Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane.

A 58-year-old female presented with intracameral retained perfluoro-n-octane (PFO) following previous retinal reattachment surgery. After 4 years of follow-up without related sequelae, the patient complained of a gradual decrease in vision secondary to corneal edema with whitish corneal precipitate inferiorly corresponding to the area of retained PFO. Three weeks after anterior chamber washout, corneal edema resolved and the patient obtained 20/40 visual acuity. Even though PFO considered to have a relatively good safety profile, early anterior chamber washout may prevent corneal toxicity and avoid later persistent corneal decompensation.

INTRODUCTION

Perfluorocarbon liquids (PFCLs) are synthetic fluorinated hydrocarbon fluids which were first used in repositioning retinal detachments in 1984 by Zimmerman and Faris. The high specific gravity, low viscosity, optical clarity, and immiscibility in water make PFCLs particularly useful for vitreoretinal surgery. Over time, many PFCLs have been evaluated for vitreoretinal surgery for unfolding and flattening the retina, displacing subretinal fluids anteriorly, and lifting a dropped nucleus from the retinal surface. The most commonly used compounds are perfluorophenanthrene, perfluorodecalin, and perfluoro-n-octane (PFO). PFO has not been previously reported as reversibly toxic to the corneal endothelium.

CASE REPORT

A 58-year-old female presented in February 2010 complaining of a gradual drop in vision in her left eye over 2 weeks. The patient had undergone bilateral cataract surgery with intraocular lens (IOL) implantation a few years before presentation. The right eye was unremarkable with 20/30 vision. The uncorrected visual acuity (UCVA) in the left eye was 4/200. Anterior segment slit-lamp examination of the left eye revealed a clear cornea, deep and quiet anterior chamber, and a mild nasal displacement of the IOL which was implanted in the sulcus due to the presence of posterior capsule rupture. A dilated fundus examination of the left eye indicated a rhegmatogenous retinal detachment with macula-off and horseshoe tear superotemporally.

The patient underwent vitreoretinal surgery of the left eye with an encircling band #41 plus #76 sleeve, pars plana vitrectomy, PFO injection and removal, air-fluid exchange, and perfluoropropane (C3F8) gas 15% flush. At the 1-week postoperative visit, retained PFO was noted to occupy 25% of the anterior chamber in a fish-egg shape. The other examination was unremarkable. We elected to observe the patient. A few weeks later, the UCVA in the left eye was 20/80.

Subsequent postoperative visits documented a stable uneventful course with the retained PFO in the anterior chamber and clear cornea with no signs of ocular inflammation over 4 years. In March 2014, the patient presented to the clinic complaining of a gradual decrease of vision in the left eye over 4 months. On examination, her visual acuity was 20/160 in the left eye and the intraocular pressure was 17 mmHg. The anterior chamber was deep and quiet with inferior corneal edema and whitish deposits on the endothelial surface corresponding to the location of the retained PFO [Figure 1]. PFO washout from the anterior chamber was performed by Simcoe irrigation/aspiration cannula with normal operative course. The postoperative course was uneventful. Three weeks postoperatively, corneal edema resolved and the patient regained UCVA to 20/40.

Figure 1

(a) Perfluoro-n-octane occupying 25% of the left eye anterior chamber with whitish deposits along the inferior endothelial surface (arrow). (b) Left eye specular microscopy showing significant endothelial cell loss, pleomorphism, and polymegathism

DISCUSSION

The safety of PFO has been investigated in a few studies. Elsing et al.1 reported five cases of retained PFO and found that young patients with 0.25 ml or more of retained PFO were probably at higher risk to have whitish proteinaceous deposits and inflammatory responses such as macrophages containing cytoplasmic PFO vacuoles. Abboud and Al-Falah2 reported a case with PFO occupying about 15% of the anterior chamber which was observed for 9 years without signs of corneal toxicity or inflammation.

Loewenstein et al.3 evaluated the safety and efficacy of PFCLs in 264 patients. They3 found a total of 12 eyes (8.4%) with detectable vitreon whereas PFO was detected in five eyes (4%). Postoperative corneal edema developed in approximately 10% of retained perfluorocarbon cases although it was aspirated from the anterior chamber as soon as it was noted.3

This observation indicates that there may be other factors such as the gas or silicone oil as causative agents of the corneal pathology. Scott et al.4 evaluated 555 eyes that underwent pars plana vitrectomy for complex retinal detachments. In their study,47.4% of eyes had retained PFO and this was not a significant factor associated with final visual outcome. Sigler et al.5 concluded that the inflammatory response for the retained PFO consists almost exclusively of macrophages and does not seem to be related to long-term intraocular pressure elevation or poor visual outcome.

Corneal toxicity to other forms of PFCLs has been previously reported. Wilbanks et al.6 reported that four of five eyes with residual perfluorodecalin developed corneal abnormalities (three edema, one deep vascularization with no edema) in the region of PFCL-endothelial contact for 4–13 weeks. Corneal edema resolved after aspiration of PFCL in one case only while other cases required penetrating keratoplasty.6 Cauchi et al.7 reported a case with corneal endothelium cell loss that required corneal grafting. Histopathologic examination of affected cornea showed epithelial edema, deficient Bowman's membrane, intrastromal vascularization with inflammatory cells infiltration, PFCL engulfed in keratocytes and macrophages around the vessels, and marked endothelial cell loss.67 Both papers67 highlighted the necessity to remove the retained residual perfluorodecalin from the anterior chamber to avoid corneal endothelial toxicity and endothelial cell loss.

Experimental studies in animals showed that the retention of high volume of PFCLs in the anterior chamber results in quick endothelial cell damage while amount under 0.025 ml appears to induce no reaction in the corneal endothelium although they cause changes in the trabecular meshwork. In human, PFCLs migrate to the anterior chamber in 22% of cases in both phakic and pseudophakic eyes, in the absence of obvious zonular dehiscence. Anterior chamber inflammatory reaction, damage to the corneal endothelial cells inducing corneal edema and endothelial cell loss, and trabecular meshwork blockage with persistent IOP elevation were noticed in eyes with retained PFCL in the anterior chamber.8 A review done by Georgalas et al.9 on the toxicity of PFCLs showed that the corneal endothelial response to PFCLs was both dose- and time-dependent and it was potentially reversible if residual PFCLs were removed from the anterior chamber in a timely fashion. The cause of PFCLs toxicity is unknown although the combination of impurities, mechanical compression, and chemical effects is an accepted mechanism.

In our patient, a large posterior capsule opening and slight IOL displacement facilitated the flow of PFO from the vitreous cavity into the anterior chamber where it was retained for 4 years. Although endothelial cell loss and edema may have resulted from the previous surgeries, the nature of the edema that disappeared after PFO washout and was occupying the inferior half of the cornea where PFO contacted the endothelium increases the likelihood of toxicity. To the best of our knowledge, PFO has not been previously reported as reversibly toxic to the corneal endothelium. Our case supports the finding of other reports that indicate the ocular toxic effect of retained PFCLs irrelevant to the compound. Although PFO is relatively safe for the cornea compared to other PFCLs, our case showed an endothelial toxic effect with progressive endothelial cell loss and subsequent corneal edema. We stress the importance of complete removal of PFO from the vitreous cavity after vitreoretinal surgery. In cases where inadvertent PFO is retained in the anterior chamber, early removal may prevent corneal toxicity which may eventually occur even years after an uneventful course.

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