Miguel A. Materin

Iris melanoma: risk factors for metastasis in 169 consecutive patients.

Abstract Objective To identify risk factors that predict distant metastases of iris malignant melanoma. Design Retrospective case series. Participants The participants included 169 consecutive patients with microscopically confirmed iris malignant melanoma managed on the Oncology Service at Wills Eye Hospital between 1974 and 1999. Main outcome measures The main outcome measure was the development of distant tumor metastasis. Cox proportional regression models were used to calculate the risk of eventual metastatic spread. Results Of 1054 patients referred with suspicious iris melanocytic tumors (rule out malignant melanoma) over a 25-year period, 169 patients (16%) had microscopically proven iris melanoma, and the remainder (84%) had clinically diagnosed iris nevus. Of the patients with iris melanoma, the mean age at the time of diagnosis was 43 years (median, 45 years; range, 1–90 years). All patients were Caucasian. The mean tumor base was 6 mm (median, 5 mm; range, 1–17 mm), and mean tumor thickness was 2 mm (median, 2 mm; range, 1–4 mm). The mean number of clock hours of tumor involvement in the iris was four, tumor seeding on the iris was four, and tumor seeding into the anterior chamber angle was four. Extraocular extension was present in 10 eyes (6%). The tumor management consisted of local resection (iridectomy, iridocyclectomy, or iridocyclogoniectomy) in 102 patients (60%), enucleation in 51 (30%), plaque radiotherapy in 9 (5%), and observation in 7 patients (4%). Metastasis developed in nine patients (5%). Using Kaplan-Meier life table analysis, metastasis was found in 3% of patients at 5 years, 5% at 10 years, and 10% at 20 years. The clinical factors at initial evaluation predictive of eventual metastasis from iris melanoma included increasing age at diagnosis ( P = 0.03), elevated intraocular pressure ( P = 0.03), posterior tumor margin at angle or iris root (versus midzone) ( P = 0.02), extraocular extension ( P = 0.02), and prior surgical treatment of the tumor elsewhere before referral (versus observation) ( P = 0.006). The method of management (resection, radiotherapy, or enucleation) did not have an impact on metastasis. Conclusions Microscopically confirmed iris melanoma demonstrates distant metastasis in 5% of patients at 10 years follow-up. Metastases are more likely to develop in those patients who are older and show tumor features of iris root/angle location with elevated intraocular pressure and extraocular extension.

Review of optical coherence tomography for intraocular tumors.

Purpose of review Optical coherence tomography has assumed an important role in the management of numerous ocular conditions. With regard to ocular oncology, optical coherence tomography can illustrate retinal changes overlying choroidal tumors. Some of these features include photoreceptor loss, intraretinal edema, and retinal thinning overlying choroidal nevus; fresh subretinal fluid with preservation of photoreceptors overlying choroidal melanoma; and intraretinal edema, retinoschisis, and retinal thinning overlying irradiated choroidal melanoma. Recent findings The optical coherence tomography features of tumors of the retinal pigment epithelium include typical findings of peaked vitreoretinal traction and retinal disorganization with combined hamartoma of the retina and retinal pigment epithelium, full-thickness retinal shadowing with congenital simple hamartoma, and photoreceptor loss and retinal thinning overlying congenital hypertrophy of the retinal pigment epithelium. Summary Optical coherence tomography of retinal tumors, such as retinoblastoma and astrocytic hamartoma, reveals full-thickness replacement of the retinal anatomic layers with the tumor and shadowing corresponding to the intralesional calcification. For all intraocular tumors, optical coherence tomography provides valuable information regarding the status of the retina and the retinal pigment epithelium and can be useful in ascertaining reasons for visual loss.

Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma.

