Purpose
To investigate the relationship between subfoveal choroidal thickness and metabolic activity in eyes with choroidal melanoma.
Design
Retrospective, interventional case series.
Methods
The medical records of 16 patients with unilateral choroidal melanoma who underwent ruthenium (Ru) 106 brachytherapy with adjuvant transpupillary thermotherapy and who had available pretreatment positron emission tomography–computed tomography (PET-CT) images were retrospectively reviewed. Subfoveal choroidal thickness was measured in tumor eyes and in unaffected fellow eyes using enhanced-depth imaging spectral-domain optical coherence tomography (EDI OCT). Tumor eyes were divided into 2 groups (metabolically active and inactive) based on PET-CT findings and subfoveal choroidal thickness was compared between groups. Additionally, choroidal thickness measurements were compared before and after treatment.
Results
Before treatment, mean choroidal thickness was 293.31 ± 46.80 μm in tumor eyes and 242.44 ± 65.37 μm in fellow eyes, a difference that was statistically significant ( P = .003). Eyes with metabolically active tumors had a significantly thicker choroid (348.00 ± 17.32 μm) than eyes with metabolically inactive tumors (280.69 ± 42.04 μm, P = .019). In tumor eyes, mean choroidal thickness significantly decreased from pretreatment values to 253.56 ± 61.27 μm 6 months after treatment ( P = .018).
Conclusion
Eyes with choroidal melanoma had thicker choroids than unaffected fellow eyes. Increased choroidal thickness was more prominent in metabolically active tumors. Choroidal thickness significantly decreased in tumor eyes 6 months after treatment.
The recent introduction of enhanced-depth imaging Spectralis optical coherence tomography (EDI OCT) techniques now allows cross-sectional visualization of the submacular choroid. Numerous studies have examined subfoveal choroidal thickness in various chorioretinal diseases, including age-related macular degeneration (AMD), central serous chorioretinopathy (CSC), Vogt-Koyanagi-Harada syndrome (VKH), leukemic choroidopathy, and Sturge-Weber syndrome. The choroidal layer is the most commonly affected layer of the eye during tumor development, with choroidal melanoma being the most common primary intraocular malignancy in adults. Cancer cells are highly metabolic and require a rich vascular supply for tumorigenesis. It is possible that choroidal melanoma tumorigenesis could induce an increase in choroidal circulation volume, which would result in a choroidal thickening. However, it is not known whether choroidal melanomas can affect subfoveal choroidal thickness or whether a change in choroidal thickness has any clinical implication.
In the present study, we investigated subfoveal choroidal thickness in eyes with choroidal melanomas not located directly beneath the fovea and in unaffected fellow eyes. The association between choroidal thickness and tumor characteristics were examined. This included measurement of metabolic activity with positron emission tomography–computed tomography (PET-CT) and the change in choroidal thickness following ruthenium (Ru) 106 plaque brachytherapy.
Methods
Patients
We retrospectively reviewed the medical records of patients with choroidal melanoma who underwent brachytherapy at the Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea, between January 1, 2010 and November 30, 2014. Of these, patients who also had available pretreatment PET-CT images and pre-/posttreatment spectral-domain OCT images were included in analyses. Patients with any of the following conditions were excluded: direct subfoveal choroid tumor involvement, past or concomitant chorioretinal disease in either eye, or previous ocular surgery in either eye. Ultimately, 16 patients with choroidal melanoma were included in our study. This study was approved retrospectively by the institutional review board of Severance Hospital.
Measurement of Choroidal Thickness and Tumor Size
All eyes were imaged using a Heidelberg Spectralis OCT (Heidelberg Engineering Inc, Heidelberg, Germany) instrument with the EDI OCT technique. During image acquisition, the OCT instrument was pushed close enough to the eye to obtain an inverted image. Each scan was obtained with the eye tracking feature enabled and was the average of 100 individual scans. The horizontal section passing through the foveal center was used for all analyses. Subfoveal choroidal thickness was defined as the distance between the outer surface of the retinal pigment epithelium (RPE) line to the inner surface of the observed sclera. Tumor largest basal diameter (LBD) and apical height were measured with B-scan ultrasonography (Ellex, Adelaide, Australia). Choroidal thickness and tumor size were compared between measurements made before and 6 months after treatment. The OCT images collected 3 months after treatment were unavailable in many patients, which prevented us from performing an adequate statistical analysis.
