IVTA联合全视网膜光凝治疗糖尿病黄斑水肿的临床分析
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摘要
目的:评价曲安奈德玻璃体腔内注射联合全视网膜光凝治疗由糖尿病视网膜病变导致的黄斑水肿的疗效和安全性。
方法:选择糖尿病视网膜病变合并黄斑水肿的患者31例50只眼,依据造影结果行全视网膜光凝治疗及向玻璃体腔内注射TA 0.4mg/0.1ml进行联合治疗。对比治疗前后视力、眼压、眼底及OCT检测黄斑中心凹厚度变化等。对结果进行统计分析,评价此种联合治疗的临床疗效及安全性。
结果:随访6个月-1年半。最终随访时视力提高42只眼(84%),视力不变5只眼(10%),视力下降3只眼(6%)。OCT显示平均黄斑中心凹厚度较治疗前明显减轻。术后高眼压的患者共有15人19只眼,发生率为38%,给予相应治疗后均缓解。31例50只眼共9人13只眼(26%)黄斑水肿复发。本研究内未见视网膜脱离、新生血管性青光眼等并发症发生。
结论:曲安奈德联合全视网膜光凝治疗糖尿病黄斑水肿疗效较好,可以减轻黄斑水肿并提高视力,对改善糖尿病患者的视功能具有重要意义。
Purposes: Macular edema is a major cause of visual acuity loss in patients with diabetic retinopathy. The apoptosis of photoreceptors is the important mechanism of visual loss resulted from macular edema. Current therapies for macular edema include medicine aimed in relieving macular edema, photocoagulation and vitrectomy. However, until now there is no proven effective treatment for patients with macular edema from diabetic retinopathy . Triamcinolone acetonide (TA) is one of artificially synthesized steroids which has strong effect to relieve imflammation, and has little toxic effects. It can be injected into the vitreous cavity directly. Intravitreal injection of TA is widely used to treat macular edema associated with various diseases. In this study we used this methodand panretinal photocoagulation to treat DME, and to observe it’s efficacy and safety. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), ophthalmic routine examination including ophthalmoscopy, slit lamps and intraocular pressure (IOP) measurement were performed to document the results.
Methods: This study included fifty eyes of thirsty-one patients with DME. Each eye received one injection of 4mg/0.1ml into the vitreous and panretinal photocoagulation. Evaluation methods include visual acuity, OCT, IOP, ophthalmoscopy, slit lamps and so on.
Results: Mean best-corrected visual acuity (BCVA) was 0.21±0.14 before treatment. One month after injection it improved to 0.45±0.24, which was significantly better than that at baseline(P﹤0.01). At the three months follow-up , BCVA improved continuously to 0.5±0.25, which was significantly better compared to that before treatment. Compared to one month follow-up, the patients whose vision continued to improve occupy 54%. At the six months follow-up BCVA was 0.39±0.17, which was significantly better than that at baseline.
The mean baseline central macular thickness (CMT) as measured by optical coherence tomography (OCT) was 533.46±187.5μm. One month after injection they decreased significantly to 240.44±67.88μm, and at the three months follow-up to 203.52±72.43μm. While six Months after injection they increased to 265.48±120.48μm. The CMT at one month after injection had an significantly decline compared to baseline, and at three months follow-up time points it was significantly better compared to that at one month follow-up time points. However at six months follow-up the CMT increased again, but they were still fewer than the baseline.
An intraocular pressure (IOP) rise to values higher than 21mmHg was observed in 19(38%) eyes. Elevation of IOP occurred at one week after the injection was 20%, at three months after the injection was 12%, at six months after the injection was 3%. In all but one eye, IOP could be lowered to the normal range with topical medicine. One eye developed refractory ocular hypertension to intravitreal injection of TA. Selective laser trabeculoplasty (SLT) had to be performed in emergency to avoid optic nerve damage and allowed to successfully control the IOP follow-up.
13 (26%) eyes experience recurrence of macular edema after injection. Excipient left in 2(4%) eyes because that it was not completely cleaned out before injection. There were 2(4%) eyes of pseudoendophthalmitis after 2 days of the injection of TA. There were 2(4%) eyes of progression of cataract and 1(2%) eyes of vitreous haemorrhage after the injection of TA.
