The PEG sealant is a water-soluble polyethylene glycol–based synthetic hydrogel sealant. This liquid is polymerized under visible xenon illumination, and becomes a clear, solid, flexible, and firmly adherent hydrogel. In our in vitro study, PEG sealant was easily delivered to a retinal tear with a 27-gauge needle and photopolymerized into a flexible mass. With PEG sealant on the retinal tear, the retina remained attached despite a forceful squirt of BSS.
Cyanoacrylate, a glue that has been evaluated by a number of investigators,
3–5,18–23 is already used to treat retinal disorders in human eyes, such as giant tears caused by perforating injury,
6 proliferative vitreoretinopathy associated with inferior retinal breaks or retinotomy,
7 retinal detachment associated with retinal breaks within a choroidal coloboma,
8,9 recurrent macular holes,
8,10 and breaks after dissection of the preretinal membrane during open-sky vitrectomy in retinopathy of prematurity.
8 However, its rapid polymerization makes application and intraocular delivery extremely difficult, even when mixed with oil, which delays polymerization. Furthermore, cyanoacrylate forms a hard mass rather than a thin sheet or membrane, and is inadequate to cover a large retinal tear. Polyethylene glycol–based synthetic sealant appears more suitable than cyanoacrylate to seal retinal breaks, including large retinal breaks, not only because it is easy to deliver, but also because it forms a flexible, thin sheet rather than a hard mass.
A sodium hyaluronate/carboxymethylcellulose absorbable film (Seprafilm; Genzyme Corporation) is a nontoxic, inert, nonimmunogenic, and biocompatible membrane that adheres strongly to moist tissues. Sueda et al.
24 previously demonstrated that the film adhered well to the retina using bovine eyecups. However, the film needed to be delivered in a dry condition and only a small piece of the film could be placed into the vitreous cavities. This means that film application is difficult when patching peripheral and large breaks, and it is suitable only for small, posteriorly located retinal breaks. On the other hand, with PEG sealant, a single liquid can be easily delivered into the vitreous cavity with a 27-gauge needle. No bulky, heavy instrument, such as a special syringe pump for hydrophobic silicone oil injection, is necessary for intraocular delivery.
Fibrin glue, which is usually refined from bovine blood or from human autologous serum, is less likely to cause a foreign body reaction, but doubts exist as to the adhesive qualities of fibrin in the posterior segment.
11,25 Coleman et al.
12 treated giant retinal tears by applying fibrin glue to the edges of the breaks after vitrectomy; however, none of the giant tears remained closed after surgery because the fibrin glues were effective for only 4 to 6 days. Although TGF-β also sealed retinal breaks, cryotherapy and internal tamponade were still necessary. The TGF-β seems to have the same disadvantage as fibrin glue, namely, temporary adhesion.
13 Polyethylene glycol–based synthetic sealant, developed as a firmly adherent hydrogel that can seal air and fluid leaks in pulmonary resection, seemed to have better adhesive qualities than fibrin glue or TGF-β.
The pH of PEG sealant in BSS was within an acceptable range as an intravitreous solution. The pH of a sodium hyaluronate/carboxymethylcellulose absorbable film in BSS was measured previously with the same modality as in our experiment, and was demonstrated to be within an acceptable range.
24
The ophthalmologic examinations and histological evaluations in our in vivo study revealed that intravitreous PEG sealant injection had no unfavorable inflammatory effect on the eye. The intravitreal injection of PEG sealant was found to have no effect on retinal function, as there was no significant difference in ERG results between the study and control groups. A similar in vivo study with a sodium hyaluronate/carboxymethylcellulose absorbable film was performed by Sueda et al.,
24 and demonstrated no retinal toxicity. Cyanoacrylate, on the other hand, was reported to have significant cytotoxicity and reactivity to the retina.
8–10
Other adhesives
6,14 evaluated for retinopexy were mussel protein and polysiloxanes. Mussel protein adhesive (Cell-Tak; Becton Dickinson, Bedford, MA, USA) caused an inflammatory response.
