Photodynamic Therapy
Photodynamic therapy with verteporfin of CNV represents an advancement in the treatment of myopic macular degeneration complicated by CNV. The aim of PDT is to treat CNV, especially located into the fovea, without the complications of laser photocoagulation. Originally developed for the treatment of solid tumors, PDT is employed to selectively occlude CNV while minimizing the degree of injury to the surrounding neurosensory retina. The mechanism of PDT is based on nonthermal light activation of verteporfin that, administered intravenously, selectively accumulates in the neovasculature. The result of PDT leads to immediate occlusion of vessels within the CNV.
Photodynamic therapy with verteporfin has been demonstrated to improve the visual prognosis of myopic patients with subfoveal CNV that was previously untreatable with conventional thermal laser (Figure 8 and Figure 9).[26,27,28,29,30,31,32,33,34] The Verteporfin in Photodynamic Therapy (VIP) study group demonstrated the benefits of PDT at 3 years post-treatment with a higher final median VA (20/64) compared with untreated patients (20/100).[29,30,31]
Myopic choroidal neovascularization along the margin of an area of chorioretinal atrophy. (A) Before and (B) after photodynamic therapy.
In summary, 15% of patients had an increase in VA and maintained it during the third year, and 73% maintained stable vision. Only a few patients lost some vision during the third year and 2% showed a vision increase during the third year.
Pece et al. evaluated the safety and effectiveness of PDT with verteporfin in a series of 62 eyes with PM.[32] The final VA, after a median follow-up of 31 months, improved by 1 or more Snellen lines in eight patients (13%), deteriorated in 20 (32%), and remained stable in 34 (55%). The baseline VA was similar in the various study groups. The final mean VA in group A (<55 years old) was 20/80 and significantly (p = 0.006) better than the 20/138 in group B (>55 years old). The mean final VA in eyes with higher refractive error at baseline (> -17D) was significantly better (p = 0.014) than in eyes with lower refractive error (-6 to -10 diopters). The size of the CNV lesion did not affect visual outcomes. PTD preserves vision in patients with CNV associated with pathologic myopia. Younger patients (<55 years old), and eyes with higher refractive error, appear more likely to benefit from PDT with verteporfin.[33] Some of these results are summarized in Table 1 .
The major drawback of laser therapy in the treatment of juxtafoveal CNV is the potential for foveolar damage that could result from an expansion of thermal radiation toward photoreceptor cells into the central fovea or from an enlargement of laser scar resulting in absolute scotoma with visual disturbances and difficulty in reading ability.[35]
Verteporfin therapy has been shown to provide significant visual and anatomic benefits for subfoveal myopic neovascularization.[35] A small case series have also investigated the effect of PDT in the treatment of juxtafoveal myopic CNV. Recently, Cohen et al. reported a benefit of the treatment on three cases.[36] A small, prospective, noncomparative trial of 11 eyes with juxtafoveal CNV was performed by Lam et al. who found a good response to PDT after 1 year of follow-up.[37] Five eyes (45.4%) improved by three or more lines of vision and six eyes (54.5%) were unchanged. These authors have similarly concluded that verteporfin therapy is a promising treatment option in treating juxtafoveal myopic CNV. Another study by Blair et al. performed a retrospective evaluation of four patients with juxtafoveal CNV[38]; in one eye VA improved by 1 line while in three eyes VA declined by a mean of 3.3 lines from baseline at 12 month follow-up due to the neovascular process continued to growth under the FAZ.
Pece et al. have evaluated the effect of PDT with verteporfin for juxtafoveal CNV in a series of 48 consecutive patients (49 eyes) with PM followed for 32 months (range: 12-56 months).[39] The cohort was divided into two groups according to age (group A < 55 years old; group B > 55 years old), in three subgroups based on CNV lesion size, and in three categories on the basis of refractive error at baseline. The results indicated that VA improved by 1 or more Snellen lines in 18 eyes (37%), decreased in 12 eyes (28%), and remained stable in 19 eyes (39%). The median number of lines gained was 2.14. The average number of lines lost was 2.38. The final mean VA in group A (mean age: 43.9 years) was 20/50 (logMAR: 0.41; standard deviation [SD] 0.3) and significantly better (p = 0.01) than the 20/105 (log minimum angle of resolution [MAR]: 0.72; SD: 0.5) in group B (mean age: 67.8 years). The size of CNV and the magnitude of dioptric error did not influence visual outcomes. The authors concluded that 'PDT is a promising treatment modality for stabilizing and improving vision in 76% of myopic eyes with juxtafoveal CNV. Younger patients appear to respond more favorably to PDT'.
