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Online Supplement. What Was Glaucoma Called Before the 20th Century? Christopher T. Leffler, MD, MPH Stephen G. Schwartz, MD, MBA Francesca M. Giliberti, MD Matthew T. Young, MD Dennis Bermudez. Includes specific pages relevant for cited books. Additional and more complete quotations and translations are provided in this supplement. Constantine the African (c. 1020-1087), translator of Hunain Ibn Is-Haq (Johannitus, 809-877 AD). The 9th century translator Hunain, later called Johannitus, wrote an important treatise on the eye. This work was translated by Constantine the African (c. 1020-1087), who spent time at the school of Salerno. Latin manuscripts of Hunain’s work attributed to Constantine and to Demetrius (Galen 1542, pp. 689-90) were identified by the ophthalmic historian Julius Hirschberg. Hirschberg believed that these represented separate translations from the Arabic. However, Lindberg had a student who evaluated the works and determined that they came from a single translation (Lindberg 1976, p. 232). Our analysis of the terms used to describe the cataract colors supports the idea that these works derive from a single translation (Online Table A). Constantine singled out venetus (Venice-blue) as an unfavorable pupillary color. It has been debated whether Venice-blue refers to the color of the waters around Venice or of the garments worn by Venetian fishermen (David Butterfield, PhD, personal communication, 2014). Benevenutus Grassus (12th or 13th century). Benevenutus Grassus authored De Oculis an ophthalmic work influential well into the seventeenth century (Leffler, Open Ophthalmology Journal, 2014). Grassus was an oculist and a teacher at Salerno and later Montpellier in the twelfth or thirteenth centuries. Grassus cited, and was influenced by, Johannitus (Hunain). Grassus presented a simplified system based on his own observations. With respect to unfavorable cataract colors, Grassus made an important change. Constantine’s translation of Johannitus identified venetus (Venice-blue) as the unfavorable pupillary color. In contrast, the only true color singled out by Grassus as incurable was green, viriditas (Grassus p. 8). With the green cataract, the eye is bleared, the onset is sudden, there may be tearing, and it may be a sequelae of pain (Grassus & Wood 1929 p. 39-40). Grassus noted a separate type of incurable cataract associated with a dilated iris (Grassus & Wood 1929 p. 40). 1 Gerard of Cremona (1114-1187), translator of Ibn Sina (Avicenna, 980-1037). Latin translations of Ibn Sina (Avicenna) also noted the poor prognosis of the green pupil. In this case, the color was specifically attributed to an abnormality of the crystalline humor (viriditate oculi) (Ibn Sina, Bk 3, Fen 3, Tract 2, Chap 34, Ibn Sina 1608 p. 551-2). Avicenna’s work was first translated into Latin in the twelfth century by Gerard of Cremona (1114-1187), who settled in Toledo (McVaugh, Ostler p. 211). Avicenna’s Canon was taught at the medical school of Montpellier by the early thirteenth century (McVaugh) through 1650 (Koh). Avicenna’s discussion of viriditate oculi can be translated as follows: On the greenness of the eye Moreover, greenness occurs either because of a cause in the tunicae or a cause in the humours. The cause in the humours is that, if it was glacial in the eye to a great quantity, and clear and white, and its position is nearer to the outer parts, both of an equal quantity, and less; the eye will be a varied green, and properly if it is not prohibited by the tunica. And if disturbance occurs in the humours, and the crystalline is low, and the white very large, darkening will occur, just like the darkening in deep water. And if the crystalline is deep, the eye will be black. Yet the cause in the tunicae will be the uvea. For if the uvea itself is black, the eye will be black because of it. And if it is green, the eye will become green. And indeed the uvea becomes green either from the deprivation of digestion, like a plant, for in the beginning, when it is born, it is not of an apparent tincture. Rather it verges towards whiteness, and then with digestion it becomes green, and because of this cause the eyes of infants are green, and varied; and the variety of this occurs according to the final humidity, or according to a decrease of the humidity, which the tincture follows, since, when it has been well digested, like a plant, when its humidity is decreased, it starts to become white. And indeed this greenness is because of the dominant dryness. And the eyes of the infirm and of old men are varied because of this reason; since the extraneous humidity is increased in old men, and the innate humidity is decreased. Or the colour emerges there in its creation, not because of the fact that it reaches the uvea, since it is not present beforehand. And sometimes it comes about on account of the clarity of the humidity from which it has been created. And sometimes it comes about for one of two things, when it occurs at the beginning of creation, and it is known through the goodness and badness of sight. And one greenness is natural, another accidental. Yet the variety comes forth from the aggregation of the causes of blackness and the causes of greenness, and it is composed from them between blackness and greenness, which is a variety. And if this variety were primitive, as Empedocles thought, the eye would be green, having been harmed because of its defect from wateriness, which is an instrument of sight. Some black ones are diminished by greens in sight, since greenness does not occur because of the harm in them. And its cause is in the fact that blackness, which is the cause of the whiteness, prevents the penetration of shapes of colours with its becoming clear, because of the fact that it is opposed to 2 translucency and just like that which occurs because of the disturbance of humidity, and likewise, if the cause is the great quantity of humidity. For if there is a great quantity, it will not even respond to the motion of palpation and egress to the front such that therefore it can be cured. And if the eye is green because of the scarcity of white humour, it will see more in the night and in shadows than in the day because of what occurs from the motion of light in a little amount of matter, and it prevents it from becoming clear: for its motion lacks clarity of things, just as it lacks the clarity of what is in shadows after the light. The black eye has less sight at night because of its humidity, for the reason that it lacks palpation and the motion of material to the exterior parts. And a great deal of material is heavier than a little. Moreover, the black eye increases the vision powerfully because of the tunica. (Book 3, Fen 3, Tract 2, Ch 34, Ibn Sina 1608, p. 551-2. Translation courtesy