Endothelial keratoplasties (DSAEK · DMEK · PDEK)

The core of 2026 activity. They treat endothelial failure (Fuchs, bullous keratopathy) by replacing only the endothelium ± a thin support, through a small incision, with no corneal suture.

DSAEK / UT-DSAEK

A graft of endothelium + Descemet + a thin layer of posterior stroma (prepared with a microkeratome). The ultra-thin (UT-DSAEK) variant reduces thickness to approach the visual performance of DMEK. The stiffer graft is easier to manipulate: DSAEK retains an advantage in complex eyes (aphakia, altered iris, drainage tubes, unstable chamber) and for the surgeon on the learning curve. Limitation: the stromal interface caps visual recovery and induces a slight hyperopic shift; the main early complication is graft dislocation.

DMEK — the reference technique

Grafting of the Descemet membrane + endothelium only (~15-20 µm), with no stroma. It is the most anatomical reconstruction, offering the best visual acuity, the fastest recovery and the lowest rejection rate (~1-2%).

Operative sequence (landmarks)

1. Descemetorhexis: removal of the recipient's diseased Descemet under air.
2. Graft preparation/staining (trypan blue); it scrolls with the endothelium facing outward; asymmetric marking (F/S) for orientation.
3. Injection into the anterior chamber via an injector (often preloaded), then controlled unfolding (tapping manoeuvres, air bubbles, fluid currents).
4. Orientation check, centring, then gas-bubble tamponade (air or SF₆ ~20%) pressing the graft against the stroma during pump-dependent adhesion.
5. Strict supine positioning postoperatively.

Complications

• Partial graft detachment — the most frequent; corrected by re-bubbling (gas reinjection).
• Primary failure (non-functioning graft, often orientation/handling related).
• Pupillary block from the gas bubble, ocular hypertension, rejection (rare).

Variants & widening indications

DMEK now extends to eyes once deemed difficult (aphakic, vitrectomised, tube-carrying) thanks to preloaded tissue and adapted anchoring techniques. Shared-tissue approaches — hemi-DMEK, quarter-DMEK — aim to treat several recipients with a single graft, a direct answer to scarcity.

PDEK (pre-Descemet EK)

A variant using a type-1 big bubble to prepare a graft including the Dua layer + Descemet + endothelium. Slightly thicker and more robust than DMEK, the graft is more manageable while preserving excellent optical quality; it allows the use of young donors (more reproducible bubble), expanding the tissue pool.

▶ Watch the videos: endothelial grafts & Fuchs dystrophy (egabison.com)

The regenerative & graft-free turn

The conceptual break of the decade: instead of transplanting donor tissue, stimulate, inject or manufacture. Five directions converge, all driven by the global shortage and by corneal biology.

1 · DSO / DWEK ± ROCK inhibitors

In selected Fuchs patients (central guttata, preserved peripheral endothelium, peripheral density > ~1000 cells/mm²), only the diseased central Descemet is removed (Descemet stripping only) without a graft: healthy peripheral endothelial cells migrate and repopulate the centre. Adding a topical Rho-kinase inhibitor (ripasudil, netarsudil) accelerates corneal clearing and promotes cell migration/function — visual recovery is faster than with observation alone in published series.

A crucial caveat on outcome: left to itself, clearing after DSO is slow and unpredictable — highly variable timelines (from a few weeks to several months) and a non-negligible proportion of non-clearing. In practice, the procedure is only conceivable combined with a Rho-kinase inhibitor: it drives both the speed and the very probability of recolonisation. A "bare" DSO without ROCK-i exposes the patient to unpredictable and often disappointing recovery.

An important nuance: DSO is an alternative, not a guarantee. Cases show excellent clearing over several years, but also late failures (recurrent guttata, neo-Descemet), some leading secondarily to DMEK — a 10-year follow-up has documented this scenario. Patient selection and counselling about the limitations are decisive.

2 · Injectable endothelial cell therapy

The most disruptive innovation, born from the work of Shigeru Kinoshita (Kyoto). The principle: culture human corneal endothelial cells ex vivo (a single donor can thus treat dozens of recipients), then inject them into the anterior chamber with a ROCK inhibitor (Y-27632) and face-down positioning, with no graft at all.

• Vyznova™ (neltependocel) — approved by the PMDA in Japan and commercially launched in September 2024 for bullous keratopathy: the world's first endothelial cell therapy to obtain regulatory authorisation.
• AURN001 (neltependocel + Y-27632, Aurion Biotech) — US development: the phase 1/2 CLARA trial met all endpoints at 12 months, followed by treatment of the first patients in the pivotal phase 3 (ASTRA study) in spring 2026. Alcon took a majority stake in Aurion in 2025.

Potential impact: turning tissue-dependent graft surgery into a standardised injection procedure, largely freeing it from corneal scarcity and graft-handling constraints.

3 · 3D-bioprinted endothelium — Precise Bio (PB-001)

The most recent breakthrough on the endothelial side: instead of injecting a cell suspension, a living endothelial graft is 3D-bioprinted. PB-001 (Precise Bio) combines human corneal endothelial cells, biomaterials and robotic layer-by-layer bioprinting: a tissue that unrolls and adopts the corneal curvature, uniting the handling of DSAEK with the optical precision of DMEK, delivered pre-loaded on a standard injector.

World first: on 29 October 2025, a first patient (legally blind in the treated eye) received PB-001 at the Rambam Medical Center (Haifa) — the world's first transplant of a functional, cell-based, bioprinted corneal endothelium. Phase 1 trial (10-15 patients, corneal oedema from endothelial dysfunction), topline results expected in the second half of 2026.

4 · Bioengineered acellular corneas

For the stroma, manufactured substitutes aim to replace donor tissue. The leader is BPCDX (bioengineered porcine construct, double crosslinked): a medical-grade type-I porcine collagen hydrogel, doubly crosslinked (chemical + photochemical), with no cells or viable biological material, classed as a class III medical device. It is implanted intrastromally by a minimally invasive technique without sutures or tissue removal, thickening and remodelling the recipient's cornea.

Pilot data (Nature Biotechnology, 2022: 20 advanced-keratoconus eyes, India/Iran, 24 months with no adverse event) were extended in 2026 by new series (e.g. a 17-eye study, stage 3-4 keratoconus, 12-month follow-up). The appeal is twofold: an answer to scarcity and access in resource-limited countries, where the graft shortage is most acute.

5 · Bioprinting, scaffolds & gene therapy

• 3D / DLP bioprinting and bio-ink scaffolds (collagen, hyaluronic acid, silk…) to rebuild an organised stroma, and even limbal structures — active translational research.
• Corneal gene therapy: allele-specific approaches and editing (CRISPR) for stromal dystrophies linked to the TGFBI/BIGH3 gene; correcting or silencing the mutant allele to prevent recurrence after grafting.
• Corneal xenotransplantation (decellularised or genetically modified pig): a route explored to widen the tissue supply.

6 · CAIRS — the allogenic additive

For keratoconus, allogenic intrastromal ring segments (shaped human corneal tissue inserted into a stromal tunnel) remodel the surface with no synthetic material and no penetrating graft. They join the "additive" logic: nothing is removed or replaced, the cornea is reinforced and regularised. Planning (number, thickness, position of segments) relies on dedicated nomograms.