Ophthalmic assessment of children before renal transplantation

Ophthalmic assessment of children before renal transplantation Abdulmutalib Behbehani, MD, FRCSC; Stephen Kraft, MD, FRCSC; J. Raymond Buncic, MD, FRCSC; Alex V. Levin, MD, MHSc, FRCSC ABSTRACT • RESUME Objective: To evaluate the usefulness of routine ophthalmic examination before renal transplantation in children. Methods: We reviewed the records of ophthalmic assessments of renal transplant recipients at The Hospital for Sick Children, Toronto, Ont., from January 1989 to June 1996. If abnormalities had been found, we determined whether they had previously been documented, were related to the renal disease or other systemic disease, had required intervention or had affected visual function. We calculated the maximum statistical chance of detecting a meaningful eye problem at the pretransplantation assessment. We also estimated the direct cost of the ophthalmic assessment and the effect, if any, of the findings on the patient's medical management. Results: We included I07 charts. Before the ophthalmic assessment, 32 patients (30%) had known eye problems. The ocular examination detected abnormalities in 46 patients (43%); the abnormalities had not been detected previously in 14 ( 13%). New, potentially vision-threatening eye disorders were found in 6 (6%) of the patients. No finding affected the short- or long-term management of any patient. Conclusion: Children with chronic renal failure had a high prevalence of ocular abnormalities, but most of the abnormalities did not affect visual function. Although ophthalmic assessment before transplantation did not alter the medical management of the renal transplant patients, consultation may be helpful in selected patients, particularly those who are not already under the care of an optometrist or ophthalmologist and those who have a visual complaint.

Objet : Evaluation de l'utilite de l'examen oculaire de routine avant Ia greffe renale chez les enfants. Methodes : Nous avons examine les dossiers d'evaluation oculaire chez les recipiendaires de greffes renales du Hospital for Sick Children, a Toronto (Ont.), entre

From the Department of Ophthalmology. The Hospital for Sick Children, University of Toronto, Toronto, Ont.

Correspondence to: Dr. Alex V. Levin, Department of Ophthalmology, Ml58, The Hospital for Sick Children, 555 University Ave., Toronto ON M5G 1X8; fax (416) 813-6261; [email protected]

*Dr. Behbehani is currently at the Faculty of Medicine, University of Kuwait, Kuwait City.

Presented in part at the Departmental Research Day, Department of Ophthalmology, University of Toronto, Toronto, Ont., May 30, 1997. This article has been peer-reviewed.

Originally received Aug. 30, 2002 Accepted for publication Apr. 2, 2003

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Ophthalmic assessment-Behbehani et al janvier 1989 et juin 1996. S'il y avait des anomalies, nous cherchions si elles avaient ete documentees, si elles etaient liees a Ia maladie renale ou a une autre maladie touchant l'organisme entier et si elles avaient entralne une intervention ou affecte Ia fonction visuelle. Nous avons calcule statistiquement Ia possibilite maximale de detecter un important probleme oculaire lors de !'evaluation qui a precede Ia greffe. Nous avons aussi estime le coOt direct de !'evaluation oculaire et, le cas echeant, l'effet des constatations sur le traitement medical du patient. Resultats : Nous avons tenu compte de I07 dossiers. Avant I' evaluation oculaire, 32 patients (30 %) avaient des problemes oculaires connus. L'examen oculaire a revele des anomalies chez 46 patients (43 %); les anomalies n'avaient pas ete decelees auparavant chez 14 patients ( 13 %). On a trouve des troubles potentiellement dangereux pour Ia vue chez 6 patients (6 %). Aucune trouvaille n'a affecte le traitement du patient a court ou a long terme.

