26 Idiopathic macular telangiectasia

INTRODUCTION

Idiopathic macular telangiectasia (IMT) was first classified as a group as idiopathic juxtafoveolar retinal telangiectasis. In 1993, Gass and Blodi modified the description of this condition, and today, it remains the most commonly used classification.1 It encompasses three different groups (or types) of rare disease entities with the common feature of telangiectasia of juxtafoveolar small vessels that predominantly occur temporally to the foveola. Data on the prevalence of any of the types of IMT are lacking. The term “idiopathic” distinguishes the incoherent group of diseases from other similar secondary vascular alterations such as after retinal vein occlusion, vasculitis, diabetes, carotid occlusive disease, or radiation therapy.1,2

According to Gass and Blodi, type 1 has a male predominance and occurs unilaterally with a marked exudative component. Type 2 occurs more frequently than type 1 and usually presents bilaterally with atrophic neuroretinal changes and no gender predilection. Further functional deterioration may occur through the development of secondary neovascular membranes or macular holes. The very rare type 3 presents with angiographically visible obliteration of the perifoveal capillary network and may occur with an associated vasculopathy of the central nervous system. Further subclassifications for each type were suggested.1 Due to the rarity of type 3 IMT and the lack of clinical treatment studies, therapy of this subtype is not further addressed in this chapter.

TYPE 1 IDIOPATHIC MACULAR

TELANGIECTASIA

Mean age of type 1 IMT was reported to be 37–56 years (range 7–74 years), with a male predominance of 61–70%.2 The disease is thought to be a developmental anomaly. The clinical hallmarks are visible aneurysmatic telangiectatic changes with cystoid retinal edema and surrounding exudates. Mean visual acuity in the affected eye was reported to be 20/40 (range 20/20–1/200) if the disease encompasses more than 2 clock-hours parafoveally.1 Deterioration of visual acuity usually occurs once the cystoid edema affects the fovea. Both, functional improvement and deterioration may occur in the long-term follow-up.

Studies to characterize the disease further using new imaging methods are lacking. Type 1 IMT may encompass a spectrum with only minimal affection of capillaries in the very vicinity to the foveal avascular zone on the one end and pronounced vascular alterations with strong exudation at the temporal posterior pole on the other end. Possibly, type 1 IMT encompasses different disease entities.

rounding retinal edema and retinal lipid exudates. The vascular changes typically involve an irregular or oval zone centered temporal to the fovea. The affected area is typically 1–2 disc diameters in size but may also encompass larger extramacular areas and rarely even involves areas in the peripheral fundus. Larger aneurysms may be associated with retinal hemorrhage. Microaneurysms and hard exudates may appear in the early disease stages. The disease manifestations may slowly progress but may also regress after years. Early-phase fluorescein angiography reveals aneurysmatic abnormalities with a diffuse leakage in late-phase angiography. The aneurysms involve the deep and superficial capillary network and some patients have minimal capillary ischemia.3 Optical coherence tomography (OCT) shows retinal thickening in the presence of cystoid macular edema. Localized neurosensory detachment may also occur.3 OCT imaging may be useful for documentation and for the evaluation of treatment effects.

THERAPY

Focal laser photocoagulation of the affected area may lead to a decrease of macular edema and improvement of visual acuity.1,4–6 Li and coworkers reported the effect using intravitreal administration of triamcinolone in a single patient in whom prior laser treatment was not successful.7 The macular edema regressed but showed a rebound effect 6 months after treatment. A similar experience was reported by our group.2 Recently, Gamulescu and co-workers presented a patient with type 1 IMT whose macular edema and visual acuity improved after a single intravitreal injection of bevacizumab,8 suggesting that vascular endothelial growth factor (VEGF) is involved in the pathogenesis of the disease. The effect remained stable within a follow-up period of 10 months.

The natural history of type 1 IMT and long-term treatment effects have not been investigated in larger trials. It should be noted that spontaneous resolution of the pathology has been reported in individual cases.1,9 Currently, no treatment recommendations based on a high level of evidence can be provided. Due to the rarity of the disease, prospective multicenter studies to elucidate the natural history of the disease further (as for type 2 IMT; see below) would be a helpful basis for future prospective interventional trials. Besides focal laser coagulation, pharmacological interventions such as VEGF antagonization might be a promising therapeutic approach. However, patients suffering from type 1 IMT are relatively young and therefore the perspective of long-term intravitreal drug application is unfavorable. With the development of safer and longer-lasting therapeutic strategies, these obstacles may be overcome.

DIAGNOSTIC APPROACH AND

CLINICAL FINDINGS

Patients usually complain about a unilateral loss of visual acuity and/ or metamorphopsia. On clinical examination, ophthalmoscopy shows retinal aneurysmatic telangiectasia temporal to the foveola with sur-

TYPE 2 IDIOPATHIC MACULAR

TELANGIECTASIA

In this most common form of IMT, subtle telangiectasia are only visible in a subgroup of patients and often are rather ectatic appearing parafoveolar capillaries. The altered capillaries can be visualized on early-

Telangiectasia Macular•Idiopathic26 chapter

phase fluorescein angiography whereas leakage from these altered vessels becomes apparent in late angiographic phases.

Gass and Blodi1 proposed five consecutive stages. Stage 1 is characterized by a diffuse juxtafoveolar hyperfluorescence in late-phase fluorescein angiography. In stage 2, a reduced parafoveolar retinal transparency becomes evident ophthalmoscopically. The hallmark of stage 3 is dilated right-angled venules and of stage 4 intraretinal proliferation of pigment epithelial cells typically along right-angled vessels. Stage 5 is characterized by secondary retinal neovascularizations. The predilection site for all these pathological changes is temporal to the foveola. Further sequels of type 2 IMT may be lamellar or full-thickness macular holes, presumably due to progressive degeneration and atrophy of neurosensory­ retina.10 A series of recent publications described characteristic­ findings on OCT imaging, which suggests this new imaging technique as an objective measure of therapeutic effects complementing angiography.

