年齡相關(guān)性黃斑變性的光動(dòng)力療法
http://www.www.srpcoatings.com
37c醫(yī)學(xué)網(wǎng)
作者：Steven Lam
單位：
關(guān)鍵詞：
眼視光學(xué)雜志990219 美國(guó)65歲以上老年人中大約有10%會(huì)發(fā)生早期年齡相關(guān)性黃斑變性(aged-related macular degeneration，簡(jiǎn)稱AR-MD)，其中6%將是嚴(yán)重類型的ARMD。嚴(yán)重類型ARMD的典型表現(xiàn)為脈絡(luò)膜新生血管化(choroidal neovascularization，簡(jiǎn)稱CNV)。CNV會(huì)使病人視力迅速下降，多數(shù)患者在確診兩年內(nèi)變盲。因此，CNV已成為當(dāng)今老年致盲的主要原因。激光光凝雖然可以延緩輕微CNV的發(fā)展，但患者的健康視網(wǎng)膜卻會(huì)被光凝損傷而導(dǎo)致視力迅速下降，而且其中5%還會(huì)復(fù)發(fā)。本文介紹一種新的、具有選擇性的CNV治療方法———應(yīng)用verteporfin(PBD-MA)的光動(dòng)力療法(photodynamic therapy，簡(jiǎn)稱PDT)。這種療法能阻止脈絡(luò)膜新生血管化進(jìn)程，因此對(duì)ARMD病人的視力有保護(hù)作用。
, 百拇醫(yī)藥
1 verteporfin光動(dòng)力療法 治療的兩個(gè)階段：①靜脈注入經(jīng)高選擇性光敏微脂粒染色的verteporfin(10分鐘6mg/m2)；②以非致熱性激光激活眼部血管中的染料，異常脈絡(luò)膜血管得以破壞而正常血管不受影響。
2 作用機(jī)制 微脂粒verteporfin一進(jìn)入血中即與低密度脂蛋白(LDL)混合形成LDL-V，而LDL-V又被具有高濃度LDL受體的異常脈絡(luò)膜血管上皮細(xì)胞吞噬。注射過(guò)程約需1分30秒。注射15分鐘后verteporfin即被紅光(689nm，50J/cm2)激活。由于激光不產(chǎn)生熱量，故視網(wǎng)膜并不受損。光化學(xué)反應(yīng)產(chǎn)生的氧自由基會(huì)損害上皮細(xì)胞。后者能激活血小板并阻塞異常血管，但視網(wǎng)膜血管則不受治療的影響。verteporfin光動(dòng)力療法雖不能使已經(jīng)受損的光感受器和視網(wǎng)膜細(xì)胞復(fù)原，但卻能通過(guò)限制CNV蔓延而維持視力，甚至還能使視力得以短期性提高(原因可能是視網(wǎng)膜下液體減少)。
, 百拇醫(yī)藥
3 預(yù)期結(jié)果 早期的研究顯示，verteporfin光動(dòng)力療法可阻止CNV的發(fā)展并防止異常血管滲漏。更重要的是研究還表明，在3個(gè)月的隨訪期內(nèi)，病人的視力已經(jīng)穩(wěn)定。該項(xiàng)技術(shù)仍處于試驗(yàn)階段，目前正在對(duì)ARMD或近視性改變的病人進(jìn)行大規(guī)模跨國(guó)廣泛性Ⅲ期測(cè)試：①光動(dòng)力療法治療ARMD(treatment of AMD with PDT，簡(jiǎn)稱TAP試驗(yàn))將于1999年獲得初步成果；②2000年將獲得使用verteporfin光動(dòng)力療法(verteporfin in photodynamic therapy，簡(jiǎn)稱VIP試驗(yàn))的初步成果。
上述研究的目的是探討用verteporfin光動(dòng)力療法治療ARMD繼發(fā)典型和潛隱性CNV病人的可能性。
Age-related macular degeneration(ARMD)and Photodynamic therapy(PDT)
Steven Lam
, http://www.www.srpcoatings.com
Clinical development remains promising for photodynamic therapy(PDT)with verteporfin(BPD-MA)，a new，selective treatment for choroidal neovascularization(CNV)associated with age-related macular degeneration(ARMD)-the major cause of blindness in the elderly[1]. The technique has the potential to prevent the progression of CNV and thereby preserve patients’vision.
Current status：Disease and treatment
Approximately 10% of people aged over 65 years in the US have early-stage ARMD[2]，and，as the average age of the population rises，the number of people with the disease is set to triple in the next 25 years[3]. The more severe form of ARMD，which is characterized by CNV，may affect up to 6% of patients[4，5].CNV causes rapid deterioration in vision and most affected patients’ eyes are classified legally blind within two years of diagnosis[1]. Laser photocoagulation helps prevent the progression of CNV in patients who have small，discrete lesions，but this group accounts for only 10%～20% of the total number of patients with CNV[3，6，7]. Photocoagulation is also limited because it destroys healthy retinal tissue and patients pay the price of an immediate loss of visual acuity following treatment in return for slower disease progression[3，8，9]. In addition 50% of patients treated with laser photocoagulation suffer from recurrences[9].
, 百拇醫(yī)藥
Fig1 In neovascular ARMD abnormal blood cells penetrate the weakened Bruch’s membrane
1 PDT with verteporfin
The procedure takes place in two stages：[10]
.A highly selective photosensitizing dye-liposomal verteporfin is administered intravenously(6mg/m2 over 10 minutes).
.The dye is activated in the eye using anon-thermal laser，resulting in the destruction of abnormal choroidal blood vessels，leaving normal vessels still functional.
, 百拇醫(yī)藥
2 Howitworks
Once in the bloodstream liposomal verteporfin complexes with lowdensity lipoprotein(LDL). The newly formed LDL-verteporfin is taken up by the endothelial cells of the abnormal choroidal blood vessels，which have high levels of LDL-receptors. Verteporfin is then activated with red light(689nm，50J/cm2)applied 15 minutes after the start of the infusion for 1.5 minutes[10]. As the laser does not generate heat the overlying retina is not harmed by the technique.
, http://www.www.srpcoatings.com
Fig2 Verteporfin concentrating in the endothelial cells of the neovasculature in the degenerating macula.
Oxygen free radicals released during the photochemical reaction cause endothelial cellular disruption which，in turn，leads to platelet activation and occlusion of the abnormal blood vessels. Retinal vessels are unaffected by the treatment. PDT with verteporfin cannot restore damaged photoreceptors or damaged retinal cells，but it may maintain vision by confining the spread of CNV. A short term improvement in vision may be observed，probably due to the reduction of subretinal fluid.
, 百拇醫(yī)藥
3 Promising results
Early studies demonstrate that PDT with verteporfin stems the growth of CNV and prevents leakage from abnormal blood vessels[10，11]. Most importantly，these studies suggest that patients’ sight stabilizes and does not deteriorate during the three month follow-up period. The technique is still an investigational procedure and is undergoing extensive Phase Ⅲ testing in patients with ARMD or myopic lesions in large-scale multi-national studies：
, 百拇醫(yī)藥
Fig3 Verteporfin activated by non-themal laser
.Treatment of ARMD with PDT-The TAP Trial，first results available in 1999
.Verteporfin in Photodynamic therpay-The VIP Trial，first results available in 2000
The purpose of these studies is to confirm the potential of PDT with verteporfin in the majority of patients with classic and occult CNV secondary to ARMD.
, http://www.www.srpcoatings.com
Fig4 Treated area showing CNV occlusion
References
1 Vinding T. Age-related macular degeneration. An epidemiological study of 1000 elderly patients. Acta Ophthalmol Scand，1995，73(Suppl.217)∶1～32
2 Klein R，Klein B，Linton K. Prevalence of age-related maculopathy. The beaver dam eye study. Ophthalmol，1992，99∶933～942
3 Hyman L. Epidemiology of AMD. In：Age-related macular degeneration：principles and practice. Hampton GR，Nelson PT，eds. New York：Raven Press，1992.100
, 百拇醫(yī)藥
4 Bressler N. Submacular Surgery：Are randomized trials necessary？ Arch Ophthalmol，1995，113∶1557～1560
5 Klein R，Klein B，Jensen S，et al. The Five-year incidence of age-related maculopathy in the beaver dam study. Invest Ophthalmol，1996，113∶301～308
6 Bressler N，Bressler S，Gragoudas E. Clinical characteristics of choroidal neovascular membranes. Arch Ophthalmol，1987，105∶209～213
7 Moisseiev J，Alhalel A，Masuri R，et al. The impact of macular photocoagulation study results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol，1995，113∶185～189
, http://www.www.srpcoatings.com
8 Bressler NM，Bressler SB，F(xiàn)ine SL. Age-related macular degeneration. Survey Ophthalmol，1988，32∶375～413
