What are intraretinal microvascular abnormalities in diabetic retinopathy?

Shunt vessels within areas of capillary nonperfusion They are shunt vessels and intraretinal new vessels that develop beside areas of capillary closure, and they mark severe retinal ischemia.

Outpouchings of the capillary wall filled with lipid

Fibrovascular fronds growing along the posterior hyaloid

Nerve fiber layer infarcts beside the arterioles

Why do intraretinal microvascular abnormalities not bleed into the vitreous?

They lie within the retina, under the internal limiting membrane Because these vessels stay inside the retina and have not broken through the internal limiting membrane, they do not leak into the vitreous as new vessels do.

They are fully occluded and carry no blood

A thick glial sheath encloses each vessel

They regress before reaching a size that can bleed

What drives the appearance of intraretinal microvascular abnormalities?

Ischemia severe enough to stimulate vascular endothelial growth factor They emerge when retinal ischemia becomes severe enough to stimulate vascular endothelial growth factor in the surrounding retina.

Vitreous traction on the inner retinal surface

Breakdown of the outer blood-retinal barrier

Lipid deposition inside the capillary wall

How are intraretinal microvascular abnormalities best detected on examination?

With a red-free filter and a high magnification lens A red-free filter and a high magnification contact lens show these faint tangles best, and the search concentrates at the border of nonperfused retina.

Under the widest beam with white light

Through an undilated pupil with a direct ophthalmoscope

By transillumination through the sclera

Which feature argues that an abnormal retinal vessel is neovascularization rather than IRMA?

It crosses a major vein or arteriole New vessels grow on the retinal or disc surface and cross large vessels, whereas IRMA stay in the plane of the retina and respect major vessels.

It lies at the border of nonperfused retina

It is finer and more irregular than a nearby venule

On fluorescein angiography, how do IRMA behave compared with retinal neovascularization?

Both leak profusely in the early phase

IRMA block fluorescence while new vessels stay dark

Neither structure fills with dye

Apart from diabetic retinopathy, in which conditions may IRMA be seen?

Retinal vein occlusion and ocular ischemic syndrome IRMA are a marker of retinal ischemia generally, so they also appear in retinal vein occlusion and in ocular ischemic syndrome.

Central serous chorioretinopathy and pattern dystrophy

Retinitis pigmentosa and choroideremia

Birdshot chorioretinopathy and posterior uveitis

What can happen to intraretinal microvascular abnormalities after treatment of the retinopathy?

They can regress after panretinal photocoagulation or anti-VEGF Panretinal photocoagulation or anti-VEGF therapy can make these vessels regress, which is one reason the grade may improve after treatment.

They calcify and remain permanently visible

They convert into hard exudates

They progress regardless of any treatment given

What is the key caution before starting anti-VEGF therapy for severe nonproliferative retinopathy?

Disease can return when treatment stops, so follow-up must be reliable Anti-VEGF can reverse the severity level without changing the underlying ischemia, and stopping it allows disease to return, so the patient must commit to follow-up.

It permanently removes the underlying retinal ischemia

It cannot be combined with panretinal photocoagulation

It raises intraocular pressure irreversibly

At what interval should an eye showing intraretinal microvascular abnormalities be reviewed?

Weeks to a few months These eyes carry widespread ischemia and a raised risk of progression, so examination intervals of weeks to a few months are used according to the other findings.

Only when the patient notices a change

Intraretinal Microvascular Abnormalities: IRMA Signs

Intraretinal microvascular abnormalities (IRMA) are shunt vessels and new intraretinal vessels that develop in areas of capillary nonperfusion in diabetic retinopathy.

They are also a sign of severe ischemia, and they are one of the three features of severe nonproliferative retinopathy.

The practical difficulty is that they can look like early neovascularization, and the distinction affects treatment.

What Are Intraretinal Microvascular Abnormalities?

IRMA are tortuous, dilated capillary segments that lie within the retina, adjacent to areas of capillary closure.

They are thought to be either remodeled preexisting capillaries or intraretinal new vessels that have not yet broken through the internal limiting membrane.

Because they remain within the retina, they do not leak into the vitreous and do not cause hemorrhage in the same way as neovascularization.

They appear when retinal ischemia reaches a degree that stimulates vascular endothelial growth factor.

The ETDRS found that IRMA, venous beading, and extensive hemorrhages predicted progression to proliferative disease.

Clinical Appearance

Fine, irregular, red intraretinal lines that run between arterioles and venules, usually at the border of nonperfused retina
Located in the posterior pole or the midperiphery, often near areas of cotton wool spots or hemorrhages
Without crossing major retinal vessels and without protruding into the vitreous
Often accompanied by venous beading and loops
Best seen with a red-free filter or a high magnification contact lens

They look like faint tangles and are sometimes mistaken for background microaneurysms.

Test your knowledge 10 questions from this article

How to Distinguish IRMA From Neovascularization

Retinal neovascularization grows on the surface of the retina or the disc, forms flat networks or fronds, and crosses large vessels.

