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 I 07 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; alex.levin@sickkids.ca

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

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

Ophthalmic assessment-Behbehani et al

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.

Can J Ophthalmol 2003;38:379-384

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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 I 07 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.

Routine 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

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 by Hanley and Lippman-Hand:

1 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)

Ophthalmic assessment-Behbehani et al

Table !-Results of ophthalmic assessment before renal transplantation in I 07 patients

No. (and %) of patients

Results By history By examination

No eye problems 75 (70) 61 (57) Ocular abnormalities 32 (30) 46 (43)

Potentially serious 7 (6) 13 ( 12) New - 14 (13)

New potentially serious - 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 I 07 patients

Diagnosis No. of patients*

Renal dysplasia 20 Obstructive uropathy 17 Reflux nephropathy 15 Cystinosis 8 Focal segmental glomerulosclerosis 6 T ubulointerstitial nephritis 6 Polycystic disease 5 Dysplasia and obstructive uropathy 4 Dysplasia and reflux nephropathy 4 Glomerulonephritis 4 Hemolytic-uremic syndrome 4 Congenital nephrotic syndrome 2 Pyelonephritis 2 Medullary cystic disease 2 Miscellaneous disorders 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 studies6- 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 studies5•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

Ophthalmic assessment-Behbehani et al

Table l-Ocular abnormalities reported or found among the I 07 patients

Abnormality* By history

Refractive error 13 Band keratopathy 0 Anterior-segment 0

crystal deposits Photophobia 6 Strabismus 5 Tortuous retinal blood 0

vessels Amblyopia 2 Cataract 2 Disc dysplasia 0 Nystagmus I Retinal pigment epithelial 0

changes Redness I Eyelid eczema 0 Epicanthal fold 0 Bell palsy I Oculomotor apraxia I Posterior embryotoxon 0 Brushfield's spots 0 Uveal coloboma I Glaucoma I Ocular hypertension 0 Asymmetric cup:optic 0

disc ratio Retinal detachment I Retinal dysplasia I Retinal crystal deposits 0 Optic atrophy or I

neuropathy Decreased visual evoked I

potential

*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

No. of patients*

Potentially By Newly vision-

examination documented threatening

13 0 9 9 7 7

6 0 6 I 5 5

3 I 3 3 I 3 3 3 2 I 2 2 2

I 0 I I I I 0 0 0 0 I I I I I 0 I I 0 I I I I I

I 0 I I 0 I I I I 0 I

0 0

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.

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Key words: renal transplantation, chronic renal failure, vision screening, immunosuppression, pediatrics