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J.Konstapel,Leiden,14-10-2026.

Aanleiding FD: ‘Ik dacht altijd: blinde mensen weer zicht geven is sciencefiction’

Nederlandse Inleiding

Blindheid ontstaat wanneer ergens in het visuele systeem iets uitvalt. Dat kan de toegang van licht tot het oog zijn, de lichtgevoelige cellen van het netvlies, de zenuwbanen of de hersenen die beelden verwerken. De plaats van de beschadiging bepaalt welke behandeling mogelijk is.

Bij staar en afwijkingen van de oogsterkte bestaan al effectieve oplossingen. Bij beschadiging van het netvlies bieden gentherapie, lichtgevoelige eiwitten en elektronische implantaten nieuwe mogelijkheden. Ook wordt onderzocht hoe beschadigde zenuwcellen kunnen herstellen en hoe signalen rechtstreeks naar de hersenen kunnen worden gestuurd. De resultaten variëren van beperkt lichtzien tot het herkennen van eenvoudige vormen en letters.

Een aanvullende mogelijkheid is beelden omzetten in geluid of tastbare signalen. Daarmee kan iemand zich beter oriënteren zonder dat het gezichtsvermogen zelf terugkeert.

De Vacuum.Net-theorie beschrijft zien als een netwerk van drie functies: licht opvangen, signalen doorgeven en informatie verwerken. Vanuit dit model ontstaat een nieuw voorstel voor implantaten: stimuleer niet alleen een lichtpunt, maar ook de omgeving ervan. Het contrast tussen licht en donker zou vormen en randen herkenbaarder kunnen maken. Of dit daadwerkelijk beter werkt, moet nog experimenteel worden aangetoond.

De hoofdconclusie is dat blindheid geen enkelvoudig probleem is. Soms bestaat de behandeling al, maar ontbreekt de toegang ertoe. In andere gevallen moet de techniek nog worden ontwikkeld.

English Essay

IntroductionAround 43 million people worldwide are blind, and most of them could once see. Behind that single word — blindness — lie very different problems: a clouded lens in one country, dying photoreceptors in another, a severed optic nerve in a third. Each demands its own remedy, and a remedy that works at one point of failure does nothing at another.

This essay presents a structured map of blindness and vision restoration. It is organised around a simple principle: seeing breaks at a specific layer, and each treatment works by restoring that layer, bypassing it, or reaching the brain by another route. The framework is drawn from the author’s Vacuum.Net theory, which describes vision in five functional layers. The result is a clear-eyed view of what medicine can do today, what is in trial, and where the field is heading as of October 2026.

The Five Layers of Seeing

The theory describes vision as a chain of closures. Light must first pass an opening (the passage); it must be caught by a light-sensing window; the signal must be passed along an edge; it must be handed over at a relay; and finally it must be held as an image in a reading ring. In anatomical terms:

Layer	Function	Anatomy
0. Passage	An opening through which light reaches the window	Cornea, lens, vitreous
1. Window	A closure with light	Photoreceptors and the RPE
2. Edge	Passing the signal on	Bipolar cells, ganglion cells, optic nerve
3. Relay	Handover to the reading ring	LGN in the thalamus
4. Reading ring	The image itself	Visual cortex

Every major cause of blindness breaks exactly one of these layers, and every treatment — from a ten-dollar pair of glasses to a thousand-electrode brain implant — can be classified by the layer it restores.

The Scale of the Problem

The Vision Loss Expert Group counted 43.3 million blind people in 2020, alongside 295 million with moderate or severe vision impairment. Without intervention, blindness is projected to reach 61 million by 2050. Among people over 50, the leading causes are cataract (45.5% of the 33.6 million blind in that age group), glaucoma (11%), undercorrected refractive error (6.6%), age-related macular degeneration (5.6%) and diabetic retinopathy (2.5%).

One finding stands out. Cataract and refractive error together account for roughly half of all blindness in people over 50 — and both have a safe, cheap, well-understood remedy. The bottleneck is not knowledge but reach: in Burundi, effective cataract surgical coverage is just 2.1%, against 77.7% in Qatar. Roughly half of those worldwide who need cataract surgery cannot get it; in Africa, three in four go untreated.

In the Netherlands, the picture is different but structurally similar: a 2008 count found 77,000 blind people, 59,000 of them aged 65 or over, with AMD (38%) and cataract (23%) leading. Around a third of the blind elderly are blind for want of a lens, glasses or an operation — not for want of a technique.

