Chapter 16: Iris Damage

PART FOUR PUPILLARY PATHOLOGY: SYMPTOMATOLOGY CHAPTER 16 Iris Damage CONTENTS A. Summary . . . . . . . . . . . . . . • . . . . . . . . . . . B. Iris Malformations . . . . . . . . • . . . . . . . . . . C. Iris Damage Caused by Trauma, Disease, or Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Trauma . . . . . . . . . . . . . . . . . . . . . . . . . 902 902 908 908 2. Iris Disease . . . . . . . . . . . . . . . . . . . . . . 3. Drug Treatment . . . . . . . . . . . . . . . . . . . D. Age-related Changes . . . . . . . . . . . . . . . . . . E. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . 909 913 914 914 A. Summary A detailed di cussion of iris malformations and disea es would exceed the confines of this book. Further, when pupillary reactions are used as indicators in neuro-ophthalmologic diagnosis, in pharmacologic tests, or in studies on retinal function , it must be assumed that the effector organ is intact. Sometimes, however, the iris i forgotten altogether: for example, in many neurologic text dealing with the pupil the word "iris" is not listed in the index, and none of the iri structures other than the sphincter and dilator muscles are mentioned. Yet pupillary movements depend as much on the condition of the iris as on neurologic events. Though the range of movement of the iris muscles is greater than that of most other muscles of the body, they too have mechanical limitations; they too--as well as other elements of the iris-may be damaged by trauma or disease; they may be malformed from the start; and they will undergo changes with advancing age. These conditions are discussed here. B. Iris Malformations Es er (1935) reported that in ancient Greece and Rome the word discoria was not always used literally to de cribe a double pupil. He cited Ovid, Plinius, and Cicero as using the expression for a malignant, false, damage-mongering, witchcraft-type of gaze. We can only guess at the troubles heaped upon the unfortunate bearers of iris anomalies then and in later times, e pecially among light-eyed people, in whom the defect is startlingly visible. Fortunately, iris malformations are quite rare. For non-ophthalmologists I have listed the terms used for pathologic conditions of the iris that affect the pupil in Table 16-1 and some literature on congenital iris defects in Table 16-2. Congenital iris anomalies range from almost complete aniridia to retardation of growth of particular elements of the iris. For example, the bottom of the optic cup may fail to close over properly, leaving a notch in the lower iris (coloboma). This gives the pupil a " keyhole" shape. Sometimes the stroma alone is affected while the posterior iris leaf is well formed. In other patients the entire iris and choroid may be included. Other pathologic pupil shapes (dyscoria)often with displacement of the pupil (ectopia)-have been described (Table 16-2,A and B): slits or ovals, with their long axis in different directions; hourglass, teardrop, square, or triangular shapes have been described. Each shape depends upon which part of the iris is hypoor hyperplastic. Congenital miosis (sometimes familial) often occurs with high myopia and other ocular defects. In arachnodactyly (Marfan's syndrome) luxation of the lenses 902 causes iris flutter (iridodonesis) , a tremulous movement of the iris when it lacks the support of the anterior surface of the lens. The tiny pupils of patients with congenital miosis, measuring barely 1 or 2 millimeters, and often distorted, are sometimes unresponsive to physiologic stimuli. In other cases they constrict further to light, to near vision, and to miotic drugs (Figure 16-1). Usually they dilate feebly to atropinic substances (to about 3 millimeters or so), and even less or not at all to cocaine and other sympathomimetic drugs. Histologic studies of iridectomy or of autopsy specimens of some patients showed hypoplasia or complete absence of the dilator muscle, or remnants of a dilator that failed to insert at the iris periphery. This is an important observation, since the miosis has been blamed erroneously on a defective sympathetic nerve supply (see "Status Dysraphicus" in Chapter 41). Rarely, eyes have been described with more than one functioning pupil (polycoria ), each surrounded by a band of sphincter muscle (Figure 16-2). The more common iris holes look like additional pupils (pseudopolycoria). The condition may occur congenitally, but pseudopolycoria is more often due to iris atrophy. A ruptured iris root or holes in an iris split by trauma or degeneration also may be mistaken for additional pupils. Because the iris is so thin at its insertion, its root is ruptured easily-producing iridodyalisis-for example, by a blunt blow to tbe eye. Some cases with iris hypoplasia have been exceedingly instructive. For example, Rubel (1913) described a 19-year-old man with almost complete aplasia of the anterior iris leaf. His irises were very thin. The posterior 16. Iris Damage / Table 16-1. 903 Terms used for iris-pupil defects albinism: absence of ecto- and of mesodermal pigment; usu iridocoloboma: coloboma of iris ally (but not always) associated wi.th general albinism iridocyclitis: inflammation of iris and cili~ry bod;Y . . . aniridia: almost complete absence of the iris; usually congenital iridodialysis: (1) torn iris root; (2) (archaic) splitting of 1r1s, -=c=o;:lo:::;bo=m=-a--o::;;f:::,i:::,r:,:is:_:-=-co-=-n=-g=e:::n:::i7tal::,-d::re:::fr:e:;;c:.t-,-;:u:;;s::u-;;,al11l~y-;o:;-ifc-11,o;;;w;;;e;;r;:--rir;:-is;;;--,-;d;f;u-;-;e;-----1 producing more than one pupil to imperfect closing of the optic cup iridodiastasis: ( archaic) iridodialysis corcctasis: abnormal dilation of the pupil (archaic) iridodonesis: visible iris flutter due to loss of lenlicular support l-c::::o~r~e:=c::to~p~1~a- '...::~d~is'.:::p~l:::ac~e~d:i=:p~u::p~il~;~s:'am=c~as:=:e::c';to:':p~i:;:a:-=-'-------- ir idomalac ia: ( archaic) softening (necrosis ) of the iris IJc,;,o=r=ee=,d::;ia~s~tas~"is;:=d~il~ate~d;:.s~ta~te~o:.f=:p::=u:;:pjil,i(ar;;-;;c;i:h:;:a;-fic;;,),---------- iridoplegia: paralysis of the pupillary sphincter coredialysis: iridodialysis ( archaic) iridoptosis: ( archaic) iris prolapse corestoma: kind of congenital miosis with pupil partly occluded iridoschisis: lamellar splitting of the iris .....