A study recently published in Eye assessed the relationship between axial length (AL) and the severity of myopic macular degeneration (MMD).
Give me some background.
Myopia is a growing public health issue worldwide, with 49.8% of the world’s population estimated to be myopic by 2050.
- If left untreated, it can develop into pathologic myopia (PM), which is characterized by degenerative changes in the choroid, retina, and sclera that can cause various sight-threatening complications, such as MMD and retinal detachment.
Let’s stick with MMD.
MMD is particularly concerning due to its irreversible nature and severe visual consequences—highlighting the need for early diagnosis and intervention.
And while previous studies have demonstrated that AL is a strong risk factor for MMD, the exact nature of its relationship with MMD severity remains unclear.
Talk about the study.
First: The research team conducted a comprehensive literature review to identify population- or hospital-based studies reporting AL across different grades of MMD.
They reviewed the following databases from their inception through October 1, 2023:
- PubMed
- Web of Science
- China National Knowledge Infrastructure (CNKI)
Then: They analyzed data from 395 eyes of 206 participants at the Beijing Tongren Hospital, Capital Medical University, Beijing, China, to validate the findings from the meta-analysis.
How was MMD severity measured?
Note: Only analyses that utilized the International Photographic Classification and Grading System for Myopic Maculopathy (META-PM) were included.
According to the META-PM classification system, MMD is organized into five categories:
- C0: No myopic retinal degenerative lesion
- C1: Tessellated fundus
- C2: Diffuse chorioretinal atrophy
- C3: Patchy chorioretinal atrophy
- C4: Macular atrophy
Findings?
In total: 20 studies (comprising 33,822 patients) were included—most of which were from Asia.
- The meta-analysis revealed a significant overall increase in AL as MMD progressed from category C0 to C4 (P < 0.0001).
Moreover: AL exhibited a consistent increasing trend from categories C0 to C3, however this trend seemed to level off between categories C3 and C4, with no further increase reported.
What about the results of the clinical study?
This trend was confirmed by the clinical portion of the analysis, wherein the following factors were significantly associated with a higher prevalence of MMD:
- Longer AL (per 1mm increase: odds ratio [OR] 1.90, 95% confidence interval [CI] 1.75-2.07, P < 0.001)
- Older age (per 1-year increase: OR 1.04, 95% CI 1.02-1.05, P < 0.001)
- Female sex (OR 1.89, 95% CI 1.24-2.89, P < 0.01)
Compared with C0, each 1 mm increase in AL was associated with an increasing likelihood of MMD progression with the subsequent ORs:
- C1: OR 2.8
- C2: OR 3.6
- C3: OR 5.2
- C4: OR 5.7
Tell me more.
The increase in OR was more pronounced in later stages (C2-C3 and C3-C4) than in earlier transitions (C0-C1 and C1-C2).
In addition: The ORs for age increased significantly from C3 to C4 and the ORs for female sex increased progressively from C2 to C4.
Expert opinion?
The underlying mechanism of AL and MMD severity is thought to involve axial elongation of the globe, leading to progressive stretching and subsequent thinning of the choroid.
- Meaning: This results in pathologic lesions and various complications in highly myopic individuals.
Separately: The study authors highlighted a previous study that suggested C3 and C4 be considered two different subtypes of advanced MMD, as progression from C3 to C4 is very uncommon.
Limitations?
These included:
- Potential biases, methodological issues, and different strategies to adjust for confounders in the original studies have have influenced the results of the meta-analysis
- AL measurements tend to be “noisier” (i.e., have decreased accuracy) in eyes with C4 compared to C3 due to the reduced ability to fixate centrally
- While the study included data from seven countries across three continents, a large proportion of participants were from China and Japan, potentially limiting the generalizability of the findings
- The number of participants in the clinical study was relatively small—underscoring the need for more population-based studies to further validate these results
Take home.
These findings demonstrate a clear trend of increasing AL with advancing MMD severity from C0 to C4.
- However: The relationship between AL and MMD progression from C3 to C4 warrants further investigation.
Further: Older age and female sex were identified as risk factors for MMD progression.