Impact of coagulation-balance gene predictors on efficacy of photodynamic therapy for choroidal neovascularization in pathologic myopia.
OBJECTIVE
To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM).


METHODS
Retrospective, consecutive, nonrandomized, interventional cases series.


METHODS
Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV.


METHODS
The enrolled patients were subdivided as responders or nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were genotyped by polymerase chain reaction in each patient.


METHODS
The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV leakage, greatest linear dimension, and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient's age, baseline visual acuity, and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy.


RESULTS
Responders to PDT-V were overrepresented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.8-5.4; P = 0.001) and, to a minor extent, among patients with better visual acuity at baseline (OR, 11.8; 95% CI, 1.6-88.0; P = 0.02). However, predictors of PDT-V lack of efficacy were patient's age (OR, 0.73; 95% CI, 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR, 0.19; 95% CI, 0.11-0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V.


CONCLUSIONS
These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.
Parmeggiani
Francesco
F
Department of Ophthalmology, University of Ferrara, Ferrara, Italy. francesco.parmeggiani@unife.it
Gemmati
Donato
D
Costagliola
Ciro
C
Semeraro
Francesco
F
D'Angelo
Sergio
S
Perri
Paolo
P
Sebastiani
Adolfo
A
Incorvaia
Carlo
C
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D001777:Blood Coagulation / Q000235:genetics; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D047728:Myopia, Degenerative / Q000150:complications*; D010641:Phenotype; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077362:Verteporfin; D014792:Visual Acuity
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D005176:Factor XIII; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase