Purpose
To report the experience of the Princess Margaret Hospital/University Health Network with the treatment of iris melanoma (IM) with 125 Iodine plaque brachytherapy.
Design
Retrospective noncomparative case series.
Methods
All cases of IM submitted to 125 Iodine plaque radiotherapy were included. Patients’ demographic, clinical, management, and follow-up data were reviewed. Outcome measures included rates of tumor control, eye preservation, systemic metastases, and brachytherapy-related complications.
Results
Fourteen IMs were included in the study. All patients had blue/green irises. Mean largest basal dimension and thickness were 7.1 ± 2.1 mm (range, 4.0 to 11.5 mm) and 2.2 ± 0.8 mm (range, 1.0 to 3.5 mm), respectively. Ten patients (71%) had seeding and 2 (14%) had glaucoma at presentation. Median follow-up was 26.6 ± 19.5 months (range, 6 to 72 months). Tumor control was achieved in 100% of the cases and no eye was enucleated because of radiation-induced complications. At last visit, all patients were alive and free of metastasis. Final visual acuity was the same as or better than before treatment in 9 patients (75%). Cataract was the most common complication (8; 75%), followed by persistent glaucoma (2; 17%) and anterior uveitis (1; 8%). No other significant complication was seen during the follow-up period.
Conclusions
Plaque radiotherapy is a safe and effective conservative treatment option for IM, although cataract is a common, yet treatable, complication. This treatment scheme circumvents an intraocular procedure and may avoid the dissemination of malignant cells, and provides a margin of safety in the treatment of clinically undetectable disease.
Iris melanoma (IM) is the least common of uveal melanomas. It comprises less than 3% of all intraocular melanomas and carries the best prognosis. Metastatic rates are 3%, 5%, and 10% on 5-, 10-, and 20-year follow-ups, respectively.
Proper management of IM is still controversial. Melanocytic lesions of the iris are usually followed until growth is detected. Natural history studies have shown that only a few of those cases change over time (4.6% at 3.9-month mean follow-up). The classical approach to enlarging lesions of the iris is surgical resection. Since surgical resection of the melanoma carries the risks associated with an invasive intraocular procedure and incomplete tumor excision, different irradiation modalities have been advocated. The experience with 125 Iodine plaque brachytherapy in the treatment of IM at the Princess Margaret Hospital/University Health Network is the subject of the report to follow.
Methods
We retrospectively reviewed all cases of IM treated with 125 Iodine plaque radiotherapy over the past 10 years. Contraindications for plaque treatment were ring melanoma (more than 180 degrees), tumor-induced glaucoma in an eye with low visual potential, peripheral corneal disease, and seeding of tumor cells away from the planned area of treatment. Only cases with documented growth and suggestive clinical features were treated and consequently included in the study. Large tumor size, prominent tumor vascularity, tumor seeding, elevated intraocular pressure (IOP), and tumor-related ocular complications are some of the described suspicious features. Even though cases with minimal ciliary body involvement were included, we did exclude cases that originated from the ciliary body, or when the bulk of the lesion was not in the iris. Patients who had no available follow-up information were excluded from the study.
Baseline Characteristics
Medical records were reviewed in order to retrieve the following information: age, gender, laterality, symptoms, past ocular history, visual acuity (VA) and IOP at presentation, iris color, pupil distortion, presence of hyphema, location of the tumor (quadrant involved), degree of pigmentation, presence of seeding, and prominent vascularity.
Ultrasound Biomicroscopic Features
Ultrasound biomicroscopy (UBM) was performed in all patients to determine the largest tumor dimension (LTD), thickness, extension, and ultrasonographic features of the tumor; internal reflectivity (high or low, homogeneous or heterogeneous); shape; presence of intralesional cavitations or associated cysts; anterior surface plaque; tumor touching the cornea; anterior and posterior tumor contour (smooth or irregular); and iris pigment epithelium breaks.
Surgical Technique
Collaborative Ocular Melanoma Study (COMS)-designed plaques were used in all cases, with diameters of 12- or 14-mm depending on the size of the tumor. Plaque size was determined according to the tumor’s largest basal dimension; a safe margin of 2 mm was added in all directions. Radiation dose was calculated considering the maximum thickness of the lesion. The energy, number, and distribution of the radioactive seeds were adjusted for each individual case so as to provide a total dose of 8500 cGy to the tumor apex at a dose rate of 50 cGy/hour over 7 days, which is the time allocated for plaque surgery in our institution. Calculations were made using the Plaque Simulator software distributed by BEBIG GmbH (Berlin, Germany). Briefly, the tumor was transilluminated after a conjunctival peritomy. Two scleral sutures were placed in the sclera and tied to 2 plaque islets. The conjunctiva was then sutured over the plaque to avoid scleral exposure and displacement of the plaque. The plaque was left in place for a week and during that time the eye was patched with a special dressing to prevent further pressure on the globe. A tobramycin 0.3%-dexamethasone 0.1% ophthalmic suspension (Isopto Homatropine; Alcon Laboratories Inc., Fortworth, Texas, USA) and homatropine (Tobradex; Alcon Laboratories Inc.) were used 3 times a day during this week, and also for the following 2 weeks after plaque removal. At that time, the patient was examined to assess corneal integrity and conjunctival healing.
