INTRAVITREAL TRIAMCINOLONE AND BEVACIZUMAB THERAPY FOR COMBINED PAPILLOPHLEBITIS AND CENTRAL RETINAL ARTERY OCCLUSION Veroˆnica Castro Lima, MD,* Tiago S. Prata, MD,† Gennady Landa, MD,* Lawrence A. Yannuzzi, MD,‡ Richard B. Rosen, MD*§
Purpose: To report a case of an idiopathic, unilateral combined central retinal artery and vein occlusion in a young, healthy patient successfully treated with combined intravitreal triamcinolone and bevacizumab injection. Methods: Interventional case report. A 38-year-old man presented with a 2-hour history of acute painless loss of vision in his right eye. Ophthalmic examination revealed count fingers visual acuity, an afferent pupillary defect, a discreet cherry red spot, optic disk edema, and scattered intraretinal hemorrhages in the right fundus. Fluorescein angiography confirmed the central retinal artery occlusion diagnosis. Results: A standard treatment for central retinal artery occlusion and a combined intravitreal triamcinolone and bevacizumab injection were performed. An exhaustive laboratory workup failed to reveal any evidence of systemic vascular, inflammatory, or hypercoagulable disorders. Transesophageal echocardiography, carotid Doppler, and magnetic resonance imaging of the orbits and brain were all unremarkable. In the month after initiation of the treatment, the patient’s visual acuity gradually improved to 20/30 and remained stable during a 12-month follow up. Conclusion: Although the visual prognosis of a combined central retinal artery and vein occlusion is generally poor, our patient experienced an excellent visual recovery more than 1 month after prompt standard of care and a combined intravitreal triamcinolone and bevacizumab injection. Further investigation is necessary to support the efficacy and safety of this approach. RETINAL CASES & BRIEF REPORTS 4:125–128, 2010
From the *Retina Service, Department of Ophthalmology, The New York Eye and Ear Infirmary; †Einhorn Clinical Research Center, The New York Eye and Ear Infirmary; ‡Vitreous-Retina-Macula Consultants of New York and the Macula Foundation, Inc., of LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; and §New York Medical College, Valhalla, New York.
combined central artery and vein occlusion is an uncommon disorder that has been reported in association with numerous conditions such as traumatic retrobulbar injections,1 vasculitis,2 neoplasms,3 inflammatory and infectious processes,4 and other systemic diseases associated with central retinal artery occlusion. It typically leads to severe vision loss and a poor visual prognosis despite standard methods of treatment such as panretinal photocoagulation.1 We report an unusual case of an idiopathic, unilateral combined central retinal artery and vein occlusion in an otherwise young, healthy patient successfully treated with standard management and a combined intravitreal triamcinolone and bevacizumab injection.
None of the authors has any financial interests to disclose. Reprint requests: Richard B. Rosen, MD, Retina Service, Department of Ophthalmology, The New York Eye and Ear Infirmary, 310 East 14th Street, New York, NY 10003; e-mail: [email protected]
RETINAL CASES & BRIEF REPORTSℜ
Fig. 1. A, Fundus photography of the right eye at the initial presentation. B, Fundus photography of the right eye 6 months after the initial presentation and treatment. Note resolution of the optic disk swelling and of the whitening surrounding the macular area.
