Type 1 Diabetes

The First Case of Diabetic Retinopathy 

(Eduard von Jaeger, Vienna 1853) by FRANZ FISCHER 

We have before us the plates and documentation of a case of retinitis (retinopathy) in diabetes mellitus, the first of its kind. It derives from the Beitrage zur Pathologie des Auges by Eduard von Jaeger for the year 1855. That it was the first such case we have the best guarantor, Theodor Leber. In 1875, he collected the cases from the literature - there were 19 in all, of which Jaeger's case was the first - and coined the term retinitis diabetica. So characterized, Jaeger's case wanders through the literature. After Leber he found no-one more appreciative. We thought it stimulating as well as conducive to the continuity of research to exhibit this case. 

It is no accident that the observation was made in Vienna, and made by Eduard von Jaeger. In the second half of the 18th century and subsequently, Vienna was very fruitful medical soil, a place where the new seed of ophthalmology could flourish. We see Joseph Barth, the gifted individualist, Georg Joseph Beer (first professor, 1818), the first teacher and founder of scientific ophthalmology, Friedrich Jaeger, Ritter von Jaxtthal (Eduard's father), Professor at the military medical Joseph's Academy (Josephinum), the most sought-out eye-surgeon in Europe. In the so-called II Vienna Medical School, Eduard von Jaeger with Ferdinand von Arlt and K. Stellwag von Carion was an outstanding champion of the specialty. As the son of Friedrich von Jaeger and grandson of the great Joseph Beer, Eduard von Jaeger had glittering prospects. 

Nevertheless, and with all his personal accomplishment, he was denied what he felt to be his heart's desire: only at the age of 65 did he become Professor at the II Ophthalmic Clinic, Vienna, not long before his death (5 July, 1884). His main creative work lay in ophthalmoscopy. The best witnesses on his account are two competent ophthalmologists: Ludwig Mauthner (in the obituary): "Eduard von Jaeger's career is inextricably bound up with the history of the ophthalmoscope. He was one of the first who turned Helmholtz's discovery to practical use. He also produced an improved form of Helmholtz's instrument very soon for everyday practice. Eduard von Jaeger was the greatest ophthalmologist the world had yet seen." Then Maximilian Salzmann (in the preface to the reworked Atlas of 1890): "The time has its expectations, which Eduard von Jaeger, linked with the appearance of his Atlas has satisfied in full measure. His work is recognized as the most important in the field of ophthalmoscopy and has become a foundation on the basis of which numerous young doctors have been introduced into this important oculists' discipline." So much for the environment and personality of our author. 

And now for the case. The description begins as follows: "The gardener Wilhelm W., then 22 years old, of slender physique and medium height, had always been healthy and strong in childhood and adolescence. However, 4 years previously, through catching cold, he developed a disorder which repeatedly kept him in bed with slight fever and swelling of the right foot, loss of strength and appearance. As this continued, the phenomenon of a diabetes emerged, coupled with marked anorexia, dry throat, frequent vomiting after eating and feelings of great decline and weakness. For a short time the patient had also complained of frequent cough with much sputum and feelings of oppression and pressure in the chest. " 

We now shorten this account. 5 weeks before he had experienced a disturbance of vision: transient seeing of flashes and "slight clouding of the outer half of the visual field in the left eye". The clouding had spread to the other eye and was increasing. The sight in the left eye had temporarily improved. The disorder had steadily increased. It is stated: "The patient presently appears very ill and low, is thin and has a sallow complexion." Then a "disturbance of the visual field in the middle" with reduction of visual acuity is described. Passing to the ophthalmoscopic findings: The media had appeared quite transparent and normal. The peripheral parts of the fundus were free from lesions. 

On the other hand, the site and vicinity of the transverse section of the optic nerve (in the extent of the extravasate illustrated in the picture) is dull in color, less translucent, more blood-red, and the optic nerve cross-section is so completely covered by the aforesaid color change as to be no longer perceived and can only be recognized by the union of the retinal vessels. 

"Anomalous redness of the optic fundus" and "radiate spreading of the optic fibers in the vicinity of the optic nerve" were reported. Then it states: "In the region of this anomalous coloring of the optic fundus there are to be perceived a considerable number of apparently uniformly distributed blood-red flecks, some punctate, some striate or otherwise shaped, of the most various size, which seem to lie in the plane of the retinal vessels, i.e., deep to the retina, are predominantly elongated, and whose arrangement and orientation correspond partly to the optic expansion and partly to the paths of the retinal vessels, particularly the veins. Between the flecks, at some distance from the optic disc, there also appear numerous irregular, rounded, light-yellow spots whose brightness makes them very obvious." 