-~byl.....:.s".=m~al~l~tuf~"t=s~at~pu?:p~il~bo:'.2,r:-"d:.::ec:.r_(,_,ar=c:.::h:.::a:.::cic~)'------------ iris bicolor: sectorial iris heterochromia 1 discoria: double pupil (archaic) iris bombe: iris ballooned forward by aqueous in the posterior dyscoria: irregular pupil shape chamber; due to pupillary plock or seclusion of the pupil ectopia pupillae: corectopia iris process: tissue connecting iris to chamber angle, bridging ectropion uveae: eversion of posterior pigment epithelium at _Pupil the angle recess border; slight ectropion is physiologic; marked ectrop1on is due to contracture of connective tissue or new-formed lii~r~it~i=s:§::~infl~;am~m~a~ti~o_::n_:o~f~th::::::e'..-;1~·rii::.s--:_ _ _ _ _ _ _ _ _ _ _ __ fibrovascular membrane on anterior iris surface keyhole pupil: pupil with coloboma ectropium uveae: (archaic) latinized form for ectropion uveae microcoria: congenital miosis entropion ( entrop ium) uveae : inversion of pup illary border; usually =po=l~y=c=o=r;:ia=:==r:...ar _;e__a~n-o_m_;al:-y-:_m_o_r_e-:th-;--a-n_o_n_e--;(:--tru-e-=-)_p_u_p-:-il;------the result of inflammation . . pseudopolycoria: boles in the iris heterocbromia iridum: color difference between one iris and the other pupillary block: impaired flow of aqueous from posterior to anbeterochromia iridis I sectorial: iris bicolor terior chamber due to the iris and lens being in contact iridectasis: ( archaic) see corectasis rubeosis iridis: reddish discoloration of the iris due to iridectopia: (archaic) see corectopia _____:n~e:..:W:...-..::f::.o~rm=e:.::d:...b::c:l:.::oo=dc.v:..:e:::s::.::s:..:e::.l::.s_ _ _ _ _ _ _ _ _ _ _ _ _ _ 1 1 iridemia: (archaic): hemorrhage in or from the iris seclusion of the puoil: 360 degree posterior synecbiae iridentropion: ( archaic) see entropion uveae siderosis : discoloration due to deposition of iron in iris stroma 1 ..;ir:::.;.c·d;:;e:.::r-:=e:=m;::i;=,ac:.:,:->-(a::;r;.. ;ca-ihs=a=::,i7c=)::-c:-'o~ng"!':::',er:iruc·ta1':rr::-,ian-::;::'i;-;r1-:-·d_i_a_ _ _ _ _ _ _ _ _ _ _ _ lSYnechiae: iris adhesions; anterior= to inner surface of cornea; iridoavulsion: 360 degree iridodialysis posterior = to anterior lens surface iridocyclochoroiditis: (archaic) panuveitis vitiligo iridis: patchy depigmentation of the iris Those underlined are the more commonly used terms. pigment epithelium was intact, and the sphincter muscle could be seen as a whitish band around the pupil. But aside from some fine tissue strands around the collarette there was no stroma. The patient had never been ill and had never had an inflammation of his eyes. He saw well. His anterior chambers were deep and his Jen cs clear. His pupils were of normal size and extraordinarily reactive: they constricted briskly over a wide range, both to light and to near vision, and they redilated promptly after such contractions. Under the influence of cocaine drops they enlarged quickly to maximal size. This case proved that the iris stroma could play little active part in pupillary movements, as had been claimed by many authors (see "Iris Mechanics" in Chapter 9). Obviously, in this case the sphincter muscle and the posterior iris leaf, containing the dilator, did all the work of pupillary dilation and contraction and the absence of the stroma helped rather than hindered the movements. Pellathy (1926) described an 11-year-old boy whose sphincter muscle was involved in addition to the stroma, and who had large, oval, ectopic, and poorly reacting pupils. Three cases with the iris split into its anterior and posterior leaf (iridoschisis) support the same conclusion (Wiegmann, 1913, 1914; Bitter, 1918; Behr, 1930). The first two were due to congenital hypoplasia and Behr's case to trauma. Behr described beautifully how the anterior (stromal) iris ring remained inert while the pupillary portion of the posterior iris leaf disappeared behind it when the pupil was dilated with cocaine; and how the posterior leaf slid out again from behind the stromal layer when the pupil was constricted with pilocarpine. Defects of iris pigmentation may be hereditary, congenital, or acquired. Many pathologic conditions may be responsible. Some of them cause all or part of the iri to become paler than the normal one, while others tend to darken it, or to give it an unusual tinge (Table 16-3). Most of these diseases affect not only the pigment but other structural elements of the iris as well, so that the pupiIJary movements are impaired. In contrast to reactions in neurologic syndromes, the pupils of such sick eyes respond poorly to all physiologic stimuli and to all instilled drugs. In albinism the eyes (as well as the rest of the body) contain only scant or no pigment. This lack, and the consequent light-scatter within the eye, impair vi ion and cause the albino pupil to look pink. In 23 albino children whom we tested with the pupillograph, the pupillary movements were normal (Figure 16-3). Similarly, the pupils of albino rabbits and guinea pigs are comparable to those of pigmented animals. True albinism is extremely rare in cats and dogs, but heterochro- Table 16-2. Congenital iris defects: Literature reviewed A . DISTORTED PUPILS YEAR AUTHOR YEAR 1874 1875 1880 1883 1884 1889 1905 1911 1912 1912 1920 1921 1921 1914 1914 1914 1915 1917 1917 Alexander Sa.melsohn Frickhoffer Auerbach H!ggins Gunn Gallenga Feilchenfeld Hirschberg Lindahl Bohm Seidel Thamascheff Streill Abelsdorlf A. Lowenstein ~ 1921 1922 1922 ~ ~ 1924 ~ ~ 1926 ~ 1927 1929 AUTHOR Niedegger Clausen van Duyse Usher Vog! Imai Sauee Holth & Berner Lawrie Pagenstecher Reitsch Guggenheim Ashby Rosenthal Sedan Charmis AUTHOR YEAR AUTHOR 1929 Longuet 1932 1934 1935 1935 Omoto Kitahara Manes Rieger Takano El Bakll de Saint-Marin Ueno Uagedoorn Mac Rae White & Fulton Begue&al. Goto & Sibata 1941 1941 1942 1948 1950 1954 1955 1956 1956 1957 Iwasaki Sautter Holst Maxwell Huerka.me Gerewitz Kadlecova Lebensohn Liu Kamel Garland& Singer Henkino von Noorden & Baller YEAR ~ Lameis ~ Mans ~ ~ ~ ~ 1937 ~ 1937 1938 1939 1958 1963 1963 B . DISPLACED PUPILS YEAR 1874 1875 1880 1883 1884 1889 1901 1905 1907 1917 AUTHOR Alexander Samelsohn Frickhoffer Auerbach Higgins Gunn Wadsworth Jones Neuburger Abelsdorff YEAR 1920 1920 1924 ~ 1925 1926 1926 ~ 1929 1929 AUTHOR Niedee:e:er Siemens Waardenburg Guggenheim Zeeman