Refer to: Oberman AE, Chatterjee SN: Ocular complications in renal transplant recipients. West J Med 123:184-187, Sep 1975

Ocular Complications in Renal Transplant Recipients ARTHUR E. OBERMAN, MD, and SATYA N. CHATTERJEE, FRCS (Eng, Edin, Glasg) Los Angeles

Twenty-five patients were examined for ocular complaints following renal transplantation. Besides the expected complications of posterior subcapsular cataract and cytomegalovirus retinitis, other findings-such as focal depigmentation of the retinal pigment epithelium, a lack of hypertensive retinopathy, elevated intraocular tensions, microaneurysms, preretinal wrinkling, serous detachments of the retina, hemorrhages and exudates-were observed. A laboratory clue to the onset of cytomegalovirus retinitis was a rapid rise in cytomegalovirus (CMV) antibody titer and a positive CMV plaque count in tissue culture.

MOST OF THE ocular complications following renal transplantation are recognized as secondary to immunosuppressive drugs, especially to the use of corticosteroids.) This report is an examination of the ocular complications in a series of patients who had received renal transplants, emphasizing the multiplicity of findings and the importance of laboratory aids to early diagnosis. Of 143 patients who received renal transplants at the Los Angeles County-University of Southern California Medical Center between March 1968 and April 1974, 25 were selected because of visual complaints. Their ages ranged from 22 to 52 years. Transplantation had been done in all of From the Departments of Ophthalmology (Dr. Oberman) and Surgery (Dr. Chatterjee), Los Angeles County-University of Southern California Medical Center, Los Angeles. Submitted April 28, 1975. Reprint requests to: A. E. Oberman, MD, LAC-USC Medical Center, P.O. Box 568, 1200 North State Street, Los Angeles, CA 90033.

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them between 5 to 61 months before eye examination. Before operation, all patients had i-eceived maintenance hemodialysis. Following transplantation, routine immunosuppression with azathioprine (Imuran;) and prednisone was administered as described by Silcott and associates.2 Antirejection therapy, when necessary, consisted of three doses of intravenously given methylprednisolone (Solu-MedrolI) administered on alternate days at a dose of 20 mg per kg body weight. Eleven of the 25 patients received, in addition, local irradiation of 200 rads to the graft on alternate days for three doses (Table 1). Transplants were done for varied reasons (Table 2), none of which was considered more pertinent than another with respect to ocular complications found in this series. Diabetes, presumed to be steroid induced, developed in the post-transplant period in five patients of the

RENAL TRANSPLANT RECIPIENTS TABLE 1.-Summary of Patients and Findings Patient Number, Age in Years and Sex

Diabetes Hypertension

1. 38 8 ....... 2. 35 9 ... 3. 33 ... 4. 49 ... 5. 48 9 . 6. 34 . 7. 41 . 8. 31 . 9. 25 . 10. 52 . 11. 49 9 . 12. 35 8 . 13. 45 9 . 14. 43 8 . 15. 49 . 16. 22 9 . 17. 36 . . 18. 30 19. 27 9 ... 20. 23 9 ... 21. 30 . 22. 25 5... 23. 37 8 . 24. 24 9 . 25. 37 8 .

No No No Yes No No No No Yes No No No Yes Yes No No No No No No No No Yes No

No

No No No Yes No Yes No Yes No Yes No Yes Yes No Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes

Deep X-ray to Graft

Cytomegalovirus Total Status Prednisone (U Viruria, B=Viremia) Dose, Grams

Neg. Neg. +U

Yes No Yes No Yes Yes No Yes No Yes No No Yes No Yes No No No No Yes No No Yes Yes No

+BU

Neg. Neg. Neg. Neg. + B U

Neg. Neg. + U + B U

Neg. Neg. + + + + + + + + + +

B U U B U BU B U U B U B U B U B U

256 .. .. .. .. .. .. 297 275 .. .. 334 345 330 .. 179 .. 225 .. .. .. 206 221 217 261

Eye Findings

Months from Transplant

Cataract retinal cyst

.. Inc. IOP Cataract Glaucoma Inc. IOP, depigmentation

Cataract, depigmentation

Cataract

Cataract, depigmentation .. Cataract Cataract Cataract Preretinal membrane Cataract, CMV retinitis Rubeosis iridis Cataract, Inc. IOP Cataract ..