It then states that the retinal vessels in the region of the optic disc were hazy. The arteries showed an especially brilliant media. The diameters of the arteries and veins were significantly increased above normal. The description ends as follows: "The left eye exhibits objectively and subjectively exactly the same appearances, though to a lesser degree and the patient is still capable with its aid of getting about in the street and even doing some work as a gardener." 

We note that plate and text are quite consistent. The text, based on the author's principle, is descriptive, not explanatory. The illustration is quite true to life and free from any exaggeration. The lithography and color printing, carried out by the Imperial and Royal Court and State Press in Vienna is an amazing technical achievement for a hundred years ago. 

What was Eduard von Jaeger describing? At the fundus: an edema of the optic disc and adjacent retina, streaked and radially arranged hemorrhages at some distance from the disc, light-yellow spots, to be explained later, as essential features. The question whether this complied with the concept of diabetic retinitis (retinopathy), then and now, may be answered as follows. Th. Leber (1875) remarked of Jaeger's case that it resembled the retinitis occurring in albuminuria. Later, the edema (with the star figure in the macula) were counted as characteristics of albuminuric (nephritic, angiospastic) retinitis as against diabetic retinitis. What can we say today? Diabetic retinopathy embraces a whole range of retinal lesions: "blood-spots (anatomically: capillary aneurysms) at the outset, hemorrhages and white degenerative foci subsequently, and finally vascular and connective tissue proliferation, vitreous hemorrhage, retinal shrinkage, etc. (retinitis proliferans), though these stages are not always observed. As always with retinopathy, the edema is not part of the fundus picture. It is the view of not a few workers today that, when an edema appears, the case is one of nephritic and not diabetic retinopathy. We believe, however, that diabetic retinopathy can, exceptionally, imitate nephritic retinopathy. Edema formation is shown especially by young diabetics, as confirmed by R. Thiels and our own observations. Frankly, we cannot share Thiels' view (1956) that this depends on the special nephropathic forms of diabetes, the KimmelstielWilson glomeruloscleroses. The fact that most Kimmelstiel-Wilson cases are heralded by retinopathy without edema formation is an argument against. Therefore nothing prevents us from acknowledging Jaeger's case as one of true diabetic retinopathy, despite any similarity with albuminuric retinitis. Jaeger's case admits of another interpretation. The indistinct disc, the numerous radially arranged hemorrhages, the markedly reduced visual acuity - all are very suggestive of a thrombosis of the central vein of the retina. This is not at all an uncommon event in older diabetics (with advanced arteriosclerosis), in any case commoner than in non-diabetics; in young diabetics it was unknown. Now, J. Dietzel and P. White have recently observed a central vein thrombosis in a young diabetic, followed by a retinitis proliferans in the other eye. This demonstrates that the angiopathy specific to diabetes (and not just the usual arteriosclerosis) is capable of producing such a picture. Jaeger's case in a 22-year-old diabetic could be interpreted in this sense; but, frankly, the fundus picture is not at all consistent and the appearance in both eyes arouses doubts. The possibility exists. Now for the "rounded light-yellow spots" in our fundus picture. That this referred to the usual retinal degenerative foci we believe can be dismissed without more ado. K. vom Hofe was the first (1938) to point out the frequency of such a finding in diabetic retinopathy, and we confirm this from our own experience. It only surprises us how little awareness of this there was until now. Vom Hofe interpreted the picture as lipid infiltration of the deep retinal layers or choroid and proved correct. For the picture certainly is not related to "choroiditis in diabetic retinopathy" as we have recently described it. How accurate, then, were Jaeger's observations!

 If we leave the fundus picture: the patient's age of 22 years leads to the following remarks. Until some 10 years ago, diabetic retinopathy below 40 years of age was an absolute rarity. Thus we find in a world-famous textbook of ophthalmology of 1935 that only a single case is quoted from the literature. A marked change has occurred here. The number of young diabetics is large and steadily increasing, due to insulin and other modern treatment. The young diabetic is becoming older and now experiences its vascular complications, notably nephropathy and retinopathYi at the age of 30 or 40, he is confronted with a gloomy fate. For us, this is the main problem of diabetes mellitus today. On the other hand, the practicality of oral treatment of diabetes is fading. 

And now back to Jaeger's case. At that time, and for one of his age, he was certainly a rarity. And it should be considered that in the pre-insulin era young diabetics died off very quickly without exception from comai young diabetics did not live to experience vascular complications. As for the duration of the diabetes - in our case barely longer than 5 years - the following may be noted. As far back as 1858, Albrecht von Graefe was struck by the fact that the ocular disorders in diabetes mellitus belonged to "an advanced stage of the general disease". It required intensive research up to our own time to reveal the role of the duration of the diabetes in the development of retinopathy. 

