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Retinal arterial macroaneurysm causing multilevel retinal hemorrhage
Optometry (2009) 80, 425-430
Retinal arterial macroaneurysm causing multilevel retinal hemorrhage Elizabeth Kester, O.D.,a and Erica Walker, O.D.b a
William Chappell VA Outpatient Clinic, Daytona Beach, Florida; and bOrlando VA Healthcare Center, Orlando, Florida.
KEYWORDS Retinal arterial macroaneurysm; Hypertension; Masquerade syndrome; Intravenous fluorescein angiography
Abstract BACKGROUND: Retinal arterial macroaneurysms are focal dilatations of the retinal arteries that present with varying degrees of retinal hemorrhage or exudation. They are most often associated with hypertension and may masquerade as many other retinal conditions. CASE REPORT: A hypertensive 59-year-old man presented to the clinic with a sudden onset of painless vision loss in the left eye. Best-corrected visual acuities were 20/20 in the right eye and counting fingers at 3 feet with eccentric viewing in the left. Dilated fundus examination found a multilevel retinal hemorrhage involving most of the superior arcade and extending into the macular area. A diagnosis of retinal arterial macroaneurysm was given after fluorescein angiography and evaluation by a retina specialist. Hemorrhage resolved without treatment, and visual acuity returned to 20/25 by the 6-month follow-up visit. CONCLUSIONS: Optometrists should be aware of presenting signs and symptoms associated with retinal macroaneurysms as well as the many differentials and possible treatments. Given the high incidence of associated systemic disease, proper knowledge of necessary systemic workup is also critical. Optometry 2009;80:425-430
Retinal arterial macroaneurysms have been described in the literature for many years. These vascular lesions can have a multitude of findings at presentation, including multilevel retinal hemorrhages, exudates, and edema. Primary eye care providers need to be familiar with the varied presentations, differential diagnoses, and management options of retinal arterial macroaneurysms. Systemic diseases, such as hypertension, have been associated with macroaneurysms; therefore, a systemic workup may be indicated. The following case report describes a patient with a macroaneurysm, from the significant hemorrhagic presentation to eventual resolution, over 18 months of follow-up. This case also shows that a multidisciplinary approach, including primary eye provider,
Corresponding author: Elizabeth Kester, O.D., William Chappell VA Outpatient Clinic, 551 National Healthcare Dr., Daytona Beach, Florida 32114. E-mail: [email protected]
retina specialist, and internist/primary care provider may be necessary.
Case report A 59-year-old man presented with complaints of sudden loss of vision in the left eye (O.S.) upon wakening that morning. He reported that a large, yellowish-red spot was blocking his central vision O.S., and he felt it had the appearance of blood. He denied pain O.S. or any loss of vision in the right eye (O.D.). He denied any recent symptoms of flashes or floaters in either eye. Medical history was significant for type 2 diabetes mellitus, hyperlipidemia, peripheral neuropathy, pernicious anemia, vitamin B12 deficiency, and actinic keratosis. Ocular history was unremarkable. The patient was examined approximately 9 months prior, and no ocular pathology was noted at that time. Current medications included glipizide, hydroxyzine pamoate, insulin novolin 70/30,
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naproxen, and propoxyphene N/APAP. Blood pressure was measured in the office at 149/89 mmHg. Best-corrected visual acuity was 20/20 O.D. and counting fingers at 3 feet with eccentric viewing O.S. Pupils were equal, round, and reactive to light without afferent pupillary defect. Ocular motility was full in both eyes (OU), and confrontation fields were full to finger counting with some difficulty O.S. Anterior-segment slit lamp examination found early nuclear sclerotic lens changes with otherwise unremarkable findings. Applanation tonometry found tensions of 16 mmHg O.D. and 14 mmHg O.S. Dilated fundus examination found vertical cup-to-disc ratios of 0.3 O.D. and 0.3 O.S. Posterior pole, macular, and peripheral examination findings were unremarkable O.D. A large retinal hemorrhage extended from the superior arcade inferiorly to the superior rim of the optic nerve and also extended through the macular area obscuring macular details (see Figure 1A). The hemorrhage was multilevel, including preretinal, intraretinal, and subretinal involvement. A possible source of the hemorrhage could be appreciated in the superior arcade, as slight vessel elevation or outpouching was noted, but obscuration by the hemorrhage made it difficult to determine. A tentative diagnosis of macroaneurysm was made, and the patient was scheduled to see a retina specialist the following day. Clinical picture and patient complaints were unchanged the following day. Intravenous fluorescien angiography (IVFA) and indocyanine green (ICG) angiography were performed but did not show any areas of active leakage or ‘‘hotspots.’’ The retina specialist felt it was a multilevel
Figure 1
retinal hemorrhage likely caused by a macroaneurysm. No treatment was recommended at that time, and a follow-up appointment was made for 1 month. Strict blood pressure control was stressed, and the patient’s primary care physician started him on lisinopril, 5 mg/day the following day. At the 1-month follow-up examination, the patient felt he may have had a minimal improvement in his vision O.S. Best-corrected visual acuity was measured at 20/20 O.D. and 20/400 O.S. Pupils, anterior segment examination, and intraocular pressures (IOPs) were unremarkable. Dilated fundus examination was unchanged O.D., and the left eye showed some resolution of the multilevel hemorrhage from presentation (see Figure 1B). Portions of the hemorrhage contained degenerating red blood cells, and this dehemoglobinization gives portions of the resolving hemorrhage a yellowish color. A small amount of exudate was visible temporal to the macula. No treatment was recommended at that time given the improvement in the clinical picture. The patient was scheduled for a re-evaluation in 1 month. The visual acuity in the left eye was still 20/400 at the 2month follow-up but the patient felt the vision was improving. On fundus examination O.S., the hemorrhage was still resolving, with most of the hemorrhage dehemoglobinized with a yellowish appearance (see Figure 1C). No new leakage or bleeding was noted that day. The retina specialist felt that if there was no resolution in 3 to 4 weeks, a 25-gauge vitrectomy would be indicated. Blood pressure at this visit had improved to 115/68 mmHg. Three months after initial presentation, the patient’s visual acuity had improved to 20/100 O.S. A preretinal
Fundus photos of the left eye at A, Initial presentation; B, 1 month; C, 2 months; D, 4 months; and E, 6 months after presentation.
