OCT-angiography for diagnosis and response to treatment of subretinal neovascularization secondary to idiopathic macular telangiectasia type 2

Abstract

Idiopathic macular telangiectasia type 2 (MacTel 2) is a slow and progressive bilateral condition that affects middle-aged and elderly individuals. Vision loss is generally mild and occurs over the course of many years. The development of sub-retinal neovascularisation (SRNV) can occur late in the disease process, and lead to more dramatic vision loss. A report is presented of 2 cases of MacTel 2 in which optical coherence tomography angiography (OCTA) was essential for the diagnosis of secondary SRNV. The commercially available OCTA Cirrus AngioPlex 5000 platform (Zeiss, Jena, Germany) was used. Subretinal neovascularization was detectable in both cases in OCTA at the level of the deep capillary plexus and the avascular layer. OCTA also allowed us to monitor disease progression and monitor response to anti-VEGF therapy.

Resumen

La telangiectasia macular idiopática tipo 2 (MacTel 2) es una afección bilateral, lenta y progresiva que afecta a individuos de mediana edad y ancianos. La pérdida de visión es generalmente leve y ocurre en el transcurso de muchos años. El desarrollo de neovascularización subretiniana (NVSR) puede ocurrir tarde en el proceso de la enfermedad y conducir a una pérdida de visión más dramática. Presentamos 2 casos de MacTel 2 donde la angiografía por tomografía de coherencia óptica (OCTA) fue fundamental para el diagnóstico de NVSR secundaria. Se utilizó la plataforma comercialmente disponible OCTA Cirrus AngioPlex 5000 (Zeiss, Jena, Alemania). La NVSR fue detectable en ambos casos con OCTA a nivel del plexo capilar profundo y en la capa avascular. La OCTA también nos permitió controlar la progresión de la enfermedad y monitorizar la respuesta a la terapia anti-VEGF.

Introduction

Idiopathic macular telangiectasia type 2, often referred to as MacTel 2 in recent literature, is a bilateral, slowly progressive condition affecting middle-aged and elderly individuals that is characterized by macular capillary changes, variable foveal cavitations, and loss of outer retinal structure with eventual macular atrophy. It can be divided into 2 stages, the nonproliferative stage characterized by perifoveal telangiectasia, crystalline deposits, pigment plaques, right-angled venules, and inner and outer lamellar cysts, and the proliferative stage, which is characterized by the presence of subretinal neovascularization (SRNV)^1,2.

The overall prevalence of MacTel 2 has been estimated at 0.1%³. The natural history of MacTel 2 generally involves a slow decline in central vision secondary to the changes described above. The development of SRNV may occur late in the disease process and lead to more dramatic vision loss. SRNV is fortunately rare (2–14%)¹ and is thought to arise from the deep capillary plexus in a process similar to the retinal angiomatous proliferation seen in AMD. SRNV is often aggressive and can cause scarring in the absence of treatment. The advent of new imaging techniques has led to a deeper understanding of the pathophysiologic and structural substrate of MacTel 2 and secondary SRNV.

Two 2 cases of MacTel 2 are described, in which optical coherence tomography angiography (OCTA) was instrumental in the diagnosis and treatment response monitoring of SRNV secondary to MacTel 2.

Clinical case 1

Female, 57, with a history of essential hypertension and hypothyroidism, referred for visual loss in the right eye (RE). She had no previous ophthalmologic history. Best corrected visual acuity (BCVA) in the RE was 0.5 and 0.7 in the left eye (LE). Intraocular pressure was 15 mmHg in both eyes (BE). Anterior segment examination only highlighted nuclear phacosclerosis in BE. Fundus examination (RE) showed bilateral perifoveal pigmentary mottling. Autofluorescence showed increased central foveal autofluorescence related to a reduction in macular pigment. Fluorescein angiography (FA) showed subtle vascular changes and the presence of profuse perifoveal leakage with accentuation in late phases. Spectral domain OCT (spectral domain OCT-DS) revealed retinal atrophy cavities resembling lamellar macular hole with areas of alteration of the ellipsoid layer (Fig. 1). Given the clinical findings and the characteristic signs of OCT-DS, a diagnosis of MacTel 2 was made and the patient was monitored every 6 months.

Fig. 1.