Layer 0: The Passage — A Problem of Delivery, Not Discovery

When the retina is healthy but light cannot reach it in focus, the remedies are established and inexpensive. Glasses and laser correction address refractive error; cataract surgery replaces the clouded lens (141,134 operations in the Netherlands in 2025, with vision improved in 94.1% of cases). Myopia control in children is advancing: high-dose atropine slows progression by about 67%, and defocus lenses reduce eye growth by 62%.

For the cornea, donor tissue remains scarce — one donor cornea for every 70 needed, with 53% of the world lacking access to transplantation — but new routes are emerging: cultured endothelial cells (one donor pair yields roughly a thousand doses; approved in Japan, in US phase 3), a bioengineered cornea of pig collagen (all 14 blind keratoconus patients in the trial regained sight), and the Boston keratoprosthesis (over 19,000 implanted, 74% retained at five years).

The lesson of this layer is commercial as much as medical: the products exist, the outcomes are proven, and the unmet need is a distribution and affordability problem.

Layer 1: The Window — Where Real Innovation Is Happening

Here the photoreceptors themselves die, through inherited dystrophies (retinitis pigmentosa, Stargardt disease, Leber congenital amaurosis), AMD, or diabetic retinopathy. Most current treatments only slow the loss: anti-VEGF injections for leaking vessels, complement inhibitors for geographic atrophy (slowing lesion growth by 14–22% but without clear acuity gains), and strict glycaemic control, which cuts new diabetic retinopathy by 76%.

Restoration, where photoreceptors are already lost, follows three distinct strategies:

1. Restore the missing part of the window. A photoreceptor’s light sensor has two fixed components: the opsin protein and the chromophore retinal. Gene therapy can supply a broken one. Luxturna, the first approved gene therapy for the eye (FDA 2017), does exactly this for RPE65 mutations: 13 of 21 treated patients passed a mobility test at 1 lux, none of the untreated. Successor programmes — laru-zova for X-linked RP (positive phase 3 readout, September 2026), CRISPR editing, RNA therapy — extend the same logic. Crucially, this works only while cells are still alive.

2. Place a new window further along the chain. When photoreceptors are gone, optogenetics gives the surviving bipolar or ganglion cells a light-sensing channel. GenSight’s GS030 restored object localisation to a man blind for 40 years (with goggles). Nanoscope’s MCO-010 works in ordinary light and gained about 2.6 lines of acuity over four years; an FDA decision is due in 2027. Restore Vision’s RV-001 moved all three high-dose patients from no light perception to light perception within a month. And Prima (Science Corp) — a 2×2 mm photovoltaic chip under the macula driven by infrared glasses — gained a mean 25.5 letters in 38 patients with geographic atrophy, 84% of whom could read letters again. Prima carries a CE mark since July 2026 and is under FDA review.

3. Transplant new cells. This remains the hardest road. A 2016 triangulation by three independent groups showed that only 1.2–4.7% of apparent photoreceptor “integration” was genuine; the rest was material transfer into host cells. RPE patches fare better (OpRegen gained up to 9 letters where coverage was extensive), because the RPE sits behind the window rather than forming part of it.

A key engineering insight from the theory: sensitivity is not a matter of amplification chains but of how long a single “window” stays open. Fast channels need bright light (goggles); slow pigments work in ambient light but smear motion. This trade-off sorts today’s products into two families, and it explains why melanopsin — extremely slow and sensitive — can restore light detection but not images.

Layer 2: The Edge — The Hard Problem

Glaucoma, the most common cause of irreversible blindness, kills ganglion cells and their axons: the windows still close, but the signal no longer travels. Everything available today is slowing, not restoring. Lowering eye pressure cuts progression — a 25% pressure reduction halved progression rates in the landmark EMGT trial, and each 1 mmHg of reduction lowers risk by about 10% — but lost ganglion cells do not return.

Restoration is only now entering first-in-human trials. The most notable is Life Biosciences’ ER-100, which uses partial cellular reprogramming (the 2020 mouse work restored vision in a glaucoma model). Its first human data, reported 8 October 2026, showed visual-field improvement in 2 of 3 glaucoma patients at the lowest dose — an uncontrolled first signal, not a result. Nicotinamide is in phase 3. For LHON, gene therapy (Lumevoq) showed bilateral effects that confounded its EU application, though it is available to named patients in France at €425,000 per injection.

