Several cyst characteristics linked to ischemia in DME

September 30, 2019
Michelle Dalton, ELS

The likelihood of macular ischemia increases with larger cyst diameters, central subfield thickness, and the extent of outer retinal damage, according to a retrospective review of 250 eyes (186 patients) with diabetic macular edema.


The likelihood of macular ischemia increases with larger cyst diameters, central subfield thickness, and the extent of outer retinal damage, according to a retrospective review of 250 eyes (186 patients) with diabetic macular edema (DME) who were treated at the Gazi University in Ankara, Turkey, between November 2011 and March 2015. {Yalcin, 2019 #29302}

Yalcin and Ozdek noted in their introduction that cystoid macular edema (CME) is but one of the morphological patterns of DME found on optical coherence tomography (OCT).

Fluid accumulates in the intercellular space during the acute phase of cyst formation, and in the chronic phase fluid forms in the intracellular space. The large cystoid spaces at the fovea and enlarged foveal avascular zone (FAZ) are related to each other; the authors sought to further clarify the relationship between cyst formation and related OCT features and both macular and peripheral retinal ischemia.

Study findings

For the purposes of this study, “cystic space” was defined as round or oval-shaped low reflective intraretinal spaces separated by hyperreflective septa. Notable exclusion to study entry included eyes that had undergone cataract surgery in the previous 6 months to exclude for Irvine-Gass syndrome, and eyes that had macular edema due to any cause other than DME.

Macular ischemia was defined as an enlarged FAZ (≥1,000 μm) or presence of capillary nonperfusion within one disc diameter (DD) from the foveal center. Peripheral ischemia was defined as hypofluorescent areas corresponding to retinal nonperfusion/capillary drop-out or intraretinal microvascular anomaly in at least a 1-DD area. It was graded as mild when the peripheral ischemia covered less than a 5-DD area and as severe when it was more than a 5-DD area when evaluated on images taken in all gaze directions.

Of the patients, 64 (34.4%) had bilateral involvement and 122 patients (65.6%) had unilateral DME. The majority (n=194 eyes; 77.6%) had received prior intravitreal injections or laser therapy. Macular ischemia was present in 110 eyes (44%). Seventy-two eyes (28.8%) had mild macular ischemia and 38 eyes (15.2%) had severe macular ischemia.

Mean central subfield thickness was significantly greater in eyes with macular ischemia (510.4±144.7 μm) compared to eyes without macular ischemia (452.1±114.6 μm); these were statistically significant (p=0.001).

Horizontal and vertical diameter of the largest cyst increased with the presence and severity of macular ischemia (p = 0.045 and p = 0.016, respectively). The remaining retinal thickness increased with the presence and severity of peripheral ischemia, but this was not statistically significant (p = 0.009).

Peripheral ischemia was present in 192 eyes (76.8%). Half of these eyes (96 eyes, 38.4%) had mild peripheral ischemia and the other half (96 eyes, 38.4%) had severe peripheral ischemia. The mean central subfield thickness was 483.91±138.7 μm in eyes with peripheral ischemia and 457.31±103.5 μm in eyes without peripheral ischemia (p=0.36)

There was a statistically significant relationship between the number of the hyperreflective foci in the cyst wall and internal reflectivity of the cyst (p=0.007). Hyperreflective foci in the cyst wall were detected in 170 eyes (68%). Most of these hyperreflective foci (155 eyes, 91%) were in the outer retinal layers.

Patients with greater central subfield thickness had a 1.04-times higher odds of having macular ischemia and 0.25-times higher odds of having outer retinal damage.

The “possibility” of macular ischemia increases when the diameter of the cyst increases. Several factors influence that dynamic, among them an increased central subfield thickness and the presence of outer retinal damage.

However, in cystoid DME, a greater central subfield threshold is associated with larger cysts, more outer retinal damage, and a higher likelihood of macular ischemia findings on fluorescein angiography.

Take-home points

While earlier studies noted the presence of a cyst was associated with decreased retinal sensitivity independent of IS/OS damage, the current study concentrated on the impact of diabetic cystic changes on the ischemic process.

“Severe peripheral retinal ischemia was more prevalent in eyes with proliferative DR,” which was expected, but no statistically significant difference was observed in the prevalence of macular ischemia between the groups according to the severity of DR or peripheral retinal ischemia.

However, the authors also acknowledged that a relationship between macular edema and peripheral ischemia was “inconclusive. We failed to show any relationship between the presence and severity of the peripheral ischemia and central subfield threshold.” {Yalcin, 2019 #29302} The DAVE study {Brown, 2016  #25655;Brown, 2018 #29309} had similar outcomes:

DME severity was not correlated with the global nonperfusion area. The current study did find a statistically significant relationship between the noncystoid retinal tissue and peripheral ischemia, with the noncystoid retinal thickness increasing with the presence and severity of ischemia in the peripheral retina.

“This may be explained by a diffuse thickening of the macula outside the cyst due to increased VEGF load in the presence of peripheral ischemia,” they said. {Yalcin, 2019 #29302}

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Diabetic Macular Edema