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Figure 1.
Kaplan-Meier estimates showing the proportion of patients free of poor visual acuity (20/200 to no light perception) over time according to tumor thickness for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Kaplan-Meier estimates showing the proportion of patients free of poor visual acuity (20/200 to no light perception) over time according to tumor thickness for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Figure 2.
Kaplan-Meier estimates showing the proportion of patients free of poor visual acuity (20/200 to no light perception) over time according to proximity of the tumor to the optic disc and foveola for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Kaplan-Meier estimates showing the proportion of patients free of poor visual acuity (20/200 to no light perception) over time according to proximity of the tumor to the optic disc and foveola for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Figure 3.
Kaplan-Meier life table curves showing the proportion of patients free of moderate loss of visual acuity (≥5 Snellen lines) over time according to tumor thickness for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Kaplan-Meier life table curves showing the proportion of patients free of moderate loss of visual acuity (≥5 Snellen lines) over time according to tumor thickness for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Figure 4.
Kaplan-Meier life table curves showing the proportion of patients free of moderate loss of visual acuity (≥5 Snellen lines) over time according to proximity of the tumor to the optic disc and foveola for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Kaplan-Meier life table curves showing the proportion of patients free of moderate loss of visual acuity (≥5 Snellen lines) over time according to proximity of the tumor to the optic disc and foveola for 1106 patients with uveal melanoma treated with plaque radiotherapy.

Table 1. 
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Univariable Analyses of the Significant Clinical Factors Related to Poor Visual Acuity of 20/200 to No Light Perception*
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Univariable Analyses of the Significant Clinical Factors Related to Poor Visual Acuity of 20/200 to No Light Perception*
Table 2. 
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Multivariable Analyses of the Significant Clinical Factors Related to Poor Visual Acuity of 20/200 to No Light Perception*
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Multivariable Analyses of the Significant Clinical Factors Related to Poor Visual Acuity of 20/200 to No Light Perception*
Table 3. 
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Estimates of Relative Risk* and Kaplan-Meier Probability† of Poor Visual Acuity of 20/200 to No Light Perception for Combinations of Clinical Factors
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Estimates of Relative Risk* and Kaplan-Meier Probability† of Poor Visual Acuity of 20/200 to No Light Perception for Combinations of Clinical Factors
Table 4. 
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Univariable Analyses of the Significant Clinical Factors Related to Loss of at Least 5 Lines of Snellen Visual Acuity*
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Univariable Analyses of the Significant Clinical Factors Related to Loss of at Least 5 Lines of Snellen Visual Acuity*
Table 5. 
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Multivariate Analyses of the Significant Clinical Factors Related to Loss of at Least 5 Lines of Snellen Visual Acuity*
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Multivariate Analyses of the Significant Clinical Factors Related to Loss of at Least 5 Lines of Snellen Visual Acuity*
Table 6. 
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Estimates of Relative Risk* and Kaplan-Meier Probability† of Loss of at Least 5 Lines of Snellen Visual Acuity for Combinations of Clinical Factors
Plaque Radiotherapy for 1106 Patients With Uveal Melanoma: Estimates of Relative Risk* and Kaplan-Meier Probability† of Loss of at Least 5 Lines of Snellen Visual Acuity for Combinations of Clinical Factors
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Clinical Sciences
September 2000

Plaque Radiotherapy for Uveal MelanomaLong-term Visual Outcome in 1106 Consecutive Patients

Author Affiliations

From the Oncology Service, Wills Eye Hospital, Thomas Jefferson University (Drs C. L. Shields, J. A. Shields, Cater, and Gündüz), and the Department of Radiation Oncology, MCP Hahnemann University (Drs Miyamoto, Micaily, and Brady), Philadelphia, Pa.

Arch Ophthalmol. 2000;118(9):1219-1228. doi:10.1001/archopht.118.9.1219
Abstract

Objective  To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma.

Design  Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models.

Participants  Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992.

Main Outcome Measures  Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [≥5 lines Snellen visual acuity]).

Results  Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (≤3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years.

Conclusions  Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola.

PLAQUE RADIOTHERAPY continues to be an important treatment method for patients with uveal melanoma.18 Previous studies9,10 have provided information on local and systemic tumor control using this method and have indicated that overall life prognosis is comparable to other management techniques such as enucleation. In addition, the ongoing prospective Collaborative Ocular Melanoma Study (COMS)11 will possibly provide information regarding systemic tumor control with plaque radiotherapy compared with enucleation.

