OPTIC NEUROPATHY of GRAVES's DISEASE by John Warren Henderson, M.D.* Papilla

OPTIC NEUROPATHY OF GRAVES'S DISEASE BY John Warren Henderson, M.D.*

Ophthalmologists who have frequent contact with people afflicted with Graves's disease are aware that many of these people complain of some blurring of vision. In the majority the disturbance of vision is caused by a change in the refraction of the eye secondary to the factor of increased pressure in the orbits. Less frequently the blurring of vision is due to some change in the cornea secondary to its exposure, or to glaucoma which develops in cases of exophthalmiios accompanied by a marked increase in orbital pressure. In an occasional case, papilledema is noted on ophthalmoscopic examination, and any defect of vision that subsequently develops is attributed to this disturbance at the optic papilla. It is not well known that a disturbance of vision among these people with endocrine exophthalmos may also (levelop due to an intrinsic disorder within the optic nerve which may not be accompanied by papilledema or any other visible manifestation of ocular dysfunction except loss of vision. In such situations the loss of vision cannot be explained except by performing studies of the visual fields. Throughout the voluminous literature on the subject of Graves's disease there are several reports of cases wherein a visual disturbance due to some lesion in the optic nerve was suspected, but because an examination of the visual field was not performed the location of the disor(ler within the optic nerve was not proved. To identify this particular type of disturbance within the optic nerve the term "retrobulbar neuritis" most frequently appears in the literature. In a recent review of the various types of disordlers thlat may affect the optic nerve during the course of en(locrine exoplhthalmos, Wagener (i) included references to reports oni "retrobulbar neuritis" and "optic neuritis." In the majority of these references only one or * From the Section of Ophthalmology, Mayo Clinic and Mayo Foundation, Roch- ester, Minn. The Mayo Foundation is a part of the Graduate School of the University of Minnesota. 354 Johin Warrent Henderson two examples are reported, and, because the observation periods are so short, a long-term evaluation of the course andl prognosis of the disease cannot be imade. Only in the reports of Igersheimer (2; six cases) and of Hedges and Scheie (3; six cases) are a sizable number of cases of this disease reported. Four of the six cases reported by Igersheimer (his Cases 2, 3, 4, and 6) can, by reason of the studies of the visual field and data reported, defi- nitely be said to be examples of so-called retrobtulbar neuritis. Although a report of six cases would not be considered a significant contribution if judged by the usual standards of medical reporting, still it seems unusual for any one ophthalmologist to have the opportunity to observe even this many cases if the paucity of reported cases of this complication is considere(d in proportion to the number of people with Graves's disease. WVhen the studies of Igersheimer and of Hedges and Scheie were published I was collecting data on six cases that had been observed at the Mayo Clinic in the period 1951 to 1955 inclusive. In view of these publications I decided not to present my dlata as a separate study of the disease but instead to correlate them with those of Igersheimer and( of Hedges andl Scheie, in order that a better over-all understandling of the behavior of this comiiplication affecting the optic nerve might be ob- tained. Such a correlation of sixteen cases sttudied by four observers permits a more lucid evaluation of the disease than would be possible if single cases from multiple observers were correlated. A soniewhat similar summary of the reports among the Eluropeani literature was published by Danis and Bastenie (6), who suimmarize(d the tlata collected fromi twelve cases that had been reportedl by eiglht differenit authors.

