How does myopia progression alter inner retinal thickness and what interventions change that trajectory?
Executive summary
Progressive myopia is linked with measurable alterations of the inner retina: instead of the normal age‑related thickening seen in non‑myopic eyes, progressing myopes show reduced inner‑layer thickening and focal thinning—changes that track with axial elongation and regional stretching of the fundus [1] [2] [3]. A growing toolbox of interventions—optical strategies that impose peripheral myopic defocus, low‑dose atropine, orthokeratology, and novel adjuncts such as repeated low‑level red‑light therapy—can slow axial elongation and so indirectly alter the retinal‑thickness trajectory, although the mechanisms linking treatment to inner retinal structure remain incompletely mapped [4] [5] [6].
1. How the inner retina changes as myopia progresses: a shift from growth to attenuation
Longitudinal imaging shows that eyes undergoing myopic axial elongation diverge from the normal developmental pattern of retinal maturation: where control eyes demonstrate generalized inner retinal thickening with age, eyes subjected to myopia development frequently show attenuated thickening and in places outright thinning—particularly in inner neuroretinal layers and the ganglion cell‑inner plexiform complex—suggesting that axial stretch changes tissue architecture rather than simply altering refractive optics [1] [2].
2. Regional fingerprints: fovea versus para‑ and perifovea
Myopic retinal remodeling is not uniform: multiple studies report relatively preserved or even increased foveal inner‑layer thickness while parafoveal and perifoveal inner retinal layers become thinner with increasing myopia, consistent with globe elongation imposing asymmetric mechanical stretch that preferentially thins eccentric macular zones [3] [7]. Clinical cohorts of moderate‑to‑high myopes show the largest thinning in peritemporal and perifoveal quadrants, a pattern that aligns with the locations most at risk for later myopic maculopathy [7] [8].
3. Mechanisms on offer: stretch, choroidal change and retinal signaling
The dominant explanatory thread links axial elongation to mechanical stretching of retinal tissue and choroidal thinning; choroidal attenuation accompanies rapid myopia progression and likely changes metabolic support and biomechanics of the inner retina, although causal pathways from optical signals to specific inner‑layer thinning are still hypothesized rather than proven [2] [9]. Animal and human imaging evidence implicates altered retinal growth signals driven by peripheral image quality and altered contrast, which may influence retinal‑to‑scleral signaling and hence structural remodeling [4] [9].
4. Animal models corroborate inner‑layer vulnerability
Non‑human primate experiments that induce myopia reproduce the human signal: marmosets with lens‑induced myopia show significantly less age‑related inner retinal thickening, with pronounced effects in the ganglion cell‑inner plexiform region over months of myopia induction—evidence that refractive growth can directly modify inner retinal architecture independent of human behavioral confounders [1].
5. Interventions that change the trajectory: what they alter and what is known
Interventions that slow axial elongation—optical strategies creating peripheral myopic defocus (multifocal spectacles, specialized contact lenses, orthokeratology), pharmacologic atropine, and emerging modalities such as repeated low‑level red‑light (RLRL) therapy—have demonstrated consistent effects on reducing axial growth in trials and thus are expected to blunt the downstream retinal thinning associated with progression; orthokeratology and peripheral‑defocus lenses are designed specifically to change retinal image profiles thought to drive axis growth, and atropine likely acts on retinal growth pathways though its exact target remains uncertain [4] [5] [10]. Recent randomized trials of RLRL show axial shortening effects in high myopia cohorts and include OCT analyses of retinal and choroidal alterations, but long‑term structural retinal endpoints and safety signals remain a focus of active study [6] [11].
6. Limits, alternative views and clinical implications
While the association between axial elongation and inner retinal attenuation is robust across animal models and human cohorts, direct causal links from specific treatments to preservation or reversal of inner retinal thickness are less well established: most trials report axial length as the primary outcome and infer downstream retinal benefit, and mechanisms (contrast modulation, defocus, biochemical pathways) remain debated among researchers and vendors with commercial interests in optical devices [4] [5]. Clinically, the implication is clear—slowing axial growth is the most evidence‑backed route to reduce structural retinal risk—but clinicians and families should be told that retinal anatomy outcomes need longer follow‑up and standardized OCT‑based endpoints to demonstrate sustained protection [5] [10].