Intravitreal injection of anti-VEGF agents reduces Telangiectatic Capillaries size in patients with DME

Vascular endothelial growth factor (VEGF) has been identified as a critical mediator of retinal neovascularization and permeability in eyes with diabetic retinopathy (DR). The management of DME has changed considerably in recent years, especially following the development of intravitreal anti-VEGF therapy, which has emerged as a first-line therapy for center involved DME.

Microvascular abnormalities such as MAs are the most characteristic signs of DR, and extravascular leakage from these can cause DME. Pathologic studies have shown that the cellular components in the lumens of the MAs are erythrocytes or polymorphonuclear leukocytes and intramural cells, endothelial cells, or pericytes and that dense hyalinized MAs are often acellular, whereas hypercellular MAs have a thin wall. The association between the vascular wall and the cellular content in MAs indicates that there are multiple types of MAs in vivo. This led Itou et al to hypothesize that the pace of reducing the size of MA in response to anti-VEGF may vary depending on each different pathology of MA.

Occasionally, microvascular abnormalities reach several hundreds of microns in diameter, and such large lesions have been termed capillary MAs. Castro-Farías et al recently proposed the name ‘telangiectatic capillaries’ (TelCaps) to describe capillary abnormalities >150 µm to avoid confusion with the term “retinal arterial microaneurysm”. TelCaps are often detected by fluorescein- and indocyanine green angiography (IA). The fluorescein molecule is only 60% to 80% bound to proteins and leaks through vessels, whereas the indocyanine green molecule is 98% bound to proteins and does not leak through vessels. This allows IA to better visualize TelCaps in DME. In this study, authors investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME, and examined the characteristics of anti-VEGF-resistant TelCaps.

Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images.

There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03).

The absence of pericytes is characteristic of MAs, possibly because VEGF abolishes pericyte coverage of nascent vascular sprouts, leading to vessel destabilization although some researchers have reported that VEGF is required for pericyte survival. Authors postulated that the injection of anti-VEGF agents may accelerate pericyte recruitment around the retinal vascular endothelial cells in TelCaps. These pericytes subsequently produce type IV collagen and multiple laminin isoforms, which reduce the depth of each TelCap. These may subsequently stabilize retinal vascular endothelial cells and reduce TelCap size. Study found that those TelCaps that remained after three consecutive anti-VEGF agent injections had a significantly larger mean size at baseline.

Authors speculated that relatively new TelCaps that occur with endothelial proliferation are smaller and more sensitive to anti-VEGF agents. In contrast, larger TelCaps may represent a more chronic and advanced stage with intraluminal material such as hyaline and fat deposition, which may possess affinity for IA. These larger TelCaps may be closely associated with less sensitive recurrent or refractory macular edema.

It was reported that eyes receiving both ranibizumab and deferred laser photocoagulation for DME exhibited better long-term vision improvement than eyes receiving ranibizumab with prompt laser photocoagulation. The current study suggest that deferred laser photocoagulation should first be performed only for some of the largest TelCaps detected by IA after TelCaps reduction by injection of anti-VEGF agents, especially when the number of TelCaps is high. In this manner, its expected to achieve a more effective minimally invasive DME therapy by selective targeting of “refractory, anti-VEGF therapy-resistant TelCaps” with lesser impaired visual function. In parallel, laser photocoagulation may be performed in some cases before anti-VEGF therapy in which single or a few isolated TelCaps are easily reachable and clearly visible to spare some injections.

“Our study showed that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation.”

Source: Itou et al; Clinical Ophthalmology 2023:17

https://doi.org/10.2147/OPTH.S393360