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hemorrhage was still present extending from the optic nerve to the macula, but given the improvement in vision, no treatment was recommended at that time. Four months after the initial visit, the visual acuity was 20/150 O.S., and a small amount of preretinal hemorrhage was still present in the macular area, as well as temporal to the optic nerve and in the superior arcade (see Figure 1D). Repeat IVFA was performed, and no leakage was noted. A return visit was scheduled for 8 weeks. At the 6-month follow-up visit, visual acuity had improved to 20/25 O.S. Almost complete resolution of the macular hemorrhage was noted, with small residual areas of preretinal hemorrhage noted in the posterior pole (see Figure 1E). A small area of perivascular sclerotic tissue was present in the superior arcade at the previous source of the macroaneurysm. The patient was encouraged to continue proper blood pressure control and to return to the clinic immediately with any changes in vision. The patient returned 1 year later, with best-corrected visual acuity of 20/20 O.D. and 20/20 O.S. Vessel sclerosis was still present at the site of the previous macroaneurysm, and a very faint preretinal heme was visible temporally to the optic nerve.
women affected.7 Several studies have reported average age on presentation of 66.1 years,4 69.7 years,8 and 73.7 years,9 respectively, with increasing age elevating risk of occurrence. Systemic risk factors include hypertension, atherosclerosis, hyperlipidemia, retinal arterial emboli,10 cerebrovascular disease, and polycythemia.4 Hypertension is the most common association, affecting approximately 75% of patients presenting with MAs.11 In fact, in a retrospective study of macroaneurysm patients by Lavin et al.,4 17 of the 18 patients examined by their medical clinic were found to have ‘‘evidence of systemic vascular or relevant metabolic disease.’’ Patients who present with MAs require full investigation for systemic disease with attention to hypertension, systemic vascular disease, and embolic disease. Recommended studies include complete blood count (with differential and platelets), fasting blood sugar and glycosylated hemoglobin, blood pressure, fasting lipid profile, carotid auscultation or carotid duplex ultrasonography, and cardiac evaluation. A prompt multispecialty approach may include primary eye provider, retina specialist, internal medicine physician, and cardiologist.
Discussion
Pathophysiology
Background
Histologic study of macroaneurysms confirms a true aneurysm formation including vessel wall thickening, change in hyaline, and elastotic degeneration.12 As arterioles age, intimal collagen replaces smooth muscle fibers, and the arterial wall becomes less elastic. These vessels are more susceptible to dilatation from elevated hydrostatic pressure.9 Hypertensive patients also experience elevated hydrostatic pressure, decreased autoregulation, and hyaline degeneration and are especially at risk. Though this setting predisposes these patients to the formation of MAs, the cause of focal arterial wall weakness is still not completely understood.8,10 Most MAs occur at arteriovenous crossings, where the 2 vessels are in contact and share a common coat. Less structural support is present in this area and the weaker vessel walls may be prone to aneurysmal formation.4 Macroaneurysms have a dynamic formation, followed by enlargement (which may or may not disrupt the blood–retinal barrier). Most MAs then undergo a gradual thrombosis, fibrosis, and spontaneous involution. The type of vessel changes classifies MAs as ‘‘saccular’’ (blow-out) or ‘‘fusiform’’ (cuffed).12,13 Fusiform MAs display circumferential widening of the retinal artery, whereas saccular MAs represent localized outpouchings of the retinal artery wall. The saccular type is more prone to bleed, as a thin, stretched aneurysmal sac is relatively easy to perforate in an area of high perfusion pressure.13 After resolution of the MA, findings often include vessel kinking at the site of the resolved MA, arteriolar constriction proximal to the MA, and arterial sheathing distal to the MA.14-16 Fluorescein angiographic findings
Retinal arterial macroaneurysms (MAs) have been described in the literature since the nineteenth century,1,2 though Robertson was the first to give the retinal finding a name and description in 1973.3 The term was applied to retinal arterial lesions with the following characteristics: (1) arterial swelling with a saccular or fusiform (‘‘blowout’’ or ‘‘cuffed’’) appearance; (2) positioned on the first 3 orders of the retinal artery tree; and (3) found mainly at arterial bifurcations. Lavin et al.4 described MAs as ‘‘local arterial dilatations with variable degrees of artery wall hyalinization and surrounding retinal exudate or hemorrhage.’’4 These vessel dilatations tend to rupture before they grow large and tend to be no larger than approximately 1/3 disc diameter in size.5,6 Symptomatic patients notice a loss of vision caused by retinal hemorrhage (on any level of the retina), exudate, or edema. Careful examination and regards to differential diagnoses are important, because MAs are often diagnosed incorrectly and are regarded as a ‘‘masquerade syndrome.’’7 Given strong associations with systemic disease, patients with macroaneurysms should also have prompt medical evaluation.
Epidemiology and risk factors Macroaneurysms are most frequently seen in elderly persons in the sixth to eighth decade with a preponderance of
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after MA resolution include widening of the capillary-free zone and intra-arterial collateral vessels.9
Presentation Macroaneurysms most commonly are seen on the first 3 orders of the retinal artery tree and are found mainly at vessel bifurcations. They are more commonly found on superotemporal and inferotemporal vessels than nasal vessels (see Figure 2).4 The most dominant feature of MAs is hemorrhage into the retinal and vitreous spaces and, less frequently, retinal exudate and edema. Amount of hemorrhage can be variable, from small hemorrhages involving 1 layer of the retina, to large, multilevel hemorrhages with or without vitreous extension. Exudation can be very insignificant in severity or can produce a massive exudative response. Retinal hemorrhage can involve subretinal, intraretinal, and preretinal spaces. It has been reported that approximately 50% of patients have an associated retinal hemorrhage, 40% have simultaneous subretinal and preretinal bleeding, and 10% have a vitreous hemorrhage.17 Vitreous hemorrhage from MAs can lead to ghost cell glaucoma and has been reported to be associated with a secondary acute angle closure glaucoma.18,19 Though some MAs that do not affect the macular area may be asymptomatic, patients most commonly present with acute, painless loss of vision. Level of vision loss depends on severity of hemorrhage or exudate. Central loss of vision is often caused by retina hemorrhage, exudate, or edema affecting the macula or a generalized loss of vision caused by vitreous hemorrhage.4 Subretinal hemorrhage is the most damaging to sight and retinal tissue, especially in the macular area, as subretinal blood can be toxic.9 Irreversible damage to photoreceptor and retinal pigmented epithelial cells can occur after 2 weeks of subretinal bleeding as seen in animal studies, which can lead to permanent loss of central vision.20 Prognosis for visual recovery depends on macular pathology. Patients with vitreous hemorrhage or premacular hemorrhage have a better visual prognosis than those with macular edema, intraretinal hemorrhage, or submacular hemorrhage.21
Differential diagnosis Clinical presentation of MAs can vary widely and is considered a ‘‘masquerade syndrome.’’7 They often are misdiagnosed before fluorescein angiography. One study found hemorrhagic MAs were misdiagnosed at a rate of 75% upon presentation.4 Differential diagnoses vary depending on ocular signs upon presentation. Differential diagnosis for a vitreous hemorrhage would include proliferative diabetic retinopathy, retinal tear, branch retinal vein occlusion, and hemorrhagic macular degeneration. When presented with hemorrhage near or involving the macula, etiologies such as macular degeneration, presumed ocular histoplasmosis syndrome (POHS), high myopia, trauma, Valsalva
Figure 2
Presentation of a retinal arterial macroaneurysm in another
patient.
