From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Palm Beach Gardens, Florida.
Supported in part by an unrestricted grant from The Palm Beach Community Trust Fund, NIH Center Grant P30 EY014801, and an unrestricted grant from Research to Prevent Blindness.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Andrew A. Moshfeghi, MD, MBA, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 7101 Fairway Drive, Palm Beach Gardens, FL 33418. E-mail: firstname.lastname@example.org
Retinal arterial macroaneurysm is an acquired large arteriolar dilation usually seen within the first three orders of the retinal arterial vasculature bifurcations, typically in the macular or post-equatorial regions.1,2 Hypertensive women in their sixth to eighth decade of life are most likely to develop retinal arterial macroaneurysms.2 This condition may lead to visual loss secondary to macular edema or hemorrhage in one or all retinal layers with poor visual prognosis for eyes complicated by submacular hemorrhage.1
Therapeutic intervention for eyes with a retinal arterial macroaneurysm include direct photocoagulation to the aneurysm itself,1 indirect photocoagulation to the retina surrounding the retinal arterial macroaneurysm2 to reduce macular edema or hemorrhage and to limit its spread, surgical removal of associated submacular hemorrhage using tissue plasminogen activator with pneumatic displacement of submacular hemorrhage (with or without pars plana vitrectomy),3 and photodisruption of the internal limiting membrane or the posterior hyaloid using Nd:YAG or argon laser allowing sub-internal limiting membrane loculated hemorrhage to be released.
We present a case of a ruptured retinal arterial macroaneurysm with associated subretinal hemorrhage extending into the macula along with vitreous hemorrhage that was treated with intravitreal injections of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) with an excellent visual outcome without the need for thermal laser photocoagulation or vitreoretinal surgical intervention.
A 79-year-old woman with a history of systemic arterial hypertension was evaluated for a 1-week history of painless decreased vision and “black spots” in the right eye. At presentation, the patient had a best-corrected visual acuity of 20/400 in the right eye and 20/25 in the left eye. Ophthalmic examination of the right eye revealed a dense and diffuse vitreous hemorrhage with a focal area of dense subretinal hemorrhage involving the inferior aspect of the macula (Fig. 1). No details of the retinal vasculature could be appreciated secondary to the overlying vitreous hemorrhage. B-scan ultrasonographic examination of the right eye demonstrated the retina to be completely attached for 360°, without signs of abnormal vitreoretinal traction or retinal tears being found. Echoes of medium intensity were detected in the vitreous cavity and these were consistent with vitreous hemorrhage (Fig. 1). Clinical examination of the retinal periphery with scleral depression did not reveal any retinal breaks to the ora serrata for 360°. The ocular media were sufficiently cloudy to preclude adequate testing with intravenous fundus fluorescein or indocyanine green angiography.
Figure 1. (A) A Color Fundus Photograph of the Right Eye Demonstrates Diffuse and Focal Vitreous and Pre-Retinal Hemorrhages that Obscure Fundus Details. The Optic Nerve Is Barely Visible. An Intravitreal Injection of Bevacizumab Was Administered on This Visit. Visual Acuity Was 20/400. (B) A Vertically Oriented Radial Line Optical Coherence Tomography Scan (StratusOCT, Zeiss, Dublin, CA) of the Right Macula Demonstrates a Diminished Optical Signal, but No Subretinal Fluid, Pigment Epithelial Detachment, or Cystoid Macular Edema Were Detected. (C) A Longitudinally Oriented B-Scan Ultrasound Focused on the Posterior Pole of the Right Eye Demonstrates Vitreous Opacities Consistent with Hemorrhage and an Elevation of the Retina in the Inferior Macula, but No Evidence of Retinal of Tears or Detachment Were Identified. (D) Eleven Days Following the Initial Intravitreal Bevacizumab Injection, the Follow-Up Fundus Photograph Demonstrated Improved Ocular Media Clarity, Decreased Vitreous Hemorrhage, and a More Well-Defined Area of Loculated Pre-Retinal Hemorrhage Along the Inferotemporal Arcade. Visual Acuity Improved to 20/125.
After written informed consent was obtained, the patient was offered and received an intravitreal injection of bevacizumab (1.25 mg) in an attempt to promote clearing of the vitreous hemorrhage and to reduce any potentially hyperpermeable pathologic process that was obscured by the vitreous hemorrhage (eg, a leaking choroidal neovascular membrane from exudative age-related macular degeneration or extraretinal fibrovascular proliferation from an occult ischemic central retinal vein occlusion). Appreciable anatomic and visual improvement was observed at the next clinical examination 2 weeks after the initial intravitreal bevacizumab injection, with the vitreous hemorrhage resolving and the best-corrected visual acuity improving to 20/50 (Fig. 1).
With the vitreous hemorrhage sufficiently cleared, fundus fluorescein angiography was performed 4 weeks after the initial intravitreal bevacizumab injection and this demonstrated a distinct retinal arterial macroaneurysm lesion along the inferotemporal arcade with associated subretinal hemorrhage (Fig. 2). The patient was offered thermal laser treatment of the retinal arterial macroaneurysm, but she deferred this approach. Instead, the patient was offered and received a second injection of intravitreal bevacizumab (1.25 mg) to consolidate the prior treatment and to provide continued reduced hyperpermeability (Fig. 3). Intraretinal and subretinal hemorrhages continued to subside with improved visual acuity to 20/20 at the final follow-up visit 12 months after the initial intravitreal bevacizumab injection.