of David Butterfield, PhD, personal communication, 2014). The colors of unfavorable cataracts in Avicenna (gypsum, green [viride], black, and yellow [citrinum]) (1608, p. 564-5) figure prominently as unfavorable indicators in subsequent writings. Avicenna’s Canon was taught at the medical school of Montpellier by the early thirteenth century (McVaugh 1990) through 1650 (Koh 2009). Muḥammad ibn Ibrāhīm Ibn al-Akfānī Muhammad ibn Ibrahim Ibn al-Akfani (c. 1286-1348 AD). Muḥammad ibn Ibrāhīm Ibn al-Akfānī Muhammad ibn Ibrahim Ibn al-Akfani (c. 12861348 AD), who died in Cairo, was a physician referred to by the historian Hirschberg as Shams Al-Din Mohammad Ibn Ibrahim Ibn Said Al-Singari Al-Misri Ibn Al-Akfani, or simply Shams Al-Din. Shams Al-Din wrote “The Discovery of Impurities in Ocular Diseases” (Kashf Al-Rayn Fi Ahwal Al-Ayn) (Hirschberg 1985, vol 2, p. 90-91, section 273.31). Shams Al-Din described “migraine of the eye” (shaqiqat al-ayn) or “headache of the pupil” (suda’ al-hadaqah), which involved deep eye pain, described as a burning or pressure sensation, opacification of the ocular fluids, and sometimes a cataract or dilated pupil (Hirschberg 1985, vol. 2, p. 188). The former term was in use by the 10th century (Hirschberg 1985, vol. 2, p. 118; Leffler, Clinical Ophthalmology, 2015). Jacques Guillemeau (1550-1613). One of the students at Montpellier in the 1500’s was Jacques Guillemeau, who later became the French royal surgeon, and published an encyclopedic system of ophthalmology which became the standard for a century (Leffler, Open Ophthalmology Journal, 2014). Guillemeau specifically cited Avicenna in his definition of glaucoma, and noted its synonym viriditas oculi (Guillemeau 1585, p. 85). Guillemeau wrote: “…glaucoma is properly used when the crystalline humor is dry and thick, and the color of it is green…Glaucoma is uncurable”. 3 Lazare Rivière (1589-1655). Lazare Rivière (1589-1655) continued the medieval Arabic teaching regarding checking the maturity of cataracts by palpation of the eye: “If this Operation be, when some part of the Suffusion floweth down (if the eye be compressed) and appeareth more large, and after returneth to its former station and figure, it is not successful; because the Cataract is not yet ripe, but thin and crude: But if by a compressing with the finger there is no change of the shape and figure of it; it is then ripe, and may be couched with a Needle.”(Riviere 1655, pp. 70-71) Jean Riolan the elder (1538-1605). The hardening of the crystalline lens in glaucoma was noted very rarely by European writers. For instance, Jean Riolan, the elder (1538-1605), who cited Aetius and Galen, wrote of glaucoma (1610, p 443-4): “…or if the crystalline humour is changed into a grey colour (albeit with the admixture of white and green), which blight is called glaucosis or glaucoma, the surface of the crystalline humour is hardened [induratur] and overcome by dryness, and that which should be bright, clear and even becomes uneven. Under glaucoma everything is seen by us obscurely, and as if through shade: light is not seen, which occurrence distinguishes it from a cataract [suffusio]. Why does glaucosis come from old age? Because it is wrinkled by dryness, a condition that is incurable, just like other diseases contracted from excessive dryness.” Jean Riolan, the younger (1580-1657). Jean Riolan, the younger (1580-1657), also wrote that the crystalline lens could be hard in glaucoma (1657, p. 142): “The thickness and hardness of the Chrystallin Humor is properly termed Glaucosis or Glaucoma, because the color thereof resembles that of an Owles Eyes: it proceeds from a cold and dry distemper, and is therefore familiar to aged Persons.” It seems most likely that the characterization of the crystalline as hard was offered as a theoretical property, no more amenable to clinical assessment than whether the humor was dried. Nothing in the statements by either Riolan suggests palpation of the eye. Perhaps by analogy with hypochyma (suffusio), it was inevitable that palpation of the eye would be recommended in glaucoma. 4 Felix Platter (1536-1614). Ancient and medieval descriptions of glaucoma, or the glaucous hue, hinted at phacomorphic or angle-closure glaucoma, but in the modern period we begin to see very clear descriptions of these conditions. Such advances were undoubtedly aided by the gradual abandonment of the view that the crystalline lens was in the center of the eye, with replacement by the recognition that the lens was positioned anteriorly enough to contact the iris. The Swiss physician Felix Platter (1536-1614), who trained at Montpellier, drew the lens anteriorly in 1583 (Lindberg 1976, pp. 175-7). He noted that an error in refraction occurred when “the Crystalline Humor doth not reside more towards the fore parts at the Apple, as it is naturally wont to do, but hath its Scituation exactly in the middle of the Eye.” (Platter 1664, p. 63) Thus, the anterior position of the crystalline was the normal position, and central positioning of the lens was an aberration. In fact, Platter noted that the anterior lens might contact the iris: “The faults of the grapy Membrane hurt the sight, when its hole, which they call the Apple...and letting in that light into the Eye, is either stopt up with some humor, or filth, or is Contracted, or Dilated;...Somtimes this hole is stopt by a Humor and the Passage for the sight is intercepted; and this come to pass somtimes from the proper humors of the Eye the Crystalline and glassy falling into it; as from the change of the Scituation of the Humors as hath been said, and from the too great largness of the Apple as shall be said, it may come to pass, and the sight may be so hindred....” (1664, p. 65) 5 Richard Banister (1570-1626). Richard Banister, the English oculist, is well-known to have described hardness of the eye in gutta serena, which he also called black cataract. This syndrome of a hard eye and longstanding optic neuropathy referred to glaucoma with clear media, such as many cases of primary open angle glaucoma. Perhaps less attention has been given to his description in another passage of green, yellow, and white “cataracts.” Banister was familiar with the writings of Grassus (through the English adaptation by Philip Barrough) and Guillemeau. These green or yellow cataracts were “uncurable” have “the Nerves stopped” (optic neuropathy), a glaucous hue of the crystalline lens (not an anterior membrane), and hardness of the eye. Banister therefore describes many of the criteria we associate with angle closure glaucoma: “Amongst imperfect Cataracts, I may speake a word or two, of Black, Green, Yellow, & White: though they be rehearsed of other Authors, as in the Method of Physicke, by Philip Barrow: For the black Cataract, there is no such disease: for a Cataract is a water congealed, before the Cristaline humour: in this there is no water congealed, therefore no Cataract: ...For the other three imperfect, and uncurable Cataracts, as the humour predominateth, that is the cause of them, so is the colour: yet all have the Nerves stopped, alteration of the colour of the Cristaline humour with a durosity or hardnesse of the whole Eye, and privation of sight.”