Objective: To evaluate the effect of intravitreal triamcinolone acetonide on patients with visually symptomatic radiation-induced maculopathy after plaque radiotherapy for choroidal melanoma. Design: In this prospective, nonrandomized, single-center case series of 31 patients with visually symptomatic radiation-induced maculopathy after plaque radiotherapy for choroidal melanoma at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, triamcinolone acetonide (4 mg/1 mL) was injected through the pars plana into the vitreous cavity using sterile technique. Status of radiation maculopathy and final visual acuity were the main outcome measures. Results: At the time of diagnosis of choroidal melanoma, visual acuity was 20/20 to 20/50 in 90% (n = 28), 20/60 to 20/200 in 10% (n = 3), and 20/400 or worse in none of the patients. The mean radiation dose to the foveola was 5,122 cGy (median, 3,280 cGy; range, 1,000–16,100 cGy). Radiation maculopathy developed at a mean of 22 months (median, 16 months; range, 6–96 months) after plaque radiotherapy. In all cases, the choroidal melanoma was regressed, and there was no retinal detachment or neovascularization of the retina, optic disk, or iris. At the time of diagnosis of radiation maculopathy, visual acuity was 20/20 to 20/50 in 19% (6/31), 20/60 to 20/200 in 58% (18/31), and 20/400 or worse in 23% (7/31) of patients. After intravitreal injection of triamcinolone acetonide, visual acuity was stable or improved in 91% (20/22) of patients by 1 month and 45% (14/31) by 6 months. Mean foveal thickness by optical coherence tomography was 417 μm at injection and 207 μm at 1 month and 292 μm at 6 months after injection. Conclusions: Intravitreal triamcinolone acetonide can stabilize or improve visual acuity in some patients with radiation-induced maculopathy, but its effect might not be lasting.

Optical coherence tomography of choroidal nevus in 120 patients.

Objective: To describe the optical coherence tomography (OCT) findings of choroidal nevi. Methods: Retrospective, single-center case series of 120 eyes of 120 consecutive patients with choroidal nevi who were evaluated by OCT. Diagnostic imaging was performed with a Zeiss StratusOCT Model 3000 (Carl Zeiss Ophthalmic Systems, Dublin, CA) using scan acquisition protocols of 6 radial lines and retinal thickness analysis overlying the nevus. Results: The mean patient age was 59 years (median, 60 years; range, 14–87 years). The choroidal nevus was a mean of 5.2 mm in basal dimension and 1.7 mm in thickness and was located a mean of 2.7 mm from the optic disk and 2.5 mm from the foveola. Related retinal findings by ophthalmoscopic evaluation included overlying retina edema (3%), subretinal fluid (16%), retinal thinning (0%), drusen (58%), and retinal pigment epithelium (RPE) detachment (2%). In comparison, related retinal findings at the site of the nevus by OCT included overlying retina edema (15%), subretinal fluid (26%), retinal thinning (22%), drusen (41%), and RPE detachment (12%). Furthermore, OCT permitted classification of the overlying retinal edema as focal cystoid (3%), diffuse cystoid (8%), coalescent cystoid (3%), and noncystoid edema (1%). By OCT, the overlying retina was normal thickness (32%), thinned (22%), or thickened (45%), and photoreceptor loss or attenuation was noted in 51% of cases. Specific OCT findings of the choroidal nevus were limited to its anterior surface with minimal penetration into the mass. These findings included increased thickness of the RPE/choriocapillaris layer (68%) and optical qualities within the anterior portion of the nevus of hyporeflectivity (62%), isoreflectivity (29%), and hyperreflectivity (9%). Hyporeflectivity was observed in 68% of pigmented nevi and 18% of nonpigmented nevi. When comparing OCT with clinical examination, OCT was more sensitive in the detection of related retinal edema, subretinal fluid, retinal thinning, photoreceptor attenuation, and RPE detachment. Conclusions: OCT is a useful diagnostic modality for imaging the retina overlying a choroidal nevus. Numerous overlying changes such as subretinal fluid, retinal edema, retinal thinning, and photoreceptor attenuation are visible by OCT.

Early Macular Morphological Changes Following Plaque Radiotherapy For Uveal Melanoma

