Introduction

Idiopathic macular telangiectasia type 2 (MacTel 2 or perifoveal telangiectasia) is an acquired vascular disease of the macula primarily involving neural and glial cell degeneration and loss. This condition, named by Yannuzzi et al.,¹ refers to idiopathic juxtaretinal telangiectasia (IJRT) type 2A according to the classification system introduced by Gass and Blodi² in 1993. It is the most common type of IJRT, and includes cases that are usually bilateral, occult, and nonexudative. The disease typically presents in the fifth and sixth decades and affects men and women equally, although various studies have reported contradictory findings on the latter point.^3,4,5

Clinically, it is characterized by loss of transparency in the foveal region, intraretinal crystalline deposit accumulation, hyperplastic retinal pigment epithelium migration, macular pigment loss, and progressive abnormalities in the juxtafoveolar retinal vessels. These include right-angle veins, subretinal and outer retinal neovascularization, and vascular invasion of the foveal avascular zone.⁶ Optical coherence tomography (OCT) allows better understanding of retinal pathologies. Characteristic findings of the disease include macular thinning, hyporeflective cavitations in the inner and outer retinal layers, development of full-thickness macular hole in the absence of vitreoretinal traction, and atrophic changes in the outer retinal layer.^7,8

From its initial description to the present day, there has been no consensus regarding the mechanism of perifoveal telangiectasia. However, it is currently believed that the degeneration of Müller cells, which serve protective and supportive functions, is the primary pathology, and the damage to the retinal layers, atrophy, and vascular changes develop secondarily.³

Optical coherence tomography angiography (OCTA) is an imaging method that visualizes the movements of blood cells using motion contrast, thus providing information about blood flow. Thusly, imaging of the retinal vascular layers is possible without the need for intravenous contrast injection. As opposed to fundus fluorescein angiography (FFA), in which layers other than the superficial vascular plexus appear only as background hyperfluorescence, OCTA enables separate imaging of the superficial and deep vascular layers and the choroidal vessels.⁹

In this study, we aimed to use OCTA to evaluate vascular anomalies in patients with MacTel 2 and elucidate the relationship between these and retinal anomalies detected on OCT.

Materials and Methods

Optovue spectral domain OCT (SD-OCT) and OCTA images were recorded simultaneously from 6 patients diagnosed with MacTel 2 in the Ophthalmology Department of the Ankara University Faculty of Medicine. Patients were considered to have MacTel 2 in the presence of findings such as reduced autofluorescence in the central macula on fundus autofluorescence; loss of retinal transparency, intraretinal pigment, presence of right-angle venules, and telangiectatic vessel appearance on fundus examination; and OCT showing interior limiting membrane drape, retinal pigment epithelium migration creating intraretinal hyperreflectivity, atrophy of the outer retinal layers, and presence of intraretinal hyporeflective cavitation. OCTA en face flow maps were created using RTVue XR Avanti version 2015.1.1.98 and Split Spectrum Amplitude Decorrelation Angiography images were obtained. Images that could not be evaluated due to low resolution were excluded. Each eye was graded based on the MacTel OCTA grading system according to Chen et al.10 (Table 1).

Results

Ten eyes of 6 patients were included in the study. Four (66%) of the patients were female, 2 (34%) were male. Their mean age was 67.6 years. The OCT and OCTA findings of the patients are shown in Table 2. Disease severity was grade 0 in 2 eyes, grade 1 in 2 eyes, grade 2 in 3 eyes, grade 3 in 1 eye, grade 4 in 1 eye, and grade 5 in 1 eye. Neovascularization was not observed in any of the grade 1, 2, or 3 eyes. In these cases, the most common findings on OCT images were thinning and atrophy in the outer retina and inner/outer segment layers, intraretinal hyporeflective cavitations, and ILM drape (Figures 1 and 2). In patients with subretinal neovascularization apparent on OCTA, B-scan images from the same cross-section revealed classic CNV or CNV scar (Figure 3). In one patient, OCT images were considered normal, whereas vascular changes consistent with grade 1 disease were observed on OCTA (Figure 4). In contrast, 2 patients who showed pronounced foveal atrophy and macular hole on B-scan imaging had only early-stage changes in OCTA (Figures 5 and 6). Another striking finding was that in some of the patients, the superficial layer was intact despite pronounced changes and neovascularization in the deep layer (Figures 7 and 8).