Layers 3 and 4: Writing Directly into the Brain

When everything in front is gone, the remaining option is to write directly into the relay (the LGN) or the cortex. This is the route of Phosphoenix, the company founded by Pieter Roelfsema that prompted the original essay: a cortical/LGN prosthesis with over 1,000 electrodes, built on a 2020 macaque experiment in which stimulated electrode patterns formed recognisable letters. A five-patient human study begins at Amsterdam UMC in early 2027, with market entry foreseen around 2032. A Harvard path (Pezaris) showed as early as 2007 that LGN microstimulation produces reliably localised phosphenes; a first human test is hoped for in late 2027.

Cortical implants — Orion, CORTIVIS, ICVP — have shown that humans can localise, count and even read simple letters through direct stimulation, but channel counts remain the binding constraint: simulations suggest 600–700 electrodes are needed merely for reading and walking, and around a million to match the retina’s output.

Where the cortex itself is damaged — stroke, cerebral visual impairment in children — implants cannot help, but training can. Rigorous daily training of the blind field (Huxlin, Rochester) raised task accuracy from about 50% to about 80%, working through a secondary route from the LGN to area MT that bypasses the destroyed V1. This is the mechanism behind “blindsight.”

The Design Rule Nobody Uses Yet

The essay’s most forward-looking contribution is a design principle drawn from the theory’s register of three values (+1, 0, −1). The retina naturally computes in three positions: an ON pathway, an OFF pathway, and centre-surround fields. Yet every clinical device reviewed — every electrode array and every clinical opsin — writes only +1. None writes −1.

Evidence from blind mice (Macé et al., 2015) shows the opportunity: exciting only ON-bipolar cells restored both ON and OFF responses, because the retina’s own circuit supplied the inhibition. The proposed rule is therefore: write a phosphene as +1 at its centre with −1 around it, at the address from which the native circuit forms the −1 itself. Whether a centre-surround phosphene is perceived more sharply than a dot has not been tested — an open, testable hypothesis and a plausible differentiator for the next generation of devices.

Substitution: Reaching the Reading Ring by Another Route

Finally, the reading ring keeps relations, not sources. Echolocation training (ten weeks of mouth-clicks) made the primary visual cortex of both blind and sighted adults respond to echoes, and cut blind participants’ maze-completion time by 58%. The vOICe converts images to soundscapes that activate the visual shape area. BrainPort renders camera images on the tongue (69% of year-long users passed object recognition). Be My Eyes passed one million blind and low-vision users in March 2026.

These routes work for every cause, at every layer, without surgery — and they work best for people who once saw, because their reading ring was already filled.

Conclusion: Three Populations, Three Strategies

Read through the five layers, the field acquires a plain commercial logic:

1. Half the world’s blind need a lens or glasses. The remedy exists, is cheap and is safe. The gap is delivery and financing, and closing it is a logistics and policy task, not a research one.
2. Those who lost their windows (RP, dry AMD) are the beneficiaries of genuine breakthroughs: Prima carries a CE mark in Europe, MCO-010 awaits an FDA decision in 2027. What returns is coarse — but it is sight.
3. Those whose edge was cut (glaucoma patients above all) still have no way back. For them, everything rests on next-generation work — reprogramming, LGN implants — reaching the clinic early in the next decade. Until then, sensory substitution and AI are what is available, today.

The strategic lesson generalises beyond ophthalmology: match the intervention to the layer that is broken, and be honest about which layer a product actually serves. A field that orders itself this way — from the $100 lens to the million-electrode cortex — becomes, as this essay demonstrates, not a list of miracles and failures, but a map.

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Annotated References

Each entry gives the source, its role in the essay, and guidance on reading it.

The occasion

1. Gras, A. (2026). “Ik dacht altijd: blinde mensen weer zicht geven is sciencefiction.” Het Financieele Dagblad, 14 October 2026.
   The interview with Pieter Roelfsema that prompted the essay: the company, the funding and the 2032 plan. Worth reading for the passage on investors, which shows how a research lab becomes a medical product.
2. Chen, X., Wang, F., Fernández, E., and Roelfsema, P. R. (2020). “Shape perception via a high-channel-count neuroprosthesis in monkey visual cortex.” Science 370, 1191–1196.
   The macaque experiment with 1,024 electrodes behind Phosphoenix: simultaneous stimulation produced letters, sequential stimulation produced motion. See the figure in which a letter is built from 8 to 15 phosphenes.
3. CORDIS (2025). “SIGHTED”, EU project 101212687.
   The EU-funded plan for the first five patients with the LGN implant, early 2027.