Whole Body, Dual-Modality Positron Emission Tomography–Computed Tomography Imaging
Before treatment, all patients underwent routine fluorodeoxyglucose (FDG) PET-CT imaging (GE Advance, Milwaukee, Wisconsin, USA). To evaluate FDG uptake by the ocular lesion before surgery, an experienced nuclear medicine specialist (A.C.) interpreted PET images using maximum standardized uptake values (SUV). If SUV was ≥2.2, the lesion was considered to be metabolically active, as determined in a previous study.
Choroidal Melanoma Treatment
All patients were treated with Ru-106 plaque with a target dose to the tumor apex of 85 Gy. In some cases, the dose was reduced to prevent a scleral dose that exceeded 1000 Gy. Three sessions of adjuvant transpupillary thermotherapy (TTT) were also performed in 3-month intervals in all patients using a diode laser with a slit-lamp delivery system. Exposure time was 1 min per spot and laser power was adjusted until the tumor surface became slightly gray.
Statistical Analyses
Data are presented as mean ± standard deviation where applicable. Data were analyzed using a commercially available statistical software program (SPSS version 20.0; SPSS, Chicago, Illinois, USA). A paired t test was used to compare choroidal thickness in tumor and fellow eyes. Correlations between choroidal thickness in tumor eyes and other baseline parameters were analyzed using Pearson correlation tests. The comparison of choroidal thickness in eyes with metabolically active and inactive tumors was performed using an independent t test. Choroidal thickness, tumor LBD, and tumor height were compared before and 6 months after brachytherapy using paired t tests. Correlations between changes in choroidal thickness and changes in tumor LBD and height were also analyzed using Pearson correlation tests. A P value <.05 was considered to be statistically significant.
Results
Sixteen eyes of 16 patients (7 male, 9 female) were ultimately included in analyses. Mean subject age was 53.56 ± 11.58 years at the time of treatment. Patient baseline characteristics are summarized in the Table . Mean tumor height was 5.97 ± 2.12 mm. Mean choroidal thickness in tumor eyes (293.31 ± 46.80 μm) was significantly thicker than that of unaffected fellow eyes (242.44 ± 65.37 μm, P = .003). No significant correlations between choroidal thickness in tumor eyes and other clinical indices, including age, LBD, and apical height, were observed. In tumor eyes, choroidal thickness was significantly greater in the metabolically active group (348.00 ± 17.32 μm) than in the metabolically inactive group (280.69 ± 42.04 μm, P = .019). Six months after treatment, choroidal thickness in tumor eyes had significantly decreased from 293.31 ± 46.80 μm before treatment to 253.56 ± 61.27 μm ( P = .018, Figure 1 ).
Metabolically Active Tumor (N = 3 Eyes) | Metabolically Inactive Tumor (N = 13 Eyes) | P a | ||
---|---|---|---|---|
Age (y) | 53.56 ± 11.58 | 55.00 ± 17.35 | 53.23 ± 10.80 | .821 |
Men/women (patients, n) | 7/9 | |||
Tumor size (mm) | ||||
Largest basal diameter | 10.93 ± 2.43 | 10.35 ± 3.93 | 11.07 ± 2.16 | .658 |
Height | 5.97 ± 2.12 | 4.41 ± 1.70 | 6.33 ± 2.10 | .166 |
Choroid thickness (μm) | ||||
Tumor eye | 293.31 ± 46.80 | 348.00 ± 17.32 | 280.69 ± 42.04 | .019 |
Fellow eye | 242.44 ± 65.37 | |||
Anterior margin (eyes, n) | >.999 | |||
Ora serrata to equator | 5 | 1 | 4 | |
Posterior to equator | 11 | 2 | 9 | |
Posterior margin (eyes, n) | NA | |||
Ora serrata to equator | 0 | 0 | 0 | |
Posterior to equator | 16 | 3 | 13 | |
Distance from posterior tumor margin to the foveola (eyes, n) | >.999 | |||
0–2.9 mm | 1 | 0 | 1 | |
3–5.9 mm | 9 | 2 | 7 | |
≥6.0 mm | 6 | 1 | 5 |