Intravitreal triamcinolone and panretinal photocoagulation seems to be an effective treatment for DME, resulting in a marked reduction in macular thickness and improved vision in most eyes treated for at least 3 months after the injection with a significant but manageable adverse event profile. However, further studies are required to demonstrate its long-term efficacy.
方法:选择糖尿病视网膜病变合并黄斑水肿的患者31例50只眼,依据造影结果行全视网膜光凝治疗及向玻璃体腔内注射TA 0.4mg/0.1ml进行联合治疗。对比治疗前后视力、眼压、眼底及OCT检测黄斑中心凹厚度变化等。对结果进行统计分析,评价此种联合治疗的临床疗效及安全性。
结果:随访6个月-1年半。最终随访时视力提高42只眼(84%),视力不变5只眼(10%),视力下降3只眼(6%)。OCT显示平均黄斑中心凹厚度较治疗前明显减轻。术后高眼压的患者共有15人19只眼,发生率为38%,给予相应治疗后均缓解。31例50只眼共9人13只眼(26%)黄斑水肿复发。本研究内未见视网膜脱离、新生血管性青光眼等并发症发生。
结论:曲安奈德联合全视网膜光凝治疗糖尿病黄斑水肿疗效较好,可以减轻黄斑水肿并提高视力,对改善糖尿病患者的视功能具有重要意义。
Purposes: Macular edema is a major cause of visual acuity loss in patients with diabetic retinopathy. The apoptosis of photoreceptors is the important mechanism of visual loss resulted from macular edema. Current therapies for macular edema include medicine aimed in relieving macular edema, photocoagulation and vitrectomy. However, until now there is no proven effective treatment for patients with macular edema from diabetic retinopathy . Triamcinolone acetonide (TA) is one of artificially synthesized steroids which has strong effect to relieve imflammation, and has little toxic effects. It can be injected into the vitreous cavity directly. Intravitreal injection of TA is widely used to treat macular edema associated with various diseases. In this study we used this methodand panretinal photocoagulation to treat DME, and to observe it’s efficacy and safety. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), ophthalmic routine examination including ophthalmoscopy, slit lamps and intraocular pressure (IOP) measurement were performed to document the results.
Methods: This study included fifty eyes of thirsty-one patients with DME. Each eye received one injection of 4mg/0.1ml into the vitreous and panretinal photocoagulation. Evaluation methods include visual acuity, OCT, IOP, ophthalmoscopy, slit lamps and so on.
Results: Mean best-corrected visual acuity (BCVA) was 0.21±0.14 before treatment. One month after injection it improved to 0.45±0.24, which was significantly better than that at baseline(P﹤0.01). At the three months follow-up , BCVA improved continuously to 0.5±0.25, which was significantly better compared to that before treatment. Compared to one month follow-up, the patients whose vision continued to improve occupy 54%. At the six months follow-up BCVA was 0.39±0.17, which was significantly better than that at baseline.
The mean baseline central macular thickness (CMT) as measured by optical coherence tomography (OCT) was 533.46±187.5μm. One month after injection they decreased significantly to 240.44±67.88μm, and at the three months follow-up to 203.52±72.43μm. While six Months after injection they increased to 265.48±120.48μm. The CMT at one month after injection had an significantly decline compared to baseline, and at three months follow-up time points it was significantly better compared to that at one month follow-up time points. However at six months follow-up the CMT increased again, but they were still fewer than the baseline.
An intraocular pressure (IOP) rise to values higher than 21mmHg was observed in 19(38%) eyes. Elevation of IOP occurred at one week after the injection was 20%, at three months after the injection was 12%, at six months after the injection was 3%. In all but one eye, IOP could be lowered to the normal range with topical medicine. One eye developed refractory ocular hypertension to intravitreal injection of TA. Selective laser trabeculoplasty (SLT) had to be performed in emergency to avoid optic nerve damage and allowed to successfully control the IOP follow-up.
13 (26%) eyes experience recurrence of macular edema after injection. Excipient left in 2(4%) eyes because that it was not completely cleaned out before injection. There were 2(4%) eyes of pseudoendophthalmitis after 2 days of the injection of TA. There were 2(4%) eyes of progression of cataract and 1(2%) eyes of vitreous haemorrhage after the injection of TA.