Ashby Pagani Alexiades Charmis Massabeili & al. YEAR 1929 1930 1930 AUTHOR Ormond KnaQQ Lameis 1930 Law 1935 Manes ~ Rieger 1935 Takano 1936 de Saint-Marin ~ Bollack & Offret ~ llagedoorn YEAR 1937 1948 1948 1949 1949 1958 1959 1959 1963 1964 AUTHOR MacRae Maxwell Ryerson Dymitrowsl<a Grignolo Garland & Singer Gregersen Walls & neath v. Noorden & Baller Reboul AUTHOR Ormond & Williams A Ormond A Thaden A Omoto Weill A* Redslob* Viallefont & Temple A YEAR 1937 AUTIIOR Pino & al A T938"" Hagedoorn !938 Laval A 1940 Jackson 1940 van Lint 1941 Iwasaki 1941 Sautter* 1941 Theobald A* 1942 Holst* YEAR 1944 1948 1949 1949 1949 ~ 1968 AUTHOR Arbenz A Maxwell Grie:nolo* van Leeuwen Sautter A* Veirs & Brown Agoston & Groot A Neiman & al. A AUTHOR Botteri Sedan Hambresin& Coe.eez El Bakll i!!:oles) Ogata (holes ) YEAR 1949 1952 C . CONGENITAL MIOSIS YEAR 1889 1902 1905 1912 1917 1922 1923 1924 1924 AUTHOR Gunn Maiou Grossman* Salle A Thursfield A Sauee* Holth &Berner* Cresswell Fowler A YEAR 1924 1929 1929 1932 1932 1933 1934 1968 D . POLYCORIA YEAR 1881 1885 1889 1911 1918 AUTHOR Rumsczewicz Higgins Gunn Jamada Giri *= extreme E 1936 1937 1953 1956 hypoplasia or absence of dilator muscle; A YEAR AUTHOR 1958 Meyer ("true") Jaffe & --Knie C'true") 1959 1962 Auvert (!!oles) 1963 Liu ("true") = patients AUTHOR Krasnov & Poliakova (!!oles) Gregersen ("false") Kojima (",escudo") Hcnkind (hole) had arachnodactyly (Marfan' s syndr.) . MORE RECENT REPORTS OF IRIS MALFORMATION - YEAR AUTHOR YEAR AUTHOR CONDITION coloboma with persistent hialoid artery familial anir idia congenital ectopia with subluxation of the lens 1976 1977 lens & eueil ectoeia congenital miosis with sexcataract ectoeia lentis & eueillae unilateral uveal ectopium and infantile glaucoma familial congenital microcoria ectopia in mice congenital miosis with hereditary seastic ataxia aniridia (chromsomal deletion) corectoeia (slit eu.eil) congenital microcoria with goniodysgenes is Bell 1971 1971 Blank Osterczy Sliwinska & starzy.Q)g_ 2 cases with sl it-shaped Shalash& Ayour eu,eils microcoria with vertebroKissel & al. acromeE:alic chan~es idioeathic stromal cyst Mullaney White 122lycoria aphakia , ir is & r etinal Zwaan defects in mice congenital (familial) Caccamise & mydriasis Townes 1973 1973 1974 1975 --1976 - CONDITION 1971 1972 904 YEAR 1920 1927 1932 -- 1979 1979 -- 1980 1982 1983 1984 1984 1986 Townes W. A . Harms Cross Gramer & Krieglstein Tawara & Inomata Rubin& Daly Dick & al, Bateman & al. RiJ2J2le Mazzeo& al . 16. Iris Damage / 905 Figure 16-1. Congenital miosis. The patient was a healthy 17year-old girl. There was no family history of eye defects. She had deeply pigmented eyes, so that her pupils and details of iris structure were difficult to see. For this reason, camera obscura drawings were made from enlarged photographs. The right eye was normal, but the left pupil was tiny, distorted, and displaced from birth (Al). The tissue on the temporal side of the pupil seemed bunched up while it was stretched on the nasal side of the pupil (A2). Because the pupil was poorly aligned in regard to the visual axis, the left eye was amblyopic. Nevertheless the left pupil reacted surprisingly well to light, both directly and consensually. In light it became an almost visible slit. Under the influence of two drops of I% cyclopentolate, it dilated feebly. In C the pupils are shown in darkness (Cl), in light (C2), and 45 minutes after cyclopentolate (C3). B shows the reactions to four short, bright light flashes (left eye stimulated) and to a I-second stimulus of the same intensity. The solid lines on top show the normal pupil, the broken lines on the bottom, the affected eye. Note that the reactions are neither sluggish nor delayed. s s 9 8 7 ~ .....s:: 6 I-< Q) 5 Q) 4 .... .....§ L B 3 "Cl :;:I §' A. Time in 0.1 sec._,. ct 906 / IV. Pupillary Pathology: Symptomatology Table 16-3. Pathologic changes in iris color TYPE OF PA THO LOGY CAUSE OF IRIS DISCOLORATION 1. Trauma Traumatic iritis; especially metallic (siderosis: xenogenous or hematoge nous); secondary infections or atrophy . 2. Benign hyperpigmentation Naevi; melanosis oculi. 3. Neoplasms Diffuse melanoma of the iris, or other tumors. 4. Iris malformations Genetic trait; toxic or other noxious influence in embryonic life. 5. Inflammation lritis or iridocyclitis due to local and/or general disease (Herpes zoster, syphilis, tuberculosis, rheumatoid arthitis, etc. 6. Atrophy Primary atrophy of unknown cause; essential iris atrophy, secondary to ischemia, as in occlusion of cephalic or ocular arterial blood supply due to trauma, arteritis, etc. ; ischemic atrophy of angle closure glaucoma. 7. Neovascularization Diabetic rubeos is iridis; ischemic neovascularization Fuchs's heretrochromic cyclitis is discussed separately and therefore is not included in this Table (see Chapter 4 1). Right Eye Left Eye Figure 16-2. Polycori a. The patient was first seen at the age of 10. Altogether she had six functioning pupils. Her eyes were brown-black- so heavily pigmented that her father, a medical practitioner, had not noticed anything wrong until it was discovered that she saw poorly with the right eye. She had two brothers and a sister who were normal, and no other member of her family was known to have such eye defects. Each eye contained three small, distorted pupils. They all reacted to light and enlarged slightly under the influence of mydriatics. T he right eye was amblyopic while the left eye had normal vision. This is not surprising, considering the eccentric placement of the right eye's pupils. The fundi seemed to be normal on both side . Because of the heavy iris pigmentation, photographs did not show the pupils well. The pictures were therefore drawn by a medical illustrator. (From J. McBride White, Austral. J. Ophthal., 2 l 1974]: 38) Figure 16-3. Pupillary reflexes of an albino child. The patient was 9 years old, with complete albinism. Her irises were pale greyish-blue, her pupils pink, and her vision poor, with marked nystagmus. She attended a school for blind children. Otherwise she was healthy. Her pupils were of normal size, and both the contraction and the dilation moveme nts were typical for children of her age. 16. Iris Damage Table 16-4. / 907 Sector and total heterochromia A. I CIDENCE OF SECTOR HETEROCHROMIA WITH A D WITHOUT IRRADIATION IN UT ERO Cheeseman & Walby Lejeune & al AUTHORS A D PLACE Belfast, 1963 Paris, 1960 ci" 1.41 -1.47 570 5 0. Total 1114 13 1.17 2266 2 0.09 3196 21 0.66 3503 33 0.94 6699 54 0. 