Ocular complications in renal transplant recipients

Ocular Complications in Renal Transplant Recipients

JEROME DAVID SOICHI

S. BERKOWITZ, S. DAVID, SAKAI,

The ocular complications in renal transplant recipients were evaluated in 44 patients and in 22 control patients with renal failure. Of the 44 patients 33 showed some ocular abnormality, but only posterior subcapsular cataracts which occurred in 34 per cent of post-transplant patients could be related to posttransplant corticosteroid therapy. There was no correlation between posterior subcapsular cataracts and either the duration of daily doses or total doses of corticosteroids in patients under 25 years of age in whom the incidence of posterior subcapsular cataracts tended to be higher than in older patients. There appeared to be a significant correlation between the duration of therapy and the total corticosteroid dose and the incidence of posterior subcapsular cataracts in the older age group.

M.D.

M.D.

M.D.*

HIROMU

SHOJI,

JHOONG

S. CHEIGH.

M.D.?

ROBERT

R. RIGGIO,

M.D. M.D.

KURT H. STENZEL,

M.D.

ALBERT

M.D.

L. RUBIN,

New York. New York

complications frequently occur after renal transplantation [l-4] and are usually attributable to corticosteroids used for immunosuppressive therapy. Renal transplantation is a relatively new procedure with a tremendous potential for restoring many people to normal life. Since, in evaluating the side-effects of corticosteroid therapy on any system, the underlying disease plays an important role in determining the type, incidence and severity of the side-effects seen [5-61, we decided to examine the ocular complications of steroid therapy in postrenal transplant patients. Ocular

PATIENTS

From the Department of Ophthalmology and the Rogosin Kidney Disease Treatment Center, New York Hospital-Cornell Medical Center, and the Department of Medicine, St. Luke’s Hospital Center-Columbia College of Physicians and Surgeons, New York, New York. Requests for ‘reprints should be addressed to Dr. David S. David, St. Luke’s Hospital Center, Amsterdam Avenue at 114th Street, New York, New York 10025. Manuscript accepted April 6, 1973. *Present address: c/o Dr. J. Sakai, 4-22-10 Nishishinjiku, Shinjiku-ku, Tokyo 160, Japan. tPresent address: Department of Orthopedic Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.

492

October

1973

The American

AND

METHODS

The 44 patients in this series (average age 26 years, range 9 to 49 years, 30 male and 14 female) all had chronic renal failure of at least 1 year’s duration, and most had been treated with regular hemodialysis (from 1 to 26 months) before receiving an allogenic renal transplant (17 from living related donors and 27 from cadavers). The daily immunosuppressive regimen consisted of prednisolone, 1.5 mg/kg body weight for the first 3 days after the transplant, being tapered, in the presence of good renal function, to 0.3 mg/kg by the 6th week after transplant, reaching a maintenance dose of 0.15 mg/kg by the 6th month after transplant. During acute rejection episodes the dose of prednisolone was increased to 1.5 to 15 mg/kg body weight for 3 days and tapered to a maintenance dose of 0.3 to 0.15 mgf kg body weight in 2 weeks’ time. The azathioprine dose was 5 mg/kg the day before the transplant, 4 mg/kg the day of the transplant, 3 mg/kg the first day after the transplant and then 2 mg/kg a day as maintenance. The dose of azathioprine was never increased during rejection; in fact, depending on the white blood cell

Journal of Medicine

Volume 55

OCULAR

count,

rt was

frequently

jection

Twenty-two

ceiving

chronic

decreased

patients

dialysis

age and sex. were

renal

severe

failure

(3 to 24 months),

and

matched

re-

after pupillary dilatation. and indirect ophthalmos-

material

were

material

was

clumps extending transparency were

seen, noted,

forward present.

into

3-t

when

coalescing

and

4-F

when

the

cortex

with

of

heavy loss

of

RESULTS

Table I shows the positive ocular findings in the 44 transplant recipients. Of 44 patients 33 (75 per cent) showed some ocular abnormality. The two most common findings were posterior subcapsular cataracts in 15 patients (34 per cent) and decreased visual acuity in 22 patients (50 per cent). Of the 22 patients in the control group (41 per cent), 9 had abnormal ocular findings, 6 (27 per cent) decreased visual acuity, 3 hypertensive retinopathy, and 1 diabetic retinopathy. Posterior subcapsular cataracts were not seen in any of the control patients with renal failure. This difference between the steroid-treated group and the controls was highly significant (P
I

Positive Ocular Findings in 44 Post-Transplant Patients Findings

No. of Patients

1. Posterior subcapsular 2. Visual acuity less than With cataracts Without cataracts 3. Other findings Elevated intraocular Congenital 6th nerve Anterior lenticonus Fabry’s disease with cornea (in patient hereditary Ad herent

cataract 20/20

7 15 pressure palsey cloudy

retinal

1

secondary

NOTE:

Some

1 due to bullous

detachment

Hypertensive patients

1

retinopathy had more than

BERKOWITZ

Renal Disease and

Duration of Disease(yr)

29 15

Duratron of Hemodialysis(mo)

4.6 (1-15) 5.3 (l-20)

NOTE: Figures in parentheses

ET AL

indicate

8.6 (O-26) 7.9 (1-18)

the range.

duration of known renal disease and duration of hemodialysis (Table I I). Nor did there seem to be a significant difference between these groups in duration of steroid therapy, the average daily dose of prednisolone (Table Ill) or the total dose of prednisolone received (Table IV). Neither sex, average serum calcium nor creatinine clearance had any effect on the incidence of cataracts (Table V). But in the younger age group the mean creatinine clearance in those with cataracts was lower (40 f 23 cc/min) than in those average

without cataracts (62 f 33 cc/min) (P
Average Daily Dose of Prednisolone Presence of Cataracts Tota,

Group

No,

~~_

___

and

Prednisolone Ox)

Patients

2.5-5

6-10

11-15

16-20

29 15

8 4

11 6

7 4

3 1

12 11

5 4

3 3

2 2

2 2

17 4

3 0

8 4

5 0

1 0

Total

to trauma Maculopathy

Total No.

Without cataracts With cataracts

1 1 1

with

nephritis) leu koma

15

RECIPIENTS

Duration of Underlying Hemodialysis

Patients

were graded as 1-F when the lense was transparent but there was evidence of clouding, 2-F when clumps opaque

TABLE II

for

l-he intraocular pressures were measured, and fields were determined in all patients. Cataracts

of opaque

IN RENAL TRANSPLANT

re-

also studied.

The eyes were examined, with a slit lamp and by direct copy. visual

during

with

COMPLICATIONS

2 one finding.

Without cataract With cataract Under age 25 Without cataract With cataract Over age 25 Without cataract With cataract

October 1973

The American Journal of Medicine

Volume 55

493

OCULAR

COMPLICATIONS

IN RENAL TRANSPLANT

Total Dose of Prednisolone

TABLE IV

RECIPIENTS-BERKOWITZ

and Presence

of Cataracts

ET AL

_~~__

Prednisolone (g)

Total No. Group

Patients

o-5

5.1-10

10.1-15

Total Without cataract With cataract

29 15

9 3

6 3

6 2

3 2

1 3

3 2

1 0

Under ,age 25 Without cataract With cataract

12 11

5 3

1 3

2 2

2 1

0 1

1 1

1 0

Over age 25 Without cataract With cataract

17 4

4 0

4 0

4 0

2 1

1 2

2 1

0 0

peared

in 34 per cent of these patients and in none of the 22 control patients with renal failure (P
Average Serum Calcium Clearance and Cataracts No. of Pabents

Group Total Without cataract With cataract NOTE:

494

Figures

29 15

in parentheses

October 1973

--20.1-25

8.8 (5.6-12.2) 8.3 (6.6-9.9)

TABLE VI

Creatinine Clearance (cc/min)

30

Posterior Subcapsular Cataracts Occurring Within 1 Year of Steroid Therapy

Weight

Average Daily Dose of Prednisolone

(yr)

(kg)

(mg)

(8)

(mo)

23 9 12 16 18

130 75 85 95 90

5 2.5 12.5 5 5

5.1 1.3 3.5 2.4 9.2

6 2 4 7 11

Age Patient E.B. K.C. K.L. L.M. H.T.

59 (10-140) 46 (13-113)

the range.

The American Journal of Medicine

25.1-30

(125 years of age) 9 of 19 patients (47 per cent) who received a total dose of prednisolone of less than 20 g had posterior subcapsular cataracts as opposed to only 1 of 15 (7 per cent) in the older age group (P CO.05). Although previous investigators have believed that the incidence of cataracts with systemic corticosteroids depends predominantly upon the dose and duration of drug therapy [7,9], this was not so in the present series. There appeared to be no correlation between the average daily dose of prednisolone and the incidence of cataracts. There did seem to be a correlation between the severity of the cataracts, however, and the daily dose of prednisolone in the younger patients. In six patients with grade l-l- cataracts the mean daily dose of prednisolone was 7.5 f 4.7 mg, whereas in the five patients with grade 2-l- to 4-t cataracts the mean daily dose was 14 f 4.1 mg (P <0.05). There was no correlation between the duration of steroid therapy and the incidence of cataract formation in the younger age group. In the older age group, however, no cataracts were noted in 12 patients who received therapy for less than 30 months, whereas cataracts were noted in 4 of 9 patients who received therapy for more than 30 months (P <0.05). The total dose of prednisolone received showed no correlation with the incidence of posterior sub-

