糖尿病黄斑水肿的检测及全视网膜光凝对黄斑的影响
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摘要
糖尿病黄斑水肿是糖尿病患者视力下降最为重要的原因，其发生率随着糖尿病病程的延长和严重程度的加重而逐渐增高。黄斑水肿临床诊断通常是在散瞳的情况下，在裂隙灯下使用间接检眼镜进行眼底检查。但是此种方法比较主观，受到多种因素的影响。光学相干断层扫描(optical coherence tomography，OCT)是近年来新兴的眼科诊断仪器，它的分辨率高达10um，可以显示活体黄斑部的断层结构并定量测量，客观性强、重复性好，是观察黄斑部变化的最佳手段。
激光全视网膜光凝(panretinal photocoagulation，PRP)是治疗重度非增殖型糖尿病视网膜病变和增殖型糖尿病视网膜病变标准的和应用最广泛的方法。尽管PRP可以延缓糖尿病视网膜病变的进展，但却可能引起黄斑水肿或使原有的黄斑水肿加重，引起视力暂时或者持久性的下降，是糖尿病视网膜病变患者接受PRP后视力下降的最常见的原因。
目的
1．对OCT与间接检眼镜在检测糖尿病黄斑水肿方面进行比较，对两种检查方法不相符的病例特点进行研究分析，从而积累OCT临床应用适应症的经验，指导其在临床中的合理应用。
2．比较PRP前后视力、黄斑厚度的改变，发现PRP后黄斑水肿的发生及演变规律，以预防和减少PRP所致的黄斑水肿的发生。
方法
1．我们检查了糖尿病患者45人，78只眼，均于散瞳后前置镜(78D)下观察以及使用OCT测量患者黄斑厚度，比较了检测糖尿病黄斑水肿方面两种方法的异同，得出了两种检查方法在检测糖尿病黄斑水肿方而的符合程度并对两种检查方法不相符的病例特点研究分析。
2．通过对接受PRP的糖尿病视网膜病变的50只眼分别于激光前、激光后1个月、3个月、6个月行视力、OCT测量黄斑厚度检查。
结果
1．间接检眼镜检查与OCT检查结果成正相关(r=0.575，P＜0.001)。间接检眼镜检查与OCT检查糖尿病黄斑水肿结果总的符合率为68％(kappa=0.359，P＜0.01)。假如排除OCT观测下的轻度黄斑水肿的病例，则间接检眼镜与OCT检查糖尿病黄斑水肿结果中，55只眼中有47只相符，总的符合率良好(86％，kappa=0.660，P＜0.001)。
2．PRP前、后各期视力无显著性差异。PRP后1个月、3个月、6个月黄斑厚度较PRP前均有不同程度的增加；其中1个月时增加幅度最大(25％)，3个月(21％)与6个月(11％)时逐渐回落。黄斑厚度的两两比较结果发现：与PRP前相比，PRP后1个月(P=0.000＜0.01)、3个月(P=0.003＜0.01)黄斑厚度显著增加，6个月(P=0.132＞0.05)则无显著性差异。PRP前、后各期黄斑厚度均与视力的负对数呈显著正相关(相关系数r=0.5～0.8)。光凝前相关系数r=0.746(P=0.000)；光凝后1个月时相关系数r=0.570(P=0.000)；光凝后3个月时相关系数r=0.518(P=0.000)；光凝后6个月时相关系数r=0.599(P=0.000)。
结论
1．在无糖尿病黄斑水肿、中度糖尿病黄斑水肿、重度糖尿病黄斑水肿的检测方面，间接检眼镜与OCT相关性较好，但是在轻度糖尿病黄斑水肿(亦称为亚临床黄斑水肿，OCT测量为201～300um)的检测时，间接检眼镜与OCT相关性较差。
2．PRP前、后各期视力无显著性差异，视力总体保持稳定。与PRP前相比，PRP后1个月、3个月黄斑厚度显著增加；但光凝后6个月时黄斑厚度逐渐回落到接近术前的水平，两者无显著性差异。OCT测量黄斑厚度与视力的负对数之间存在着显著的正相关，也就是说，黄斑部视网膜越厚，视力越呈低下的趋势。
Diabetic macular edema is a leading cause of vision loss in patients withdiabetes mellitus. The incidence and prevalence of macular edema increase withlonger duration of diabetes and with increasing severity of concurrent retinopathy.Usually, the clinical diagnosis of macular edema is viewing the fundus using indirectophthalmoscope at the slitlamp through a pharmacologically dilated pupil. This is asubjective process that is dependent on many factors. Optical coherence tomography(OCT) is a new diagnostic technique in recent years that can provide cross-sectionalimages of macula in vivo and quantify macular thickness variation with a precision of10um. It appears to be more objective and reproducible which indicates that OCTmay be the best choice to investigate macular changes.
