, induced by adrenaline alone or in combination with physostigmine[51]. | \n\t\t
1909 | \n\t\t\tExtensive clinical use of adrenaline has confirmed the beneficial results, but it has also brought to light the clear-cut untoward effects, ie, the drug may cause further elevation of pressure and even precipitate acute attacks in certain eyes. | \n\t\t
1923 | \n\t\t\tHamburger reintroduces adrenaline; new, more potent, more stable preparations for topical use are becoming available. Untoward effects in certain eyes are rediscovered [63]. | \n\t\t
1932 | \n\t\t\tGonioscopy furnishes the answer to the unfavorable response of certain eyes to topical adrenaline. | \n\t\t
A summary of the early phases of the glaucoma medical treatment.
Cervical cancer is one of the most common cancers among the female population with the fourth most common after breast, colorectal, and lung cancer. In 2018, there were approximately 570,000 new cases of cervical cancer with 311,000 deaths [1]. Treatment of cervical cancer is composed of surgery, radiotherapy and systemic treatment. Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer (LACC) and the combination of external beam radiotherapy (EBRT) and brachytherapy (BT) maximizes the local control while minimizing the risk of toxicity. Standard EBRT should deliver a dose of 45–50.4 Gy to the whole pelvis encompassing the uterus, adnexal structures, parametria, and pelvic lymph nodes. With BT, various dose fraction schedules are used, applying a dose of 5.5–8 Gy by 3–5 fractions and the total combined dose with EBRT and BT should be in the range of 80–90 Gy [2]. From the publications of Han et al. and Gill et al. BT is one of the major components for curative radiotherapy for LACC [3, 4, 5]. Completion of the radiation program within a suitable time is an important goal as it has a direct correlation to the outcome. The current recommendation is to finish the entire protocol of EBRT and BT within 8 weeks [2].
Brachytherapy was used to increase the curative dose to cervical cancer from the year when Todd and Meredith et al. introduced the Manchester system with radium [6, 7]. The using of point A, bladder point, and rectum point (identified in orthogonal X-rays) were reported with ICRU 38 concepts [8, 9]. The intrauterine tandem and intravaginal applicators were used in many institutes to treat cervical cancer, with acceptable results. Figure 1 shows orthogonal X-rays for conventional planning.
Point A (black triangle), point B (white circle), ICRU bladder (black star), ICRU rectum (white star) and 5-mm vagina points (black circle) from The Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University.
The concepts of volume-based brachytherapy in magnetic resonance imaging (MRI) started by the publications of the Groupe European de Curietherapie and the European Society for Radiotherapy and Oncology GEC-ESTRO in 2005–2006 to propose the definitions of targets (high-risk clinical target volume; HR-CTV and intermediate-risk clinical target volume; IR-CTV) and normal tissues (Organs at risk (OARs); bladder, rectum and sigmoid) with dose constraints for evaluation [10, 11]. Moreover, the additional concepts of HR-CTV were extrapolated to CT since 2007 and developed to many international publications [12, 13, 14, 15]. Figure 2 shows the HR-CTV and IR-CTV according to GEC-ESTRO recommendations.
HR-CTV and IR-CTV on MRI and CT related to GEC-ESTRO recommendations from the division of radiation oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University.
In comparison to conventional brachytherapy (point A), IGBT keeps the cumulatively curative dose to the target (HR-CTV) while sparing the cumulative dose to normal tissues [16, 17, 18, 19]. After the first clinical results of IGBT were reported by Pötter et al. in 2007, many institutes started to develop IGBT around the world [20]. The selected publications of IGBT are shown in Table 1 and shown promising results in local control and toxicity.
Studies | Imaging | FU time | LC | Gr 3-4 Toxicities | |
---|---|---|---|---|---|
Pötter et al. [21] | 156 | MRI | 42 months | 95% | 11 events |
Lindegaard et al. [22] | 140 | MRI | 36 months | 91% | 1%(GU), 3%(GI) |
Sturdza et al. [23] | 731 | MRI > > CT | 43 months | 91% | 5% GU, 7% GI, 5% vagina |
Tinkle et al. [24] | 111 | MRI with IPSA | 42 months | 94% | 8% |
Castelnau-Marchand et al. [25] | 225 | MRI | 38.8 months | 86.4% | 6.6% |
Mahanshetty et al. [26] | 94 | MRI | 39 months | 90.1% | 3% (GU), 9%(GI) |
Murakami et al. [27] | 51 | CT | 39 months | 91.7% | 2% (GI) |
Ohno et al. [28] | 80 | CT | 60 months | 94% | 1% (GU) |
Tharavichitkul et al. [29] | 47 | CT | 26 months | 97% | 2.1%(GU) 2.1% (GI) |
Pötter et al. [30] | 1341 | MRI | 51 months | 92% | 6.8% (GU), 8.5% (GI) |
Selected studies of IGBT.
