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Visual Fields in Retinoblastoma Survivors
David H. Abramson, MD;
Mark R. Melson, MD;
Camille Servodidio, RN, MPH, CRNO
Arch Ophthalmol. 2004;122:1324-1330.
ABSTRACT
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Objective To describe the visual field defects in retinoblastoma survivors and relate those defects to characteristics such as tumor size, tumor location, and treatment modality.
Methods Thirty-one patients treated for retinoblastoma were included in this study. Humphrey visual fields were determined in 33 eyes.
Results Twenty-seven patients (29 eyes, 68 tumors) had sufficient diagnosis and treatment data available for further analysis. Twenty-six of the 27 patients had both absolute and relative visual field defects. Four types of visual field defects were observed and correlated with location of the tumor and therapy to the individual tumors: (1) no residual defect, (2) absolute scotoma, (3) arcuate and sector scotoma, and (4) "pseudo"–visual field defects caused by relative enophthalmos resulting from radiation.
Conclusions Patients with retinoblastoma demonstrate a variety of long-term visual field defects after treatment for their intraocular disease. Characteristics that determine the size and type of defects are tumor size, tumor location, and treatment method.
INTRODUCTION
A number of studies have examined various long-term outcomes in survivors of retinoblastoma. Among the measures that have been thoroughly reviewed are patient survival, tumor recurrence, ocular survival, visual acuity, motor and psychological development, and nonocular tumor incidence. As our ability to treat these patients has significantly improved during the past few decades, the overwhelming majority of children in this country not only survive but also retain near-normal to normal vision in at least 1 eye.1 Many treatment centers are now further refining techniques to help preserve sight as well as the affected eye(s), while not compromising long-term patient survival. For patients with germline retinoblastoma mutations, much of this effort is concentrated on therapies that minimize the risk of developing radiation-related nonocular tumors later in life.2-4
We are unaware of any studies specifically examining long-term visual fields in successfully treated patients with retinoblastoma. There are only limited case reports5 and other studies6-8 that even mention this topic in the current literature. Several authors have explored this question in patients treated for ocular melanoma,9-13 nonmalignant melanocytoma,14 other benign choroidal neoplasia,15-16 and metastatic ocular disease,17-18 but here, too, there is a scarcity of literature.
Since retinoblastoma is a tumor of infancy and early childhood, it is impossible for the physician to obtain pretreatment visual fields in patients with this illness. However, many of these patients continue to be followed up closely throughout life by ophthalmologists, making it possible to perform visual field testing on them when they become young adults. Survival will remain the primary outcome measure in this patient population; however, we cannot ignore the morbidity caused by treatments that affect either central acuity or peripheral vision. An examination of the visual fields of retinoblastoma survivors may provide insight as to which tumor characteristics and therapies destroy (and which preserve) peripheral vision for these patients.
METHODS
Thirty-one patients with retinoblastoma treated at our New York center were included in this study. Demographic and clinical data collected from patient charts included age at retinoblastoma diagnosis, tumor laterality and location, and family history of retinoblastoma. We also obtained previous treatment data, including type and number of times a particular method was used, fundus drawings, and fundus photographs, when available.
Using the Humphrey field analyzer (Model 630; Zeiss Humphrey Systems, Dublin, Calif), we performed a merged central 30-2, peripheral 30-60-2 threshold test on 26 of the 31 patients. A central 30-2 threshold test was performed on 2 patients and a merged central 30-1 threshold test on 1 patient. A merged central 30-1, peripheral 30-60-1 threshold test was performed on 1 patient and a full-field 120-point screening test on 1 patient. Tests were performed with appropriate near-vision correction for the central 30° and without correction for the peripheral 30° to 60°. Visual acuity was measured in 26 eyes by means of the Snellen chart with best correction.
After undergoing visual field testing, 4 of the 31 patients were excluded from this study because of incomplete data regarding their retinoblastoma treatment.
