HYPHEMA AFTER INTRAVITREAL INJECTION OF RANIBIZUMAB OR BEVACIZUMAB Tushar M. Ranchod, MD, Mark K. Walsh, MD, PhD, Antonio Capone, Jr., MD, Tarek S. Hassan, MD, George A. Williams, MD
Background: Exudative age-related macular degeneration is commonly treated with intravitreal injection of medications containing antibodies against vascular endothelial growth factors, including ranibizumab (Lucentis, Genentech, South San Francisco, CA) and bevacizumab (Avastin, Genentech). To the best of our knowledge, hyphema has not previously been reported as a complication of intravitreal injection of ranibizumab or bevacizumab. Methods: Retrospective case series. Results: Three patients developed hyphema after intravitreal injection of anti-vascular endothelial growth factor medications: one after ranibizumab and two after bevacizumab. Two patients were pseudophakic and taking warfarin in combination with low-dose aspirin, and one was phakic and not taking any coagulation-altering medications. A total of 26,184 intravitreal injections of ranibizumab or bevacizumab were given during the study period, for an estimated incidence of hyphema after intravitreal injection of approximately 1 in 10,000. Conclusion: The authors describe hyphema, either gross or microscopic, as a complication of intravitreal injection of anti-vascular endothelial growth factor medications. In all three patients, best-corrected vision returned to baseline after resolution of the hyphema and subsequent injections occurred without complication. RETINAL CASES & BRIEF REPORTS 5:87–90, 2011
ocular inflammatory reactions have been documented after ranibizumab and bevacizumab injections, and published reports have documented cases of ocular hypertension, vitreous hemorrhage, central retinal artery occlusion, and retinal ischemia.3–6 All these complications occur at a rate of less than 0.1%. Patients with AMD may also experience new subretinal hemorrhages or rips of the retinal pigment epithelium after intravitreal injection of anti-vascular endothelial growth factor medications.5 We report a series of three patients who developed hyphema after intravitreal injection of ranibizumab or bevacizumab. Hyphema has not previously been described in the medical literature as a complication of intravitreal injection of either medication.
From the Associated Retinal Consultants, Royal Oak, Michigan.
A
ge-related macular degeneration (AMD) is one of the leading causes of blindness in elderly adults in the United States.1 The exudative form of AMD is commonly treated with intravitreal injections of ranibizumab (Lucentis, Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech), which consist of antibody fragments and monoclonal antibodies to vascular endothelial growth factor, respectively.2 Ocular complications of intravitreal ranibizumab or bevacizumab injection are rare and include endophthalmitis and retinal detachment, both of which are presumably due to the intravitreal injection rather than the specific medication injected.3 Noninfectious
Material and Methods
Neither of the authors have a conflict of interest or financial disclosures relevant to this study, nor was any funding provided for this study. Reprint requests: Tushar M. Ranchod, MD, 3535 W, 13 Mile Rd, Ste 344, Royal Oak, MI 48073; e-mail: [email protected]
Retrospective Case Series A search was conducted of our practice billing database for patients diagnosed with hyphema after 87
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intravitreal injection with either ranibizumab or bevacizumab for any indication between August 1, 2007, and July 31, 2009. A total of 26,184 intravitreal injections of ranibizumab or bevacizumab were given during the study period (18,804 ranibizumab injections and 7380 bevacizumab injections). Three cases of hyphema were identified. All three patients received intravitreal injections for treatment of exudative AMD after application of topical proparacaine, subconjunctival 2% lidocaine, and topical 10% povidone–iodine solution. A lid speculum was used in all cases, and injections were delivered with a 30-gauge needle approximately 3.5 mm posterior to the limbus in either the superotemporal or inferotemporal quadrant. Topical antibiotics (fourth-generation fluoroquinolones) were applied immediately after injection and then prescribed for use at least 3 times daily for 3 days subsequently.