SUMMARIZED REPORTS OF CASES CASE i. A white main, sixty-four years of age, underwent initial examiination at the clinic on July 17, 195 1. Thyroid status.-Basal metabolic rate, +36 percent. Diagnosis: exophthal- mic goiter. Ocular findings.-Visual acuity in right eye, 6/15; in left eye, 6/12. Results of ophthalmoscopic examination, negative. Hertel measurements: right, 23; left, 21; at base, 99. Eyelids retracted moderately; soft tissues of orbits were not edematous; globes were not chemotic. Examination of the visual fields showed bilateral central scotomas (Figure i). Treatment and course of disease.-Subtotal thyroidectomy performed oni July 26. At final examination on August 3, 1951, the patient's vision was normal. The scotomas had disappeared but the degree of exophtlhalmos and retraction of the eyeli(ds remained unchanged. Optic Neuropatihy of Graves's Disease 355 V.0.S.: 6/12 V.0.D.: 6/30 Test objects: 9/1,000 white Test objects: 9/1,000 white 1/1,000 white 1/1,000 white

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FIGURE 5. CENTRAL SCOT1-OMA, LEFT FIGUEE SC.ILATERALCEN1MRAL EYE SCOTOMAS 356 John Warren Henderson CASE 2. A white woman, sixty-one years of age, was examined at the clinic on May 6, 1953. Thyroid status.-Treated with radioactive iodine during September, 1952, for hyperthyroidism. Exophthalmos noted in February, 1953. Four weeks prior to examination at clinic visual blurring was noted. Basal metabolic rate, 4 i8 percent. Diagnosis: residual hyperthyroidism of minimal degree. Ocular findings.-Visual acuity in right eye, 6/30; in left eye, 6/12. Results of ophthalmoscopic examination, negative. Hertel measurements: right, 26; left, 27; at base, 1i6. Marked edema of the eyelids, moderate congestion of globes with minimal chemosis and moderate ophthalmoplegia. Eyelids not retracted. Visual fields showed central depression with arcuate scotomas below the fixation points (Figure 2). Treatment and course of disease.-Lugol's solution and desiccated thyroid were prescribed, and a course of X-ray treatment was given to the orbits. Examination elsewhere (4) on October 19, 1955, showed visual acuity in right eye, 6/6; in left eye, 6/7 (4). Hertel measurements: right, 21 /2; left, 23; at base, 105. CASE 3. A fifty-year-old white woman was first examined at the clinic on Sep- tember 20, 1951. Thyroid status.-History of partial thyroidectomy for "goiter" in February, 195o; onset of exophthalmos in September, 1950; blurring of vision first noted in March, 1951. Unknown amount of X-ray therapy had been administered to each orbit and propylthiouracil had been prescribed. Basal metabolic rate, -12 percent. Considered euthyroid. Ocular findings.-Visual acuity in left eye, 6/6o; in right eye, limited to ability to count fingers. Ophthalmoscopic examination gave negative results. Hertel measurements: right, 29; left, 28; at base, 112. Marked ophthalmoplegia and swelling of eyelids noted; moderate congestion and chemosis of globes. Visual fields showed central scotomas and peripheral contraction (Figure 3). Treatment and course of disease.-Bilateral orbital decompression was carried out on October 3, 195i. At final examination on October 29, visual acuity had improved: Right eye, 6/12; left eye, 6/15. Some recession of chemosis noted; proptosis and ophthalmoplegia remained unchanged. CASE 4. A white woman, forty-six years of age, underwent initial examination at the clinic on June 5, 1952. Thyroid status.-History of "thyroid operation" in December, 1950. In January, 1952, given "thyroid" because of dry skin. Exophthalmos noted in February. Visual blurring noted three weeks prior to coming to clinic. Had had rheumatoid arthritis for ten years. Basal metabolic rate, -i6 percent. Diagnosis: mild myxedema. Ocular findings.-Visual acuity in each eye, 3/60. Results of ophthalmoscopic examination, negative. Hertel measurements: right, 24½2; left, 25; at base, 105. Moderate ophthalmoplegia, swelling of the soft tissues, congestion of globes, marked retraction of eyelids, minimal chemosis. Examination of the visual fields disclosed central scotomas (Figure 4). Treatment and course of disease.