Outcome
The first postoperative tumor measurements were accomplished at 3 and 6 months postoperatively and every 6 months thereafter. Tumor response was defined by loss of vascularity, decrease in tumor thickness, and UBM changes, such as an increase in internal reflectivity. At each visit, the patient was screened for metastatic disease (liver enzymes and abdominal ultrasound) and a complete ophthalmologic evaluation, including VA, IOP, presence of complications, and tumor measurements by UBM, was performed. Subsequent surgical interventions were also recorded. A list of potential complications included: delayed corneal and/or conjunctival healing; corneal epitheliopathy; scleral and/or corneal necrosis; endothelial decompensation; persistent anterior uveitis and/or glaucoma; cataract; radiation retinopathy; radiation optic neuropathy; and neovascular glaucoma.
Results
Clinical Features
Fourteen IMs were included in the study. On average, patients were followed for 32 ± 43 months before treatment was indicated. Age at presentation was 51.0 ± 13.8 years (range, 27 to 72) and 11 of the patients (79%) were women. All patients had blue/green irises. Eight patients (57%) had the left eye affected. The majority of patients had no symptoms at presentation (n = 11, 79%). Three patients had vision blurring, 2 attributable to hyphema and 1 attributable to cataract. One other patient was pseudophakic with a posterior chamber intraocular lens implanted. Mean IOP was 16 ± 4 mm Hg. Two patients presented with unilateral glaucoma. Other clinical features are detailed in Table 1 .
| Characteristics | Values |
|---|---|
| Age (years) | |
| Mean | 51 |
| SD | 13.8 |
| Range | 27 to 72 |
| Gender, n (%) | |
| Women | 11 (79%) |
| Men | 3 (21%) |
| Laterality, n (%) | |
| OD | 6 (43%) |
| OS | 8 (57%) |
| Iris color, n (%) | |
| Blue/Green | 14 (100%) |
| Brown | 0 |
| Visual acuity, n (%) | |
| 20/20 | 9 (64%) |
| 20/30 | 4 (29%) |
| 20/40 | 1 (7%) |
| IOP (mm Hg) | |
| Mean | 16 |
| SD | 4 |
| Range | 12 to 28 |
| Corectopia, n (%) | |
| Present | 5 (36%) |
| Absent | 9 (64%) |
| Location (quadrant), n (%) | |
| Inferior | 9 (64%) |
| Nasal | 3 (21%) |
| Temporal | 1 (7%) |
| Superior | 1 (7%) |
| Anterior tumor margin, n (%) | |
| Pupil | 11 (79%) |
| Midzone | 3 (21%) |
| Iris root | 0 |
| Posterior tumor margin, n (%) | |
| Midzone | 1 (6%) |
| Iris root | 13 (93%) |
| Pigmentation, n (%) | |
| Melanotic | 10 (71%) |
| Amelanotic | 2 (14%) |
| Mixed | 2 (14%) |
| Pigment seeding | |
| Present | 10 (71%) |
| Absent | 4 (29%) |
| Vascularity, n (%) | |
| Present | 8 (57%) |
| Absent | 6 (43%) |
Tumor Characteristics
Thirteen of the IMs (93%) were located at sun-exposed areas of the iris. Mean largest basal dimension and thickness were 7.1 ± 2.3 mm (range, 4.0 to 11.5 mm) and 2.3 ± 0.7 mm (range, 1.0 to 3.5 mm), respectively. Ten IMs (71%) were pigmented, 2 (14%) showed varied pigmentation, and 2 (14%) were amelanotic. Ten cases (71%) showed seeding on the adjacent iris surface and/or angle. Prominent intrinsic vasculature was seen in 8 cases (57%), and 5 of the tumors (36%) caused distortion of the pupil. Eleven cases (79%) showed involvement of the pupillary margin, while in 13 cases (93%) the root of the iris was compromised (10 cases [71%] had both). UBM showed extension to the ciliary body in 5 cases (36%). All (2) amelanotic tumors had low internal reflectivity. Among the (10) melanotic ones, 3 had high and 7 had low internal reflectivity. Other UBM features are exposed in Table 2 .
| Baseline Features | n (%) |
|---|---|
| Shape | |
| Nodular | 6 (43%) |
| Fusiform | 2 (14%) |
| Diffuse | 3 (21%) |
| Irregular | 3 (21%) |
| Largest basal dimension (mm) | |
| Mean | 7.1 |
| SD | 2.3 |
| Range | 4.0–11.5 |
| Thickness (mm) | |
| Mean | 2.3 |
| SD | 0.7 |
| Range | 1.0–3.5 |
| Internal structure | |
| Homogeneous | 5 (36%) |
| Heterogeneous | 9 (64%) |
| Internal reflectivity | |
| High | 3 (21%) |
| Low | 11 (79%) |
| Surface plaque | |
| Present | 6 (43%) |
| Absent | 8 (57%) |
| Anterior surface | |
| Smooth | 7 (50%) |
| Irregular | 7 (50%) |
| Posterior surface | |
| Smooth | 8 (57%) |
| Irregular | 6 (43%) |
| Corneal touch | |
| Present | 7 (50%) |
| Absent | 7 (50%) |
| Breaks in IPE | |
| Present | 8 (57%) |
| Absent | 6 (43%) |
| Iris root involvement | |
| Present | 13 (93%) |
| Absent | 1 (7%) |
| CB involvement | |
| Present | 5 (36%) |
| Absent | 9 (64%) |
| Cavitations | |
| Present | 1 (7%) |
| Absent | 13 (93%) |
| Associated cysts | |
| Present | 3 (21%) |
| Absent | 11 (79%) |
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