MILESTONES IN RETINA

Expert perspectives on the evolution of retina practice, procedures, technologies and instrumentation.

MILESTONE

PFO Liquid

Daniel J. Oh, MD; Royce W.S. Chen, MD; Stanley Chang, MD

The seminal work in the 1980s on the development of perfluorocarbon liquid (PFCL) was a milestone in vitreoretinal surgery. With much of the pioneering work led by Dr. Stanley Chang, PFCL has continued to serve as an invaluable tool to repair retinal detachments and thus the treatment of incalculable patients across the globe.

Stanley Chang, MD

PFCL’s properties are uniquely developed for the very function it serves: to “squeegee” subretinal fluid in retinal detachments from existing breaks or large tears and to provide excellent visibility for the application of intraoperative photocoagulation. As such, PFCL is optically clear, with an index of refraction slightly different from saline. It does not absorb the wavelengths used in the lasers for photocoagulation, thus there is no risk of intraocular vaporization. PFCL is more dense than water, with a specific gravity between 1.7 and 2.3 g/cm[3]. Other properties include immiscibility with water, blood, and silicone oil, high internal surface tension, and a boiling point higher than that of water[1]. For the vitreoretinal surgeon, each characteristic is relevant when utilizing PFCL for its purpose of stabilizing the retina in cases of giant retinal tears, proliferative vitreoretinopathy, intraocular foreign body, floating a dislocated intraocular lens or crystalline lens, or evacuating hemorrhage from the subretinal or suprachoroidal space[9,10].

The first use of PFCLs in medicine was from Dr. Leland Clark, Jr. and Dr. Frank Gollan in 1966. PFCL was found to have a capacity to carry oxygen and was developed as a blood substitute. However, its use in retina began in the 1980s. Intraocular gases were already in existence before the advent of PFCL. Dr. Edward Norton at the Bascom Palmer Eye Institute, was a specialist in giant retinal tears and gave his Jackson lecture on using sulfur hexafluoride (SF6) to treat giant retinal tears, specifically by applying cryotherapy and then rolling a small expansile gas bubble under the giant tear to unfold it. The patient would promptly be placed in prone position and the success rates were reportedly quite high even before the advent of vitrectomy. In the early 1980s, perfluorocarbon gases were being utilized by Dr. Harvey Lincoff which were longer lasting than SF[6]. Around that time, many people were also considering that some sort of heavy liquid would be useful for vitrectomy, for fixing retinal detachments and treating PVR, by flattening out the retina at the time of surgery. Viscoelastics and fluorosilicone were being trialed. Dr. Chang and Dr. Neal Zimmerman considered the use of PFCL for retinal detachment surgery as a tamponade agent. From the experience of developing perfluorocarbon gases, such substances were known to be inert. After several hundred surgeries on rabbit eyes using heavier-than-water PFCLs, it became apparent that PFCLs could immediately flatten iatrogenic retinal detachments. Dr. Chang collaborated with Dr. Janet Sparrow, a post-doctoral fellow at Rockefeller University, who performed tissue culture studies to evaluate the properties of various PFCLs. Another important member of the team was Dr. Takeo Iwamoto who studied the pathology of the rabbit and pig eyes after injection with PFCLs. Initially, with impure PFCLs, the rabbit eyes were found to have irregularly shaped defects in the outer segment of photoreceptors as early as two days[2]. Dr. William Miller, a renowned fluorine chemist, was consulted to help purify the PFCLs. With more pure PFCLs, there was less inflammation in the rabbit eyes. 

Edward W.D. Norton, MD, courtesy of Harry T. Flynn, Jr., MD, FASRS

Dr. Chang broadened the consideration of PFCL’s use not merely as a tamponade agent but rather as an intraoperative tool that could flatten the retina and be taken out at the end of surgery to be replaced with a longer-acting tamponade, such as gas or silicone oil. Several kinds of PFCLs have been applied in different countries. Perfluoro-octane (PFO) is now most commonly used. 

Dr. Chang recounted his first use of PFO with Dr. Lincoff: “There was a teenage girl with a 270-degree giant tear. Harvey Lincoff wanted to see how I used retinal tacks, so we started with the vitrectomy. When I placed a tack, it bled profusely from the RPE – after the blood cleared, it was clear the retina was still very detached. I was worried about putting another tack in. Harvey suggested putting in fluorosilicone, but I told him I had another substance that was very pure. I placed the PFO, and it blew our minds away how great it worked. The retina flattened, and we placed C3F8 gas. Harvey was amazed, and it was a pretty awesome moment. Unfortunately, the operation ultimately failed because of aggressive PVR, but this was the start, and after that we got an IRB for using PFO in advanced PVR cases. These patients did well, and this study made up our first reported case series.” 