Panretinal photocoagulation (PRP) is a standard and mostly common usedmethod for the treatment of severe nonproliferative diabetic retinopathy andproliferative diabetic retinopathy. Also PRP can delay the progression of diabeticretinopathy, but macular edema may be induced or increase, with either transient orsustained decrease of vision, that is the most common cause of visual loss in patientswith diabetic retinopathy after the treatment of PRP.
Objectives
1. To compare the two methods of OCT to indirect ophthalmoscope for the detectionof diabetic macular edema, search for case characteristics that predict disagreement,begin to build an evidence-based framework for clinical application of OCTmeasurement in diabetic retinopathy.
2. To compare the changes of visual acuity and macular thickness before and after PRP, find the incidence and evolution of macular edema after PRP, and to prevent andreduce the incidence ofmacular edema induced by PRP.
Methods
1. We examined 45 patients with diabetes mellitus, 78 eyes. After pupil dilated, allpatients were under observation using pre-microscopy (78-diopter) and OCT tomeasure the macular thickness.
2. 50 eyes of patients who were receiving panretinal photocoagulation, were under theobservation of eyesight, macular thickness by OCT before and 1, 3, 6 months aftertreatment.
Results
1. The indirect ophthalmoscopy was positively correlated with the results of OCT(r=0.575, P＜0.001). The overall agreement of indirect ophthalmoscopy and OCT onthe detection of diabetic macular edema was 68% (kappa=0.359, P＜0.01). Theoverall agreement excluding cases with mild edema by OCT was good (86%, kappa=0.660, P＜0.001), 47 cases of 55 were in line.
2. There was no significant difference between the visual acuity before and after PRP.The macular thickness after 1 month, 3 months, 6 months of PRP had increased invarying degrees; among them, 1 month had the largest increase(25%), 3 months(21%)and 6 months(11%) edged down. We compared the macular thickness every two andfound: With the comparison of macular thickness before PRP, 1 month(P=0.000＜0.01) and 3 months (P=0.003＜0.01) after PRP, the macular thicknessincreased significantly; but 6 months (P=0.132＞0.05) after PRP, there was nosignificant differecne. The macular thickness was significantly positive correlatedwith the negative logarithm of visual acuity before and 1, 3, 6 months after PRP (thecorrelation coefficient r=0.5～0.8). Before PRP the correlation coefficient r=0.746 (P=0.000); after 1 month the correlation coefficient r=0.570(P=0.000); after 3 months the correlation coefficient r=0.518 (P=0.000); after 6 months the correlationcoefficient r=0.599 (P=0.000).
Conclusions
1. In nondiabetic macular edema, moderate diabetic macular edema, severe diabeticmacular edema detection, there was better relevance, but in mild diabetic macularedema (also known as sub-clinical macular edema, 201～300um-OCT measurement)detection, there was poor relevance.
2. There was no significant difference of the visual acuity before and 1, 3, 6 monthsafter PRP. Visual whole, maintained stability. With the comparison of macularthickness before PRP, 1 month and 3 months after PRP, the macular thicknessincreased significantly; but 6 months after photocoagulation, the macular thicknessdecreased nearly to the levels before photocoagulation, there was no significantdifferecne between them. Macular thickness measured by OCT had significantlynegative correlation with eyesight. That's the thicker of the macular thickness, thetrend of low vision was increasingly.
