**1. Introduction**

At the present time it is much easier to recognize and to assess glaucomatous changes at the optic nerve than it used to be. This is possible thanks to modern devices and imaging techni‐ ques 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 ev‐ eryday practice, and to mention a couple i.e. CVF, HRT, GDX, OCT, PACHIMETRY, FUN‐ DUS 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 lega‐ cy 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.

However, Archigenes, who practised at Rome in the time of Trajan (98-117 AD), used the

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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

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 night‐

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 in‐ curable condition that involved an effusion in which the pupil becomes thickly coagulated

**Figure 2.** 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

term "ophthalmosglaucos" for a curable blindness that was not caused by cataract.

eyes."

shade.

and dried.

**Figure 1.** Healthy optic disc

Every disease has its history, as much in diagnosing-discovering it, as in quality and ade‐ quate 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 approxi‐ mately 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 his‐ torians 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 combina‐ tion, were described in published texts. Finally, the third period starts with the introduction of the ophthalmoscope (Helmholtz, 1854) to the present.

#### **1.** 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 men‐ tioned in Hippocrates' *Aphorisms* (Figure 2.),lists among the infirmities of the aged a condi‐ tion he called "glaucosis" which he associated with "dimness of vision". Later Aristotel did not mention any diseases called glaucoma particularly, although he helped create the foun‐ dation for research into the pathology of the disease, thus giving his contribution to early glaucoma research.

It is interesting that most authors, by the Roman era, used the term *glaucoma* for what is now known as *cataract*. For example, Oribasius (325-400 AD) quotes Ruphus from Ephesus (1st century AD) as using the term for "that condition of the crystalline body in which the same loses its original colour and instead becomes blue-grey".

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 night‐ shade.

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 in‐ curable condition that involved an effusion in which the pupil becomes thickly coagulated and dried.

**Figure 1.** Healthy optic disc

268 Glaucoma - Basic and Clinical Aspects

glaucoma research.

Every disease has its history, as much in diagnosing-discovering it, as in quality and ade‐ quate 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 approxi‐ mately 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 his‐ torians 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 combina‐ tion, were described in published texts. Finally, the third period starts with the introduction

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 men‐ tioned in Hippocrates' *Aphorisms* (Figure 2.),lists among the infirmities of the aged a condi‐ tion he called "glaucosis" which he associated with "dimness of vision". Later Aristotel did not mention any diseases called glaucoma particularly, although he helped create the foun‐ dation for research into the pathology of the disease, thus giving his contribution to early

It is interesting that most authors, by the Roman era, used the term *glaucoma* for what is now known as *cataract*. For example, Oribasius (325-400 AD) quotes Ruphus from Ephesus (1st century AD) as using the term for "that condition of the crystalline body in which the same

of the ophthalmoscope (Helmholtz, 1854) to the present.

loses its original colour and instead becomes blue-grey".

**1.** First period (400 BC to 1600 AD)

**Figure 2.** 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

could often be obtained; since this seemed to point to the real location of the disease, it be‐

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271

The clinical features of advanced glaucoma, occasionally preceded by attacks of blurred vi‐ sion that recurred with a high degree of uniformity, was first recorded in St. Yves' "Treatise

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 Universi‐ ty of Leipzig. As a distinct clinical symptom, hardness of the eyeball was apparently gener‐ ally 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

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 distin‐ guished 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 pos‐

Duke-Elder in his *System of Ophthalmology,* also, in detail described this second period[2].

With Eduard Jaeger, the grandson and son of distinguished Austrian ophthalmologist, be‐ gan modern ophthalmology and modern ophthalmic exam. He was the first investigator who described and documented with the picture, ophthalmoscopic appearance of the glau‐ comatous disc in the literature. It was a picture from the monocular indirect ophthalmo‐ scope, on which was described the glaucomatous disc as a swelling of the papillary tissues

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 ele‐ vated intraocular pressure. The ring-shaped zone around the disc was officialy named - *halo glaucomatosus*. At the von Graefe's clinic, after many examinations on rabbits with congenital fundus anomalies (i.e. coloboma of the uvea an optic nerve), examiners could not agree from ophthalmoscopic examinations whether observed parts of the fundus are elevated or de‐ pressed. The anatomic examination revealed tissue depression. This was confirmed by von Graefe's assistant, Adolf Weber[5], who will later in his life made significant contributions to the understanding of the mechanisms of glaucoma. His analysis of the monocular indirect

came a prominent sign listed in the literature of the 181h and early 191h centuries.

of the Diseases of the Eyes" (1741) and was described in more detail by Weller (1826).

Germany (1826).

terior sclerotomy to relieve the abnormal hardness.