Discussion

OCTA provides valuable information regarding disease severity and neovascularization activity in patients with parafoveal telangiectasia. In a study using OCTA, Spaide et al.⁹ demonstrated that FFA primarily shows the superficial vascular network of the retina and is inadequate for visualizing the deep capillary layer and the choroid. Consistent with other OCTA studies, in our series we observed that the superficial vascular network of some MacTel 2 patients was remarkably well preserved, even in advanced disease, while pronounced changes were evident in the deep capillary network. In addition, abnormalities may occur in the deep vascular network even in early disease stages where OCT is within normal limits, and FFA alone is not sufficient to evaluate these patients. It has also been shown that FFA findings which may be evaluated as perifoveal vascular leakage and lead to unnecessary injections in clinical practice are due to telangiectatic vessels in the deep vascular layer.¹¹ OCTA clearly demonstrates that leakage simulating choroidal neovascularization on FFA is not a result of the formation of new vessels. Other advantages over FFA are that it is easy to perform, can be repeated frequently, and is non-invasive.

In the current series, OCTA evaluation of patients with advanced atrophic changes in the foveal region and macular hole revealed minimal changes consistent with grade 0 or 1 disease in the foveal vascular network. These findings support the theory that retinal structural changes seen in MacTel 2 are not secondary to vascular anomalies, but are a primary condition.^12,13 Müller cells are known to play important roles in the maintenance of foveal structural integrity, neuronal support, and continuity of the blood-retina barrier.^14,15 It is believed that macular hole and intraretinal cavitation arise due to neural atrophy and disruption of the foveal structure resulting from the destruction of Müller cells.13 These findings appear independent of vascular changes and show the clinical importance of en face circulation maps in combination with B-scan OCT.

On the other hand, a patient with grade 2 disease in the left eye exhibited no pronounced abnormality in the right eye on OCT, while OCTA revealed reduced vascular density and telangiectatic vessels in the deep vascular plexus. On careful examination of SD-OCT images of this eye, it was noted that the foveal pit was asymmetric. Similarly, Charbel Issa et al.¹⁶ studied patients with marked MacTel 2 in one eye and apparently healthy fellow eyes and detected foveal pit asymmetry and temporal foveal thinning which were associated with very early disease.

Another finding we observed in our cases is that the formation of new vessels was not limited to the choroid, but could also occur between the outer retinal layer and the choroidal vascular network, which is usually avascular. This finding is also similar to those observed by Spaide et al.^17,18 In their OCTA studies of MacTel 2, they emphasized the antiangiogenic properties of Müller cells, stating that hypoxia due to deep vascular network dysfunction and suppression of antiangiogenic factors due to Müller cell degeneration may lead to intraretinal neovascularization. Several previous studies have indicated that neovascularization in MacTel 2 originates more from retinal vascular structures rather than the choroid.^19,20 In their study using OCTA, Zhang et al.²¹ showed that these subretinal neovascular complexes may not be only retinal, but may also be connected to the choroidal vasculature.

The fact that the severity of intraretinal and vascular changes are mutually independent supports the view that the primary pathology of MacTel 2 is not vascular. Moreover, it has been shown that Müller cell loss may be another factor that leads to telangiectasia.²² Spaide et al.^17,18 also emphasized the importance of Müller cells in intraretinal vascular circulation and retinal support. Thus, it seems that Müller cell loss is responsible not only for intraretinal neural cell death and morphologic changes, but also vascular telangiectasia, leakage, and neovascularization.

Conclusion

The results of this pilot study demonstrate that OCTA, which has recently been introduced into clinical use, offers insight into the pathogenesis of MacTel 2 and is useful as an auxiliary method to OCT in patient follow-up, but does not directly correlate with OCT findings in terms of the extent of anatomic abnormalities.

Ethics

Ethics Committee Approval: Ankara University Faculty of Medicine Clinical Research Ethics Committee (13-827-17).

Informed Consent: The study is retrospective in nature.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: Sibel Demirel, Figen Şermet, Emin Özmert, Concept: Sibel Demirel, Figen Şermet, Emin Özmert, Hilal Nalcı, Design: Sibel Demirel, Figen Şermet, Emin Özmert, Hilal Nalcı, Data Collection or Processing: Hilal Nalcı, Sibel Demirel, Analysis or Interpretation: Hilal Nalcı, Sibel Demirel, Literature Search: Hilal Nalcı, Writing: Hilal Nalcı, Sibel Demirel, Figen Şermet, Emin Özmert.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.