The surgical treatment of myopic CNV is currently a controversial topic owing to its difficulty in assessing the exact role of subretinal surgery in the management of patients with subfoveal CNV secondary to PM.
Submacular surgery involves the creation of a retinotomy, usually temporal to the macula, to gain access to the subretinal space via pars plana vitrectomy. A small number of case series have been published in the literature. Maas et al. reported that two out of four patients who underwent submacular surgery for CNV due to PM had significant improvement in VA.[40]
Adelberg et al. reported that VA had improved by two Snellen lines in two of five myopic eyes with subfoveal CNV excised by submacular surgery; the remaining three eyes lost no VA following surgery.[41,42] The Submacular Surgery Trials (SST), sponsored by National Eye Institute, have determined that submacular surgery is not beneficial.
Possible complications after submacular surgery include cataract onset, retinal detachment, recurrences (8-57%, up to 72%[17]) and RPE defect.[42,43,44] The major postoperative complication is RPE defect and its expansion over time. However, the natural history of a myopic CNV may also lead to a final scar, that is on average 2.6-times larger than the original CNV.[42]
A second type of surgical treatment is the macular translocation: it consists of the surgical moving of the central neurosensory retina or fovea in an eye with recent onset of subfoveal lesion to a new location with presumably healthier RPE and choriocapillaris away from the lesion, where the fovea may be able to recover or maintain its visual function.[44]
Two different techniques are currently in use to perform macular translocation:
Full macular translocation: macular translocation with 360° or complete circumferential retinotomy
Limited macular translocation (macular translocation with punctuate retinotomy)
Macular translocation may actually improve VA and reading ability. Full macular translocation has the best functional outcomes,[44] but it also has the highest risk of postoperative complications, such as retinal detachment, macular fold requiring reoperation, macular hole and progression of chorioretinal atrophy. Limited macular translocation has as major complication insufficient translocation and, therefore, enlargement or recurrence of the CNV, or expansion of the chorioretinal atrophy, involving the new foveal location.
Transpupillary thermotherapy with 810-nm infrared diode laser can be another alternative for the management of myopic CNV. TTT differs from standard photocoagulation therapy in that it uses infrared laser light to apply over a larger area. A low-energy, longer exposure diode (810 nm) laser application gently heats up the CNV leading to closure of abnormal neovasculature sparing the overlying neurosensory retina. Laser energy is applied for 60 s. There are no external drugs used along with this laser treatment as there are in PDT. Therefore, there is no risk of photosensitivity and patients can go back to their normal routine after the treatment. The goals of TTT treatment are to seal the leaking vessels and the preservation of vision. Repeated treatments may be required in recurrent or persistent CNV.
Few reports on the effect of TTT on myopic CNV have been published in the ophthalmic literature. In a retrospective analysis of a case series of myopic CNV treated with TTT, Ozdek et al.[45] concluded that TTT seems to stabilize myopic CNVs both clinically and as revealed by angiography, with a significant decrease in the activity of lesions.[40] TTT considering the new therapeutical options is no longer used.
Currently, new therapeutic options are available for the management of myopic macular degeneration complicated by CNV. Anti-angiogenic and angiostatic drugs administered intravitreally can represent a new method of treatment. Besides, PDT combined with intravitreal triamcinolone acetate (IVTA), and the anti-VEGF inhibitors are very promising. Since the introduction of intravitreal anti-VEGF, there has been a gradual reduction in the use of PDT and a new style of patients management during the postinjection follow-up. Many patients receiving anti-VEGF agents show visual improvement or stabilization despite long-term leakage shown on angiography. Herein, we describe the current status of these novel therapeutic agents.
Expert Rev Ophthalmol. 2008;3(3):311-323. © 2008 Expert Reviews Ltd.
Cite this: Management of Choroidal Neovascularization in Myopic Macular Degeneration - Medscape - Jun 01, 2008.
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