Figure 2. Three Weeks Following the Initial Intravitreal Bevacizumab Injection, a Red-Free Fundus Photograph (A), and a Fundus Fluorescein Angiogram in Early (B), Middle (C), and Late (D) Recirculation Phases Demonstrated a Leaking Retinal Arterial Macroaneurysm Along the Inferotemporal Arcade with Persistent Pre-Retinal, Intraretinal, and Subretinal Hemorrhages. A Second Intravitreal Bevacizumab Injection Was Administered on This Visit. Visual Acuity Measured 20/50.
Figure 3. Color Fundus Photographs of the Right Eye at Various Time Points Following Intravitreal Bevacizumab Injections, Demonstrating Progressively Decreasing Pre-Retinal, Intraretinal, and Subretinal Hemorrhages. (A) Three Weeks Following the First Intravitreal Bevacizumab Injection, a Second Injection Was Given. Visual Acuity Measured 20/50. (B) One Month Following the Second Intravitreal Bevacizumab Injection, Visual Acuity Measured 20/40. (C) Two Months Following the Second Intravitreal Bevacizumab Injection, the Pre-Retinal, Intraretinal, and Subretinal Hemorrhages Continued to Subside and the Visual Acuity Measured 20/40. (D) Five Months Following the Second Intravitreal Bevacizumab Injection, Most of the Hemorrhages Have Resolved, Retinal Pigment Epithelial Mottling Is Seen in the Area Previously Occupied by the Subretinal Hemorrhage, and Visual Acuity Improved to 20/30.
Making the initial diagnosis of retinal arterial macroaneurysm may be difficult, especially in the presence of a dense vitreous hemorrhage blocking the view of the retina and limiting the utility of funduscopy and fundus fluorescein angiography. In our case, the initial injection of intravitreal bevacizumab provided rapid clearance of the vitreous hemorrhage and significant improvement in the clarity of the ocular media, reduction of pre-retinal, subretinal, and intraretinal hemorrhages, and correlative improvement in visual acuity.
Subretinal hemorrhage associated with retinal arterial macroaneurysm threatening the macular region may result in poor visual outcomes due to hemosiderin exposure to the outer retina.3 Surgical removal of submacular hemorrhage using tissue plasminogen activator and pneumatic displacement of submacular hemorrhage have been used with improvement in visual acuity. However, this is typically reserved for cases in which subfoveal hemorrhage is already present. In our case, two intravitreal injections of bevacizumab at 4-week intervals led to total resolution of the associated pre-retinal, intraretinal, and subretinal hemorrhages and improved visual acuity. Chanana and Azad4 described their experience with intraretinal bevacizumab for the management of cystoid macular edema associated with a leaking retinal arterial macroaneurysm lesion, but their case was not complicated by a ruptured and hemorrhagic retinal arterial macroaneurysm lesion. However, no cystoid macular edema was seen in our patient on the initial optical coherence tomography test to explain her decreased vision. To our knowledge, this case represents the first published report in the peer-reviewed literature detailing the use of intravitreal bevacizumab for the management of a ruptured retinal arterial macroaneurysm with pre-retinal and intraretinal hemorrhages, as well as a macula-threatening subretinal hemorrhage.
A larger prospective randomized and controlled study would be necessary to establish the true benefit of intravitreal bevacizumab injections in the treatment of retinal arterial macroaneurysm. Based on our clinical experience with intravitreal bevacizumab for this and for a variety of additional retinovascular diseases,5–7 we suspect that intravitreal bevacizumab may be valuable in future management of vitreous hemorrhea associated with retinal arterial macroaneurysm and macular-threatening subretinal hemorrhages.
- Tonotsuka T, Mai M, Saito K, Iijima H. Visual prognosis for symptomatic retinal arterial macroaneurysm. Jpn J Ophthalmol. 2003;47:498–502. doi:10.1016/S0021-5155(03)00104-7 [CrossRef]
- Van Nouhuys E, Deutman AR. Argon laser treatment of retinal macroaneurysms. Int Ophthalmol. 1980;2:45–53. doi:10.1007/BF00149255 [CrossRef]
- Ohji M, Saito Y, Hayashi A, Lewis JM, Tano Y. Pneumatic displacement of subretinal hemorrhage without tissue plasminogen activator. Arch Ophthalmol. 1998;116:1326–1332.
- Chanana B, Azad RV. Intravitreal bevacizumab for macular edema secondary to retinal macroaneurysm. Eye. 2009;23:493–494. doi:10.1038/eye.2008.98 [CrossRef]
- Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2005;36:331–335.
- Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging. 2005;36:336–339.
- Rich RM, Rosenfeld PJ, Puliafito CA, et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina. 2006;26:495–511. doi:10.1097/01.iae.0000225766.75009.3a [CrossRef]