RETINAL ARTERIAL MACROANEURYSM

Signs and Symptoms

Retinal arterial macroaneurysms (RAM) are acquired saccular or fusiform dilatations of the large arterioles of the retina.1-7 They are usually observed within the first three orders of bifurcation and can occur at arteriovenous crossings as well.4,7 Patients who develop RAM are typically between the ages of 50 and 80.1-7 They rarely occur in younger patients, but when they do the most consistently associated systemic disease is hypertension.7 There appears to be a female preponderance.4-6 The most common comorbidity is systemic arterial hypertension, occurring in approximately 80% of patients.1-7 There is also an increased incidence of cardiovascular disease and arteriosclerosis.5,6

Ophthalmoscopically, RAM appear as an exudative, dilated arteriole within a major vascular branch within the first three bifurcations.1-9 In rare circumstances, they can occur just off of the optic disc.10 RAM are typically unilateral, but may be bilateral or multifocal.3,5 In many cases, unruptured lesions remain asymptomatic until discovered during routine dilated exams.1,2 Even without loss of function, by the time the patient presents to the clinician, there has often been significant leakage into surrounding areas, manifesting as visible exudates with variable presentations of pre-, intra- or subretinal hemorrhage.1-9 Vitreous hemorrhage may also occur with RAM.11-18 Occasionally, spontaneous pulsation of an unruptured aneurysm may be noted.6

When there is extensive intraretinal or pre-retinal bleeding, it is often difficult to identify RAM as the cause, especially if they are in an unusual position such as closer to the disc.10 In these cases, neovascularization is often misdiagnosed as the source.10 If focal dilatation is questionable ophthalmoscopically, OCT and fluorescein angiography can provide diagnostic evidence.1,6,9 Eyes with RAM imaged with spectral domain-OCT demonstrate a round hyperreflective wall with a hyporeflective lumen.9 With fluorescein angiography, the aneurysms will hyperfluoresce early in the angiogram, revealing a characteristic balloon appearance that demonstrates leakage in the recirculation phase.5,7 In cases where OCT or fluorescein imaging is contraindicated secondary to extensive hemorrhage, indocyanine green (ICG) angiography, which images in the infrared spectrum, may support visualization through blood, fluid and lipid, identifying the aneurysmal dilatation.7,11,12

Vision and field loss from RAM are directly related to the size and location of leakage (blood and products, lipid and macular edema).1-21 RAM rupture has a strong association with the development of macular holes and retinal detachment, which can leave patients with profound vision loss despite complete resolution of the leakage from the initial lesion.19-25 Additionally, RAM have been seen in association with retinal telangiectasias, arterial emboli and vein occlusion.5,26

Pathophysiology

Retinal arterial macroaneurysms are acquired out-pouchings of the retinal arterioles.1-5 These balloon-like formations are caused by a break in the internal elastic lamina of the arteriole wall, through which serum, lipids and blood exude into the surrounding retina.27 The lesions seem to have an affinity for the bifurcations of vessels where structural integrity is weakest.7 Aging arterioles demonstrate an increase in intimal collagen and replacement of medial muscle fibers by collagen, making them less elastic.5 This loss of elasticity makes arterioles more susceptible to dilatation from elevated hydrostatic pressure occurring in hypertension.5 The strong association of RAM with hypertension/atherosclerosis supports this process and mechanism. There are two types of RAM: saccular, where the vessel develops one or more prominent out-pouchings; and fusiform, where there is less obvious focal widening and more general widening of the affected artery.4-7

Management

The natural course of RAM typically involves spontaneous sclerosis and thrombosis, particularly after hemorrhaging.5,6,27-31 For this reason, so long as there is no increased threat of macular hemorrhage, periodic observation is indicated.27-31 Asymptomatic nonleaking RAM may be monitored at four to six month intervals. If there is leakage in the form of exudation, hemorrhage, or both, that does not threaten the macula, then monitoring at one to three month intervals is indicated.27-31

If hemorrhage threatens or involves the macula or if there is persistent macular edema reducing vision or creating visual field loss, then direct photocoagulation of the RAM may speed resolution.1,4-6,28,30-34 In these cases, moderately intense photocoagulation is applied directly to the RAM so as not to produce complete occlusion of the involved artery, but to induce coagulation and subsequent thrombosis.23 Alternately, to avoid potential arterial occlusion, perianeurysmal laser application can be performed.32 In the event a nonhemorrhagic RAM is observed to be spontaneously pulsating, immediate direct photocoagulation is indicated, as ensuing rupture is likely.23,32

The tunable dye yellow laser seems to provide the greatest flexibility in these circumstances.33 Laser therapy works as heat conduction extends into overlying nonpigmented and adjacent cells.34 This approach is laden with complications, including enlarged laser scars, the potential for choroidal neovascularization, branch retinal artery occlusion, increased retinal traction with symptomatic metamorphopsia and subretinal fibrosis.34 Recent advances in laser application techniques have produced the technique known as subthreshold laser photocoagulation/therapy.34 Here, retinal hyperthermia is created below the cell death threshold by using a subvisible clinical endpoint.34 Selective RPE damage is hypothesized to lead to an improved balance in angiogenic factors and cytokine release, improving endpoints and minimizing complications.34,35 Studies have shown promise in creating similar clinical outcomes without the side effects seen with other lasers.34,35

The visual prognosis for eyes with ruptured or leaking RAM depends on the degree and type of macular involvement. In the majority of cases, there is gradual and spontaneous involution concurrent with hemorrhage resorption.5,6,13,36 Eyes with vitreous hemorrhage or premacular subhyaloid hemorrhage typically recover good vision, while the vision in those with submacular hemorrhage generally remains poor.13 Early vitrectomy is recommended for RAM-related vitreous hemorrhage to allow for observation of the fundus, particularly the macula.11,32-40

In cases where there is significant preretinal hemorrhage, resolution and drainage can be greatly assisted by Nd:YAG laser rupture of the internal limiting membrane in front of the hemorrhage.13,20,37-39 Laser photodisruption of the posterior hyaloid membrane releases the preretinal hemorrhage into the vitreous space, where it can be more easily resorbed or surgically removed. More concerning and urgent are submacular hemorrhages that develop from RAM rupture, as they have the greatest potential for residual visual morbidity.32,37-39 Submacular surgery to remove accumulated hematoma should be performed within several days of the development of submacular hemorrhage in order to prevent permanent photoreceptor damage. 11,13,18,38,39 Alternately, pneumatic displacement of the submacular hematoma can help reduce permanent vision loss.38,39 Researchers are currently investigating anti-VEGF drugs for their ability to decrease the permeability of retinal arteries and normalize vascular walls by localized inhibition of VEGF.19,41,42 Intravitreal Avastin (bevacizumab, Genentech) has shown promise as an effective therapy for complicated RAM and cases with submacular exudation. Reports have documented improved acuity along with normalized arterial and retinal thickness in treated cases.19,41,42

Clinical Pearls

In cases of unexplained vitreous, pre-, intra- or subretinal hemorrhage, consider RAM as the cause. RAM is an entity with the potential to produce hemorrhage anywhere from the subretina to the vitreous.

When the characteristic balloon appearance is not readily observable ophthalmoscopically, then OCT, fluorescein or ICG angiography may aid diagnosis by providing a clearer portrait of the vessel’s characteristic dilatation.

There is a high rate of mortality in patients with RAM due to cardiovascular disease. Patients discovered to have RAM should be referred to a cardiologist for systemic evaluation.

Laboratory testing, including a fasting blood glucose, complete blood count with differential and platelets, fasting lipid profile, blood pressure evaluation and electrocardiogram, are indicated.

Macroaneurysms can occur also in a venule, but this is much more rare than occurrence in an arteriole.

Physical exertion can cause rupturing of RAM.

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