All visual field test results were interpreted by the attending ophthalmologist (D.H.A.). An absolute scotoma was defined as 3 or more contiguous points of greater than 10 000 apostilbs (ASB) and a relative scotoma was defined as 3 or more contiguous points with a defect ranging from 251 to 10 000 ASB. Using pretreatment fundus drawings and posttreatment fundus photographs (when available), we predicted the magnitude of the visual field defect and correlated its position on the retina on the basis of the size and location of a particular tumor. We then classified defects as larger, smaller, or equal to the predicted finding and noted whether their locations were consistent with our predictions.
RESULTS
Visual field testing was performed in 33 eyes in 31 patients. Of these, 27 patients (29 eyes) had sufficient previous treatment data useful for additional study. The average age at retinoblastoma diagnosis for the 27 patients was 1.2 years (range, 1 week to 84 months). The average follow-up from date of diagnosis was 21.8 years (range, 9.8-38.8 years). There were 68 tumors in the 29 eyes. The number of tumors per eye ranged from 1 to 7 (median, 2). Various treatment modalities, often combinations of 2 or more methods to control a single tumor, were used in these patients (Table 1).
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Tumor Characteristics, Treatments, and Corresponding Visual Field Data*
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Twenty-six of the 27 patients had both absolute (>10 000 ASB) and relative ( 251 ASB,  10 000 ASB) visual field defects related to their tumor (Table 1, Figure 1, and Figure 2). One patient had no detectable visual field defect directly related to his tumor (Figure 3). Sixteen patients had detectable visual field loss in both the central 30° and peripheral 30° to 60° portion of the test. Twenty patients had defects within the central 30° of the visual field, whereas 19 patients had defects within the peripheral 30° to 60°. The near-vision corrective lens was inadvertently left in place for 3 patients in the study, thus resulting in a false ring scotoma in the peripheral 30° to 60° that corresponded to the border of the corrective lens. Visual acuity was tested in 26 of the 29 eyes examined for visual field data. Of these, 24 were found to have 20/40 or better visual acuity.
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Figure 1. Pretreatment fundus drawing and corresponding visual field (merged central 30 and peripheral 30-60-2) (A) and fundus photograph (B) of a patient with retinoblastoma demonstrating precise correlation between tumor location and visual field defect.
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Figure 2. Pretreatment fundus drawing and corresponding visual field (merged central 30 and peripheral 30-60-2) of a patient with retinoblastoma demonstrating excellent correlation between multiple tumors and discrete scotomas.
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Figure 3. Pretreatment fundus drawing and corresponding visual field (central 30-2 only) (A) and fundus photograph (B) of a patient with retinoblastoma with a small macular tumor that underwent a type 0 regression after external beam radiotherapy.
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Of the 68 total tumors, 20 produced defects that were larger than would be predicted on the basis of tumor size alone (Figure 4). Eight produced defects that were smaller than predicted and 19 produced defects that were approximately equal to what was predicted. We could not adequately assess the defect size in 1 patient, as the extent of disease-related retinal damage made it impossible to determine what portion of field loss was attributable to a particular tumor. The remaining 20 tumors were located anterior to the equator, and the eyes involved did not demonstrate any visual field defects from these tumors by means of the Humphrey programs we used.
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Figure 4. Pretreatment fundus drawing and corresponding visual field (merged central 30 and peripheral 30-60-2) (A) and fundus photographs (B and C) of a patient with retinoblastoma with a visual field defect larger than that suggested by tumor size alone. C is an enlargement of the area superotemporal to that shown in B. In A, dd indicates disc diameter.
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Nineteen patients had an enlarged brow-nose defect. For purposes of this study, an enlarged brow-nose defect was defined as a nasal defect extending greater than 10° nasally and a superior defect extending greater than 20° superiorly (Figure 5). Four patients did not have an enlarged brow-nose defect. Of the remaining 4 patients, 2 had only the central 30° of the visual field tested (thus making assessment of the brow-nose defect impossible) and the remaining 2 had such large absolute field defects that it was impossible to determine whether there was an enlarged brow-nose defect.