1 IRRADIATED children seen . sector heterochromia % heterochromia Total 507 544 OT IRRADIATED children seen sector heterochromia % heterochrom ia 9 B. I CIDE CE OF SECTOR HETEROCHRO1\1IA A D OF TOTAL HETEROCHROMIA Weiss & Janower, Montgomery County, l\Id., 1966 children seen sector heterochromia total (simple) heterochromia incidence of heterochromia 4 07 47 3 50 (100%) (0. 9 %) (0. 06%) (1. 04%) Of the 50 mothers with heterochromic children only 4 had had X-rays during pregnancy From Loewenfeld and Thompson, Survey Ophthal. 17(1973):394-414 mia is common. Heterochromia, or uneven color of the two eyes, can result from several conditions: (1) In "simple' hereditary heterochromia without other defects the two irises can be of distinctly different color-for example dark brown in one eye and blue in the other. Quite often the difference is not as marked: one eye may have a greenish tinge while the other is plain grey; one may be clear blue and the other greyish blue, one hazel and the other light brown. One entire iris may be paler than its fellow, or only portions of the iris in one or in both eyes may differ from the general color (uni- or bilateral sector heterochromia). These areas may be of various ize and shapes, such as quadrantic, wedge-shaped, etc., and sometimes it is difficult to draw the line between "sector heterochromia" and common iris freckles. (2) Slight iris hypopla ia and hypochromia may result from damage to the ocular sympathetic nerve supply. This is mo t common and most pronounced when the injury occurs at birth or in infancy, but may be found (when looked for) to a slight degree in adult patients, u ually a long time after a sympathetic lesion. It has been said that such sympathetic heterochromia can be hereditary but this is an error. However, cervical ribs do occur as familial traits, and they can cause congenital Horner' syndrome by pressing on the sympathetic nerve fibers as they leave the cervical cord to join the peripheral sympathetic chain. The early sympathetic damage then causes a pale iris on that side. (3) In Waardenburg's syndrome (a dominant genetic defect, q.v.) the anterior stromal layer of the iris is hypoplastic or absent. Since this layer contain the cells that normally carry most of the stromal pigment, these eyes have a peculiar pale blue color. Both eyes or only one may be affected; and one or both fundi may have reduced or patchy pigmentation. All other ocular structures are intact, and the eyes are healthy. But other genetic defects, especially an anomaly of the palpebral fissures, and deafness, are associated findings. This type of iris hypo- or heterochromia is found in all human populations and in many animal species. (4) In Fuchs's heterochromic cyclitis (q.v.) the affected eye usually (but not invariably) is paler than the normal one. This disease has been blamed on a defective sympathetic nerve supply, but it is a low-grade chronic iridocyclitis of unknown cause. The question has been raised as to whether factors such as X-irradiation during embryonic life or later would cause iris heterochromia. Results of population studies on this subject were not striking (Table 16-4). In none of these statistical surveys was there consideration of whether heterochromia was due to hyper- or hypochro- 908 / IV. Pupillary Pathology: Symptomatology mia of one eye. Kumer and van Sallmann (1927-28) followed forty-one infants who had received unilateral X-ray treatment for lid angioma. None of these children developed subnormal iris pigmentation in the treated eye, but in a number the iris became darker in the treated than in the non-irradiated fellow eye from 6 months to 6 years after the treatment. The difference between the two eyes wa more marked in brown-eyed than in blue-eyed children, and babies with untreated angioma did not develop uch asymmetries. Among eighteen adult patients treated with radium for cancer of the lid, five showed similar darkening of the iris; but only in one was the color difference clearly beyond the physiologic variability between the right and left eyes of normal persons. This difference between the effects of early compared with later injury is shown also after perforating trauma. Sugar (1968) described a darker iris on the side of injury in all of eleven patients in whom the injury had occurred before the age of 10 years, while in ten patients who had been injured later no iris hyperchromia was observed. C. Iris Damage Caused by Trauma, Disease, or Drugs Any pathologic proce s that harms the iris may, of cour e, affect the pupil, and no comprehensive survey of such conditions is given here. 1. Trauma The iri can be damaged in many ways. Commonly trauma causes the sphincter muscle to rupture or the iris root to tear. Krimer in 1825 described the case of a young man who punctured hi own cornea with a fingernail while drunk. The iris was caught in the corneal wound and Krimer could not push it back and therefore cut it off. After a period of inflammation, the eye healed. The pupil had the shape of a triangle, base down; and there were two large secondary holes on each side of the triangle, from 1 to 4 and from 8 to 11 o'clock, so that only narrow iris bridges remained between these holes and the pupil. The patient saw singly despite his three " pupils.' Any kind of trauma to the iris can, of course, cause tran ient or permanent pupillary dysfunction. In patients with metallic intraocular foreign bodies, a large, fixed pupil is an important early sign. In addition to accidental trauma, ocular surgery may be responsible. This occu rs frequently after keratoplasty in patients with keratoconus, and sometimes also after surgery for retinal detachment and after pan-retinal photocoagulation in diabetes. In many of these, a tonic pupil develops later during the recovery stage. ln such cases with surgery or with visible tissue destruction or hemorrhages the traumatic origin of the pupil defect is certain. Sometimes, however, a large, fixed, or poorly reacting pupil is blamed on a previous accident, but there is reason to doubt the patient's (or the patient's lawyer's) statement, because no sign of injury in or around the eye can be detected, although the damage is said to be recent. It is then necessary to rule out (1) an early tonic pupil, and (2) self-administration of an atropinic drug. This can be done with the help of cholinergic drugs. 