John Freke, the first ophthalmic surgeon in Britain started practising at St Bart’s around the time when the Bristol Royal Infirmary opened its doors, but it was not until Baron de Wenzel’s appointment in 1772 that the specialty gained its true recognition. After becoming an oculist to King George III, de Wenzel perfected his skill in removing the cataracts, which was seen at a time as an almost miraculous deed of evangelical magnitude (1).

The restoration of vision was what brought the ophthalmology into the realm of the proper medical sciences. However, removing the closure of the anterior eye was a mere release of the perceptive function that was already there.

In that, de Wenzel was not an inventor; he merely replicated what was already well-described at the time of the “old” empire of Pharaohs, when the first Unknown Egyptian wrote the hieroglyphic word    (the brain).  With a spot-on analysis, the Unknown described that the loss of function is not always located in the organ that is faulty.

The loss of vision, thus, was not confined to the mechanical structure of the eye, but rather to the perceptive cells that handle the signal (2).

Five thousand years passed since the publication of the manuscript, and still, patients with retinitis pigmentosa or age-related macular degeneration face a prospect of an incurable loss of vision. Due to the degeneration of outer retinal photoreceptor layers, it is extremely difficult to recreate these cells, especially if the disease has already taken its toll and the destruction is permanent.

New cells to replace the lost ones

Luckily, a new treatment appears to be on the horizon, and it comes, unsurprisingly, from the realm of regenerative medicine. Despite great advances in basic sciences, the cell transplantation and gene therapy have not been very successful (3). It would not be a novel finding to report that the brain and retina-derived cells fail to integrate into the outer layer and differentiate into the new photoreceptors.

However, when taken at an earlier stage of development (peak of rod genesis), the transplanted cells seem to be able to integrate and successfully differentiate, form synaptic connections, and finally improve the vision clinically (3). These studies indicate that there is a potential to catch the cell in its under differentiated from and to trick it into developing further, after a change of environments. By preserving the naivety of the cell, clinicians may be able to achieve more of its native function.

Gene therapy on the rise

Another way of achieving the regeneration would be to deliver a non-mutated version of a gene that is impaired in a congenital disease of the eye. One example would be the treatment of Leber’s congenital amaurosis. There are reports (4,5) of using a vector: an adeno-associated virus, injected under the fovea, to supply the CHM gene to the retinal pigment epithelium.

Two of the six patients in the recent study (6) reported a long-term improved visual acuity in the treated eyes, despite the degeneration of the untreated eye. This was sustained after 3.5 years post-op and constitutes a promising, yet currently inefficient way of curing the disease.

Image showing how DNA or RNA is introduced into the desired site in the retina during gene therapy (left, source), and image showing how AAV vector is used to mediate gene transfer (right, source)

Diagram showing different ocular target tissues and strategies for glaucoma gene therapy. C: conjunctiva; TM: trabecular meshwork; CP: ciliary process; CM: ciliary muscle; R: retina; ON: optic nerve. Eye diagram adapted from National Eye Institute (source)

(A) Illustration of the two anatomical sites for gene therapy administration: retina and superior colliculus. (B) Superior colliculus, the site at which retinal ganglion cell axons innervate in the brain. (C) Schematic drawing describing the rationale of neurotrophic factor gene therapy and the role of retinal cells and superior collicular cells play in the cellular level. BDNF: Brain-derived neurotrophic factor (source).

Towards the Bionic Eye

The mechanical visual implants may seem like a far-fetched sci-fi delusions, rather than something available on the NHS, yet 29 blind (in the literal sense) participants were recently enrolled into a trial of such devices (7). Out of these, four patients gained the ability to read letters and 13 reported improvements in useful visual functions that enhanced their daily living.

The implant was an effective way of restoring the vision in patients with only light or no visual perception. This constitutes a new potential route of replacing the lost cells with something that is completely mechanically engineered and provides an invaluable chance of regaining sight in people with almost no visual ability at all. You can read more about the case – Blind woman’s joy as she is able to read the time thanks to ‘bionic eye’.

The future of ophthalmology

With the advent of new techniques and function-replacing equipment, the restoration of the sense of vision can be an incredibly exciting field, emerging on the crossovers of ophthalmology and neurosurgery. These two specialties can start working together in the translational research of repairing or even replacing the faulty elements of the visual tract, with the aim of finally defying the pessimistic prognosis given by the Unknown Egyptian.

Thanks to the advances modern medicine, the lame can already walk, and the death can enjoy music again. Perhaps it’s the high time blind could finally get their sight back.