**2.** Third period (1854. to the present day)

with respect to the surrounding retina[3].

**Figure 3.** Anatomy of the Eye, according to Galen as the Arabs transferred to the West

**2.** 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 emer‐ gence of four characteristics: (1) the consistent failure of cataract operations to improve vi‐ sion, (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 majori‐ ty 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 be‐ came 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 vi‐ sion 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 Universi‐ ty of Leipzig. As a distinct clinical symptom, hardness of the eyeball was apparently gener‐ ally 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 distin‐ guished 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 pos‐ terior sclerotomy to relieve the abnormal hardness.

Duke-Elder in his *System of Ophthalmology,* also, in detail described this second period[2].

**2.** Third period (1854. to the present day)

**Figure 3.** Anatomy of the Eye, according to Galen as the Arabs transferred to the West

This period is marked by the rising awareness among ophthalmologists that technology is a

Glaucoma became more distinct when it comes to adult or elderly patients with the emer‐ gence of four characteristics: (1) the consistent failure of cataract operations to improve vi‐ sion, (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

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 majori‐ ty 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

**2.** Second period (1600 TO 1854)

key to a proper diagnostic.

270 Glaucoma - Basic and Clinical Aspects

pressure.

With Eduard Jaeger, the grandson and son of distinguished Austrian ophthalmologist, be‐ gan modern ophthalmology and modern ophthalmic exam. He was the first investigator who described and documented with the picture, ophthalmoscopic appearance of the glau‐ comatous disc in the literature. It was a picture from the monocular indirect ophthalmo‐ scope, 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 ele‐ vated intraocular pressure. The ring-shaped zone around the disc was officialy named - *halo glaucomatosus*. At the von Graefe's clinic, after many examinations on rabbits with congenital fundus anomalies (i.e. coloboma of the uvea an optic nerve), examiners could not agree from ophthalmoscopic examinations whether observed parts of the fundus are elevated or de‐ pressed. The anatomic examination revealed tissue depression. This was confirmed by von Graefe's assistant, Adolf Weber[5], who will later in his life made significant contributions to the understanding of the mechanisms of glaucoma. His analysis of the monocular indirect ophthalmoscopy revealed several factors, partly optic and partly perceptual, which caused misinterpretations of relative depth in the fundus.

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.

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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).

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 ophthal‐ moscopically observed depression of the optic disc. In his theory that was a result of an ab‐ normally 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

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

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 glaucoma‐ tous process in the optic nerve. It was the earliest sign and for a long time the only glaucom‐ atous 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 *the* glaucomatous atro‐ phy. Schnabel saw the mechanism of the glaucomatous optic nerve disease in a process of imbibition of pathologic fluid from the vitreous by the nerve fibres, a process independent of the intraocular pressure. His findings were partly confirmed and partly refuted by subse‐

Another perspective on the origin and nature of the glaucomatous optic neuropathy was in‐ troduced 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

This Priestley Smith's original notion that the rise in pressure may cause damage to the tis‐ sues of the disc through its influence on blood circulation is valid until the present day.

around its margin which require a considerable time for their full development.

sharp edge of the excavation. Consequence of that was optic nerve atrophy.

The Anglo-Saxon literature preferred terms as acute, subacuteand chronic glaucoma

*primary* and *secondary glaucoma*.

**2. Glaucoma – An optic nerve disease**

and pathologic facts of glaucoma were revealed.

quent investigators.

Later, pathological findings confirmed ophthalmoscopic findings of the optic disc depres‐ sion, what was interpreted as an effect of the elevated intraocular pressure, or- *pressure exca‐ vation of the papilla.* This had profound effect on von Graefe's theory and made him examine all known symptoms of glaucoma and their link with elevated intraocular pressure. This re‐ search turned intraocular pressure from a simple symptom to an "essence" of glaucoma.

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 vi‐ sion. Partial vision recovery with temporary remission mostly occurred spontaneously or re‐ sponding 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 irrita‐ tion, congestion or swelling; lengthen gradually and fused in a chronic form, characterized with the anterior ciliary veins dilatation, shallow anterior chamber, iris atrophy, glaucoma‐ tous 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 *glaucomatous diseases* for a disorders or conditions which secondarily lead to glaucoma and thereby may result in blindness.

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 *glaucoma simplex,* for the glaucoma without anterior segment manifestations and other complications, and *glaucoma with ophthal‐ mia,* for those disorderswhere other manifestations appeared, especially in the anterior seg‐ ment. The common cause of all glaucoma-the elevated intraocular pressure, Doners ascribed to a hyper secretion of intraocular fluid due to irritation of secretory nerves.

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 *primary* and *secondary glaucoma*.