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Figure 5. Pretreatment fundus drawing and corresponding visual field (merged central 30 and peripheral 30-60-2) of a patient with retinoblastoma demonstrating a brow-nose defect after external beam radiotherapy. This defect is caused by the anatomy of the patient's skull, not retinal disease. dd indicates disc diameter.
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All 27 patients had either absolute or relative defects that crossed the vertical meridian. Twenty-three of the 27 patients had defects that crossed the horizontal meridian. Fifteen tumors in 13 patients had at least a portion of their border in the arcuate nerve fiber pathway, but only 4 patients had evidence of an arcuate visual field defect (Figure 6).
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Figure 6. Pretreatment fundus drawing and corresponding visual field (merged central 30 and peripheral 30-60-2) of a patient with retinoblastoma demonstrating a posterior tumor location and corresponding arcuate visual field defect. dd indicates disc diameter.
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In summary, 4 types of defects were observed: (1) no residual defect (in a patient with a type 0 regression (Figure 3); (2) an absolute scotoma corresponding to the residual tumor scar reflecting initial size and focal treatment (Figure 1 and Figure 2); (3) arcuate and sector scotomas representing disruption of nerve fiber transmission through a scar (Figure 4A, Figure 4B, and Figure 6); and (4) a "pseudo"–field defect (the brow-nose defect) resulting from the enophthalmos caused by radiation (Figure 4C and Figure 5).
COMMENT
Our analysis of computerized visual fields, attempted on 31 retinoblastoma survivors, demonstrated that this type of testing can be completed in this patient population. This encouraging finding provides evidence that more of these patients will be able to undergo such testing in the future to help us further correlate defects in peripheral vision with tumor and treatment characteristics.
In a previous study of visual fields of choroidal melanomas, Abramson reported, "the visual field defect caused by a melanoma is characteristic, diagnostic, and almost unique."9 In that study, 100% of the tumors were associated with both an absolute scotoma and a visual field defect (relative scotoma) in the area of the tumor itself. Ninety-nine percent of the tumors in that study produced defects that were larger than the tumors with which they were associated.9
Our visual field analysis in this study could be divided into 4 groups: no residual defect, absolute scotoma, arcuate scotoma, and pseudo–visual field defect.
For a number of reasons, the defects seen in retinoblastoma do not appear to be as predictable as those seen in choroidal melanoma. Although the primary findings attributable to the tumor itself are essentially consistent with what we would expect on the basis of size and location, the effect of tumor treatment on the visual fields is more variable than with ocular melanoma. When comparing the findings among these tumor types, one must keep in mind that we were able to much more precisely describe defects related to melanoma than to retinoblastoma. We were able to obtain pretreatment and posttreatment visual fields for patients with melanoma and were thus able to better assess the effects of treatment on the patient's visual fields. Furthermore, patients with retinoblastoma were often treated with multiple therapies, thus making it much more difficult to clearly delineate the long-term effects related to one treatment vs another.
Of the 27 patients tested, all but one had a visual field defect that could be directly attributed to either a tumor or its treatment. This patient had a solitary macular tumor (Figure 3) that was treated with external beam radiotherapy and subsequently underwent a type 0 regression pattern,19 with no evidence of residual tumor or scar. Despite this tumor's location, this patient retained 20/20 visual acuity in the eye. This suggests that external beam radiotherapy may be the only treatment modality that has the potential to not only cure the disease but also spare the patient from significant long-term visual complications. Although a type 0 regression pattern occurs in only 10% to 15% of tumors treated with radiotherapy,19 physicians who encounter it can likely expect no visual field defect related to retinal disease. This interesting finding warrants further study of these tumors to better characterize their cells of origin, depth of retinal invasion, and specific mechanism(s) of cell death after treatment. It is important to note that patients who have tumors that undergo type 0 regressions may still have the brow-nose anatomic defect that we describe in this study. In the patient described herein, we were unable to perform peripheral 30° to 60° testing and thus were unable to assess whether this patient had such a defect.