Today, many workers, notably Dolger (USA) adopt the standpoint that every diabetic will experience the "vascular complications" of nephropathy, retinopathy, etc., if he lives long enough, for 20 years or more. On the other hand, Joslin's school in the USA advances the view that the vascular complications can be prevented or at least postponed by precise management of the diabetes from the outset without interruption, with proper treatment and surveillance. The advocates of the "free diet" (which actually is not a free diet) for diabetic children and adolescents rather incline to Dolger's view. We ourselves acknowledged Joslin's requirements in various articles though, like other authors, we were well aware that in by no means a few cases, and despite the best monitoring of the diabetes, a retinopathy (and nephropathy) develops after quite a short duration of the diabetes, while others remain unaffected despite continuously poor monitoring and overlong duration of the disease (30 or more years). We sought to explain the "bad" cases by a special penetrating power of the diabetes on an unherited basis. 

We are further of the opinion that, not only the diabetes as such, but also the associated vascular constition are inherited, and in a decisive manner. On this, the findings have yet to be made known. Jaeger's case, with its relatively short duration of diabetes, therefore also falls outside the rule in this respect and requires a special explanation, as given above. What does the case tell us otherwise? We may pass over the classical diabetes symptoms. Nothing is said relating to albuminuria or nephritis. Th. Leber felt this as a defect in the completion of his task. Thanks to the exact illustration, we can say with fair certainty that a nephropathy did exist, indeed in the uremic end-stage. This is not surprising, since we know how much alike are diabetic retinopathy and nephropathy, both clinically and pathologically; and it is just in young diabetics that nephropathy, as Kimmelstiel-Wilson's glomerulosclerosis, runs a deleterious course. 

That the report contains nothing about the blood-pressure only evokes the late development of blood-pressure measurement. A hypertension would not be surprising; according to our findings, it is associated just like the nephropathy with the retinopathy of young diabetics. The disease was ushered in by an infection, as we know well today. We amplify: the course of the diabetes was also unfavorably influenced by infection. Unfortunately, the eradication of focal sepsis has been pushed into the background in modern diabetes treatment. The description even suggests pulmonary tuberculosis. Over and again, this disease plays a noteworthy yet too little noted role in juvenile diabetes, being the second cause of death after uremia. 

We may conclude: The case reported by Eduard von Jaeger in 1855 is unusual as regards age, duration of diabetes and fundus findings. It withstands any check by current standards. We are right to see in it the first observation of diabetic retinopathy. The strictly scientific approach of the author has saved the case from oblivion. Yet it is quite remarkable that our acquaintance with diabetic retinopathy should have begun in such an unusual way. And what is even stranger is that in Jaeger's case we encounter the problem case of diabetes mellitus today. Eduard von Jaeger published this case in his Beitriigen zur Pathologie des Auges (1855-1856). 

Just listen, in conclusion, to what our historian, J. Hirschberg, writes on this: "No sacrifice for science was too heavy for him. For his wonderful Contributions to the Pathology of the Eye he plunged into a debt of 20,000 gulden, which he gradually paid off from his earnings." Such was Eduard von Jaeger. May he be a model to all young ophthalmologists!

 Summary 

The priority of the case is certified by Th. Leber (1875). That the observation was made in Vienna and by Eduard von Jaeger (1855) is not a matter of chance. Though this case of diabetic retinopathy is unusual in many respects, the diagnosis is beyond doubt and satisfies any check. The author's comprehensive and very factual approach gives us cause, even today, for valuable inferences and reflections, and not only as regars the fundus appearances. The spirit of a true natural scientist reveals itself. 