Purpose: To evaluate the time of onset and risk factors for the development of macular edema following plaque radiotherapy for uveal melanoma, using optical coherence tomography (OCT). Methods: This observational case series included 135 consecutive patients with uveal melanoma treated with Iodine125 plaque radiotherapy and adjunctive transpupillary thermotherapy (TTT) laser. Patients were evaluated at baseline and 6-month intervals following treatment using ophthalmoscopy, B-scan ultrasonography, fundus photography, and OCT. Results: Median follow-up was 24 months. The mean time to onset of macular edema by OCT was 12 months. Median best-corrected logMAR visual acuity at the time of onset of OCT-evident macular edema was 0.3 (equivalent to 20/40 Snellen). The development of OCT-evident macular edema was significantly associated with maximum tumor thickness (P = 0.0016), largest tumor base (P < 0.0001), radiation dose, and dose-rate to the tumor base (P = 0.0315 and P = 0.0204, respectively). Neither radiation dose to the foveola nor treatment with adjunctive TTT laser was significantly associated with the development of macular edema. Conclusions: OCT is useful in the early detection of radiation-induced macular edema, before clinical signs of radiation maculopathy develop and before substantial visual loss occurs. The development of macular edema is significantly associated with larger initial tumor size.

Intravitreal triamcinolone acetonide for acute radiation papillopathy.

Objective: To evaluate intravitreal triamcinolone acetonide for patients with visually symptomatic acute radiation-induced papillopathy. Methods: In a prospective, nonrandomized, single-center case series, intravitreal triamcinolone acetonide (4 mg/0.1 mL) was injected through the pars plana using sterile technique in 9 patients with radiation papillopathy after plaque radiotherapy for choroidal melanoma. Status of radiation papillopathy and final visual acuity were the main outcome measures. Results: At the time of diagnosis of the choroidal melanoma, visual acuity was 20/20 to 20/40 (n = 6), 20/60 (n = 2), and 20/100 (n = 1). The mean radiation dose to the optic disk was 6,175 cGy (median, 5,994 cGy; range, 3,571–12,760 cGy). Radiation papillopathy developed a mean of 18 months (median, 17 months; range, 6–33 months) after plaque radiotherapy. In all cases, the choroidal melanoma was regressed, and there was no retinal detachment or neovascularization of the retina, optic disk, or iris. Concomitant radiation maculopathy was found in 8 eyes manifesting as macular edema (n = 8), intraretinal dot hemorrhages (n = 6), intraretinal exudation (n = 6), or nerve fiber layer infarction (n = 3). The radiation papillopathy findings included optic disk hyperemia (n = 9), edema (n = 9), and circumpapillary hemorrhage (n = 8). At the time of diagnosis of radiation papillopathy, visual acuity was 20/70 (n = 1), 20/100 (n = 4), 20/200 (n = 1), and counting fingers (n = 3). At 1 week after injection of triamcinolone acetonide, visual acuity improvement was found in seven patients, and resolution of optic disk hyperemia and edema was noted for four and three patients, respectively. At a mean follow-up of 11 months (median, 9 months; range, 6–19 months), visual acuity was stable or improved in 7 patients, and resolution of optic disk hyperemia and edema was found in all 9 patients. The mean time to improvement in visual acuity by ≥2 lines was 3 weeks (median, 1 week; range, 1–12 weeks). The mean time to complete resolution of radiation papillopathy was 4 months. The two patients with worse final visual acuity also had macular hole and central retinal vein obstruction. The only complication of this therapy was possibly related cataract in three patients. Conclusion: During short-term follow-up, acute radiation-induced papillopathy appears to respond rapidly to intravitreal triamcinolone acetonide injection with resolution of optic disk hyperemia and edema and modest return of visual acuity. The long-term effects remain unknown.

Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: a randomized controlled trial.

OBJECTIVE To determine the efficacy and safety of periocular triamcinolone acetonide (40 mg) for the prevention of macular edema in patients undergoing plaque radiotherapy for uveal melanoma. DESIGN Prospective, randomized, controlled clinical trial. PARTICIPANTS AND CONTROLS One-hundred sixty-three patients with newly diagnosed uveal melanoma undergoing iodine 125 plaque radiotherapy were entered into the study. Fifty-five patients were randomized to the control group and 108 to the triamcinolone group. Eighteen-month data were available for 143 (88%) of the 163 patients. INTERVENTION Periocular injection of triamcinolone acetonide (40 mg in 1 ml) at the time of plaque radiotherapy and 4 months and 8 months later. Optical coherence tomography was performed at each patient evaluation. MAIN OUTCOME MEASURES Optical coherence tomography-evident macular edema, moderate vision loss, and poor final visual acuity. RESULTS Optical coherence tomography-evident macular edema occurred significantly less often in the triamcinolone group compared with the control group up to 18 months after plaque radiotherapy (hazard estimate, 0.45; 95% confidence interval, 0.19-0.70; P = 0.001). At the 18-month follow-up, moderate vision loss (loss of 3 lines or more of best-corrected visual acuity [BCVA]) and severe vision loss (BCVA <5/200 Snellen) occurred significantly less frequently in the triamcinolone group than in the control group (31% vs. 48% [P = 0.039] and 5% vs. 15% [P = 0.048], respectively). Rates of elevated intraocular pressure and cataract progression were similar in both groups. CONCLUSIONS Periocular triamcinolone is beneficial in reducing the risk of macular edema up to 18 months after plaque radiotherapy for uveal melanoma and significantly reduces the risk of moderate vision loss and poor visual acuity in these patients.

