WOUND LEAK AFTER INTRAVITREAL INJECTION OF BEVACIZUMAB Sanjeewa S. Wickremasinghe, BSC, MBBS, FRCOPHTH,* Kira Michalova, MD, FRANZCO,† Robyn H. Guymer, RH, MBBS, FRANZCO, PHD,*† C. Alex Harper, MBBS, FRANZCO*†
Purpose: To report an occurrence of wound leak from the injection site after intravitreal injection of bevacizumab. A possible underlying etiology is discussed. Methods: A single injection of bevacizumab was given for treatment of choroidal neovascularization complicating previous choroidal rupture. Results: A reduction in vision and hypotony were noted 1 day after injection. With conservative management, there was spontaneous resolution of the wound leak. Conclusion: The risk of wound leak after intravitreal injection may be higher for younger patients and those who have undergone vitrectomy. All patients and clinicians, however, should be alert to vision decline after injection, and prompt evaluation should be performed to ascertain the cause. For patients with persistent wound leak, surgical intervention may be required. RETINAL CASES & BRIEF REPORTS 2:245–246, 2008
From the *Medical Retina Unit, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; and the †Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
reported worsening vision with “swelling” arising from the area of injection. Visual acuity was 20/60, and intraocular pressure was 4 mmHg. There were retinal folds at the macula but no evidence of retinal or choroidal detachment. There was a Seidel test–positive area as well as a bleb over the injection site (Fig. 1). Topical antibiotic treatment was continued, and the eye was not padded. When evaluated 3 days later, the patient thought that his vision had improved, and the “swelling” had resolved. At examination, visual acuity was 20/30, and intraocular pressure was 10 mmHg. No leak was apparent with 2% fluorescein.
I
ntravitreal injections for treatment of choroidal neovascularization are now common practice. Several complications after intravitreal drug delivery have been reported, including cataract, retinal detachment, and endophthalmitis. We report the development of a wound leak after intravitreal injection of bevacizumab using a 30-gauge needle.
Discussion There is limited literature on wound leaks after 30-gauge injections into the vitreous cavity. A case of a persistent unsealed sclerotomy site, after a single 30-gauge injection of triamcinolone for treatment of diabetic macular edema, was reported.1 The patient had previously undergone pars plana vitrectomy for a nonclearing vitreous hemorrhage and presented with hypotony and chemosis 5 days after injection. Surgical exploration revealed a punctiform scleral wound without vitreous incarceration, which required closure with a 10-0 nylon suture. In another case, a 29-year-old patient with a history of panuveitis who had undergone pars plana vitrectomy for vitreous opacities was given an intravitreal injection of triamcinolone with a 30-gauge needle.2
Case Report A 27-year-old man presented with choroidal neovascularization complicating an old choroidal rupture. Immediately before the injection, visual acuity in the right eye was 20/30, and intraocular pressure was 17 mmHg. An intravitreal injection of 0.05 mL of bevacizumab was given 4 mm behind the superotemporal limbus, using a 30-gauge, 0.5-in needle. The following day, the patient C.A.H. and R.H.G. are on advisory boards of Pfizer and Novartis and have received honoraria, speakers’ fees, research funding, and travel and accommodation payments from either or both companies. Reprint requests: Sanjeewa S. Wickremasinghe, Royal Victorian Eye and Ear Hospital, University of Melbourne, 32 Gisborne Street, East Melbourne 3002, Victoria, Australia; e-mail: [email protected]
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Fig. 1. Color photographs of the anterior segment showing a bleb (A) and a Seidel test–positive area with 2% fluorescein at the injection site (B).
