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US surgeons perform first whole eye transplant (medicalxpress.com)
229 points by PaulHoule on Nov 15, 2023 | hide | past | favorite | 83 comments



I spoke to Sunwoo Kwon about human optics. https://scholar.google.com/citations?user=3Lrjfs4AAAAJ&hl=en

He deals with restoring partial sight when normal methods fail, and talks about primative eye tracking like the ability to sense direction can still be signaled even if there is no "sight". Blind cave fish for example still use their eyes to track even with no vision. It is possible the eye can not "see" but still signal.


I think this is the relevant paper [1]. It appears to be about the inverse problem, though. The guy in the article has a healthy brain but damaged eyes, so his brain isn't getting any visual signals to interpret. The patients in the paper have healthy eyes but damaged brains, so their brain is getting visual signals but it can't interpret them.

That is interesting regardless. It's like the brain lost the ability to process visual data into images, but is still able to derive some information from it. Makes me wonder how many variations of sight there are. Is it possible to detect motion without sight? Or to have depth perception without sight? I guess depth perception without sight would be like complete colorblindness, almost like lidar.

1: https://elifesciences.org/articles/67573


Yes. A brain damaged blind man walked past obstacles without seeing what to avoid.

https://www.newscientist.com/article/dn16324-blind-man-sees-...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747232/

Since the eye is signaling and he his brain is also healthy, he may have more cues that are not visual. Object avoidance and facial recognition might not be visual according to n=1. Kwon and related researchers have confirmed that the brain can rewire to brain to use more primative means of visualizing, so her saying never say never may be to temper expectations to the layman. I'd be very surprised if she didn't know of this research.


The brain is actually receiving signals from the eye, as far as they can tell, but he cannot see [1].

[1] https://youtube.com/watch?v=I7aprt7l42s&t=213


Also see previous discussion:

https://news.ycombinator.com/item?id=38209680

Doctors complete first successful face and whole-eye transplant (scientificamerican.com) 5 days ago | 70 comments


As qup says, >>Maybe re-introduce some neuroplasticity... Would the Yamanaka factors and brain-nerve remapping(that it might invoke) be a path?


The retina technically is part of the brain. It does all sorts of signal compression and visual pre-processing before sending the signal (not pixels) to the visual cortex via the optical nerve.

Somebody made some calculations on Quora - it is a factor of 6600 to 1 compression ratio or 40 exabytes from the rod/cone cells down to 6 petabytes along the optic nerve.


Interesting stats. Could you elaborate on the data you mentioned please? What does the 40 exabytes represent? Is that a single “frame” of an image captured by the eye? Or perhaps its data per second?


We know from studying lower life forms that they absolutely do not send some pixel accurate representation of an image(barring some incredible compression/encoding) From the seminal paper What the Frogs Eye Tells the Frogs Brain https://web.archive.org/web/20110928024235/http://jerome.let... to Guinea pig eyes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564115


From Quora

"Each eye has 137 million rods and cones. If we assume 8 bits per pixel and 60 frames per second for 2.5 billion seconds, then the total information from both eyes is 3.3 x 10^20 bits, or about 40 exabytes (40 million terabytes).

More realistically, the retina does not transmit pixels directly to the brain. Instead, it detects low level features such as center-surround contrast and movement. Each optic nerve contains about 1 million fibers. We can't see events lasting less than about 0.1 seconds, so let us assume an information rate of 10 bits per second per nerve fiber. This is a total of 10^6 fibers x 2 optic nerves x 10 bits per second x 2.5 x 10^9 seconds = 5 x 10^16 bits, or 6 petabytes. This represents a lossy compression ratio of 6600 to 1.

The brain's visual cortex compresses this data further by detecting a hierarchy of increasingly complex shapes such as edges, lines, angles, characters, shapes, and objects such as faces. In a 1986 study in which people were asked to learn and recall thousands of pictures, Tom Landauer estimated that human long term memory is on the order of 10^9 bits, or 1 bit per second. If we assume that 40% of our long term memory is visual (in proportion to the size of the visual cortex), then it suggests that the retina and brain compress visual data at a rate of (3.3 x 10^20 / 4 x 10^8) = 825 billion to 1."

https://qr.ae/pKofqQ


Ah so it's the input data over the course of a human lifetime. Thanks!