Conclusion : Les enfants qui avaient une insuffisance renale chronique avaient une plus forte prevalence d'anomalies oculaires, parmi lesquelles Ia plupart n'avaient pas affecte Ia vue. Bien que !'evaluation oculaire precedant Ia greffe n'eut pas modifie le traitement medical des patients ayant re~u une greffe renale, Ia consultation pourrait etre utile pour des patients selectionnes, notamment ceux qui ne sont pas deja suivis par un optometriste ou un ophtalmologiste et ceux qui se plaignent de problemes oculaires.

outine ophthalmology consultation before transplantation has become standard practice in some centres. The purpose of the consultation is to establish a baseline and to identify factors that might predispose to ocular complications of transplantation (e.g., activation of a toxoplasmosis chorioretinal scar owing to immunosuppression). Because many children are hypertensive before renal transplantation, they are often screened for hypertensive retinopathy and the adverse effects of metabolic imbalances, such as ocular surface calcification. If the cause of the chronic renal failure is unknown, ocular findings may help in arriving at a diagnosis, especially if the renal failure is part of a syndrome (e.g., Alport syndrome). Currently, 3 hospitals in Ontario perform renal transplantation in children. Indications for ophthalmic screening before renal transplantation include a) diagnosis of end-stage renal disease of unknown origin, b) treatment with prednisone, c) cystinosis, d) history of increased intraocular pressure (lOP) and e) persistent hypertension (Renal Transplant Service, The Hospital for Sick Children, Toronto, Ont.: personal communication). At The Hospital for Sick Children, all children are routinely assessed by the Department of Ophthalmology before renal transplantation. The value of routine ocular examination before renal transplant surgery remains unproven. It was our empirical feeling that the positive yield of these

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examinations was very low, and we were concerned that this routine screening might represent an unnecessary cost to the health care system, inconvenience to the family and discomfort to the child. We therefore assessed how ophthalmologic screening before renal transplantation affects the management of patients and estimated the cost of these assessments to the health care system. We are unaware of previous studies published in the English literature that addressed ocular findings and routine screening in an exclusively pediatric population before renal transplantation. METHODS

We reviewed the charts of all patients who had received their first renal transplant at The Hospital for Sick Children, Toronto, Ont., between January 1989 and June 1996. Patients who had been transferred to other hospitals after transplantation were excluded from our study. During this period, all potential kidney recipients had received a complete eye examination as a part of their evaluation before transplantation surgery. Each patient had been questioned by the ophthalmologist about past or present eye problems. We noted from the records if the patients had eye problems on arrival at The Hospital for Sick Children's ophthalmology service. If abnormalities had been

Ophthalmic assessment-Behbehani et al found, we determined whether they had previously been documented, had been related to the renal disease or other systemic disease, had required intervention or had affected visual function. We analyzed 3 factors to evaluate the usefulness of ophthalmologic examination before transplantation: 1) the predicted or recommended effect of the assessment on the ophthalmic or systemic management of the children, 2) the maximum chance of detecting a meaningful eye problem and 3) the estimated cost of these assessments to the health care system. If the child had required no treatment or no additional treatment because of the findings, we concluded that the assessment had no effect on medical management. To calculate the maximum chance of detecting a meaningful eye problem, we used an equation developed 1 by Hanley and Lippman-Hand: maximum risk = 3/n, where n =number of patients examined. We calculated the direct cost of the ophthalmology consultation at The Hospital for Sick Children as the amount of money paid to the physician from the Ontario Health Insurance Plan. We considered but did not calculate other costs, such as those of time off work, transportation and parking for the parents, time of the clinic clerk and the hospital inpatient transport clerk, and clinical time of physicians that could have been devoted to other needs. RESULTS

We reviewed 112 charts. All 112 patients had undergone their first transplantation and follow-up at our institution. We excluded the 5 patients who had no available ophthalmology records; we were unable to determine whether these 5 children had or had not had eye examinations. The charts of the remaining 107 patients were entered into the study. Of the 107 patients, 69 (64%) were male. The mean age at the time of examination was 7.8 years (standard deviation [SD] 3.3 years, range 9 months to 15.5 years). The mean age at the time of renal transplantation was 8.6 years (SD 3.4 years, range 1 to 16 years). As Table 1 shows, of the 107 patients, 75 (70%) did not have any eye symptoms at the time of presentation for the pretransplant ocular assessment, but 32 (30%) had 1 or more current or prior eye problems; 7 of the 32 (7% of the 107) had previously diagnosed serious or potentially serious eye problems. On examination by our ophthalmology service, 61 (57%) of the 107 patients were found to have normal eyes and 46 (43%) to have abnormalities; of the 46, 13 (12% of the 107)