Two days later, the patient was noted to have a choroidal detachment and unrecordable intraocular pressure. Surgical exploration revealed that the 30-gauge incision site was open, with no signs of wound healing. The wound was closed with a 10-0 nylon suture. Finally, the same investigators2 described a further case of persistent open sclerotomy in a 55-year-old man after two separate injections of tissue plasminogen activator and SF6 gas for treatment of a submacular hemorrhage. They made no comment regarding hypotony in their report, and the open wound was discovered only after conjunctival peritomy, before vitrectomy. This patient required excision of the incarcerated vitreous from the sclerotomy site. The cause of the wound leak in the current case is not clear. In two of the three cases described above, the patients had undergone vitrectomy. These patients presented with hypotony. The final case, in which there was an unsealed sclerotomy, was not associated with wound leak, and the open sclerotomy was discovered only at the time of vitrectomy. It has been suggested that vitreous incarceration into the wound may be responsible for keeping wounds open, as in the third case. However, vitreous incarceration has been found in 72% of sclerotomies done at the time of vitrectomy.3 Although, incarceration may lead to trac-
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tion on the vitreous base, there is no evidence that it leads to wound leak. In a study by Lo´pez-Guajardo et al,3 the investigators found no relation between presence of vitreous entrapment and presence of postoperative conjunctival blebs. We therefore speculate that a small degree of vitreous incarceration into the wound, during removal of the needle, may be responsible for keeping small scleral wounds closed. In support of this hypothesis, hypotony was noted only in vitrectomized eyes, even though all previously described patients had open wounds. In our patient, hypotony may have resulted from an absence of vitreous from the wound, due to limited cortical vitreous liquefaction in a young patient. In older patients, persistent wound leak may be less common because there is a progressive increase in the volume of liquefied spaces, as well as the volume of optically dense areas within the vitreous body.4,5 This change may allow the migration of vitreous to the wound, leading to “plugging” of the sclerotomy. An alternative explanation for the wound leak may be the angle of needle entry with respect to the sclera. Oblique entry wounds during port creation for vitrectomy have been shown to be associated with a reduced incidence of “blebs” overlying the entry site.3,6 It is possible that cases of wound leak after intravitreal injection may be due to more perpendicular entry. Our case highlights that, in spite of their simplicity, intravitreal injections are invasive procedures that require clinicians to be alert to symptoms in the initial period after injection. For younger patients and those who have undergone pars plana vitrectomy, a smallergauge needle or an oblique entry through the sclera may reduce the risk of wound leak. Key words: bevacizumab, hypotony, intravitreal injection. References 1.
2.
3.
4.
5. 6.
Gambrelle J, Kodjikian L, Abi-Ayad N, et al. Persistent unsealed sclerotomy after intravitreal injection of triamcinolone acetonide with a 30-gauge needle. J Fr Ophtalmol 2006;29:e22. Rodrigues EB, Meyer CH, Schmidt JC, et al. Unsealed sclerotomy after intravitreal injection with a 30-gauge needle. Retina 2004;24:810–812. Lo´pez-Guajardo L, Vleming-Pinilla E, Pareja-Esteban J, TeusGuezala MA. Ultrasound biomicroscopy study of direct and oblique 25-gauge vitrectomy sclerotomies. Am J Ophthalmol 2007;143:881–883. Los LI, van der Worp RJ, van Luyn MJ, Hooymans JM. Age-related liquefaction of the human vitreous body: LM and TEM evaluation of the role of proteoglycans and collagen. Invest Ophthalmol Vis Sci 2003;44:2828–2833. Sebag J. Ageing of the vitreous. Eye 1987;1:254–262. Rodrigues EB, Meyer CH, Grumann A, et al. Tunneled scleral incision to prevent vitreal reflux after intravitreal injection. Am J Ophthalmol 2007;143:1035–1037.
Purpose: To report an occurrence of wound leak from the injection site after intravitreal injection of bevacizumab. A possible underlying etiology is discussed. Methods: A single injection of bevacizumab was given for treatment of choroidal neovascularization complicating previous choroidal rupture. Results: A reduction in vision and hypotony were noted 1 day after injection. With conservative management, there was spontaneous resolution of the wound leak. Conclusion: The risk of wound leak after intravitreal injection may be higher for younger patients and those who have undergone vitrectomy. All patients and clinicians, however, should be alert to vision decline after injection, and prompt evaluation should be performed to ascertain the cause. For patients with persistent wound leak, surgical intervention may be required. RETINAL CASES & BRIEF REPORTS 2:245–246, 2008
From the *Medical Retina Unit, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; and the †Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
reported worsening vision with “swelling” arising from the area of injection. Visual acuity was 20/60, and intraocular pressure was 4 mmHg. There were retinal folds at the macula but no evidence of retinal or choroidal detachment. There was a Seidel test–positive area as well as a bleb over the injection site (Fig. 1). Topical antibiotic treatment was continued, and the eye was not padded. When evaluated 3 days later, the patient thought that his vision had improved, and the “swelling” had resolved. At examination, visual acuity was 20/30, and intraocular pressure was 10 mmHg. No leak was apparent with 2% fluorescein.
I
ntravitreal injections for treatment of choroidal neovascularization are now common practice. Several complications after intravitreal drug delivery have been reported, including cataract, retinal detachment, and endophthalmitis. We report the development of a wound leak after intravitreal injection of bevacizumab using a 30-gauge needle.