Best-corrected visual acuity was 20/60 in the right eye and 20/20 in the left eye. Intraocular pressures were 11 mmHg in both eyes and 15 mmHg in the left eye. Pupils, motility, external examination, and visual fields to confrontation were normal bilaterally. Anterior segment examination was notable only for 2+ nuclear sclerotic cataracts bilaterally. Dilated fundus examination revealed trace subretinal hemorrhage adjacent to an atrophic scar in the right eye and a large nonexudative atrophic scar in the left eye. Fluorescein angiography revealed choroidal neovascularization in the right eye. Bevacizumab was injected intravitreally in the right eye. Three days after injection, the patient presented with a complaint of pain the evening after her injection, which subsided somewhat over the following days, as well as more difficulty reading than before her injection. Best-corrected visual acuity in both the eyes was 20/200, and the intraocular pressure was 10. Anterior segment examination was notable for quiet conjunctiva, 3+ red blood cells in the anterior chamber. No vitreous cell was present. The patient was started on atropine 1% eyedrops twice daily in the right eye. Subsequent examinations demonstrated resolution of the microhyphema over a 4-day period with improvement of best-corrected visual acuity to 20/80. The patient subsequently received two more intravitreal injections of bevacizumab and had improvement of visual acuity to 20/60 in both eyes without any complications.
Case 1 An 81-year-old white man presented with decreased vision in his left eye. Ocular history was notable only for cataract surgery both eyes 5 years prior. Medical history was notable for hypertension, hypercholesterolemia, myocardial infarction, abdominal aortic aneurysm repair, femoral artery bypass surgery, benign prostatic hypertrophy, and gout. Medications included warfarin, low-dose aspirin, pentoxifylline, metoprolol, terazosin, simvastatin, amlodipine, colchicine, and furosemide. Best-corrected visual acuity was 20/30 OD and 20/40 OS. Intraocular pressures were 15 mmHg both eyes and 16 mmHg in the left eye. Pupils, motility, external examination, and visual fields to confrontation were normal bilaterally. Anterior segment examination was notable only for posterior chamber intraocular lenses bilaterally. Dilated fundus examination revealed drusen and pigmentary changes in the right macula and subretinal fluid with hemorrhage in the left subfoveal region. Fluorescein angiography confirmed subfoveal choroidal neovascularization in the left eye. Ranibizumab was injected intravitreally into the left eye. The patient was seen 1 week after intravitreal injection at a scheduled visit with no subjective complaints at that time. Bestcorrected visual acuity was 20/25 left eye, and the intraocular pressure was 13. Anterior segment examination was notable for quiet conjunctiva, 2+ red blood cells in the anterior chamber and trace red blood cells on the anterior lens capsule inferiorly. No vitreous cells were present either anteriorly or posteriorly. The anterior chamber was quiet at the next follow-up visit 3 weeks later with visual acuity remaining 20/25, and the patient received a subsequent intravitreal injection of ranibizumab without incident.
Case 2 A 77-year-old white woman presented for follow-up of exudative AMD in the right eye and nonexudative AMD in the left eye. Her ocular history included 4 intravitreal injections of pegaptanib sodium (Macugen; [OSI] Eyetech, New York, NY), 4 intravitreal injections of bevacizumab, and 18 previous intravitreal injections of ranibizumab, all in the right eye over a 3-year period. Medical history was notable for hypertension, hypercholesterolemia, and arthritis. Medications included simvastatin and lisinopril.
Case 3 An 85-year-old white woman presented for follow-up of bilateral exudative AMD. Ocular history was notable for cataract surgery bilaterally as well as verteporfin photodynamic therapy combined with intravitreal triamcinolone acetonide (Kenalog 40; BristolMyers Squibb, Princeton, NJ) in the right eye, one intravitreal bevacizumab and four intravitreal ranibizumab injections in the right eye. The left eye had previously received seven intravitreal injections of ranibizumab. Medical history included hypertension, arthritis, coronary artery disease with stent placement 8 years before, and colon cancer in remission for 10 years. Medications included warfarin, low-dose aspirin, quinapril, nifedipine, and simvastatin. Best-corrected visual acuity was 20/400 in both eyes (decreased from 20/200 the previous month) and 20/40 in the left eye. Intraocular pressures were 14 mmHg in both eyes. Pupils, motility, external examination, and visual fields to confrontation were normal bilaterally. Anterior segment examination was notable only for posterior chamber intraocular lenses bilaterally. Dilated fundus examination revealed central macular scarring with macular edema in both the eyes and dry macular pigment changes in the left eye. Optical coherence tomography confirmed intraretinal edema in the right macula. Bevacizumab was injected intravitreally in the right eye. The patient presented the day after injection complaining of painless vision loss in the right eye. Best-corrected visual acuity was counting fingers in the right eye, and the intraocular pressure was 16 mmHg. Anterior segment examination was notable for quiet conjunctiva, 3+ red blood cells in the anterior chamber, a 1-mm hyphema, and an irregular pupil. Mild vitreous hemorrhage was present. The patient was treated with atropine 1% eyedrops twice daily and prednisolone acetate drops four times daily in the right eye. Over the following 4 weeks, the hyphema and mild vitreous hemorrhage resolved, the pupil returned to normal, and the bestcorrected visual acuity improved to 20/200. The patient subsequently received two intravitreal injections of ranibizumab in each eye without any complications.