With any organ preservation technique comes the practical question of organ function. Regarding the eye, organ function is usually measured as visual acuity. Results of previous studies,68,1224 using many different analytical techniques and visual acuity end points, have indicated that visual acuity is generally preserved in patients with smaller uveal melanomas situated farther from the optic disc and foveola. In 1984, Cruess et al12 reported visual acuity results in a group of 77 patients treated with cobalt 60 plaque radiotherapy and found that a radiation dose of 5000 cGy or more has a toxic effect on the optic disc and fovea. They found final visual acuity of 20/200 or better with this dose in only 65% of eyes at the optic disc and 52% at the foveola.12 Similar results with proton beam radiotherapy13,14 and helium ion radiotherapy15 identified factors related to poor visual outcome, including greater tumor thickness, closer proximity to optic disc and foveola, submacular fluid, worse pretreatment vision, and increasing radiation dose to optic disc, foveola, and lens.13,16

In this article, we analyze our experience with 1106 consecutive patients with visual acuity of 20/100 or better managed on the Oncology Service at Wills Eye Hospital, Philadelphia, Pa, with plaque radiotherapy over a period of 16 years. The impact of clinical and treatment factors on ultimate visual acuity was analyzed, and practical interpretation of this data is provided.

PATIENTS AND METHODS

The clinical records of all patients with the diagnosis of uveal melanoma treated on the Oncology Service between July 1976 and June 1992 were reviewed. Patients with initial visual acuity of 20/100 or better in the affected eye were selected for inclusion in this study. Clinical data were gathered regarding patient and tumor features and radiation variables and then were analyzed for outcome of final visual acuity.

In the following paragraphs, reference categories used in subsequent statistical analyses are marked with an asterisk (*). Patient features at initial examination included age, race (African American, Hispanic, Asian, or white*), sex (female or male*), medical problems (none,* diabetes mellitus, hypertension, or hypercholesterolemia), and previous or present chemotherapy. Ocular data included best-corrected Snellen visual acuity measurement at 20 feet (20/20, 20/25, 20/30, 20/40, 20/50, 20/60, 20/70, 20/80, 20/100, 20/200, 20/400, counting fingers, hand motions, light perception, or no light perception), lens (normal,* cataract, pseudophakia, or aphakia), glaucoma, and intraocular pressure.

Tumor data included anatomical location (iris, ciliary body, or choroid*), meridional location of tumor epicenter (superior, superotemporal, temporal, inferotemporal, inferior, inferonasal,* nasal, superonasal, or macula), proximity to optic nerve and foveola (in millimeters), anterior and posterior tumor margins (iris, ora serrata, between ora serrata and equator, or posterior to equator*), largest basal dimension (based on ophthalmoscopy, in millimeters), largest thickness (based on ultrasonography, in millimeters), shape (dome,* mushroom, diffuse, or plateau), and subretinal fluid (absent* or present)

Radiation plaque data included radioisotope (iodine 125,* ruthenium 106, cobalt 60, or iridium 192); plaque shape (round,* notched, curvilinear, or rectangular); plaque size; hours of radiation exposure; radiation dose (in centigray) to the tumor apex, tumor base, optic disc, foveola, and lens; and radiation rate (in centigray per hour) to the tumor apex, tumor base, optic disc, foveola, and lens. Adjuvant treatment of laser photocoagulation or thermotherapy was not applied in any case.

Follow-up examinations were generally made at 3- to 6-month intervals for up to 5 years and at 6- to 12-month intervals thereafter. Follow-up data included the date and treatment of tumor recurrence. Tumor recurrence was defined as any amount of documented tumor growth in thickness or base detected by ophthalmoscopy or ultrasonography. At date last seen, the final best-corrected Snellen visual acuity was noted.

STATISTICAL ANALYSIS

The main outcome in this study was final visual acuity. Visual acuity was analyzed for 2 end points: final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and loss of visual acuity (minimal [<5 Snellen lines] vs moderate [≥5 Snellen lines]).

In the final visual acuity analyses, patients who ultimately underwent enucleation were combined with the poor visual acuity group (20/200 or worse and visual acuity decrease of ≥5 Snellen lines). In the loss of visual acuity analysis, pretreatment and posttreatment visual acuity at date last seen were analyzed for a decrement of at least 5 Snellen lines of acuity by a Cox proportional hazards model using time to event as the end point. The loss of a "line of acuity" was defined as a decrease from one visual acuity level to the next, such as from 20/100 to 20/200 or counting fingers to hand motions.