1 A tonic pupil will be more than normally sensitive to mecholyl or to weak pilocarpine; a pupil with traumatic iridoplegia (without gross iris damage) usually contracts somewhat to strong pilocarpine, though the response usually is poor; and an atropinized pupil remains unaffected by mecholyl and pilocarpine. Aside from these differences in pharmacologic response, the pupillary reactions in early pupillotonia and in acute iridoplegia may look very much alike. Pupillographic records, however, reveal subtle differences in these movements (Figures 16-4 and 16-5). (1) ln tonic pupils the residual light reflexes in answer to both weak and strong stimuli are delayed and prolonged; but in traumatic iridoplegia the latencies are longest with weak light flashes, and they shorten when the light intensity is increased. (2) In tonic pupils with residual light reflexes, repeated stimulation with short stimuli tends to lead to continuous contraction with extremely shallow individual oscillations because redilation after light-induced contractions is so slow. In contrast, in traumatic iridoplegia the pupil tends to "escape" the relatively ineffective short light stimuli and to redilate progressively from each flash to the next. A large pupil that responds poorly to both physiologic stimuli and drugs is also seen in eyes injured by foreign bodies. When the eye contains a metal splinter (especially iron), siderosis-shown by a yellowish-brown discoloration of the iris-will, in time develop. But sometimes the patient is unaware of the problem: an apparently trivial accident has been forgotten; and the mydriasis, developing months later, may precede all other visible signs of the injury. Unexplained internal ophthalmoplegia should serve to alert the ophthalmologist to the possibility of such a condition; and iris discoloration or minute scars should be looked for diligently, since untreated siderosis may destroy the eye. With strictly local acute trauma, caused by a small object hitting the eye, transient deformation of the pupil 1. In acute cases it may be best to wait for a time before using cholinergic drugs because a hemorrhage may be started in patients with fresh trauma. Such a waiting period is desirable also because it will allow time for pupillotonia to become more distinct, and for traumatic iridoplegia to improve. These changes should, if possible, be documented with flash photographs taken (I) in darkness and (2) in light. Drug use is sometimes revealed by such records showing erratic changes in pupil size from one examination to the next. 16. Iris Damage I 909 may result. Bakker (1944) described such an accident to his own eye. A small spring on which he was working escaped his fingers and struck his eye near the limbus; and when he looked into the mirror he was astonished to see the pupil drawn out into a long, thin triangle, with the apex almost at the limbus near the site of impact. This lasted only a short time, and then the eye returned to normal. We saw a 6-year-old boy who had been hit in the eye with a small pebble. A pupil segment on the side of the injury bulged out so that the pupil was pearshaped. During light reflexes the bulging part of the pupil lagged behind the round portion, and the pear became elongated. Within the next 2 hours the bulge receded and the pupil became oval and then returned to its normal round shape. Such short-lasting pupillary distortions probably are caused by transient dysfunction of short ciliary nerve twigs (our case) or stimulation of long ciliary nerve twigs (Bakker) rather than by injury to the iris muscles. 2. Iris Disease The iris is involved in many general and eye diseases, and numerous reports exist describing various pathologic pupil shapes and movements. A few cases are shown in Figure L6-6,C to J. Among infectious diseases, herpetic and syphilitic iritis, iridocyclitis, and choroiditis were especially common. After attacks of ophthalmic herpes zoster, patchy iris discoloration and sector or complete iris atrophy with various pupil signs are not s~-A-----------1 4 I 3 l-rm~rhrmTTTri~-rTTTTTTm'~TTTTTTrm'rTTTTTTTTrhrrrTTTTTrTTTTTTrrrfrrmnrmTTTrrr1 Figure 16-4. Early pupillotonia. The patient was 32 years old. Three weeks before examination she had noticed blurred vision in her right eye. She looked into the mirror to see what was wrong and was startled to discover that the right pupil was much larger than the left one. The pupillogram showed, however, that in darkness the bad pupil (solid lines) was slightly smaller than the good one (broken lines; see Chapter 24 for an explanation of this feature). lt reacted very slugglishly to all types of light stimuli: short (A) or longer (B to D); dim (Band C, attenuated with neutral grey filters of 2- and 4-log density, as indicated) or bright (A and D). In all reactions the contraction and the dilation were distinctly delayed (see small arrows at the beginning of these movements). Note that in A the right pupil was barely able to follow a 1-persecond stimulation rate, due to the extremely slow and delayed redilations. Figure 16-5. Traumatic iridoplegia. Three weeks before examination the patient, a 52-year-old nurse's aide, sustained a glancing blow to her right eye by a patient's finger as she was trying to lift him into bed. For 2 days the eye was red , tearing, and painful; and on slit-lamp examination a corneal abrasion and a large, fixed pupil were found. When the pupillogram was recorded the affected right pupil was substantially larger than the normal left pupil. Small (residual or regained) light reflexes were present. These were delayed and prolonged as in the tonic pupil shown in Figure 16-4 when dim light flashes were used (B). However, they became somewhat prompter when the light intensity was increased (C), and the timing was almost normal with bright light (D). In addition , the pupillary oscillations evoked by short, repeated light flashes (A) were more lively than those recorded in the patient with the tonic pupil, and the pupil of the injured eye " escaped," due to the relative ineffectiveness of the short light stimuli. In this case the use of an atropinic drug could be excluded, (1) because the residual light reflexes of atropinized eyes are shortened rather than prolonged, and (2) because the patient's right pupil constricted to weak pilocarpine, though not as extensively as the left pupil. The patient was examined twice more, 4 and 9 weeks after the first test. Her pupil gradually recovered fully. 