diabetic vacuolation of the iris pigment epithelium

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DIABETIC VACUOLATION OF THE IRIS PIGMENT EPITHELIUM MORTON E. SMITH, M.D., AND PETER GLICKMAN, M.D. St. Louis, Missouri Vacuolation of the pigment epithelium of the iris, a characteristic finding in diabetes mellitus, was first described in 1887. 1 The phenomenon, observed clinically 2 ' 3 and his- tologically, 4 ' 5 is considered almost pathog- nomonic for diabetes mellitus (Fig. 1). The material within these vacuoles was shown to be glycogen by histochemistry 6 and by elec- tron microscopy. 7 This "lacy" vacuolation, however, is not a consistent finding. In one histologie study of 20 enucleated diabetic eyes, eight had un- equivocal vacuolation. 4 This inconsistency has never been fully explained, and attempts to correlate the finding with some common denominator have been unsuccessful. The presence of vacuolation in the pigment epithelium is not correlated with the degree of retinopathy. 8 Most speculation has focused on the concept that the pigment epithelium of the iris has the ability to accumulate or store the glycogen from the aqueous humor, like the diabetic renal tubules accumulate and store glycogen.* This phenomenon in the kidney, referred to as Armanni-Ebstein diabetic nephropathy (Fig. 2), histologically consists of glycogen vacuolation in the straight portion of the proximal convoluted tubule of the kidneys of diabetics who die in ketoacidosis with mark- edly elevated blood glucose levels, and who have glycosuria in the 72-hour period prior to death. 9 Is the same process occurring in the eye ? Is the pigment epithelium of the iris accumulating or storing glycogen when blood glucose levels are elevated? We searched for clinical evidence to support this concept. From the Department of Ophthalmology, Wash- ington University Medical Center, St. Louis, Mis- souri. This study was supported in part by research grant EY 00004 from the National Eye Institute. Reprint requests to Morton E. Smith, M.D., Washington University School of Medicine, De- partment of Ophthalmology, 660 S. Euclid Ave., St. Louis, MO 63110. MATERIAL We found 57 postmortem cases in which adequate material was available for a cor- relation between antemortem clinical and lab- oratory findings, postmortem ocular histol- ogy, and postmortem kidney histology. RESULTS There were two separate groups of diabetic patients. One group of 34 showed no vacu- olation of the iris pigment epithelium, and 33 of these had blood glucose levels below 200 mg/100 ml in the 72-hour period prior to death. Furthermore, 31 of these 33 showed no Armanni-Ebstein nephropathy. The other group of 23 showed unequivocal vacuolation of the iris pigment epithelium. Nineteen of the 23 had blood glucose levels greater than 200 mg/100 ml in the 72-hour period prior to death. Furthermore, 17 of the 19 showed the analogous phenomenon in the kidney (Armanni-Ebstein nephropathy). ;s33 \ > - ■*■■;■. Fig. 1 (Smith and Glickman). Histopathologic appearance of "lacy" vacuolation of pigment epithelium of iris in diabetes (χ150). 875

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Page 1: Diabetic Vacuolation of the Iris Pigment Epithelium

DIABETIC VACUOLATION OF T H E IRIS PIGMENT EPITHELIUM

MORTON E. SMITH, M.D., AND PETER GLICKMAN, M.D.

St. Louis, Missouri

Vacuolation of the pigment epithelium of the iris, a characteristic finding in diabetes mellitus, was first described in 1887.1 The phenomenon, observed clinically2'3 and his-tologically,4'5 is considered almost pathog-nomonic for diabetes mellitus (Fig. 1). The material within these vacuoles was shown to be glycogen by histochemistry6 and by elec­tron microscopy.7

This "lacy" vacuolation, however, is not a consistent finding. In one histologie study of 20 enucleated diabetic eyes, eight had un­equivocal vacuolation.4 This inconsistency has never been fully explained, and attempts to correlate the finding with some common denominator have been unsuccessful. The presence of vacuolation in the pigment epithelium is not correlated with the degree of retinopathy.8 Most speculation has focused on the concept that the pigment epithelium of the iris has the ability to accumulate or store the glycogen from the aqueous humor, like the diabetic renal tubules accumulate and store glycogen.*

This phenomenon in the kidney, referred to as Armanni-Ebstein diabetic nephropathy (Fig. 2) , histologically consists of glycogen vacuolation in the straight portion of the proximal convoluted tubule of the kidneys of diabetics who die in ketoacidosis with mark­edly elevated blood glucose levels, and who have glycosuria in the 72-hour period prior to death.9 Is the same process occurring in the eye ? Is the pigment epithelium of the iris accumulating or storing glycogen when blood glucose levels are elevated? We searched for clinical evidence to support this concept.

From the Department of Ophthalmology, Wash­ington University Medical Center, St. Louis, Mis­souri. This study was supported in part by research grant EY 00004 from the National Eye Institute.

Reprint requests to Morton E. Smith, M.D., Washington University School of Medicine, De­partment of Ophthalmology, 660 S. Euclid Ave., St. Louis, MO 63110.

MATERIAL

We found 57 postmortem cases in which adequate material was available for a cor­relation between antemortem clinical and lab­oratory findings, postmortem ocular histol­ogy, and postmortem kidney histology.

RESULTS

There were two separate groups of diabetic patients. One group of 34 showed no vacu­olation of the iris pigment epithelium, and 33 of these had blood glucose levels below 200 mg/100 ml in the 72-hour period prior to death. Furthermore, 31 of these 33 showed no Armanni-Ebstein nephropathy.

