Alternative therapies for choroidal neovessels resulting from age-related macular degeneration

Classic neovessels (CNVs) identified on fluorescein angiography may benefit from thermal laser photocoagulation when sparing the fovea. If they extend into it, photodynamic therapy may halt the natural progression to a central scotoma. Occult CNVs, when subfoveal, may benefit from photodynamic therapy when isolated (not associated with classic CNV or with a pigment epithelium detachment). A number of therapeutic approaches are being evaluated in order to diversify the therapeutic choices available for treatment of CNVs. Transpupillary thermotherapy, which causes a limited increase in retinal temperature, could produce a sclerosis of occult isolated CNV. This approach has shown interesting results in pilot studies but also carries a risk for iatrogenic effects. The American randomized clinical trial currently under way will provide an evaluation of this treatment. An antiangiogenic therapy currently in progress is studying anecortave acetate and another is investigating anti-VEGF compounds. Anecortave acetate, which demonstrated its angiostatic activity in experimental models as well as in a phase II study, is now in a worldwide randomized clinical trial. The anti-VEGF molecules (antibodies and oligonucleotides) have shown very interesting preliminary results and are being evaluated in a large number of patients. Finally, a preventive therapy consisting of oral supplementation with antioxidants (vitamins C, E, and A) and zinc is a major step forward, providing the possibility of a real and effective prevention of the complications of age-related maculopathy.     

New occult choroidal vessels in age-related macular degeneration

We studied the clinical characteristics and the natural course of occult choroidal new vessels (CNV) in 78 eyes with age-related macular degeneration (AMD). Cases were included in 2 groups characterized respectively by ill-defined subretinal ooze (group 1) and serous detachment of the retinal pigment epithelium (RPE) with adjacent areas of mottled pigmentation (group 2). Both these forms of occult CNV showed to have a slower evolution compared to the classic CNV occurring in AMD, but they also led to disciform scar and severe visual loss. Occult CNV of group 2, contrary to those of group 1, were often multifocal and extrafoveal. They had a greater tendency to hemorrhages and a faster and less gradual progression to fibrovascular scarring and visual loss. Fluorescein angiography showed choroidal filling delay in the macular region of 47% of eyes of group 1. A perfusion defect of the macular choroid could be the basis of the low perfusion pressure and the consequent low activity of CNV with the angiographic pattern of ill-defined ooze.     

Bevacizumab for occult subfoveal neovascularization in age-related macular degeneration

PURPOSE: To report on the treatment of exudative age-related macular degeneration by intravitreal bevacizumab (Avastin). METHODS: A 78-year-old patient experienced a progressive loss of visual acuity in her right eye due to an occult subfoveal neovascular membrane in age-related macular degeneration. She received an intravitreal injection of 1.5 mg bevacizumab. RESULTS: Within 4 weeks after the injection, visual acuity improved from 0.40 to 0.60 with complete resolution of subretinal and intraretinal leakage and edema as shown on optical coherence tomography. Pre-existing metamorphopsias disappeared. Intraocular pressure remained in the normal range. During the follow-up, there were no sings of intraocular inflammation or any other intraocular pathology induced by the intravitreal injection. CONCLUSIONS: Intravitreal bevacizumab may potentially be helpful in the treatment of exudative age-related macular degeneration and may deserve further evaluation.     

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). METHODS: Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range: 12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.     

Transpupillary thermotherapy for occult subfoveal neovessels in age-related macular degeneration: importance of patient pigmentation for the determination of laser settings

BACKGROUND: Presently the indication for transpupillary thermotherapy (TTT) is the treatment of retrofoveal occult subretinal neovascular membranes (OSRNM) for which PDT (photodynamic therapy) has a limited effect. The diode laser power settings given by the manufacturer (Iridex Co, Mountain View, California) have to be modulated according to several criteria including patient pigmentation. The purpose here was to report on a group of patients that presented chorioretinal atrophy after TTT. METHODS: Thirty-eight eyes of 37 patients with OSRNM due to age-related macular degeneration underwent TTT. Indications to treat were diffuse exudative membranes, limited subfoveal OSRNM with a visual acuity of less than 0.4, or a drop of visual acuity of 3 Snellen lines or more since the previous examination. Dual fluorescein and indocyanine green angiography were used for angiographic follow-up. Treatment was performed according to the manufacturer's parameters. The group of patients that presented chorioretinal atrophy after TTT was analysed in this study RESULTS: Five patients presented a limited or spot-size related post-TTT chorioretinal atrophy. Pre-laser visual acuity was 0.34 +/- 0.13 and post-TTT visual acuity was 0.25 +/- 0.15. The OSRNM had disappeared in all cases. The common denominator in these patients was that they were white haired but upon questioning all happened to be dark-haired in their youth. CONCLUSIONS: Evolution towards atrophy can occur after TTT and probably depends on several factors. We showed that pigmentation is a parameter to be evaluated carefully before TTT and that laser power settings should progressively be diminished with increasing patient pigmentation. In white haired persons the original pigmentary status should be part of the patient history.     