It's true that the retina and optic nerve do a lot of processing, but that doesn't make them part of the brain. The spinal cord does its own processing too (including reflexes), but it's not part of the brain either.

According to your logic, my USB-connected webcam is part of my computer's CPU (or at least motherboard). It isn't, even though it does a lot of processing on its own and probably has a CPU of its own inside.


Reflexes are simply a hardwired circuits because waiting for high order thought processing up to the brain in response to certain stimuli (pain) will end up you being rather dead or badly injured.

The retina has the same layered architecture of a scaffold of neurons and support cells as your cerebral cortex.


Also amazing to read in the article that this was done as part of a face transplant which is now considered standard care for severe disfigurement instead of experimental! It doesn't feel like all that long ago we were reading about the first successful face transplant ever performed.

Love the patient's attitude about already getting a new face, so why not try the eye too and see how well it works since he'd be doing transplant care regardless. Seems like he completely understands it might not work fully or at all, but that there was stuff to be learned regardless.


It's not the standard of care, a doctor said it SHOULD be standard of care. Transplants for nonvital organs are very rare. It has been possible to transplant things like arms and legs for a long time- see Guðmundur Felix Grétarsson, who is able to feel things in his arms now and use them for light tasks.

https://en.wikipedia.org/wiki/Gu%C3%B0mundur_Felix_Gr%C3%A9t...

But maybe 100 people total have transplanted arms. They are rare because insurance doesn't cover them; medically they're considered investigational. Growing nerves back is still a complete crapshoot, and you'll certainly never get back normal function.

That's a pretty significant issue, because even arm transplants compromise your life in new and terrible ways. You're required to take prednisone, ciclosporin etc for the rest of your life. You trade off one crippling disability for another- a massively compromised immune system. Potentially that can kill you, if you get sick and are unlucky.

You can open a door and use a broom with a hook. You get very little quality of life from feeling tingles in your elbow. Is that worth risking your life and taking expensive steroids every day which can drastically change the way you think and feel? Probably not.

Is it worth it to be able to hold hands with your wife? To be able to feel the heat of a coffee mug? To not need help putting your arms on? Medical literature does not typically value those things. Objectively they're small, momentary inconveniences. Many, many people are happy without them. They might mean the world to others.

In cases like the OP it's cut and dry, IMO. Look at him (image fairly disturbing): https://static.scientificamerican.com/sciam/assets/Image/202...

That tissue on his face, even after 50+ surgeries, is agonizing. There just isn't enough skin and what's left is fragile. Cuts and blisters get pulled open and don't want to heal. Every movement sucks. That person would not mind wearing someone elses face; they aren't wearing their own face any more. It's completely unsurprising that their quality of life is improved, even with all the immunosupressants.


Just commenting to thank you for the before/after picture and to say wow to the incredible work of giving this man literally a new face. Even if the eye doesn't ever see, it's still a beautiful thing that he can have normal facial features again instead of a painful reminder of his injury.


Wow that image looks completely primitive, like something out of Bioshock. I’m actually surprised our medical system is not able to do something better than that.


By all means, apply to medical school, complete all the training, and try for yourself. Or continue to shit remotely from a distance on other people’s work you can’t possibly comprehend.


It's a face transplant, not surgery to make someone else's face look like his. Of course it doesn't look natural.

Natural isn't good. Rotationplasty is way, way better than any of the alternatives (amputation, transderal prosthesis etc). It involves reattaching the foot to the knee backwards so that the ankle acts like a new knee.

https://walkwithoutpain.com.au/wp-content/uploads/2016/05/ba...

You walk almost naturally and keep more strength than any electronic prosthesis. It's has less pain than an amputation and no phantom limb sensation. It may look primitive, but it's far and away superior to anything else right now.


They absolutely can do a much better job, but the patient has to have enough material remaining for them to work with.