(1622, p. 60-1) Antoine Maitre Jan (1650-1730). A more detailed description of this condition was offered by French surgeon Antoine Maitre Jan (1650-1730) in 1707. He described a condition called “protuberance of the crystalline,” which he said was often confused with glaucoma. Maitre Jan stated that this condition was often confused with glaucoma, a term which Maitre Jan reserved for a small, dry crystalline lens which was blue (bleu), green (verd), yellow, or white (1707, p. 213). With respect to protuberance of the crystalline, Maitre Jan noted: “This malady is a very particular alteration of the crystalline, in which it is augmented in volume, loses its transparency and natural figure, and becomes more solid than it should be naturally.” (1707, p. 210) Patients experienced loss of vision in one or both eyes, and saw shadows. The pupil was slightly dilated and fixed and sometimes irregular due to pressure from the swollen crystalline lens. The color of the crystalline was like a white horn. (1707, p. 211) Maitre Jan assumed that pain in the eye or head was due to other causes. The condition was incurable. The membrane covering the cyrstalline was thicker and harder (1707, p. 213) It is unclear if this statement was made on clinical grounds, based on his interpretation of ancient teachings, or based on the dissection he performed of a dog who had this condition (1707, p. 216). Maitre Jan’s treatise also contained his observations supporting the new theory of cataract, i.e. that the structure displaced by couching was the lens, rather than a hardened substance anterior to the lens (Hirschberg 1984, vol. 3, pp. 18-19, 226). 6 John Thomas Woolhouse (1664-1733/4). Woolhouse was an English oculist who practiced in Paris. Woolhouse vociferously objected to the theory of Brisseau and Maitre Jan that the cataract was an opacified lens, on the basis that the ancients had always termed disorders of the crystalline lens glaucoma. Woolhouse was indeed familiar with the classical writings, as well as those of Grassus, Riolan, Guillemeau, and Banister (Leffler, Open Ophthalmology Journal, 2014). But Woolhouse added an extra finding which had not been stated explicitly by the ancients: palpable hardness of the eye. As early as April 1707, Woolhouse wrote that the finger could determine whether the crystalline humor was hard in glaucoma (Woolhouse 1717, p. 36): “But I have found an infinity of glaucomas of the crystalline humor, where the vitreous and aqueous humor were healthy. In these one feels a hard crystalline, resisting the finger, which distinguishes them from true cataracts, and no author, that I know, has remarked on the following symptoms and diagnostics that my late father, celebrated English oculist, taught me, and which I never fail to see: a true glaucoma comes ordinarily little by little to the two eyes over time, after severe headaches, after blows to the eyes, after long illnesses, or with advanced age.” The mention of the finger demonstrates that this is not a theoretical concept, but a physical property which could be clinically assessed through palpation of the eye. Woolhouse added: “In looking obliquely or to the side within the pupil (always almost dilated and immobile) one will clearly see that it is only just the crystalline changed…the hard crystalline being thrown forward and strongly pressed forward against the sluice of the iris while dilating the opening makes us believe that the natural position remains there. The most often the little arteries of the adnexa we see totally swollen.” (Woolhouse 1717, p. 36-38) Woolhouse read both Maitre Jan and Kennedy (James 1934). In his lectures of 1721, Woolhouse stated: “But cataracts are in this different from glaucomas. Ye cataracts adhere to ye inside of ye fringe of ye iris and are as it were glued to it. And looking on one side, one may see its threads above or below or only right or left side. But ye glaucoma adheres not to ye Iris unless it be quite unsheathed and fallen out of its calix of ye glassy humor, which all very ripe and hard glaucomas will do in process of time and thereby imitate so perfectly a true cataract if there will be no distinguishing ye one from ye other by a sudden inspection. And then ye feeling is ye only way to have a true knowledge thereof, for such a hard and dry glaucoma reclining upon ye inside of ye iris dilates ye apple of ye eye and makes it immoveable, and without spring if it chance to be pushed upon ye hole in ye iris as a stone in a sling.”(Woolhouse 1721, p. 51.) 7 The same descriptions (with more polished wording) are in the version of the Woolhouse lectures from the early 1720s published by an anonymous student in 1745 (1745, p. 35-36, 99). Woolhouse noted that a glaucoma grown “older and harder” can press against and hinder the motion of the iris (1745, p. 36): “As the Glaucoma [the diseased lens] grows older and harder, it advances more and more towards the pupil, thrusting forwards in the watry humour [aqueous]…When the chrystalline humour is altogether dryed, and become thoroughly opaque, it falls naturally out of its proper sinus…and even touches the inward part of the iris, hindering its muscular motion.”(1745, pp. 35-36) The published version of the lecture notes explicitly noted that palpation could move the lens backwards and thereby leave the eye softer: “Upon this accident the forepart of the eye will feel harder than usual to the finger; and upon reclining the head backwards, and rubbing the eye, the chrystalline humour will fall back…and leave the fore-part again softer.”(1745, p. 99) Modern ophthalmologists speak of an “attack” of angle-closure glaucoma. Woolhouse used the expression “attaquez” (p. 36) or “attaquée” (p. 164) to describe the onset of glaucoma. He also noted of glaucoma, ”This distemper appears to the patient sometimes like little spangles.” (1745, p. 96). Woolhouse stated that the glaucoma was amenable to the “palliative cure” of depression (couching) (1717, pp. 21, 298; 1745 p. 18, 33, 36, 61). Peter Kennedy (b. 1685, flourished 1713). Meanwhile, the English surgeon Peter Kennedy (b. 1685) cited Maitre Jan in 1713, but made one semantic change: like Woolhouse, Kennedy included protuberance of the crystalline lens as a type of glaucoma (1713, (pp. 94-5): “Of the Glaucoma, or Disease of the Christaline Humour. It’s certain, the Christaline is subject to Diseases...especially Decay and preternatural Bigness, both which commonly pass under the Name of Glaucoma...; the first sort is commonly of a light Sky blue, or bright Sea Green...the Pupil keeps its former bigness, whereas in the other sort it enlarges, or the Uvea shrinks, by reason of the Bigness of the Christaline, and its advancing or forcing forward upon the said Tunica; in this case it is generally of a whiter Colour...either sort being confirmed, causes a total Deprivation of Sight, nor is there any Remedy for one or t’other.” 