Intraoperative use of GenTeal gel linked to subconjunctival necrotizing granulomata

July 15, 2017

A study of 11 patients who developed postoperative subconjunctival necrotizing granulomata after ophthalmologic surgical procedures involving large conjunctival incisions indicates an association between intraoperative use of GenTeal gel and the development of postoperative subconjunctival necrotizing granulomata, potentially related to retained subconjunctival Carbopol 980.

"Topical ophthalmic lubricants containing hydroxypropyl methylcellulose are commonly used to maintain corneal clarity during vitreoretinal surgical procedures," says Andrew J. Barkmeier, M.D., Ophthalmology, at Mayo Clinic's campus in Rochester, Minnesota. "GenTeal gel has been increasingly used for this purpose because of its ability to maintain corneal clarity."

GenTeal contains both hydroxypropyl methylcellulose, a hydrophilic polymer that forms a viscous hydrogel, and Carbopol 980 as a thickener. "Biocompatibility studies of highly cross-linked, polyacrylic acid polymers have found that these compounds may stimulate chronic inflammation and macrophage infiltration. Intraoperative exposure to a similar high molecular weight polyacrylic acid polymer, Carbopol 934, has been associated with nonhealing, disfiguring lipoplasty wounds characterized by palisading necrotizing granulomata on histopathology," says Dr. Barkmeier.

Dr. Barkmeier and Raymond Iezzi, M.D., Ophthalmology, at Mayo Clinic's campus in Minnesota, performed all vitreoretinal surgeries for patients involved in the study between 2010 and 2015. Clinical and histopathologic features of study participants include:

  • 10 of the 11 affected patients had a 360-degree conjunctival peritomy. The remaining patient had a 4 × 4 millimeter (mm) conjunctival cutdown to supplement retrobulbar anesthesia.
  • Single surgery anatomic success was achieved for all patients with respect to the initial surgical indication.
  • Mean age of the patients at initial surgery was 52 ± 13 years.
  • Best-corrected visual acuity was 20/191 preoperatively and 20/60 at last follow-up.
  • Diffuse multifocal yellow elevated subconjunctival lesions were noted in all patients who had 360-degree conjunctival peritomy incisions. The remaining patient had a single large granulomata at the site of a 4-mm conjunctival cutdown incision.
  • A total of six lesional biopsies were performed on three patients. One patient required scleral buckling explantation owing to persistent postoperative discomfort.

All biopsy specimens shared similar histopathologic features with palisading histiocytic reactions surrounding areas of necrosis. Histochemical stains for microorganisms were negative. There was no growth from bacterial, fungal or mycobacterial cultures. The research team performed multiple investigations looking for other potential causes of granulomatous inflammation, including microbial cultures and mass spectrometry studies of surgical gloves, suture materials and scleral buckling components, but results were unrevealing.

No patient experienced significant clinical progression after diagnosis, but persistent granulomata were visible at last follow-up for all patients. Eight patients required topical corticosteroid therapy beyond the standard postoperative regimen to control inflammation and discomfort, and three of the eight required a continued, indefinite course of topical anti-inflammatory management.

"Our research team did not identify any postoperative subconjunctival granulomata over the same time frame after procedures in which Goniosol or Balanced Sterile Saline Solution was used to maintain corneal clarity," says Dr. Barkmeier, "or in patients who underwent transconjunctival microincision vitrectomy surgery procedures without conjunctival cutdown incisions, with or without the use of GenTeal gel. None of the affected patients had a known systemic condition associated with necrotizing granulomatous inflammation.

"Although direct causality cannot be established by this retrospective investigation alone, ongoing animal studies appear to support the hypothesis."

Recommendations

"When larger conjunctival incisions are required, surgeons should consider either avoiding the use of intraoperative GenTeal gel or performing an extensive ocular surface irrigation before conjunctival closure," says Dr. Barkmeier. "In clinical practice, prior intraoperative exposure to high molecular weight, cross-linked polyacrylic acid polymers should be considered in the differential diagnosis for patients presenting with subconjunctival granulomatous inflammation."

Study results were published in Ophthalmology in 2016.

For more information

Dalvin LA, et al. Necrotizing subconjunctival granulomata and intraoperative use of topical GenTeal gel. Ophthalmology. 2016;123:2262.