The article by Frank Schaeffel and Barbara Swiatczak, published in the *Myopia Research Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Switzerland*, explores the mechanisms of emmetropization and the factors that can disrupt this process, leading to myopia. The authors review the evidence from animal models and human studies to understand how the refractive state is optimized during postnatal development through a closed-loop negative feedback system that uses retinal image defocus as an error signal. This system, called emmetropization, involves the retina and/or the retinal pigment epithelium (RPE) releasing biochemical messengers to adjust choroidal thickness and modulate scleral growth rates. Key findings include: 1. **Emmetropic Retina's Response**: The emmetropic retina can distinguish between real and simulated defocus, triggering transient axial eye shortening or elongation. However, the myopic retina has reduced ability to inhibit eye growth when positive defocus is imposed. 2. **Bi-directional Response**: The bi-directional response of the emmetropic retina is elicited with low spatial frequency information below 8 cyc/deg, suggesting that higher-order optical aberrations do not play a significant role. 3. **Retinal Mechanism for Defocus Detection**: The retinal mechanism for detecting the sign of defocus involves comparing defocus blur in the blue (S-cone) and red (L + M + cones) ends of the spectrum, but the myopic retina is not responsive in short-term experiments. The authors also discuss the limitations of deprivation myopia as a model for emmetropization, noting that it represents an open-loop condition where eye growth cannot improve retinal image quality. They highlight the importance of understanding the inhibitory pathways that control eye growth, which are distinct from the growth-stimulating pathways. The article concludes with a discussion on the role of accommodation and the potential roles of the retinal ON-OFF system in emmetropization, emphasizing the need for further research to fully understand these mechanisms.The article by Frank Schaeffel and Barbara Swiatczak, published in the *Myopia Research Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Switzerland*, explores the mechanisms of emmetropization and the factors that can disrupt this process, leading to myopia. The authors review the evidence from animal models and human studies to understand how the refractive state is optimized during postnatal development through a closed-loop negative feedback system that uses retinal image defocus as an error signal. This system, called emmetropization, involves the retina and/or the retinal pigment epithelium (RPE) releasing biochemical messengers to adjust choroidal thickness and modulate scleral growth rates. Key findings include: 1. **Emmetropic Retina's Response**: The emmetropic retina can distinguish between real and simulated defocus, triggering transient axial eye shortening or elongation. However, the myopic retina has reduced ability to inhibit eye growth when positive defocus is imposed. 2. **Bi-directional Response**: The bi-directional response of the emmetropic retina is elicited with low spatial frequency information below 8 cyc/deg, suggesting that higher-order optical aberrations do not play a significant role. 3. **Retinal Mechanism for Defocus Detection**: The retinal mechanism for detecting the sign of defocus involves comparing defocus blur in the blue (S-cone) and red (L + M + cones) ends of the spectrum, but the myopic retina is not responsive in short-term experiments. The authors also discuss the limitations of deprivation myopia as a model for emmetropization, noting that it represents an open-loop condition where eye growth cannot improve retinal image quality. They highlight the importance of understanding the inhibitory pathways that control eye growth, which are distinct from the growth-stimulating pathways. The article concludes with a discussion on the role of accommodation and the potential roles of the retinal ON-OFF system in emmetropization, emphasizing the need for further research to fully understand these mechanisms.