Purpose
To report the outcomes of choroidal nevi monitoring and to compare the detection of ultrasonographic hollowness, a risk factor of malignant transformation, from a B-scan with results from an A-scan examination.
Design
Retrospective cohort study.
Methods
Standardized A- and B-scan echography and ophthalmoscopy in 358 consecutive patients with median age 69 years and baseline choroidal nevus higher or lower than 1.5 mm in 51 (14%) and 307 (86%) eyes, respectively.
Results
No growth or change in echographic or ophthalmoscopic features were found in 307 nevi with a median elevation of 0.9 mm (range, 0.7 to 1.5 mm) and a median follow-up of 6 years (range, 4 to 9 years). After 2 to 6 years, decreased internal reflectivity on standardized A-scan and ultrasonographic hollowness on B-scan were detected in 7 (18%) of 38 initially highly reflective choroidal nevi (thickness, 1.98 ± 0.37 mm); 2 (5%) nevi grew into melanoma 15 years after the first observation. Of 13 choroidal nevi (thickness, 2.75 ± 0.66 mm), with initial atypical medium to high reflectivity on standardized A-scan (100%) and hollowness on B-scan (85%), 6 (46%) were plaqued 6 to 15 months later because of the presence of multiple risk factors.
Conclusions
No changes in thickness or echographic features of choroidal nevi elevated up to 1.5 mm were recorded during the follow-up period. In initially typical choroidal nevi higher than 1.5 mm, strong agreement was detected between decreased reflectivity on standardized A-scan and ultrasonographic hollowness on B-scan found after up to 15 years of stability. The vast majority of choroidal nevi with initial atypical standardized A-scan features showed ultrasonographic hollowness.
Choroidal nevi are common among patients who visit an ophthalmologic practice. Given the 6% reported rate of choroidal nevi in the United States population and assuming that all choroidal melanomas arise from pre-existing nevi, the estimated rate of malignant transformation of choroidal nevi is approximately 1 in 9000 cases in the United States white population.
Seven mostly ophthalmoscopically detectable factors were identified recently as predictive of the transformation of choroidal nevi into melanoma in 2514 consecutive cases; echographic surveillance of choroidal nevi was needed to identify 2 of the 7 risk factors: thickness exceeding 2 mm and ultrasonographic hollowness on a B-scan examination. When growth or signs of the malignant transformation of choroidal nevi into melanoma are observed, currently radiation therapy is advised. Because tumor size strongly correlates with patient prognosis, early detection at a time when the malignancy is small in cases of uveal melanoma is critical in terms of improving patient survival.
The purpose of this article is to report our long-term experience with the diagnosis and follow-up of elevated choroidal nevi with a special focus on the detection of echographic signs of malignant transformation and a comparison of the 2 methods of examination, that is, standardized A-scan and B-scan echography.
Methods
Our institutional review board (the Local Ethical Committee at the Padua University Hospital, Padua, Italy) retrospectively approved the research. Data accumulation were in conformity with state laws, and informed consent was obtained from all participants. Moreover, this retrospective cohort study adhered to the tenets of the Declaration of Helsinki.
Three hundred fifty-eight consecutive patients were referred to our echographic service for the assessment of choroidal nevus from 2005 to 2010. Those patients underwent thorough ophthalmologic evaluations of the choroidal lesions, including indirect ophthalmoscopy, 78- or 90-diopter lens slit-lamp biomicroscopy of the fundus, and standardized A-scan and B-scan echography (Cinescan S; Quantel Medical, Clermont-Ferrand, France). Fundus drawings or photographs were completed or obtained from all patients. The following data were collected: location of tumor (inferior, temporal, superior, or nasal), tumor thickness and largest tumor basal diameter (in millimeters), and tumor color (pigmented or nonpigmented).
Follow-up examinations were planned at 3- to 12-month intervals, based on the size of the choroidal lesion and the number of risk factors related to malignant transformation. The charts of 15 (4%) of the 358 original patients who previously had visited the echographic service since 1990 were reviewed by the same experienced examiner (D.D.).
In all examined patients, a standardized A-scan of the choroidal nevus was performed at tissue sensitivity, and the thickness, internal reflectivity, and structure of all choroidal nevi were evaluated. Growth was defined as an increase of at least 0.5 mm in thickness by means of standardized echography examination. High internal reflectivity with regular structure and medium to high reflectivity with irregular structure were considered to be the acoustic features of typical and atypical choroidal nevi, respectively. Hollowness was defined as a low echogenic area visible within the solid choroidal lesion on contact B-scan examination at approximately 90-dB gain setting on the echographic unit. Occasionally, optical coherent tomography, fundus autofluorescence, and fluorescein angiography of the lesions were performed. Patients with choroidal nevi were examined specifically for 7 clinical risk factors of malignant transformation: thickness more than 2 mm, subretinal fluid, symptoms, orange pigment, closeness to the optic disc, ultrasonographic hollowness, and no halo of depigmentation.
SPSS software version 13.0 (SPSS, Inc, Chicago, Illinois, USA) and Microsoft Office Excel 2003 (Microsoft, Redmond, Washington, USA) were used for all statistical tests. Measurements were analyzed using the Fisher exact test and the Mann–Whitney U test. P values of at least .05 were considered to be statistically significant.
