Table I.

Key points of primary tumor diagnosis and treatment.

Diagnosis				Treatment
Tumor location	Clinical examination (Refs.)	Tests and imaging (Refs.)	Relevant studies (Refs.)	Type (Refs.)	Relevant studies (Refs.)
Iris melanoma	-Type: Circumscribed tumor (most cases); diffuse iris melanoma (10% of cases, undefined, flat, infiltrative form) (39,40); ring melanoma (rare, angle location with a ring pattern of growth, glaucoma) (41); color: Different levels of pigmentation (from amelanotic to pigmented); diameters; location (inferior quadrant in 45% of cases) (10); associated findings: Heterochromia, corectopia, bleeding, ectropion uveae, extraocular extension, glaucoma (10); -Gonioscopy: Angle involvement (10); -Transillumination: Ciliary body involvement (10). -Anterior segment-optical coherence tomography (size and posterior and posterior extension) (10);	-Ultrasound biomicroscopy; Anterior (size and posterior extension) (10); -Photographic documentation (tumor growth) (10); -fine-needle biopsy (doubtful cases, genetic profile) (58).	ABCDEF acronym (26) (predictive factors for differentiating an iris melanoma from a nevus): A: Young age; B: Blood; C: Clock-hour (inferior location); D: Diffuse flat shape; E: Ectropion uveae; F: Feathery margins.	-Resection (small melanoma) iridectomy, iridotrabeculectomy, iridocyclectomy; -Radiotherapy (non-resectable lesion; seeding): Proton beam and plaque radiotherapy, good local tumor control (102,103); -Enucleation (large tumors, poor visual function, recurrent tumors, multifocal melanoma and diffuse melanoma).	Shields et al, 2013 (104): 144 iris melanomas treated with iodine-125 plaque radiotherapy: 15% local recurrence at 7 years, 1% metastasis rate at 7 years.
Ciliary body melanoma	-Slit lamp examination and dilated fundoscopy with scleral indentation; -Transillumination (10).	-Ultrasound biomicroscopy: Useful for small melanomas (<4 mm) (47).	-In most cases tumors are diagnosed when are large: Baseline mean tumor base of 11.7 mm and mean thickness of 6.6 mm (47).	Posterior UM (including both ciliary body melanoma and choroidal melanoma): -Brachytherapy: Tumors <10 mm thickness and	Posterior UM (including both ciliary body melanoma and choroidal melanoma): -COMS trial: Medium
Choroidal melanoma	-Dilated fundus examination: Configuration dome-shaped (75% of cases), mushroom-shaped (20% of cases), diffuse (5% of cases) (43); color pigmented (55% of cases), mixed (30% of cases), non-pigmented (15% of cases) (43); associated features subretinal fluid; orange pigment; bleeding.	-Ocular ultrasonography: (B-scan, A-scan) low-medium reflectivity/ ultrasonographic hollowness (10,49); -Fluorescein and indocyanine green angiography: Progressive hyperfluorescence, 'double circulation' pattern (51);		<18 mm maximum basal diameter (62); apex dose 70-100 Gy (105); Ruthenium-106 lower penetration depth (tumors <6 mm thickness) (106); local recurrence rate: 3% for palladium-103, 7-10% for iodine-125, 14.7% for ruthenium-106 (2);	choroidal melanoma (2.5-10 mm apical height and maximum basal tumor diameter ≤16 mm) randomized to iodine-125 brachytherapy (85 Gy apex dose) or enucleation. No survival differences: 5-, 10- and 12-year all-cause mortality rate was 19, 35 and 43% in the
		-Optical coherence tomography: Posterior location; accurate for detecting subretinal fluid; useful for small lesion (50); -Photographic documentation: Tumor growth, follow-up; -Fine-needle biopsy (mainly for genetic profile) (58).	-TFSOM UHHD acronym (30) (predictive factors for differentiating a small melanoma from a nevus): Thickness (>2 mm); fluid (subretinal fluid); symptoms; orange pigment (lipofuscin); margin (≤3 mm from optic disc); tumor ultrasonographic hollowness; halo (absent); drusen (absent); -TFSOM DIM (54): Thickness (>2 mm); fluid (subretinal fluid on optical coherence tomography); symptoms; orange pigment (on autofluorescence), ultrasonographic hollowness, diameter >5 mm (photography).	-Proton beam radiotherapy: Tumor control and prognosis comparable to brachytherapy (113); tumor control over 90%, and 5-year overall survival of 70-85% (112); preferred to brachytherapy for posterior pole location (112); in large melanomas (>10 mm thickness or >16 mm largest diameter) good tumor control but risk of ischemic and inflammatory complications (115); -Stereotactic radiotherapy (comparable to proton beam) (117); -Enucleation: Thickness >10 or 12 mm and/or a basal diameter >18 mm (62,119); -Orbital exenteration: Extensive extraocular growth or orbital invasion (10,106); -Local resection (exoresection, endoresection): Selected cases.	brachytherapy arm, and 19, 35 and 41% in the enucleation arm, respectively; 5-, 10- and 12-year metastasis-related mortality rate (histopathologically confirmed) was 10, 18 and 21% in the brachytherapy arm, and 11, 17 and 17% in the enucleation arm, respectively (72). Brachytherapy 'as safe as enucleation' (108); -Papakostas et al, 2017 (116): More than 300 patients affected by large choroidal melanoma (>10 mm thickness or >16 mm largest basal diameter) treated with proton beam radiotherapy: 70% Eye retention at 10 years; 60% 10-year mortality (comparable with enucleation); 87% 10-year local tumor control; poor visual outcome: 20/200 or better in 8.7% at 10 years; 25% neovascular glaucoma.

COMS, Collaborative Ocular Melanoma Study; Gy, gamma ray; UM, uveal melanoma.