-Desiccated thyroid and Lugol's solution were prescribed. At final examination on September i6, 1953, visual acuity had improved: right eye, 6/io; left eye, 6/6. A tiny central scotoma dense to Optic Neuropathly of Graves's Disease 357 i-mm. wlhite target at distance of 2 meters still present in the right visual field; the visual field of left eye was normal. Slight abatement noted in the ophthalmoplegia and exophthalmos. CASE 5. A white miianl, sixty-three years of sage, cam11e to the clinic for initial exaIIin1atioIn oIn December 17, 1952. Thlyroid status.-Treated for eleven years for low basal metabolic rate. Bilateral exoplhthalmos and decreased vision in left eye noted in spring of 1952. In July his basal metabolic rate was high; a(dministration of thyroid pills was discontinued and that of propylthiouracil commencedl. Basal metabolic rate, -7 percent. Considered euthyroid. Visual acuity in right eye 6/7; in left eye, 2/6o. Ophthalmoscopic examination gave negative results. Hertel measuremients: right, 26; left, 28; at base, io-. Moderate congestion and chemosis of globes. Examiniation of visual fields showed a central scotoma in left eye (Figure 5). Treatoment and colirse of disease.-Patient given desiccated tlhyroid and Lugol's solution. Examination elsewhere (5) in June, 1955, slhowed visual acuity corrected to 6,/6 in right eye andl to /i15 in left eye. Scotomas were not (1emnonstrable with1 the 2/1,000 white test object. CASE 6. A forty-nine-year-old white woman was exanmined at the clinic in April, i954- Thyroid statuls.-History of swelling of the ankles, nervousness, and pain in the eyes of one year's duration. Basal metabolic rate, +44 percent. Diagnosis: hyperthyroidism. Normal vision, no exophthalmnos. Radioactive iodine was given. In January, 1955, the patient seemed euthyroid clinically. In March, 1 955, visual blurring was noted. July, 1955, basal metabolic rate, -12 percent. She was still considered euthyroid. Ocular findings.-Hertel measurements: right, 25; left, 26; at base, 105. Moderate oplhthalmoplegia, marked chemosis. Visual acuity in each eye, 6/60. Bilateral central scotomas in visual fields (Figure 6). Treatment and cou-se of (lisease.-IIn August, 1955, bilateral transfrontal orbital decompression was carried out. October, 1955, visual acuity of right eye improved to 6/15 and scotoma was smaller; visual acuity in left eye decreased to ability to count fingers and scotoma was larger and denser. Final examination at the clinic in Junie, 1956: visual acuity in right eye, 6/6; in left eye, 6/12. Scotoma in right eye not demonstrable with small test objects but a tiny scotoma above the blind spot was still demonstrable in the left eye. The patient was euthyroid and the degree of exoplhthalmos was less. The findings in these six cases have been correlated with findings in four of the cases in Igersheimer's report and with those in the six cases of Hedges and Scheie-an over-all total of sixteen cases-in Table i.

RESULTS OF COMBINED STUDY

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4-OC C Ca CO()W d0 a CaC' 4.) SC .) C.) C.)>.)6 36o John Warren Henderson and Scheie the patient's age was not stated) the ages ranged from thirty- seven to eighty-eight years. These two extremes of age were represented by female patients. The ages of the four men ranged from fifty-six to sixty-nine years. Excluding the upper and lower age limits, the number of patients in each of the fifth, sixth, and seventh decades were nearly equal. The average age of the fifteen patients was fifty-six and one-half years.

THYROID STATUS When the thyroid status of the sixteen patients was considered, there seemed to be a hodgepodge of findings. In six patients hyperthyroidism or thyrotoxicosis might have been a factor at the onset of the visual disturbance, and in another three cases, although hyperthyroidism had once been present, it seemed to be under control or was considered in remission at the time the patient was examined. Five of the patients were considered to be in a euthyroid state; one of them had previously undergone an operation on the thyroid. In one other patient an operation had been performed on the thyroid prior to the visual difficulty, but this patient had mild myxedema when visual blurring occurred.