Table !-Results of ophthalmic assessment before renal transplantation in I07 patients No. (and %) of patients Results

By history

No eye problems Ocular abnormalities Potentially serious New New potentially serious

75 (70) 32 (30) 7 (6) -

By examination 61 46 13 14

(57) (43) ( 12) (13)

6 (6)

had vision-threatening or potentially vision-threatening abnormalities. The examination revealed new abnormalities in 14 patients (13% ); these abnormalities were potentially vision-threatening for only 6 patients (6% ). Twenty-two patients (20% ), including those who had problems that compromised their vision, had received eye care previously, 13 (12%) from an ophthalmologist and 9 (8%) from an optometrist. Table 2 shows the primary renal diagnoses of these children's conditions. Some children had more than 1 cause for their renal failure. Some children had systemic syndromes or diseases: 3 had Down syndrome, 3 had brachio-oto-renal syndrome, and 1 each had VATER association (vertebral, anal, tracheal, esophageal and renal anomalies), Alagille syndrome, spinocerebellar ataxia and hepatic fibrosis. Table 2-Primary renal diagnoses in the I07 patients Diagnosis Renal dysplasia Obstructive uropathy Reflux nephropathy Cystinosis Focal segmental glomerulosclerosis T ubulointerstitial nephritis Polycystic disease Dysplasia and obstructive uropathy Dysplasia and reflux nephropathy Glomerulonephritis Hemolytic-uremic syndrome Congenital nephrotic syndrome Pyelonephritis Medullary cystic disease Miscellaneous disorders

No. of patients* 20 17 15

8 6 6 5 4 4 4 4 2 2 2

8

*Some patients had more than I cause for their renal failure.

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Refractive error, photophobia and strabismus were the most common eye problems reported (Table 3) by or for 13, 6 and 5 patients, respectively. All those who had photophobia had cystinosis with crystalline keratopathy. Amblyopia, advanced glaucoma, retinal detachment, cataract, nystagmus, coloboma, retinal dysplasia and optic atrophy were the vision-threatening or potentially vision-threatening conditions reported for 7 patients. The most common abnormalities found on examination (Table 3) were refractive error, band keratopathy, anterior-segment crystal deposits, photophobia and strabismus, in 13, 9, 7, 6 and 6 patients, respectively. Vision-threatening or potentially vision-threatening abnormalities found on examination, in 13 patients, were amblyopia, cataract, nystagmus, uveal coloboma, high lOP, retinal detachment, retinal dysplasia and optic neuropathy. The most common newly documented ocular abnormalities (Table 3) were band keratopathy, anterior-segment crystal deposits, tortuous retinal blood vessels, disc dysplasia and retinal pigment epithelial changes. Other findings, although newly documented, were consistent with the already established systemic diagnoses; these included epicanthal fold and Brushfield's spots (Down syndrome), posterior embryotoxon (Alagille syndrome) and nystagmus (spinocerebellar disease). Vision-threatening or potentially vision-threatening conditions that were newly found were amblyopia, exotropia, a small posterior subcapsular cataract, elevated lOP, and asymmetric ratio of cup to optic disc with normal lOP. However, except for the amblyopia, none of these newly documented findings affected visual function at the time of diagnosis. The results of the examinations did not lead to any changes to the systemic or ocular diagnosis or therapy for any patient, as none required new or additional treatment for their eye disorders except for the patient with amblyopia, who was to receive follow-up in the community. The cost of an ophthalmology consultation at the time of this study was approximately $68 (Can.). Thus, for the 107 patients in our study the cost of consultation was $7276. However, the total cost to society was higher, as the $7276 does not include the costs of nursing care or indirect costs, such as those of transportation and time off work for the parents. In addition, 20% of the patients had already been seen by other ophthalmologists or optometrists. We cannot exclude the possibility that disease may have emerged or evolved between the prior eye exam and our examination.