The theoretical framework

4. Konstapel, J. (2026). One Window: Light-Gated Channels, the 2026 Nobel Prize in Medicine, and the Closure Rule of the Vacuum.Net. Constable Research, Leiden, 10 October 2026.
   Source of the window with one free place, the three-position register, and the address/tension distinction. Sections 3, 6 and 7 are most relevant; note that the essay corrects its “factor fifty” claim.
5. Konstapel, J. (2026). From Cell to Mind: How Excitable Cells, Nerve Nets, Brains and Minds Evolved. Constable Research, Leiden, 14 October 2026.
   The biology of excitable cells and senses, kept separate from the theory. Chapter A6 holds the response-time data used in the speed/sensitivity analysis.
6. Konstapel, J. (2026). Life and Consciousness from One Rule: Closure in the Net. Constable Research, Leiden, 29 September 2026.
   The ring of 3 and 6, the membrane as edge, and the reading ring as an image that keeps relations. Sections 4, 6 and 7.
7. Konstapel, J. (2026). Vacuum.Net Theory: hoe massa, energie en ruimte één net vormen. constable.blog, 28 September 2026.
   The mesh as an opening between strands, on which the passage layer is read.
8. Konstapel, J. (2026). What Fits, Stays: Designer Molecules, the Closure Rule of the Vacuum.Net, and Three Simple Roads to a Medicine. Constable Research, Leiden, 10 October 2026.
   The “mesh instead of a substance” road, which optogenetics and Prima follow.

The size of the problem

9. GBD 2019 Blindness and Vision Impairment Collaborators and Vision Loss Expert Group (2021). “Causes of blindness and vision impairment in 2020 and trends over 30 years.” Lancet Global Health 9, e144–e160.
   The core table of blindness by cause. Table 4 covers people over 50; the appendix holds all-ages data.
10. Bourne, R. et al. (2021). “Trends in prevalence of blindness and distance and near vision impairment over 30 years.” Lancet Global Health 9, e130–e143.
    The 43.3 million blind in 2020 and the 2050 forecast.
11. Limburg, H., Keunen, J. E. E., and van Rens, G. H. M. B. (2009). “Hoeveel slechtzienden en blinden zijn er in Nederland?” Tijdschrift voor Gerontologie en Geriatrie 40, 149–155.
    The only Dutch count by cause, split between care homes and independent living. Shows that a third of blind elderly people need only a lens or glasses.
12. McCormick, I. et al. (2026). “Effective cataract surgical coverage in 68 countries, 2000–2030.” Lancet Global Health, online 10 February 2026.
    Coverage by country, from 2.1% in Burundi to 77.7% in Qatar — the essay’s key evidence that layer 0 is a delivery problem.

Layer 0: the passage

13. Gain, P. et al. (2016). “Global survey of corneal transplantation and eye banking.” JAMA Ophthalmology 134, 167–173.
    One donor cornea for every 70 needed.
14. Holden, B. A. et al. (2016). “Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050.” Ophthalmology 123, 1036–1042.
    The forecast that half the world will be myopic by 2050.
15. Rafat, M. et al. (2022). “Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus.” Nature Biotechnology 41, 70–81.
    A cornea made of pig collagen restored sight to all 14 blind patients in the trial — a potential answer to the donor shortage.

Layer 1: the window

16. Moiseyev, G. et al. (2005). “RPE65 is the isomerohydrolase in the retinoid visual cycle.” PNAS 102, 12413–12418.
    What the Luxturna gene does: it makes the chromophore, one of the two fixed places of the window.
17. Russell, S. et al. (2017). “Efficacy and safety of voretigene neparvovec in patients with RPE65-mediated inherited retinal dystrophy.” The Lancet 390, 849–860.
    The pivotal trial behind the first approved gene therapy for the eye.
18. Sahel, J.-A. et al. (2021). “Partial recovery of visual function in a blind patient after optogenetic therapy.” Nature Medicine 27, 1223–1229.
    The first person to see again through a light-gated channel. Read for what he could do with goggles — and could not do without them.
19. Holz, F. G., Le Mer, Y., Muqit, M. M. K. et al. (2025). “The PRIMA subretinal photovoltaic implant in geographic atrophy.” New England Journal of Medicine 394, 232–242.
    The Prima trial: 38 patients, a mean gain of 25.5 letters — the strongest restoration result in dry AMD to date.
20. Macé, E. et al. (2015). “Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV restores ON and OFF visual responses in blind mice.” Molecular Therapy 23, 7–16.
    The experimental basis for the design rule: an exciting opsin at the right address recruits the retina’s own inhibition. Note the strychnine experiment, which removes the OFF responses.
21. Pearson, R. A. et al.; Santos-Ferreira, T. et al.; Singh, M. S. et al. (2016). Nature Communications 7, 13029; 13028; 13537.
    Three independent groups showing that most “integrated” photoreceptors after transplant were host cells carrying donor material — the sobering baseline for cell therapy.
22. Lin, B., Koizumi, A., Tanaka, N., Panda, S., and Masland, R. H. (2008). “Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin.” PNAS 105, 16009–16014.
    A slow, sensitive pigment gives light detection but not shape — the illustrative case that sensitivity trades off against image formation.

