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Axial elongation in high myopia

No clear molecular factors involved in myopic macular degeneration

Dermot McGrath

Posted: Wednesday, July 29, 2020


Gemmy Cheung FRCOphth

Axial elongation is the most important mechanism contributing to the development of myopic macular degeneration (MMD), with no clear evidence of molecular factors specifically associated with development of the condition, according to Gemmy Cheung FRCOphth.

“This was a small pilot study and while we clearly identified certain molecular factors associated with axial elongation, we did not identify any specific to the development of MMD,” she told delegates attending a symposium on myopia at the 19th EURETINA Congress in Paris.

Explaining the rationale behind the study, Prof Cheung, Head and Senior Consultant, Medical Retina Department, Singapore National Eye Centre, Singapore, said that it is important to differentiate pathologic myopia from high myopia.

“We know with high myopia there is axial elongation, whereas with pathologic myopia there are characteristic changes in the sclera, choroid, and retinal pigment epithelium (RPE) with compromised visual function. Previously described risk factors for MMD include severity of myopia, and other factors such as age or gender, but the question we wanted to answer is why don’t all myopic eyes with elongated axial lengths develop MMD? With that in mind, we carried out this pilot study to determine if there are molecular processes specifically associated with the development of MMD in eyes that are already axially elongated,” she said.

The study team obtained aqueous humour during routine cataract surgery of 14 emmetropic control eyes, 12 eyes with high myopia without macular changes and 12 eyes with MMD. High myopia was defined as axial length greater than 26.5mm. Eyes with myopic choroidal neovascularisation at any stage were excluded. Axial length and subfoveal choroidal thickness were recorded for all eyes.

The study focused on four key molecular factors of interest, said Prof Cheung: extracellular matrix remodelling – matrix metalloproteinase 2 (MMP), tissue inhibitor of metalloproteinase (TIMP); vascularity – vascular endothelial growth factor isoform A (VEGF-A), pigment epithelium-derived factor (PEDF), and angiopoietin (Ang-2); Bruch’s membrane elongation – amphiregulin ; and inflammation – interleukin (IL-6, IL-8, and C-reactive protein (CRP)).

The results showed that VEGF-A concentration in aqueous humour linearly decreased and the MMP-2 concentration linearly increased with longer axial length. However, after adjusting for axial length, none of the molecular factors were associated with MMD, said Prof Cheung. For choroidal thickness the researchers found a correlation with MMP-2 but surprisingly no association with VEGF-A.

“The correlation between choroidal thickness and MMP-2 but not VEGF-A suggests that axial elongation rather than ischemia may be the predominant underlying mechanism leading to choroidal thinning. So this pilot study suggests that it may be more mechanical stretching rather than primarily ischemic phenomena at work here,” she concluded.

Gemmy Cheung: gemmy.cheung.c.m@singhealth.com.sg