激光全视网膜光凝(panretinal photocoagulation，PRP)是治疗重度非增殖型糖尿病视网膜病变和增殖型糖尿病视网膜病变标准的和应用最广泛的方法。尽管PRP可以延缓糖尿病视网膜病变的进展，但却可能引起黄斑水肿或使原有的黄斑水肿加重，引起视力暂时或者持久性的下降，是糖尿病视网膜病变患者接受PRP后视力下降的最常见的原因。
目的
1．对OCT与间接检眼镜在检测糖尿病黄斑水肿方面进行比较，对两种检查方法不相符的病例特点进行研究分析，从而积累OCT临床应用适应症的经验，指导其在临床中的合理应用。
2．比较PRP前后视力、黄斑厚度的改变，发现PRP后黄斑水肿的发生及演变规律，以预防和减少PRP所致的黄斑水肿的发生。
方法
1．我们检查了糖尿病患者45人，78只眼，均于散瞳后前置镜(78D)下观察以及使用OCT测量患者黄斑厚度，比较了检测糖尿病黄斑水肿方面两种方法的异同，得出了两种检查方法在检测糖尿病黄斑水肿方而的符合程度并对两种检查方法不相符的病例特点研究分析。
2．通过对接受PRP的糖尿病视网膜病变的50只眼分别于激光前、激光后1个月、3个月、6个月行视力、OCT测量黄斑厚度检查。
结果
1．间接检眼镜检查与OCT检查结果成正相关(r=0.575，P＜0.001)。间接检眼镜检查与OCT检查糖尿病黄斑水肿结果总的符合率为68％(kappa=0.359，P＜0.01)。假如排除OCT观测下的轻度黄斑水肿的病例，则间接检眼镜与OCT检查糖尿病黄斑水肿结果中，55只眼中有47只相符，总的符合率良好(86％，kappa=0.660，P＜0.001)。
2．PRP前、后各期视力无显著性差异。PRP后1个月、3个月、6个月黄斑厚度较PRP前均有不同程度的增加；其中1个月时增加幅度最大(25％)，3个月(21％)与6个月(11％)时逐渐回落。黄斑厚度的两两比较结果发现：与PRP前相比，PRP后1个月(P=0.000＜0.01)、3个月(P=0.003＜0.01)黄斑厚度显著增加，6个月(P=0.132＞0.05)则无显著性差异。PRP前、后各期黄斑厚度均与视力的负对数呈显著正相关(相关系数r=0.5～0.8)。光凝前相关系数r=0.746(P=0.000)；光凝后1个月时相关系数r=0.570(P=0.000)；光凝后3个月时相关系数r=0.518(P=0.000)；光凝后6个月时相关系数r=0.599(P=0.000)。
结论
1．在无糖尿病黄斑水肿、中度糖尿病黄斑水肿、重度糖尿病黄斑水肿的检测方面，间接检眼镜与OCT相关性较好，但是在轻度糖尿病黄斑水肿(亦称为亚临床黄斑水肿，OCT测量为201～300um)的检测时，间接检眼镜与OCT相关性较差。
2．PRP前、后各期视力无显著性差异，视力总体保持稳定。与PRP前相比，PRP后1个月、3个月黄斑厚度显著增加；但光凝后6个月时黄斑厚度逐渐回落到接近术前的水平，两者无显著性差异。OCT测量黄斑厚度与视力的负对数之间存在着显著的正相关，也就是说，黄斑部视网膜越厚，视力越呈低下的趋势。
Diabetic macular edema is a leading cause of vision loss in patients withdiabetes mellitus. The incidence and prevalence of macular edema increase withlonger duration of diabetes and with increasing severity of concurrent retinopathy.Usually, the clinical diagnosis of macular edema is viewing the fundus using indirectophthalmoscope at the slitlamp through a pharmacologically dilated pupil. This is asubjective process that is dependent on many factors. Optical coherence tomography(OCT) is a new diagnostic technique in recent years that can provide cross-sectionalimages of macula in vivo and quantify macular thickness variation with a precision of10um. It appears to be more objective and reproducible which indicates that OCTmay be the best choice to investigate macular changes.
Panretinal photocoagulation (PRP) is a standard and mostly common usedmethod for the treatment of severe nonproliferative diabetic retinopathy andproliferative diabetic retinopathy. Also PRP can delay the progression of diabeticretinopathy, but macular edema may be induced or increase, with either transient orsustained decrease of vision, that is the most common cause of visual loss in patientswith diabetic retinopathy after the treatment of PRP.
Objectives
1. To compare the two methods of OCT to indirect ophthalmoscope for the detectionof diabetic macular edema, search for case characteristics that predict disagreement,begin to build an evidence-based framework for clinical application of OCTmeasurement in diabetic retinopathy.
2. To compare the changes of visual acuity and macular thickness before and after PRP, find the incidence and evolution of macular edema after PRP, and to prevent andreduce the incidence ofmacular edema induced by PRP.
