Management of Choroidal Neovascularization in Myopic Macular Degeneration

Alfredo Pece; Vincenzo Isola; Lucia Vitale

Disclosures

Expert Rev Ophthalmol. 2008;3(3):311-323. 

In This Article

Photodynamic Therapy Plus Triamcinolone Acetate

Triancinolone acetate is a corticosteroid with anti-inflammatory properties produced by inhibitory activity of arachidonic acid formation combined with antiangiogenic functions. Marticorena et al. evaluated VA changes and safety of combined treatment with PDT and IVTA injection in 12 myopic eyes with CNV in a prospective interventional case series.[46] The combination of PDT and IVTA may increase the possibility of improving or stabilizing VA in patients with subfoveal myopic CNV. The combination of PDT plus IVTA generally results in the need for fewer PDT retreatments.

Recently, Chan et al. treated 22 eyes with a combination of triamcinolone and PDT but the authors did not observe a better visual outcome compared with PDT monotherapy, except in selected patients with worse initial VA or larger myopic CNV.[47]

The new and promising strategies for treating CNV include the use of drugs against VEGF, in particular isoform A, which is the most potent promoter of angiogenesis and vascular permeability. This therapy has been applied for AMD patients and, in the future will be used more diffusely for myopic CNV.

In general, the first ocular anti-VEGF agent is pegaptanib sodium (OSI/Eyetech Pharmaceutical, NY, USA), an aptamer designed to target VEGF165, the most representative isoform of VEGF-A in ocular disease. The VEGF Inhibition Study In Ocular Neovascularization (VISION) study has demonstrated the efficacy of this drug in all CNV subtypes in AMD patients even if patients losing more than 15 letters were still approximately 40% despite injections every 6 weeks in a 2-year study.[48] Literature is very poor regarding the use of pegaptanib in myopic CNV.

Bennett et al. reported a successful case of pegaptanib for myopic choroidal CNV refractive to laser photocoagulation, PDT and intravitreal triamcinolone acetonide: VA improved from counting fingers to 20/40 after five, 6-weekly pegaptanib injections.[49]

Bevacizumab (Avastin®, Genentech) is an anti-VEGF antibody approved for the treatment of metastatic colon cancer, and has an off-label use in CNV secondary to AMD, with good short-term safety but uncontrolled series of patients.

Ruiz-Moreno et al. in a prospective, nonrandomized, multicenter, interventional pilot study, described the anatomical and visual outcome of subfoveal and juxtafoveal CNV in 26 highly myopic eyes treated by intravitreal bevacizumab.[50] They concluded that bevacizumab seems to be effective, but further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.

Chan et al. also evaluated the safety and efficacy of intravitreal bevacizumab in the treatment of CNV secondary to pathologic myopia in a prospective, consecutive, nonrandomized, interventional case series.[51] A total of 22 participants (22 eyes) received an initial course of three monthly intravitreal injections of bevacizumab. Three additional monthly injections were performed in eyes with persistent CNV leakage after 3 months. Treatment resulted in complete absence of angiographic leakage in 90.9% of eyes at 3 months and two (9.1%) eyes required further treatment up to 6 months. The 6-month outcomes suggest intravitreal bevacizumab to be a promising treatment method for CNV secondary to pathologic myopia, resulting in both visual improvement (the mean lines of improvements at 1 and 6 months compared with the baseline were 1.7 and 2.6 lines, respectively) and anatomic improvement.

Other authors reported the effectiveness of bevacizumab in treating this disease, even if the follow-up is short and the number of patients is poor.[50,51,52,53,54] The authors stressed that the therapy seems to be safe and potentially effective. Moreover, Yamamoto noted that most of the eye received only one injection in a mean follow-up of 153 days.[52]

Ranibuzumab (Lucentis®, Genetech/Roche) is an antibody fragment that binds all active isoform of VEGF-A, modifying a murine monoclonal antibody to have a fragment for improving VEGF binding. In the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the Treatment of Neovascular AMD (MARINA) study for minimally classic or occult CNV in AMD patients with monthly injection patients had a stability or improvement of vision in over 90% of the cases at the end of 24-month study and an improvement of vision in approximately 30% of the cases.[55] Also in Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial for predominantly classic CNV secondary to AMD results were even better and therefore very positive on a 24-month basis with an improvement of vision up to 40% of patients.[56]

We currently do not have any report of ranibizumab in myopic CNV but from personal experience it seems very promising with good results and fewer injections (Figure 10, Figure 11 and Figure 12).

Myopic choroidal neovascularization. (A) Before and (B) after photodynamic therapy. Note the hypofluorescent spot following the photodynamic shut down of the choroidal neovascularization.

Fluorescein angiography. (A) Before and (B) after intravitreal injection of ranibizumab shows decreased leakage from myopic choroidal neovascularization.

Marked reduction of leakage is evident 1 month after intravitreal injection.

All the drugs described are used as off-label treatments. Problems arise considering their different cost and returning every month for years is an emotional and psychological burden for not only the patient but also for the family. Moreover, we have to consider the possibility of ocular risks related to the injection process itself and systemic effects of anti-VEGF therapy. Regarding the ocular risks, we have to consider that the complications are decreased dramatically after using better systems of sterility in the operating room, while for the systemic ones we have very poor data and this depends on the different drug used. Bevacizumab's half-life in the systemic circulation is approximately 20 days compared with 12 h for ranibizumab. Genentech released data that in the Safety Assessment of Intravitreal Lucentis for AMD (SAILOR) trial 0.5 mg dose had a significant risk of stroke compared with the 0.3 mg dose (1.2 vs 0.3%; p = 0.02). These data seems to be overexpressed considering the very low incidence of side effects in the daily clinical experience.

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