retinopathy, idiopathic polypoidal choroidal vasculopathy, or choroidal neovascularization from any cause should be considered.22 When presented with retinal hemorrhaging or exudation, differentials should include diabetic retinopathy, central or branch retinal vein occlusion, venous macroaneurysms, Coat’s disease, retinal telangiectasias, radiation retinopathy, cavernous hemangioma, and retinal capillary angiomas. Leakage of blood beneath the sensory retina from MAs can appear as a dark mass that may simulate choroidal melanoma.23 Larger retinal macroaneurysms may present with large amounts of retinal exudation and hemorrhage and can simulate metastatic intraocular tumor.5 Because macroaneurysms can mimic many retinal conditions, fluorescein angiography often establishes the diagnosis. Fluorescein angiography of fusiform MAs shows rapid filling in early arterial phase, whereas saccular MAs showed minimal early filling, with good filling in the middle to late phases.4 Filling in the early arterial phase may be segmental in nature due to clot formation or scarring from blockage of the lumen by thrombosis or endothelial cell formation.24 Angiography of MAs that have ‘‘self-sealed’’ may show no leakage, as in the case discussed above. Fluorescein may also show changes in capillaries adjacent to the MAs, including dilatation, telangiectasia, and closure. In cases in which retinal hemorrhage blocks visual inspection of the aneurysm, as well as adequate imaging with fluorescein angiography, ICG has been useful. ICG’s dye absorption and emission peak is in the near-infrared spectrum, and allows better penetration through dense hemorrhage, exudates, and retinal pigmented epithelial changes.25,26 Fluorescein angiography uses blue or green light in the shorter wavelengths and does not have this ability. ICG is also 98% protein bound (compared with 60% for fluorescein), so it leaks less and provides sharper, more well-defined images, especially of the choroid and choroidal pathology.27 ICG can pinpoint the exact location of the macroaneurysm in cases of dense hemorrhage, which is useful in planning surgery or treatment. ICG of MAs will show well-defined areas of hyperfluoresence. Standardized A-scan and B-scan echography can also be helpful
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in diagnosing MAs before vitrectomy when dense vitreous hemorrhage obscures the retina. Echographic features characteristic of MAs include irregular internal reflectivity and a pulsatile vascular structure at the anterior aspect of the lesion.28
Treatment The decision to treat a macroaneurysm or the hemorrhages associated with it depends on several factors. Because the majority of MAs will undergo spontaneous involution, with no residual vision loss, a strong case can be made for observation.17 Vander et al.29 suggested the following general recommendations: (1) patients with good vision and no macular involvement should be observed; (2) patients with decreased vision on the basis of intraretinal, preretinal, or vitreous hemorrhage should be observed over several months for spontaneous resolution before treatment is given; and (3) patients with macular involvement (edema, exudates, or submacular hemorrhage) or retinal detachment should be treated. The treatment options for MAs include direct and indirect laser photocoagulation and, in some cases, surgical excision with vitrectomy. Laser photocoagulation, whether direct or indirect, uses Argon green or dye yellow tunable laser at low energy levels to create light to medium burns on the retina. The goal of direct treatment is to accelerate the involution of the macroaneurysm, thereby eliminating the source of leakage. Indirect treatment applies laser burns to the retina surrounding the MA, forming a barrier between the leaking MA and the macula. The complications from direct and indirect laser treatment include arteriolar occlusion, severe foveal capillary dropout, and subretinal scarring.30 In cases in which the MA is too large or cannot be treated by photocoagulation, or when recurrences are a problem, surgical excision has emerged as an alternative.31 The complications are similar to those of laser photocoagulation, and although photocoagulation remains the first treatment of choice for MAs, surgical excision may be a suitable option for severe cases.31 Vitreous hemorrhage associated with MAs has a good prognosis for visual recovery and can usually be observed. In general, pars plana vitrectomy should be considered for nonclearing hemorrhage (usually considered after 3 to 6 months) or when the hemorrhage interferes with additional treatment needed to prevent vision loss.32 Preretinal (subinternal limiting membrane) hemorrhage can also spontaneously resorb with no vision loss; however, the potential exists for epiretinal membrane formation and irreversible retinal damage caused by the toxic effects of the preretinal blood.33,34 Historically, when treatment was indicated, pars plana vitrectomy was performed.35 However, for recent, dense preretinal hemorrhage, the use of neodymiumyttrium-aluminum-garnet (Nd:YAG) laser has been reported.36 The focal disruption to the internal limiting membrane allows the hemorrhage to drain into the vitreous where it can be absorbed more quickly.33,36,37 However, it must be
429 noted that visual improvement may be limited if a subretinal/submacular hemorrhage exists or if the resultant vitreous hemorrhage is dense and nonclearing, eventually requiring a vitrectomy.33,35 The Nd:YAG laser procedure also has potential complications such as macular hole and retinal detachment.35 Before this procedure can be established as the standard of care, a randomized, prospective study is needed to compare observation, primary vitrectomy, and Nd:YAG laser treatment.35,38 Intraretinal hemorrhages associated with retinal arterial macroaneurysms usually resorb completely and spontaneously with little or no visual compromise.9,17,34 However, a subretinal hemorrhage has the potential to be visually devastating, especially if submacular, and the best treatment is not known. In cases of localized, thin-layered hemorrhage, the prognosis for visual recovery is better than in cases of dense, thick-clotted hemorrhage caused by the toxic effects of prolonged bleeding to the photoreceptors and retinal pigment epithelium and the development of fibrin within the clots.17,39 Clearance of the subretinal blood is essential to improve cellular functioning and prevent further vision loss.20,36 This can be accomplished via submacular surgery or pneumatic displacement. Both procedures have been studied using tissue plasminogen activator (tPA) to facilitate fibrinolysis and thrombolysis.36,40 Submacular surgery attempts to remove the hemorrhage via pars plana vitrectomy, drainage of the submacular hemorrhage through a retinotomy, a fluid-air exchange, and then insufflation with an intravitreal gas. The patient is required to have facedown head positioning for about 1 week.39,40 An alternative to submacular surgery is pneumatic displacement. Pneumatic displacement is less invasive than submacular surgery; it uses an intraocular gas bubble and facedown head positioning to move or displace the hemorrhage, rather than remove it.36 Pneumatic displacement offers a simpler procedure at a lower cost compared with submacular surgery. Both procedures share potential complications, such as cataract formation, retinal breaks or detachment, epiretinal membrane formation, proliferative vitreo-retinopathy, and endophthalmitis. However, pneumatic displacement might be expected to have less frequent and less severe complications.36
Conclusion Optometrists should be aware of the many presentations and differential diagnoses of retinal arterial macroaneurysms. Given the high percentage of associated systemic disease, a systemic workup may be required. A multidisciplinary approach, including primary eye provider, retina specialist, and internist/primary care provider may be necessary. Treatment options may include laser photocoagulation, vitrectomy, and surgical excision. Although, as seen in the case discussed, careful observation often is sufficient for an excellent prognosis.