Harvey A. Lincoff, MD, courtesy of Norah Lincoff, MD

A previous patent for PFCLs was obtained by Dr. Clark as a blood substitute. Notably, he was a chemist who himself had a retinal detachment. Through Cornell University, a patent was written for the use of PFCLs in treating complex retinal detachments to get the company Phamacia interested in licensing the patent. After 12 months of negotiations, the company decided against it. Ultimately, two British chemists, Dr. Nigel Simpson and David Slinn, split off the technology from their fluorine chemistry company to form their own company, FluoroSystems, in a home laboratory.  Another small company, Infinitech, licensed the patent from Cornell, bottled PFCLs and sterilized it for market. A successful clinical trial was organized that ended with FDA approval in 1997.  Once approved, Infinitech and FluoroSystems were both acquired by Alcon.

PFO changed the management of complex detachments involving proliferative vitreoretinopathy (PVR)7 as membrane peeling was initially done anteriorly to open up the periphery and membranes were thus peeled front-to-back. PFO allowed the reverse maneuver, peeling and dissecting from back-to-front which was possible as the PFO could stabilize and flatten the retina[3]. PFO also allows opening of the funnel retina, as a result of PVR membranes, to visualize the proliferative membranes for removal. It became clear that PFO allowed for the more complete removal of PVR membranes. 

For rhegmatogenous retinal detachments, the use of PFO has helped avoid the creation of an iatrogenic drainage retinotomy[7] and prevention of macular folds. For giant retinal tears, the success rate of retina attachment was greater than 90% with the use of PFCL[4]

PFCL has been used to float intraocular and crystalline lens to prevent iatrogenic retinal damage from the maneuvers needed to mobilize the lens10. In addition, a similar principle has been used for the removal of intraocular foreign bodies, while preventing iatrogenic retinal breaks and migration of subretinal hemorrhage10. It is difficult to imagine, but there was a time when PFCL did not exist. Surgeons would operate on patients strapped upside-down in a modified Stryker bed developed by Dr. Robert Machemer. Today, despite its introduction over 30 years ago, PFCL remains a true and tried adjunct in the treatment of complex retinal detachments. 

References:

  1. Chang S. Low viscosity liquid fluorochemicals in vitreous surgery. Am J Ophthalmol. 1987;103(1):38-43. 
  2. Chang S, Zimmerman NJ, Iwamoto T, Ortiz R, Faris D. Experimental vitreous replacement with perfluorotributylamine. Am J Ophthalmol. 1987;103(1):29-37
  3. Chang S, Ozmert E, Zimmerman NJ. Intraoperative perfluorocarbon liquids in the management of proliferative vitreoretinopathy. Am J Ophthalmol. 1988;106(6):668-674.
  4. Chang S, Lincoff H, Zimmerman NJ, Fuchs W. Giant retinal tears. Surgical techniques and results using perfluorocarbon liquids. Arch Ophthalmol. 1989;107(5):761-766.
  5. Chang S. Perfluorocarbon liquids in vitreoretinal surgery. Int Ophthalmol Clin. 1992;32(2):153-163.
  6. Chang S, Reppucci V, Zimmerman NJ, Heinemann MH, Coleman DJ. Perfluorocarbon liquids in the management of traumatic retinal detachments. Ophthalmology. 1989;96(6):785-791; discussion 791-792.
  7. Comaratta MR, Chang S. Perfluorocarbon liquids in the management of complicated retinal detachments. Curr Opin Ophthalmol. 1991;2(3):291-298.
  8. Georgalas I, Ladas I, Tservakis I, et al. Perfluorocarbon liquids in vitreoretinal surgery: a review of applications and toxicity. Cutan Ocul Toxicol. 2011;30(4):251-262.
  9. Peyman GA, Schulman JA, Sullivan B. Perfluorocarbon liquids in ophthalmology. Surv Ophthalmol. 1995;39(5):375-395.
  10. Yu Q, Liu K, Su L, Xia X, Xu X. Perfluorocarbon liquid: its application in vitreoretinal surgery and related ocular inflammation. Biomed Res Int. 2014;2014:250323.

Published 9.2021