BT, brachytherapy, CT, computed tomography, GI, gastrointestinal toxicity, GU, genitourinary toxicity, MRI, magnetic resonance imaging, IPSA, inverse planning simulated annealing.
Ultrasound in medicine was firstly developed by the military (as “sonar”) and was firstly investigated in the 1940s by the method of echo-reflection to detect tumors, exudates, or abscesses [31]. Ultrasound developed very much in obstetrics and gynecology to evaluate the growing fetus and examinations in gynecological conditions [32]. Using ultrasound in clinical practice of brachytherapy divides into three aspects a) applicator guidance, b) CT-based contouring, and c) planning process. The most common use of ultrasound in brachytherapy for cervical cancer is to guide insertion of intrauterine tandem to prevent uterine perforation. Although, in this era, the incidence of uterine perforation was 3% from Segedin et al. [33]. The use of ultrasound can support accurate and safe application in brachytherapy procedures in cervical cancer. Moreover, ultrasound can help the practitioner to adjust the applicator to be a suitable position before patient transportation to the next steps. Figure 3 shows uterine perforation by TAUS.
Uterine perforation during insertion by TAUS from The Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University.
To guide CT-based contouring is very new for using ultrasound. This comes from the pain point of CT-based contouring is an overestimation in comparison to MRI-based contouring [12]. To find the support equipment, some researchers found that the US in transabdominal (TAUS) or transrectal (TRUS) approaches showed a correlation in measurement with MRI [34, 35, 36, 37]. Moreover, the publication from Schmid et al. showed TRUS is superior to CT as it yields systematically smaller deviations from MRI, with good to excellent image quality [38] and Mahanshetty et al. published the correlation of MRI-based contouring versus CT-based contouring supported by TRUS [37]. In recently, the latest publication from IBS-GEC ESTRO-ABS recommended TRUS to support CT-based contouring in IGBT for cervical cancer [39].
The use of TAUS in the planning process was firstly developed by Peter MacCallum Cancer Center, Melbourne, Australia [40]. This process developed from the measurement by TAUS showed a correlation to MRI [35]. In Peter MacCallum Cancer Center, the cooperation of TAUS and MRI (in first application) supported the high-end treatment in brachytherapy for cervical cancer. With this implementation, international publications were reported to support TAUS in brachytherapy [34, 35, 40, 41]. In 2014, they published a survival outcome that showed a 5-year overall survival rate of 65% [42].
The developments of US guidance for brachytherapy are concluded in Table 2.
Studies | N | Modality | Findings |
---|---|---|---|
Van Dyk et al. [40] | 2 | TAUS | TAUS is portable, nonexpensive, and simple to use and allows for accurate, conformal, re-producible, and adaptive treatments. |
Van Dyk et al. [34] | 71 | TAUS | TAUS plan in comparison to two-dimensional MRI image was comparable for target volume ( |
Mahanshetty et al. [43] | 20 | TAUS | TAUS correlated with MR in evaluating uterus, cervix, and central disease for IGBT. |
Van Dyk et al. [35] | 192 | TAUS | The mean differences between TAUS and two-dimensional MRI images were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. |
Narayan et al. [42] | 292 | TAUS | At median FU time of 41 months, 5-yr overall survival rate was 65%. |
Schmid et al. [44] | 19 | TRUS | TRUS is better than CT as it produces systematically smaller deviations from MRI, with good to excellent image quality. |
Van Dyk et al. [41] | 191 | TAUS | At median FU time of 5.3 years, 5-yr overall survival rate was 63%. Late toxicities were 3% for GI, 1.6% for GU, and 2% for vagina. |
Mahanshetty et al. [37] | 25 | TRUS | CT-based delineation using MRI at diagnosis and TRUS during BT seems comparable with MRI-based approach in IGBT for cervical cancer. |
Tharavichitkul et al. [45] | 92 | TAUS | At median FU time of 41 months, pelvic control rate was 84.8%. |
Selected studies showed progression of US guidance in brachytherapy.
BT, brachytherapy; CT, computed tomography; FU, follow up; GI, gastrointestinal; GU, genitourinary; IGBT, image-guided brachytherapy; MRI, magnetic resonance imaging; TAUS, transabdominal ultrasound; TRUS, transrectal ultrasound.
In the Faculty of Medicine, Chiang Mai University, TAUS-guided was implemented 10 years ago to support the conventional brachytherapy during the transformation process from 2D to 3D brachytherapy since 2011. The concepts of TAUS-guided brachytherapy were adapted from Van Dyk et al. [34, 40]. From our process, we performed brachytherapy as an outpatient basis. The workflow of our procedure is shown in Figure 4.