The effect of individual clinical variables on the development of each outcome was analyzed by a series of univariate Cox porportional hazards regressions.25 Correlation among the variables was determined using Pearson correlations. All variables were analyzed as discrete variables except for patient age, intraocular pressure, tumor base, tumor thickness, proximity to the optic disc, proximity to the foveola, percentage overhang of the optic disc, radiation dose, and radiation rate, which were analyzed as continuous variables and later grouped into discrete categories to derive cutoff values. Variables that were significant on a univariable level (P<.05) were entered into a stepwise regression analysis. For variables that showed a high degree of correlation, only one variable from the set of associated variables was entered at a time in subsequent multivariate models. A final multivariable model fitted variables identified as significant predictors (P<.05) in the stepwise model and variables deemed clinically important for the visual acuity outcome.

We also analyzed individually the 5 most important risk factors and the combined impact of 2, 3, 4, and all 5 predictive factors on ultimate visual acuity. Empirical data were tabulated regarding the number and percentage of patients demonstrating poor visual acuity (analysis 1) or moderate loss of visual acuity (analysis 2) for individual factors and a combination of factors. Using Kaplan-Meier estimates,26 the raw percentages were then adjusted for differing lengths of follow-up among the patients, and 5-year estimates of percentage of poor visual acuity (analysis 1) or moderate visual acuity loss (analysis 2) with various combinations of risk factors were calculated.

Relative risks (RRs) were calculated for poor visual acuity (analysis 1) or moderate loss of visual acuity (analysis 2) given a single factor or a constellation of factors. All of the covariates were fit simultaneously into a final multivariable model, and the risk estimates were computed for each covariate. The formula for computing the RR for combinations of factors was as follows25:

For a 2-factor model in analysis of combined risks for poor visual acuity, fl1 was the parameter estimate for the first factor (eg, tumor thickness; fl1 = 0.642, RR = 1.9) and fl2 was the parameter estimate for the second factor (eg, proximity to foveola <5 mm; fl2 = 0.405, RR = 1.4). The combined risk was then exponentiation (0.642 + 0.405) = exponentiation (1.047) = 2.9.

Kaplan-Meier survival estimates were used to analyze the development of poor visual acuity (20/200 to no light perception) and loss of more than 5 Snellen visual acuity lines as a function of time. Additional Kaplan-Meier estimates were performed to assess the previous 2 visual acuity end points over time as a function of tumor size graded as small (≤3.0 mm), medium (3.1-8.0 mm), and large (>8.0 mm) as well as proximity to the visually important structures of the optic disc and foveola (>5.0 mm from both).

RESULTS
GENERAL DATA

There were 1300 consecutive patients with uveal melanoma managed with plaque radiotherapy during the 16 years of this study. The mean age of the 1106 patients who had an initial visual acuity of 20/100 or better at the time of plaque treatment was 58 years (median, 59 years; range, 10-91 years). There were 1092 whites (99%), 11 African Americans (1%), 2 Hispanics (<1%), and 1 Asian (<1%); 548 patients (50%) were male and 558 (50%) were female.

Initial visual acuity was 20/20 to 20/30 in 696 patients (63%) and 20/40 to 20/100 in 410 (37%). The anatomical location of the tumor was iridic in 10 patients (<1%), iridociliary in 7 (<1%), iridociliochoroidal in 2 (<1%), ciliochoroidal in 101 (9%), and choroidal in 986 (89%). The tumor meridional location was superior in 63 patients (6%), superotemporal in 247 (22%), temporal in 123 (11%), inferotemporal in 263 (24%), inferior in 69 (6%), inferonasal in 139 (13%), nasal in 59 (5%), superonasal in 133 (12%), and macula in 10 (<1%). Mean proximity to the optic nerve was 5.1 mm (median, 5 mm; range, 0-20 mm) and to the foveola was 4.7 mm (median, 4 mm; range, 0-22 mm). In 26 eyes (2%), the tumor overhung the optic nerve. The mean largest tumor basal dimension was 10.3 mm (median, 10 mm; range, 1.5-20.0 mm) and the mean largest tumor thickness was 4.7 mm (median, 4 mm; range, 0.3-12.2 mm). The tumor shape was dome in 991 eyes (90%), mushroom in 111 (10%), diffuse in 2 (<1%), and plateau in 2 (<1%). Subretinal fluid was present in 750 patients (68%).

