Older Age, Female Sex Shown to Be Risk Factors for MMD Progression, Study Shows

Measuring the axial length of high myopes is one way of tracking their potential to progress to worse stages of myopia macular degeneration. Graph modified from Mu T, et al. Eye. April 25, 2025. Photo by Kengo Hayashi, MD. Click image to enlarge. Axial length (AL) is a critical parameter in the assessment of both myopia and high myopia, making it an ideal metric for monitoring the development and progression of myopic macular degeneration (MMD). Since high myopia has become a significant public health issue, especially in East Asian countries where it’s highly prevalent, researchers sought to further investigate the relationship between AL and the severity of MMD. In a recent meta-analysis, they found a consistent trend of increasing axial length with advanced MMD progression in all but the most severe cases, after which AL becomes less sensitive to further changes. The findings were reported in the journal Eye.A total of 20 high-quality studies from seven countries (mostly in Asia) were included, comprising 33,822 patients studied. To further validate the findings, researchers analyzed data from 395 eyes of 206 participants at Beijing Tongren Hospital in  China.The meta-analysis revealed that an increase in axial length tracks with MMD progression as a patient progresses through the first four stages of a five-level categorization system for the condition. This correspondence was confirmed in the researchers’ new dataset, where they noted that each 1mm increase in axial length was associated with a 1.9-times higher likelihood of progressing to a more severe grade of MMD. Older age (per one-year increase) and female sex were also correlated with progression.   In the two most advanced stages, termed “C3” (patchy chorioretinal atrophy) and “C4” (macular atrophy) in the classification system, the association between axial length and clinical status weakens, possibly because they could be considered as two different subtypes of advanced MMD, the researchers suggested in their paper. One possible explanation is the inherent “noise” in axial length measurement for eyes with macular atrophy (C4), which was not mentioned in previous studies, the authors explained. “Unlike eyes with patchy atrophy (C3), those with macular atrophy often exhibit reduced central fixation ability, which could increase variability in AL measurements,” rendering the metric less reliable in these categories, the authors wrote in their paper on the work.The odds ratios for progression increased MMD significantly from C3 to C4 in line with advancing age in their research. Previous studies have reported that older age is independently associated with MMD, while others have shown that this is associated with age-related degenerative changes in the eyes, including decreased density of photoreceptor cells, ganglion cells, retinal pigment epithelium and optic nerve fibers.The sex of the patient may also correlate with disease course. “Some studies on myopia suggested that women are at higher risk for myopia development, which may in turn lead to an increased risk of MMD,” the authors explained in their article. “Also, changes in the balance of sex hormones in the body may affect the physiology of the eye by sex steroid hormones receptors in eyes, leading to an increased risk of MMD in women.”The authors suggest that future research should focus on the relationship between hormonal factors and MMD in women, as well as determining whether C4 represents a distinct pathological change rather than a continuation of C3. “Advanced imaging techniques, such as optical coherence tomography angiography, alongside longitudinal studies, may be essential in uncovering the specific characteristics and progression patterns of C4,” the authors concluded. Click here for the journal source.  Mu T, He H-L, Chen X-Y, et al. Axial length as a predictor of myopic macular degeneration: a meta-analysis and clinical study. Eye. April 25, 2025. [Epub ahead of print.]