HYPHEMA AFTER INTRAVITREAL INJECTION
89
Discussion Intravitreal injection of anti-vascular endothelial growth factor medication is now the standard of care for treatment of exudative AMD. Ranibizumab and bevacizumab are both commonly used throughout the United States by retinal specialists in the treatment of exudative AMD. In addition, bevacizumab has been increasingly used to treat a variety of other retinal conditions including diabetic macular edema and macular edema due to branch and central retinal vein occlusion.7–10 Complications from intravitreal injection of ranibizumab or bevacizumab are rare and include endophthalmitis, retinal detachment, vitreous hemorrhage, sterile inflammation, ocular hypertension, central retinal artery occlusion, retinal ischemia, subretinal hemorrhage, and rips of the retinal pigment epithelium.3–5 We report hyphema as a complication of intravitreal injection of both ranibizumab and bevacizumab. Based on the total number of injections given during the study period, we estimate an incidence of approximately 1 in 10,000 for hyphema after intravitreal ranibizumab or bevacizumab injection. This is probably an underestimation of the incidence of hyphema after intravitreal injection, however, because not all patients were examined within the week after injection and hyphema may present asymptomatically as in Case 1. Our injections were performed in a standardized manner approximately 3.5 mm posterior to the limbus. Although calipers were not routinely used for intravitreal injections, this practice is representative of clinical practice outside research studies. Our series of three patients includes both phakic and pseudophakic patients. All patients experienced a decrease in best-corrected visual acuity at the time of hyphema diagnosis and subsequently returned to their preinjection visual acuity after resolution of hyphema. Two patients were taking both warfarin and aspirin, whereas one patient was not taking any medications affecting coagulation. It is unclear whether anticoagulation increases the risk of postinjection hyphema, and a study specifically examining the incidence of hyphema within a week post injection relative to the prevalence of anticoagulant use would be necessary to answer that question. Whereas one patient presented with a 1-mm hyphema, the other two patients presented with only microhyphema. It is likely that microhyphema is underdiagnosed as a complication of intravitreal injection as it may be missed on cursory examination, mistaken for white blood cells representing a mild inflammatory reaction, or resolved by the time of next
Fig. 1. Intravitreal injection through the pars plana usually results in needle entry through the vitreous base. Hemorrhage from the needle tract is contained within the vitreous base (A). In the case of anomalous anatomy or anterior needle entry, the needle may enter closer to the pars plicata. In this case, hemorrhage from the needle tract may gain access to the posterior chamber and subsequently to the anterior chamber (B).