The radioisotope used in the plaque was iodine 125 in 649 patients (59%), ruthenium 106 in 60 (5%), cobalt 60 in 300 (27%), and iridium 192 in 97 (9%). The plaque shape was round in 852 patients (77%), notched in 234 (21%), curvilinear in 15 (1%), and rectangular in 5 (<1%). The most common plaque size was 15 mm. Mean time of radiation exposure was 141.2 hours (median, 121.9 hours; range, 8.5-511.3 hours). Mean radiation dose to the tumor apex was 9517 cGy (median, 9090 cGy; range, 1200-9780 cGy), to the tumor base was 34,128 cGy (median, 33,000 cGy; range, 9000-70,300 cGy), to the optic disc was 7064 cGy (median, 4118 cGy; range, 47-62,055 cGy), to the foveola was 8694 cGy (median, 5276 cGy; range, 95-42,577 cGy), and to the lens was 2408 cGy (median, 1470 cGy; range, 33-31,450 cGy). Mean radiation rate to the tumor apex was 80 cGy/h (median, 78 cGy/h; range, 9-126 cGy/h), to the tumor base was 280 cGy/h (median, 261 cGy/h; range, 41-412 cGy/h), to the optic disc was 66 cGy/h (median, 40 cGy/h; range, 3-418 cGy/h), to the foveola was 82 cGy/h (median, 52 cGy/h; range, 1-462 cGy/h), and to the lens was 23 cGy/h (median, 14 cGy/h; range, 0.3-282 cGy/h).

At date last seen, the final best-corrected Snellen visual acuity was good (20/20-20/100) in 539 patients (49%) and poor (20/200 to no light perception) in 567 (51%). Loss of less than 5 Snellen lines of visual acuity was noted in 515 patients (46%) and loss of 5 or more lines was found in 591 (54%).

ANALYSIS 1: FINAL VISUAL ACUITY

On univariable analysis, factors related to poor visual acuity outcome (20/200 to no light perception) included patient age of 60 years or older; tumor location in superior, temporal, inferotemporal, or superonasal portions of the fundus; tumor base of 10 mm or more; tumor thickness greater than 8 mm; mushroom tumor shape; proximity to the optic disc (decreasing); proximity to the foveola less than 5 mm; tumor overhang of the optic disc by 50% or more; anterior tumor margin posterior to the equator; presence of subretinal fluid; use of the radioactive isotope iridium; notched plaque shape; a radiation dose at the tumor apex of 9000 cGy or higher; a radiation dose at the tumor base of 33,300 cGy or higher; increasing radiation dose and rate at optic disc; increasing radiation rate at lens and tumor recurrence (Table 1).

On multivariable analysis, the best combination of factors related to poor visual acuity outcome (20/200 to no light perception) were patient age of 60 years or older, poor initial visual acuity, increasing tumor thickness, proximity to foveola less than 5 mm, anterior tumor margin posterior to the equator, presence of subretinal fluid, radioactive isotope (ruthenium, cobalt, and iridium), notched plaque shape, and tumor recurrence (Table 2).

Using Kaplan-Meier estimates, 3% of patients had poor visual acuity at 1 year, 34% at 5 years, 68% at 10 years, and 87% at 15 years. When evaluating final visual acuity as a function of tumor thickness using Kaplan-Meier estimates, eyes with a small melanoma demonstrated poor vision in less than 1% of patients at 1 year, 24% at 5 years, and 60% at 10 years. Eyes with a medium melanoma demonstrated poor vision in 3% of patients at 1 year, 31% at 5 years, and 69% at 10 years. Eyes with a large melanoma displayed poor vision in 8% of patients at 1 year and 64% at 5 years (too few patients were available for a reliable 10-year estimate) (Figure 1).

When evaluating final visual acuity as a function of tumor proximity to visually vital structures, eyes with uveal melanoma within 5 mm of the optic disc or foveola showed poor visual acuity in 2% of patients at 1 year, 35% at 5 years, and 73% at 10 years. Eyes with uveal melanoma 5 mm or more from the optic disc and foveola showed poor visual acuity in 4% of patients at 1 year, 25% at 5 years, and 57% at 10 years (Figure 2).

