What is the retinal 'sweet spot' for myopia treatments?

Paper title: Retinal "sweet spot" for myopia treatment

Authors: Swiatczak, Barbara (1); Scholl, Hendrik PN (2,3); Schaeffel, Frank (4,5,6)

1. Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland. 

2. University of Basel, Basel, Switzerland.
3. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
4. Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
5. Section of Neurobiology of the Eye, Ophthalmic Research Institute, University of Tuebingen, Tuebingen, Germany.
6. Zeiss Vision Lab, Institute of Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.

Date: Nov 2024 

References: Swiatczak B, Scholl HPN, Schaeffel F. Retinal "sweet spot" for myopia treatment. Sci Rep. 2024 Nov 5;14(1):26773

[Link to open access paper]

The response of the peripheral retina to imposed optical defocus has been examined in several studies and has advised the development of several myopia control therapies currently available.¹

Animal studies presenting optical defocus presented to the nasal visual field of rhesus monkeys and chickens saw altered axial length and refractive error in the temporal retinas, leading to the suggestion that eye growth is controlled locally. Another study found a region 20° from the fovea may play a role in emmetropisation.^2-4

A study investigating emmetropisation in humans found retinal responses were dependent on the degree and location of induced blur, with electroretinogram readings showing more response in areas of 6-12° of eccentricity. Other animal and human studies have observed choroidal thickness increases after exposure to optical defocus, inhibiting the the eye’s overall push for growth.^2-10

This study aimed to explore areas of the retina which may generate eye growth signals in response to imposed defocus.

Twenty adults (average age 28yrs) were recruited to the study. They were near-emmetropes with healthy eyes and astigmatism no higher than 1D. Non-cycloplegic refraction and axial length measurement were performed at baseline.

A custom-built infra-red (IR) binocular eye tracker was used to confirm the participants had normal binocular function and continuous fusion while watching a screen.¹¹ 

Across 4 subsequent visits (performed at the same time of day for each participant to avoid diurnal differences), the participants watched a movie on a screen at 2m away while resting their head on a chin-rest to avoid head movement. A +3.50D lens placed infront of the right eye to induce +3D defocus at 2m distance. The uncovered left eye allowed the screen to be seen clearly and also acted as a control.

The IR eye tracker camera was placed at 50cm and used the pupil of the left eye and the 1^st Purkinje image to track eye fixation as participants watched the screen. This information was shared with software which generated real-time grey pixellated patches on to the movie frames and covered respective areas around the fixation points.

The patches generated were:

1. A central patch to cover 0-3-degree eccentricity of the central foveal area
2. An annular patch which kept the central fovea clear but covered the 3-9-degree eccentricity near-peripheral retina
3. A combined patch consisting of a central 0-3-degree patch, a surrounding clear annulus for the 3-6-degree near-peripheral retina and a further patch covering the 6-9-degree peripheral retina
4. A large full-field patch with only the 6-10-degree near peripheral area uncovered

Axial length data was recorded at each appointment for both eyes after 20 and 40mins of watching the movie on the screen.

The eye tracker recorded no differences in eye fixation positions with any of the field of view patches.

The effect of imposing defocus on the retina with varying areas of the retina occluded were compared to the control left eyes and to the effect of the full field defocus.

Reduced axial length was seen with patch A covering the central fovea (-9 ± 14μm at 20mins and -14 ± 17μm at 40mins) and the full-field defocus patch D with only the peripheral area uncovered (-10 ± 14μm at 20mins and -11 ± 12μm at 40mins), but not with either the 3-9-degree near-peripheral patch (patch B) or the combined central 3-degree and 6-9-degree peripheral patches (patch C) where the defocus effect was suppressed and axial lengths were no different to the control eyes receiving no defocus.

No significant changes were seen for axial length in the control eyes at 20 or 40mins under any patching scenario.

After systematically identifying areas of the retina most responsive to defocus, this study found the 6-10-degree eccentricity near periphery plays a role in detecting positive defocus.

These results confirm previous studies which identified the fovea as having only a minor role in emmetropisation and little influence on axial length shortening and that retinal areas between 6-12-degree eccentricity were more sensitive to blur.

If eye growth is regulated in this area then this has important implications for learning more about long-term refractive change and emmetropisation. Myopia control could be considered early and targeted more effectively if product designs were able to enhance the myopia control effects where the retina is more receptive to defocus. If this area differs slightly between individuals, this may extend to personalising treatments based on patient-specific responses, which could improve outcomes generally.

This study showed that imposing defocus on the fovea and certain paracentral areas is ineffective in influencing axial length.

• More understanding is needed on how these areas differ in terms of photo-receptor distribution and density and of how growth signals are transmitted from the retinal periphery to the centre or from the retina to the choroid.

Limitations to this study include considering only annular patches around the fovea, where some studies have suggested the superior retina may also be receptive to defocus blur, and measuring axial length in the fovea when the blur signals were detected more peripherally.¹²

Title: Retinal "sweet spot" for myopia treatment

Authors: Barbara Swiatczak, Hendrik P N Scholl, Frank Schaeffel

Purpose: We studied which retinal area controls short-term axial eye shortening when human subjects were exposed to + 3.0D monocular defocus. 

Methods: A custom-built infrared eye tracker recorded the point of fixation while subjects watched a movie at a 2 m distance. The eye tracker software accessed each individual movie frame in real-time and covered the points of fixation in the movie with a uniform grey patch. Four patches were programmed: (1) foveal patch (0-3 degrees), (2) annular patch (3-9 deg), (3) foveal patch (0-3 deg) combined with an annular patch (6-9 deg), and (4) full-field patch where only 6-10 deg were exposed to the defocus. 

Results: Axial eye shortening was elicited similarly with full-field positive defocus and with the foveal patch, indicating that the fovea made only a minor contribution (-11 ± 12 μm vs. -14 ± 17 μm, respectively, n.s.). In contrast, patching a 3-9 degrees annular area or fovea together with an annular area of 6-9 degrees, completely suppressed the effect when compared with full-field defocus (+ 3 ± 1 μm or -2 ± 13 μm vs. -11 ± 12 μm, respectively, p < 0.001). 

Conclusions: Finally, we found that the near-peripheral retina (6-10 degrees) is a "sweet spot" for positive defocus detection and alone can regulate eye growth control mechanism, and perhaps long-term refractive development (-9 ± 8 μm vs. full-field: -11 ± 12 μm, n.s.).

[Link to open access paper]