OCULAR FINDINGS Of the sixteen patients surveyed, eleven showed involvement of both eyes and five showed involvement of only one eye. The disorder, then, seemed to occur twice as frequently in both eyes as in one eye. On the basis of Hedges and Scheie's report alone (four unilateral and two bilateral cases), however, quite the opposite impression might be gained, whereas in my own six cases (five bilateral and one unilateral involvement) the disease was predominantly bilateral. In trying to assess the severity of the hyperophthalmopathy on the basis of the amount of exophthalmos and the intensity of changes of the soft tissue and ophthalmoplegia in relation to the incidence of involvement of the eye, the data were studied from the standpoint of whether the orbital changes were mild, moderate, or severe. Although it had been my earlier impression that the ocular disorder occurred in severer instances of hyperophthalmopathy, no correlation could be found in this series of cases; as many cases occurred in association with mild hyperophthalmopathy as with severe orbital disturbance. Regarding vision itself, all degrees of visual impairment were noted. In most instances of bilateral involvement the visual loss was not the same in the two eyes. At no time did any of the patients show a visual loss beyond the ability to count fingers. Although the rapidity with Optic Neuropathy of Graves's Disease 36i which vision was lost was a factor difficult to assess accurately, it was lily impression, based on the report by Hedges and Scheie as well as on nmy ownI1 cases, that the vistual decrease occurred fairly rapidly; that is, over a periodl of from two to six weeks in most of the cases. The defects in the visual fields showed a fairly consistent pattern, the loss of vision being clue to a central or paracentral scotoma, to a defect of a nerve-fiber bundle, or to a combination of the two. The majority of patients showed the central scotoma type of dlefect, the scotoma pos- sessing very sharp borders with a density varying from i/i,ooo up to and including 35/1,000 wAhite test objects, and varying in size from 5 degrees in diamneter up to 30 degrees. As a rule, the periphery of the visual fields in these patients was unaffected. The ophthalimioscopic exam miIlation among these patients consistently failedl to show an explanation for the visual loss except in one of Iger- sheimiier's patients. In his Case 2, temporal Pallor of one optic disc was note(d and doubtful temporal pallor of the other optic disc was recorded. In this particular case the pallor of the disc probably reflected the long duration of the visual loss. In one patient of Hedges and Scheie's series a papilledcema was present, but this was not believed to account for the type of defect that was present in the visual fields. COURSE OF DISEASE AND TREATMIENT A perusal of the sixteen cases revealed that in fourteen the course of the disease was characterize(d by a tendency of the visual loss to reach a climax andl then to abate. In the two exceptions (one case reported by Igersheimer and one case reported by Hedges and Scheie in which there was bilateral involvement) the visual acuity in at least one eye of each patient remained poor due to the onset of optic atrophy. In the Igersheimer case, pallor of the disc was noted at initial examination; in the case of Hedges and Scheie, papilletlemnia was noted on the initial examinationi of the eye. On this basis it would seem that the presence of either pallor of the disc or papilledeema at the time of the initial examination would prognosticate an unfavorable trend in so far as recovery of vision is concernied, but it muitist be pointed out that although the other eye of the patient whose case waCs reported by Hedges and Scheie also exhibited lpal)illedlelnia a simiiilar loss of vision was not present. The degree of visual recovery varied considerably. On the basis of the report by Hedges and Scheie the evidence favored an excellent prognosis, because in five of their six platieIits vision returned to normal. However, among the remiaininlg ten cases only one patienit recovered 362 John Warren Henderson normal vision in both eyes, and in four patients a final vision of 6/6 was noted in one of the involved eyes. In no instance was the patient left helpless by reason of poor vision in both eyes. The patients of this combined study received a very representative cross section of nonsurgical as well as surgical treatment now in common usage for basic thyroid dysfunction. One or more of these patients received propylthiouracil, radioactive iodine, desiccated thyroid, Lugol's solution, corticotropin, X-ray irradiation to the orbits, subtotal thyroidectomy, or decompression of the orbit, or combinations of several treatments during the course of observation. The course of the disease seemed independent of the treatments attempted. In the survey of various cases collected among the literature as carried out by Danis and Bastenie (6), rather similar conclusions were reached as to the ineffec- tiveness of treatment on the course of the disorder.