This man took 7200 volts directly to the face.


I hope face transplants become a routine procedures. We need an equivalent to password resets for biometric authentication.


The amount of elective cosmetic surgery to the body and face this last decade and the normalization of it has made that statement sounds too obvious to me.


"Transplant" is the critical factor here. Introducing foreign tissue is significantly more complicated than shuffling around native tissue.


You're right I confused it with grafting. I thought that facial transplants meant grafting 'extra' skin onto the face. Still think there's carryover from other fields like plastic surgery and probably cancer treatments to make this easier.


Plastic surgery isn't inherently cosmetic; plastic surgery training includes things like facial reconstruction/burn grafts, plus some minor training in related cosmetic procedures. Cosmetic surgery training OTOH focuses strictly on cosmetic procedures.

It's not uncommon for a single doctor to be both a licensed plastic surgeon and a licensed cosmetic surgeon, but they are distinct licenses.


If you're speaking about the US, you are incorrect on the legality.

A license is issued by a state to a physician, and carries no qualification of specialty. A licensed physician can do anything for which they have informed consent.

A board certification is a piece of paper put out by an Academy or Society or College that says a physician has been trained in a particular specialty and passed their post-training exams.

I am a board certified anesthesiologist. I also hold a license to practice medicine in the state where I live. I can do neurosurgery, if I can find a facility and a patient willing to let me (and although that sounds like a joke, how else would you describe placing an epidural for labor during childbirth but "minor neurosurgery"? Which is why a license to practice medicine is necessarily broad.). That doesn't mean anyone would insure me, or that any sane hospital would let me, but it would be legal.


Ah, good terminology catch there—I did indeed mean "board certified" :)

And re. epidurals, "minor neurosurgery" honestly sounds about right! Doesn't that thing literally go in your spinal cord? You can't mess around there unless you know what you're doing...


Inside the spinal column (the bones), not into the cord itself but just outside a thin layer (the dura mater - Latin for "tough mother") around it (thus "epidural" - "outside the dura"). Labor epidurals (which are most epidurals) are placed in the lower lumbar region. The five lumbar vertebrae are creatively named L1 through L5; the spinal cord itself ends around L2, and below that level the spinal column just provides a space for the nerve roots to be protected. Whatever; the local anesthetic diffuses across it just fine.

But yes, you do have to keep in mind things like timing of anticoagulant usage (it's bad if you have a bleeding spot that doesn't want to stop, but it's catastrophic if you have a bleeding spot inside a bony cavity that can't expand - you can easily have a big bleed whose pressure compresses and damages the spinal cord higher up).


I believe that historically the direction is the other way around - that elective cosmetic facial surgery was enabled by the experience of the many surgeons performing the many reconstructive surgeries for facial injuries which were needed on a mass scale in the years during and after the world wars.


Unmentioned is whether the optic muscles were connected and/or usable: iris, cilia, 6 motor muscles/nerves to move the eyeball. The cosmetic benefit over a glass eye depends entirely on whether the eyeball moves somewhat normally, if not the iris responding normally.

Beyond that I'd offer zero hope of restoring any kind of visual acuity.

The term "Nerve" is used both for the bundle of neurons and for each neuron. Virtually all neurons, but particularly those in the eye, have a body-mapping to a corresponding area in the brain (and in the case of vision, across 2 sets of neurons). For vision, these nerves end in a columnar organization such that secondary neurons essentially observe these primary ones to detect e.g., motion across an axis at that point.

Even if you just clipped one optic nerve bundle and then tried to have it grow back together, there's no way you'd get even most of the connections right for the million+ neurons. So I see no hope for doing that with someone else's eye. So there's no real visual-function reason to try the eye transplant.

Worse, transplant drugs generally suppress the body's immunological response, in the normal compartments (blood and lymph). I'm not sure anyone's really tested transplantation in the brain compartment. I suppose an option for rejection is to remove the eye, but how much of the nerve would have to be removed? How much brain surgery would be require for that?

Or perhaps worse, imagine signals do get through but hugely messy. If/since flashing lights and swerving horizons can produce headache and nausea, I can't imagine what this visual garbage would do.