8 Charles de Saint Yves (1667-1731). Subsequent definitions of glaucoma contain many of the elements contained in angle closure glaucoma. The 1722 description of French oculist Charles de Saint Yves seems to imply visual field defects: “That Disease is called Glaucoma, in which the Cristalline is of the Colour of Sea-water…afterwards it becomes whitish, or greyish…a Sort of Alteration in the Cristalline, which supervened to a Palsy of the Visual Nerves…This Palsy is, at first, known by a Dilatation of the Pupil…They still can see Objects, but imperfectly, and only at the Corner of their Eye, because some Fibres remain not totally obstructed...the Patients feel an acute Pain in the Fund of the Eye, and in the Temples; a Gutta Serena follows this Fluxion, and a Glaucoma ensues.” (pp. 231-232) “The Prognostick of this Disease is very fatal; for, when it is once formed, Remedies are of no Service; and, when one Eye is afflicted with it, the other is in great Danger.” (Saint-Yves 1741, p. 234) Later in this work (p. 291) St. Yves gives an excellent description of an afferent pupillary defect in Gutta Serena, but notes that in Glaucoma, the pupil is fixed and dilated. Benedict Duddell (fluorished 1718-1759). Benedict Duddell (fluorished 1718-1759), who studied with Woolhouse, wrote in 1729 that glaucoma merely implied a gray opacity, of the crystalline, lens capsule, or vitreous (p. 166), and in general had no special prognostic significance. However, there was a particular type of gray opacity of the crystalline lens: “Those Opacities of the Crystalline, which happen from Strokes or Defluxions, some are of a grayish Yellow, others of a white bluish Gray…the Crystalline presses against the Edge of the Pupil, and the Pupil is without Movement…there is very rarely Success by the Needling of them.” pp. 108-9. 9 Michel Brisseau (1676-1743). In 1705, French physician Michel Brisseau (1676-1743) stated (correctly) that the structure displaced by couching was the crystalline humor, rather than an anterior membrane (Hirschberg 1984, vol. 3, pp. 14-18). Brisseau was not an eye surgeon, though he made important postmortem observations about the nature of cataract. Brisseau proposed that the green pupil noted by others in glaucoma might relate to a vitreous disorder. Here is our translation of Brisseau (1709, p. 42): “My opinion on these two maladies, is that a Cataract, which is ordinarily white, or closely approaching this color, is only an obscuration and induration of the crystalline, and Glaucoma, which is incurable, is an obscuration of the vitreous humor changed to green, of which the color appears across the crystalline, as if it is this last part which was itself green.” Brisseau wrote that he knew of vitreous opacities in two cases of glaucoma (1709, p. 210). A physician named Barbaroux sent Brisseau the eye from a soldier killed at Dunkerque (Dunkirk). Brisseau found both the lens and the vitreous to be opaque, and therefore, concluded that the soldier had both a cataract and glaucoma. No clinical information about the soldier’s eye condition (if any existed) before death was provided (Brisseau 1709, p. 111). Brisseau also told the story of one Mr. Bourdelot, who was treated by Mareschal, surgeon to the king (premier Chirurgien du Roy) (1709, p. 210). All who saw Bourdelot in life thought that he had a true cataract in both eyes. Postmortem dissection of Bourdelot’s eyes showed a slight yellow discoloration of the portion of the vitreous close to the lens. Brisseau concluded that Bourdelot must have had glaucoma (1709, pp. 154-156). Based on these two cases, it seems that Brisseau never observed a vitreous opacity in a patient who was observed to have a green pupil or diagnosed with glaucoma in life. These limitations notwithstanding, Brisseau believed the green color of glaucoma appeared to emanate from deep within the eye because of its origin in the vitreous (Brisseau 1709, p. 117). 10 Lorenz Heister (1683-1758). Heister was an early adopter of Brisseau’s theory that a vitreous disorder could produce a green pupil. Heister described what he called glaucoma in a 40-year-old man with a dilated and sea-green or gray pupil, sudden pain, vision loss, inflammation in the eye, no hyphema, and a green color deep within the pupil (Heister 1755, pp. 656-7). Here is Heister’s case report: ““Mr. Brunschwitz, a surgeon of Breslau, sent me, June 25, 1721, the account of the case of count Hatzfeld…A gentleman, about forty years of age, had formerly been troubled with the piles, and with gouty complaints, which went off, but were succeeded by a violent hemicrania, and an inflammation of his right-eye, the pupil of which was so much dilated, that scarcely any of the iris could be seen, and he became blind with that eye, the pupil appearing now like a grey cloud: the other eye had also suffered a good deal, and was become weaker, so that he could not bear the light…”(p. 656) “Upon examining his eye, I perceived, upon viewing the pupil, that it had no black appearance, as in a gutta serena, but was of a grey colour, as the surgeon had related, or rather of a sea-green, the cloudiness lying deep in the eye, and not just behind the pupil; so that it was, in my opinion, rather a glaucoma, or opacity of the vitreous humour…”(p. 657) 11 John Taylor (1703-1772). The English oculist John Taylor (1703-1772), who called himself the “Chevalier”, should have known of Duddell’s works, which rebutted Taylor by name. Although often derided as a charlatan, Taylor wrote in 1736 one of the most complete descriptions of glaucoma, which contains many elements consistent with angle closure (pp. 27-29): “And this preternatural Plenitude of the Contents of these Vessels by degrees so increases the Volume of the whole Chrystalline, as to place its anterior Surface immediately behind the inner Circumference of the Pupil…the Volume of the Chrystalline is so greatly augmented, as to raise the Circumference of the Pupil towards the Cornea, and violently press on the Uvea. And by this great Increase of the Volume of the Chrystalline, the Plenitude of the Globe is greatly augmented, as to occasion Degrees of a preternatural Pressure on the immediate Organ of Sight. And this preternatural Pressure on the Uvea and immediate Organ of Sight, is attended with Degrees of a violent Pain immediately in the Fund of the Globe…” (p. 27) “Of the diagnostic and