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Finding Better Ways to Image the Retina

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Two light microscopy fields of the retina showing small blue dots (rods) surrounding larger yellow dots (cones)
Credit: Johnny Tam, National Eye Institute, NIH

Every day, all around the world, eye care professionals are busy performing dilated eye exams. By looking through a patient’s widened pupil, they can view the retina—the postage stamp-sized tissue lining the back of the inner eye—and look for irregularities that may signal the development of vision loss.

The great news is that, thanks to research, retinal imaging just keeps getting better and better. The images above, which show the same cells viewed with two different microscopic techniques, provide good examples of how tweaking existing approaches can significantly improve our ability to visualize the retina’s two types of light-sensitive neurons: rod and cone cells.

Specifically, these images show an area of the outer retina, which is the part of the tissue that’s observed during a dilated eye exam. Thanks to colorization and other techniques, a viewer can readily distinguish between the light-sensing, color-detecting cone cells (orange) and the much smaller, lowlight-sensing rod cells (blue).

These high-res images come from Johnny Tam, a researcher with NIH’s National Eye Institute. Working with Alfredo Dubra, Stanford University, Palo Alto, CA, Tam and his team figured out how to limit light distortion of the rod cells. The key was illuminating the eye using less light, provided as a halo instead of the usual solid, circular beam.

But the researchers’ solution hit a temporary snag when the halo reflected from the rods and cones created another undesirable ring of light. To block it out, Tam’s team introduced a tiny pinhole, called a sub-Airy disk. Along with use of adaptive optics technology [1] to correct for other distortions of light, the scientists were excited to see such a clear view of individual rods and cones. They published their findings recently in the journal Optica [2]

The resolution produced using these techniques is so much improved (33 percent better than with current methods) that it’s even possible to visualize the tiny inner segments of both rods and cones. In the cones, for example, these inner segments help direct light coming into the eye to other, photosensitive parts that absorb single photons of light. The light is then converted into electrical signals that stream to the brain’s visual centers in the occipital cortex, which makes it possible for us to experience vision.

Tam and team are currently working with physician-scientists in the NIH Clinical Center to image the retinas of people with a variety of retinal diseases, including age-related macular degeneration (AMD), a leading cause of vision loss in older adults. These research studies are ongoing, but offer hopeful possibilities for safe and non-intrusive monitoring of individual rods and cones over time, as well as across disease types. That’s obviously good news for patients. Plus it will help scientists understand how a rod or cone cell stops working, as well as more precisely test the effects of gene therapy and other experimental treatments aimed at restoring vision.


[1] Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope. Dubra A, Sulai Y, Norris JL, Cooper RF, Dubis AM, Williams DR, Carroll J. Biomed Opt Express. 2011 Jul 1;2(7):1864-76.

[1] In-vivo sub-diffraction adaptive optics imaging of photoreceptors in the human eye with annular pupil illumination and sub-Airy detection. Rongwen L, Aguilera N, Liu T, Liu J, Giannini JP, Li J, Bower AJ, Dubra A, Tam J. Optica 2021 8, 333-343.


Get a Dilated Eye Exam (National Eye Institute/NIH)

How the Eyes Work (NEI)

Eye Health Data and Statistics (NEI)

Tam Lab (NEI)

Dubra Lab (Stanford University, Palo Alto, CA)

NIH Support: National Eye Institute

New Director for NEI

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Michael Chiang Swearing In
At a virtual ceremony on Nov. 16, 2020, Michael F. Chiang was sworn in as the new director of the National Eye Institute (NEI). We are excited to welcome Michael to our NIH leadership.

Singing A Fun Farewell Song

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Earlier in the month, I posted a photo taken during the retirement ceremony of Paul Sieving, director of the NIH’s National Eye Institute. I’ve since discovered this video recording of the song that I played for Paul during the ceremony. It’s the popular 1970s song, “I Can See Clearly Now” with special lyrics to mark the occasion. Credit: National Eye Institute

Best Wishes to Paul Sieving

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Sieving Farewell Ceremony
Best wishes to my friend Paul Sieving (left) upon his retirement as director of NIH’s National Eye Institute (NEI), On September 5, 2019, I joined the NIH family at a special ceremony to thank Paul for his nearly 20 years of leadership and scientific achievement at NEI. Afterwards, we posed for this photograph and to talk about old times. Paul and I were colleagues at the University of Michigan 30 years ago. In the next chapter of his research career, Paul will join the faculty at the University of California, Davis, where he will establish its Center for Ocular Regenerative Therapy. All the very best, Paul! Credit: NIH

Studying Color Vision in a Dish

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Credit: Eldred et al., Science

Researchers can now grow miniature versions of the human retina—the light-sensitive tissue at the back of the eye—right in a lab dish. While most “retina-in-a-dish” research is focused on finding cures for potentially blinding diseases, these organoids are also providing new insights into color vision.

Our ability to view the world in all of its rich and varied colors starts with the retina’s light-absorbing cone cells. In this image of a retinal organoid, you see cone cells (blue and green). Those labelled with blue produce a visual pigment that allows us to see the color blue, while those labelled green make visual pigments that let us see green or red. The cells that are labeled with red show the highly sensitive rod cells, which aren’t involved in color vision, but are very important for detecting motion and seeing at night.

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