9 Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Arch Opthalmol，1993，111∶1200～1209
10 Gragoudas ES，Schmidt-Erfuth U，Sickenberg M，et al. Results and preliminary dosimetry of photodynamic therapy for choroidal neovascularization in age-related macular degeneration in a phaseⅠ/Ⅱ study. Invest Ophthalmol Vis Sci，1997，38∶S17
11 Schmidt-Erfuth U，Miller JW，Sickenberg M，et al. Photodynamic therapy for choroidal neovascularization in a phaseⅠ/Ⅱ study：preliminary results of multiple treatments. Invest Vis Sci Ophthalmol，1997，38∶S17
From CIBA Vision Medical Affairs，Hong Kong
(收稿：1999-04-25，陳浩譯), 百拇醫(yī)藥
單位：
關(guān)鍵詞：
眼視光學(xué)雜志990219 美國(guó)65歲以上老年人中大約有10%會(huì)發(fā)生早期年齡相關(guān)性黃斑變性(aged-related macular degeneration，簡(jiǎn)稱AR-MD)，其中6%將是嚴(yán)重類型的ARMD。嚴(yán)重類型ARMD的典型表現(xiàn)為脈絡(luò)膜新生血管化(choroidal neovascularization，簡(jiǎn)稱CNV)。CNV會(huì)使病人視力迅速下降，多數(shù)患者在確診兩年內(nèi)變盲。因此，CNV已成為當(dāng)今老年致盲的主要原因。激光光凝雖然可以延緩輕微CNV的發(fā)展，但患者的健康視網(wǎng)膜卻會(huì)被光凝損傷而導(dǎo)致視力迅速下降，而且其中5%還會(huì)復(fù)發(fā)。本文介紹一種新的、具有選擇性的CNV治療方法———應(yīng)用verteporfin(PBD-MA)的光動(dòng)力療法(photodynamic therapy，簡(jiǎn)稱PDT)。這種療法能阻止脈絡(luò)膜新生血管化進(jìn)程，因此對(duì)ARMD病人的視力有保護(hù)作用。
, 百拇醫(yī)藥
1 verteporfin光動(dòng)力療法 治療的兩個(gè)階段：①靜脈注入經(jīng)高選擇性光敏微脂粒染色的verteporfin(10分鐘6mg/m2)；②以非致熱性激光激活眼部血管中的染料，異常脈絡(luò)膜血管得以破壞而正常血管不受影響。
2 作用機(jī)制 微脂粒verteporfin一進(jìn)入血中即與低密度脂蛋白(LDL)混合形成LDL-V，而LDL-V又被具有高濃度LDL受體的異常脈絡(luò)膜血管上皮細(xì)胞吞噬。注射過(guò)程約需1分30秒。注射15分鐘后verteporfin即被紅光(689nm，50J/cm2)激活。由于激光不產(chǎn)生熱量，故視網(wǎng)膜并不受損。光化學(xué)反應(yīng)產(chǎn)生的氧自由基會(huì)損害上皮細(xì)胞。后者能激活血小板并阻塞異常血管，但視網(wǎng)膜血管則不受治療的影響。verteporfin光動(dòng)力療法雖不能使已經(jīng)受損的光感受器和視網(wǎng)膜細(xì)胞復(fù)原，但卻能通過(guò)限制CNV蔓延而維持視力，甚至還能使視力得以短期性提高(原因可能是視網(wǎng)膜下液體減少)。
, 百拇醫(yī)藥
3 預(yù)期結(jié)果 早期的研究顯示，verteporfin光動(dòng)力療法可阻止CNV的發(fā)展并防止異常血管滲漏。更重要的是研究還表明，在3個(gè)月的隨訪期內(nèi)，病人的視力已經(jīng)穩(wěn)定。該項(xiàng)技術(shù)仍處于試驗(yàn)階段，目前正在對(duì)ARMD或近視性改變的病人進(jìn)行大規(guī)模跨國(guó)廣泛性Ⅲ期測(cè)試：①光動(dòng)力療法治療ARMD(treatment of AMD with PDT，簡(jiǎn)稱TAP試驗(yàn))將于1999年獲得初步成果；②2000年將獲得使用verteporfin光動(dòng)力療法(verteporfin in photodynamic therapy，簡(jiǎn)稱VIP試驗(yàn))的初步成果。
上述研究的目的是探討用verteporfin光動(dòng)力療法治療ARMD繼發(fā)典型和潛隱性CNV病人的可能性。
Age-related macular degeneration(ARMD)and Photodynamic therapy(PDT)
Steven Lam
, http://www.www.srpcoatings.com
Clinical development remains promising for photodynamic therapy(PDT)with verteporfin(BPD-MA)，a new，selective treatment for choroidal neovascularization(CNV)associated with age-related macular degeneration(ARMD)-the major cause of blindness in the elderly[1]. The technique has the potential to prevent the progression of CNV and thereby preserve patients’vision.
Current status：Disease and treatment
Approximately 10% of people aged over 65 years in the US have early-stage ARMD[2]，and，as the average age of the population rises，the number of people with the disease is set to triple in the next 25 years[3]. The more severe form of ARMD，which is characterized by CNV，may affect up to 6% of patients[4，5].CNV causes rapid deterioration in vision and most affected patients’ eyes are classified legally blind within two years of diagnosis[1]. Laser photocoagulation helps prevent the progression of CNV in patients who have small，discrete lesions，but this group accounts for only 10%～20% of the total number of patients with CNV[3，6，7]. Photocoagulation is also limited because it destroys healthy retinal tissue and patients pay the price of an immediate loss of visual acuity following treatment in return for slower disease progression[3，8，9]. In addition 50% of patients treated with laser photocoagulation suffer from recurrences[9].