examination. Clues such as red blood cells on the inferior anterior surface of the lens capsule may be helpful in making the diagnosis. Additionally, these patients had quiet conjunctivae, suggesting that an inflammatory or infectious process was unlikely. The mechanism of hyphema after intravitreal injection is likely due to the needle tract being located anterior to the anterior edge of the vitreous base and is unlikely related to the drug itself. Because all injections were performed through the pars plana with the needle aimed posteriorly, a mild isolated vitreous
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hemorrhage might be expected if bleeding were to occur along the course of the needle tract entering the vitreous base, and this complication has been previously reported in the literature.5 If the injection was given more anteriorly than desired or aberrant anatomy was present, the needle would pass through the anterior pars plana, the pars plicata, or the posterior ciliary body. Additionally, the needle would pass through the posterior chamber and anterior hyaloid face. Any bleeding along this more anterior tract would result in blood in the posterior chamber, and thus, this blood would have access to the anterior chamber and not the vitreous that would be blocked by the anterior hyaloid (Figure 1). This seems to be the most plausible mechanism to describe the mild hyphemas seen in this series. Key words: bevacizumab, hyphema, intravitreal injection, ranibizumab. References 1. Klein R, Klein BE, Lee KE, Cruickshanks KJ, Gangnon RE. Changes in visual acuity in a population over a 15-year period: the Beaver Dam Eye Study. Am J Ophthalmol 2006;142: 539–549. 2. Ip MS, Scott IU, Brown GC, et al. Anti-vascular endothelial growth factor pharmacotherapy for age-related macular
3.
4.
5.
6.
7.
8.
9.
10.
degeneration: a report by the American Academy of Ophthalmology. Ophthalmology 2008;115:1837–1846. Fung AE, Rosenfeld PJ, Reichel E. The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 2006;90: 1344–1349. Bakri SJ, McCannel CA, Edwards AO, Moshfeghi DM. Persisent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol 2008;246: 955–958. Wong LJ, Desai RU, Jain A, et al. Surveillance for potential adverse events associated with the use of intravitreal bevacizumab for retinal and choroidal vascular disease. Retina 2008;28:1151–1158. Wickremasinghe SS, Michalova K, Gilhotra J, et al. Acute intraocular inflammation after intravitreous injections of bevacizumab for treatment of neovascular age-related macular degeneration. Ophthalmology 2008;115:1911–1915. Haritoglou C, Kook D, Neubauer A, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006;26:999–1005. Kriechbaum K, Michels S, Prager F, et al. Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a prospective study. Br J Ophthalmol 2008;92:518–522. Prager F, Michels S, Kriechbaum K, et al. Intravitreal bevacizumab (Avastin(R)) for macular edema secondary to retinal vein occlusion—twelve-month results of a prospective clinical trial. Br J Ophthalmol 2009;93:452-456. Scott IU, Edwards AR, Beck RW, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114:1860–1867.
Background: Exudative age-related macular degeneration is commonly treated with intravitreal injection of medications containing antibodies against vascular endothelial growth factors, including ranibizumab (Lucentis, Genentech, South San Francisco, CA) and bevacizumab (Avastin, Genentech). To the best of our knowledge, hyphema has not previously been reported as a complication of intravitreal injection of ranibizumab or bevacizumab. Methods: Retrospective case series. Results: Three patients developed hyphema after intravitreal injection of anti-vascular endothelial growth factor medications: one after ranibizumab and two after bevacizumab. Two patients were pseudophakic and taking warfarin in combination with low-dose aspirin, and one was phakic and not taking any coagulation-altering medications. A total of 26,184 intravitreal injections of ranibizumab or bevacizumab were given during the study period, for an estimated incidence of hyphema after intravitreal injection of approximately 1 in 10,000. Conclusion: The authors describe hyphema, either gross or microscopic, as a complication of intravitreal injection of anti-vascular endothelial growth factor medications. In all three patients, best-corrected vision returned to baseline after resolution of the hyphema and subsequent injections occurred without complication. RETINAL CASES & BRIEF REPORTS 5:87–90, 2011
ocular inflammatory reactions have been documented after ranibizumab and bevacizumab injections, and published reports have documented cases of ocular hypertension, vitreous hemorrhage, central retinal artery occlusion, and retinal ischemia.3–6 All these complications occur at a rate of less than 0.1%. Patients with AMD may also experience new subretinal hemorrhages or rips of the retinal pigment epithelium after intravitreal injection of anti-vascular endothelial growth factor medications.5 We report a series of three patients who developed hyphema after intravitreal injection of ranibizumab or bevacizumab. Hyphema has not previously been described in the medical literature as a complication of intravitreal injection of either medication.
From the Associated Retinal Consultants, Royal Oak, Michigan.
