Elsevier

Ophthalmology

Volume 121, Issue 1, January 2014, Pages 225-233
Ophthalmology

Original article
Vascular Endothelial Growth Factor Gene and the Response to Anti-Vascular Endothelial Growth Factor Treatment for Choroidal Neovascularization in High Myopia

Presented at: The American Academy of Ophthalmology Annual Meeting, November 10–13, 2012, Chicago, Illinois.
https://doi.org/10.1016/j.ophtha.2013.06.043Get rights and content

Purpose

To investigate the association between the vascular endothelial growth factor (VEGF) gene polymorphism and the response to anti-VEGF treatment for choroidal neovascularization (CNV) in highly myopic eyes.

Participants

A total of 357 unrelated highly myopic Japanese patients with axial lengths ≥26.0 mm in both eyes were eligible, and 83 patients who received anti-VEGF therapy for CNV and could be followed for more than 1 year were included.

Methods

We genotyped a functional single nucleotide polymorphism in the VEGF gene, rs2010963. The associations between the distribution of the rs2010963 genotype and the number of eyes with maintained or improved visual acuity (VA) were analyzed. Furthermore, multivariable logistic regression analysis was performed to adjust for 7 possible prognostic factors, including age, sex, CNV size, CNV location, administration of loading dose, pretreatment VA, and number of additional treatments.

Main Outcome Measures

The primary end point was maintenance of VA, and secondary end points were progression of chorioretinal atrophy (CRA) and recurrence of CNV.

Results

Mean age and mean axial length were not significantly different among 3 genotypes of rs2010963. The percentage of eyes with maintained or improved VA was significantly higher with the G allele of rs2010963 (P =0.016), and stepwise analysis revealed that both rs2010963 and CNV size were associated with VA maintenance (P =0.040 and 0.033, respectively). The secondary analysis revealed that administration of a loading dose was significantly associated with both CRA progression (P =0.031) and recurrence of CNV (P =0.020), whereas rs2010963 was not.

Conclusions

These results suggest that the VEGF polymorphism influences the VA prognosis in highly myopic eyes with CNV within 1 year after anti-VEGF treatment. This association was still observed after removing its confounding effect through CNV size. The rs2010963 polymorphism was not associated with CNV recurrence or CRA progression, which indicates that these changes are not tied to intrinsic factors and may be controllable by improving treatment methods.

Section snippets

Methods

All procedures in this study adhered to the tenets of the Declaration of Helsinki. The institutional review board and ethics committee of each institute involved approved the protocols of this study. All patients were fully informed of the purpose and procedures of this study, and written consent was obtained from each patient.

Results

There were 83 patients with CNV in highly myopic eyes who underwent treatment with bevacizumab (62 eyes), pegaptanib (3 eyes), or ranibizumab (18 eyes). All patients were followed for at least 12 months. Anti-VEGF therapy was initiated by a single injection in 65 eyes (initial loading dose [−] group) and by 3 monthly injections in the other 18 eyes (initial loading dose [+] group). Demographic information and characterization of the patients are shown in Table 1. The CNV was subfoveal in 73.5%

Discussion

In the present study, we demonstrated a significant association between the VEGF rs2010963 genotype and the maintenance of vision after treatment for CNV with anti-VEGF therapy in highly myopic eyes. Parmeggiani et al19 also evaluated the genetic association for response to myopic CNV treatment. They showed a significant association between 2 genes and CNV responsiveness to PDT. Although the results gave us clinically important information, anti-VEGF therapy is now becoming the first choice for

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    Financial Disclosure(s): Supported in part by grants-in-aid for scientific research (Nos. 21249084 and 200791294) from the Japan Society for the Promotion of Science, Tokyo, Japan, and the Japan National Society for the Prevention of Blindness, Tokyo, Japan. The funding organizations had no role in the design or conduct of this research.

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