In this case, I'd be concerned this electrical lineman was caught up in the surgeon's desire to make a name for himself.


> caught up in the surgeon's desire to make a name for himself.

Clinical trials often give people a ray of hope and I would imagine this trial was done without coercion. Remember that insulin, coronary bypass surgery and literally every medical treatment today was once experimental.


The first heart transplant (1967, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062759/ ) made newspaper front page headlines and was not smooth sailing: "Although the patient, Mr. Louis Washansky, died after only 18 days, Barnard soon carried out a second transplant, and this patient led an active life for almost 19 months. Remarkably, Barnard’s fifth and sixth patients lived for almost 13 and 24 years, respectively."


Usually, candidates considered for heart transplants don't have a great alternative - i.e. healthy enough to survive the surgery but without the surgery these candidates would have deteriorated regardless


That is very interesting..


Exactly. If there is something new to learn and both sides are somehow beneficial there is no problem.


The brain is not a permanently shaped integrated circuit. Neuroplasticity could potentially accommodate the difference in nerve mapping.

We shouldn't be so bold as to rule out the possibility.


He got the experimental eye transplant because he was already going to get a face transplant. Even if the eye doesn't work, it offers some cosmetic value but, more importantly, it helps advance a field of medicine that he no doubt feels passionate about.

He stated in an interview that he was amply warned about potential risks and complications, he knew that it was highly experimental, and he knew that it's unlikely that he will ever develop vision or voluntary control of the eye -- but he wanted to go ahead anyway.

They only offered him the option because he is already going to be on transplant drugs and will require ongoing medical care for the rest of his life.


The eye doesn't have to fully work to be useful. Even being able to differentiate light / dark would likely be useful.


I’m sure you know more than the ophthalmologist and the rest of the surgical team. What are your credentials to opine so confidently on this topic?


It seems like every thread has a few “well actually” top-level comments. It’d be interesting to do some sentiment analysis to see the numbers.


This is incredible, but I can't help but wonder where they got the new part of the face and the eye?

A donor can't just donate that like they can with blood or a kidney. Is it only done with donations after death?


> “The donor hero was a young man in his 30s who came from a family that strongly supports organ donation. He, in support by his family, generously donated tissues leading to this successful face and eye transplant, but also saved three other individuals between the ages of 20 and 70, donating his kidneys, liver, and pancreas,” said Leonard Achan, RN, MA, ANP, president and CEO of LiveOnNY.

https://nyulangone.org/news/nyu-langone-health-performs-worl...


almost certainly a post-mortem donation. there's no shortage of people dying, after all. 150,000 a day, and not all elderly.


Unfortunately, very few people opt-in for organ donation. Thousands of people die a year waiting for transplants.


And even then, it has no actual legal effect if you do, because at death your body becomes the property of your next of kin. It's just another part of the estate. They absolutely can override your wishes, and the most you can do is put a clause in your will that says "if my organs are not offered for donation, Andrew gets $0.10 (ten cents) inheritance; if they are, he receives 100%".


Which is weird, because I've never spoken with anybody who hasn't opted in. I think there's a legal disconnect somewhere, where the simple opt-in at the DMV doesn't end up counting as a 'real' opt-in.


>Unfortunately, very few people opt-in for organ donation.

Wait, really?

This always seemed like a no-brainer to me. Why would people be opposed to this?


There is a theory that doctors won’t try as hard to save you if you’re an organ donor.


This is such a ludicrous theory that is sadly repeated often. It is extremely unlikely that your set of organs will be compatible with someone they know who needs organs. Even then, a nurse or allied health professional is much more likely to make a medical error which kills you. You'd be surprised at how thin the line between life and death is, especially for people on death's door.


I'm thankful I live in a country where opt-out is the norm.


To each their own. From a purely objective standpoint, I hope you or a loved one don't need a liver transplant one day (and consent to receiving one).


I think you misunderstand. The default in your correspondent's country is for people to be organ donors.


Yes, exactly, "norm" as in "legal norm".