910 / IV. Pupillary Pathology: Symptomatology rare (see Chapter 32). Anatomic specimens in such cases howcd the atrophy to be ccondary to severe ciliary perineuritis and periarteritis, with thrombosed vessels, pigment migration, and ynechiae. General diseases like sarcoidosis and amyloidosis al o may cause internal ophthalmoplegia (often followed by the tonic pupil yndrome), due to invasion of the ciliary ganglion of the eye ( ee Chapter 24). The common association betwen distorted Argyll Robert on or fixed miotic pupils and iris damage in patient with neurosyphili prompted some authors to believe that the iris rather than the central nervous y tern wa the ite respon ible for these pupillary syndrome . Other held that the iris defect in such patients was caused by the spa tic miosis: the atrophy wa aid to be due to "chronic ovcrstretching" of the iris. However, many patients with tiny Argyll Robertson pupils had a perfectly normal iris; others had had the pupil syndromes for many years and even decades •. • , • 83 . 84 - • •- •- •- •• A5 85 A6 86 l--l--c,-,- 1 - 1 -1-1-1 Figure 16-6. Pupillary size and shapes in different cond itions. The pictures are outline drawings made from enlarged (X 15) infrared cinematographic film negatives. For these pictures the patients looked straight into the camera lens to avoid distortions of the images. A scale for pupillary size is given at the lower left margin of each picture. A and B show pupils in normal experimental subjects, C to J those of patients with various diseases. All experiments were done in darkness. A and B: All subjects were healthy unless indicated otherwise, and none of them felt ill on the day of examination . Their vision was normal, and their pupils reacted well to all stimuli. In row A the pupils were round, in 8 they were not. The subjects were: A', a 9-year-old girl; A2, a 20-year-old woman: A', a 55-year-old man with essential hypertension; A4, a 62-year-old man; A', a 70-year-old woman; A•, a 91-year-old woman. B', a 23-year-old man with depressive psychoneurosis; 8 2, a 27-year-old man; H', a 55-year-old man with progressive hypertension; 84, a 63-year-old woman with esse ntial hypertension; 8', a 76-year-old man; n•, a 78-year-old woman. before iris pathology developed; in still others iris damage was present by not Argyll Robertson pupils. The iris defects therefore could not have caused the pupillary syndrome (or the reverse): the two conditions were linked by the disease that caused them both. An iris damaged by syphilitic iritis may react poorly or not at all to instilled drugs. Some authors have blamed this unresponsiveness on a defective autonomic nerve supply. Poor reactions of Argyll Robertson pupils to mydriatic drugs were said to prove that the miosis in that syndrome was due to impaired sympathetic nerves. However, in the absence of iris damage Argyll Robertson pupils react well to atropinic and to sympathomimetic drugs; and further, Argyll Robertson pupils that enlarge poorly to mydriatics also contract poorly to motics: all drug responses are reduced or lost because the effector organ (the iris) is impaired. In a number of other diseases also, the ocu lar defects were blamed on sympathetic nerve deficit. For example, the pale iris in Fuchs's heterochromic cyclitis, and the discolored irises and congenital miosis sometimes seen in Marfan's syndrome and in essential facial hemiatro- •• • .F'• C to F: The pictures were derived as for A and 8. The patients were in darkness. They had the following non-specific pathological conditions: C', and C' and C3 were women 26, 32, and 37 years old, respectively. Each of them had a tonic pupil on the left side, while the right eye was normal; D', a 60-year-old man with a leftsided preganglionic Horner's syndrome; D', a 60-year-old man with a left postganglionic I lorner's syndrome; D', a 27-year-old man with left heterochromic cyclitis (Fuchs's syndrome) . Note the distorted pupil; it reacted poorly to both physiologic stimuli and to drugs. E', a SJ-year-old man who had sustained a brain injury and had bilaterally sluggish pupils; E', a 35-year-old woman after severe head trauma, with sluggish pupils on both and extraocu lar motor deficit on the left side; E3, a 46-year-old man with an orbital tumor on the left side. F', a 37-year-old woman with diabetes mellitus and somewhat sluggish pupils; F', a 59-year-old man with two fairly small, slow pupils and diabetes mellitus· F', a 59-year-old woma n with a posthcrpetic fixed , small pupil on the left. 16. Iris Damage / 911 phy, as well as the poor pupil reflexes and inextensive drug reactions of these eyes, all were attributed to congenital defects of sympathetic nerves; and a preposterous theory was invented, " uniting' these fundamentally different pathologic conditions under the umbrella of this explanation (see Chaper 41 below). The pupil signs in these diseases are, however, due to iris damage (for an analysis of these questions, see Loewenfeld and Thompson, 1973). In diabetes mellitus iris damage probably causes or contributes to the peculiar sluggishness of pupil movements seen so often in that disease (see Chapter 34). A typical defect of the posterior pigment leaf is fairly common in diabetes: the posterior pigment cells are loosened and bloated with glycogen; further, there arc many small vacuoles, blisters, and cysts. These tend to burst and to release pigment granules. The iris vessels are thin and sclerosed, and stromal atrophy and depigmentation may develop. Rubeosis iridis, a reddish discoloration of the iris because of new formation of a network of very fine vessels and supporting connective tissue on .62. •"• - •• J2. .Jl. -· --R--l 63 H3 13 J3 G to J: Distorted pupils in syphilitic diseases. Experiments and graphing as in the