Workflow of TAUS-based brachytherapy.
After walk-in, patients were adjusted to lithotomy position and skin preparation was performed. Then, Foley’s application was performed and at least 200 ml of NSS were filled into the bladder to improve the image quality of TAUS. TAUS was performed during uterine sound and intrauterine tandem applications to prevent uterine perforation. After the application finished, TAUS was performed to measure the dimension of the cervix. Eight measurements (L1-L4 and A1-A4) of cervix dimensions (from intrauterine tandem to the uterine wall) were performed (sagittal and transverse approaches) at the level of the cervical OS, and 2 cm cranially to the cervical OS, adapted from previous work by Van Dyk et al. [40]. Figure 5 shows the measurement of the cervix by TAUS.
Measurements in sagittal and axial views by TAUS from The Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University.
The planning processes of TAUS-guided brachytherapy in our institute were defined as the two methods for delivering TAUS measurements into treatment planning software. When we started TAUS-guided brachytherapy in 2011, conventional brachytherapy by orthogonal X-rays was utilized by the PLATO workstation. At that time, an indirect process (to transfer the measurements from TAUS to the orthogonal X-ray) was performed. After we installed the new Oncentra workstation in 2014, a direct process (to import the DICOM images of TAUS in sagittal view to the workstation) adapted from Peter MacCallum Cancer center [34, 42] was developed to use in our patients. After applicator reconstruction by manual process or applicator library, the eight dimensions were generated to be eight cervix reference points correlated to intrauterine tandem in lateral and anteroposterior view. Figure 6 shows the cervix reference points in the sagittal view of ultrasound sound.
TAUS images showed cervix reference points (black star) in sagittal view from The Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University.
After generation of eight cervix reference points, dwell weight or time was optimized to achieve a sufficiently minimal dose to the cervix reference points of at least prescribed dose (6–7 Gy per fraction). Figure 7 shows dose distribution by TAUS.
Isodose distribution for TAUS-guided brachytherapy for cervical cancer (red line is 100% of prescribed dose that focus on the first 2 centimeter of uterus) from The Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University.
From our experiences, TAUS-guided brachytherapy improved the dose to the normal tissues. It reduced the cumulative overdose to the bladder (>80 Gy) and rectum (>75 Gy) in comparison to standard point A treatment and our intermediate-term results showed the 2-year local control of 88% [45]. From 2012 to 2018, more than 100 patients were treated with this technique. Nowadays, after CT was installed in our brachytherapy unit in 2019, we totally transformed to 3D (volume-based) brachytherapy. We still use TAUS to evaluate proper placement and support our CT contouring.
However, TAUS still has some limitations in patients who cannot have a full bladder (cystostomy or vesicovaginal fistula), and the concept of TAUS in adaptive treatment is still on point-based planning (e.g., cervix reference points). The concept of volume-based approaches via 3D ultrasound is pending [31]. However, TAUS is inexpensive, portable, non-ionizing, and real-time equipment. TAUS supports application safely, CT contouring, and planning itself. TAUS encourages treatment quality in low-resource and high-workload centers to propose improvement in conventional brachytherapy (point A) to adaptive point-based planning (adaptive plan to cervix reference points; 2.5D). Further studies in ultrasound in CT-based contouring and planning should be performed to support the alternatives for brachytherapy in place in which MRI or CT are inaccessible.
Although trends of brachytherapy turned from point-based to volume-based plans via MRI or CT, not all cancer centers can access this equipment. To improve the quality of the point-based plan, ultrasound supports the whole process of brachytherapy, for example, applicator insertion, CT-based contouring, and planning process. TAUS-guided brachytherapy shows promising results by international publications and the cost of TAUS is cheap, and portable. Ultrasound can be applied to all levels of the cancer center to improve the quality of brachytherapy.
The author offers many thanks to all staff of the Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, and Chiang Mai University for supporting all works.
The authors declare no conflict of interest.
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Their distributions can be monitored by satellite remote sensing. Many images of aerosol properties are available from websites as the by-products of the atmospheric correction of the satellite data. Their qualities depend on the accuracy of the atmospheric correction algorithms. The approaches of the atmospheric correction for land and ocean are different due to the large difference of the ground reflectance between land and ocean. A unified atmospheric correction (UAC) approach is developed to improve the accuracy of aerosol products over land, similar to those over ocean. This approach is developed to estimate the aerosol scattering reflectance from satellite data based on a lookup table (LUT) of in situ measured ground reflectance. The results show that the aerosol scattering reflectance can be completely separated from the satellite measured radiance over turbid waters and lands. The accuracy is validated with the mean relative errors of 22.1%. 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. 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},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. 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She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. 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