Intravitreal triamcinolone and panretinal photocoagulation seems to be an effective treatment for DME, resulting in a marked reduction in macular thickness and improved vision in most eyes treated for at least 3 months after the injection with a significant but manageable adverse event profile. However, further studies are required to demonstrate its long-term efficacy.
引文
1.Gaudric A, Massin-Korobelnik P,Diabetic maculopathy classification, epidemiology spontaneous outcome, treatment DiabeteMetab1993,19;422-429
2.Guyot-Argenton C ,E1 Maftouhi A. Failure of photocoagulation therapy for diabetic macular edema .J Fr Ophtalmol. 2004 Jun;27(6Pt 1):597-603
3.Lashay AR, Rahimi A , Chams H,et al. Evaluation of the effect of acetzolamide on cystoid macular edema in patients with Behcet’s disease. Eye ,2003,17:762-766
4.Campochiaro PA. The C99-PKC412-003 Study Group. Reduction of diabetic macular edema by oralad ministration of the kinase inhibitor PKC412. Invest Ophthalmol Vis Sci, 2004,45:922-931
5.Stefaniotou M, Aspiotis M, Kalogeropoulos C, et al. Vitrectomy results for diffuse diabetic macular edema with and without inner limiting membrane removal. Eur J Ophthalmol, 2004,14:137-143
6.Micelli Ferrari T, Cardascia N, Durante G, et al. Pars plana vitrectomy in diabetic macular edema..Doc Ophthalmol,1999,97:471-474
7.Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophalmol, 1999,127:688-693
8.Michael R, Hee, PhD, Carmen A, et al. Topography of diabetic macular edema with optical coherence tomography. Ophthalmology, 1998,105:360-370
9.李秋明 郑广瑛,主编. 眼科应用解剖学. 郑州大学出版社,2002.131
10 . Kanai K, AbeT, Awaiefa K, et al. Retinal thickness and it saging changes[J].ARVO,1998,498
11.Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography . Am J Ophthalmol,1999,127:688-693
12. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema :Early treatment Diabetic Retinopathy Study report number. Arch Ophthalmol, 1985,103:1796-1806
13.高自清 糖尿病性黄斑水肿的激光治疗 蚌埠医学院学报 2005 年 5 月第30 卷第 3 期
14.Gass JDM. Pathophysiologic and histopathologic bases for interpretation of fluorescein angiography. In:JDM. Stereoscopic atlas of macular diseases: diagnosis and treatment[M]. 4th ed. Stlouis, Mo:Moshy-year Book Inc, 1997.40-41
15. Antcliff RJ,Marshall J. The pathogenesis of edema in diabetic maculopathy .Sem in Ophthalmol, 1999,14:223-232
16.Farla LJR, Bernardes R . Novel imaging technipues for diabetic macular edema[J]. Doc Ophthal Surg 1999:30(8):544-549
17.Funatsu H ,Yamashita H, Ikeda T, et al. Angiotensin Ⅱand vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders[J]. Am J Ophthalmol ,2002,133(4):537-543
18.Yamamoto S, Yamamoto T, Hayashi M, et al. Morphological and functional analyses of diabetic macular edema by optical coherence tomography and multifocal electroretinograms[J]. Graefes Arch Clin Exp Ophthalmol,2001,239(2):96-101
19.Roy MS. Diabetic reinopathy in African Americans with type 1 diabetes: therisk factors [J]. Arch Ophthalmol,2000,118(1):105-115
20.Davis MD, Fishear MR, Gangnon RE ,et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss:Early Treatment Diabetic Retinopathy Study Report 18#[J],Invest Ophthalmol Vis Sci ,1998,39(2):233-252
21.Beer PM, Bakri SJ, Singh RJ, et al. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology, 2003,110(4):681-686
22.Jonas JB. Intraocular availability of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol, 2004, 137 (3): 560-562
23.McCuen BW, Bessler M, Tano Y, et al. The lack of toxicity of intravitreally administered triamcinolone acetonide. Am J Ophthalmol, 1981;91:785-788
24.Jonas JB, Kreissig I, Sofker A, et al. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arc Ophthalmol,2003,121:57-61
25.Penfold PL, Wen L, Madigan MC, et al. Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1(ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol, 2000; 121:458-465