, 百拇醫(yī)藥
Fig1 In neovascular ARMD abnormal blood cells penetrate the weakened Bruch’s membrane
1 PDT with verteporfin
The procedure takes place in two stages：[10]
.A highly selective photosensitizing dye-liposomal verteporfin is administered intravenously(6mg/m2 over 10 minutes).
.The dye is activated in the eye using anon-thermal laser，resulting in the destruction of abnormal choroidal blood vessels，leaving normal vessels still functional.
, 百拇醫(yī)藥
2 Howitworks
Once in the bloodstream liposomal verteporfin complexes with lowdensity lipoprotein(LDL). The newly formed LDL-verteporfin is taken up by the endothelial cells of the abnormal choroidal blood vessels，which have high levels of LDL-receptors. Verteporfin is then activated with red light(689nm，50J/cm2)applied 15 minutes after the start of the infusion for 1.5 minutes[10]. As the laser does not generate heat the overlying retina is not harmed by the technique.
, http://www.www.srpcoatings.com
Fig2 Verteporfin concentrating in the endothelial cells of the neovasculature in the degenerating macula.
Oxygen free radicals released during the photochemical reaction cause endothelial cellular disruption which，in turn，leads to platelet activation and occlusion of the abnormal blood vessels. Retinal vessels are unaffected by the treatment. PDT with verteporfin cannot restore damaged photoreceptors or damaged retinal cells，but it may maintain vision by confining the spread of CNV. A short term improvement in vision may be observed，probably due to the reduction of subretinal fluid.
, 百拇醫(yī)藥
3 Promising results
Early studies demonstrate that PDT with verteporfin stems the growth of CNV and prevents leakage from abnormal blood vessels[10，11]. Most importantly，these studies suggest that patients’ sight stabilizes and does not deteriorate during the three month follow-up period. The technique is still an investigational procedure and is undergoing extensive Phase Ⅲ testing in patients with ARMD or myopic lesions in large-scale multi-national studies：
, 百拇醫(yī)藥
Fig3 Verteporfin activated by non-themal laser
.Treatment of ARMD with PDT-The TAP Trial，first results available in 1999
.Verteporfin in Photodynamic therpay-The VIP Trial，first results available in 2000
The purpose of these studies is to confirm the potential of PDT with verteporfin in the majority of patients with classic and occult CNV secondary to ARMD.
, http://www.www.srpcoatings.com
Fig4 Treated area showing CNV occlusion
References
1 Vinding T. Age-related macular degeneration. An epidemiological study of 1000 elderly patients. Acta Ophthalmol Scand，1995，73(Suppl.217)∶1～32
2 Klein R，Klein B，Linton K. Prevalence of age-related maculopathy. The beaver dam eye study. Ophthalmol，1992，99∶933～942
3 Hyman L. Epidemiology of AMD. In：Age-related macular degeneration：principles and practice. Hampton GR，Nelson PT，eds. New York：Raven Press，1992.100
, 百拇醫(yī)藥
4 Bressler N. Submacular Surgery：Are randomized trials necessary？ Arch Ophthalmol，1995，113∶1557～1560
5 Klein R，Klein B，Jensen S，et al. The Five-year incidence of age-related maculopathy in the beaver dam study. Invest Ophthalmol，1996，113∶301～308
6 Bressler N，Bressler S，Gragoudas E. Clinical characteristics of choroidal neovascular membranes. Arch Ophthalmol，1987，105∶209～213
7 Moisseiev J，Alhalel A，Masuri R，et al. The impact of macular photocoagulation study results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol，1995，113∶185～189
, http://www.www.srpcoatings.com
8 Bressler NM，Bressler SB，F(xiàn)ine SL. Age-related macular degeneration. Survey Ophthalmol，1988，32∶375～413
9 Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Arch Opthalmol，1993，111∶1200～1209
10 Gragoudas ES，Schmidt-Erfuth U，Sickenberg M，et al. Results and preliminary dosimetry of photodynamic therapy for choroidal neovascularization in age-related macular degeneration in a phaseⅠ/Ⅱ study. Invest Ophthalmol Vis Sci，1997，38∶S17
11 Schmidt-Erfuth U，Miller JW，Sickenberg M，et al. Photodynamic therapy for choroidal neovascularization in a phaseⅠ/Ⅱ study：preliminary results of multiple treatments. Invest Vis Sci Ophthalmol，1997，38∶S17
From CIBA Vision Medical Affairs，Hong Kong
(收稿：1999-04-25，陳浩譯), 百拇醫(yī)藥