Complex cases of retinal detachment (RD) are defined by the presence of an RD associated with giant retinal tear, proliferative diabetic retinopathy, viral retinitis, ocular trauma, and proliferative vitreoretinopathy (PVR). These conditions remain a challenge for vitreoretinal surgeons, despite advancements in ophthalmic knowledge and vitreous microsurgical techniques. PVR usually occurs in association with recurrent RD, but occasionally it may be associated with primary RD and may be considered the major complication and the main reason for unsatisfactory anatomical and functional outcomes following RD surgery.¹ Pars plana vitrectomy (PPV), removal of the epiretinal membranes, treatment of the retinal breaks, and injection of a tamponade agent are the standard treatment for RD with PVR. In some cases, a removal of the lens (crystalline lens or intraocular lens) is performed. Intraocular tamponades are useful surgical tools that have improved the prognosis of many vitreoretinal diseases.²

Conventional endotamponades include gases and silicone oils (SOs). The gases currently available are air, sulfur hexafluoride (SF₆), octafluoropropane (C₃F₈) and hexafluroethane (C₂F₆). In clinical use, we currently use 2 classes of silicone oils (SOs): lighter-than-water SOs, which are the most commonly used, and heavier-than-water SOs (heavy SOs). Conventional lighter-than-water SOs include 1,000-centistoke SO and 5,000-centistoke SO composed of 100% poli-dimethyl-siloxane (PDMS) with different viscosity (1,000 and 5,000 centistokes, respectively). They float in the vitreous cavity and are effective in the treatment of RDs, especially with involvement of the superior retinal periphery, which can be supported in the upright position. However, these agents with lighter-than-water specific gravity may not support the entire retina because of the presence of an area of unsupported retina in the upright or supine position. The development of PVR depends on the presence of a mixture of aqueous humor and growth factors (“PVR soup”), which are concentrated in the lower retinal periphery areas that are not covered by the silicone oil tamponade: the PVR soup shifts to the premacular area, increasing the risk of the development of postoperative PVR, premacular epiretinal membranes, and cystoid macular edema.³

HEAVY TAMPONADES

Heavier-than-water intraocular tamponades have an increased density and provide a good endotamponade for both the inferior and the posterior pole in normal head positioning.^4-6 Three groups of heavy tamponades have been introduced into surgical practice: heavy SOs, perfluorocarbon liquids (PFCLs) and semifluorinated alkanes, such as perfluorohexyloctane (F₆H₈). PFCLs include perfluoro-n-octane (C₈F₁₈) and perfluorodecalin (C₁₀F₁₈) and their specific gravity ranges from 1.7 g/cm³ to more than 2.0 g/cm³.

Heavy SOs are Oxane HD (Bausch + Lomb) and Densiron 68 (Labtician Ophthalmics; available outside the United States). They have a specific gravity of 1.02 and 1.06 g/cm³ respectively and are less toxic than PFCLs. A heavy SO is obtained by mixing appropriate amounts of semifluorurate, ether, an alkane, and silicone oil. Densiron 68 (Fluoron Co; available outside the United States) is a solution of perfluorohexyloctane (F₆H₈) and 5,000-centistoke silicone oil. The advantage of this solution is that it increases the viscosity of F₆H₈ from 2.5 to 1,387 millipascal-seconds (mPas), thereby reducing its tendency to disperse.⁷ Densiron 68 was the heavy tamponade of choice in the Heavy Silicone Oil Study (HSO), the first multicenter comparative trial of heavy vs conventional silicone oil tamponades.⁸ Oxane HD is the other heavy SO endotamponade approved for clinical use, and it is a mixture of 5,700-centistoke silicone oil and RMN-3 (a partially fluorinated olefin) with a viscosity of 3,300-3,500 mPas. HSV-45 3000 (Fluoron Co; available outside the United States) is another heavy agent that seems to be well tolerated in treating complicated inferior RD.⁹

Thanks to their heavier-than-water density, heavy oils could be more effective compared to other endotamponades in the treatment of retinal detachments with inferior breaks, PVR, or cases that need retinotomy in the lower periphery. The proliferative mixture of residual aqueous, inflammatory, and RPE cells are displaced away from the lower retina and the posterior pole, with the aim of obtaining a faster and lasting reattachment of the macula. Open communication between the subretinal space/retinal pigment epithelium (RPE) and the preretinal space is interrupted to lower the risks of PVR development and a reopening of the break. Cases of redetachments are likely to occur predominantly in the superior periphery, where they are easier to treat with gas tamponades.¹