Case Report A 38-year-old white man presented with a sudden painless loss of vision of his right eye, which occurred ⬍2 hours before presentation and appeared to worsen as the day proceeded. He denied any recent eye trauma. His medical, ocular, and family history were unremarkable. Review of systems was unremarkable, and he also denied taking any medication, alcohol, tobacco, or illicit drug use. Best-corrected visual acuity was count fingers at 2 inches in the right eye and 20/30 in the left eye. Biomicroscopy examination revealed that extraocular motility and intraocular pressure (16 mmHg) were within normal limits in both eyes. A relative afferent pupillary defect was detectable in the right eye. The vitreous was clear in both eyes, and in the left eye, the fundus examination revealed it to be normal. The right eye revealed retinal whitening surrounding the macula with a faint cherry red spot, scattered intraretinal and superficial hemorrhages in four quadrants, and mild macular edema. Moderate optic disk swelling was present, and retinal veins appeared dilated and markedly tortuous (Figure 1). No embolus was detected anywhere in the retinal arterial vessels. Fluorescein angiography in the early phase demonstrated delayed arterial filling and prolonged arterial--venous transit time as well as venous engorgement and tortuosity in the late phase (Figure 2, A and B). Optical coherence tomography revealed intense hyperreflectivity of the inner retina with loss of definition of the internal retinal layers and intraretinal fluid (Figure 3). After informed consent, the patient received a combined intravitreal injection of triamcinolone (4 mg) and bevacizumab (1.25 mg) in the right eye followed immediately by paracentesis of the anterior chamber leaving the intraocular pressure at 0 mmHg.
Then, he was admitted for hourly doses of 10 minutes of Carbogen inhalation therapy (95% oxygen, 5% carbon dioxide) and intravenous solumedrol (60 mg every 12 hours). Oral pentoxifylline therapy (400 mg every 8 hours) and antiplatelet therapy with aspirin (325 mg/day) were also initiated. Preliminary systemic workup, including blood cell count, chemistry panel, coagulation parameters, erythrocyte sedimentation rate, and C-reactive protein, was within normal limits. Carotid Doppler ultrasonography as well as transesophageal echocardiography and magnetic resonance imaging of the orbits and brain were normal. Subsequent hypercoagulability workup, including sickle cell prep, homocysteine level, factor V Leiden, antiphospholipid antibody, protein C and S levels, and fibrinogen, was negative. After 1 month, the patient presented best-corrected visual acuity of 20/30 in the right eye with significant improvement of the optic disk swelling and intraretinal hemorrhages. Fluorescein angiography disclosed a normal perfusion status of the macula (Figure 4, A and B). After 6 months, no signs of neovascularization were found, and the patient maintained good functional and anatomical results (Figures 1 and 3).
Discussion We report a case of an idiopathic, unilateral combined central retinal artery and vein occlusion in a young, healthy patient successfully treated with an intravitreal triamcinolone and bevacizumab injection and standard treatment for arterial occlusion. A combined central retinal artery and vein occlusion is an
Fig. 2. A, Fluorescein angiography demonstrating delayed arterial filling. At 25 seconds postinjection, the arteries are not completely filled. B, Late-phase fluorescein angiography reveals dilated and tortuous retinal veins, areas of blockage by superficial and intraretinal hemorrhages, and late staining of the optic disk.
PAPILLOPHLEBITIS AND ARTERY OCCLUSION
Fig. 3. A, The optical coherence tomography B-scan of the right eye at the initial presentation showing macular hyperreflectivity and loss of definition of the inner retinal layers. B, The optical coherence tomography B-scan 6 months after treatment. Note reduction of the retinal thickness and increased definition of the inner retinal layers.
uncommon but not rare event in the retinal physician environment. A myriad of causative associations is well known in the literature with systemic associations such as trauma, inadvertent retrobulbar injection with hemorrhage, intrasheath injection, vasculitis, neoplasm, inflammatory and infectious diseases, and a variety of hypercoagulable disorders.1-4 The visual prognosis of this condition is reported as generally poor, and the principal concern relates to the retinal artery occlusion, which can induce diffuse and permanent ischemia and severe vision loss. Moreover, the established standard treatment regimen is disappointing with regard to inducing reperfusion and improvement in visual function. Although spontaneous improvement can rarely occur, most patients experience severe loss of vision. As many as 80% will develop rubeosis and neovascular glaucoma over a mean time interval of 6 weeks, putting them at risk of a blind and painful eye.1 Isolated central retinal vein occlusion can be observed in young adults, and in most cases, it occurs in an otherwise healthy patient with no known systemic or ocular disease, although 1 previous report5 showed some systemic abnormalities in up to 50% of affected individuals. Inflammation of the optic disk causing compression of the central retinal vein and venous insufficiency has been proposed as the etiology in these cases, hence the term papillophlebitis. It often
Fig. 4. A, Early-phase fluorescein angiography 1 month after the intravitreal treatment showing macular reperfusion. B, Late-phase fluorescein angiography 1 month after the intravitreal treatment.