previous two pictures. G', a 40-year-old man with syphilis but with normal pupillary movements; G2, a 32-yearold woman with neurosyphilis and slow, inextensive light reflexes on both sides; G', a 41-year-old woman whose pupils were fixed to light but dilated well to psycho-sensory stimuli; H', a 33-year-old man with general paresis a nd bilaterally sluggish pupillary reflexes ; H2, a 40-year-old man with lues cerebri and very sluggish pupils on both ides; H3, a 36-year-old man with congenital syphilis and almo t fixed pupils; I', a 63-year-old man with tabes dorsalis and sluggi h, asymmetric light reflexes (R > L)· 12, a 50-yearold woman with tabes dorsalis and bilateral Argyll Robert on pupils; 13, a 40-year-old man with bilateral Argyll Robertson syndrome. J', a 46-year-old woman with neurosyphilis and an Argyll Robertson pupil on the right, a sluggish pupil on the left side; J2, a 45-year-old man with lues cerebri, a sluggish right pupil, and an Argyll Robert on left pupil; J', a 58-year-old woman with lues cerebri and bilaterally luggi h pupil . the anterior iris surface, may develop as a result of tissue hypoxia, presumably from ischemia. These structural changes need not be obvious to impede iris movements. For example, Friedman, Feinberg and Podolak (1967) found the light reflex latent period prolonged in diabetic patients (compared to normal subjects of matched age) even when no iris damage was clinically obvious; and many authors have described poor pupillary dilations to mydriatic drugs in diabetic eyes without visible iris defects. Histologic studies in such eyes revealed more damage than could be detected clinically. The same is true in patients with myotonic dystrophy (Steinert, q.v.), whose sluggish pupils resemble those of patients with diabetes; histologic examination of such eyes revealed previously un uspected iris pathology. Recently electron-microscopic studies have shown subtle degenerative changes of sympathetic and parasympathetic nerve endings in the iris of diabetic eyes. Pathology in these eyes is thus complex. Iris neovascularization, like neovascularization elsewhere in the body, is probably a response to ischemia, and it is found in many conditions beside diabetes: after inflammations, in eyes with tumors or with vascular occlusions, and after surgical procedures that interfere with the ocular blood supply. Even more remote vascular conditions such as the aortic arch or subclavian steal syndromes, vertebro-basilar insufficiency, carotid occlusion, carotid-cavernous fistula, or cranial arteritis may prompt neovascularization or atrophy of the iris. In generalized dysautonomic states with marked va cular hypotension, such as the Shy-Drager syndrome, iris atrophy also occurs. Besides these postinflammatory and ischemic processes, other kinds of iris atrophy may occur. The troma alone or the entire iris may be affected, so that iris holes develop. The reason for this (usually unilateral) essential iris atrophy is unknown (Figure 16-7 and Table 16-5). Another form of iris atrophy is hyaline degeneration, with iris tissues transformed into a transparent, homogeneous mass, especially near the pupil border. A. Lowenstein and Foster (1945) described a rare form of progressive atrophy of the anterior iris layer called iridoschisis. The iris stroma separates from the posterior leaf, and shreds of its radial fibers 'float in the aqueous in much the same fashion of seaweed in a pool of water" (Haik et al., 1952). These fibrils have come loose at their pupillary end while they remain attached at the peripheral end. The posterior iris leaf remains uni_mpair~d.' and pupillary movements are preserved. This cond1t1on develops without known cause. Idiopathic atrof!hY of the posterior epithelial layer also occurs: the dep1gmented patches on the posterior iris surface can be demons~rated by transillumination of the eye (Scheie and Fle1schhauer, 1953). Pigment that is released forms de_posits on the cornea similar to Axenfeld-Krukenberg spmdles; and secondary glaucoma may develop due to clogged aqueous outflow channels. 912 / IV. Pupillary Pathology: Symptomatology Table 16-5. YEAR 1875 1879 1901 1903 1904 1909 1910 1911 1912 Iris atrophy: Literature surveyed AUTHOR Samelsohn Hutchinson Siegrist Meller Meller {age} Seefelder Axenfeld Igersheimer Attias YEAR 1913 1914 1918 1929 1929 1932 1934 1935 AUTHOR Axenfeld Reitsch Fuchs Longuet Massabeili &a] Hambresini & Co22ez Barr Muirhead YEAR 1937 1937 1948 1949 1949 1953 1954 1955 1958 AUTHOR YEAR v . Grosz 1958 McKeown Lasley 1959 Chang & Ojers Zanen 1959 Heath 1960 Alaerts 1962 Huerkamp 1966 Krasnov & Poliakova AUTHOR Scheie & Fl e ischhauer Gedda& BerardMagistretti Gregersen Gazala Fenton & Hunter Rohm.er & Leutert (age) ll Only literature directly related to pupil movements was surveyed . A detailed consideration of these pathologic processes exceeds the subject matter of this book. Figure 16- 7. E sential iris atrophy. In A and B the ~am~ ~ye is shown in different stages of the disease. C shows d1fl usc ms atrophy in a differe nt patient. T he white dots outline the pupil edge. (P hotographs by courtesy of Dr. H.S. Sugar, Detroit, Mich. ) C ... 16. Iris D amage Table 16-6. . old eyes Clinical and hi tologic changes m PATIE TS # - 83 2 -3 71 -- 2 4 85 5 -6 -7 75 73 8 71 9 69 -- 83 -10 ns 11 71 -13 -14 76 -- -12 79 78 PUPIL B mm A HISTOLOGJC EXAMI ATION - ---- PUPILLARY l\'lARGI ' Depigmentation Homogenous membrane Hyaliniza zation of iris border Muscular Degeneration Arteriosclerosis sphincter dilator 2.5 mm 2.5 +++ - ++ +++ +++ +++ 3.0 3.0 + + +++ +++ +++ +++ +++ +++ ++ ++ 4.5 +++ ++ +++ 3.0 ++ ++ +++ ++ ++ +++ +++ ++ ++ ++ ++ + - + ++ +++ ? + -- --3.0 4.0 - - --- - - --3.5 5 . 0 ---3 . 0 5.0 --0 -33.0 -5 .. 5 6.0 --0 6. 0 -32.5.--6 .0 -3 .--0 6. 5 --0 6. 5 ---43.5.7.0 -3.5- --7.5 913 or WI·thout fixed miotic pupils CLINICAL EXAMJ ATIO AGE years 1 WI"th / ++ ++ - ++ + ++ ++ +++ ++ + ? +++ - + - - + + - - ? + ' - - + + - - ++ ++ ++ ++ - - - ++ - - - ? - - - - - Slightly modified after Larsson & bsterlind, 1943. B = before drugs, and A = after mydriasis induced by instilled 1% atropine or 1% homatrop_ine plus 2% cocaine; measurements are for pupillary diameter; the symbols mean the followmg : +++, ++, and + are degreed of pathologic change; - = no pathology, and ?