Initial presentation of the 2 patients at the time of diagnosis of idiopathic macular telangectasia type 2 (MacTel 2). Retinography, autofluorescence, fluorescein angiography, and OCT are shown with typical signs of MacTel 2. Note the great asymmetry in case 2, where the RE shows subtle signs of MacTel 2 compared to the LE.

Three years after diagnosis, the patient developed abrupt visual loss in the LE with BCVA of 0.4. RE examination revealed increased pigmentary mottling in BE and faint macular hemorrhage in the LE. OCT-DS showed the previous foveal alterations in the RE. However, in the LE, the presence of homogeneous retinal thickening that was not present in the previous controls was striking, there was no intraretinal or subretinal fluid (SRF) (Fig. 2). These findings were inconclusive for the diagnosis of secondary neovascularization. OCTA was performed using the Cirrus Angioplex 5000 (Zeiss, Jena, Germany), without any image modification or post-processing. OCTA confirmed the presence of SRNV at the level of the deep capillary plexus and in the avascular layer (Fig. 2). Once SRNV was demonstrated, treatment with intravitreal ranibizumab was started and, at present, after one dose of anti-VEGF the patient exhibits a visual gain of 0.6 with anatomical improvement on OCT-DS and a clear decrease in SRNV with a decrease in central vascular density on OCTA (Fig. 3).

Fig. 2.

Study of cases with SD OCT and OCTA 3 × 3 mm at the time of diagnosis of subretinal neovascularization (SRNV). On OCTA, SRNV can be visualized in the deep capillary plexus and avascular layer. The corresponding B-Scans show the corresponding abnormal flow in each case.

Fig. 3.

Comparative images of SRNV in avascular layer of OCTA 3 × 3 mm before and after ranibizumab treatment in both cases. In each case in the avascular layer, the decrease in SRNV size is seen. The color map shows a reduction in vascular density after treatment with ranibizumab. In each case in the lower part of the chart is shown a comparative quantitative reduction of vascular density in the area that would correspond to the SRNV.

Clinical case 2

Female 41, with a history of essential hypertension and well-controlled type 2 diabetes mellitus, was referred to our centre for an unaffiliated maculopathy in the LE. BCVA was 0.9 in the RE and 0.5 in the LE. Anterior segment examination was normal. RE examination showed a rather asymmetric perifoveal pigmentary mottling in BE that affected more the LE. Autofluorescence showed asymmetric foveal fluorescence alterations predominantly in the LE. The FA study showed subtle vascular changes in the RA. However, in the LE, FA showed telangiectatic vessels in the temporal perifoveal area with leakage in late phases. OCT-DS in the RE showed a minimal foveal cavity bordered by the inner limiting membrane and in the LE a wide disruption of all outer retinal layers from the fovea to the temporal perifovea; another OCT slice showed small cavities due to retinal atrophy (Fig. 1). With these findings, a diagnosis of MacTel 2 with asymmetric presentation was made and the patient was monitored every 6 months.

At 4 years of follow-up the patient developed visual loss in BE with BCVA of 0.16. RE examination revealed increased pigmentary mottling with no signs of SRNV in BE. In the RE the OCT-DS showed a subtle intraretinal cavity that had become more accentuated in the last 6 months, while the LE evidenced increased disorganization of retinal layers and the presence of an area of homogeneous hyperreflective material that corresponded to inner retinal layers collapsing through atrophic defects in the outer retina. A foveal hyporeflective area representing an area of unoccupied retinal atrophy could be mistaken for FSR (Fig. 2). Likewise, as in case 1, these findings were not conclusive for the diagnosis of secondary neovascularization. Therefore, we resorted to the OCTA study which confirmed the presence of SRNV at the level of the deep capillary plexus and the avascular layer (Fig. 2). Once SRNV was demonstrated, treatment with ranibizumab was started and after one dose of anti-VEGF, the patient presented a visual gain of 0.4 and, similarly to the previous case, anatomical improvement was shown in the OCT-DS together with a clear decrease in SRNV with diminished central vascular density in the OCTA (Fig. 3).

