Macular and Retinal Ischaemia

Overview

Diabetes causes a breakdown of the endothelial cell-cell junctions, a thickening of the basement membrane and eventually an occlusion of the retinal capillaries, resulting in poor perfusion of the macula.

Early macular ischaemia may precede clinically visible diabetic retinopathy (Takase, Retina 2015). Macular ischaemia is difficult to detect on funduscopy, however OCT Angiography (OCTA) allows detailed visualisation of the retinal capillary network and areas of non-perfusion.

OCTA signs of macular ischaemia include an enlargement of the foveal avascular zone (FAZ) and areas of paramacular capillary non-perfusion. As macular ischaemia progresses, the FAZ size increases and more areas of capillary non-perfusion arise.

Ischaemia may also occur in other areas of the retina, again due to capillary dropout. Intraretinal microvascular abnormalities (IRMA) and neovascularisation elsewhere (NVE) typically develop adjacent to areas of retinal ischaemia. NVE may lead to sight-threatening consequences such as retinal detachment and pre-retinal and/or vitreous haemorrhage as discussed elsewhere in this resource (select the tab "proliferative diabetic retinopathy" at the bottom of this page for further information).

It is important to also note however that macular ischaemia by itself is also a potential cause of vision loss.

OCT Signs

Recent studies have identified a clinical finding termed DRIL (disorganization of the retinal inner layers), which is used to describe poorly-defined boundaries of key inner retinal structures including the ganglion cell layer-inner plexiform layer (GCL-IPL) complex, inner nuclear layer (INL), and outer plexiform layer (OPL).

DRIL affecting more than 50% of the central 1-mm area of the retina is considered clinically significant. DRIL typically occurs in the central subfield of the ETDRS grid, and studies have shown that a 300 µm increase in DRIL is associated with a 1-line reduction in acuity.

The presence of DRIL has high diagnostic accuracy for identifying areas of non-perfusion (sensitivity 84.4%, specificity 100%). It is important to note however that not all areas of non-perfusion show signs of DRIL.

Case Examples

  • Case 1: Retinal ischaemia, intraretinal microvascular abnormalities (IRMA) and neovascularisation elsewhere (NVE)

    A 39-year-old male with type 2 diabetes, diagnosed 5 years previously. He reports his HbA1c to be "high" but is unsure of the number. He also has untreated systemic hypertension. His best corrected visual acuity in the right eye is 6/6 (20/20). This case will focus on the right eye only.

    Optomap widefield image and green separation image (right eye)

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    Optomap widefield image and green separation image (right eye)

    Widefield imaging shows numerous microaneurysms, dot/blot haemorrhages and cotton wool spots. Hard exudates are present in the temporal outer macula, consistent with non-centre involving diabetic macular oedema.

    IRMA is visible superior to the disc and neovascularisation inferonasal to the disc, although these are more evident in the magnified images.

    Green separation (widefield) image and OCT Angiography (right eye superior retina)

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    Green separation (widefield) image and OCT Angiography (right eye superior retina)

    Areas of IRMA are marked on both images by the blue arrows. On green separation, IRMA appears as very fine vessels that are difficult to distinguish. On OCTA they appear as unusual vessel branching adjacent to areas of retinal ischaemia, but lack the "tangled" appearance of neovascularisation.

    The IRMA is seen here adjacent to a large area of capillary dropout and retinal non-perfusion.

    Green separation (widefield) image and OCT Angiography (right eye, inferior retina)

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    Green separation (widefield) image and OCT Angiography (right eye, inferior retina)

    An area of neovascularisation elsewhere (NVE) is present inferonasal to the disc, in the retinal midperiphery, as marked by the blue arrow in both images.

    On green separation, the NVE appears as a tangled net of very fine vessels. This is more evident on OCTA which clearly shows the extent of the vascular network and the adjacent areas of retinal non-perfusion and capillary dropout.

  • Case 2: Severe retinal ischaemia

    A 28-year-old male with type 1 diabetes, diagnosed at the age of 14. His most recent HbA1c was 8.4% and best corrected visual acuity is 6/6 (20/20) in each eye.

    OCTA findings and corresponding retinal photos (right eye)

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    OCTA findings and corresponding retinal photos (right eye)

    Retinal photos show numerous dot/blot haemorrhages and microaneurysms, cotton wool spots and hard exudates.

    OCTA shows large areas of capillary dropout temporal to the macula and inferior to the disc. There are some anomalous vessels adjacent to these areas, consistent with IRMA. Numerous microaneurysms are also visible in the image.

    Note that the internal limiting membrane of this patient is still highly reflective in the retinal photos due to his relatively young age and this should not be confused with a sign of retinal ischaemia. In this case, the clinical signs of retinal ischaemia are subtle and it is best appreciated on the OCTA images or by undertaking fluorescein angiography.

    OCTA findings and corresponding retinal photos (left eye)

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    OCTA findings and corresponding retinal photos (left eye)

    In the left eye, retinal photos again show widespread dot/blot haemorrhages and microaneurysms, cotton wool spots and hard exudates.

    OCTA in this eye shows large areas of capillary dropout temporal to the macula and in the inferior midperiphery. There are more obvious anomalous vessels adjacent to these areas of non-perfusion, consistent with IRMA.

  • Case 3: Retinal ischaemia and DRIL

    82 yo male with history of bypass heart surgery over 20 years ago and diagnosis of type 2 diabetes with recent HbA1c levels of 7%. Previous smoker, quit 12 months previous. VA OS 6/12-2 (pinhole 6/12+)

    Optos widefield imaging and fundus autofluoresence imaging (FAF)

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    Optos widefield imaging and fundus autofluoresence imaging (FAF)

    Widefield imaging reveals moderate non-proliferative diabetic retinopathy .

    Spectralis OCT line scan (left macula)

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    Spectralis OCT line scan (left macula)

    OCT shows disruption of the inner retinal layers (DRIL) temporal to the macula – note the lack of differentiation between the GCL-IPL, the inner nuclear layer and outer plexiform layer in the area of the blue arrow .

    OCT Angiography

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    OCT Angiography

    OCTA shows an enlarged foveal avascular zone and reduced capillary rperfusion, particularly temporal to the macula, confirming a diagnosis of diabetic macular ischaemia. Some distortion of the foveal pit can be noted on the OCT image. likely the result of previous vitreomacular traction.

Differential Diagnosis

Hypertensive retinopathy

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Retinal arterial occlusion

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Ocular ischaemic syndrome

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References

Duh, E. J., Sun, J. K., & Stitt, A. W. (2017). Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI insight, 2(14).

Johannesen, S.K., Viken, J.N., Vergmann, A.S. and Grauslund, J. (2019), Optical coherence tomography angiography and microvascular changes in diabetic retinopathy: a systematic review. Acta Ophthalmol, 97: 7-14.

Tran, Khoi; Pakzad-Vaezi, Kaivon (2018) Multimodal imaging of diabetic retinopathy, Current Opinion in Ophthalmology: November - Volume 29 - Issue 6 - p 566-575

Tripathi, Alka; Gaur, Shagun; Agarwal, Richa; Singh, Neha; Singh, Amit; Parveen, Shadman; Singh, Nivedita; Rima, Nani. Disorganization of retinal inner layers as an optical coherence tomography biomarker in diabetic retinopathy: A review. Indian Journal of Ophthalmology 73(9):p 1245-1250, September 2025.