COMMENT In all case reports of this disorder wherein studies of visual fields were included, the observers have placed the site of the disturbance in the optic nerve. In general, particularly in cases in which papilledema was not present, the retrobulbar portion of the nerve has been suspected as harboring the pathologic change responsible for the scotomas. In- deed, the central scotomas and arcuate defects of the nerve-fiber bundle are very similar in configuration to the defects in the visual fields of patients with retrobulbar neuritis who do not have Graves's disease. Several observers, for these reasons, have designated this visual complication occurring during the course of Graves's disease as a retrobulbar neuritis, and the clinical behavior of these two disorders, characterized by a fairly rapid decrease in vision followed by some degree of improvement, is quite similar. On the possibility that the factors responsible for the common type of retrobulbar neuritis not associated with Graves's disease are different from the factors contributing to the onset of the disorder of the optic nerve under discussion, and to help differentiate the two disorders clinically even though they have a common anatomic location, it is my suggestion that the term "optic neuropathy of Graves's disease" be used rather than the term "retrobulbar neuritis" until such time as the etiologic factors responsible for the disease are elucidated. There is much speculation regarding the etiology and pathogenesis of this neuropathy. Terms such as "neurotoxic origin" or "toxic origin" have been used by several observers to explain the pathogenesis. In a situation such as that represented in Case i of my series, wherein the Optic Neuropathy of Graves's Disease 363 patient's recovery was exceedingly rapid on relief of the thyrotoxicosis, such a theory of neurotoxins would be difficult to refute. This theory, however, cannot explain all cases. The other theory, the mechanical one, is a natural evolution from the clinical observation of increased volume of the retro-orbital tissues as well as increased orbital pressure that accompanies so many of the cases of so-called hyperophthalmopathy of Graves's disease. This theory, like the preceding one, does not apply to all cases, for there were many patients in this survey who did not exhibit a severe degree of hyperophthalmopathy. Likewise, I have seen many patients with hyperopthal- mopathy of a degree much severer than that of any of the patients described in this survey who did not have any loss of vision due to a disturbance within the optic nerve. If mechanical factors such as high orbital pressure do affect the optic nerve, I would be inclined to hold these factors responsible for the papilledema that is seen in some cases rather than the neuropathy under discussion. I believe that the lesion also might be produced not by mechanical or toxic factors acting directly on the nerve fibers but by factors affecting the optic nerve indirectly through the medium of its vascular sup- ply. An ischemic edema of the nerve (a transient spasm of one of the nutrient vessels within the retrobulbar portion of the optic nerve followed by a transudation of fluid into the tissues with subsequent return of normal tone to the vessel and absorption of fluid) similar to that seen with a so-called central serous retinopathy might occur during the course of the hyperophthalmopathy. In disorders characterized by an ischemic edema there is often an initial severe degree of functional embarrassment of the part affected with return of function as the edema subsides. If such a pathogenesis did exist, however, I have no idea as to the factor that triggers off the initial vascular spasm. In the few patients who did not show visual improvement, the initial spasm may have been of such duration as to impair the nutrition of the nerve fibers beyond the point of reversibility, a pallor of the disc being the end result. Attention was directed earlier to the clinical fact that the majority of these patients do not show any papilledema or "papillitis." This does not preclude the possibility that papilledema may occur, as it does in a few instances, but when both central scotomas and papilledema are present in the same eye I consider it coincidental. The factors producing the papilledema are more likely to be the mechanical forces, and the patients having hyperophthalmopathy who show only papilledema do not have loss of vision in the initial stages. If the papilledema 364 John4Warren HeITIderson in these particular cases is of short dutrationi, vision will not be impaired; btut if the papilledeema is chronic or of loing dutiration, then secondary optic atrophy will occur. In this latter situation, dlefects of the visual field usually will involve first the periphery of the field (gen- eralized contraction) rather than producing the central scotomas characteristic of the neuropathy under discussion. In short, then, I consider the optic neuropathy of Graves's disease and papilledema to be mani- festations of different mechanisms affecting the optic nerve d(uring the course of the hyperophthalmopathy. In the first several cases of this disor(ler that I observed I was quite anxious that the patients undergo orbital decomiipressioni, lest vision become irreversibly lost. WVhen some of the patients reftused this well- meaning advice, I was greatly relieved, as was Igersheimer, to learn that vision improved without this surgical aid. As I have obscrvedl more patients having this condition, and as I have benefited fromll the reports of other physicians who have encountered similiar cases, I have come to the