Layer 2: the edge

23. Heijl, A. et al. (2002). “Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial.” Archives of Ophthalmology 120, 1268–1279.
    The measured effect of lowering pressure: slowing, not restoring.
24. Lu, Y. et al. (2020). “Reprogramming to recover youthful epigenetic information and restore vision.” Nature 588, 124–129.
    The mouse work behind the first human regeneration trial in glaucoma.
25. Life Biosciences (2026). “First-in-human data from ongoing phase 1 trial evaluating ER-100 in optic neuropathies.” Press release, 8 October 2026.
    The first signal of restored visual field in glaucoma: 2 of 3 patients, uncontrolled. Read it as a first signal, not a result.

Layers 3 and 4: relay and reading ring

26. Pezaris, J. S., and Reid, R. C. (2007). “Demonstration of artificial visual percepts generated through thalamic microstimulation.” PNAS 104, 7670–7675.
    The case for the LGN as the place to write when the eye and optic nerve are gone.
27. Fernández, E. et al. (2021). “Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex.” Journal of Clinical Investigation 131, e151331.
    A blind woman sees letters through 96 electrodes in V1.
28. Jazayeri, M., Lindbloom-Brown, Z., and Horwitz, G. D. (2012). “Saccadic eye movements evoked by optogenetic activation of primate V1.” Nature Neuroscience 15, 1368–1370.
    The first sign that light on V1 is genuinely seen by a primate; the basis for an optogenetic cortical prosthesis.
29. Ajina, S. et al. (2015). “Human blindsight is mediated by an intact geniculo-extrastriate pathway.” eLife 4, e08935.
    The second reading route that survives after V1 is lost — the mechanism that field training exploits.
30. Cavanaugh, M. R. et al. (2017). “Vision recovery in cortical blindness.” Neurology; and Huxlin, K. R. et al. (2009). Journal of Neuroscience 29, 3981–3991.
    Training brings the blind field of stroke patients back into use.

Other routes to the reading ring

31. Norman, L. J., Hartley, T., and Thaler, L. (2024). “Brain changes after 10 weeks of click-based echolocation training in blind and sighted adults.” Cerebral Cortex 34, bhae239.
    Ten weeks of clicking, and V1 answers to echoes in blind and sighted adults alike. Read with Norman et al. (2021), PLoS ONE 16, e0252330, for the effects on daily life.
32. Amedi, A. et al. (2007). “Shape conveyed by visual-to-auditory sensory substitution activates the lateral occipital complex.” Nature Neuroscience 10, 687–689.
    Sound that carries shape reaches the visual shape area — substitution is not metaphor but cortical reality.

Background

33. Fernández, E., and Robles, J. A. (2024). Review of visual prostheses. PLoS Biology 22, e3002896.
    A review of every prosthesis route, including the estimate of 600–700 electrodes needed for reading and walking. See the section on channel counts.
34. Land, M. F., and Nilsson, D.-E. (2012). Animal Eyes, 2nd ed. Oxford University Press.
    How eyes arose at least 40 times independently, and what each design can and cannot do.

Bronnen

ources:

• One Window — constable.blog
• Metaphor as Closure / Carried Across — constable.blog
• Book: From Cell to Mind — constable.blog
• AAO 2026: MCO-010 sustains vision gains through 4 years
• Restore Vision: GPCR-based optogenetic therapy
• Scientific American: echolocation in 10 weeks
• Sensory substitution in blind users (PMC)

Englisch Sientific Article