The rate of PVR in patients treated with heavy SO is similar to that in PDMS-treated patients, but heavy SO tends to shift the site of PVR to the upper retina above the horizontal meridian. However, in cases of RDs associated with PVR and inferior retinal breaks, the interim analysis of the HSO study, which compared Densiron 68 with conventional silicone oil, reported that, at 12 months, there were no significant differences in the anatomic success rate or visual outcomes between heavy SO tamponades and conventional silicone oil tamponades.¹⁰ In patients affected by complex inferior RDs, no significant differences in anatomic or visual outcomes were reported comparing Oxane HD and conventional silicone oil as tamponades, combined or not with scleral buckling.^11,12

The limit of this study was the small number of patients and the short follow-up. In the case of inferior retinal break that lies just posteriorly to a scleral encircling, silicone oil may not provide a useful tamponade effect, because the bubble does not conform well with the shape of the retinal encircling, facilitating PVR development and retinal detachment recurrence. Despite toxicity problems, some studies have reported beneficial results using PFCLs as short- to medium-term tamponade agents in patients with inferior or complex retinal detachment.^13-15

OUR EXPERIENCE: HEAVY TAMPONADES IN THE MANAGEMENT OF COMPLEX RETINAL DETACHMENT

We evaluated functional outcomes and anatomic reattachment rate of the retina following heavy tamponade removal in complicated cases of RD. A heavy agent provides a good tamponade for the inferior retina, and this overcomes the disadvantage of silicone oil, making it suitable for cases where scleral buckling or vitrectomy with gas or conventional silicone oil tamponade may not be successful.

Of the latest generation of heavier-than-water tamponades, Densiron 68 seems to have more favorable results.^16-19 We reviewed the records of 49 eyes of 49 patients affected by complex inferior RD who underwent PPV at Careggi University Hospital in Florence. All of the patients had undergone only one previous vitreoretinal procedure. We performed 25- or 23-gauge PPV. No encircling buckling was combined. In eyes tamponaded with standard silicone oil in previous surgery, the oil was removed during the surgery; in patients who underwent scleral buckling in previous surgery, the buckling was not removed during surgery. Peripheral vitreous remnants were checked and a shaving vitrectomy was extended when needed. Vital dye (Dual Blue, DORC International; available outside the United States) was injected into the vitreous chamber on the retinal contraction area to evidence epiretinal PVR. Perfluorodecalin (F Decalin; Fluoron Co, available outside the United States) was injected to flatten the retina up to the periphery and stabilize detached retinal movement during PVR peeling. If the retina contraction did not relax sufficiently after the peeling, a retinectomy was performed. In all the cases a 360-degree endolaser was performed. Every case was tamponed with Densiron 68 heavy SO. To remove Densiron 68, a 23-gauge PPV was selected to facilitate the extraction of a heavy tamponade and to avoid the risk that the tamponade sank in the vitreous chamber, with a consequent increase of surgical time. After SO extraction, dyeing of the epiretinal membrane remnants was performed and then laser treatment was applied over any new retinal breaks. Finally, an endotamponade was chosen depending on the retinal status and any additional steps performed during surgery (Figure 1).

The rate of retinal reattachment after first surgery was 61.2% (30 eyes). All redetachment cases underwent vitrectomy, with gas tamponade in 3 cases and standard SO tamponade in 16 cases. The final retinal reattachment rate was 81.6% (40 eyes). All the cases included in our study were very complicated and characterized by PVR (at least grade C1) associated with inferior retinal breaks. The retinal re-attachment rate in our case series is slightly inferior compared with literature which reports a final reattachment rate after 1 or more surgical procedures between 75% and 93%.^5,23

Several complications have been reported due to heavy SO surgery, such as prolonged intraocular inflammation and secondary intraocular pressure (IOP) increase with a possible relation to the emulsification of heavy SO.^20-25 In fact, heavy tamponades have proven to be unsuitable as long-term internal tamponade agents, due to the high rate of associated complications such as early emulsification and development of intraocular inflammation or physical damage to the retina surface. Retinal alterations, such as narrowing of the outer plexiform layer, distortions of photoreceptor outer segments, outer and inner photoreceptor damage, and inflammatory responses due to ischemic effects, have been reported after the use of perfluorocarbon, fluorosilicone, and F₆H₈.^26-27 PFCL toxicity seems to be not primarily due to high specific gravity or chemical impurities, but rather to an inability to dissolve ions. In comparison with PDMS, the use of heavy SO is more frequently associated with inflammatory reactions and increase in IOP in young patients or in the case of ocular trauma. In our experience, we had inflammatory complications in 13 cases (26.5%): emulsion and inflammation in the anterior chamber. In 17 (34.7%) cases we found ocular hypertension with Densiron permanency that needed medical treatment; after Densiron 68 removal, ocular pressure returned to a normal value in 4 cases (23.5%), the remaining 13 cases continued with the medical treatment. No eyes needed incisional glaucoma surgery. Two cases of corneal opacification and 1 case of phthisis occurred. In 6 cases, we had anterior-chamber inflammation and ocular hypertension at the same time. In 1 case, we registered a central vein occlusion during the silicone tamponade.