conclusion that loss of vision due to this disor(ler of the optic nerves needl not be considered a positive indication for decompression. On the other hand, it is my feeling that for patients who have Graves's disease accompanied by papilledema, orbital decompression should be seriously considered as the treatment of choice. SUMMIARY Six cases of an infrequent and seldomii recogniized (lisor(ler of the optic nerve occurring during the course of Graves's (lisease are described. These six cases are correlatedl with ten other cases recently reported from two different sources. On the basis of the study of this combined series, some conclusions are drawn as to the behavior of the disease. The disorder is manifested by the demonstration of either central scotomas or defects of the nerve-fiber bundlle on testing of visual fields. Its clinical course is similar to so-callecl retrobulbar neuritis. To help differentiate retrobulbar neuritis from the disor(ler uni(ler discuLssion the term "optic neturopathy of Graves's (lisease" is prolposed. Neither the clinical status of the thyroi(d gland at the onset of the disorder nor the usual treatments prescribed for the basic thyroid-pittuitary dysfunction seemn to have any influence on the course of the optic neuropathy. The (lisease has a good prognosis in that the miajority of the patients have return of useful vision. Some theories as to the possible pathogenesis of the optic neuiropatlhy are discussed. Optic Neuropathy of Graves's Disease 365 REFERENCES i. Wagener, H. P., Lesions of the optic nerve in exophthalmos of endocrine origin, Am. J. M. Sc., 232:226-39, 1956. 2. Igersheimer, Joseph, Visual changes in progressive exophthalmos, Arch. Ophth., 53:94-104, 1955- 3. Hedges, T. R., Jr., and H. G. Scheie, Visual field defects in exophthalmos associated with thyroid disease, Arch. Ophth., 54:885-92, 1955. 4. Fralick, F. B., Personal communication to the author. 5. Robinson, S. T., Personal communication to the author. 6. Danis, P., and P. Bastenie, Les atteintes du nerf optique au course des exophtalmies oedetmateuses endocriniennes, Ophthalmologica, 126:65-90, 1953. I)ISC USSION DR. JOHN WOODNVORT-i HENDERSON. I should like to congratulate Dr. Hender- son on his concise and well-organized paper on a subject which is often con- fusing, both in the literature and in clinical patients. It is regrettable that the paper could not have been presented in its entirety, and I would recommend reading it in its entirety in the final published form. In reviewing our material at the University Hospital prior to discussing the paper today, I was able to find eight cases in which visual reduction had been an outstanding feature in progressive exophthalmos of thyroid disease. In only one was there a clear-cut central defect such as has been demonstrated by the author. This was in a twenty-nine-year-old man with a sudden onset of unilateral, then bilateral, exophthalmos with acute orbital congestion, no abnormalities of the nerve heads, and eventual visual reduction to 4/6o O.D. and i/6o O.S. His status was euthyroid, and on administration of thyroid extract by mouth his vision and fields returned to normal over a year's period, with regression of the exophthalmos by 14 mm. O.D. and 12 mm. O.S. Three cases showed central visual reduction in both eyes, but visual fields were unsatisfactory with central defects suspected. All improved to normal. Three cases demonstrated visual reduction during acute orbital congestion. Relative central field loss was present, and two of the three exhibited final optic atrophy. Persistent visual loss of varying degree occurred in all three. The final case raises other questions. The patient, a fifty-one-year-old Negro woman, had undergone thyroidectomy for toxic goiter, followed by recurrent hyperthyroidism. Radio-iodine treatment was succeeded by severe progressive exophthalmos. A complicating severe glaucoma ensued, with inadequate control of intraocular pressure on miotics and Diamox. A normal facility of out- flow was recorded on two occasions. Progressive visual loss followed. Bilateral orbital decompressions failed to produce more than transient visual improvement, and her visual acuity has now dlropped to counting fingers O.U. This despite nerve heads which show no cupping or atrophy, and an intraocular pressure which is now normalized with pilocarpine alone. Her visual fields are not characteristic of glaucoma. Dr. Henderson has gauged the amount of orbital congestion as mild, moderate, or severe. I wonder whether severity alone is important unless one correlates it with the acuteness of the process with lack of time for orbital 366 John Warren Henzderson compensation to follow. It appears that the acuteness of orbital congestion with insufficient time for compensation to occur has been a factor in irreversi- ble visual loss in certain of our cases, both with and without papilledema. Is there any indication of such a relationship in his cases-all of which improved? Since an atypical glaucoma has been a complicating factor in several of our patients, was there any relationship between the recorded intraocular pressure and the findings in his series? DR. JOSEPH IGERSHEINIER. I think it is a very good idea to call the involvement of the optic nerve in cases of Graves's disease an optic neuropathy and not a retrobulbar neuritis as one finds it occasionally in the literature. I personally think that it is not the thyroid or the pituitary condition which is responsible for the field changes in the exophthalmos. I saw, for instance, a patient with a unilateral exophthalmos whose orbit was explored and whose exophthalmos was due to a lymphoma