Analysis of the combined effects of the predictive factors at the time of treatment revealed ultimate poor visual acuity in 19% of patients with no risk factors and in a mean of 39% of patients with 1 factor, 49% with 2 factors, 58% with 3 factors, 64% with 4 factors, and 50% with 5 factors (Table 3). The combination of clinical factors most predictive of poor visual outcome were an age of 60 years or older, tumor thickness greater than 8 mm, and the presence of subretinal fluid (80% of patients developed poor visual acuity by 5 years). Analysis of the combined effects of the RRs of the predictive factors at the time of treatment revealed a RR for poor visual acuity of 1.3 to 2.6 with 1 factor, 1.8 to 3.6 with 2 factors, 2.5 to 5.1 with 3 factors, 3.6 to 7.1 with 4 factors, and 9.3 with 5 factors.

ANALYSIS 2: LOSS OF VISUAL ACUITY

On univariable analysis, factors related to loss of visual acuity (≥5 lines of Snellen visual acuity) included patient age of 60 years or older, underlying diabetes mellitus or hypertension, tumor location in superonasal fundus, tumor base of 10 mm or more, tumor thickness of 3 mm or more, mushroom tumor shape, retinal invasion by uveal melanoma, proximity to the optic disc less than 5 mm, proximity to the foveola less than 5 mm, tumor overhang of the optic disc by 50% or more, anterior tumor margin posterior to the equator, presence of subretinal fluid, notched plaque shape, a radiation dose at the tumor apex of 9000 cGy or higher, a radiation dose at the tumor base of 33,300 cGy or higher, increasing radiation dose and rate at optic disc, and tumor recurrence (Table 4).

On multivariable analysis, the best combination of factors related to loss of visual acuity (≥5 lines of Snellen visual acuity) were patient age of 60 years or older, medical problems of diabetes mellitus or hypertension, worse initial visual acuity, tumor thickness (>8 mm), proximity to foveola less than 5 mm, presence of subretinal fluid, notched plaque shape, and tumor recurrence (Table 5).

Using Kaplan-Meier estimates, 3% of patients had loss of visual acuity at 1 year, 33% at 5 years, 69% at 10 years, and 88% at 15 years. When evaluating loss of visual acuity as a function of tumor thickness using Kaplan-Meier estimates, eyes with a small melanoma demonstrated loss of visual acuity in less than 1% of patients at 1 year, 26% at 5 years, and 62% at 10 years. Eyes with a medium melanoma demonstrated loss of visual acuity in 3% of patients at 1 year, 32% at 5 years, and 70% at 10 years. Eyes with a large melanoma displayed loss of visual acuity in 7% of patients at 1 year, 61% at 5 years, and 87% at 10 years (Figure 3).

When evaluating loss of visual acuity as a function of tumor proximity to visually vital structures, eyes with uveal melanoma within 5 mm of the optic disc or foveola showed loss of visual acuity in 2% of patients at 1 year, 36% at 5 years, and 74% at 10 years. Eyes with uveal melanoma 5 mm or more from the optic disc and foveola showed loss of visual acuity in 3% of patients at 1 year, 26% at 5 years, and 59% at 10 years (Figure 4).

Analysis of the combined effects of the predictive factors at the time of treatment revealed loss of visual acuity (≥5 lines of Snellen visual acuity) in 15% of patients with no clinical risk factors and in a mean of 42% of patients with 1 factor, 53% with 2 factors, 63% with 3 factors, and 64% with 4 factors (Table 6). The combination of clinical factors with greatest predictive value for loss of visual acuity were tumor thickness greater than 8 mm, presence of subretinal fluid, tumor proximity within 5 mm of foveola, and underlying medical problems of diabetes mellitus or hypertension (83% of patients developed loss of visual acuity). Analysis of the combined effects of the RRs of the predictive factors at the time of treatment revealed a RR for loss of visual acuity of 1.3 to 2.5 with 1 factor, 1.7 to 3.5 with 2 factors, 2.4 to 4.9 with 3 factors, 3.3 to 6.4 with 4 factors, and 8.3 with 5 factors present.

COMMENT

The ideal treatment for uveal melanoma is not certain. The primary goal of treatment is to eradicate the tumor and provide the best life prognosis for the patient. Secondary goals of treatment include retention of the globe and visual function. Options for management include enucleation, plaque radiotherapy, charged particle radiotherapy, local resection, thermotherapy, and combinations of these methods.1,2 These techniques, in various previous studies,1,3,5,10 have been found to be equivalent in securing life prognosis. In addition, the added benefit of possible visual function is provided by the conservative techniques that spare the eye.