Depigmentation

Cataract, depigmentation Cataract Cataract, CMV retinitis Cataract, Inc. IOP

36 5 15 17 7 13 29 41 25 44 61 20 21 32 40 13 54 18 16 16 8 37 13 37 17

Inc. IOP=Increased intraocular pressure CMV= Cytomegalovirus

blood. Complement fixation (CF) studies with

TABLE 2.-Causes of Primary Renal Failure Disorder

Number

............. Glomerulonephritis ......... Pyelonephritis ............ .............. Nephrosclerosis ........... .............. ................... Polycystic kidney .... .......... Hypoplasia of the kidney .......

Disseminated lupus erythematosus .....

.....

13 3 4 2 2 1

cytomegalovirus (Strain AD-169) antigen were performed by the microtiter modification of the

Kolmer technique (California State Health Department). The highest dilution of serum resulting in 3 + or 4 + fixation was considered as the CF titer.

Results group. Blood glucose was maintained at a level of 200 to 300 mg per 100 ml by dietary and drug therapy. Sixteen of the patients had persistent diastolic blood pressures greater than 100 mm of mercury, despite treatment with antihypertensive drugs. The eye examination consisted of measurement of visual acuity with and without correction, slit lamp examination, applanation tonometry, indirect ophthalmoscopy and color fundus photography. Viral cultures in human fibroblast cultures were obtained from blood (buffy coat) and urine, as described by Fiala and associates.3 Isolation of cytomegalovirus required 10 to 30 days from urine specimens and 20 to 40 days from buffy coat cells separated from heparinized peripheral

Ocular complications were found in 21 of the 25 patients. In some cases, more than one complication was present. In 15 patients the presence of cataract was noted; all cataracts being bilateral and posterior subcapsular in type. The opacity varied in appearance, from wispy cortical strands causing no visual impairment to dense white posterior plaques causing significant visual loss. The total dose of prednisone given after transplantation to the patients with cataract varied from 179 to 484 grams (Table 1). The next most frequent ocular complication was bilateral depigmentation of the retinal pigment epithelium, noted in five patients. Many variations in extent and degree of depigmentation were noted; however, no case was accompanied by pigment clumping. The depigmentation THE WESTERN JOURNAL OF MEDICINE

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of vision in one eye prompted examination of the patient; in the other, it was a chance discovery on routine indirect ophthalmoscopy. The syndrome was identified by the distinctive pattern of widespread retinal necrosis and vasculitis.4 Despite the fact that 16 of the 25 patients. were hypertensive (sustained diastolic blood pressure

greater than 100 mm of mercury), retinal vascular changes of hypertension were infrequently

seen. In only two patients was there segmental arteriolar narrowing, and in seven patients there were scattered superficial retinal hemorrhages. Less frequent complications noted were microaneurysms, deep retinal hemorrhages, hard exudates, soft exudates, preretinal wrinkling and serous detachment of the retina.

Discussion Figure 1.-Fundus photograph of multiple irregular areas of depigmentation of the retinal pigment epithelium in a renal transplant recipient.

The true frequency of ocular complications, after renal transplantation and the necessary immunosuppressive therapy, cannot be determined by this study, since only patients with complaint of ocular symptoms were examined. Previous reports have defined the major complications of cataract and cytomegalovirus retinitis.4-8 The development of posterior subcapsular cataract has been firmly related to the extended use of systemic steroids.1"9 The total dose that is critical to cataract formation is considered in conflicting reports." 8 In this study, the density of cataract and consequent visual loss could not be related to total corticosteroid dose, the duration of survival from the time of transplant or the age of the

patient. Cytomegalovirus retinitis is

Figure 2.-Acute retinitis due to cytomegalovirus. Hemorrhagic vasculitis of the superior temporal retinal vessels surrounded by massive white banks of retinal necrosis.

was frequently in the perimacular area, and occasionally seen in multiple areas of the mid-periphery of the fundus (Figure 1). Elevated intraocular tension, as measured by tonometry, was found in five patients of the series. Glaucomatous cupping of the optic disc was noted, however, in only one of these. The major disabling ocular complication was bilateral cytomegalovirus (CMV) retinitis, discovered in two patients (Figure 2). In one, loss 186

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an example of a retinal response to an organism of low virulence in an immunologically compromised host. The ineffectiveness of reducing systemic steroids to halt the fulminating course of the disease confirmed other reports.4'5 Detection of retinitis is aided by careful monitoring of buffy coat culture plaque count and recognition of a rising complement fixation titer of antibody. Findings, other than cataract and retinitis, have not been previously considered characteristic of this patient population. The lack of hypertensive retinopathy in a patient group, the majority of which were hypertensive, is most unusual.7 Focal depigmentation, if related to transplantation and antirejection therapy, is a new finding. Since these patients were relatively young, senile degeneration could not be considered an etiologic factor. One possibility would be an unidentified