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References 1. Doyne RW. Case of peculiar condition of the retina due possibly to the formation of small aneurysms and large extravasation of blood which has become decolourised. Trans Ophthalmol Soc UK 1896;16:94. 2. Loring FB. Peculiar anatomical development of one of the central arteries of the retina. Trans Am Ophthalmol Soc 1881;3:40-2. 3. Robertson DM. Macroaneurysms of the retinal arteries. Ophthalmology 1973;77:55-67. 4. Lavin MJ, Marsh RJ, Peart S, et al. Retinal areterial macroaneurysms: a retrospective study of 40 patients. Br J Ophthalmol 1987;71(11): 817-25. 5. Ohno- Matsui K, Hayano M, Futagami S, et al. Spontaneous involution of a large retinal arterial macroaneurysm. Acta Ophthalmol Scand 2000;78(1):114-7. 6. Brown GC, Weinstock F. Arterial macroaneurysm on the optic disk presenting as a mass lesion. Ann Opthalmol 1985;17:519-20. 7. Spalter HF. Retinal macroaneurysms: a new masquerade syndrome. Trans Am Ophthalmol Soc 1982;80:113-30. 8. Panton RW, Goldberg MF, Farber MD. Retinal arterial macroaneurysms: risk factors and natural history. Br J Ophthalmol 1990;74(10): 595-600. 9. Moosavi RA, Fong KC, Chopdar A. Retinal artery macroaneurysms: clinical and fluorescein angiographic features in 34 patients. Eye 2006;20(9):1011-20. 10. Colucciello M. Retinal vascular disease in hypertension. Risk factor modification optimizes vision outcomes. Postgrad Med 2005;117(6): 33-8, 41-2. 11. Sekuri C, Kayikcioglu M, Kayikcioglu O. Retinal artery macroaneurysm as initial presentation of hypertension. Int J Cardiol 2004;93(1): 87-8. 12. Fitche C, Streeten BW, Freedman AH. A histopathologic study of retinal arterial aneurysms. Am J Ophthalmol 1978;85:509-18. 13. Abdel-Khalk MN, Richardson J. Retinal macroaneurysm: natural history and guideline for treatment. Br J Opthalmol 1986;70(1):2-11. 14. Palestine AG, Robertson DM, Goldstein B. Macroaneurysms of the retinal arteries. Am J Ophthalmol 1982;93:164-71. 15. Lewis RA, Norton EWD, Gass JDM. Acquired arterial macroaneurysm of the retinal arteries. Br J Ophthalmol 1976;60:21-30. 16. Cleary PE, Kohner EM, Hamilton AM, et al. Retinal macroaneurysms. Br J Ophthalmol 1975;59:355-61. 17. Rabb M, Gagliano D, Teske M. Retinal arterial macroaneurysm. Surv Ophthalmol 1988;33(2):73-96. 18. Spraul CW, Grossniklaus HE. Vitreous hemorrhage. Surv Ophthalmol 1997;42(1):3-39. 19. Arthur SM, Mason J, Roberts B, et al. Secondary acute angle closure glaucoma associated with vitreous hemorrhage after ruptured retinal arterial macroaneurysm. Am J Ophthalmol 2004;138(4):682-3. 20. Toth CA, Morse LS, Hjelmeland LM, et al. Fibrin directs early retinal damage after experimental subretinal hemorrhage. Arch Ophthalmol 1991;109(5):723-9. 21. Tonotsuka T, Imai M, Saito K, et al. Visual prognosis for symptomatic retinal arterial macroaneurysm. Jpn J Ophthalmol 2003;47(5): 498-502.
Optometry, Vol 80, No 8, August 2009 22. Lindgren G, Sjodell L, Lindblom B. A prospective study of dense spontaneous vitreous hemorrhage. Am J Ophthalmol 1995;119(4): 458-65. 23. Sheilds CL, Sheilds JA. Subretinal hemorrhage from a retinal arterial macroaneurysm simulating a choroidal melanoma. Ophthalmic Surg Lasers 2001;32(1):86-7. 24. Brent BD, Gonce M, Diamond JG. Pars plana vitrectomy for complications of retinal arterial macroaneurysms a case series. Ophthalmic Surg 1993;24(8):534-6. 25. Bischoff PM, Flower RW. Ten years experience with choroidal angiography using indocyanine green dye: a new routine examination or an epilogue? Doc Ophthalmol 1985;60(3):235-91. 26. Townsend-Pico WA, Meyers SM, Lewis H. Indocyanine green angiography in the diagnosis of retinal arterial macroaneurysms associated with submacular and preretinal hemorrhages: a case series. Am J Ophthalmol 2000;129(1):33-7. 27. Guyer DR, Yannuzi LA, Slakter JS, et al. Digital indocyanine-green videoangiography of occult choroidal neovascularization. Ophthalmology 1994;101(10):1727-35. 28. Tang WM, Pulido JS, Connor TB, et al. Echographic characteristics of retinal arterial macroaneurysm. Retina 1998;18(6):559-63. 29. Vander JF, Duker JS, Jaeger EA. Miscellaneous diseases of the fundus. In: Tasman W, Jaeger E, eds. Duane’s clinical ophthalmology. Revised ed. Vol 3. Philadelphia: Lippincott-Raven; 1997:8-10. 30. Brown DM, Sobol WM, Folk JC, et al. Retinal arteriolar macroaneurysms: long term visual outcome. Br J Ophthalmol 1994;78:534-8. 31. Oie Y, Emi K. Surgical excision of retinal macroaneurysms with submacular hemorrhage. Jpn J Ophthalmol 2006;50:550-3. 32. Goff MJ, McDonald HR, Johnson RN, et al. Causes and treatment of vitreous hemorrhage. Compr Ophthalmol Update 2006;7(3):97-111. 33. Gedik S, Gur S, Yilmaz G, et al. Retinal arterial macroaneurysm rupture following fundus fluorescein angiography and treatment with Nd: YAG laser membranectomy. Ophthalmic Surg Lasers Imaging 2007; 38(2):154-6. 34. Gurwood A, Nicholson CR. Retinal arterial macroaneurysm: a case report. J Am Optom Assoc 1998;69:41-8. 35. Ulbig MW, Mangouritsas G, Rothbacher HH, et al. Long-term results after drainage of premacular subhyaloid hemorrhage into the vitreous with a pulsed Nd:YAG laser. Arch Ophthalmol 1998; 116(11):1465-9. 36. Wu TT, Sheu SJ. Intravitreal tissue plasminogen activator and pneumatic displacement of submacular hemorrhage secondary to retinal artery macroaneurysm. J Ocul Pharmacol Ther 2005;21(1):62-7. 37. Iijima H, Satoh S, Tsukahara S. Nd:YAG laser photodisruption for preretinal hemorrhage due to retinal macroaneurysm. Retina 1998;18(5): 430-4. 38. Celebi S, Kukner AS. Photodisruptive Nd:YAG laser in the management of premacular subhyaloid hemorrhage. Eur J Ophthalmol 2001;11(3):281-6. 39. Tan CS, Au Eong KG. Surgical drainage of submacular haemorrhage from ruptured retinal arterial macroaneurysm. Acta Ophthalmol Scand 2005;83(2):240-1. 40. Humayun M, Lewis H, Flynn HW Jr, et al. Management of submacular hemorrhage associated with retinal arterial macroaneurysms. Am J Ophthalmol 1998;126:358-61.
Retinal arterial macroaneurysm causing multilevel retinal hemorrhage Elizabeth Kester, O.D.,a and Erica Walker, O.D.b a
William Chappell VA Outpatient Clinic, Daytona Beach, Florida; and bOrlando VA Healthcare Center, Orlando, Florida.
KEYWORDS Retinal arterial macroaneurysm; Hypertension; Masquerade syndrome; Intravenous fluorescein angiography
Abstract BACKGROUND: Retinal arterial macroaneurysms are focal dilatations of the retinal arteries that present with varying degrees of retinal hemorrhage or exudation. They are most often associated with hypertension and may masquerade as many other retinal conditions. CASE REPORT: A hypertensive 59-year-old man presented to the clinic with a sudden onset of painless vision loss in the left eye. Best-corrected visual acuities were 20/20 in the right eye and counting fingers at 3 feet with eccentric viewing in the left. Dilated fundus examination found a multilevel retinal hemorrhage involving most of the superior arcade and extending into the macular area. A diagnosis of retinal arterial macroaneurysm was given after fluorescein angiography and evaluation by a retina specialist. Hemorrhage resolved without treatment, and visual acuity returned to 20/25 by the 6-month follow-up visit. CONCLUSIONS: Optometrists should be aware of presenting signs and symptoms associated with retinal macroaneurysms as well as the many differentials and possible treatments. Given the high incidence of associated systemic disease, proper knowledge of necessary systemic workup is also critical. Optometry 2009;80:425-430
Retinal arterial macroaneurysms have been described in the literature for many years. These vascular lesions can have a multitude of findings at presentation, including multilevel retinal hemorrhages, exudates, and edema. Primary eye care providers need to be familiar with the varied presentations, differential diagnoses, and management options of retinal arterial macroaneurysms. Systemic diseases, such as hypertension, have been associated with macroaneurysms; therefore, a systemic workup may be indicated. The following case report describes a patient with a macroaneurysm, from the significant hemorrhagic presentation to eventual resolution, over 18 months of follow-up. This case also shows that a multidisciplinary approach, including primary eye provider,
Corresponding author: Elizabeth Kester, O.D., William Chappell VA Outpatient Clinic, 551 National Healthcare Dr., Daytona Beach, Florida 32114. E-mail: [email protected]
retina specialist, and internist/primary care provider may be necessary.
Case report A 59-year-old man presented with complaints of sudden loss of vision in the left eye (O.S.) upon wakening that morning. He reported that a large, yellowish-red spot was blocking his central vision O.S., and he felt it had the appearance of blood. He denied pain O.S. or any loss of vision in the right eye (O.D.). He denied any recent symptoms of flashes or floaters in either eye. Medical history was significant for type 2 diabetes mellitus, hyperlipidemia, peripheral neuropathy, pernicious anemia, vitamin B12 deficiency, and actinic keratosis. Ocular history was unremarkable. The patient was examined approximately 9 months prior, and no ocular pathology was noted at that time. Current medications included glipizide, hydroxyzine pamoate, insulin novolin 70/30,
1529-1839/09/$ -see front matter -This is a U.S. government work. There are no restrictions on its use. Published by Elsevier, Inc. on behalf of the American Optometric Association.
doi:10.1016/j.optm.2008.12.009
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naproxen, and propoxyphene N/APAP. Blood pressure was measured in the office at 149/89 mmHg. Best-corrected visual acuity was 20/20 O.D. and counting fingers at 3 feet with eccentric viewing O.S. Pupils were equal, round, and reactive to light without afferent pupillary defect. Ocular motility was full in both eyes (OU), and confrontation fields were full to finger counting with some difficulty O.S. Anterior-segment slit lamp examination found early nuclear sclerotic lens changes with otherwise unremarkable findings. Applanation tonometry found tensions of 16 mmHg O.D. and 14 mmHg O.S. Dilated fundus examination found vertical cup-to-disc ratios of 0.3 O.D. and 0.3 O.S. Posterior pole, macular, and peripheral examination findings were unremarkable O.D. A large retinal hemorrhage extended from the superior arcade inferiorly to the superior rim of the optic nerve and also extended through the macular area obscuring macular details (see Figure 1A). The hemorrhage was multilevel, including preretinal, intraretinal, and subretinal involvement. A possible source of the hemorrhage could be appreciated in the superior arcade, as slight vessel elevation or outpouching was noted, but obscuration by the hemorrhage made it difficult to determine. A tentative diagnosis of macroaneurysm was made, and the patient was scheduled to see a retina specialist the following day. Clinical picture and patient complaints were unchanged the following day. Intravenous fluorescien angiography (IVFA) and indocyanine green (ICG) angiography were performed but did not show any areas of active leakage or ‘‘hotspots.’’ The retina specialist felt it was a multilevel
Figure 1
retinal hemorrhage likely caused by a macroaneurysm. No treatment was recommended at that time, and a follow-up appointment was made for 1 month. Strict blood pressure control was stressed, and the patient’s primary care physician started him on lisinopril, 5 mg/day the following day. At the 1-month follow-up examination, the patient felt he may have had a minimal improvement in his vision O.S. Best-corrected visual acuity was measured at 20/20 O.D. and 20/400 O.S. Pupils, anterior segment examination, and intraocular pressures (IOPs) were unremarkable. Dilated fundus examination was unchanged O.D., and the left eye showed some resolution of the multilevel hemorrhage from presentation (see Figure 1B). Portions of the hemorrhage contained degenerating red blood cells, and this dehemoglobinization gives portions of the resolving hemorrhage a yellowish color. A small amount of exudate was visible temporal to the macula. No treatment was recommended at that time given the improvement in the clinical picture. The patient was scheduled for a re-evaluation in 1 month. The visual acuity in the left eye was still 20/400 at the 2month follow-up but the patient felt the vision was improving. On fundus examination O.S., the hemorrhage was still resolving, with most of the hemorrhage dehemoglobinized with a yellowish appearance (see Figure 1C). No new leakage or bleeding was noted that day. The retina specialist felt that if there was no resolution in 3 to 4 weeks, a 25-gauge vitrectomy would be indicated. Blood pressure at this visit had improved to 115/68 mmHg. Three months after initial presentation, the patient’s visual acuity had improved to 20/100 O.S. A preretinal
Fundus photos of the left eye at A, Initial presentation; B, 1 month; C, 2 months; D, 4 months; and E, 6 months after presentation.
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hemorrhage was still present extending from the optic nerve to the macula, but given the improvement in vision, no treatment was recommended at that time. Four months after the initial visit, the visual acuity was 20/150 O.S., and a small amount of preretinal hemorrhage was still present in the macular area, as well as temporal to the optic nerve and in the superior arcade (see Figure 1D). Repeat IVFA was performed, and no leakage was noted. A return visit was scheduled for 8 weeks. At the 6-month follow-up visit, visual acuity had improved to 20/25 O.S. Almost complete resolution of the macular hemorrhage was noted, with small residual areas of preretinal hemorrhage noted in the posterior pole (see Figure 1E). A small area of perivascular sclerotic tissue was present in the superior arcade at the previous source of the macroaneurysm. The patient was encouraged to continue proper blood pressure control and to return to the clinic immediately with any changes in vision. The patient returned 1 year later, with best-corrected visual acuity of 20/20 O.D. and 20/20 O.S. Vessel sclerosis was still present at the site of the previous macroaneurysm, and a very faint preretinal heme was visible temporally to the optic nerve.
women affected.7 Several studies have reported average age on presentation of 66.1 years,4 69.7 years,8 and 73.7 years,9 respectively, with increasing age elevating risk of occurrence. Systemic risk factors include hypertension, atherosclerosis, hyperlipidemia, retinal arterial emboli,10 cerebrovascular disease, and polycythemia.4 Hypertension is the most common association, affecting approximately 75% of patients presenting with MAs.11 In fact, in a retrospective study of macroaneurysm patients by Lavin et al.,4 17 of the 18 patients examined by their medical clinic were found to have ‘‘evidence of systemic vascular or relevant metabolic disease.’’ Patients who present with MAs require full investigation for systemic disease with attention to hypertension, systemic vascular disease, and embolic disease. Recommended studies include complete blood count (with differential and platelets), fasting blood sugar and glycosylated hemoglobin, blood pressure, fasting lipid profile, carotid auscultation or carotid duplex ultrasonography, and cardiac evaluation. A prompt multispecialty approach may include primary eye provider, retina specialist, internal medicine physician, and cardiologist.
Discussion
Pathophysiology
Background
Histologic study of macroaneurysms confirms a true aneurysm formation including vessel wall thickening, change in hyaline, and elastotic degeneration.12 As arterioles age, intimal collagen replaces smooth muscle fibers, and the arterial wall becomes less elastic. These vessels are more susceptible to dilatation from elevated hydrostatic pressure.9 Hypertensive patients also experience elevated hydrostatic pressure, decreased autoregulation, and hyaline degeneration and are especially at risk. Though this setting predisposes these patients to the formation of MAs, the cause of focal arterial wall weakness is still not completely understood.8,10 Most MAs occur at arteriovenous crossings, where the 2 vessels are in contact and share a common coat. Less structural support is present in this area and the weaker vessel walls may be prone to aneurysmal formation.4 Macroaneurysms have a dynamic formation, followed by enlargement (which may or may not disrupt the blood–retinal barrier). Most MAs then undergo a gradual thrombosis, fibrosis, and spontaneous involution. The type of vessel changes classifies MAs as ‘‘saccular’’ (blow-out) or ‘‘fusiform’’ (cuffed).12,13 Fusiform MAs display circumferential widening of the retinal artery, whereas saccular MAs represent localized outpouchings of the retinal artery wall. The saccular type is more prone to bleed, as a thin, stretched aneurysmal sac is relatively easy to perforate in an area of high perfusion pressure.13 After resolution of the MA, findings often include vessel kinking at the site of the resolved MA, arteriolar constriction proximal to the MA, and arterial sheathing distal to the MA.14-16 Fluorescein angiographic findings
Retinal arterial macroaneurysms (MAs) have been described in the literature since the nineteenth century,1,2 though Robertson was the first to give the retinal finding a name and description in 1973.3 The term was applied to retinal arterial lesions with the following characteristics: (1) arterial swelling with a saccular or fusiform (‘‘blowout’’ or ‘‘cuffed’’) appearance; (2) positioned on the first 3 orders of the retinal artery tree; and (3) found mainly at arterial bifurcations. Lavin et al.4 described MAs as ‘‘local arterial dilatations with variable degrees of artery wall hyalinization and surrounding retinal exudate or hemorrhage.’’4 These vessel dilatations tend to rupture before they grow large and tend to be no larger than approximately 1/3 disc diameter in size.5,6 Symptomatic patients notice a loss of vision caused by retinal hemorrhage (on any level of the retina), exudate, or edema. Careful examination and regards to differential diagnoses are important, because MAs are often diagnosed incorrectly and are regarded as a ‘‘masquerade syndrome.’’7 Given strong associations with systemic disease, patients with macroaneurysms should also have prompt medical evaluation.
Epidemiology and risk factors Macroaneurysms are most frequently seen in elderly persons in the sixth to eighth decade with a preponderance of
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after MA resolution include widening of the capillary-free zone and intra-arterial collateral vessels.9
Presentation Macroaneurysms most commonly are seen on the first 3 orders of the retinal artery tree and are found mainly at vessel bifurcations. They are more commonly found on superotemporal and inferotemporal vessels than nasal vessels (see Figure 2).4 The most dominant feature of MAs is hemorrhage into the retinal and vitreous spaces and, less frequently, retinal exudate and edema. Amount of hemorrhage can be variable, from small hemorrhages involving 1 layer of the retina, to large, multilevel hemorrhages with or without vitreous extension. Exudation can be very insignificant in severity or can produce a massive exudative response. Retinal hemorrhage can involve subretinal, intraretinal, and preretinal spaces. It has been reported that approximately 50% of patients have an associated retinal hemorrhage, 40% have simultaneous subretinal and preretinal bleeding, and 10% have a vitreous hemorrhage.17 Vitreous hemorrhage from MAs can lead to ghost cell glaucoma and has been reported to be associated with a secondary acute angle closure glaucoma.18,19 Though some MAs that do not affect the macular area may be asymptomatic, patients most commonly present with acute, painless loss of vision. Level of vision loss depends on severity of hemorrhage or exudate. Central loss of vision is often caused by retina hemorrhage, exudate, or edema affecting the macula or a generalized loss of vision caused by vitreous hemorrhage.4 Subretinal hemorrhage is the most damaging to sight and retinal tissue, especially in the macular area, as subretinal blood can be toxic.9 Irreversible damage to photoreceptor and retinal pigmented epithelial cells can occur after 2 weeks of subretinal bleeding as seen in animal studies, which can lead to permanent loss of central vision.20 Prognosis for visual recovery depends on macular pathology. Patients with vitreous hemorrhage or premacular hemorrhage have a better visual prognosis than those with macular edema, intraretinal hemorrhage, or submacular hemorrhage.21
Differential diagnosis Clinical presentation of MAs can vary widely and is considered a ‘‘masquerade syndrome.’’7 They often are misdiagnosed before fluorescein angiography. One study found hemorrhagic MAs were misdiagnosed at a rate of 75% upon presentation.4 Differential diagnoses vary depending on ocular signs upon presentation. Differential diagnosis for a vitreous hemorrhage would include proliferative diabetic retinopathy, retinal tear, branch retinal vein occlusion, and hemorrhagic macular degeneration. When presented with hemorrhage near or involving the macula, etiologies such as macular degeneration, presumed ocular histoplasmosis syndrome (POHS), high myopia, trauma, Valsalva
Figure 2
Presentation of a retinal arterial macroaneurysm in another
patient.
retinopathy, idiopathic polypoidal choroidal vasculopathy, or choroidal neovascularization from any cause should be considered.22 When presented with retinal hemorrhaging or exudation, differentials should include diabetic retinopathy, central or branch retinal vein occlusion, venous macroaneurysms, Coat’s disease, retinal telangiectasias, radiation retinopathy, cavernous hemangioma, and retinal capillary angiomas. Leakage of blood beneath the sensory retina from MAs can appear as a dark mass that may simulate choroidal melanoma.23 Larger retinal macroaneurysms may present with large amounts of retinal exudation and hemorrhage and can simulate metastatic intraocular tumor.5 Because macroaneurysms can mimic many retinal conditions, fluorescein angiography often establishes the diagnosis. Fluorescein angiography of fusiform MAs shows rapid filling in early arterial phase, whereas saccular MAs showed minimal early filling, with good filling in the middle to late phases.4 Filling in the early arterial phase may be segmental in nature due to clot formation or scarring from blockage of the lumen by thrombosis or endothelial cell formation.24 Angiography of MAs that have ‘‘self-sealed’’ may show no leakage, as in the case discussed above. Fluorescein may also show changes in capillaries adjacent to the MAs, including dilatation, telangiectasia, and closure. In cases in which retinal hemorrhage blocks visual inspection of the aneurysm, as well as adequate imaging with fluorescein angiography, ICG has been useful. ICG’s dye absorption and emission peak is in the near-infrared spectrum, and allows better penetration through dense hemorrhage, exudates, and retinal pigmented epithelial changes.25,26 Fluorescein angiography uses blue or green light in the shorter wavelengths and does not have this ability. ICG is also 98% protein bound (compared with 60% for fluorescein), so it leaks less and provides sharper, more well-defined images, especially of the choroid and choroidal pathology.27 ICG can pinpoint the exact location of the macroaneurysm in cases of dense hemorrhage, which is useful in planning surgery or treatment. ICG of MAs will show well-defined areas of hyperfluoresence. Standardized A-scan and B-scan echography can also be helpful
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in diagnosing MAs before vitrectomy when dense vitreous hemorrhage obscures the retina. Echographic features characteristic of MAs include irregular internal reflectivity and a pulsatile vascular structure at the anterior aspect of the lesion.28
Treatment The decision to treat a macroaneurysm or the hemorrhages associated with it depends on several factors. Because the majority of MAs will undergo spontaneous involution, with no residual vision loss, a strong case can be made for observation.17 Vander et al.29 suggested the following general recommendations: (1) patients with good vision and no macular involvement should be observed; (2) patients with decreased vision on the basis of intraretinal, preretinal, or vitreous hemorrhage should be observed over several months for spontaneous resolution before treatment is given; and (3) patients with macular involvement (edema, exudates, or submacular hemorrhage) or retinal detachment should be treated. The treatment options for MAs include direct and indirect laser photocoagulation and, in some cases, surgical excision with vitrectomy. Laser photocoagulation, whether direct or indirect, uses Argon green or dye yellow tunable laser at low energy levels to create light to medium burns on the retina. The goal of direct treatment is to accelerate the involution of the macroaneurysm, thereby eliminating the source of leakage. Indirect treatment applies laser burns to the retina surrounding the MA, forming a barrier between the leaking MA and the macula. The complications from direct and indirect laser treatment include arteriolar occlusion, severe foveal capillary dropout, and subretinal scarring.30 In cases in which the MA is too large or cannot be treated by photocoagulation, or when recurrences are a problem, surgical excision has emerged as an alternative.31 The complications are similar to those of laser photocoagulation, and although photocoagulation remains the first treatment of choice for MAs, surgical excision may be a suitable option for severe cases.31 Vitreous hemorrhage associated with MAs has a good prognosis for visual recovery and can usually be observed. In general, pars plana vitrectomy should be considered for nonclearing hemorrhage (usually considered after 3 to 6 months) or when the hemorrhage interferes with additional treatment needed to prevent vision loss.32 Preretinal (subinternal limiting membrane) hemorrhage can also spontaneously resorb with no vision loss; however, the potential exists for epiretinal membrane formation and irreversible retinal damage caused by the toxic effects of the preretinal blood.33,34 Historically, when treatment was indicated, pars plana vitrectomy was performed.35 However, for recent, dense preretinal hemorrhage, the use of neodymiumyttrium-aluminum-garnet (Nd:YAG) laser has been reported.36 The focal disruption to the internal limiting membrane allows the hemorrhage to drain into the vitreous where it can be absorbed more quickly.33,36,37 However, it must be
429 noted that visual improvement may be limited if a subretinal/submacular hemorrhage exists or if the resultant vitreous hemorrhage is dense and nonclearing, eventually requiring a vitrectomy.33,35 The Nd:YAG laser procedure also has potential complications such as macular hole and retinal detachment.35 Before this procedure can be established as the standard of care, a randomized, prospective study is needed to compare observation, primary vitrectomy, and Nd:YAG laser treatment.35,38 Intraretinal hemorrhages associated with retinal arterial macroaneurysms usually resorb completely and spontaneously with little or no visual compromise.9,17,34 However, a subretinal hemorrhage has the potential to be visually devastating, especially if submacular, and the best treatment is not known. In cases of localized, thin-layered hemorrhage, the prognosis for visual recovery is better than in cases of dense, thick-clotted hemorrhage caused by the toxic effects of prolonged bleeding to the photoreceptors and retinal pigment epithelium and the development of fibrin within the clots.17,39 Clearance of the subretinal blood is essential to improve cellular functioning and prevent further vision loss.20,36 This can be accomplished via submacular surgery or pneumatic displacement. Both procedures have been studied using tissue plasminogen activator (tPA) to facilitate fibrinolysis and thrombolysis.36,40 Submacular surgery attempts to remove the hemorrhage via pars plana vitrectomy, drainage of the submacular hemorrhage through a retinotomy, a fluid-air exchange, and then insufflation with an intravitreal gas. The patient is required to have facedown head positioning for about 1 week.39,40 An alternative to submacular surgery is pneumatic displacement. Pneumatic displacement is less invasive than submacular surgery; it uses an intraocular gas bubble and facedown head positioning to move or displace the hemorrhage, rather than remove it.36 Pneumatic displacement offers a simpler procedure at a lower cost compared with submacular surgery. Both procedures share potential complications, such as cataract formation, retinal breaks or detachment, epiretinal membrane formation, proliferative vitreo-retinopathy, and endophthalmitis. However, pneumatic displacement might be expected to have less frequent and less severe complications.36
Conclusion Optometrists should be aware of the many presentations and differential diagnoses of retinal arterial macroaneurysms. Given the high percentage of associated systemic disease, a systemic workup may be required. A multidisciplinary approach, including primary eye provider, retina specialist, and internist/primary care provider may be necessary. Treatment options may include laser photocoagulation, vitrectomy, and surgical excision. Although, as seen in the case discussed, careful observation often is sufficient for an excellent prognosis.
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Optometry, Vol 80, No 8, August 2009 22. Lindgren G, Sjodell L, Lindblom B. A prospective study of dense spontaneous vitreous hemorrhage. Am J Ophthalmol 1995;119(4): 458-65. 23. Sheilds CL, Sheilds JA. Subretinal hemorrhage from a retinal arterial macroaneurysm simulating a choroidal melanoma. Ophthalmic Surg Lasers 2001;32(1):86-7. 24. Brent BD, Gonce M, Diamond JG. Pars plana vitrectomy for complications of retinal arterial macroaneurysms a case series. Ophthalmic Surg 1993;24(8):534-6. 25. Bischoff PM, Flower RW. Ten years experience with choroidal angiography using indocyanine green dye: a new routine examination or an epilogue? Doc Ophthalmol 1985;60(3):235-91. 26. Townsend-Pico WA, Meyers SM, Lewis H. Indocyanine green angiography in the diagnosis of retinal arterial macroaneurysms associated with submacular and preretinal hemorrhages: a case series. Am J Ophthalmol 2000;129(1):33-7. 27. Guyer DR, Yannuzi LA, Slakter JS, et al. Digital indocyanine-green videoangiography of occult choroidal neovascularization. Ophthalmology 1994;101(10):1727-35. 28. Tang WM, Pulido JS, Connor TB, et al. Echographic characteristics of retinal arterial macroaneurysm. Retina 1998;18(6):559-63. 29. Vander JF, Duker JS, Jaeger EA. Miscellaneous diseases of the fundus. In: Tasman W, Jaeger E, eds. Duane’s clinical ophthalmology. Revised ed. Vol 3. Philadelphia: Lippincott-Raven; 1997:8-10. 30. Brown DM, Sobol WM, Folk JC, et al. Retinal arteriolar macroaneurysms: long term visual outcome. Br J Ophthalmol 1994;78:534-8. 31. Oie Y, Emi K. Surgical excision of retinal macroaneurysms with submacular hemorrhage. Jpn J Ophthalmol 2006;50:550-3. 32. Goff MJ, McDonald HR, Johnson RN, et al. Causes and treatment of vitreous hemorrhage. Compr Ophthalmol Update 2006;7(3):97-111. 33. Gedik S, Gur S, Yilmaz G, et al. Retinal arterial macroaneurysm rupture following fundus fluorescein angiography and treatment with Nd: YAG laser membranectomy. Ophthalmic Surg Lasers Imaging 2007; 38(2):154-6. 34. Gurwood A, Nicholson CR. Retinal arterial macroaneurysm: a case report. J Am Optom Assoc 1998;69:41-8. 35. Ulbig MW, Mangouritsas G, Rothbacher HH, et al. Long-term results after drainage of premacular subhyaloid hemorrhage into the vitreous with a pulsed Nd:YAG laser. Arch Ophthalmol 1998; 116(11):1465-9. 36. Wu TT, Sheu SJ. Intravitreal tissue plasminogen activator and pneumatic displacement of submacular hemorrhage secondary to retinal artery macroaneurysm. J Ocul Pharmacol Ther 2005;21(1):62-7. 37. Iijima H, Satoh S, Tsukahara S. Nd:YAG laser photodisruption for preretinal hemorrhage due to retinal macroaneurysm. Retina 1998;18(5): 430-4. 38. Celebi S, Kukner AS. Photodisruptive Nd:YAG laser in the management of premacular subhyaloid hemorrhage. Eur J Ophthalmol 2001;11(3):281-6. 39. Tan CS, Au Eong KG. Surgical drainage of submacular haemorrhage from ruptured retinal arterial macroaneurysm. Acta Ophthalmol Scand 2005;83(2):240-1. 40. Humayun M, Lewis H, Flynn HW Jr, et al. Management of submacular hemorrhage associated with retinal arterial macroaneurysms. Am J Ophthalmol 1998;126:358-61.