prognostick Signs, and Cure of the several Species of the Glaucoma. When the Patient begins to complain of a Diminution of Sight, on inspecting the Pupil, we perceive Degrees of a small Opacity continu’d thro’ the whole Seat of the Chrystalline…the Volume of the Chrystalline is so increas’d, as to appear immediately plac’d behind the inner Circumference of the Pupil. In the second State of this Disease, the Patient complains of Degrees of the most violent Pain in the fund of the Globe, and of such a Diminution of Sight, as to be unable, from any Direction of the Axis of the Eye, to see more than the Shades and Colours of certain Objects. On examining the Pupil, we perceive the Volume of the Chrystalline to be so greatly augmented, as to have raised the Circumference of the Pupil towards the Cornea, to near ¼ of the healthful Thickness of the anterior Chamber of the aqueous, that the alter’d Chrystalline continues to maintain its healthful Figure, and appears of a dark bluish Colour. In the last State of this Disease, the Patient complains no longer of Pain, but of such an entire Loss of Sight, as to be insensible of Light…that the alter’d Chrystalline…appears of a pale Green Colour.”(p. 28-30) Taylor’s evaluation of the vision with “any Direction of the Axis of the Eye” implies a least a crude evaluation of the visual field. Taylor performed couching, which he believed worked only in the earliest stages of the disease. 12 Johannes Zacharias Platner (1694-1747). German surgeon, and former Woolhouse student, Johannes Zacharias Platner has traditionally been credited with first calling the palpably hard eye glaucoma (Terson 1907; Hirschberg 1986, vol. 6, p. 158) in his 1000-page long Institutiones Chirurgiae, published the first of many times in 1745. In this work, Platner cited Taylor’s treatise on disorders of the crystalline. According to Platner, in glaucoma (Hirschberg 1986, vol. 6, p. 158): “The main pathology lies in the crystalline lens which swells up. This can be recognized with the index fingers. The hard eye will resist finger pressure. In severe cases there will be pain. The color in the eye will change to sea blue [marinae aquae, Platner p. 769]. In older cases the pupil will dilate and this is called mydriasis. With that all faculty of vision disappears and amaurosis begins.” George Chandler (d. 1823). The English surgeon George Chandler (d. 1823) cited Platner in 1775, and wrote: p. 1213. “Another vitiated state of the chrystalline besides those mentioned, is, if that with its covering is much, and in such manner tumefied, as that the other parts of the eye are compressed by it; this is known by the following marks, a hard eye resisting to the finger, swelled and more prominent than is naturally usual to it; there is a certain sensation of weight and pain in it; that which is opposed to view within the eye hath the colour of the sea: At length, if the disease hath been of long standing, the pupil is dilated, and a mydriasis comes on; but because both the vitreous humour and the retina are pressed by the lens, which is much swelled, the faculty of seeing entirely perishes, and a gutta serena takes place; they call this disease a glaucoma.” (p. 12-13) Antonio Scarpa (1752-1832). The Italian anatomist Antonio Scarpa (1752-1832) wrote in 1816: “In general, those cases of amaurosis may be regarded as incurable…those in which the pupil is immoveable…where it has lost its circular figure, or is so much dilated as to appear as if the iris were wanting, having also an unequal or fringelike margin; in which the bottom of the eye, independently of the opacity of the crystalline lens, has an unusual paleness, similar to horn, sometimes inclining to green [verde, Scarpa p. 221], reflected from the retina, as if from a mirror; which are accompanied with pain of the whole head, and with a constant or an intermitting sense of painful tension in the eyeball…” (Scarpa/Briggs, p. 454-455) Scarpa seems to have recognized the relevant signs, but, like Celsus, did not necessarily group them together into a single pathologic entity. 13 James Wardrop (1782-1869). James Wardrop of Scotland, in the 1818 volume of his Morbid Anatomy, defined glaucoma as bluish-gray cataract with a dilated, immovable pupil (plate XII, Fig 2) p. 263. He also noted that vitreous has dull greenish color with insensibility of retina in glaucoma (p. 127). Antoine-Pierre Demours (1762-1836). French oculist Antoine-Pierre Demours, MD stated in 1821 that after cancer, glaucoma was the most serious disease to attack the eye (1821, p. 553). The light of a candle might be covered by a cloud with the colors of the rainbow at the borders (1821, p. 554). Pain, a dilated and irregular pupil appearing the color of the sea, vision loss, and an augmented crystalline ensue (1821, p. 554-5). Conjunctival vessels are injected and the globe becomes hard to the touch (“le globe devient dur au toucher.”) (1821, p. 555) The attack may impair the appetite (1821, p. 555) 14 George C. Monteath (1788-1828), translator of Carl Heinrich Weller (flourished 1817-1831). Georg Josef Beer (1763-1821) of Vienna, Austria, described a condition he termed cataracta viridis or cataracta glaucomatosa, which influenced numerous of his students. One such student, German ophthalmologist Carl Heinrich Weller recorded European ophthalmic teaching, including that of Beer in 1819 (Leffler 2012). Weller's description of glaucoma was translated by Scottish ophthalmologist George C. Monteath in 1821: “A greenish, grey opacity of the vitreous humour, by which the sight is entirely destroyed, or considerably impaired, is called Glaucoma.” This condition involves “increasing, piercing, and rending pains, bursting as it were the eyeball,…the pupil dilates, and becomes elongated towards both canthi, and the sight progressively decreases…After the opacity of the vitreous humour has proceeded to a greater or less length, the lens not unfrequently becomes gradually muddy or cataractous, and assumes a greenish, grey aspect, (Cataracta Viridis, Cataracta Glaucomatosa, which consequently can never be operated upon with success,) increases in circumference, fills the posterior chamber, pushes the iris forwards, seats itself in the already much enlarged pupil, and now even diminishes considerably the anterior chamber.” (Weller 1821, vol. 2, p. 27-28) Weller reprinted a figure from Beer showing the glaucomatous cataract, which he described as sea-green in color, with an irregular pupil (Weller 1821, vol. 2, Plate 2, Fig. 8, pp. 286-291). In summary, the eighteenth and early nineteenth centuries made observations in glaucoma which were consistent with angle-closure. Ophthalmologists in many cases incorporated elevated eye pressure and a greenish hue to the pupil in the diagnosis. On the other hand, even Beer and his followers recognized that the greenish hue was not perfectly sensitive or specific for the syndrome with lens swelling (Weller 1821, vol. 2, p. 291). Weller (1821, vol. 1 or 2) makes no mention of examining patients with a candle or catoptrics. Weller recommended “extract of Hyosciamus or of Belladona” preoperatively (vol 2, p. 17), and for the treatment of iritis (vol. 2, pp. 50-51), or before examining the eye (vol. 2, p. 176). The pupil could be examined with a glass (vol. 2, p. 176). 