_=no pat_hology coul~ be determined ( consult original publication for further details) . Note that dep1gme?t3:t10n and hyal_me changes at the iris border did not hinder extensive pupillary responses to mydriatic drugs, while vascular and iris muscle pathology paralleled the functional deficit more closely . It has been aid that denervation of the phincter or dilator of the pupil will, in time, lead to atrop hy of these muscle . And uch damage early in life doe appea r to interfere with their normal development. Fenton and Hunter (1965) de cribed phincter hypopla ia in two eye denervated for more than 40 year ( one of them since birth). The dilator mu de and other iri tructures were normal. However, mooth mu de in genera l do not deteriorate readily when they are deprived of their nerve upply, a triated mu de do. And ector or total denervation of the pupillary phincter (in tonic pupils) or of the dilator (in Horner· ndrome) u ually go together with supemomwl contraction of the affected muscle egment to cholinergic or to adrenergic drugs, respectively. The e reaction could not take place if the denervated mu de had atrophied. 3. Drug Treatment Vogt ( 1921) noticed the appearance of iri cy t at the pupillary border in patient treated inten ively with pilocarpine or e erine. The cy t developed o er a few months and then vani hed uddenly, apparently becau e they bur t. Thi wa later encountered on a larger cale when children were treated for quint with trong miotic like Mintacol or DFP (Gerewitz, 1954; Hallermann , J954; wan, 1954; Funder, 1955; trau and Courads, 1955; Christensen et al. , 1956; Weeker and Gush in, 1958; and later authors). Prolonged miotic treatment in glaucoma also has been said to affect iris structure and to make the pupil permanently smaller than it otherwise would be, even though the drug do e are much lower than they were in squint therapy (Weekers and Gushin, 1958). We have reservations about this statement. When we recorded the pupillary reactions of patients with unilateral glaucoma 72 to 96 hour after pilocarpine treatment had been stopped, the pupil of the glaucomatous eye was sometimes larger, sometimes smaller, and sometimes the same size as the pupil in the normal eye. Further, the pupillary reflexes did not seem impaired: in many cases the curves for the good and for the bad eye ran entirely parallel (Schoenberg an d Lowenstein, l 942, and cases seen since in our laboratory). Others who have recorded pupillograms in patients with unilateral glaucoma appear to have had . imilar experience (Nicolato, 1943; Citroni, 1955; Matteucci, I 956; Marone, 1959). Even if relatively small pupils were the rule in eyes treated for long periods with miotics the treatment need not be responsible. Everyone's pupils become smaller with age; and except in unilateral case , it is difficult to judge whether iris c~anges (if present) are caused by the treatment, by the d1 ea e, or by the aging process. 914 / IV. Pupillary Pathology: Symptomatology Long-term treatment with atropine does not seem to damage the iris, at least in adults. For example, Fuchs (1918) described a woman thirty-eight years old whose eye had been treated with atropine for twenty-five years. When the drug was discontinued, the iris looked healthy and the pupil resumed normal reflexes, equal to those on the untreated side. Our experience was similar: in a 69-year-old man whose right eye had been treated with atropine for eighteen months we could not discover the slightest anomaly of pupil size or reactions in detailed pupillographic tests, once the drug had worn off. D. Age-related Changes It ha been known for a long time that in old age the pupils become smaller and less mobile than they are in the young; and some old eyes have miotic pupils that react only poorly-if at all-to physiologic stimuli and to instilled drug . Fuchs, Meller, Axenfeld, and many others decribed hyaline degeneration in the iris stroma, especially near the pupil edge, in the area between the sphincter muscle and the posterior pigment epithelium. In advanced cases the entire area was tran formed into a homogenous, transparent ring of hyaline tissue, and the darkly pigmented iris ruff at the pupil margin was lost in segments of the iris or all around the pupil. These changes were thought to be respon ible for the sluggishness and poor drug reactions of the pupil in such eyes. Lar son and Osterlind found, however (1943), that this kind of degenerative damage was not always present in old eyes with small, fixed pupils; and further, it could be seen in eyes whose pupils dilated well to drugs. These authors' histologic studies indicated that miosis and poor drug re- sponses are observed when there are atrophic changes in the iris muscles, and when the iris vessels show sclerosis, thickening and other degenerative defects of their walls (Table 16-6). Such marked functional and structural defects, under the name of "senile miosis," were blamed on age alone. But there are many old people whose pupils constrict briskly to light and dilate well to psychosensory stimulation and to mydriatic drugs. Age alone thus does not suffice to bring on "senile miosis," which must be considered the result of pathologic processes of late onset. The gradual decline of pupillary size with advancing years that occurs in healthy eyes begins soon after the period of growth and development has come to an end, and then progresses linearly, decade after decade, to old age. It begins long before senile iris changes can be discovered, and is due to neurologic changes, not iris defects. This development, as well as other subtle age changes of pupillary movements, are described in the physiologic section of this book (see Chapter 10). E. Conclusion It makes no sense to go on enumerating the many pathologic processes that can involve the iris and thereby alter pupillary shape and reactions. They are the proper subject of a text on ocular pathology. The point we want to stress is this: pupillary anomalies need not always be caused by neurologic lesions. A defective iris-brought about by the disease process under study or occurring coincidentally-may be at fault. If this simple fact had been kept in mind firmly at all times, a great deal of nebulous speculation could have been avoided.