Plaque radiotherapy continues to be one of the most popular methods of conservative management for uveal melanoma. Plaque radiotherapy results in ocular salvage in 94% of patients.27 However, ocular radiation complications remain problematic and vary depending on tumor location, size, and other factors.2224 In an extensive review17 of 136 patients with ciliary body melanoma treated with plaque radiotherapy, radiation complications at 5 years included cataract in 48% of patients, neovascular glaucoma in 21%, retinopathy in 20%, scleral necrosis in 12%, vitreous hemorrhage in 11%, and papillopathy in 3%. Most of these complications contributed to associated visual acuity loss. In contrast, a review18 of 630 patients with choroidal melanoma in the visually sensitive macular region revealed complications at 5 years of cataract in 32% of patients, neovascular glaucoma in 8%, retinopathy (maculopathy) in 40%, scleral necrosis in less than 1%, vitreous hemorrhage in 9%, and papillopathy in 13%. Reasons for visual acuity loss differed substantially between these 2 groups. However, visual acuity decrement by 3 or more Snellen lines was similar at 40% at 5 years in both groups of patients.

Several studies during the past 2 decades have focused specifically on visual results after radiotherapy of choroidal melanoma. Cruess and associates12 in 1984 evaluated 77 eyes with posterior uveal melanoma treated with cobalt plaque radiotherapy. They evaluated patients with initial visual acuity of 20/25 or better only. Therefore, their study was designed to assess visual results in a subset of patients with only excellent initial visual acuity. At 36 months, 81% had visual acuity better than 20/200 and 62% had visual acuity better than 20/50. When assessing visual acuity with regard to tumor size, 95% of eyes with a small or medium posterior uveal melanoma had visual acuity better than 20/200 at 36 months, whereas only 48% of eyes with a large tumor demonstrated visual acuity better than 20/200. They also found that worse visual results occur with tumors near the optic disc or fovea, especially when the radiation dose to these structures exceeds 5000 cGy.

In 1986, Seddon and coworkers13 reported visual outcome in 440 eyes with posterior uveal melanoma treated with proton beam radiation. The scope of their study was slightly greater than that of Cruess et al12 in that they13 included all patients with initial visual acuity of 20/200 or better. They identified important risk factors for poor visual outcome, including greater tumor thickness, proximity to optic disc and fovea, and pretreatment visual acuity. They noted that tumors with a thickness of 5.0 mm or less, distance from the disc and fovea greater than 3.0 mm, and pretreatment visual acuity of 20/40 or better were most likely to offer the best visual prognosis.

In 1996, Char and associates15 reported on 426 eyes with ciliochoroidal melanoma that were eligible for randomization (enucleation vs plaque radiotherapy) in the COMS11 but were treated outside the study with radiotherapy (helium ion or plaque). They found that 36 months after treatment, 36% of eyes had visual acuity of 6/12 or better. The length of visual retention depended most on tumor thickness; tumor location with respect to the optic nerve, fovea, and ciliary body; and patient age. They concluded that some patients eligible for COMS randomization to enucleation vs plaque radiotherapy can retain excellent long-term vision, and this should be explained to each candidate prior to randomization.

The previous studies added to our understanding of visual outcome after plaque radiotherapy for uveal melanoma. In our analysis, we attempted to be comprehensive and included all 1106 patients who were not legally blind (20/100 or better) and assessed their risk to become legally blind (20/200 or worse) in the affected eye. We did not analyze only tumors at certain sites in the eye with certain thicknesses, as in the COMS eligibility criteria, but we assessed all tumors at all sites in the eye to provide a realistic view of visual acuity after ocular radiotherapy.

Many of the previously identified risk factors for poor vision1216 were confirmed in our analysis of this larger group of patients. In the multivariable analysis we found that factors that significantly predict poor visual outcome of 20/200 or worse were numerous and included older patient age (≥60 years), poor initial visual acuity, increasing tumor thickness, posteriorly situated tumor less than 5.0 mm to the foveola, presence of associated subretinal fluid, notched plaque shape (because of the proximity of the tumor ≤2.0 mm from the optic disc), use of a radioisotope other than iodine 125 (eg, cobalt 60, iridium 192, or ruthenium 106), and ultimate tumor recurrence (Table 2). When assessing the most important of these factors, the presence of 1 of these factors leads to a 39% chance for ultimate poor vision and the presence of 2 or more factors leads to an approximately 50% or greater chance for poor ultimate vision (Table 3). Five years after treatment, 24% of patients with a small melanoma had poor vision, whereas 31% with a medium tumor and 64% with a large tumor had poor visual acuity (Figure 1).