Methods
1. We examined 45 patients with diabetes mellitus, 78 eyes. After pupil dilated, allpatients were under observation using pre-microscopy (78-diopter) and OCT tomeasure the macular thickness.
2. 50 eyes of patients who were receiving panretinal photocoagulation, were under theobservation of eyesight, macular thickness by OCT before and 1, 3, 6 months aftertreatment.
Results
1. The indirect ophthalmoscopy was positively correlated with the results of OCT(r=0.575, P＜0.001). The overall agreement of indirect ophthalmoscopy and OCT onthe detection of diabetic macular edema was 68% (kappa=0.359, P＜0.01). Theoverall agreement excluding cases with mild edema by OCT was good (86%, kappa=0.660, P＜0.001), 47 cases of 55 were in line.
2. There was no significant difference between the visual acuity before and after PRP.The macular thickness after 1 month, 3 months, 6 months of PRP had increased invarying degrees; among them, 1 month had the largest increase(25%), 3 months(21%)and 6 months(11%) edged down. We compared the macular thickness every two andfound: With the comparison of macular thickness before PRP, 1 month(P=0.000＜0.01) and 3 months (P=0.003＜0.01) after PRP, the macular thicknessincreased significantly; but 6 months (P=0.132＞0.05) after PRP, there was nosignificant differecne. The macular thickness was significantly positive correlatedwith the negative logarithm of visual acuity before and 1, 3, 6 months after PRP (thecorrelation coefficient r=0.5～0.8). Before PRP the correlation coefficient r=0.746 (P=0.000); after 1 month the correlation coefficient r=0.570(P=0.000); after 3 months the correlation coefficient r=0.518 (P=0.000); after 6 months the correlationcoefficient r=0.599 (P=0.000).
Conclusions
1. In nondiabetic macular edema, moderate diabetic macular edema, severe diabeticmacular edema detection, there was better relevance, but in mild diabetic macularedema (also known as sub-clinical macular edema, 201～300um-OCT measurement)detection, there was poor relevance.
2. There was no significant difference of the visual acuity before and 1, 3, 6 monthsafter PRP. Visual whole, maintained stability. With the comparison of macularthickness before PRP, 1 month and 3 months after PRP, the macular thicknessincreased significantly; but 6 months after photocoagulation, the macular thicknessdecreased nearly to the levels before photocoagulation, there was no significantdifferecne between them. Macular thickness measured by OCT had significantlynegative correlation with eyesight. That's the thicker of the macular thickness, thetrend of low vision was increasingly.
引文
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47 Catier A, Tadayoni R, Paques M, et al. Characterization of macular edema from various etiologies by optical coherence tomography. Am J Ophthalmol. 2005 Aug;140(2):200-6.
48 Hussain A, Hussain N, Nutheti R. Comparison of mean macular thickness using optical coherence tomography and visual acuity in diabetic retinopathy. Clin Experiment Ophthalmol. 2005 Jun;33(3):240-5.
1 Aiello LP, Cahill MT, Cavallerano JD. Growth factors and protein kinase C inhibitors as novel therapies for the medical management diabetic retinopathy. Eye, 2004, 18:117-125.
2 Tolentino MJ,McLeod DS,Taomoto M,et al.Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate.AM J Ophthalmol,2002,133:373-385.
3 Ishida S, Usui T, Yamashiro K,et al. VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci, 2003,44:2155-2162.
4 Frank RN. Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol, 2002,133:693-698.
5 Campochiaro PA;C99-PKC412-003 Study Group. Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412.Invest Ophthalmol Vis Sci, 2004,45:922-931.
6 The Effect of Ruboxistaurin on Visual Loss in Patients With Moderately Severe to Very Severe Nonproliferative Diabetic Retinopathy: Initial Results of the Protein Kinase C {beta} Inhibitor Diabetic Retinopathy Study (PKC-DRS) Multicenter Randomized Clinical Trial. Diabetes, 2005,54:2188-2197.
7 Hang JZ, Gao L, Widness M,et al. Captopril inhibits glucose accumulation in retinal cells in diabetes. Invest Ophthalmol Vis Sci, 2003,44:4001-4005.
8 Nagai N, Noda K, Urano T,et al. Selective suppression of pathologic, but not physiologic, retinal neovascularization by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci, 2005,46: 1078-1084.
9 Growth Hormone Antagonist for Proliferative Diabetic Retinopathy Study Group. The effect of a growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology, 2001,108: 2266-2272.