has a better natural course compared with central retinal vein occlusion in older adults, and it is not commonly associated with arterial occlusion. Although no embolus was found in the clinical examination and no carotid or cardiac abnormality was found in the systemic investigation, we believe that our patient had a venous occlusive event with a significant arterial component as demonstrated by clinical fluorescein angiography and optical coherence tomography examinations. Finally, arterial insufficiency secondary to a compartment syndrome at the optic disk head could be a plausible explanation for this case. In the treatment of macular edema resulting from central retinal vein occlusion, both intravitreal triamcinolone and bevacizumab have a recent history of off-label use in clinical practice. Each has been shown to decrease macular thickness and improve visual acuity, presumably by antiinflammatory and antipermeability properties, respectively.6,7 Although the use of intravitreal triamcinolone has demonstrated rapid improvement of the visual function and anatomy, these results are often short-lived.6 Regarding intravitreal bevacizumab therapy for macular edema in patients with central retinal vein occlusion, short-term results have been reported as promising.7 However, long-term evaluation and outcomes are still pending. Our patient presented with combined vascular occlu-
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sion with macular edema, which appeared primarily intracellular based on the original optical coherence tomography examination. This appearance consisted of uniform hyperreflectivity of the inner retina with the absence of the discernible inner retinal structures. It is characteristic of arterial occlusion as opposed to cystoid-appearing extracellular edema more suggestive of venous occlusion disease on optical coherence tomography. Although extracellular macular edema is a reversible cause of vision loss, intracellular edema resulting from macular ischemia is usually not. Little is known about the effect of antivascular endothelial growth factor therapy on retinal ischemia; however, some evidence has suggested that intravitreal bevacizumab has a positive effect on the retinal ischemia in patients with diabetic retinopathy.8 In addition, a number of experimental studies of cerebral ischemia have also demonstrated the effectiveness of vascular endothelial growth factor-blocking agents in reducing the volume of postinfarction cerebral ischemia.9,10 Because minimization of ischemia and edema were primary goals to be achieved, it appears that the combination of agents used in this case may have played a decisive role in its successful outcome. A standard management for central retinal artery occlusion was performed acutely, and it may have influenced the outcome in this case. However, with the prospect of permanent and severe vision loss in a young patient who was also at high risk for neovascularization, the decision was made to use both intravitreal triamcinolone and bevacizumab in an attempt to reverse the ischemic process. The fact that such a favorable outcome was achieved is extremely atypical for the usual course of this condition. One could speculate that the combination of antiinflammatory properties of one drug and antipermeability and antivasogenic actions of the other were synergistic in their ability to control the macular edema and minimize permanent damage. Perhaps the mechanism of the arterial insufficiency in this particular case was more amenable to the treatment with these drugs than other causes of combined occlusion. In either case, although the rationale for this approach remains to be definitively
tested, it seems safe and reasonable, especially in light of typical results with the isolated standard care. In summary, this unprecedented clinical approach demonstrated satisfactory anatomic and functional results, which have persisted through ⬎12 months of follow-up. Despite the severe initial presentation, our patient had excellent visual recovery, far exceeding the response that is reported as the natural course of the disease. This unusually good outcome warrants further consideration of this approach for the management of this condition in the future. Key words: bevacizumab, central retinal artery and vein occlusion, papillophlebitis, triamcinolone. References 1.
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