14 Adhesive polysiloxanes are advantageous in that they can be delivered in an aqueous environment, but cause a localized granulomatous tissue reaction.
6
Among other previously described adhesives with limitations in adhesion, delivery, or safety, polyethylene glycol hydrogel, including PEG sealant, seems to be a better adhesive as a retinal glue. Margalit et al.
25 tested the suitability of some biologic adhesives for ophthalmic use in a study of three polyethylene glycol hydrogels, commercial fibrin sealant, autologous fibrin sealant, mussel adhesive, and three photocurable glues, and proved that hydrogels were superior for intraocular use in terms of consistency, adhesiveness, stability, impermeability, and safety. There were two disadvantages of hydrogels used as retinal glue: one was the need to mix the two components of the glue (one gel and the other liquid) for polymerization,
24 and the other was the long duration required for polymerization, which was 2 to 3 minutes in the previous study.
25 Because of these disadvantages, the application area is limited to the posterior pole of the eye. When applied to peripheral breaks, the liquid descends as the result of gravity from the area of application. Moreover, when liquid glue is applied to retinal breaks, the glue tends to slip under the retina. Sueda et al.
15 partially solved these problems by using a double syringe system and a modification to the DuraSeal dural sealant (Confluent Surgical, Waltham, MA, USA), of which the curing time was 8 to 10 seconds. However, it was still difficult to handle the liquid glue, as they observed a case with glue entering the subretinal space in their experimental retinal detachment surgery.
Polyethylene glycol–based synthetic sealant fundamentally appears to solve the disadvantage of hydrogel, as it is a single liquid and photocurable. Polyethylene glycol–based synthetic sealant is considered to be suitable as a retinal glue as it photopolymerizes with xenon intraocular illumination, which we already use in daily surgery. Because liquid glue is unnecessary for curing the gel, it is less likely for the glue to slip under the retina, and the glue can be applied to the retinal periphery.
At present, the intraocular tamponade materials widely used in clinical practice are gases, perfluorocarbon liquids, and silicone oils. Although they are not sealants, they are hydrophobic materials that have high surface tension with the aqueous humor, and form an interface with the aqueous environment of the eye that can be effective in closing retinal breaks and holding the retina in place against the retinal pigment epithelium. On the other hand, PEG sealant is a hydrophilic material and closes retinal breaks by adhering to the retina. Although these tamponade materials and the PEG sealant are totally different in terms of hydrophobicity and hydrophilicity, they share the characteristic that they interrupt open communication between the subretinal space/RPE cells and the preretinal space. Silicone oils and carbon liquids need to be removed, as they are not soluble materials, but PEG sealant does not need to be removed, as it is water soluble.
This study has several limitations. First, in our in vitro study, we tested the adhesion quality of PEG sealant using cadaveric eyecups, in which the mechanisms of retinal adhesion are significantly impaired and changed overall. Second, we did not detect extensive ERG impairment in our in vivo study, although there was a lack of measurements under photopic conditions and 30-Hz flicker in our ERG examinations. Third, possible retinal toxicity needs to be discussed. In our in vivo study, we tested the unpolymerized form of the PEG sealant rather than the polymerized form. Furthermore, toxicity assessments of retinal contact with PEG sealant will be needed. Long-term follow-up and immunohistochemical analyses, such as glial fibrillary acidic protein, CD68, and Iba1 immunolabeling also will be needed to determine possible toxicity. Further studies are warranted to evaluate the efficacy and safety of PEG sealant as a retinal break sealing material by performing vitreous surgery for experimental retinal detachment using animals. The experiment should contain the following procedure: (1) making an experimental retinal detachment with a break during vitrectomy; (2) after performing fluid-air exchange, apply PEG sealant to cover the retinal breaks; and (3) perform air-fluid exchange and finish the operation without intraocular tamponade. It also needs to be confirmed that no sealant-related mechanical complication occurs, as PEG sealant swells after being polymerized from water absorption.
Polyethylene glycol–based synthetic sealant appeared to effectively seal retinal breaks and was not toxic to the eye. Polyethylene glycol–based synthetic sealant has the potential to be used as a material for sealing retinal breaks.