Discussion There is limited literature on wound leaks after 30-gauge injections into the vitreous cavity. A case of a persistent unsealed sclerotomy site, after a single 30-gauge injection of triamcinolone for treatment of diabetic macular edema, was reported.1 The patient had previously undergone pars plana vitrectomy for a nonclearing vitreous hemorrhage and presented with hypotony and chemosis 5 days after injection. Surgical exploration revealed a punctiform scleral wound without vitreous incarceration, which required closure with a 10-0 nylon suture. In another case, a 29-year-old patient with a history of panuveitis who had undergone pars plana vitrectomy for vitreous opacities was given an intravitreal injection of triamcinolone with a 30-gauge needle.2
Case Report A 27-year-old man presented with choroidal neovascularization complicating an old choroidal rupture. Immediately before the injection, visual acuity in the right eye was 20/30, and intraocular pressure was 17 mmHg. An intravitreal injection of 0.05 mL of bevacizumab was given 4 mm behind the superotemporal limbus, using a 30-gauge, 0.5-in needle. The following day, the patient C.A.H. and R.H.G. are on advisory boards of Pfizer and Novartis and have received honoraria, speakers’ fees, research funding, and travel and accommodation payments from either or both companies. Reprint requests: Sanjeewa S. Wickremasinghe, Royal Victorian Eye and Ear Hospital, University of Melbourne, 32 Gisborne Street, East Melbourne 3002, Victoria, Australia; e-mail: [email protected]
245
246
RETINAL CASES & BRIEF REPORTSℜ
Fig. 1. Color photographs of the anterior segment showing a bleb (A) and a Seidel test–positive area with 2% fluorescein at the injection site (B).
Two days later, the patient was noted to have a choroidal detachment and unrecordable intraocular pressure. Surgical exploration revealed that the 30-gauge incision site was open, with no signs of wound healing. The wound was closed with a 10-0 nylon suture. Finally, the same investigators2 described a further case of persistent open sclerotomy in a 55-year-old man after two separate injections of tissue plasminogen activator and SF6 gas for treatment of a submacular hemorrhage. They made no comment regarding hypotony in their report, and the open wound was discovered only after conjunctival peritomy, before vitrectomy. This patient required excision of the incarcerated vitreous from the sclerotomy site. The cause of the wound leak in the current case is not clear. In two of the three cases described above, the patients had undergone vitrectomy. These patients presented with hypotony. The final case, in which there was an unsealed sclerotomy, was not associated with wound leak, and the open sclerotomy was discovered only at the time of vitrectomy. It has been suggested that vitreous incarceration into the wound may be responsible for keeping wounds open, as in the third case. However, vitreous incarceration has been found in 72% of sclerotomies done at the time of vitrectomy.3 Although, incarceration may lead to trac-
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2008
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VOLUME 2
●
NUMBER 3
tion on the vitreous base, there is no evidence that it leads to wound leak. In a study by Lo´pez-Guajardo et al,3 the investigators found no relation between presence of vitreous entrapment and presence of postoperative conjunctival blebs. We therefore speculate that a small degree of vitreous incarceration into the wound, during removal of the needle, may be responsible for keeping small scleral wounds closed. In support of this hypothesis, hypotony was noted only in vitrectomized eyes, even though all previously described patients had open wounds. In our patient, hypotony may have resulted from an absence of vitreous from the wound, due to limited cortical vitreous liquefaction in a young patient. In older patients, persistent wound leak may be less common because there is a progressive increase in the volume of liquefied spaces, as well as the volume of optically dense areas within the vitreous body.4,5 This change may allow the migration of vitreous to the wound, leading to “plugging” of the sclerotomy. An alternative explanation for the wound leak may be the angle of needle entry with respect to the sclera. Oblique entry wounds during port creation for vitrectomy have been shown to be associated with a reduced incidence of “blebs” overlying the entry site.3,6 It is possible that cases of wound leak after intravitreal injection may be due to more perpendicular entry. Our case highlights that, in spite of their simplicity, intravitreal injections are invasive procedures that require clinicians to be alert to symptoms in the initial period after injection. For younger patients and those who have undergone pars plana vitrectomy, a smallergauge needle or an oblique entry through the sclera may reduce the risk of wound leak. Key words: bevacizumab, hypotony, intravitreal injection. References 1.
2.
3.
4.
5. 6.
Gambrelle J, Kodjikian L, Abi-Ayad N, et al. Persistent unsealed sclerotomy after intravitreal injection of triamcinolone acetonide with a 30-gauge needle. J Fr Ophtalmol 2006;29:e22. Rodrigues EB, Meyer CH, Schmidt JC, et al. Unsealed sclerotomy after intravitreal injection with a 30-gauge needle. Retina 2004;24:810–812. Lo´pez-Guajardo L, Vleming-Pinilla E, Pareja-Esteban J, TeusGuezala MA. Ultrasound biomicroscopy study of direct and oblique 25-gauge vitrectomy sclerotomies. Am J Ophthalmol 2007;143:881–883. Los LI, van der Worp RJ, van Luyn MJ, Hooymans JM. Age-related liquefaction of the human vitreous body: LM and TEM evaluation of the role of proteoglycans and collagen. Invest Ophthalmol Vis Sci 2003;44:2828–2833. Sebag J. Ageing of the vitreous. Eye 1987;1:254–262. Rodrigues EB, Meyer CH, Grumann A, et al. Tunneled scleral incision to prevent vitreal reflux after intravitreal injection. Am J Ophthalmol 2007;143:1035–1037.
