An Unusual Macular Appearance

A73-year-old female presented with a 3-4 week history of increasingly distorted and blurred vision affecting the left eye.  On presentation, best-corrected vision in the left eye was 6/12. Fundus examination and photography of the left macula showed extensive nasal hard exudates (solid black arrows) as well as a nasal intraretinal haemorrhage (dotted black arrow).

• What other history would you like?

• What are the differential diagnoses?

• What other investigations and imaging would be useful in making a diagnosis?

Further History

On further questioning, the patient reported being in good health with no known history of diabetes mellitus or hyperlipdaemia. There was a history of systemic hypertension which was well-controlled with the use of Karvea. There was no known family history of ocular disease. There was a history of previous uncomplicated bilateral cataract extraction surgery and IOL insertion.

Assessment

Visual acuity was R 6/7.5 L 6/12. Anterior segment examination showed well-positioned posterior chamber IOLs with mild posterior capsule opacification (PCO) only in the right eye. Pupil reactions were normal and brisk, and there was no evidence of a relative afferent pupillary defect (RAPD). Colour vision testing was full in the right eye (14/14 plates) and mildly reduced in the left eye (11/14 plates).

SD-OCT scanning was performed which confirmed significant macular oedema affecting the left nasal macula (highlighted by the “hot” red zone on thickness map analysis). Further analysis of the cross-sectional OCT scan showed mixed subretinal fluid (SRF), intraretinal fluid (IRF) and intraretinal hard exudates in the nasal macula (Figure 1).

Figure 1. SD-OCT thickness maps are only useful when considering the macular ultrastructure in cross-sectional view, and identifying the location and cause of abnormal findings. In this case, the nasal macular thickening is due to a mixture of subretinal fluid (SRF) and intraretinal fluid (IRF). Additionally, physiological variations mean that individuals can have localised thickening or thinning of the macula that are not necessarily pathological.

Diagnosis & Management

The patient underwent fundus fluorescein angiography (FFA) which confirmed leakage (hyperfluorescence) in the late stages (Figure 2A). OCT angiography (OCT-A) showed corresponding abnormal vascularisation within the Avascular Complex (Figure 2C) as well as dilatation of the intraretinal vessels in the Deep Vascular Complex (DVC) (Figure 2B).

Figure 2A (left/top). Fundus fluorescein angiography (FFA) showing late stage leakage (hyperfluorescence) (white block arrow).

Figure 2B (centre). OCT-angiography (OCT-A) of the Deep Vascular Complex (DVC) showing dilatation of the intraretinal vessels inferiorly (below the white dashed line).

Figure 2C (right/bottom). OCT-A of the Avascular Complex showing abnormal neovascularisation (white circle).

Approach

Mixed intraretinal and subretinal exudation in the macula can be attributed to a number of conditions, including but not limited to branch retinal vein occlusions (BRVO), diabetic macular oedema (DME), idiopathic juxtafoveal telangiectasia (IJT) and choroidal neovascularisation (CNV).

Retinal angiomatous proliferation (RAP) is a sub-type of neovascular (wet) age-related macular degeneration (AMD). It is also referred to as Type 3 CNV and differs from Types 1 (occult) and 2 (classic) CNV in that the origin of abnormal neovascularisation is in the retina as opposed to the sub-RPE and subretinal spaces (Table 1).  Most RAP lesions occur in the peripheral macula given the lack of retinal capillaries in the foveal avascular zone (FAZ). RAP lesions are generally bilateral but can present sequentially in each eye, years apart.

Table 1. Gass’ Classification of Choroidal Neovascularisation (CNV)

In RAP lesions, vascular proliferation starts in the deeper capillaries and avascular complex of the retina, which then progresses more posteriorly and breaks into the subretinal space. Pre- and intra-retinal haemorrhages, intraretinal exudates and pigment epithelial detachments (PED) are commonly observed with RAP lesions. Eventually choroidal neovascularisation occurs when a retinal-choroidal anastomosis is formed (Figure 3).

Intravitreous anti-VEGF injections with ranibizumab (Lucentis®) or aflibercept (Eylea®) are generally successful in treating RAP lesions. Laser ablation of the abnormal anastomosis can also be considered for lesions that are sufficiently distal to the central fovea, and where visual function will not be affected.

Figure 3. The 3 stage pathogenesis of RAP lesions (Type 3 CNV). Unlike Type 1 CNV which originates from the sub-RPE space, and Type 2 CNV which originates from the sub-retinal space, Type 3 CNV starts in the retina itself resulting in intraretinal haemorrhages and exudation, subretinal extension, and ultimately retinal-choroidal anastomosis.

“Multi-modal diagnostic imaging can be invaluable in making a final diagnosis.”

                                                  – Inez Hsing

This case re-familiarises readers with the pathogenesis of CNV and the various presentations of CNV in the eye. While many CNV lesions secondary to neovascular AMD are Type 1 and Type 2, it is important to recognise RAP lesions which can mimic the appearance of other macular pathology such as branch retinal vein occlusions (BRVO) or diabetic macular oedema (DME). Multi-modal diagnostic imaging such as fundus photography, SD-OCT scanning, OCT-angiography (OCT-A) and FFA (if available) can be invaluable in making a final diagnosis.

Accurate identification of a RAP lesion can have significant implications with respect to how soon treatment is required (RAP lesions generally exhibit more aggressive exudation than that seen with BRVO or DME) and long-term prognosis for the fellow eye, given that RAP lesions are often bilateral. Adequate counselling and monitoring is critical in detecting early exudation from a RAP lesion in the contralateral eye.