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Biomedicine

An improved gel for detached retinas

Surgical repair of a detached retina involves the injection of a gas or silicone oil into the eye to hold the retina in place. The development of a gel with more-desirable properties than these substances might improve the success of this procedure.

Detachment of the retina is a serious condition that must be surgically corrected to avoid permanent sight loss. The surgery involves replacement of the vitreous body — a clear gel that allows light from the cornea and lens to be transmitted to the back of the eye. For more than 50 years, eye surgeons have been using gases1 or silicone oil2 as vitreous-body replacements, but this strategy has potentially harmful side effects. Writing in Nature Biomedical Engineering, Hayashi et al.3 describe a gel that can be easily implanted as a vitreous-body replacement. If it stands up to further testing, the gel could revolutionize the treatment of retinal detachment and other ocular disorders.

In young people, the vitreous body is viscous, acting as a shock absorber that decelerates the inertial forces on the retina during eye movement. Age-related changes can cause the vitreous body to liquefy and collapse, pulling on the retina and heightening the risk of tears in the retina. Eye movement and swirling currents in the vitreous body allow fluid to pass through a tear, separating the retina from the wall of the eye and causing retinal detachment.

Vitrectomy is the most common way to repair a detached retina. The vitreous body is cut and aspirated, removing the traction from the retinal tears. The retina is then reattached surgically and lasers are applied to the tears so that the retina adheres to the back of the eye, preventing the passage of fluid under the retina. A gas bubble or silicone oil is then used to fill the space left by the vitreous body, keeping the retina in position until strong adhesion occurs. Gases are absorbed by the body after a month or two, and replaced by natural aqueous humour (a main component of the vitreous body), whereas silicone oil can later be removed from the eye.

However, many aspects of this strategy are problematic. For instance, because both gas and silicone oil are less dense than water, they rise to the top of the eye. As a result, patients must tilt their heads forward into a prone position — sometimes for weeks — to keep the gas or oil bubble pushing against the retina, and to allow nutrients from the surrounding fluid to flow around the bubble and reach the lens to prevent the development of a cataract. Recurrent retinal detachments occur more commonly at the bottom of the eye, because the bubble rises when the head is not prone. Denser oils have been developed to push against the lower retina4, but have not been approved for use in the United States.

In addition, the presence in the eye of both gases and silicone oil can impair vision, because they refract light differently from the vitreous fluid. The use of gas bubbles also temporarily limits air travel, because a sudden rise in altitude results in expansion of the bubble and a rapid increase in intraocular pressure, which can close the central retinal artery. And if silicone oil is left in place long-term, tiny droplets can break off, blocking the eye's drainage channels and causing a subsequent rise in intraocular pressure that can damage the optic nerve — a condition called glaucoma that may persist even after the oil's removal.

An inert, biocompatible hydrogel (a water-absorbing network of crosslinked polymers) could be better suited than gas or silicone oil for vitreous-body replacement. A gel that has the mechanical stability to hold the retina in place would not require head positioning, and would allow patients to maintain normal activities during their recovery. Such a gel might also be a safe repository for drugs to treat different disorders of the retina, because drugs could be attached to the polymers, and released in a sustained manner as the gel gradually breaks down over time.

However, existing hydrogels are prone to swelling in the eye owing to high osmotic pressure, which causes water to enter the gel. The osmotic pressure can be lowered by reducing the gel's polymer content, but this leads to another potential problem: the gel might not be firm enough to hold the retina in place for adequate periods of time. Moreover, low-concentration polymers crosslink slowly, whereas fairly rapid crosslinking is needed for a gel to become firm during surgery, after the detached retina is repositioned but before the surgical procedure is finished.

Hayashi et al. have now developed a two-step process for the formation of a hydrogel with a low polymer content and desirable properties for vitreous-body replacement (Fig. 1a). They started with star-like polymers that had either thiol groups or maleimide groups at their termini. As a first step, the authors mixed these mutually reactive polymers in two separate reactions, using either an excess of thiol groups or an excess of maleimide groups. They stopped this reaction, through dilution, before it formed a gel, to obtain polymer clusters whose surfaces displayed predominantly thiol groups (in one reaction) or maleimide groups (in the other). In a second step, the authors mixed the two types of cluster, to obtain a low-concentration hydrogel that does not swell.

Figure 1: A fresh look at retinal surgery.
figure1

Hydrogels are water-absorbing networks of crosslinked polymers. Hayashi et al.3 have designed a hydrogel for use in surgery to repair detached retinas. a, The authors began with two reactive star-shaped polymers, one with thiol groups at its termini, the other with maleimide termini. These are mixed in two different reactions, in which one or other polymer is present in stoichiometric excess. The reactions are stopped by dilution, producing crosslinked polymer clusters in solution that display predominantly one group at their surfaces. Mixing the clusters leads to the rapid formation of a low-density hydrogel. b, When solutions of the two clusters are injected into the eyes of rabbits, the rapidly forming hydrogel can hold the retina in place as it reattaches to the back of the eye. (Figure based on Fig. 2a of ref. 3.)

The gel can crosslink within as little as 10 minutes of the clusters being mixed. The authors tested their gel by injecting it into the eyes of rabbits with detached retinas (Fig. 1b). The retinas remained reattached after 410 days, with minimal evidence of toxicity or inflammation — so the gel is seemingly more biocompatible than gases or silicone oil1,2. Moreover, the gel remained optically clear, circumventing the visual problems associated with gases and oils.

These preliminary results are undoubtedly promising, but questions remain. Does the authors' low-concentration polymer have the mechanical properties needed for the repair of retinal detachment in model organisms such as pigs or primates, whose retinas are more similar to those of humans in terms of thickness and vascularity? Furthermore, the kinetics of gel disintegration were not studied here, and it would be helpful to know how long the gel can maintain its mechanical stability before it liquefies. Is there a safe method for reversing crosslinking after placement in the eye, or can the gel be easily removed if there are surgical or postoperative complications? It will also be important to determine whether the gel stays clear if blood or proteins are released in the eye, as can happen in people who have diabetic retinopathy or other vascular retinal disorders.

The field of vitreous substitutes has been neglected because safety studies require long periods of time and have low commercial returns. It is refreshing to see Hayashi and colleagues' promising work in this area. It could help the thousands of people globally who develop retinal detachment each year.Footnote 1

Notes

  1. 1.

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References

  1. 1

    Chang, S. in RETINA 4th edn, Vol. 3 (eds Ryan, S., Schachat, A., Wilkinson, C. & Hinton, D.) 2165–2177 (Elsevier Mosby, 2006).

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    Parel, J.-M., Milne, P., Gautier, S., Jallet, V. & Villain, F. in RETINA 4th edn, Vol. 3 (eds Ryan, S., Schachat, A., Wilkinson, C. & Hinton, D.) 2191–2210 (Elsevier Mosby, 2006).

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    Hayashi, K. et al. Nature Biomed. Eng. 1, 0044 (2017).

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    Sandner, D., Herbrig, E. & Engelmann, K. Graefe's Arch. Clin. Exp. Ophthalmol. 245, 1097–1105 (2007).

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Correspondence to Stanley Chang.

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Chang, S. An improved gel for detached retinas. Nature 543, 319–320 (2017). https://doi.org/10.1038/nature21898

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