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Given that none of the detected abnormalities affected the functional vision or the ongoing management of the screened population of 107 patients, the maximum statistical long-term chance of such an abnormality occurring is 2.8% (3/n, n being the number of patients examined [95th percentile confidence limit]). 2 DISCUSSION

In our experience, routine ophthalmic assessment before renal transplantation did not alter the children's ophthalmic or systemic management. However, in 6% of the patients, potentially vision-threatening disorders were newly discovered. The visual system can be adversely affected by chronic renal disease through several mechanisms: uremia and hypertension, complications of treatment, vascular events and ocular disease accompanying the primary syndrome, such as Senior-Loken syndrome, cystinosis and Bardet-Biedl syndrome. 3 Our study is the first in the English literature, to our knowledge, that addresses ocular findings in a purely pediatric population just before transplantation. Nearly onethird of our study patients had a history of ocular symptoms or previously documented signs, 7% of which reflected conditions that may compromise vision. This high incidence of symptoms and signs prior to screening may reflect the nature of some of the primary systemic diagnoses (e.g., all patients with photophobia had symptomatic cystinosis) and the eye care these patients had received (20% had already been seen by an ophthalmologist or optometrist). On examination by our service, 43% of children with chronic renal failure were found to have eye abnormalities. This proportion is in keeping with the results of previous studies. 4 •5 Other studies 6- 13 have shown a wide variation in findings, with an incidence ranging from 5% to 87%, and including abnormalities that would be unexpected in childhood, such as diabetic retinopathy and central retinal vein occlusion. The variability in incidence seems to reflect wide variation in sample size (n = 22 to 115) and subject age (7 to 71 years, but indeterminate in many studies). The types of abnormalities that we found (amblyopia, strabismus and congenital defects) are characteristic of a pediatric population. Our children shared with the pediatric patients of other studies 5 •7 ·9•10 •14 the high incidence of refractive error and corneal-conjunctival calcification, even though the latter was minimal in our patients. Conversely, certain conditions, such as

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Table l-Ocular abnormalities reported or found among the I07 patients No. of patients*

Abnormality* Refractive error Band keratopathy Anterior-segment crystal deposits Photophobia Strabismus Tortuous retinal blood vessels Amblyopia Cataract Disc dysplasia Nystagmus Retinal pigment epithelial changes Redness Eyelid eczema Epicanthal fold Bell palsy Oculomotor apraxia Posterior embryotoxon Brushfield's spots Uveal coloboma Glaucoma Ocular hypertension Asymmetric cup:optic disc ratio Retinal detachment Retinal dysplasia Retinal crystal deposits Optic atrophy or neuropathy Decreased visual evoked potential

By history

By examination

Newly documented

13

13

0 0

9 7

0 9 7

6 5 0

6 6 5

0 I 5

2 2 0

3 3 3

I 0

2 2

I I 3 I

2

I 0 0 I I 0 0 I I 0 0

I I I 0 0 I I I I I I

0 I I 0 0 I I 0 0 I I

I I 0 I

I I I I

0 0 I 0

I

0

0

Potentially visionthreatening

3 3

2

I I

I I I

*Some patients had more than I abnormality.

hypertensive retinopathy, cataract, diabetic retinopathy and optic atrophy, were less common in our population. Only 13% of the children in our study had their ocular findings first detected during our screening examination. Almost 6% of our patients had newly documented potentially vision-threatening conditions but none that actually affected visual function at the time

of the consultation, except for 1 patient who had amblyopia. No newly documented problem needed any new treatment. This examination did not make any additional contribution to the medical management of any patient except the child with newly diagnosed amblyopia, for whom follow-up after discharge was recommended. Furthermore, these children were often not well and were subjected to numerous tests.