Does anybody remember that movie Minority Report with Tom Cruise?

Eye transplants were available in that realist dys/utopian future.


This was the first movie I tried to pirate. I think I was downloading in divx format from LimeWire or Kazaa over my 1mbs cable modem.

I came back a couple hours later and I had about 20 minutes of the movie that I could start to play while the rest downloaded. I remember it started so hard that I just ended up leaving and going to the movies to see the rest of it.

I realized then that damn these movie studios are doing it all wrong.


It’s the best scifi movie out there by far. Of course everyone remembers it.


Should have ended after he gets put in jail. But no, Spielberg had to Spielberg and shoe horn a happy ending.


Tldr: no sight


yet


What is the ETA?


It has been 6 months. This is a CNS nerve, so you'd usually expect to see something in 3-6 months. CNS nerves are much less likely to heal, and it was 3 months between the eye being removed and the transplant.

IMO it seems unlikely that there will be any restoration of vision, but having an eye at all is an absolutely incredible accomplishment surgically. All those tiny things being attached inside the skull is just amazing.


We have to wait and see.


thanks


Pretty incredible, though I am doubtful of the optic nerve regeneration because of the absolutely insane density of the nerve fiber. Seems like something that will be beyond the grasp of science for the foreseeable future, but the possibility of the unexpected is exciting.


> I am doubtful of the optic nerve regeneration because of the absolutely insane density of the nerve fiber. Seems like something that will be beyond the grasp of science for the foreseeable future

It's been done quite successfully in mice [0]. Last I checked, it was being tested on primates. The method relies on activating the Yamanaka factors used in stem cell research.

[0] https://hms.harvard.edu/news/vision-revision


Your link is about gene therapy in the eyes of mice, and is specifically a method designed as an alternative to transplant:

> “This new approach, which successfully reverses multiple causes of vision loss in mice without the need for a retinal transplant, represents a new treatment modality in regenerative medicine.”

And that's just retinal transplant, much less whole-eye transplant.


The link provided is also about about a method to produce optic nerve regeneration, regardless of whether there has been a transplant or not. Unless you have a reason to believe that it would not work in the case of a transplant.


Retina or optic nerve: how do the regenerative methods differ?

Visual system > System overview: https://en.wikipedia.org/wiki/Visual_system :

> Mechanical: Together, the cornea and lens refract light into a small image and shine it on the retina. The retina transduces this image into electrical pulses using rods and cones. The optic nerve then carries these pulses through the optic canal. Upon reaching the optic chiasm the nerve fibers decussate (left becomes right). The fibers then branch and terminate in three places. [1][2][3][4][5][6][7]

>Neural: Most of the optic nerve fibers end in the lateral geniculate nucleus (LGN).

https://news.ycombinator.com/item?id=36912925 , ... :

- "Direct neuronal reprogramming by temporal identity factors" (2023) https://www.pnas.org/doi/10.1073/pnas.2122168120#abstract

- "Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration" (2022) https://www.cell.com/current-biology/fulltext/S0960-9822(22)...

- "Genetic and epigenetic regulators of retinal Müller glial cell reprogramming" (2023) https://www.sciencedirect.com/science/article/pii/S266737622...

- https://en.wikipedia.org/wiki/Tissue_nanotransfection#Techni... Ctrl-F "neurons"

Regeneration in humans > Induced regeneration: https://en.wikipedia.org/wiki/Regeneration_in_humans#Induced...


I absolutely have a reason to think optic nerve regeneration will be less effective in a transplant. In a transplant, the nerve has been severed!


The article mentions that vision has been at least partially restored following transplantation in animals.


I couldn't actually find anything optimistic after a quick search though. This 2017 study just looked at the biological viability of the eye, not function:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417899/

And indeed, a popular article from a few days ago has this quote:

> “Whole eye transplants in animal models have shown that a whole eye transplant is surgically feasible, in that the tissue can be transplanted and major blood vessels and nerves can be reconnected, and the graft can survive in the short term,” [ophthalmologist Yvonne Ou] said. “However, no models have demonstrated restoration of vision, which is a major challenge to the field.”

https://www.aao.org/eye-health/news/did-surgeons-just-transp...

