Anti-Vascular Endothelial Growth Factor Treatment for Proliferative Macular Telangiectasia Type 2.

Idiopathic macular telangiectasia type 2 (IMT 2), is the most common type of a heterogeneous group of disorders, characterized by telangiectatic alterations of the juxtafoveolar capillary network. Vision loss is due to retinal atrophy and subretinal neovascularization (SRN). Here, we report the outcomes of intravitreal anti-vascular endothelial growth factor injections, bevacizumab or ranibizumab, in four cases with proliferative IMT 2. Baseline best corrected visual acuity (VA) ranged from 20/50 to 20/100. Follow-up time ranged from 12 months to 24 months. One of four patients received one injection, two patients received three injections, and one patient received seven injections. VA improved in three eyes (≥1 line improvement) and decreased in one eye (≥1 line decrease) over time. Final acuity ranged from 20/30 to 20/100. There were no cases of leakage after the cessation of treatment. SRN, which is a complication of IMT 2, should be recognized and treated accordingly.

INTRODUCTION

Idiopathic macular telangiectasia (IMT), also known as idiopathic juxtafoveolar telangiectasia, is an uncommon bilateral disease that affects the juxtafoveolar region of the macula.1 IMT was first described by Reese in 1956 and was classified into three groups by Gass and Blodi in 1993.2 IMT type 1 is unilateral and associated with an exudation and macular edema. IMT type 2 (IMT 2) is bilateral and associated with minimal macular edema, deep hyperfluorescence on fluorescein angiography (FA), loss of macular transparency, superficial white crystals, depletion of macular pigment, progressive foveal thinning and edema in the nonproliferative stages, and subretinal neovascularization (SRN) in the proliferative stage. Type 3 is less frequent and characterized by macular ischemia.1

We report four cases of IMT 2 with the proliferative transformation that underwent intravitreal bevacizumab (IVB) or ranibizumab (IVR) on an “as needed” treatment regimen with a beneficial outcome. All the cases had no previous treatment.

CASE REPORTS

Case 1

A 51-year-old female patient was referred to our department with a macular lesion in both eyes diagnosed by an ophthalmologist. On examination, best corrected visual acuity (BCVA) was 20/25 in the right eye (RE) and 20/50 in the left eye (LE). The clinical appearance of the macular lesion of the LE was consistent with IMT 2 complicated by SRN [Figure 1a]. FA showed a subfoveal classic choroidal neovascularization (CNV) associated with leakage in the LE [Figure 1b]. Optical coherence tomography (OCT) showed a high reflective area located subfoveally and associated with an intra- and sub-retinal fluid collection, and the central retinal thickness (CRT) was 318 μ in the LE [Figure 1c]. The patient was diagnosed with proliferative IMT 2. BCVA was 20/100 and CRT was 258 μ in the LE following seven injections of IVB (1.25 mg/0.05 ml). Stable clinical and OCT findings with minimal leakage on FA were maintained until the 18th month of follow-up [Figure 1d–f].

Figure 1

The color fundus of the left eye (case 1) showed the clinical appearance of idiopathic macular telangiectasia type 2 complicated by subretinal neovascularization before (a), fundus fluorescein angiography revealed a subfoveal classic choroidal neovascularization associated with leakage before therapy (b), optical coherence tomography detected a high reflective area located subfoveally and associated with intra- and sub-retinal fluid collection before therapy (c), and after seven intravitreal bevacizumab injections (d), and reduced leakage after injections (e). Optical coherence tomography confirmed the absence of intra- or sub-retinal fluid and a significant reduction in retinal thickness in the macula (f)

Case 2

A 55-year-old female patient was admitted to our clinic with metamorphopsia in her LE with duration of 6 months. On ocular examination, BCVA was 20/63 in both eyes. Funduscopy revealed right-angled venules and loss of retinal transparency in the fovea in both eyes and juxtafoveal hyperpigmented scar in the LE. FA showed perifoveolar retinal leakage in both eyes and a subfoveal classic CNV associated with leakage in the LE. OCT demonstrated lamellar cysts in the fovea in both eyes and a subfoveal hyperreflective area associated with an intra- and subretinal fluid collection in the LE. CRT was 324 μ in the LE. The patient was diagnosed with proliferative IMT 2 and underwent a single injection of IVB in the LE. After a single injection of IVB (1.25 mg/0.05 ml), BCVA increased to 20/50 and both the clinical and angiographic features showed significant improvement and absence of intra- or sub-retinal fluid on OCT. BCVA was stable at 20/50 during 24 months of follow-up. There was a complete cessation of leakage over the duration of follow-up. At the last examination, CRT was 273 μ.