References 

F. Fischer: Probleme der diabetischen Retinopathie. Klin. Mbl. f. Augenheilkunde 125 (1954): 666 - Einst und jetzt. Die historische Entwicklung der Retinopathia diabetica. Miinchner med. Wschr. 44 (1954)1287. - Die Retinopathie des jungen Diabetikers (unter 40 Jahren). Graefes Arch. 1957. - J. Hirschberg: Geschichte der Augenheilkunde. In Handbuch Graefe-Saemisch, Bd. XV, 1916. - Eduard von Jaeger: Beitrage zur Pathologie des Auges. 2. Lieferung, S. 33, Tafel XII. K. K. Hof- und Staatsdruckerei, Wien 1855. - Th. Leber: Uber die Erkrankungen des Auges bei Diabetes mellitus. Arch. f. Ophthalm. 21, 3 Abtlg. (1875): 206 - Die Krankheiten der Netzhaut. In Handbuch Graefe-Saemisch, Bd. VII12 (1914): 969. -1. Mauthner: Eduard von Jaeger. Wiener Med. Wschr. 28 (1884): 878 - Th. Puschmann: Die Medizin in Wien wahrend der letzten 100 Jahre. M. Pedes, 1884. - M. Salzmann: Ophthalmoskopischer Handatlas von Eduard von Jaeger, neubearbeitet und vergr6Bert. F. Deutike, Leipzig und Wien 1890. - L. Schonbauer: Das Medizinische Wien. Geschichte, Werden, Wiirdigung. Urban & Schwarzenberg Berlin und Wien 1944. in: Wiener Medizinische Wochenschrift 107 (1957) 969-972.

Griesinger in 1859 published an analysis of 225 cases of diabetes; and though only eight were his own and the others all from the litera ture, his contribution was valuable for clinical experiments and sound judgment. He compiled the first evidence indicating excess in sugars and starches as a cause of diabetes, but concluded that it could not be the most important cause, or many more persons and some entire races would have diabetes. He overthrew various current errors, but somehow convinced himself in painstaking experiments that diabetics may excrete large quantities of sugar in the sweat, as reported by several other authors. From the negative findings in necropsies, he regarded diabetes as generally a functional disorder. His most notable achievement was the demonstration, in three separate experiments on a single patient, of sugar excretion equalling exactly 60 percent of the protein of the diet.“ These facts, remaining constant under varied conditions, cannot be accidental; they seem much more to contain the law of the relation in which, in this individual on exclusive meat diet, the production and excretion of sugar stands to the quantities of ingested meat."

Although advocating the employment of vegetable diet in cases of diabetes of the second class, I do not wish it for a moment to be supposed that I agree with Piorry in thinking that the cause of death, even in this form of diabetes, arises from the loss of sugar; for, on the contrary, I think it springs from the inability of the body to assimilate the sugar it possesses. In such cases, therefore, I give vegetable food, not because it contains sugar, but because it possesses many of the other substances necessary for the purposes of nutrition, which neither exist in the same quantity nor in so easily an assimilated form in animal diet. 

It is well known from the reports of travellers among savage nations, that men restricted solely to animal diet must consume an almost fabulous amount in order to obtain sufficient of all the ingredients requisite in the processes of life. "We know, too, that an animal can be most effectually starved by limiting him to one particular element of food, although that element be even albumen. The benefits derivable from Piorry's plan of treatment, therefore, in my opinion, arise from the fact that when he gives sugar he at the same time ceases to restrict the patient to animal diet, and that in the mixed food they find many of the materials essential to life much more abundantly and in a more easily assimilated form than in animal diet. I shall now give a few typical cases illustrative of the two principal forms of diabetes. 

Diabetes from Excessive Formation. 

In the beginning of 1860 a young gentleman, aged 19, suffering from diabetes, was brought to me by his brother, a Medical Practitioner, who had detected the disease two year previously. This patient had already been under various systems of treatment. What appeared to agree with him best was animal diet, coupled with. small doses of chlorodyne. 

To look at the patient one would have thought that he was a perfectly healthy individual. His weight was 135 lbs. ; the appetite was moderate ; and the amount of urine passed was not at that time excessive. The object of bringing the patient to me, it appeared, was in order that I might, if possible, suggest some remedy to replace the chlorodyne, the constipating effects of which were anything but agreeable. On carefully inquiring into the history of the patient, the case appeared to be one of diabetes by excess, and the origin of the mischief could in some measure be traced to some irritation in the liver, which was painful at its lower margin, the pain being much increased on pressure. Having an intelligent Practitioner to deal with, I at once gave my view of the case, and explained how, as scarcely any two cases of diabetes are precisely alike, it would be necessary to try the effects of different forms of treatment in order to discover what would be best for this particular case. The following table is an abstract of the results : 

TABLE 

The average amount of sugar passed by this patient during the next six months being from fifty to sixty grammes (775 to 930 grains) and his -weight 156 pounds, a quantitative analysis of the sugar -was no longer thought necessary. I may add that-when I last saw the gentleman in August, 1864 (on the occasion of his bringing to me a poor lad, -whose case I shall presently relate), he looked in excellent health, being, as he said, -without any feelings of discomfort, although he had still to continue his medicine, for as soon as he neglected it, the sugar again increased.