In the 26 patients with demonstrable visual field defects, the location of the tumor was correlated with the center of the scotoma found in our testing (Figure 1 and Figure 2). Although this correlation has not been previously characterized, we assumed its existence on the basis of previous studies of other intraocular tumors. The nature of the damage to the retina that causes the visual field defect has not yet been definitively characterized in either retinoblastoma or choroidal melanoma. In Abramson's previous study of choroidal melanomas, the scotoma overlying the tumors had been presumptively attributed to photoreceptor damage in the region of the tumor.9 When the size of the scotoma increased after therapy, he speculated that the increase was due to radiation damage to photoreceptors or impairment of local circulation with radiation retinopathy, or was secondary to a long-standing serous detachment of the overlying retina. However, in several of the cases in that study, the size of the scotoma decreased after treatment. Unfortunately, we were unable to compare pretreatment and posttreatment visual fields in this study and were thus unaware of whether such seemingly temporary damage exists for retinoblastoma. Regardless of the mechanism of defect formation, the existence of the tumor-scotoma correlation provides valuable data that should aid the treating ophthalmologist in predicting posttreatment visual impairment for these patients. Such information can be useful when discussing the long-term complications of therapy with the patient and his or her family.
When symptomatic, patients with choroidal melanoma often have complaints related to visual field defects when they are first examined. Measurement of these defects can aid the clinician in observing the progress of treatment of a given lesion. Because of the ages at presentation for retinoblastoma, such complaints are virtually never elicited from these patients. Detailed visual testing, including visual field analysis, is usually impossible because of the subjective nature of many of these tests. Thus, we cannot observe treatment progress in retinoblastoma by means of visual field testing. In this study, we compared the defect that would be expected on the basis of the tumor size alone with the defect found after treatment and noted that larger defects were most often associated with tumors treated with external beam radiotherapy.
Eighteen of the 28 patients in this study were found to have enlarged brow-nose defects (Figure 5). Of this group, 14 had received external beam radiotherapy as part of their retinoblastoma management. This finding is not surprising when we consider the incidence of orbital and midface hypoplasia associated with this treatment modality in patients treated at the ages found in this study.20 Some patients clearly manifested more pronounced physical defects than others, and the magnitude of brow-nose defects seen on visual field testing varied as well. From our observations, the extent of the defect was not necessarily correlated with the tumor burden of a particular eye, but with the facial and orbital structure of the patient. We can thus conclude that this visual field defect is anatomic and not related directly to optic nerve or retinal disease, since the changes did not correlate with areas directly impacted by a tumor. This finding is interesting and provides further justification for the cautious use of external beam radiotherapy in patients with retinoblastoma. In some cases, however, the benefits of external beam radiotherapy clearly outweigh the known risks associated with this treatment modality, especially for tumors that have not responded to other therapies.
It is important to emphasize that the brow-nose defect we are describing originates from a change in the bony architecture of the child's skull. In individuals with normal orbits, the boundaries of the visual field extend approximately 60° superiorly, 75° inferiorly, 100° temporally, and 60° nasally. The prominence of the brow accounts for the discrepancy between the superior and inferior fields, and the nose accounts for that between the nasal and temporal fields. The brow-nose defect is thus not restricted to children who have received radiotherapy for retinoblastoma. Any change (or relative change) in the size of the patient's nose or brow can alter peripheral vision. A patient who has received radiotherapy to the skull or even healthy children and adults who have prominent brows and/or noses may have a brow-nose defect on visual field testing. In our series, 4 of the 18 patients who met the criteria for this defect did not receive external beam radiotherapy as part of their retinoblastoma treatment and thus fall into this latter category.
As alluded to already, the numerous concerns regarding the potential side effects of external beam radiotherapy have caused physicians to become more wary of its use as a primary therapeutic choice in this patient population. In the past 25 years, much attention has been directed toward the increased risk of second tumors in patients with hereditary disease. In light of this, ophthalmic oncologists are increasingly turning to local methods of tumor control. Of these, the 2 most frequently used treatments are photocoagulation (transpupillary thermotherapy) and cryotherapy. Recently, there has been significant interest in using chemoreduction before focal therapy for improved tumor control.4, 21-25 To reduce the systemic toxic effects associated with the chemotherapeutic agents used, a number of centers have begun to evaluate periocular drug delivery for these patients.26-28 While we do not expect that the chemoreduction itself would contribute to a new visual field defect (unless the agent itself is associated with significant retinal toxic effects), we must consider the effect that the local therapy that follows it might have on the patient's peripheral vision.