Discussion

MacTel 2 is a progressive bilateral condition affecting middle-aged and elderly individuals that is characterized by macular capillary changes, variable foveal cystic changes, and loss of outer retinal structure with eventual macular atrophy^1,2. Although MacTel 2 was originally defined by its vascular features, histopathology and recently described animal models indicate that it may be a primary neurodegeneration involving Müller cells^4,5.

The hallmark of the disease is retinal vascular ectasia and neural atrophy of the macula⁴. This early stage condition can present a diagnostic challenge when evaluated with indirect ophthalmoscopy due to subtle foveal findings. Initially, the only finding on RE examination may be a decrease in temporal retinal transparency to the fovea. Other clues to the diagnosis in the early nonproliferative phase of this condition may be an increase in central foveal autofluorescence related to a reduction in macular pigment, as shown in our patients.

FA usually shows leakage of abnormal temporal retinal vessels into the fovea. OCT-DS has offered great insight into the pathogenesis of this condition where in advanced stages it shows atrophic abnormalities in all layers of the foveal retina, consisting of cystic degenerative retinal cystic lesions resembling lamellar hole with presence of inner limiting membrane and areas of disruption of the ellipsoid zone⁶ (Fig. 1). In the present cases, the characteristics of the OCT-DS of the initial examination suggest that the disease had been evolving for several years, where the slow and progressive decrease in vision delayed our patients' awareness until they finally requested the initial consultation.

The rather asymmetric presentation of case 2 is highlighted, where only in the last controls of the less affected eye the characteristic signs of MacTel 2 could be evidenced in the OCT-DS. SRNV can arise in the proliferative phase and form connections with the choroidal vessels⁷. In the cases we present, SRNV manifested with a rapid drop in vision in the affected eye, where OCT-DS showed the presence of homogeneous foveal hyperreflective material but no subretinal or intraretinal fluid. The presence of this SRNV in both cases could not be identified with FA due to the presence of a clouding phenomenon caused by the prominent foveal leakage that hindered the visualization of the vascular lesions.

OCTA allows detection of blood flow through the retinal and choroid plexuses without intravenous dye injection. OCTA can facilitate the diagnosis of all stages of MacTel 2 and essentially avoids the need for FA, which does not discriminate between superficial and deep retinal vasculature. Findings described on OCTA in eyes with MacTel 2 include loss of capillary density in the superficial retinal capillary plexus, alterations in the deep retinal vascular plexus, including dilation, telangiectasia, and intraretinal and subretinal neovascularization with prominent anastomoses^8,9. In the present cases, OCTA was the fundamental tool in the detection of SRNV, and it was also very useful in demonstrating the response to treatment, showing a decrease in SRNV. It is known that there are currently no normative databases for quantitative measurement of macular vascular density with OCTA; however, for follow-up or monitoring of response to treatment, the comparison of vascular density in the same patient can be very useful. In fact, in our patients, a quantitative response data of SRNV to anti-VEGF may be the observed decrease in central vascular density (52% in case 1 and 20% in case 2) (Fig. 3).

Currently, the literature is still limited on the characteristics of OCTA in patients with SRNV secondary to MacTel 2. Our cases show the clinical features of MacTel 2, both in its nonproliferative and proliferative forms, highlighting the diagnostic value of OCTA both in the diagnosis and in monitoring response to treatment of SRNV (Figs. 2 and 3). SRNV, unlike choroidal neovascularization, originates from the retinal circulation and can form retinochoroidal anastomoses^8,9 and these can occur without exudative signs¹⁰, as shown in the OCT-DS of our cases, which did not show exudative signs and OCTA had to be used to detect SRNV, which was evident in the deep capillary plexus and in the avascular layer. Regarding the location of the neovascularization, we believe that the term "subretinal" neovascularization may generate controversy, so we propose that the more appropriate term is more inclusive. We suggest the broader term "macular neovascularization" to denote neovascularization secondary to MacTel 2.

Conclusion

OCTA is a new, rapid, noninvasive imaging technology that was instrumental in diagnosing SRNV secondary to MacTel 2. In the present cases, OCTA not only facilitated diagnosis but also enabled monitoring of disease progression and response to anti-VEGF therapy. Hopefully, future studies with OCTA will bring out additional features of MacTel 2 and secondary SRNV and provide a better understanding of this disease.

Conflict of interest

The authors declare that they have no commercial interest and have not received financial support for the work.