The other group of 23 showed unequivocal vacuolation of the iris pigment epithelium. Nineteen of the 23 had blood glucose levels greater than 200 mg/100 ml in the 72-hour period prior to death. Furthermore, 17 of the 19 showed the analogous phenomenon in the kidney (Armanni-Ebstein nephropathy).

;s33

\ > - ■ * ■ ■ ; ■ .

Fig. 1 (Smith and Glickman). Histopathologic appearance of "lacy" vacuolation of pigment epithelium of iris in diabetes (χ150).

875

Page 2: Diabetic Vacuolation of the Iris Pigment Epithelium

876 AMERICAN JOURNAL OF OPHTHALMOLOGY MAY, 1975

Fig. 2 (Smith and Glickman). Histopathologic appearance of Armanni-Ebstein diabetic nephrop­athy. Note vacuoles in the convoluted tubule (X600).

DISCUSSION

These data support evidence that the lacy vacuolation of the iris pigment epithelium in the diabetic is a reflection of the level of glu­cose within the vascular system, and prob­ably aqueous humor as well.

Two points concerning our data need emphasis. We could not correlate in a quan­titative way the degree of vacuolation with the level of blood glucose; for example, the last blood glucose level on a particular pa­tient might have been 1,000 mg/100 ml, but that did not necessarily mean the vacuolation of the iris pigment epithelium was any worse than in a patient with a blood glucose level of 300 mg/100 ml.

We feel this phenomenon of vacuolation is transient. Some of the patients in our series were admitted to the hospital with markedly elevated blood glucose levels that were brought under control, and levels of blood glucose drawn in the days prior to death were within normal range, showing no vacuolation histologically. Furthermore, ac­cording to a letter received Nov. 7,1974, from T. Kuwabara concerning the experimental animal, transient vacuolation of the iris pig­

ment epithelium can be produced by raising the blood glucose level with parenterally in­jected glucose.

We can only speculate as to what mech­anism is appropriate now. Yanoff, Fine, and Berkow7 showed that glycogen is normally present in the cells of the iris pigment epithelium and that with vacuolation of these cells in diabetes, there may either be no ac­cumulation of additional glycogen but only a redistribution of the existing material or that two forms of glycogen may be present, one in a particulate form and one that is soluble. In the kidney, the affected segment of the nephron may possess a greater ca­pacity for glycogenesis than for glycogenol-ysis when faced with excessive concentra­tions of glucose. Perhaps the pigment epithelium of the iris acts similarily.

The metabolic disturbance in these patients is complex and the usual distortion of electro­lyte and fluid distribution may be influential rather than glucose levels alone.

SUMMARY

In a postmortem study of 57 diabetic pa­tients, 19 of 23 patients with blood glucose levels greater than 200 mg/100 ml in the 72-hour period before death showed the char­acteristic histologie findings of "lacy" vac­uolation of the iris pigment epithelium as well as vacuolation of the renal tubules (Ar­manni-Ebstein nephropathy). Conversely, 33 of the remaining 34 patients with blood glu­cose levels below 200 mg/100 ml in the 72-hour period prior to death showed no vac­uolation in the iris or kidney.

REFERENCES

1. Kamocki, V. : Pathologisch-anatomische Un­tersuchungen von Augen diabetischen Individuen. Al­brecht von Graefe's Archiv. Ophthalmol. Augen-heükd. 17:247,1887.

2. Hvidberg-Hansen, J. : Pigment granules in iris pigment epithelium of diabetics. Acta Ophthalmol. 120(Suppl.) :68, 1973.

3. Ohrt, V. : Diabetic iridopathy. Dan. Med. Bull. 15:244, 1968.

4. Yanoff, M. : Ocular pathology of diabetes mellitus. Am. J. Ophthalmol. 67:21, 1969.

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VOL. 79, NO. 5 DIABETIC VACUOLATION 877

5. von Schupbach, M. : Über die zystoide De­generation des Pigmentepithels der Iris bei Dia­betes mellitus. Klin. Monatsbl. Augenheilkd. 150:1, 1967.

6. Yamashita, T., and Becker, B. : The basement membrane in the human diabetic eye. Diabetes 10: 167, 1961.

7. Yanoff, M., Fine, B., and Berkow, J. : Diabetic

lacy vacuolation of iris pigment epithelium. Am. J. Ophthalmol. 69:201, 1970.

8. Hogan, M., and Zimmerman, L. : Ophthalmic Pathology, 2nd ed. Philadelphia, W. B. Saunders and Co., 1962, p. 408.

9. Ritchie, S., and Waugh, D. : The pathology of Armanni-Ebstein diabetic nephropathy. Am. J. Pathol. 33:1035, 1957.

OPHTHALMIC MINIATURE

The patient wasn't hard to find; a nice light roan cow which looked at us carefully, one eye almost closed. From between the lashes a trickle of tears made a dark stain down the hairs of the face, and there was an eloquent story of pain in the cautious movements of the quivering lids.

"There's something in there," murmured Siegfried. "Aye, ah know!" Mr. Kendall always knew. "She's got a flippin'

great lump of chaff stuck on her eyeball but I can't get to it. Look here." He grabbed the cow's nose with one hand and tried to prise the eyelids apart with the fingers of the other, but the third eyelid came across and the whole orbit rolled effortlessly out of sight leaving only a blank expanse of white sclera.

"There!" he cried. "Nowt to see. You can't make her keep her eye still!"

James Herriot Let Sleeping Vets Lie

Michael Joseph, Ltd., 1973