Heavy SO surgery can obtain satisfying results in complicated surgical cases, but surgeons should always consider potential complications when making the decision to use or to remove heavy SO in complicated retinal surgery.^28-30 The retinal reattachment rate after 1 surgical operation in our case series is slightly inferior compared to the literature; however, we have to consider the complexity of the cases we selected. We usually use Densiron 68 as a second choice for inferior RD recurrence in eyes that have already undergone PPV with gas or standard SO endotamponade, which should contrast upper retinal PVR development. During a second surgery for inferior RD recurrence, Densiron efficiently tamponades the inferior retinal periphery and may lower the risk of PVR in the inferior quadrant, thanks to the displacement of the proliferative mixture of residual aqueous and inflammatory and RPE cells away from the lower retina and the posterior pole to the upper quadrants where a previous endotamponade had been used.

We recently evaluated the short-term tamponade effect of a PFCL in 12 patients affected by a recurrent inferior RD associated with choroidal detachment, previously treated with encircling buckling. The literature, in general, presents an encouraging percentage of primary attachment (69% to 93%). In our patients, we obtained good final results (attachment rate of 91.6%) without inflammation and severe toxicity-related complications and without evidence of retained subretinal PFCL. The choice of using encircling buckling to relax peripheral vitreous and retinal contraction induced an irregularity on the retinal surface that was difficult to tamponade completely using SO. PFCL ensures a better tamponade than heavy SO on irregular retinal surfaces such as those induced by scleral buckling indentation. Keeping the endotamponade in situ for a shorter period has been associated with fewer inflammatory complications, such as tamponade emulsification, increased IOP, or corneal opacities. Also, the surgical time for PFCL removal is faster than heavy SO due to the higher viscosity of the latter.

CONCLUSION

Both endotamponades demonstrate good final anatomical results with no statistically significant difference in inferior RD recurrence complicated by advanced PVR. PFCL shows better results after only 1 surgical intervention and with less inflammatory complications. However, PVR remains the main cause of RD recurrence, and any endotamponade used can only dislocate the area of PVR proliferation; it cannot avoid it. Further studies are needed to confirm our results and to evaluate the use of heavy tamponades in vitreoretinal surgery. RP