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Dietary for the diabetic:

May Eat:

Butcher's meat of all kinds, except liver.

Ham, bacon.

Poultry.

Game.

Fish.

Animal soups.

Eggs, cheese, cream, butter.

Greens, spinach, lettuce, nuts sparingly.

Must avoid Eating:

Sugar, bread, Rice, Potatoes, Cauliflower, peas, broccoli, and many more.

The two great types of diabetes, that due to excessive formation, the other to diminished assimilation of saccharine matter, require, of course, as far as animal dieting is concerned, opposite modes of treatment ; for while in the former class of cases it is a most important — I might almost say an essential — adjunct to the other treatment, in the latter it is either detrimental, or, at best, of no use at all. 

Even in the most favourable cases for restricted diet, we must never allow ourselves to be deluded into the idea that, because we are mitigating the symptoms, and reducing the amount of sugar in the urine, we are necessarily curing the disease, or we shall frequently be doomed to sad disappointment. In keeping a patient on restricted diet, we are merely with-holding from him the straw and mortar out of which the bricks are made — not removing the makers — so that, as soon as the straw and mortar is refurnished to them, they will again be found at work as actively as ever. It is true that it occasionally happens during the withdrawal of the straw and mortar the makers disappear; but this, unfortunately, is by no means invariably or even frequently the case; it is rather, indeed, the exception than therule. We must therefore rely on other means for the removal of the makers. Of these other means I shall presently speak. 

Meanwhile, let me explain that by the term restricted diet we mean not only the avoidance of all sugars, and substances containing saccharine matter, but also of all kinds of food convertible during the process of digestion into sugar. The foods convertible into sugar in the digestive canal are those containing starch (not gums), such as arrowroot, tapioca, sago, flours of all the different kinds of cereals (wheat, barley, oats, peas, beans, etc.), potatoes, carrots, beetroot, parsnips, turnips, and other edible roots. 

Green vegetables, on the other hand, such as spinach, cabbage, turnip tops, Brussels sprouts, and lettuce need not be forbidden, as they contain too small an amount of starch to do much injury. 

As for animal foods, on the other hand, every imaginable kind of fish, fllesh, and fowl may be indulged in, so that even on the most restricted diet the patient has still a large margin for selection — beef, mutton, pork, venison, poultry, game, and wild fowl, oysters, lobster, crabs, prawns, salmon, cod, turbot, etc., Iceland and Irish moss, calf's foot or gelatine jellies, butter sauces, and salad oils. 

The only true hardship, in fact, the patient suffers is the deprivation of ordinary bread, and that appears to be a more severe one than most people imagine. I have known patients in whom the craving became at last almost intolerable, as if nature were crying out for some indispensable element of food. In order to mitigate this hardship, a great number of plans of depriving bread of the forbidden element, starch, have been suggested, and many of them have been in a great measure successful. Thus, we have bran, gluten, almond, and glycerine breads and biscuits constantly kept in stock by many of our London bakers, (a) After a time patients get very tired of these substitutes, so it is as well to know that we may occasionally indulge them with well done toast, or very crisp pulled bread, the extra heat having destroyed a considerable portion of the starch normally contained in the article. 

As regards drinks, all such as contain saccharine matter are to be avoided ; such, for example, as sweet sparkling wines, whether they be champagnes, moselles, or hocks. An embargo is also to be put on all liqueurs and fruity wines, such as young port, RoussUlon, etc. ; sweet ales, stout, and porter are also to be shimned. If the patient is to be indulged in wines at all, let him have dry Lisbon, old Madeira, Manzanilla, or Amontillado sherries, Chablis, Niersteiner, or old Sauteme ; sound clarets may also be indulged in. "When stimilants are deemed requisite, brandy, whisky, rum, or Hollands may be used ; but these ought always to be employed with caution for the reasons previously given, when speaking of the artificial production of diabetes by means of stimulants introduced into the portal circulation. All that has now been said regarding regimen has of course only had reference to that form of diabetes arising from excessive formation. There are no restrictions either as regards food or drink requisite in cases springing from defective assimilation. On the contrary, the duty of the Practitioner is to select for his patient not only that which is most nourishing, but also that most easy of assimilation. He will often find, too, that such cases not only tolerate but even demand the free use of stimulants, in order to support the flagging vital energies, and enable the weakened organs to perform their work. I think if I were asked what is the best remedy for diabetes, I might venture to answer, in the language of Opie, when the student inquired what he mixed his colours with, "Brains, Sir." For to say that any one remedy or particular line of treatment is suitable to all cases of diabetes would be simply charlatanism of the worst sort.