Cryotherapy was used in the treatment of 14 tumors in this study. This method is most often used to treat small tumors anterior to the equator. Of the tumors examined in this study, 10 treated with cryotherapy were anterior to the equator. The 4 tumors located posterior to the equator that received cryotherapy also underwent additional treatment with different methods. We are therefore unable to separately evaluate the visual field defect specifically associated with cryotherapy. Its use, however, raises an interesting question. Do tumors anterior to the equator cause any visual field defects, and, if so, what are they? In this study, we found no demonstrable visual field defects from these lesions. From this, we can conclude that the therapeutic choice for treating tumors anterior to the equator does not have a material impact on long-term peripheral vision if the effects of the treatment do not extend posterior to the equator and there is no damage to the anterior components of the visual axis.
Photocoagulation was used in the treatment of 18 tumors in this study. Six of these tumors were anterior to the equator and thus presented the problem described earlier in relation to cryotherapy. Six tumors posterior to the equator were treated with photocoagulation alone. In 4 of these cases, the visual field defect detected by our testing was larger than that predicted on the basis of fundus drawings of the tumor (Figure 4). This is most likely because retinoblastoma photocoagulation involves destruction of the blood vessels feeding the tumor. In many cases, areas of retina bordering these vessels are destroyed as well, and we thus see a scotoma larger than the tumor itself.
We have noted that the large majority of the tumors described produced visual field defects that crossed either or both of the vertical or horizontal meridians. This is not surprising when we consider that the defects are correlated with tumor locations, and we would not expect the tumors themselves to have a particular location preference with regard to the vertical or horizontal meridians. This is important insofar as it impacts later ophthalmologic examination of these patients and can permit ophthalmologists to distinguish defects related to retinoblastoma from those seen in more common conditions such as glaucoma.
Among the most surprising findings of this study was the small number of arcuate visual defects we encountered. Although 15 tumors in 13 patients were totally or partly in the region of the arcuate fiber bundle, only 4 produced this classic defect.10 We cannot explain this phenomenon, but it certainly raises important questions about the type of damage caused to retinal cells by tumors and subsequent therapy. It is important to recognize that arcuate pathway defects in these patients should not always be attributed to retinoblastoma. In fact, as the findings in this study suggest, we do not expect most tumors in the posterior pole to produce such defects. If they are encountered, the treating ophthalmologist should explore the possibility of causes other than retinoblastoma.
In the past 30 years, the management of retinoblastoma has changed dramatically. Increasing numbers of patients are surviving and retaining sight in at least 1 eye. In this study, we have examined another important outcome measure in this disease: long-term visual field results. It is our hope that the findings presented herein will provide useful information for physicians as they assess tumors and choose among therapeutic modalities. We also hope that this information serves the additional purpose of helping to predict and inform patients with retinoblastoma and their families about the long-term complications of their disease. Retinal imaging technology now enables us to precisely document tumor size and appearance throughout patients' lives. Those now benefiting from these advances will soon be able to have their visual fields accurately tested, and these improvements should significantly enhance our ability to assess the correlation between tumor or treatment damage and peripheral vision.
AUTHOR INFORMATION
Correspondence: David H. Abramson, MD, Ophthalmology Oncology Service, Memorial Sloan-Kettering Cancer Center, 70 E 66th St, New York, NY 10021 (ICANCERMD{at}aol.com).
Submitted for publication June 17, 2002; final revision received February 12, 2004; accepted April 6, 2004.
From the Ophthalmology Oncology Service, Departments of Surgery, Radiation Oncology, and Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY (Dr Abramson); Massachusetts Eye and Ear Infirmary, Boston (Dr Melson); and Department of Radiation Oncology, Hartford Hospital, Hartford, Conn (Ms Servodidio). The authors have no relevant financial interest in this article.
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