REFERENCES

1. Heimann H, Stappler T, Wong D. Heavy tamponade 1: a review of indications, use, and complications. Eye (Lond). 2008;22(10):1342-1359.
2. Rizzo S, Barca F. Vitreous substitute and tamponade substances for microincision vitreoretinal surgery. Dev Ophthalmol. 2014;54:92-101.
3. Wetterqvist C, Wong D, Williams R, Stappler T, Herbert E, Freeburn S. Tamponade efficiency of perfluorohexyloctane and silicone oil solutions in a model eye chamber. Br J Ophthalmol. 2004;88(5):692-696.
4. Wolf S, Schon V, Meier P, Wiedemann P. Silicone oil-RMN3 mixture (“heavy silicone oil”) as internal tamponade for complicated retinal detachment. Retina. 2003;23(3):335-342.
5. Wong D, van Meurs JC, Stappler T et al. A pilot study on the use of a perfluorohexyloctane/silicone oil solution as a heavier than water internal tamponade agent. Br J Ophthalmol. 2005;89(6):662-665.
6. Rizzo S, Genovesi-Ebert F, Belting C, Vento A, Cresti F. A pilot study on the use of silicone oil-RMN3 as heavier- than-water endotamponade agent. Graefes Arch Clin Exp Ophthalmol. 2005;243(11):1153-1157.
7. Kim YK, Gunther B, Meinert H. A new, heavier-than-water silicone oil: a solution of perfluorohexyloctane in polydimethylsiloxane. Eur J Ophthalmol. 2005;15(5):627-637.
8. Joussen AM, Kirchhof B, Schrage N, Ocklenburg C, Hilgers RD; HSO Study Group. Heavy silicone oil versus standard silicone oil as vitreous tamponade in inferior PVR (HSO Study): design issues and implications. Acta Ophthalmol Scand. 2007;85(6):623-630.
9. Rizzo S, Romagnoli MC, Genovesi-Ebert F, Belting C. Surgical results of heavy silicone oil HWS-45 3000 as internal tamponade for inferior retinal detachment with PVR: a pilot study. Graefes Arch Clin Exp Ophthalmol. 2011;249(3):361-367.
10. Joussen AM, Rizzo S, Kirchhof B, Schrage N, Li X, Lente C, Hilgers RD; HSO Study Group. Heavy silicon oil versus standard silicone oil in as vitreous tamponade in inferior PVR (HSO Study): interim analysis. Acta Ophthalmol. 2011:89(6):e483-e489.
11. Wickham L, Tranos P, Hiscott P, Charteris D. The use of silicone oil-RMN3 (Oxane HD) as heavier-than-water internal tamponade in complicated inferior retinal detachment surgery. Graefes Arch Clin Exp Ophthalmol. 2010;248(9):1225-1231.
12. Boscia F, Furino C, Recchimurzo N, Besozzi G, Sborgia G, Sborgia C. Oxane HD vs silicone oil and scleral buckle in retinal detachment with proliferative vitreoretinopathy and inferior retinal breaks. Graefes Arch Clin Exp Ophthalmol. 2008;246(7):943-948.
13. 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.
14. Drury B, Bourke RD. Short-term intraocular tamponade with perfluorocarbon heavy liquid. Br J Ophthalmol. 2011;95(5):694-698.
15. Chang S. Low viscosity liquid fluorochemicals in vitreous surgery. Am J Ophthalmol. 1987;103(1):38-43.
16. Schwartz SG, Flynn HW, Jr, Lee WH, Wang X. Tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy. Cochrane Database Syst Rev. 2014;2:CD006126.
17. Li W, Zheng J, Zheng Q, Wu R, Wang X, Xu M. Clinical complications of Densiron 68 intraocular tamponade for complicated retinal detachment. Eye (Lond). 2010;24(1):21-28.
18. Rizzo S, Genovesi-Ebert F, Vento A, Cresti F, Miniaci S, Romagnoli MC. Heavy silicone oil (Densiron-68) for the treatment of persistent macular holes: Densiron-68 endotamponade for persistent macular holes. Graefes Arch Clin Exp Ophthalmol. 2009;247(11):1471-1476.
19. Romano MR, Stappler T, Marticorena J, et al. Primary vitrectomy with Densiron-68 for rhegmatogenous retinal detachment. Graefes Arch Clin Exp Ophthalmol. 2008;246(11):1541-1546.
20. Herbrig E, Sandner D, Engelmann K. Anatomical and functional results of endotamponade with heavy silicone oil—Densiron 68—in complicated retinal detachment. Ophthalmic Res. 2007;39(4):198-206.
21. Theelen T, Tilanus MAD, Klevering BJ. Intraocular inflammation following endotamponade with high-density silicone oil. Graefes Arch Clin Exp Ophthalmol. 2004;242(7):617-620.
22. Sandner D, Engelmann K. First experiences with high-density silicone oil (Densiron) as an intraocular tamponade in complex retinal detachment. Graefes Arch Clin Exp Ophthalmol. 2006;244(5):609-619.
23. Sandner D, Herbrig E, Engelmann K. High-density silicone oil (Densiron) as a primary intraocular tamponade: 12-month follow up. Graefes Arch Clin Exp Ophthalmol. 2007;245(8):1097-1105.
24. Lappas A, Kirchhof B, Konen W. [Effects of the long-term tamponade with Densiron on the lens]. Klin Monbl Augenheilkd. 2007;224(5):434-437.
25. Cheung BTO, Lai TYY, Yuen CYF, Lai WWK, Tsang CW, Lam DSC. Results of high-density silicone oil as a tamponade agent in macular hole retinal detachment in patients with high myopia. Br J Ophthalmol. 2007;91(6):719-721.
26. Majid MA, Hussin HM, Biswas S, Haynes RJ, Mayer EJ, Dick AD. Emulsification of Densiron-68 used in inferior retinal detachment surgery. Eye (Lond). 2008;22(1):152-157.
27. Doi M, Refojo MF. Histopathology of rabbit eyes with silicone-fluorosilicone copolymer oil as six months internal retinal tamponade. Exp Eye Res. 1995;61(4):469-478.
28. Schatz B, El-Shabrawi Y, Haas A, Langmann G. Adverse side effects with perfluorohexyloctane as a longterm tamponade agent in complicated vitreoretinal surgery. Retina. 2004;24(4):567-573.
29. Russo A, Morescalchi F, Donati S, et al. Heavy and standard silicone oil: intraocular inflammation. Int Ophthalmol. 2018;38(2):855-867.
30. Shwarzer H, Mazinani B, Plange N, Fuest M, Walter P, Roessler G. Clinical observation and occurrence of complications following heavy silicon oil surgery. Biomed Res Int. 2014;2014:706809.