Similarly, risks for loss of 5 Snellen lines of visual acuity paralleled the above findings. In the multivariable analysis, risks for visual acuity loss of 5 Snellen lines included older patient age (≥60 years), medical problems of diabetes mellitus or hypertension, poor initial visual acuity, greater tumor thickness, presence of subretinal fluid, proximity of the tumor less than 5.0 mm to the foveola and 2.0 mm or less to the optic disc (notched plaque), and ultimate tumor recurrence (Table 5). When assessing the most important of these factors, the presence of 1 of these factors leads to a 42% chance for an ultimate 5 lines of visual loss, and 2 or more factors leads to approximately 50% or greater risk for visual acuity loss (Table 6). Five years after treatment, 26% of patients with a small melanoma had visual acuity loss of at least 5 Snellen lines, whereas 32% with a medium tumor and 61% with a large tumor showed similar visual acuity loss (Figure 3).

Factors that offered the worst ultimate visual results were patient age of 60 years or older, tumor thickness greater than 8 mm, and presence of subretinal fluid, and these clinical factors were associated with poor visual acuity in 80% of patients (Table 3). Factors that provided the greatest risk for loss of at least 5 lines of Snellen visual acuity were tumor thickness greater than 8 mm, presence of subretinal fluid, tumor within 5 mm of the foveola, and underlying medical problems such as diabetes mellitus and hypertension, causing visual loss in 83% of affected eyes (Table 6). The combinations of risk factors affecting vision were calculated in our study and will be important in counseling of patients for plaque radiotherapy, allowing them reasonable expectations for visual outcome.

Our study has potential limitations. This retrospective study reflects our experience over a 16-year period as a tertiary care referral center. Thus, we may have managed more difficult cases, which would engender poorer visual outcome. Included in this study are patients with large tumors who refused enucleation and patients with large uveal melanoma in their only seeing eye, situations that lead to referral to our service and subsequent irradiation of the tumor that would otherwise have been managed with enucleation. Also included are patients who refused or were not eligible for randomization into the COMS.11 Many of those not eligible had juxtapapillary choroidal melanoma that we subsequently treated with custom-designed plaque radiotherapy, realizing that the visual prognosis would be guarded.19 In addition, there may be a bias in this study toward management of uveal melanoma with irradiation, whereas other surgeons would have preferred enucleation or local surgical resection.

The subset of patients with hope for long-term good vision after plaque radiotherapy for choroidal melanoma include younger patients with small tumors at sites remote from the optic disc and foveola. It is important for all patients treated with plaque radiotherapy for choroidal melanoma to realize that the globe is usually salvaged, in 94% of cases,27 using this organ-sparing technique, but the visual function of the eye is limited and ultimate visual outcome is generally poor. However, even with relatively poor visual outcome, Tunc and associates28 found that quality of life was best in patients who received irradiation for choroidal melanoma compared with enucleation and tumor resection. Others29 have reported that the choice of treatment for choroidal melanoma does not seem to be associated with large differences in quality of life in the long term.

The results of our study may be useful for more accurate counseling of patients with uveal melanoma with regard to visual expectations. It is hoped that tumor control and visual results can be improved with newer combination techniques of plaque radiotherapy and adjunctive thermotherapy. Visual results after these newer therapeutic modifications will not be available for several years. Providing a lower radiation dose30 in tumors treated with combined modalities is possible, with the goal to avoid long-term radiation complications. Newer methods of transpupillary thermotherapy alone may also reasonably spare vision for smaller tumors in the paramacular and peripapillary region.31 With these advances, it is possible that patients will have a better visual outcome after conservative treatment for uveal melanoma.

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Article Information

Accepted for publication February 11, 2000.

This study was supported by the Macula Foundation, New York, NY (Dr C. L. Shields); the Paul Kayser International Award of Merit in Retina Research, Houston, Tex (Dr J. A. Shields); The Lions Eye Foundation, Philadelphia, Pa (Dr J. A. Shields); and the Eye Tumor Research Foundation, Philadelphia (Dr C. L. Shields).

Reprints: Carol L. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.

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