A
ge-related macular degeneration (AMD) is one of the leading causes of blindness in elderly adults in the United States.1 The exudative form of AMD is commonly treated with intravitreal injections of ranibizumab (Lucentis, Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech), which consist of antibody fragments and monoclonal antibodies to vascular endothelial growth factor, respectively.2 Ocular complications of intravitreal ranibizumab or bevacizumab injection are rare and include endophthalmitis and retinal detachment, both of which are presumably due to the intravitreal injection rather than the specific medication injected.3 Noninfectious
Material and Methods
Neither of the authors have a conflict of interest or financial disclosures relevant to this study, nor was any funding provided for this study. Reprint requests: Tushar M. Ranchod, MD, 3535 W, 13 Mile Rd, Ste 344, Royal Oak, MI 48073; e-mail: [email protected]
Retrospective Case Series A search was conducted of our practice billing database for patients diagnosed with hyphema after 87
88
RETINAL CASES & BRIEF REPORTS´ 2011 VOLUME 5 NUMBER 1
intravitreal injection with either ranibizumab or bevacizumab for any indication between August 1, 2007, and July 31, 2009. A total of 26,184 intravitreal injections of ranibizumab or bevacizumab were given during the study period (18,804 ranibizumab injections and 7380 bevacizumab injections). Three cases of hyphema were identified. All three patients received intravitreal injections for treatment of exudative AMD after application of topical proparacaine, subconjunctival 2% lidocaine, and topical 10% povidone–iodine solution. A lid speculum was used in all cases, and injections were delivered with a 30-gauge needle approximately 3.5 mm posterior to the limbus in either the superotemporal or inferotemporal quadrant. Topical antibiotics (fourth-generation fluoroquinolones) were applied immediately after injection and then prescribed for use at least 3 times daily for 3 days subsequently.
Best-corrected visual acuity was 20/60 in the right eye and 20/20 in the left eye. Intraocular pressures were 11 mmHg in both eyes and 15 mmHg in the left eye. Pupils, motility, external examination, and visual fields to confrontation were normal bilaterally. Anterior segment examination was notable only for 2+ nuclear sclerotic cataracts bilaterally. Dilated fundus examination revealed trace subretinal hemorrhage adjacent to an atrophic scar in the right eye and a large nonexudative atrophic scar in the left eye. Fluorescein angiography revealed choroidal neovascularization in the right eye. Bevacizumab was injected intravitreally in the right eye. Three days after injection, the patient presented with a complaint of pain the evening after her injection, which subsided somewhat over the following days, as well as more difficulty reading than before her injection. Best-corrected visual acuity in both the eyes was 20/200, and the intraocular pressure was 10. Anterior segment examination was notable for quiet conjunctiva, 3+ red blood cells in the anterior chamber. No vitreous cell was present. The patient was started on atropine 1% eyedrops twice daily in the right eye. Subsequent examinations demonstrated resolution of the microhyphema over a 4-day period with improvement of best-corrected visual acuity to 20/80. The patient subsequently received two more intravitreal injections of bevacizumab and had improvement of visual acuity to 20/60 in both eyes without any complications.
Case 1 An 81-year-old white man presented with decreased vision in his left eye. Ocular history was notable only for cataract surgery both eyes 5 years prior. Medical history was notable for hypertension, hypercholesterolemia, myocardial infarction, abdominal aortic aneurysm repair, femoral artery bypass surgery, benign prostatic hypertrophy, and gout. Medications included warfarin, low-dose aspirin, pentoxifylline, metoprolol, terazosin, simvastatin, amlodipine, colchicine, and furosemide. Best-corrected visual acuity was 20/30 OD and 20/40 OS. Intraocular pressures were 15 mmHg both eyes and 16 mmHg in the left eye. Pupils, motility, external examination, and visual fields to confrontation were normal bilaterally. Anterior segment examination was notable only for posterior chamber intraocular lenses bilaterally. Dilated fundus examination revealed drusen and pigmentary changes in the right macula and subretinal fluid with hemorrhage in the left subfoveal region. Fluorescein angiography confirmed subfoveal choroidal neovascularization in the left eye. Ranibizumab was injected intravitreally into the left eye. The patient was seen 1 week after intravitreal injection at a scheduled visit with no subjective complaints at that time. Bestcorrected visual acuity was 20/25 left eye, and the intraocular pressure was 13. Anterior segment examination was notable for quiet conjunctiva, 2+ red blood cells in the anterior chamber and trace red blood cells on the anterior lens capsule inferiorly. No vitreous cells were present either anteriorly or posteriorly. The anterior chamber was quiet at the next follow-up visit 3 weeks later with visual acuity remaining 20/25, and the patient received a subsequent intravitreal injection of ranibizumab without incident.