behind the globe. After the operation the proptosis again increased very much and it was decided to give him some X-ray treatment. He had a certain reduction of vision and a fine central scotoma for colors only. After the third treatment the protrusion decreased and in a short time the vision became io/io again, the scotoma disappeared, and the exophthalmos was reduced to 2 or 3 mm. Such observations indicated the possibility that it may be the pressure inside the orbit upon the optic nerve which results in visual changes. There are no anatomical findings in this respect as far as the malignant exophthalmos is concerned. There are also very few such anatomical investigations in cases of tumors in the orbit. But I will show you a few slides of cases whiclh I described in a former publication. The first slide shows a transection of an optic nerve in a tumor of the orbit. There was clinically a central scotoma and some reductiotn of the vision, and anatomically the degeneration was in the inner parts of the nerve, while the periphery did not show degeneration. The second slide gives you the whole content of the orbit containing melanomatous tissue surrounding the optic nerve. This melanoma was grow- ing from the sinuses into the orbit. Clinically there was a reduction of vision andI a central, as well as paracentral, scotoma. In this case the main pathology was in the region of the central vessels about i millimeter behind the optic disc. There was a terrific vascular stasis. In front and behind this stasis the optic nerve was degenerated. These cases, which have in themselves nothing to do with the malignant exophthalmos, give a good picture of what one can see clinically in malignant exophthalmos: central scotoma with normal ophthalmoscopic picture (occasionally temporal pallor) and on the other hand central visual changes to- gether with a kind of papilledema. DR. HAROLD G. SCHEIE. I should like to make two or three points. First of all, like Dr. Henderson, we found no explanation for the visual loss. There seemed to be no correlation with any facet of the disease by which it could be explained. We also found that the prognosis was excellent. I hope this holds true, because at the moment I have under my care a lady in whose only eye visual loss has occurred leaving her with a residual nasal field. The scotoma has broken through entirely, and she has vision of only eccentric hand move- Optic Neuropathy of Graves's Disease 367 ments. I also have another patient with a comparable scotoma occurring in her better eye. I have been following these cases for six to eight weeks, since the height of the lesion or the greatest decrease of vision, and there has been no tendency toward improvement. The increase in pressure has also interested me. We have not infrequently seen at least borderline pressures. The second lady who was referred for care, who had the depression in her good eye, also had an elevated tension in this eye. She was on Diamox at the time of her first visit to our office. The eyes were depressed, each eye in a position of slight downward gaze, the eye under discussion more than the other. Lateral gaze was impaired in each eye. On taking the tension with the patient in the ordinary front position the superior rectus muscle was apparently tugging against a fibrotic inferior rectus, and as a result it caused a rise in tension up to 40. If you depressed her head to per- haps a 30-degree angle, so that you took her tension with the eye in a position of downward gaze, the tension was 17. That may well be the explanation for the pressure in certain cases. DR. F. C. CORDES. I had a case of a rapidly progressive exophthalmos following thyroidectomy, in which the field of vision in one eye finally was limited to a small sector in the nasal field. The patient started to develop a central scotoma in the other eye. An orbital decompression was done at the time, and with that most of her field returned in the poor eye and 20/20 vision in the other. This case led me to try to determine a cause. In looking up things I find that it is not a bad idea at times to go back to the writings of Fuchs. As you know, in the very early twenties there were many cases reported of depressive exophthalmos following thyroidectomy for Graves's disease. Fuchs's explanation for at least some of these seems fairly reasonable. He felt that in those cases where there was a sore optic nerve a rapidly progressive exophthalmos might put sufficient stretch on the nerve to interfere with its conductivity, and therefore if that pressure could be relieved the fields would return to normal. If, on the other hand, the progression was gradual, he felt that the nerve had an opportunity of readjusting itself to it. In the case that I saw there were no visual ophthalmoscopic changes. DR. JOHN WARREN HENDERSON. I am particularly pleased with the discussions of Dr. Igersheimer and Dr. Scheie. I have quoted from both of them in the written text. I know of their interest in the disease. Neither of them has had an opportunity to read the full paper. Their information is supplemental to my own. Certainly we must know more about this disease as the years go by, and one of the objects in calling your attention to it was that you should be on the lookout for it. Answering the question from my namesake in Ann Arbor, I have not noted any correlation between the onset of this trouble and intraocular pressure. In all of our cases the intraocular pressure has been normal. I will go over my series again with the possibility of correlating them with the rapidity of the onset of hyperophthalmia. At the moment I do not believe it is a factor.