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration

Purpose. To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). Methods. Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. Results. For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50–20/500). Average follow-up was 27 weeks (range: 12 weeks–55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. Conclusion. Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.     

Indocyanine green angiography and occult neovascularization in age-related macular degeneration

INTRODUCTION: Since early 90th, infra-red angiography using indocyanine green, is an additional examination done after fluorescein angiography (FA) very often used in ARMD allowing deep retinal layers and choroid analysis. ICG angiography increases occult new vessels delimitation poorly defined by FA, thus extending the scope of therapy. Clinical applications: CONCLUSION: ICG angiography, with better choroidal visualization, is nowadays of great importance in ARMD exploration.     

老年性黄斑变性的放射治疗

老年性黄斑变性是与年龄相关的一种严重的不可逆性致盲眼病,常因脉络膜新生血管形成导致中心视力的迅速下降。由于致病机制未明,目前仍无有效的治疗方法。20世纪90年代以来,国外展开了使用小剂量放射治疗抑制脉络膜新生血管的临床研究,初步结果显示该方法能抑制脉络膜新生血管的生长,并发症较少。对放射治疗的原理、技术、在老年性黄斑变性（ARMD）治疗中的临床应用效果、并发症等作一综述。     

Radiation therapy in exudative age-related macular degeneration

It has been suggested that ionizing radiation at doses relatively safe to the optic nerve and retina exert an inhibitory and occlusive effect on the endothelial proliferation of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). The encouraging results of early studies in preservation or improvement of visual acuity and regression of the CNV gave rise to many clinical trials in different centers. Disparate radiation doses, dose fractions, type and rate of radiation administration have been used to determine the efficacy of radiotherapy in AMD. Conflicting treatment responses have been reported by different centers. Some studies provided evidence of beneficial treatment outcome in AMD, and others could not show any efficacy of ionizing radiation in the visual and morphological evolution of the disease. Data from the literature and our experience indicate that radiotherapy can be effective in regressing the leakage of the CNV in AMD. However, despite treatment visual deterioration continues and new CNV lesions develop. The observation of morphological progression in the disease process might be related to an unfavorable effect of radiation on the pathogenesis of AMD.     

Verteporfin and intravitreal triamcinolone acetonide combination therapy for occult choroidal neovascularization in age-related macular degeneration

PURPOSE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with verteporfin combined with intravitreal triamcinolone (IVTA) in occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Single center, nonrandomized interventional case series. METHODS: A prospective, noncomparative, interventional case series of 41 eyes of 41 patients with a two-year follow-up period. Verteporfin PDT was performed using the recommended standard procedure for approved forms of AMD. A solution containing 25 mg of crystalline triamcinolone acetonide was injected intravitreally 16 hours post PDT. The procedure was repeated after three months in case of persistent CNV leakage. RESULTS: The mean number of treatments needed was 1.8. Thirty-four eyes (82.9%) required one retreatment at three months. No additional retreatments were necessary. Visual acuity improved gradually in most of the patients with mean values of 20/133 and 20/115 at baseline and three months; 20/101 and 20/84 at six and twelve months; and 20/83 and 20/81 at eighteen and twenty-four months. Eleven of 41 treated study eyes (26.8%) underwent cataract surgery between six and fifteen months after the first treatment. Nine patients required local or systemic glaucoma therapy because of a transient steroid induced intraocular pressure increase. CONCLUSIONS: Verteporfin PDT combined with intravitreal triamcinolone may improve the outcome of standard verteporfin PDT in the treatment of occult CNV secondary to AMD. An improvement in visual acuity was observed in most of the treated patients and was maintained during a two-year follow-up period. Retreatment numbers were lower than expected from monotherapy trials.