Case 2 A 77-year-old white woman presented for follow-up of exudative AMD in the right eye and nonexudative AMD in the left eye. Her ocular history included 4 intravitreal injections of pegaptanib sodium (Macugen; [OSI] Eyetech, New York, NY), 4 intravitreal injections of bevacizumab, and 18 previous intravitreal injections of ranibizumab, all in the right eye over a 3-year period. Medical history was notable for hypertension, hypercholesterolemia, and arthritis. Medications included simvastatin and lisinopril.
Case 3 An 85-year-old white woman presented for follow-up of bilateral exudative AMD. Ocular history was notable for cataract surgery bilaterally as well as verteporfin photodynamic therapy combined with intravitreal triamcinolone acetonide (Kenalog 40; BristolMyers Squibb, Princeton, NJ) in the right eye, one intravitreal bevacizumab and four intravitreal ranibizumab injections in the right eye. The left eye had previously received seven intravitreal injections of ranibizumab. Medical history included hypertension, arthritis, coronary artery disease with stent placement 8 years before, and colon cancer in remission for 10 years. Medications included warfarin, low-dose aspirin, quinapril, nifedipine, and simvastatin. Best-corrected visual acuity was 20/400 in both eyes (decreased from 20/200 the previous month) and 20/40 in the left eye. Intraocular pressures were 14 mmHg in both eyes. Pupils, motility, external examination, and visual fields to confrontation were normal bilaterally. Anterior segment examination was notable only for posterior chamber intraocular lenses bilaterally. Dilated fundus examination revealed central macular scarring with macular edema in both the eyes and dry macular pigment changes in the left eye. Optical coherence tomography confirmed intraretinal edema in the right macula. Bevacizumab was injected intravitreally in the right eye. The patient presented the day after injection complaining of painless vision loss in the right eye. Best-corrected visual acuity was counting fingers in the right eye, and the intraocular pressure was 16 mmHg. Anterior segment examination was notable for quiet conjunctiva, 3+ red blood cells in the anterior chamber, a 1-mm hyphema, and an irregular pupil. Mild vitreous hemorrhage was present. The patient was treated with atropine 1% eyedrops twice daily and prednisolone acetate drops four times daily in the right eye. Over the following 4 weeks, the hyphema and mild vitreous hemorrhage resolved, the pupil returned to normal, and the bestcorrected visual acuity improved to 20/200. The patient subsequently received two intravitreal injections of ranibizumab in each eye without any complications.
HYPHEMA AFTER INTRAVITREAL INJECTION
89
Discussion Intravitreal injection of anti-vascular endothelial growth factor medication is now the standard of care for treatment of exudative AMD. Ranibizumab and bevacizumab are both commonly used throughout the United States by retinal specialists in the treatment of exudative AMD. In addition, bevacizumab has been increasingly used to treat a variety of other retinal conditions including diabetic macular edema and macular edema due to branch and central retinal vein occlusion.7–10 Complications from intravitreal injection of ranibizumab or bevacizumab are rare and include endophthalmitis, retinal detachment, vitreous hemorrhage, sterile inflammation, ocular hypertension, central retinal artery occlusion, retinal ischemia, subretinal hemorrhage, and rips of the retinal pigment epithelium.3–5 We report hyphema as a complication of intravitreal injection of both ranibizumab and bevacizumab. Based on the total number of injections given during the study period, we estimate an incidence of approximately 1 in 10,000 for hyphema after intravitreal ranibizumab or bevacizumab injection. This is probably an underestimation of the incidence of hyphema after intravitreal injection, however, because not all patients were examined within the week after injection and hyphema may present asymptomatically as in Case 1. Our injections were performed in a standardized manner approximately 3.5 mm posterior to the limbus. Although calipers were not routinely used for intravitreal injections, this practice is representative of clinical practice outside research studies. Our series of three patients includes both phakic and pseudophakic patients. All patients experienced a decrease in best-corrected visual acuity at