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The immortal Ologen: persisting 10 years after trabeculectomy

Published:April 30, 2019DOI:https://doi.org/10.1016/j.jcjo.2019.03.004
      The surgical management of glaucoma has been evolving over the past few decades. In an attempt to improve the results of trabeculectomy, a number of modifications have been tried, of which Ologen (Aeon Astron, Leiden, The Netherlands) is one adjunct.
      • Sawchyn A.K.
      • Slabaugh M.A.
      Innovations and adaptations in trabeculectomy.
      • Zelefsky J.R.
      • Hsu W.-C.
      • Ritch R.
      Biodegradable collagen matrix implant for trabeculectomy.
      Ologen is being extensively used for filtering surgeries and is known to undergo complete biodegradation within 90–180 days of implantation.
      • He M.
      • Wang W.
      • Zhang X.
      • Huang W.
      Ologen implant versus mitomycin C for trabeculectomy: a systematic review and meta-analysis.
      We report a case of trabeculectomy failure in both eyes (BE) of a patient who had undergone augmented trabeculectomy with Ologen, which was seen to be retained for 10 years postsurgery.
      A 33-year-old male patient with juvenile-onset primary open-angle glaucoma presented to us. There was no family history of glaucoma and the patient had no known systemic illness. His records revealed that he presented in 2008 with baseline intraocular pressures (IOP) of 32 and 36 mm Hg, pachymetry of 456µ and 469µ, open angles on gonioscopy, and cup-to-disc ratio (CDR) of 0.7:1 and 0.75:1 in the right eye (RE) and left eye (LE), respectively. In the same year he underwent trabeculectomy of BE augmented with subconjunctival 0.04% mitomycin-C (MMC)–soaked sponge for 2 minutes, and adjuvant subscleral and subconjunctival Ologen placement, LE followed by the RE. The postoperative course was uneventful, with an IOP of 12 mm Hg BE when discharged. The patient was subsequently lost to follow-up.
      He returned to us in 2018 with an IOP of 26 mm Hg in RE and 18 mm Hg in LE on no medications and BE CDR 0.9:1. There had been a progression of the glaucomatous optic neuropathy since his initial surgery. His visual acuity was 6/9 BE and slit-lamp examination showed bilateral solid-appearing superior blebs that were well elevated and distinctly demarcated, and contained hardly any cystic component, which was confirmed on ultrasound biomicroscopy (UBM, 35 MHz, 60 dB gain) (Vumax; Sonomed Escalon, New York, NY) of BE (Fig. 1A–C). As this was unusual and correlated with the patient's past records, we suspected the persistence of Ologen. On gonioscopy, we also found a fibrillar matrix–like structure protruding from patent ostium in both eyes, probably the remnant subscleral Ologen (Fig. 1D). We started him on topical glaucoma medications in both eyes. On a 3-hourly diurnal evaluation of IOP done 6 weeks after usage of topical timolol maleate BE and additional travoprost and brinzolamide in the RE, the IOP ranged from 18 to 28 in the RE and 14 to 18 in LE. Having noted structural progression and failure to achieve target IOP in the RE, we decided to proceed with repeat trabeculectomy augmented with MMC for RE.
      Fig 1
      Fig. 1(A, B) Slit-lamp biomicroscopic diffuse illumination photographs showing the well-circumscribed, discrete, solid-appearing blebs containing retained subconjunctival Ologen of right and left eye, respectively. (C) Ultrasound biomicroscopy photograph (35 MHz, 60 dB gain) of the bleb showing subconjunctival uniform high reflectivity and micropores with hardly any cystic spaces. A patent ostium and protruding subscleral Ologen is also prominent. (D) Indirect gonioscopic photograph showing the superior angle with protruding subscleral Ologen through the patent trabeculectomy ostium.
      Under peribulbar block, the eye was cleaned and draped. A 6-0 polygalactan corneal traction suture was passed for visualization of the surgical field. The superior conjunctiva was incised posterior to the pre-existing bleb and peritomy done, which exposed the solid, discrete, nondegraded Ologen (Fig. 2). It was dissected and separated from the scleral bed in-toto using a crescent blade, and the sample was sent for histopathological evaluation. This was followed by subconjunctival application of 0.02% MMC-soaked sponge for 2 minutes, after which a partial-thickness scleral flap was subsequently raised. The scleral bed was scarred, and we removed the remnants of the subscleral Ologen. While lifting the flap, the patent ostium was identified. Without any further manipulation, the sclera flap was sutured with 10-0 polygalactan and conjunctiva closed with 8-0 polygalactan.
      Fig 2
      Fig. 2Intra-operative photograph exposing the discrete, solid, nondegraded Ologen after peritomy at the bleb site.