26.Ip MS, Gottlieb JL, Kahana A, et al. Intravitreal triamcinolone for the t reatment of macular edema associated with central retinal vein occlusion. Arch Ophthalmol, 2004; 122 (8): 1131- 1136
27.Singh IP, Ahmad SI, Yeh D, Challa P, Herndon LW, Allingham RR, Lee PP: Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol , 2004; 138: 286-287
28.Jonas JB ,Kreissig I ,Degenring RF .Intrvitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes ArchClin Exp Ophthalmol ,2002,240:782-783
29.Benhamou N, Massia P, Haouchine B ,et al. Intravitreal triamacinolone for refractory pseudophakic macular edema . Am J Ophthalmol ,2003,135:246-249
30.Otani T ,Kishi AS. Tomographic findings of foreal hard exudates in diabetic macular edema. Am J Ophthalmol,2001,131:50-54
31.Paul M. Beer, MD, Sophie J. Bakri, MD, Ravinder J. Singh, PhD, et al:lntraocular Concentration and Pharmacokinetics of triamcinolone acetone after a single intravitrea injection. Ophthalmology, 2003, 110 (4): 681-86
32.Francois Au dren, Micbel Tod,Pascale Massin, et al,Pharmacokinetic-Pharmacodynamic, Modeling of the Effect of Triamcinolone Acetonide on Central Macular Thinkness in Patients with Diabetic Macular Edema .Macular IOVS,2004,45:3433-3441
33.Massin P, Audren F, Haouchine B, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema preliminary results of a prospective controlled trial. Ophthalmology, 2004,111:218-224
34.Singh IP, Ahmad SI, Yeh D, Challa P, Herndon LW, Allingham RR, Lee PP: Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol , 2004; 138: 286-287
35.Roth DB, Chieh J, Spirn MJ, et al. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol, 2003, 121: 1279 -1282
36.Sutter FK, Gillies MC. Pseudo-endophthalmitis after intravitreal Injection of triamcinolone. Br J Ophthalmol, 2003, 87: 972-974
37.Jonas JB, Kreissig I, Degenring RF. Endophthalmitis after Intravitreal injection of triamcinolone acetonide. Arch Ophthalmol, 2003, 121: 1663- 1664
38.Nelson ML, Tennant MT, Sivalingam A, et al. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection.Retina,2003,23:686-691
39.Moshfeghi DM ,Kaiser PK ,Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol ,2003,136:791-796
2.Guyot-Argenton C ,E1 Maftouhi A. Failure of photocoagulation therapy for diabetic macular edema .J Fr Ophtalmol. 2004 Jun;27(6Pt 1):597-603
3.Lashay AR, Rahimi A , Chams H,et al. Evaluation of the effect of acetzolamide on cystoid macular edema in patients with Behcet’s disease. Eye ,2003,17:762-766
4.Campochiaro PA. The C99-PKC412-003 Study Group. Reduction of diabetic macular edema by oralad ministration of the kinase inhibitor PKC412. Invest Ophthalmol Vis Sci, 2004,45:922-931
5.Stefaniotou M, Aspiotis M, Kalogeropoulos C, et al. Vitrectomy results for diffuse diabetic macular edema with and without inner limiting membrane removal. Eur J Ophthalmol, 2004,14:137-143
6.Micelli Ferrari T, Cardascia N, Durante G, et al. Pars plana vitrectomy in diabetic macular edema..Doc Ophthalmol,1999,97:471-474
7.Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophalmol, 1999,127:688-693
8.Michael R, Hee, PhD, Carmen A, et al. Topography of diabetic macular edema with optical coherence tomography. Ophthalmology, 1998,105:360-370
9.李秋明 郑广瑛,主编. 眼科应用解剖学. 郑州大学出版社,2002.131
10 . Kanai K, AbeT, Awaiefa K, et al. Retinal thickness and it saging changes[J].ARVO,1998,498
11.Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography . Am J Ophthalmol,1999,127:688-693
12. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema :Early treatment Diabetic Retinopathy Study report number. Arch Ophthalmol, 1985,103:1796-1806
13.高自清 糖尿病性黄斑水肿的激光治疗 蚌埠医学院学报 2005 年 5 月第30 卷第 3 期
14.Gass JDM. Pathophysiologic and histopathologic bases for interpretation of fluorescein angiography. In:JDM. Stereoscopic atlas of macular diseases: diagnosis and treatment[M]. 4th ed. Stlouis, Mo:Moshy-year Book Inc, 1997.40-41