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Any reduction in their medical encounters before transplantation would likely be a psychosocial benefit. Our study was retrospective, a design with inherent weaknesses. The eye examinations had been carried out by a number of ophthalmologists, who likely varied in their assessment of certain subtle or subjective ocular findings. Because of our exclusion criteria, we did not review the charts of all patients who had renal transplants during the study period. For instance, we did not look at the possibility that children who had multiple transplants (14 patients) were at higher risk for eye abnormalities; and the 40 transferred patients and 5 patients with incomplete records may have had abnormalities. The referral and discharge patterns in our province do not lead us to suspect any particular difference between the population followed at our institution and that transferred elsewhere. In summary, although across all age groups a high proportion (43%) of children with chronic renal failure waiting for kidney transplantation had ocular abnormalities, only 6% had findings that were new and could potentially compromise vision. Routine ophthalmic assessment before renal transplantation revealed undiagnosed abnormalities in 13% of our patients, but none that affected visual function. Including those with more serious eye problems, 20% had already received eye care from ophthalmologists or optometrists. No children required changes in their ocular or renal care as a result of the eye examination before renal transplantation. Our study suggests that formal ophthalmic consultation is necessary and cost-justified only in patients who are not already under the care of an ophthalmologist or optometrist, fail a standard visualacuity screening test performed by their pediatrician or family physician, or have specific ocular concerns. REFERENCES

1. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. lAMA 1983;249: 1743-5.

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2. Jovanovic BD, Zalenski RJ. Safety evaluation and confidence intervals when the number of observed events is small or zero. Ann Emerg Med 1997;30:301-6. 3. Knox DL. Ocular complications of chronic renal diseases. Transplant Proc 1987;19(Suppl 2):73-4. 4. Aydin P, Oto S, Kadayif~ilar S, Dursun D. Ophthalmological problems in renal transplant patients. Transplant Proc 1996;28:2312-3. 5. Hardie I, Matsunami C, Hilton A, Dyer J, Rumbach 0. Ocular complications in renal transplant recipients. Transplant Proc 1992;24: 177. 6. Saito S, Matsuno T, Tanaka N, Orita K, Sakagami K, Fujiwara T. Ocular complications in renal allograft recipients with special reference to steroid cataractogenic factor. Transplant Proc 1996;28: 1474-5. 7. Bourquia A, Zaghloul K, Berrada S, Essanadu HE, Ramdani B, Ben Youssef S, eta!. [Ophthalmologic manifestations in patients undergoing chronic hemodialysis]. Ann Med Interne (Paris) 1992;143:18-21. 8. Das T, Gupta A, Sakhuja V, Gupta KL, Minz M, Chung KS. Ocular complications in renal allograft recipients. Nephrol Dial Transplant 1991;6:649-55. 9. Hilton AF, Harrison JD, Lamb AM, Petrie JJB, Hardie I. Ocular complications in haemodialysis and renal transplant patients. Austr J Ophthalmol1982;10:247-53. 10. Vallino F, Santambrogio S, Elli A, Cattani F, Bertoni G, Quarto Di Palo F, eta!. [Ocular complications in patients undergoing long-term hemodialysis and renal transplants from cadavers]. Minerva Chir 1980;35:735-8. 11. Pfefferman R, Gombos GM, Kountz SL. Ocular complications after renal transplantation. Ann Ophthalmol 1977;9:467-70, 473. 12. Berkowitz JS, David DS, Sakai S, Shoji H, Cheigh JS, Riggio RR, et a!. Ocular complications in renal transplant recipients. Am J Med 1973;55:492-5. 13. Porter R, Crombie AL, Gardner PS, Uldall RP. Incidence of ocular complications in patients undergoing renal transplantation. Br Med J 1972;3:133-6. 14. Klaassen-Broekema N, van Bijsterveld OP. The red eye of renal failure: a crystal induced inflammation. Br J Ophthalmol1992;76:578-8l. Key words: renal transplantation, chronic renal failure, vision screening, immunosuppression, pediatrics