15 George Guthrie (1785-1856). Weller’s description of glaucoma was cited by George Guthrie, who wrote in 1823: “The disease termed Glaucoma consists essentially in an alteration of the component parts of the vitreous humour…The lens is generally at last implicated…It is never primarily affected…The eye has a general unhealthy appearance, arising from a turbid state of the cornea, which has lost its brilliancy, although in no one part has it become opaque. “ On the sclera appear “several tortuous dark red vessels”. “If the eye is examined by the touch, it will be found rather firmer or harder than natural…The dilatation of the pupil is always accompanied by a marked irregularity of its edge, sometimes rendering it angular, whilst it is always perfectly fixed or immoveable, and occasionally drawn to one side, sometimes to both, rendering the pupil oval. The patient cannot distinguish light from darkness. The diagnosis of a disease that cannot be relieved by operative surgery is now sufficiently established…the pupil, instead of looking of a brilliant black, seems dull…This concave appearance [of the pupil] soon becomes of a dull yellowish colour, tending to green…As the disease advances, and the other symptoms become more marked, the greenish yellow colour increases in intensity, and the space occupied by the lens now becomes gradually implicated by it, the lens swells, presses the iris forwards into the anterior chamber, and a cataracta glaucomatosa is completely formed.” (1823, p. 214-5) Guthrie continued: “The patient cannot distinguish between light and darkness. This capability was lost under symptoms of amaurosis, of flashes of light of various colours, in the eye; and, above, all, the progress of the disease has been, and in all probability continues to be, marked by pain, of a severe and often excruciating nature, not only as affecting the eye, but the forehead and the side of the head. The disease may have come on slowly, it may have developed itself under an attack of acute inflammation, or it may have appeared suddenly…” (Guthrie 1823, p. 216) Guthrie did not describe trauma. Guthrie believed that inflammation of the iris or of the choroid could produce glaucoma (Guthrie 1823, p. 218). The disorder could be characterized as an “attack”. (Guthrie 1823, p. 219) Surgery can be tried if the patient can see light, as without surgery certain blindness will result (Guthrie 1823, p. 219). 16 George Frick (1793-1870). George Frick, an American ophthalmologist who trained under Beer, wrote in 1826 of one type of iritis in which: “The iris is more contracted, the pupil is not dilated uniformly, but acquires an oval or oblong shape. The pupillary margin of the iris projects backwards towards the lens, so that nothing of the smaller circle of this membrane is perceptible. The pains now increase and the vitreous humour becomes affected, presenting a greyish green appearance, or opacity at the bottom of the eye. The lens is soon affected in like manner, exhibits a sea-green colour, swells, and appears to project forward into the anterior chamber, giving rise to the cataracta viridis, or is better denominated by Professor Beer, cataracta glaucomatosa. During these changes, the attacks of pain are rendered more violent and continued, and the varicose state of the eye increases. The cornea having lost its lustre, appears as if completely dead, and the vision is totally destroyed.” (p. 73) 17 William Mackenzie (1791-1868). Scottish ophthalmologist, William Mackenzie, the former student of Beer, and then partner of Monteath, wrote in 1833: “The eyeball, in glaucomatous amaurosis, always feels firmer than natural” (p. 475) “Indeed, in the earliest stage, the greenish reflection, which we designate by the name of glaucoma, appears to come from the very bottom of the eye. As the disease advances, the apparent opacity always of a greenish colour, and often sea-green, is seen as if occupying the centre of the vitreous humour, and at last appears to be immediately behind the lens” (p. 584) “It not unfrequently happens, after glaucoma has continued for some time, that the lens becomes opaque…Ultimately the pupil is dilated, and the retina becomes insensible to light…the pressure of the accumulated fluid within the eye, is probably the cause of the total blindness which results at last…A green cataract is always attended with glaucoma. On dilating the pupil by belladonna, the green appearance presented in simple glaucoma seems to retire to a greater depth behind the iris…Glaucoma is frequently combined with arthritic inflammation…the sclerotic and conjunctiva become loaded with varicose vessels of a livid colour, the pupil dilates irregularly, the lens becomes opaque, and is pushed forward so as almost to touch the cornea; the junction of the sclerotic and cornea becomes of a pearly-white colour; racking pain is complained of in the eye and head, and vision becomes totally extinct. After some time, the inflammatory symptoms subside, and the contents of the eyeball begin to be absorbed, so that it shrinks to less than its natural size, and, instead of the preternatural hardness which it formerly presented, becomes boggy. The symptoms…are the following: viz. sensations of fiery and prismatic spectra, muscae volitantes, misty and indistinct vision, and pain across the forehead…In some instances the glaucomatous eye is still sensible to objects placed to one or other side of the patient, while in every other direction it distinguishes nothing.” (p. 587-588) “In its fully formed stage, glaucoma is absolutely incurable.” (p. 589) “The removal of the crystalline lens from a glaucomatous eye not only lessens very much the greenish appearance of the humours, but improves the vision of the patient.” (p. 590) Mackenzie opined that lens extraction might prevent glaucoma at an early stage, but noted that results were variable due to inflammation in some cases. (p. 590) Mackenzie’s 1833 text contains no references to catoptrics. Mackenzie does note that one Dr. Brewster examined a conical cornea with a candle, and noted aberrations in the reflection (Mackenzie 1833, p. 438), but Mackenzie never states that he examined a patient himself with a candle. Mackenzie mentioned belladonna 93 times (1833), both for diagnosis (1833, p. 477), therapy of central cataracts (p. 482), and preoperatively (p. 502). 