10 Grant MB, Mames RN, Fitzgerald C,et al. The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Diabetes Care, 2000, 23: 504-509.
11 Jonas J, Heatley G, Spaide R, Varma R. Intravitreal triamcinolone acetonide and secondary ocular hypertension. J Glaucoma, 2005, 14: 168-171.
12 Martidis A, Duker JS, Greenberg PB,et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology, 2002,109:920-927.
13 Jonas JB, Kreissig I, Softer A, Degenring RE Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol, 2003, 121:57-61.
14 Dagher Z, Park YS, Asnaghi V, et al.Studies of rat and human retinas predict a role for thepolyol pathway in human diabetic retinopathy. Diabetes, 2004, 53: 2404-2411.
15 Obrosova IG, Minchenko AG, Vasupuram R, et al. Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats. Diabetes, 2003, 52: 864-871.
16 Usick M, Chew EY, Ferris F 3rd, et al. Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein angiographic lesions in galactose-fed dogs. Arch Ophthalmol, 2003,121:1745-1751.
17 Itt AW. Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol, 2001, 85: 746-753.
18 Kern TS, Engerman RL. Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin. Diabetes, 2001, 50:1636-1642.
19 Pta A, Gupta V, Thapar S, et al. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am J Ophthalmol, 2004,137:675-682.
20 Gordon B, Chang S, Kavanagh M,et al. The effects of lipid lowering on diabetic retinopathy. Am J Ophthalmol, 1991,112: 385-391.
21 The DAMAD Study Group.Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. The DAMAD Study Group. Diabetes, 1989, 38: 491-498.
22 Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology, 1991, 98(5 Suppl):757-765.
23 Renu A. Kowluru, Anjaneyulu Kowluru, Subrata Chakrabarti,et al. Potential contributory role of H-Ras,a small G-protein,in the development of retinopathy in diabetic rat. Diabetes, 2004, 53: 775-783.
24 Mayer-Davis EJ, Bell RA,Reboussin BA,et al. Antioxidant nutrient intake and diabetic retinopathy: the San Luis Valley Diabetes Study. Ophthalmology, 1998, 105:2264-2270.
25 Bhisitkul RB. Anticipation for enzymatic vitreolysis. Br J Ophthalmol, 2001, 85: 1-2.
1 Ko TH, Fujimoto JG, Schuman JS,et al. Comparison of ultrahigh-and standard-resolution optical coherence tomography for imaging macular pathology. Ophthalmology. 2005 Nov; 112(11): 1922. Epub 2005 Sep 23.
2 Wojtkowski M,Srinivasan V, Fujimoto JG, et al. Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology. 2005 Oct;112(10):1734-46.
3 Witkin AJ,Ko TH,Fujimoto JG,et al. Redefining lamellar holes and the vitreomacular interface: an ultrahigh-resolution optical coherence tomography study. Ophthalmology. 2006 Mar;113(3):388-97.
4 Gloesmann M,Hermann B,Schubert C,et al. Histologic correlation of pig retina radial stratification with ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1696-703.
5 Anger EM,Unterhuber A,Hermann B,et al. Ultrahigh resolution optical coherence tomography of the monkey fovea. Identification of retinal sublayers by correlation with semithin histology sections. Exp Eye Res. 2004 Jun;78(6):1117-25.
6 Van Velthoven ME,Verbraak FD. Comment on 'Ultrahigh resolution optical coherence tomography of the monkey fovea. Identification of retinal sublayers by correlation with semithin histology sections' by E.M. Anger et al. [Exp. Eye Res. 78 (2004) 1117-1125]. Exp Eye Res. 2005 Mar;80(3):447-8; author reply 449-50.
7 Ko TH,Fujimoto JG,Duker JS,et al. Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair. Ophthalmology. 2004 Nov;111(11):2033-43.
8 Drexler W,Sattmann H,Hermann B,et al. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch Ophthalmol. 2003 May;121(5):695-706.
9 Pieroni CG,Witkin AJ,KO TH,et al. Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration. Br J Ophthalmol. 2006 Feb;90(2):191-7.
10 Chen TC,Cense B,Pierce MC,et al. Spectral domain optical coherence tomography: ultra-high speed, ultra-high resolution ophthalmic imaging. Arch Ophthalmol. 2005 Dec;123(12):1715-20.
