Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma.

BACKGROUND: Uveal melanoma is the most frequent primary tumour of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight ultraviolet (UV) exposure on the aetiology of uveal melanoma is a matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV-induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma. METHODS: We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays. RESULTS: We detected a TERT mutation in only one case of a 57-year-old white male patient with clinical and histopathological features typical for uveal melanoma. The tumour showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1 and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumours among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports, GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse. CONCLUSION: These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumour progression.

Intravitreal triamcinolone acetonide as primary treatment for diffuse diabetic macular edema: a prospective noncomparative interventional case series.

PURPOSE: To evaluate the efficacy and safety of one intravitreal injection of 25 mg of triamcinolone acetonide as primary treatment for diffuse diabetic macular edema. METHODS: Intravitreal triamcinolone acetonide injection was performed in 30 eyes with previously untreated diabetic macular edema. The main outcome measures were logMAR visual acuity (VA) and central macular thickness (CMT) at 1, 3, and 6 months. A secondary outcome was intraocular pressure progression. RESULTS: Visual acuity results for 30 eyes that had a follow-up of at least 6 months are presented. Twenty of them were followed up to 10.1+/-2.38 months. Preoperatively, VA was 0.54+/-0.27. At 1, 3, and 6 months follow-up, VA was 0.44+/-0.29 (p=0.001), 0.43+/-0.28 (p=0.001), and 0.45+/-0.29 (p=0.006), respectively. Preoperatively, CMT was 417.3+/-143.5 microm. At 1, 3, and 6 months follow-up, CMT was 277.3 +74.0 microm (p<0.0001), 279.6+/-94.4 microm (p<0.0001), and 297.07+/-114.87 microm (p=0.002), respectively. For the 20 eyes with a follow-up of 10.1+/-2.38 months, VA was 0.5+/-0.25 and 0.50+/-0.32 at baseline and at the last follow-up visit, respectively (p>0.05). Preoperatively, intraocular pressure (IOP) was 15.13+/-1.48 mmHg. IOP was 18.26+/-2.71 mmHg, 20.07+/-4.27 mmHg, and 20.4+/-6.18 mmHg, at 1, 3, and 6 months, respectively (p<0.0001). Four eyes underwent uncomplicated filtrating surgery for intractable glaucoma. CONCLUSIONS: Intravitreal triamcinolone as primary treatment effectively increases VA and reduces CMT due to diffuse diabetic macular edema. Longer follow-up and randomized clinical trial are warranted. Safety results highlight the need to further study the relationship between triamcinolone and intraocular pressure.

Intravitreal triamcinolone acetonide as primary treatment for diffuse diabetic macular edema: A prospective noncomparative interventional case series.

PURPOSE: To evaluate the efficacy and safety of one intravitreal injection of 25 mg of triamcinolone acetonide as primary treatment for diffuse diabetic macular edema. METHODS: Intravitreal triamcinolone acetonide injection was performed in 30 eyes with previously untreated diabetic macular edema. The main outcome measures were logMAR visual acuity (VA) and central macular thickness (CMT) at 1, 3, and 6 months. A secondary outcome was intraocular pressure progression. RESULTS: Visual acuity results for 30 eyes that had a follow-up of at least 6 months are presented. Twenty of them were followed up to 10.1+/-2.38 months. Preoperatively, VA was 0.54+/-0.27. At 1, 3, and 6 months follow-up, VA was 0.44+/-0.29 (p=0.001), 0.43+/-0.28 (p=0.001), and 0.45+/-0.29 (p=0.006), respectively. Preoperatively, CMT was 417.3+/-143.5 micronm. At 1, 3, and 6 months follow-up, CMT was 277.3 +74.0 micronm (p<0.0001), 279.6+/-94.4 micronm (p<0.0001), and 297.07+/-114.87 micronm (p=0.002), respectively. For the 20 eyes with a follow-up of 10.1+/-2.38 months, VA was 0.5+/-0.25 and 0.50+/-0.32 at baseline and at the last follow-up visit, respectively (p>0.05). Preoperatively, intraocular pressure (IOP) was 15.13+/-1.48 mmHg. IOP was 18.26+/-2.71 mmHg, 20.07+/-4.27 mmHg, and 20.4+/-6.18 mmHg, at 1, 3, and 6 months, respectively (p<0.0001). Four eyes underwent uncomplicated filtrating surgery for intractable glaucoma. CONCLUSIONS: Intravitreal triamcinolone as primary treatment effectively increases VA and reduces CMT due to diffuse diabetic macular edema. Longer follow-up and randomized clinical trial are warranted. Safety results highlight the need to further study the relationship between triamcinolone and intraocular pressure. (Eur J Ophthalmol 2006; 16: 129-33).