18 It is only in 1841 that Mackenzie becomes interested in catoptrics, which he defined as “the theory of reflected light” (p. 6), and the Purkinje images from the front and back of the cornea and lens (pp. 212-214). Mackenzie cites Purkinje’s 1828 paper (Mackenzie 1841, pp. 212-214) William Lawrence (1783-1867). English ophthalmologist William Lawrence wrote in 1844: “The name of glaucoma…is now used to denote an affection of the eye attended with alteration in the colour of the pupil…The first symptom is pain in the head, usually situated over the brow…At the same time, the patient begins to complain of dimness or weakness of sight; and, if we examine the eye, we find that instead of exhibiting its natural black colour, the pupil is sea green, clear green, muddy green, or yellowish green. There is a discolouration, which, if we look at it in a strong light, appears like a yellowish metallic reflection, and sometimes concave; it looks almost as if there was a portion of metal at the bottom of the eye. The pupil at the same time is rather dilated, and the iris sluggish…Sometimes vision is impaired in one eye and not in the other, though the pupil may be equally discoloured in both. In the progress of the disease, vision gradually grows worse…The affection does not always stop at this point, but sometimes attacks the lens, and renders it opaque, so that it is no uncommon thing for cataract to occur subsequently in an eye which was originally attacked by glaucoma. (p. 494) The cataract thus produced is greenish, yellowish, or dirty white, (catararcta viridis or glaucomatosa). Sometimes the lens and iris are pushed forwards, so that the latter is convex; it may even be in contact with the cornea. The external vessels of the globe are sometimes enlarged and varicous… It takes place at or after the middle period of life… The situation of the discolouration has naturally led to the supposition that it arose from change of structure in the vitreous humour, and it has accordingly been assumed, without direct evidence, that inflammation of this structure produces the phenomena of glaucoma….(p. 495) The phenomena of glaucoma, according to these dissections, must be referred to disease of the choroid and retina… The discolouration of the pupil arising from glaucoma, and that from cataract, may be distinguished by the tint of colour. In glaucoma it is green or yellowish green, and if we look at the eye laterally, we see no discolouration, whilst in cataract the pupil is grey, or greyish white, and it has the same appearance in whatever direction it is viewed…(p. 497) The prognosis in glaucoma is unfavourable, we have no means of changing that condition of the internal parts, on which the loss of transparency depends…we 19 cannot restore the vision which has been lost; and all we can expect to do, is to preserve the little sight which remains.” (p. 498) Lawrence recommended bleeding and medications, but not surgery (Lawrence, 1844, pp. 498-9). Albrecht von Graefe (1828-1870). The observers best-suited to understand the greenish hue of glaucoma might be those who were trained to observe it in the pre-ophthlamoscopic era, but could correlate these observations with ophthalmoscopic findings. Albrecht von Graefe (1828-1870) noted “The name glaucoma formerly indicated a vague, expressionless symptom — a sea-green, bottle-green, or dirty-green background of the eye, seen through a fixed, dilated pupil.” (1859, p. 288) For the north European authors (e.g. Platner, Chandler), the color of the sea was sometimes explicitly stated to be green (e.g. Kennedy, Saint Yves, Mackenzie, Graefe) and indicated glaucoma. Graefe continued, “We see glaucoma, in its most typical variety, sometimes occurring in previously healthy eyes in the form of acute inflammatory attacks.” (1859, p. 290) He also noted “…the iris in glaucoma appears more convex anteriorly…” (p. 294) and a patient may see “rainbows around the flame of a candle” and experiences “pains in the forehead and temples” (p. 297) with “the pupil irregularly dilated.” (p. 298) Graefe found iridectomy an effective treatment in glaucoma (p. 313). Graefe also noted some cases of glaucoma after trauma involving “swelling of the lens” which makes contact with the iris (p. 371). Not only iridectomy, but also cataract extraction, if it can be accomplished, is curative in these cases (p. 372). Elsewhere he noted, a “very common cause of increased pressure is a swollen, cataractous lens…” and he noted a case in which extraction of the lens was curative after the failure of iridectomy. (p. 378) He listed “removal of the swollen or displaced lens” as adjunctive treatment, even if iridectomy was primary (p. 380). Although some contemporaries called cases with a similar excavation of the optic nerve “glaucoma”, Graefe was not willing to use this terminology in 1857.(p. 305-8) Of course, Graefe’s contemporaries ultimately prevailed, and expanded the scope of the term glaucoma. By 1858, Graefe became willing to include some other causes under the rubric of glaucoma if they caused the type of damage to the optic nerve due to elevated intraocular pressure that was seen in typical glaucoma (1859, p. 380). Graefe observed this greenish hue of the pupil in his own patients. He described a woman: “in her fortieth year…The left eye had many years before become very weak, and gradually blind…On the right side there had occurred, also many years ago, periodical obscurations and, for more than a year, increasing weakness of 20 vision. On examination, I found on both sides the well-marked appearances of chronic glaucoma: the globes tense…the aqueous humour slightly turbid, the pupils much dilated…on both sides perfectly fixed, of a greenish appearance; the anterior chamber flattened, the iris in spots very discoloured and atrophied. The ophthalmoscope showed…the optic nerve was on both sides very much excavated…functional examination showed on the left side only a trace of quantitative perception of light; on the right side fingers could yet be counted as far off as three to four feet…The field of vision was extremely contracted” (pp. 350-351). Her condition improved with iridectomy. Graefe explained this glaucomatous hue: “The muddiness of the aqueous humour, and the dulness of the posterior surface of the cornea, with the irregular refraction of light (mydriasis) and the yellow lens (age of the patient), are the chief causes of the glaucomatous hue of the pupil…(p. 301-2).” By 1858, Graefe was willing to consider certain disorders involving excavation of the optic nerve to be types of glaucoma if he believed they involved elevated intraocular pressure (1859, p. 380). At this point, he still did not consider amaurosis with excavation of the optic nerve to be a type of glaucoma. However, by 1864, it was established that many, even if not all, cases of such quiet eyes, which Donders called glaucoma simplex, did involve elevated intraocular pressure (Keyser 1864, pp. 4546). Indeed, by 1864, even Graefe was willing to accept such cases as a type of glaucoma (Keyser 1864, p. 45). 