Autofluorescence of choroidal nevus in 64 cases.

Purpose: To describe the autofluorescence features of choroidal nevi. Design: Noncomparative case series. Participants: Sixty-four consecutive patients. Methods: Correlation of fundus photography with autofluorescence photography. Main Outcome Measure: Autofluorescence features of choroidal nevus and overlying retinal pigment epithelium (RPE). Results: The mean patient age was 62 years. The choroidal nevus was a mean of 5 mm from the optic disk and foveola. The mean tumor basal dimension was 5.0 mm and mean tumor thickness was 1.0 mm. The choroidal nevus showed hypoautofluorescence in 56%, isoautofluorescence in 19%, and hyperautofluorescence in 25%. The autofluorescence features appeared unaffected by tumor thickness, but increasing tumor base and disrupted overlying RPE appeared to produce slightly brighter autofluorescence. Nevi located in the macular region showed darker hypoautofluorescence than those outside the macular region. Overlying RPE hyperplasia, atrophy, and fibrous metaplasia were generally hypoautofluorescent. Drusen, subretinal fluid, and orange pigment were generally hyperautofluorescent. The brightest hyperautofluorescence was found with orange pigment. Conclusions: Choroidal nevus shows little intrinsic autofluorescence. Overlying RPE alterations show dramatic autofluorescence ranging from dark hypoautofluorescence of RPE atrophy to bright hyperautofluorescence of orange pigment.

Autofluorescence of choroidal melanoma in 51 cases

Aim: To describe the autofluorescence features of choroidal melanoma. Design: Non-comparative case series. Participants: 51 consecutive patients. Methods: Standard fundus photography and autofluorescence photography (580 nm excitation, 695 nm barrier filter) were performed on all patients. Clinical features were correlated with autofluorescence features. Main outcome measure: Autofluorescence features of choroidal melanoma and overlying retinal pigment epithelium (RPE). Results: The mean patient age was 59 years. The choroidal melanoma was a mean of 3.6 mm from the optic disc and 2.6 mm from the foveola. The mean tumour basal dimension was 11 mm and the mean tumour thickness was 4 mm. The choroidal melanoma showed intrinsic hypoautofluorescence (39%), isoautofluorescence (6%) and hyperautofluorescence (55%). Slightly increased hyperautofluorescence of the melanoma was found in pigmented tumours (versus non-pigmented), those with greater thickness and basal dimensions, and those with overlying disrupted RPE. Related RPE hyperplasia and atrophy showed hypoautofluorescence, drusen, RPE detachment and subretinal fluid showed slight hyperautofluorescence, and orange pigment displayed the brightest hyperautofluorescence. Conclusions: Choroidal melanoma generally shows slight intrinsic hyperautofluorescence and the brightness increases with pigmented tumours, larger tumours, and those associated with disrupted RPE. Overlying orange pigment shows remarkably bright hyperautofluorescence.

Regression of Extrafoveal Choroidal Osteoma Following Photodynamic Therapy

revealed progression of pancytopenia to bone marrow failure during 12 months. Concurrently, patchy cutaneous hypopigmented maculae on the back, ridged finger nails, and longitudinal furrows on the ventral surface of the hands and feet suggested the diagnosis of dyskeratosis congenita (Figure 2A and B). Genetic analysis revealed abnormality in chromosome Xq28, confirming the diagnosis. Allogeneic stem cell transplantation was performed for the bone marrow failure, with recovery of bone marrow function at 6-months’ follow-up.