Case 3

A 52-year-old female was presented with decreased vision in her RE for a month. Ocular examination revealed VA of 20/100 in the RE and 20/25 in the LE. Fundus examination showed the presence of right-angled venules and a graying of the foveal region in both eyes, and elevated yellow fibrous tissue with black retinal pigmented epithelial hyperplasia in the central fovea of the RE. FA demonstrated an intraretinal staining pattern in both eyes and some degree of leakage in the fovea secondary to the neovascular membrane. OCT revealed numerous microcysts and larger hyporeflective compartments in the RE. CRT was 391 μ in the affected eye. The patient treated on “as needed” basis. Three ranibizumab injections (0.5 mg/0.05 ml) were administered during the entire course of treatment. Twelve months after the initial ranibizumab injection, BCVA improved to 20/30. Minimal hyperfluorescence was observed on FA. At the last examination, CRT was 303 μ.

Case 4

A 20-year-old female was suffered with a 3-month history of gradual visual impairment in the LE. She was a known diabetic on treatment for the past 12 years. On examination, BCVA was 20/25 in the RE and 20/100 in the LE. Fundus examination revealed a grayish retina temporal to the fovea with multiple yellowish crystalline deposits and pigments in both eyes. A clinical diagnosis of proliferative IMT 2 in the LE was confirmed with FA indicating active leakage and scarring. OCT findings included the presence of intra- and sub-retinal fluid and a hyperreflective line corresponding to the neovascular membrane located subfoveally. The patient received three sequential injections of bevacizumab (1.25 mg/0.05 ml) and then did not subsequently recur. BCVA improved to 20/63. Both the clinical and angiographic features showed significant improvement with minimal leakage on FA and absence of intra- or sub-retinal fluid on OCT. These findings were maintained until the last follow-up visit at 18th month.

DISCUSSION

Yannuzzi et al.3 proposed a simplified classification termed as IMT with two distinct types (type I, or aneurysmal telangiectasia, and type II, or perifoveal telangiectasia) to better understand the entities. Macular telangiectasia type 2 is mainly divided into two stages, in the case of treatment. The first stage is the nonproliferative stage, which is characterized by slow, progressive visual loss in association with outer retinal atrophy. The second stage is the proliferative stage, which is characterized by the presence of SRN.1234 Several treatment options have been evaluated for the nonproliferative stage. However, most were ineffective due to the degenerative and progressive nature of this disease.4 In contrast, the proliferative stage was successfully treated with photodynamic therapy (PDT), intravitreal anti-vascular endothelial growth factor (VEGF) injections, and combination therapies.1

Engelbrecht et al.5 revealed that the natural course of proliferative IMT 2 resulted in very poor prognosis including VA of 1/20 or less in 80% of the cases.

A retrospective case series by Potter et al.6 showed that PDT was effective for stabilizing the vision in five of seven eyes. However, the improved vision was achieved only in three of seven eyes and there was no improvement in median VA over a mean follow-up time of 21 months.

Anti-VEGF agents have rapidly become the mainstay of therapy against any type of CNV in various diseases, including proliferative IMT 2.178910 A case series of six eyes reported that median VA improved from 20/200 to 20/100, and the mean CRT decreased from 263 μ to 201 μ over a mean follow-up time of 4.2 months.8 The results in the aforementioned study were fairly good; however, the follow-up time was very limited.8 Roller et al.9 also reported beneficial results of IVB in nine patients. In their study, after a mean follow-up time of 17 months and mean of 4.9 bevacizumab injections (range: 1 injection-15 injections), the mean VA improved 1.1 lines, and mean central macular thickness decreased by 48 μ. In addition, the VA either remained stable or improved in seven of nine eyes (78%) and the CNV completely resolved in eight of nine eyes (89%) after treatment.9 Karagiannis et al.10 reported that monthly injections of ranibizumab were effective in a patient with proliferative IMT 2. They reported that the VA improved from 1/20 to 3/10 after 12 monthly IVR injections.

In our cases, all the patients were treated with intravitreal anti-VEGF agents, bevacizumab, or ranibizumab on “as needed” treatment regimen. Complete cessation of leakage was observed in one eye postintervention. Partial reduction of leakage was noted in three of the remaining eyes with residual late staining. Despite case 1, the VA improved in the remaining three cases. Lack of visual improvement may be attributed to structural changes of the photoreceptors as shown in previous studies.3

CONCLUSION

Nonproliferative IMT 2 patients should be educated with symptoms such as decreased vision and metamorphopsia that are associated with proliferative transformation. Nonproliferative IMT 2 patients should be followed regularly to deliver timely treatment in the case of transformation. IVB or IVR injections on an “as needed” treatment regimen may be effective in proliferative IMT 2. Although the investigation of a large series is difficult due to the relative paucity of patients with proliferative IMT 2, further studies are required to evaluate the safety and efficacy of intravitreal anti-VEGF agents in this group of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.