Coagulation gene predictors of photodynamic therapy for occult choroidal neovascularization in age-related macular degeneration.
OBJECTIVE
To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).


METHODS
The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidence of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided into responders and nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms (i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G) were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness.


RESULTS
Regression models documented that PDT-V nonresponders were more frequently patients with the hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative of an overrepresentation of PDT-V responders among the combined carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not significantly influence the short-term CNV responsiveness to PDT-V.


CONCLUSIONS
These data provide evidence of the presence of a pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in patients with AMD with occult CNV.
Parmeggiani
Francesco
F
Department of Ophthalmology, University of Ferrara, Ferrara, Italy. francesco.parmeggiani@unife.it
Costagliola
Ciro
C
Gemmati
Donato
D
D'Angelo
Sergio
S
Perri
Paolo
P
Campa
Claudio
C
Catozzi
Linda
L
Federici
Federica
F
Sebastiani
Adolfo
A
Incorvaia
Carlo
C
D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D005165:Factor V / Q000235:genetics; D026122:Factor XIIIa / Q000235:genetics; D005260:Female; D006147:Guanine; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000150:complications*; D008297:Male; D009154:Mutation; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011166:Porphyrins / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011516:Prothrombin / Q000235:genetics; D012189:Retrospective Studies; D013941:Thymine; D016896:Treatment Outcome; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D006147:Guanine; D005165:Factor V; D011516:Prothrombin; D026122:Factor XIIIa; D013941:Thymine