In addition, IRMA stays in the plane of the retina and does not cross large vessels.

On fluorescein angiography, neovascularization leaks profusely and early, while IRMA shows mild leakage or none and stays within the retinal layers (see fluorescein angiography patterns).

OCT angiography can also show IRMA as abnormal vessels in the inner retinal layers and neovascularization as flow above the internal limiting membrane (see OCT angiography).

When in doubt, angiography is useful, since treating a patient as if neovascularization is present changes both the urgency and the follow-up.

Clinical Significance

IRMA indicates widespread ischemia and an increased risk of progression to proliferative disease within a year
Moderate to severe IRMA is one component of the 4-2-1 rule (see diabetic retinopathy classification)
Clinicians may see IRMA with other ischemic conditions, including retinal vein occlusion and ocular ischemic syndrome
It can regress after panretinal photocoagulation or anti-VEGF therapy

Patients with IRMA need closer follow-up, with examination intervals of weeks to a few months, according to the other findings and the guideline.

Clinical eye photograph illustrating Intraretinal Microvascular Abnormalities

Management for Intraretinal Microvascular Abnormalities

Management follows the stage of retinopathy and the presence of macular edema.

Eyes with severe nonproliferative disease may be observed closely, or treated early with panretinal photocoagulation or anti-VEGF injections, especially when follow-up is unreliable (see panretinal photocoagulation and anti-VEGF therapy).

Control of blood glucose, blood pressure, and lipids is essential.

A rapid improvement in glycemic control can briefly worsen retinopathy.

Pregnant patients and those scheduled for cataract surgery need particular attention, because progression can be rapid (see diabetic retinopathy in pregnancy).

Tell patients that the finding is a warning sign and not yet a threat to vision, and that regular follow-up is the way to catch the next step.

A Short Practical Checklist

Examine with a red-free filter and a high-power lens, and look at the border of nonperfused retina
Compare the vessel with a neighboring venule: IRMA is finer and more irregular
Ask whether the vessel crosses a major vein or arteriole, which suggests neovascularization
Obtain angiography when the result will change the decision
Look for IRMA in the periphery with a widefield image

Intraretinal Microvascular Abnormalities: Treatment Timing

Studies of early panretinal photocoagulation in severe nonproliferative disease showed a reduction in progression, with a modest absolute benefit. Anti-VEGF agents, in contrast, can reverse the severity level without necessarily changing the underlying ischemia.

Because stopping anti-VEGF treatment can lead to a return of disease, patients who start it need to be committed to follow-up.

The choice is individualized according to the patient’s reliability, the other eye, and the presence of macular edema.

Document IRMA with a drawing or a photograph at the first visit.

Patients who are pregnant, have rapidly improved their glucose levels, or are due for surgery on the eye deserve a shorter interval to the next examination.

References

Early Treatment Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology. 1991;98:823-833.
Wilkinson CP, Ferris FL III, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1677-1682.
Ryan SJ, Schachat AP, Wilkinson CP, et al, eds. Retina. 6th ed. Elsevier; 2018.
American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous. AAO; current edition.

Test yourself

A few questions straight from this article.

1 / 10 0 correct

What are intraretinal microvascular abnormalities in diabetic retinopathy?
They are shunt vessels and intraretinal new vessels that develop beside areas of capillary closure, and they mark severe retinal ischemia.
Why do intraretinal microvascular abnormalities not bleed into the vitreous?
Because these vessels stay inside the retina and have not broken through the internal limiting membrane, they do not leak into the vitreous as new vessels do.
What drives the appearance of intraretinal microvascular abnormalities?
They emerge when retinal ischemia becomes severe enough to stimulate vascular endothelial growth factor in the surrounding retina.
How are intraretinal microvascular abnormalities best detected on examination?
A red-free filter and a high magnification contact lens show these faint tangles best, and the search concentrates at the border of nonperfused retina.
Which feature argues that an abnormal retinal vessel is neovascularization rather than IRMA?
New vessels grow on the retinal or disc surface and cross large vessels, whereas IRMA stay in the plane of the retina and respect major vessels.
On fluorescein angiography, how do IRMA behave compared with retinal neovascularization?
Neovascularization leaks profusely and early, while IRMA show little or no leakage and remain confined to the retinal layers.
Apart from diabetic retinopathy, in which conditions may IRMA be seen?
IRMA are a marker of retinal ischemia generally, so they also appear in retinal vein occlusion and in ocular ischemic syndrome.
What can happen to intraretinal microvascular abnormalities after treatment of the retinopathy?
Panretinal photocoagulation or anti-VEGF therapy can make these vessels regress, which is one reason the grade may improve after treatment.
What is the key caution before starting anti-VEGF therapy for severe nonproliferative retinopathy?
Anti-VEGF can reverse the severity level without changing the underlying ischemia, and stopping it allows disease to return, so the patient must commit to follow-up.
At what interval should an eye showing intraretinal microvascular abnormalities be reviewed?
These eyes carry widespread ischemia and a raised risk of progression, so examination intervals of weeks to a few months are used according to the other findings.