Title: Discussion by Peter Kroll, MD, Lutz Hesse, MD
Abstract: Over time, numerous treatment modalities have been replaced by less invasive procedures. As an example, subretinal hemorrhages are now treated by an intravitreal injection of tissue plasminogen activator and gas instead of mechanical extraction of the clot by a pars plana vitrectomy.1Hesse L Kroll P Successful treatment of acute subretinal hemorrhage in age-related macular degeneration by combined injection of recombinant tissue plasminogen activator and gas.Adv Ther. 1997; 14: 275-280PubMed Google Scholar, 2Hesse L Schmidt J Kroll P Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas.Graefes Arch Clin Exp Ophthalmol. 1999; 237: 273-277Crossref PubMed Scopus (167) Google Scholar, 3Hassan A.S Johnson M.W Schneiderman T.E et al.Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement.Ophthalmology. 1999; 106 (discussion 1906–7): 1900-1906Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar The authors have presented their experience treating proliferative diabetic vitreoretinopathy (PDVR) by intravitreal injection of autologous plasmin enzyme (APE) before vitrectomy. In this disease the vitreous cortex acts as a metabolic barrier and as a scaffold for proliferating cells.4Faulborn J Bowald S Microproliferations in proliferative diabetic retinopathy and their relationship to the vitreous corresponding light and electron microscopic studies.Graefes Arch Clin Exp Ophthalmol. 1985; 223: 130-138Crossref PubMed Scopus (73) Google Scholar Late stages of the disease result from vitreous contractions and subsequent tractional-rhegmatogenous detachment. The rationale of an enzymatic treatment in PDVR is to detach the posterior vitreous cortex. Six patients with a mean follow-up period of 14 months were included. Posterior vitreous detachment was achieved in all APE-treated eyes. In the past, several enzymes have been used to induce a posterior vitreous detachment. Hyaluronidase, collagenase, chondroitinase, dispase, plasmin and tissue plasminogen activator (tPA) were tested in animals (Hageman GS, Russell SR, Invest Ophthalmol Vis Sci 1994;35:1260)5Pirie A Effect of hyaluronidase injection on vitreous humor of the rabbit.Br J Ophthalmol. 1948; 33: 678-684Crossref Scopus (14) Google Scholar, 6O’Neill R Shea M The effects of bacterial collagenase in rabbit vitreous.Can J Ophthalmol. 1973; 8: 366-370Crossref PubMed Scopus (46) Google Scholar, 7Verstraeten T.C Chapman C Hartzer M et al.Pharmacologic induction of posterior vitreous detachment in the rabbit.Arch Ophthalmol. 1993; 111: 849-854Crossref PubMed Scopus (164) Google Scholar, 8Tezel T.H Del Priore L.V Kaplan H.J Posterior vitreous detachment with dispase.Retina. 1998; 18: 7-15Crossref PubMed Google Scholar but only plasmin and tPA, both enzymes of the fibrinolytic process, were applied in humans with more or less success.9Hesse L Chofflet J Kroll P Tissue plasminogen activator as a biochemical adjuvant in vitrectomy for proliferative diabetic vitreoretinopathy.German J Ophthalmol. 1995; 4: 323-327PubMed Google Scholar, 10Hesse L Kroll P Enzymatically induced posterior vitreous detachment in proliferative diabetic vitreoretinopathy.Klin Monatsbl Augenheilkd. 1999; 214: 84-89Crossref PubMed Scopus (29) Google Scholar, 11Le Mer Y Korobelnik J.F Morel C et al.TPA-assisted vitrectomy for proliferative diabetic retinopathy. Results of a double-masked, multicenter trial.Retina. 1999; 19: 378-382Crossref PubMed Scopus (31) Google Scholar, 12Chow D.R Williams G.A Trese M.T et al.Successful closure of traumatic macular holes.Retina. 1999; 19: 405-409Crossref PubMed Google Scholar, 13Trese M.T Williams G.A Hartzer M.K A new approach to stage 3 macular holes.Ophthalmology. 2000; 107 (discussion 1611): 1607-1611Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar The mechanism of plasmin-induced posterior vitreous detachment (PVD) is not completely understood. The internal limiting membrane (ILM) is composed mainly of type-IV collagen, fibronectin, and laminin.14Kohno T Sorgente N Ishibashi T et al.Immunofluorescent studies of fibronectin and laminin in the human eye.Invest Ophthalmol Vis Sci. 1987; 28: 506-514PubMed Google Scholar At present, it is not known which components of the ILM must be dissolved by plasmin to provoke a PVD. Possibly “linker molecules” like lectins, integrins, and chondroitin sulfate responsible for the attachment of the vitreous cortex to the ILM may be the target of an unspecific protease like plasmin. The use of an enzyme immediately before vitrectomy is the most comfortable technique for both patient and surgeon. Plasmin acts immediately after injection, whereas tPA needs some hours to generate plasmin from its precursor plasminogen.10Hesse L Kroll P Enzymatically induced posterior vitreous detachment in proliferative diabetic vitreoretinopathy.Klin Monatsbl Augenheilkd. 1999; 214: 84-89Crossref PubMed Scopus (29) Google Scholar, 15Hesse L Nebeling B Schroeder B et al.Induction of posterior vitreous detachment in rabbit by intravitreal injection of tissue plasminogen activator following cryopexy.Exp Eye Res. 2000; 70: 31-39Crossref PubMed Scopus (69) Google Scholar From these results, we concluded that tPA, in contrast to plasmin, cannot be applied at the beginning of pars plana vitrectomy. This seems to be the significant advantage of plasmin in contrast to tPA. For the resolution of a diabetic macular edema in APE-treated eyes in contrast to non-APE-treated eyes, we still do not have any explanation. In many articles, a regression of diabetic macular edema was observed after removing the posterior vitreous cortex16Harbour J.W Smiddy W.E Flynn Jr, H.W Rubsamen P.E Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane.Am J Ophthalmol. 1996; 121: 405-413Abstract Full Text PDF PubMed Scopus (310) Google Scholar, 17Tachi N Ogino N Vitrectomy for diffuse macular edema in cases of diabetic retinopathy.Am J Ophthalmol. 1996; 122: 258-260Abstract Full Text PDF PubMed Scopus (308) Google Scholar and even the ILM.18Gandorfer A Messmer E.M Ulbig M.W Kampik A Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane.Retina. 2000; 20: 126-133Crossref PubMed Scopus (330) Google Scholar On the basis of our current knowledge, it remains unclear why, after vitrectomy, the macular edema only disappeared in the APE-treated eyes and not as well in the non-APE-treated eyes where a complete vitrectomy had also been performed. A reason could be that remnants of a vitreoschisis in the non-APE-treated eyes were not removed completely during vitrectomy. This may also be the reason for the development of a redetachment in one of the three non-APE-treated eyes. Our current high-tech mechanical instrumentation is wonderful, but the future will most likely belong to biologic treatment modalities like the application of enzymes. In the future surgical intervention in macular holes, macular edema, PVR, PDVR and other disorders may be obsolete, as well as many other of our current indications for pars plana vitrectomy. Particularly in the prevention of many vitreoretinal diseases, enzymatic applications may be helpful to circumvent further surgery.
Publication Year: 2001
Publication Date: 2001-10-01
Language: en
Type: article
Indexed In: ['crossref']
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