作者：Retinal pigment epithelial and choroidal atrophy in wet age-related macular degeneration treated with multiple transpupillary themotherapy:A case report    作者单位：Department of Ophthalmology, Xijing Hospital, the Fourth Military Medicas University, Xi'an 710032, Shaanxi Province, China (Dr. Lin Wang is now with Department of Ophthalmology, Xi'an Gaoxin Hospital, Xi'an 710075, Shaanxi Province, China)

【摘要】  　　To report a case of wet age-related macular degeneration (AMD) treat with multiple transpupillary themotherapy (TTT) and choroidal neovascularization (CNV) disappeared but retinal pigment epithelial (PRE) and choroidal atrophy occurred with a low vision at the end point. METHODS: Clinical data including fundus photographs, fundus fluorescein angiography(FFA), indocyanine angiography (ICGA) and optical coherence tomography(OCT) was reviewed. RESULTS: A 72-year-old man complained about blurred vision of his left eye and FFA revealed polypoidal choroidal vasculopathy (PCV) in the macula. His left eye had stable vision of 0.1 for 6 years without any treatment of CNV. About 2 years later, his right eye presented a piece of CNV. During the period of 3 years, the lesion remained more (3×5 PD) and less (1×2 PD) in size with remarkable exudates and bleeding, and 7 sessions of TTT were applied with 80-280mW, 2mm of spot, and 60 seconds exposure and with the interval of 3 months or more. The CNV lesion finally disappeared, but there left a white area in the macula and vision decreased from 0.3 to 0.04. CONCLUSION: Although CNV lesion can be eliminated by TTT, obvious atrophy of RPE cells and the choroids can happen and this may not be of help for patient vision. It suggests that the parameters of TTT will be lower than 120 mW/mm and limited less two sessions if applicable, especially for Asia people.

【关键词】  age-related macular degeneration (AMD); transpupillary themotherapy (TTT); choroidal neovascularization (CNV); retinal pigment epithelium (RPE)

　　INTRODUCTION

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in aging people. The most common cause of visual loss is the formation of choroidal neovascularization (CNV) under the macular area. There are several options for choice to be applied to treat CNV, such as laser photocoagulation for extra- and juxtafoveal CNV, photodynamic therapy (PDT) with verteporfin for subfoveal predominantly classic CNV, transpupillary therapy (TTT) and recently anti-vascular endothelial growth factor (VEGF) therapy. However, PDT treatment had minimal cost effectiveness mainly due to the high cost of the drug, the need of many re-treatments, and continuing visual decline in most patients even with multiple treatments. This situation is particularly true in China. Transpupillary therapy (TTT) is a technique using an 810-nm infrared diode laser to treat choroidal lesions including melanomas and minimal classic and occult subfoveal CNV. It is significantly less expensive than PDT and accepted more widely by Chinese patients with wet AMD before the era of anti-VEGF therapy.

    The effectiveness of TTT in treatment of wet AMD is controversy. Some authors reported that TTT showed good stability with little visual loss and few recurrences and no deleterious side effects in treating occult subfoveal CNV[1-3]. While others reported that TTT appeared to have been of no benefit in preventing further visual loss in patients with occult CNV[4]. Furthermore, it was found that some patients presented chorioretinal atrophy with CNV disappearance after treatment with TTT[5]. We report herein a case of wet AMD with similar outcome.

    CASE REPORT

    A 72-year-old man complained about blurred vision of his left eye on May 9, 2000 and fundus fluorescein angiography (FFA) and indocyanine angiography (ICGA) revealed a 3× 3 PD lesion of polypoidal choroidal vasculopathy (PCV) in the macula (Figure 1). His left eye had stable vision of 0.1 for 6 years without any treatment of CNV (Figure 2).