15. Antcliff RJ,Marshall J. The pathogenesis of edema in diabetic maculopathy .Sem in Ophthalmol, 1999,14:223-232
16.Farla LJR, Bernardes R . Novel imaging technipues for diabetic macular edema[J]. Doc Ophthal Surg 1999:30(8):544-549
17.Funatsu H ,Yamashita H, Ikeda T, et al. Angiotensin Ⅱand vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders[J]. Am J Ophthalmol ,2002,133(4):537-543
18.Yamamoto S, Yamamoto T, Hayashi M, et al. Morphological and functional analyses of diabetic macular edema by optical coherence tomography and multifocal electroretinograms[J]. Graefes Arch Clin Exp Ophthalmol,2001,239(2):96-101
19.Roy MS. Diabetic reinopathy in African Americans with type 1 diabetes: therisk factors [J]. Arch Ophthalmol,2000,118(1):105-115
20.Davis MD, Fishear MR, Gangnon RE ,et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss:Early Treatment Diabetic Retinopathy Study Report 18#[J],Invest Ophthalmol Vis Sci ,1998,39(2):233-252
21.Beer PM, Bakri SJ, Singh RJ, et al. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology, 2003,110(4):681-686
22.Jonas JB. Intraocular availability of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol, 2004, 137 (3): 560-562
23.McCuen BW, Bessler M, Tano Y, et al. The lack of toxicity of intravitreally administered triamcinolone acetonide. Am J Ophthalmol, 1981;91:785-788
24.Jonas JB, Kreissig I, Sofker A, et al. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arc Ophthalmol,2003,121:57-61
25.Penfold PL, Wen L, Madigan MC, et al. Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1(ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol, 2000; 121:458-465
26.Ip MS, Gottlieb JL, Kahana A, et al. Intravitreal triamcinolone for the t reatment of macular edema associated with central retinal vein occlusion. Arch Ophthalmol, 2004; 122 (8): 1131- 1136
27.Singh IP, Ahmad SI, Yeh D, Challa P, Herndon LW, Allingham RR, Lee PP: Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol , 2004; 138: 286-287
28.Jonas JB ,Kreissig I ,Degenring RF .Intrvitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes ArchClin Exp Ophthalmol ,2002,240:782-783
29.Benhamou N, Massia P, Haouchine B ,et al. Intravitreal triamacinolone for refractory pseudophakic macular edema . Am J Ophthalmol ,2003,135:246-249
30.Otani T ,Kishi AS. Tomographic findings of foreal hard exudates in diabetic macular edema. Am J Ophthalmol,2001,131:50-54
31.Paul M. Beer, MD, Sophie J. Bakri, MD, Ravinder J. Singh, PhD, et al:lntraocular Concentration and Pharmacokinetics of triamcinolone acetone after a single intravitrea injection. Ophthalmology, 2003, 110 (4): 681-86
32.Francois Au dren, Micbel Tod,Pascale Massin, et al,Pharmacokinetic-Pharmacodynamic, Modeling of the Effect of Triamcinolone Acetonide on Central Macular Thinkness in Patients with Diabetic Macular Edema .Macular IOVS,2004,45:3433-3441
33.Massin P, Audren F, Haouchine B, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema preliminary results of a prospective controlled trial. Ophthalmology, 2004,111:218-224
34.Singh IP, Ahmad SI, Yeh D, Challa P, Herndon LW, Allingham RR, Lee PP: Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol , 2004; 138: 286-287
35.Roth DB, Chieh J, Spirn MJ, et al. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol, 2003, 121: 1279 -1282
36.Sutter FK, Gillies MC. Pseudo-endophthalmitis after intravitreal Injection of triamcinolone. Br J Ophthalmol, 2003, 87: 972-974
37.Jonas JB, Kreissig I, Degenring RF. Endophthalmitis after Intravitreal injection of triamcinolone acetonide. Arch Ophthalmol, 2003, 121: 1663- 1664
38.Nelson ML, Tennant MT, Sivalingam A, et al. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection.Retina,2003,23:686-691
39.Moshfeghi DM ,Kaiser PK ,Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol ,2003,136:791-796