21 Type of Lighting Used to View the Pupil. One hypothesis offered to explain the green pupil is that early 19 th century physicians observed the pupil with candle light or daylight, as opposed to the ophthalmoscope (Snyder 1965). To be fair, the author never claimed there was any evidence for this theory, and never claimed he or his contemporaries had observed a green pupil in any eye diseases with any type of lighting. The author merely asked whether the type of lighting might make a difference. The author characterized candle light and day light as “yellow light”, and characterized the ophthalmoscope as “white light.” In reality, the spectrum of light can be quite complicated and irregular for certain types of light, such as fluorescent lighting. Nonetheless, for many radiant light sources, the emitted spectrum can be summarized by the temperature of a black body which emits a similar spectrum. The hotter the color temperature, the flatter the spectrum over the visible wavelengths (400-700 nm). The sun is quite hot, and has a color temperature of approximately 5000 K to 7000 K (Davis 1931, p. 5, 18). In contrast with Snyder’s statement, daylight is considered to be a source of white light (Davis 1931, p. 3-4), because all wavelengths are represented about equally over visible wavelengths. Candle light has a color temperature of 1900 K (Davis 1931, p. 19), which might be considered yellow light. Tungsten incandescent filaments have a color temperature of 2600 to 3100 K (Davis 1931, p. 19). Thus, tungsten light is intermediate between the candle light and sunlight. In addition to characterizing sunlight as yellow, when it is really white, the author focused on one particular author (Mackenzie). It is true that Mackenzie had developed an interest in catoptrics, which he defined as “the theory of reflected light,” in his later works (by 1841). In practice, catoptrics involved examining the eye with a candle, and noting the Purkinje images from the cornea and lens. But this was a later development not only for Mackenzie, but also for the field of ophthalmology. We must remember that the green pupil had been observed for over 500 years. And if the ancient Greek and Roman and medieval Arabic terms for the glaucous hue implied green in some pathologic cases, then this hue was seen for nearly 2 millennia. During most of that time, daylight, which is actually a white light, would have been the most common light source—not candle light. Moreover, we have to remember that it was not until the early 19th century that authors routinely used belladonna to dilate the pupil to examine the eye. But the green pupil and/or mydriasis were observed well before the 19th century. (The ancients knew about dilating agents, but did not routinely use them to examine the eye.) Photographs show that neither candle light nor sunlight is required to observe a green hue in angle closure glaucoma. Nonetheless, Snyder’s hypothesis that the light might make a difference is reasonable, and worthy of further study. We believe William Lawrence’s observations regarding the direction of incident light are relevant (see above). When one views the eye through an operating microscope, one might see a red reflex if the cataract is not too dense. If one pulls away from the microscope and looks at the eye from an oblique angle, the lens will look green. We have observed a similar phenomenon in angle closure glaucoma. The angle of the incident light and the angle of viewing are relevant. 22 Chronic hyphema depositing “blood pigments” in the anterior lens capsule. An alternate explanation for the green hue is that neovascularization produces chronic hyphema (Drews 2006). The hyphema results in the deposition of “blood pigments” in the anterior lens capsule (Drews 2006). Four of the eight figures in this article (50%, Drews 2006) have either a hyphema, or a ghost cell hypopyon. Some of the cataracts did look somewhat green. All 8 of the cataracts were exceedingly dense, so that one did not get the sense was seeing green light scattered from deep within the pupil. It appeared that one was seeing the color of the capsule and most anterior layers of cortex. This appearance fits with the proposed mechanism of pigments deposited on the anterior lens capsule. Some of the historical descriptions did not discuss the depth within or behind the pupil which seemed to be accounting for the greenish hue. But when this issue was discussed (e.g. Brisseau, Heister, Wardrop, Frick, Mackenzie, Lawrence), there was a consensus that the green color was coming from deep within the eye, behind the pupil. In fact, many authors used that appearance to support their contention that the posterior structures (vitreous, choroid, or retina) were primarily affected in glaucoma. We have shown that for many centuries, if not millennia, observers have been astute enough to observe mydriasis and an anteriorly prominent lens. The green pupil has often been noted in association with either or both of these findings. The theory of a neovascular/hyphema-origin of the green pupil might be supported if one could find examples in the historical literature of a green pupil associated with hyphema and incurability, but without mydriasis and without an anteriorly prominent lens. We have not come across such an example yet. Even if such an example exists, this mechanism does not seem to be a dominant theme accounting for the green pupil. 23 References (alphabetical by author): Banister R. A Treatise of One Hundred and Thirteene Diseases of the Eye London 1622. New York, De Capo Press, 1971, pp. 60-1. Bartisch G, Blanchard DL (translator). Ophthalmodouleia. 1996. J.P.Wayenborgh. Ostend. pp. 52-58. Barton K. Secondary Glaucoma. In: DJ Spalton, RA Hitchings, PA Hunter (ed). Atlas of Clinical Ophthalmology, 3rd ed. Philadelphia, Elsevier Mosby, 2005, p. 225 Baxter JM, Alexander P, Maharajan VS. Bilateral, acute angle-closure glaucoma associated with Guillain-Barre syndrome variant. 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Offenbach sur le Main, Bonaventure de Launoy, 1717, pp. 21-298 Woolhouse JT. A Treatise of ye Cataract & Glaucoma. Royal Society of Medicine manuscript. 1721, p. 51 Woolhouse JT. A treatise of the cataract and glaucoma: in which the specific distinctions of those two diseases, and the existence of membranous cataracts, are clearly demonstrated…Compiled from the dictates of the late learned and ingenious Mr. Woolhouse, as taken from him in writing, by one of his pupils. London : printed for M. Cooper, at the Globe in Pater-Noster-Row; and G. Woodfall, at the King's-Arms, Charing-Cross, 1745, pp. 18-99 29