the time of hyphema diagnosis and subsequently returned to their preinjection visual acuity after resolution of hyphema. Two patients were taking both warfarin and aspirin, whereas one patient was not taking any medications affecting coagulation. It is unclear whether anticoagulation increases the risk of postinjection hyphema, and a study specifically examining the incidence of hyphema within a week post injection relative to the prevalence of anticoagulant use would be necessary to answer that question. Whereas one patient presented with a 1-mm hyphema, the other two patients presented with only microhyphema. It is likely that microhyphema is underdiagnosed as a complication of intravitreal injection as it may be missed on cursory examination, mistaken for white blood cells representing a mild inflammatory reaction, or resolved by the time of next
Fig. 1. Intravitreal injection through the pars plana usually results in needle entry through the vitreous base. Hemorrhage from the needle tract is contained within the vitreous base (A). In the case of anomalous anatomy or anterior needle entry, the needle may enter closer to the pars plicata. In this case, hemorrhage from the needle tract may gain access to the posterior chamber and subsequently to the anterior chamber (B).
examination. Clues such as red blood cells on the inferior anterior surface of the lens capsule may be helpful in making the diagnosis. Additionally, these patients had quiet conjunctivae, suggesting that an inflammatory or infectious process was unlikely. The mechanism of hyphema after intravitreal injection is likely due to the needle tract being located anterior to the anterior edge of the vitreous base and is unlikely related to the drug itself. Because all injections were performed through the pars plana with the needle aimed posteriorly, a mild isolated vitreous
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hemorrhage might be expected if bleeding were to occur along the course of the needle tract entering the vitreous base, and this complication has been previously reported in the literature.5 If the injection was given more anteriorly than desired or aberrant anatomy was present, the needle would pass through the anterior pars plana, the pars plicata, or the posterior ciliary body. Additionally, the needle would pass through the posterior chamber and anterior hyaloid face. Any bleeding along this more anterior tract would result in blood in the posterior chamber, and thus, this blood would have access to the anterior chamber and not the vitreous that would be blocked by the anterior hyaloid (Figure 1). This seems to be the most plausible mechanism to describe the mild hyphemas seen in this series. Key words: bevacizumab, hyphema, intravitreal injection, ranibizumab. References 1. Klein R, Klein BE, Lee KE, Cruickshanks KJ, Gangnon RE. Changes in visual acuity in a population over a 15-year period: the Beaver Dam Eye Study. Am J Ophthalmol 2006;142: 539–549. 2. Ip MS, Scott IU, Brown GC, et al. Anti-vascular endothelial growth factor pharmacotherapy for age-related macular
3.
4.
5.
6.
7.
8.
9.
10.
degeneration: a report by the American Academy of Ophthalmology. Ophthalmology 2008;115:1837–1846. Fung AE, Rosenfeld PJ, Reichel E. The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 2006;90: 1344–1349. Bakri SJ, McCannel CA, Edwards AO, Moshfeghi DM. Persisent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol 2008;246: 955–958. Wong LJ, Desai RU, Jain A, et al. Surveillance for potential adverse events associated with the use of intravitreal bevacizumab for retinal and choroidal vascular disease. Retina 2008;28:1151–1158. Wickremasinghe SS, Michalova K, Gilhotra J, et al. Acute intraocular inflammation after intravitreous injections of bevacizumab for treatment of neovascular age-related macular degeneration. Ophthalmology 2008;115:1911–1915. Haritoglou C, Kook D, Neubauer A, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006;26:999–1005. Kriechbaum K, Michels S, Prager F, et al. Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a prospective study. Br J Ophthalmol 2008;92:518–522. Prager F, Michels S, Kriechbaum K, et al. Intravitreal bevacizumab (Avastin(R)) for macular edema secondary to retinal vein occlusion—twelve-month results of a prospective clinical trial. Br J Ophthalmol 2009;93:452-456. Scott IU, Edwards AR, Beck RW, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114:1860–1867.