and Creatinine

Serum Calcium (mg/lOO ml)

indicate

15.1-20

Volume 55

Total Dose Time of TransPredplant nisolone Studied

OCULAR COMPLICATIONS IN RENAL TRANSPLANT RECIPIENTS

capsular cataracts were not found of age. But in the older age groups

in 13 patients posterior sub-

capsular cataracts were not found in 13 patients whose total dose of prednisolone was less than 15 g, whereas in 4 of 8 patients who received more than 15 g of prednisolone posterior subcapsular cataracts developed (P
RFRKOWITZ ET AL

of posterior subcapsular cataracts and the incidence of other side-effects of corticosteroids, including the carbohydrate abnormalities. Most of our patients demonstrated the classic signs of an iatrogenic Cushing’s syndrome. Intraocular pressure is only occasionally increased with the use of systemic corticosteroids [6], and occurred in only 1 of the 44 post-transplant patients. Hoveland and Ellis [3], however, noted it in 8 of 26 post-transplant patients; a much higher incidence than previously reported. The high incidence (50 per cent) of decreased visual acuity seen in post-transplant patients receiving steroids was not related to the presence or absence of posterior subcapsular cataracts, being noted in 7 patients with posterior subcapsular cataracts and in 15 without posterior subcapsular cataracts. Decreased visual acuity was also seen in 6 of 22 control patients with renal failure. Since many of the patients with decreased visual acuity gave a history of poor vision during their end-stage renal failure which improved with dialysis, and since many also showed disrupted macular pigmentation, it is believed that the decreased visual acuity was a residua from uremic retinal edema infarcts and inflammation associated with fluid overload and hypertension in patients with renal failure [12,13]. One patient in fact had a residua of severe maculopathy due to bullous retinal detachment that occurred prior to dialysis therapy, which improved after dialysis. Although many patients have mild degrees of renal hypertension after transplantation, which may be aggravated by steroid therapy [5,6], only two of our patients had evidence of hypertensive retinopathy after transplant. The incidence of diabetic retinopathy due to corticosteroid-induced carbohydrate abnormality is extremely low [14] and was not seen in any of our post-transplant patients.

REFERENCES 1.

2. 3. 4. 5.

6. 7.

Kern R, Zaruba K, Scheitlin W: Ocular side-effects of lonq-term immunosuppressive therapy in recipients of cadaver kidney transbiants. Ophthal k& 1: 21; 1970. Porter R, Crombie AL, Gardner PS, Uldall RP: Incidence of ocular complications in patients undergoing renal transplantation. Brit Med J 3: 133. 1972. Hoveland KR, Ellis PP: Ocular changes in renal transplant patients. Amer J Ophthal 63: 283, 1967. Thiel G. Mahlich J: Cortisone cataract after renal transplantation. Deutsch Med Wschr 97: 860, 1972. David DS, Grieco MH. Cushman P Jr: Adrenal glucocorticoids after twenty years: a review of their clinically relevant consequences. J Chron Dis 22: 637, 1970. David DS, Berkowitz JS: Ocular effects of topical and systemic corticosteroids. Lancet 2: 149, 1969. Braiver D, Richards RD, Good TA: Posterior subcapsular cataracts in steroid treated children. Arch Ophthal 77: 161, 1967.

8. 9.

10. 11. 12.

13.

14.

October 1973

Furst C, Smiley WK, Ansell BM: Steroid cataract. Ann Rheum Dis 25: 364, 1966. Giles CL, Mason FL, Duff IF, McLean JA: The association of cataract formation and systemic corticosteroid therapy. JAMA 182: 719, 1962. Berlyne GM, Ari JB. Danovitch GM, Blumenthal M: Cataracts of chronic renal failure. Lancet 1. 509. 1972. Stewart WK. Maclean H: Cataracts of chronic renal failure. Lancet 1: 791, 1972. Klein BA: lschemic infarcts of the choroid: a cause of retinal separation in hypertensive disease with renal insufficiency. Amer J Ophthal 66: 1069, 1968. Paris GL. Macoul KL: Reversible bullous retinal detachment in chronic renal disease. Amer J Ophthal 67: 249, 1969. Sprague RG, Randall RV, Salossa RM. Scholz DA, Priestly JT. Walters W, Bulbulian AH: Cushing’s syndrome: a progressive and often fatal disease. Arch Intern Med (Chicago) 98: 389. 1956. The American Journal of Medicine

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