My guess is that the OP article is just wrong, possibly because they confused corneal and retinal transplants (which can restore some vision) with whole-eye transplants.


> the graft can survive in the short term,” [ophthalmologist Yvonne Ou] said. “However, no models have demonstrated restoration of vision,

So the power lines (VCC, GND) are connected, but the IO lines are not.


I thought we just recently learned to sort-of, kind-of reconnect nerves. The solution for spinal tears was essentially to bluetooth (literally device on one side of tear and one on the other) data between torn spinal cord, and this was a huge accomplishment.

So, in short, this seems to be a bionic glass eye in the short term? Still cool.


> A team of surgeons in New York has performed the world's first transplant of an entire eye in a procedure widely hailed as a medical breakthrough, although it isn't yet known whether the man will ever see through the donated eye.

That's an important bit to know, and I imagine there will be a lot of people reading just the headline and not realizing that sight has not been granted with this transplant.


> The transplanted left eye appears very healthy, said retinal ophthalmologist Vaidehi Dedania. It has a good blood supply, is maintaining its pressure, and is generating an electrical signal, though James is not yet able to see. "But we have a lot of hope," she added.

Not that it didn't work, but that it's too early to tell. Fingers crossed.


Though later on the article also says, less optimistically:

> Given the time that has passed since the surgery, Washington said she did not think it likely that James's eye would regain vision, but "I never say something is impossible," she added.


I imagine a lot of people reading the comments won't realize that this same procedure has restored partial sight in animals.


If we stick a visual input into the brain, it's almost certainly going to use it in some capacity, even if it doesn't become "normal" vision.

Maybe re-introduce some neuroplasticity...


Given the signal isn’t blocked by scar tissue on nerve endings, I see this happening. The brain is amazing. It can reroute. It can form new routes given stimulus and a need. I have no doubt that if the patients nerve endings are good and the eye was attached proper (sounds like it was) then it’s a matter of time before the brain reconnects the shutdown pathways.

It takes some effort, some real effort, on the patients part though. Meditation. Visualizing the brain making the connections. Eating right. Exercising. And healing.

Not guaranteed but the best environment is crucial to regain mobility/ability.

This is coming from someone who has broken their back, their legs, arms, fingers, wrists, skull, and a few broken toes. Obviously not all at once. I have had 1 surgery, the rest I declined. The body knows itself. Don’t get in the way of it correcting itself. Just provide the best environment you can. You may not be able to reach your bum today, but you will.


Indeed, if they just slapped it in there like a modular daughter-card and hooked it up the the power supply (blood, etc) but it doesn't actually work for what most people consider eyes to be most useful for, it's a significant datum that radically changes the interpretation. Still cool, but important detail.


I think maybe the reason people will read the headline and expect a fully functional eye is because most people will drastically underestimate what an incredible feat this is. It isn't much of a stretch to say eyes are a part of the brain that's sticking out.

If a headline talked about the first dorsal amblugda transplant (or some non-made-up component of the brain's anatomy), I would not expect it to be functional. I would be very impressed that they managed to "slap it in there like a modular daughter-card and hook it up the the power supply" although it wouldn't occur to me to use a metaphor that makes it sound in any way simple.


What if a colorblind person received a non-colorblind person’s eyes? I wonder if the brain would have trouble with the new color information?


Everyone's eyes are going to be different, so matter what kind of eye was transplanted, the patient's brain would no doubt have to spend some time getting accustomed to it (assuming that vision was restored, which hasn't been done yet in humans). However, growing the nerves necessary to restore vision would also take time, so they probably would not notice color in particular being confusing. Everything would be confusing while the nerves regrow.

After vision was fully restored, they presumably would just have reduced color vision in that eye, but their other eye (if they had one) would pick up the slack. It wouldn't be that different from people who are partially blind in one eye; the brain puts together the information from both eyes and constructs a single coherent image from it, such that it's not really noticeable to them that their two eyes see differently.




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