Results
A retrospective analysis showed that 358 white patients (34% of the sample were male, and the remaining 66% were female) with an age ranging from 47 to 93 years (median, 69 years) had a unilateral, pigmented (98%) choroidal nevus located in the inferior (21%), temporal (42%), superior (19%), or nasal (18%) sector, with a thickness ranging from 0.7 to 3.6 mm (median, 1.6 mm) and a largest tumor basal diameter ranging from 1 to 11 mm (median, 5.5 mm) at the initial observation. Seven (2%) patients had unilateral, minimally pigmented or nonpigmented choroidal nevi.
The thickness of the choroidal nevi in the patient sample did not exceed 1.5 mm in 307 patients and was higher than 1.5 mm in 51 patients. All of the 307 (86%)patients with a median follow-up period of 6 years (range, 4 to 9 years) and 38 (74%) of the 51 (14%) patients had initial lesions with the typical echographic features of choroidal nevus on standardized A-scan examination ( Table 1 and Figure 1 ).
| Risk Factors | Typical Nevi (n = 38; 100%) | Atypical Nevi (n = 13; 100%) | P Value, a Odds Ratio (95% Confidence Interval) |
|---|---|---|---|
| Thickness >2 mm | 18 (47) | 11 (85) | .05, 6.1 (1.2 to 31.3) |
| Subretinal fluid | 0 | 2 (15) | |
| Symptoms b | 0 | 1 (8) | |
| Orange pigment | 1 (5) | 2 (15) | |
| Closeness to the optic disc c | 0 | 1 (8) | |
| Ultrasonographic hollowness d | 0 | 11 (85) | <.0001, NA |
| No halo of depigmentation | 0 | 1 (8) |
b Blurred vision, or flashes or floaters.
c Posterior margin within 3 mm from optic disc.
The initial thickness of the latter 38 of the 51 choroidal nevi ranged from 1.6 to 3.0 mm (median, 2.0 mm), and the median follow-up for this group of 38 was 7.0 years (range, 2 to 18 years). Thirteen (25%) of the 51 patients had suspicious atypical nevi; the initial thickness of these lesions ranged from 1.8 to 3.6 mm (median, 2.6 mm), and the median follow-up was 1.2 years (range, 0.5 to 2 years; Table 2 ).
| No. of Choroidal Nevi/Initial Thickness (mm)/Presentation | 358 Choroidal Nevi | ||||
|---|---|---|---|---|---|
| Median Follow-up, y (Range) | Growth, n (%) | Decreased A-Scan Reflectivity, n (%) | Hollowness on B-Scan, n (%) | Plaqued, n (%) | |
| 307/< 1.5/typical | 6 (4 to 9) | 0 | 0 | 0 | 0 |
| 38/> 1.5/ typical | 7 (2 to 18) | 3 (8) | 9 (24) | 9 (24) | 1 (3) a |
| 13/> 1.5/atypical | 1.2 (0.5 to 2) | 2 (33) | 13 (100) b | 12 (92) | 6 (46) |
a One patient 15 years after first observation; another patient declined enucleation.
b Atypical nevi maintained initial predominantly medium internal reflectivity on standardized A-scan.
The baseline thickness of the choroidal nevi as measured by standardized A-scan echography was significantly different in 38 nevi designated as typical (1.98 ± 0.37 mm) compared with that of 13 suspicious nevi (2.75 ± 0.66 mm; P = .0002, Mann–Whitney U test). Moreover, 18 typical (47%) versus 11 atypical (84%) choroidal nevi had thicknesses exceeding 2 mm ( P < .05, Fisher exact test). Nevi thickness of more than 2 mm was 6 times more frequent in the atypical versus the typical choroidal nevi (odds ratio, 6.1; 95% confidence interval, 1.2 to 31.3; Table 1 ). The mean thickness exceeding 2 mm was significantly different in the 2 groups of choroidal nevi (2.3 ± 0.3 mm vs 2.9 ± 0.6 mm for typical vs atypical, respectively; P < .0001, Mann–Whitney U test). Ultrasonographic hollowness on B-scan was detected in 11 (85%) of the 13 atypical nevi with medium to high internal reflectivity on the standardized A-scan and in none of the typical nevi ( P < .0001, Fisher exact test; Table 1 ). All other risk factors could be found in approximately half of the atypical nevi, but orange pigment was found in only 1 (2%) of the typical nevi ( Table 1 ).
During the follow-up, no changes in ophthalmoscopic appearance, elevation, or reflectivity (A-scan) and no acoustic hollowness as measured by standardized echography were recorded in all of the 307 nevi with a median elevation of 0.9 mm (range, 0.7 to 1.5 mm). After a 2- to 6-year follow-up period in 38 initially typical nevi with elevation higher than 1.5 mm, decreased A-scan reflectivity and hollowness on B-scan sections were observed in 7 of the nevi (18%); 1 nevus (3%) slowly grew to 1.1 mm after 6 years of observation ( Table 2 and Figure 2 ). None of these 7 choroidal nevi were subjected to conservative treatment.