RENAL TRANSPLANT RECIPIENTS

virus in the immunosuppressed tissue. The fact that cytomegalovirus inclusions have been found in pigment epithelium of renal transplant recipients4'6 should raise the possibility that other viruses also could be present. In an unrelated ocular disorder called acute posterior multifocal placoid pigment epitheliopathy,'0 a characteristic alteration of the pigment epithelium is considered to be of possible viral cause. Another mechanism for depigmentation -may be hypertensive changes in the choroid. Lack of sufficient hypertensive retinal findings makes this unlikely. REFERENCES 1. Porter R, Crombie AL, Gardner PS, et al: Incidence of ocular complications in patients undergoing renal transplantation. Br Med J 3:133-136, Jul 15, 1972

2. Silcott GR, Barbour BH, Mendez R, et al: Functional recovery from acute rejection as a guide to ultimate renal graft survival. Arch Surg 104:791-793, Jun 1972 3. Fiala M, Edmondson L, Guze LB: Simplified method for isolation of cytomegalovirus and demonstration of frequent viremia in renal transplant patients. Proc Soc Exp Biol Med 144:872-876, Dec 1973 4. DeVenecia G, Zu Rhein GM, Pratt MV, et al: Cytomegalic inclusion retinitis in an adult-A clinical, histopathologic, and ultrastructural study. Arch Ophthalmol 86:44-55, Jul 1971 5. Aaberg TM, Cesarz TJ, Rytel MW: Correlation of virology and clinical course of cytomegalovirus retinitis. Am J Ophthalmol 74:407 417, Sep 1972 6. Wyhinny GJ, Apple DJ, Guastella FR, et al: Adult cytomegalic inclusion retinitis. Am J Ophthalmol 76:773-781, Nov 1973 7. Berkowitz JS, David DS, Sakai S, et al: Ocular complications in recent transplant recipients. Am J Med 55:492495, Oct 1973 8. Hovland KR, Ellis PP: Ocular changes in renal transplant patients. Am 3 Ophthalmol 63:283, 1967 9. Black RL, Oglesby RB, Von Sallman L, et al: Posterior subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. JAMA 174:166, 1960 10. Ryan SJ, Maumanee AE: Acute posterior multifocal placoid pigment epitheliopathy. Am J Ophthalmol 74:1066-1074, Dec 1972

Cocaine: Its Use in Otolaryngology Cocaine is the only local anesthetic with inherent vasoconstrictive abilities, a sine qua non for effective intranasal surgery. Other applications include shrinkage of mucous membranes, vasoconstriction and anesthesia. If we grant then the myriad usage of cocaine in ear, nose and throat practice, why the objection to its use? The answer lies in its toxicity. In spite of the warning issued 50 years ago against the usage of cocaine mud (a mixture of cocaine flakes and 1:1,000 epinephrine), it is still widely accepted. The effectiveness of vasoconstrictors in retarding absorption of injected local anesthetics is proven, but the addition of epinephrine in topical application may actually be harmful. Vasoconstrictors do not retard absorption from the mucous membrane and while they may intensify the shrinkage of the mucous membrane, deleterious effects of the epinephrine itself should preclude its use in combination with cocaine. In addition, cocaine sensitizes the patient to exogenous epinephrine. Is there an acceptable alternative? A totally suitable synthetic topical anesthetic has not been forthcoming. No one compound, nor even a combination of substances, has been able to provide the mucous membrane anesthesia, tissue shrinkage, vasoconstriction, duration of action and acceptable level of toxicity possessed by the extract of Erythroxylon coca. We are led then to the inevitable conclusion that cocaine remains a vital instrument in the otolaryngologist's armamentarium, and can make the following recommendations: Cocaine in the hands of knowledgeable and cautious physicians is an unexcelled topical anesthetic and is certainly not habit forming to the patient. -NICHOLAS L. SCHENCK, MD, El Paso Extracted from Audio-Digest Otorhinolaryngology, Vol. 7, No. 23, in the Audio-Digest Foundation's subscription series of tape-recorded programs. For subscription information: 1930 Wilshire Blvd., Suite 700, Los Angeles, CA 90057.

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Refer to: Oberman AE, Chatterjee SN: Ocular complications in renal transplant recipients. West J Med 123:184-187, Sep 1975 Ocular Complications in Re...
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