bevacizumab injections after a mean follow-up period of 18 months.22 The effect of the anti-VEGF treatment, monitored by fluorescein angiography and OCT imaging, decreased after 3–4 months. Further treatments showed similar effects within the follow-up period. Maia Junior and co-workers published an observation after intravitreal bevacizumab injection (1.25 mg) in three nonproliferative eyes with foveal detachment on OCT analysis.23 The foveal anatomy regained a normal configuration and visual acuity significantly increased after a single intravitreal injection of bevacizumab.

In conclusion, there is as yet insufficient information on potential treatment benefits for nonproliferative type 2 IMT to make any general recommendation. Generally, visual deficits seem to evolve very slowly early in the course of the disease. Therefore, short-term observations after therapeutic interventions might not be sufficient to evaluate potential treatments for this chronic disease. Moreover, the functional parameters to monitor treatment effects have to be chosen carefully. For instance, the development or changes of characteristic paracentral scotomata appear to be a functional outcome measure which might respond differently to therapeutic interventions than visual acuity.2,22 It was suggested that therapeutic strategies such as intravitreal inhibition of VEGF might be most effective in a temporary “active” disease stage with marked vascular alterations.22 However, confirmation of such an active disease is lacking. In this regard, results from a large international multicenter natural history study (www.mactelresearch. org) may provide further insights. A progressive neurosensory atrophy with secondary involvement of retinal vessels was suggested to underlie the disease. In this case, the long-term success of treatments targeting altered retinal capillaries may be limited and antagonization of the neuroprotective properties of VEGF may even be unfavorable. Regardless of the underlying pathophysiology, the potential gain of function might be limited by the atrophic neurosensory changes before therapy and therefore, initial phenotypic and functional characterization is most important.

PROLIFERATIVE STAGE

Development of secondary neovascularizations represents a major cause of severe vision loss in type 2 IMT1,25 and various therapeutic approaches have been tried to limit the consequences of this disease stage. Park and co-workers found little change in the size of the fibrovascular tissue over time and consequently questioned the usefulness for treatment in stage 5 eyes.24 Therefore, interventions appear to be most beneficial in early and active proliferative disease stages (i.e., while a neovascular membrane grows) before the development of fibrotic membranes.

Several approaches to treat proliferative type 2 IMT have been reported: focal laser photocoagulation,27,28 PDT alone29–34 or combined with intravitreal injection of triamcinolone,26 transpupillary thermotherapy,35 posterior juxtascleral administration of steroids19 and, recently, intravitreal injection of VEGF inhibitors.21,23,36–38

Visual stabilization as well as deterioration has been reported after argon laser photocoagulation in stage 5 type 2 IMT.27,28 This treatment approach seems to be relatively safe in terms of recurrence of the membranes. However, large parafoveal scars, as reported in the literature, might severely interfere with, e.g., reading ability. However, this functional outcome measure was not reported.

PDT with verteporfin has been shown to be beneficial for the treatment of subfoveal choroidal neovascularization secondary to agerelated macular degeneration or other diseases. PDT was first reported in a patient with recent decrease in visual acuity due to proliferative type 2 IMT by Potter and co-workers.30 After two treatments in accordance with the standard protocol established for age-related macular degeneration, visual acuity improved 2 lines and remained stable within a follow-up period of 7 months. Interestingly, leakage from the neovascular membrane disappeared whereas parafoveal leakage typical for type 2 IMT continued. The largest series, a retrospective analysis, encompassed seven eyes of six patients.29 Patients received on average 2.4 treatments and mean follow-up after the last treatment was 21 months. Median initial and final visual acuity was 20/80. More than

2 lines decrease or increase in visual acuity was observed in one eye each while the other five eyes remained stable. Hussain and co-workers treated six eyes of three patients three times with an interval of 2 months.32 Their patients had a stable visual acuity after a median follow-up of 10 months (range 6–21 months). The researchers noted associated retinal pigment epithelium collateral damage in all six eyes of their study. There is the theoretical concern that the photosensitizing drug may leak out of the retinal vessels in the macula and potentially cause harm.30,32 Indeed, Shanmugam et al. showed atrophy of the retinal pigment epithelium (along with a decrease in visual acuity) corresponding to the size of the laser spot.34 However, others did not observe any side-effects.29,30 Snyers and co-workers reported their results after treating four eyes of four patients with PDT.33 Within a follow-up period of 9–23 months, three eyes maintained a stable visual acuity after 1–3 treatments. One eye deteriorated significantly within 14 months’ follow-up despite four treatment sessions. Based on a single case report, Hershberger and colleagues emphasized that the neovascular membranes in type 2 IMT might tend to reperfuse rapidly.31 Smithen and Spaide treated a patient with combined PDT and intravitreal injection of triamcinolone (4 mg).26 They found a regression of the neovascular membrane along with significant improvement of visual acuity. Within a follow-up period of 12 months, a second combined therapy was performed at 9 months due to recurrence of angiographically visible leakage.

In a retrospective report studying the effect of transpupillary thermotherapy, the majority (92%) of 14 eyes showed stabilization or improvement in visual acuity as well as regression of the vascular membrane.35 Posterior juxtascleral administration of anecortave acetate resulted in stabilization or improvement of lesion size, resolution of leakage, and stabilization of vision in five eyes of four patients.19

Intravitreal application of bevacizumab for proliferative type 2 IMT was first described by Jorge and co-workers.38 A single injection of 1.5 mg in their patient presenting with an extrafoveal membrane resulted in the absence of signs of activity and significant improvement of visual acuity within a follow-up period of 6 months. Later, similar single observations of significant functional and anatomical improvement in a proliferative disease stage were reported in individual patients with23 or without36 accompanying foveal detachment. In a patient with a larger subfoveal membrane, no increase in visual acuity despite anatomical improvement was achieved.21 In a case series including six eyes of six patients with a follow-up of 3–6 months, visual acuity improved by more than 2 lines in all but one patient.37 A second injection was only necessary in one eye.

There are two reports on subretinal surgery with removal of subfoveal vascular membranes in two eyes with type 2 macular telangiectasia.39,40 Due to the adherence of the membranes to the neurosensory retina, removal proved to be difficult and visual outcome was poor.

In summary, there is as yet insufficient evidence on treatment benefits and too short follow-up periods to make any general recommendations for the treatment of proliferative type 2 IMT. Moreover, the natural course of neovascular membranes in this disease, once developed, may be less aggressive compared to, e.g., those in agerelated macular degeneration. Therefore, stabilization of visual acuity in eyes with neovascular type 2 IMT that have been stable for several months may not be an adequate outcome measure. More information about the natural history of this disease entity will most likely influence treatment recommendations. Until studies with a higher evidence level become available, PDT and intravitreal inhibition of VEGF seem to be the most promising treatment approaches in patients with recent visual loss. Patients with stable visual function and constant size of the neovascular membrane (Figure 26.2) may just be observed rather than treated for the time being.

SUMMARY AND KEY POINTS

In summary, IMT presents in three different types (type 1, 2, and 3), with type 2 being the most common form. Establishing the diagnosis is generally straightforward, but treatment of the condition may be chal-

Pharmacotherapy to Amenable Diseases Retinal • 3 section

Telangiectasia Macular•Idiopathic26 chapter