      On postoperative day 1, the bleb was well formed and diffuse, with an IOP of 14 mm Hg. Four weeks postoperatively, the bleb remained diffuse with an IOP of 10 mm Hg (Fig. 3). The histopathology revealed invasion of few fibroblasts amidst the fibres of the collagen implant peripherally (Fig. 4).
      Fig 3
      Fig. 3Four weeks postoperative slit-lamp photograph showing the bleb to be diffuse and moderately elevated.
      Fig 4
      Fig. 4Histopathology image (haematoxylin and eosin stain, 40 × magnification) showing collagen (Ologen) invaded by patient's fibroblasts (black arrows).
      Ologen is a bioengineered 3-dimensional matrix made of lyophilized porcine collagen and glycosaminoglycans. It is usually cylindrical in shape, measuring 4 × 7 mm and porous in structure, with pore size ranging from 20 to 200 µm, letting it act as an effective spacer as well as an aqueous reservoir in the short-term, and more importantly, as a scaffold to guide fibroblast ingrowth, inducing a controlled, well-organized healing with minimal scarring in the long-term.
      • Yuan F.
      • Li L.
      • Chen X.
      • Yan X.
      • Wang L.
      Biodegradable 3D-porous collagen matrix (Ologen) compared with mitomycin C for treatment of primary open-angle glaucoma: results at 5 years.
      Biodegradable scaffolds have the property of forming structures close to the normal.
      • Zelefsky J.R.
      • Hsu W.-C.
      • Ritch R.
      Biodegradable collagen matrix implant for trabeculectomy.
      Therefore, when Ologen implants undergo biodegradation, they leave behind a diffuse, elevated, uniform, mature bleb.
      • Yuan F.
      • Li L.
      • Chen X.
      • Yan X.
      • Wang L.
      Biodegradable 3D-porous collagen matrix (Ologen) compared with mitomycin C for treatment of primary open-angle glaucoma: results at 5 years.
      A recent meta-analysis concluded that Ologen implants are comparable to MMC in improving the success of trabeculectomy, in terms of IOP reduction and tolerability.
      • He M.
      • Wang W.
      • Zhang X.
      • Huang W.
      Ologen implant versus mitomycin C for trabeculectomy: a systematic review and meta-analysis.
      Recent studies have also shown equivalent safety profile between MMC and Ologen-augmented trabeculectomies.
      • Cillino S.
      • Casuccio A.
      • Di Pace F.
      • Cagini C.
      • Ferraro L.L.
      • Cillino G.
      Biodegradable collagen matrix implant versus mitomycin-C in trabeculectomy: five-year follow-up.
      Although Ologen implants are known to disappear within 180 days of implantation, we have anecdotally seen the presence of Ologen for up to 1 year. An anterior segment optical coherence tomography study showed that, at 90 days of implantation, 39% of the blebs still showed some evidence of Ologen on imaging.
      • Boey P.-Y.
      • Narayanaswamy A.
      • Zheng C.
      • et al.
      Imaging of blebs after phacotrabeculectomy with Ologen collagen matrix implants.
      However, there have been no reports in literature of Ologen retention beyond 180 days. The implanted Ologen is supposed to undergo a complex enzymatic degradation by in vivo physiological proteases such as the collagenases present at the local site.
      • Song M.
      • Lee S.
      • Choe D.
      • Kim S.
      • Roh Y.H.
      • Rho S.
      Clinical and biological evaluations of biodegradable collagen matrices for glaucoma drainage device implantation.
      The reason for the absence of biodegradation of Ologen in our patient is a matter of curiosity, unresolved at present. Occurrence of bleb encapsulation and formation of “ring of steel” when MMC-soaked Ologen implants were used is known, and is hypothesized due to prolonged localized effect of MMC and resultant excessive fibroblast proliferation in the surrounding.
      • Cillino S.
      • Casuccio A.
      • Di Pace F.
      • Cagini C.
      • Ferraro L.L.
      • Cillino G.
      Biodegradable collagen matrix implant versus mitomycin-C in trabeculectomy: five-year follow-up.
      • Min J.K.
      • Kee C.W.
      • Sohn S.W.
      • Lee H.J.
      • Woo J.M.
      • Yim J.H.
      Surgical outcome of mitomycin C-soaked collagen matrix implant in trabeculectomy.
      However, persistence of Ologen was not noted in these studies. Subconjunctival hyperblastosis with Ologen has been noted in animal studies in the short-term.
      • Niu W.
      • Shen G.
      • Yuan Y.
      • et al.
      Biodegradable PTLGA terpolymers versus collagen implants used as an adjuvant in trabeculectomy in rabbit eye.
      Ologen, by acting as a space-occupying lesion and possibly inducing localization of the bleb, could also be postulated to result in outflow resistance and bleb failure. On removal of the Ologen and revising trabeculectomy, a diffuse low-lying bleb had formed, achieving the desired control of IOP. Hence, one must consider that retention of Ologen itself could be contributory to bleb failure.

      Footnotes and Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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