    Figure 1 FFA and ICGA on May 9, 2000 revealed a lesion of polypoidal choroidal vasculopathy(PCV) in the macula of the left eye

    Figure 2 Fundus photograph of the left eye with stable vision of 0.1 for 6 years without any treatment of CNV on Nov. 21, 2005

    On January 13,2001, FFA and ICGA showed uneven low filling of fluorescence in the lower part of the macula in his right eye on a routine examination of follow-up(Figure 3). One year later, he presented metamorphopsia and decreased vision in the right eye on February 28,2002. The visual acuity of the right eye decreased from 0.5 one year ago to 0.3. With ophthalmoscopy, slight exudates and hemorrhage were seen in the macula and the fovea reflex disappeared without obvious drusen. FFA and ICGA showed a small piece of CNV (Figure 4). Since he could not afford for PDT therapy, TTT was accepted to treat his neovacular AMD in the right eye. During the period of 3 years and 2 months from that time to May 9, 2005, the lesion including exudate area remained more (3×5PD) and less (1×2PD) in size with remarkable exudates and bleeding (Figure 5,6). Totally 7 sessions of TTT were applied with the parameters of 80-280mW, 2mm of spot, and 60 seconds exposure with the interval of 3 months or more. We chose lower power of 80-140 mW for small CNV (1×2PD) with less exudates and hemorrhage and higher power of 150-280mW for larger CNV（>2PD) with more exudates and bleeding. The laser exposure focused on CNV lesion itself according to FFA and ICGA. Unfortunately, the CNV lesion was active over time for 38 months even with multiple TTT applications but finally disappeared. At the end point, there was a white area of 1.5PD in size in the macula, corresponding to the original location of CNV and vision acuity dropped from 0.3 to 0.04 (Figure 7). OCT revealed normal but thin foveal appearance without obvious subretinal scarring tissue in the macula.

    Figure 3 ICGA on Jan. 13, 2001 showing uneven low filling of fluorescence in the lower part of the macula in the right eye

    Figure 4 Fundus photograph (upper) on Feb. 28, 2002 showing slight exudates and hemorrhage and FFA (lower) showing a small piece of CNV of the right eye with metamorphopsia and decreased vision

    Figure 5 Fundus photograph (upper) on Oct. 22, 2002 showing exudates and bleeding and ICGA (lower) showing CNV of the right eye

    Figure 6 ICGA on Apr. 20, 2004 showing a new piece of CNV of the right eye after 4 sessions of TTT

    Figure 7 Fundus photograph (upper) and FFA (lower) on Nov. 21, 2005 showing a white macula, indicating RPE and choroidal atrophy of the right eye after 7 sessions of TTT

    DISCUSSION

    TTT is a technique in which heat is delivered to the choroid and retinal pigment epithelium through the pupil using an 810-nm infrared diode laser. The laser has theoretical advantages over other wavelengths of light because there is little absorption in the xanthophyll layer and thus damage to the neurosensory retina is minimized. It is also poorly absorbed by hemoglobin and this allows an ability to treat through subretinal hemorrhage. The 810-nm wavelength of the laser is mainly absorbed by melanin at the level of the choroid and retinal pigment epithelium, enabling treatment of choroidal lesions. It has been used to treat neovacular AMD for several years.

    However, besides the controversy of the effectiveness of TTT in treatment of wet AMD, side effects are another issue of the therapy. Auer and associates [5] reported a group of patients that presented chorioretinal atrophy after TTT. They observed 38 eyes of 37 patients with occult CNV due to AMD underwent TTT. They found that 5 patients presented limited or spot-size post-TTT chorioretinal atrophy. The visual acuity was 0.34±0.13 pre-laser and 0.25±0.15 post-TTT and the CNV had disappeared in all cases. They concluded that chorioretinal atrophy could occur after TTT and probably related to several factors including patient pigmentation and laser power settings. Morales and associates[6] recently reported an in vitro study and they found that blood could significantly block the transmission of the 810-nm diode TTT laser. She and associates[7] used the laser power of 50-150mW in a rat model and found that the range of laser power of TTT had adverse effects on the overlying retina. These results indicate that the laser can induce tissue damage due to absorption of the light by melanin contained in RPE cells and the choroidal matrix. In our case, the laser power applied was much lower (80-280mW) than that (460-1200mW)[3] usually applied in white patients. But finally the RPE and choroidal atrophy occurred even with such low power of the laser. We therefore presume that multiple treatments of TTT may accumulate heating damage to the tissue. At present, anti-VEGF therapy has been widely used in treatment of neovacular AMD. However, TTT may still use in some cases. To avoid significant tissue damage, we suggest that the parameters of TTT should be lower than 120mW/mm and limited less two sessions if applicable, especially for Asia people.

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