NONPROLIFERATIVE STAGE

In disease stages without neovascular membranes (i.e., stages 1–4 following the classification of Gass and Blodi), argon laser photoco­ agulation,1,4,11–13 photodynamic therapy (PDT),14 intravitreal injection of steroids alone,15–17 or in combination with indocyanine green (ICG)- mediated photothrombosis18 and posterior juxtascleral administration of steroids19 have been tried. As in type 1 IMT, the effect of intravitreal injections of VEGF inhibitors8,20–23 has recently suggested a pathophy­ siological involvement of VEGF in type 2 IMT.

Hutton and co-workers, who were the first to describe type 2 IMT as a distinct disease entity with a possible genetic background, reported the successful treatment of two patients by focal argon laser photocoagulation.13 In four eyes of three patients, the treatment resulted in a reduction of metamorphopsia and improvement of visual acuity within a follow-up period between 6 months and 3.5 years. Park and coworkers retrospectively analyzed the long-term outcome (median follow up time 73 months) in 10 eyes of eight patients after argon laser photocoagulation.11 Visual acuity did not change significantly and a reduction of macular edema was only achieved in 20% of treatments. Previous laser photocoagulation was associated with an increased distortion of retinal vessels, new fibrovascular tissue, increased changes of the retinal pigment epithelium, new draining venules, and retinal hemorrhages. The authors concluded that patients with type 2 IMT did not benefit from argon laser photocoagulation within the area of leakage. In a series by Gass and Blodi,1 10 eyes of 10 patients received laser treatment. Of eight eyes with long-term follow-up (mean 43 months, range 33–52 months), visual acuity remained unchanged in four eyes and worsened by 2 or more lines in four eyes. Of the untreated fellow eyes, four worsened, three remained unchanged and one improved. Overall, there may be an increased risk of the development of new fibrovascular membranes after argon laser photocoagulation in

type 2 IMT.1,11,24,25

PDT (using the standard parameters adopted from treatment of wet age-related macular degeneration) was applied in two eyes of two patients with nonproliferative type 2 IMT.14 In both patients, the authors did not observe significant changes in visual acuity, fluorescein angiographic leakage, or findings in OCT imaging. It was therefore concluded that PDT does not have beneficial effects in this disease.

The clinical course of individual patients after intravitreal injection of triamcinolone was reported by several authors.15–17 A reduction of the late-phase hyperfluorescence in fluorescein angiography with17 or without15,16 significant improvement (i.e., more than 2 lines) in visual acuity was reported. However, Smithen and Spaide found no changes after intravitreal injection of 4 mg triamcinolone in a nonproliferative eye, neither functionally nor angiographically.26 The eye of the patient presented by Martinez showed an increase in visual acuity from initially 20/63 to 20/30 after 6 weeks and 20/25 after 6 months.17 Cakir and co-workers documented a reduction in retinal thickness after intravitreal injection of triamcinolone and a waning effect of the therapy at a follow-up 9 months after treatment.16 Fernando Arevalo and coworkers suggested a combined therapy of intravitreal injection of tri-

amcinolone with ICG-mediated photothrombosis to be more effective.18 ICG-mediated photothrombosis is thought to produce a selective endothelium-bound intraluminal photothrombosis following an intravenous injection of a highly concentrated ICG solution and focal activation with a low-irradiance, 810-nm laser light. It is thought that this technique largely preserves the retinal architecture with minimal loss of visual cells. However, confirmatory evidence of this pilot study is lacking.

A recent study reported the effect of posterior juxtascleral administration of 15 mg anecortave acetate, an angiostatic synthetic cortisol derivative with negligible corticosteroid bioactivity.19 In the two nonproliferative eyes of this study, visual acuity was stabilized over a period of 24 months. However, no data were provided with regard to the natural history in the fellow eye for comparison, the angiographic effects, or alterations on OCT imaging.

A new pharmacological approach in nonproliferative type 2 IMT, the intravitreal inhibition of VEGF, was first proposed by our group. In an initial report, we showed that intravitreal application of 1.5 mg of the VEGF antagonist bevacizumab resulted in a marked decrease of juxtafoveolar leakage without an apparent increase in visual acuity.20 Shortterm effects on angiography and retinal thickness in six nonproliferative eyes were subsequently analyzed.21 Two injections were performed with an interval of 4 weeks. Four weeks after the second treatment, there was a decrease in retinal thickness within the central 3 mm of the retina in all eyes. Assessment of fluorescein angiography revealed a reduction of ectatic capillaries seen in the early phase as well as of late-phase leakage (Figure 26.1). Visual acuity improved in a subset of patients. An increase of more than 15 ETDRS letters was observed in one eye and of 10–15 ETDRS letters in two eyes, while the other four eyes remained stable. Gamulescu and co-workers observed decreased leakage on angiography and a stable visual acuity in two patients after three initial injections in monthly intervals over a follow-up period of 11 and 12 months.8 Retinal thickness did not decrease; however, they only reported measurements at baseline and the end of follow-up. A further study of our group reported the long-term effects of intravitreal

Figure 26.1  Early (top) and late (bottom) fluorescein angiography of the left eye of a patient with nonproliferative type 2 idiopathic macular telangiectasia before (left column) and after (right column) intravitreal application of 1.5 mg bevacizumab. The telangiectatic capillaries in earlyas well as the late-phase leakage in late-phase angiography show a marked reduction after therapy. At the same time, retinal thickness decreased within the corresponding area. Visual acuity did not change significantly. (Eye number 5 from reference 21.)