11 Lynda Charters.High-resolution, cross-sectional images offer clearer distinction of retinal layers, expert asserts.Ophthalmology Times.Mar 15, 2006.
12 Ergun E,Hermann B,Wirtitsch M,et al. Assessment of central visual function in Stargardt's disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2005 Jan;46(1):310-6.
13 Chan A,Duker JS,Ko TH,et al.Ultra-high resolution optical coherence tomography of retinal pigment epithelial tear following blunt trauma.Arch Ophthalmol. 2006 Feb; 124(2):281-3.
14 Chan A, Ko TH, Duker JS.Ultrahigh-resolution optical coherence tomography of canthaxanthine retinal crystals.Ophthalmic Surg Lasers Imaging. 2006 Mar-Apr;37(2): 138-9.
15 Paunescu LA,Ko TH,Duker JS,et al. Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahigh-resolution optical coherence tomography. Ophthalmology. 2006 Jan;113(1):48-57. Epub 2005 Dec 15.
16 Witkin AJ,Duker JS,Ko TH,et al. Ultrahigh resolution optical coherence tomography of birdshot retinochoroidopathy. Br J Ophthalmol. 2005 Dec;89(12): 1660-1.
17 Schocket LS, Witkin AJ, Fujimoto JG,et al. Ultrahigh-resolution optical coherence tomography in patients with decreased visual acuity after retinal detachment repair. Ophthalmology.2006 Apr;113(4):666-72.
18 Wollstein G,Paunescu LA,Ko TH,et al. Ultrahigh-resolution optical coherence tomography in glaucoma. Ophthalmology. 2005 Feb;112(2):229-37.
19 Burgoyne CF. Image analysis of optic nerve disease. Eye. 2004 Nov;18(11):1207-13.
20 Linnola RJ,Findl O,Hermann B,et al. Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography Pseudophakic human autopsy eyes. J Cataract Refract Surg. 2005 Apr;31(4):818-23.
21 Linnola RJ,Findl O,Hermann B,et al. Reply: Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography: pseudophakic human autopsy eyes. J Cataract Refract Surg. 2006 Feb;32(2):187.
22 Liu DT,Lee VY,Lam DS. Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography: pseudophakic human autopsy eyes. J Cataract Refract Surg. 2006 Feb;32(2): 186-7.
23 Schmidt-Erfurth U,Leitgeb RA,Michels S,et al. Three-dimensional ultrahigh-resolution optical coherence tomography of macular diseases. Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3393-402.
2 Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985 Dec;103(12):1796-806.
3 Zeimer RC, Shahidi M, MoriMT, et al. In vivo evaluation of a noninvasive method to measure the retinal thickness in primates. Arch Ophthalmol. 1989 Jul;107(7):1006-9.
4 Hee MR, Puliafito CA, Duker JS, et al. Topography of diabetic macular edema with optical coherence tomography. Ophthalmology. 1998 Feb;105(2):360-70.
5 Schaudig UH, Glaefke C, Scholz F, et al. Optical coherence tomography for retinal thickness measurement in diabetic patients without clinically significant macular edema. Ophthalmic Surg Lasers. 2000 May-Jun;31(3): 182-6.
6 Yang CS, Cheng CY, Lee FL, et al. Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography. Acta Ophthalmol Scand. 2001 Jun;79(3):266-70.
7 Neubauer AS, Priglinger S, Ullrich S, et al. Comparison of foveal thickness measured with the retinal thickness analyzer and optical coherence tomography. Retina. 2001;21(6):596-601.
8 Strom C, Sander B, Larsen N, et al. Diabetic macular edema assessed with optical coherence tomography and stereo fundus photography. Invest Ophthalmol Vis Sci. 2002 Jan;43(1):241-5.
9 Sanchez-Tocino H, Alvarez-Vidal A, Maldonado MJ, et al. Retinal thickness study with optical coherence tomography in patients with diabetes. Invest Ophthalmol Vis Sci. 2002 May;43(5): 1588-94.
10 Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002 May;109(5):920-7.
11 Strom C, Sander B, Larsen N, et al. Diabetic macular edema assessed with optical coherence tomography and stereo fundus photography. Invest Ophthalmol Vis Sci. 2002 Jan;43(1):241-5.
12 Moreira RO, Trujillo FR, Meirelles RM, et al. Use of optical coherence tomography (OCT) and indirect ophthalmoscopy in the diagnosis of macular edema in diabetic patients. Int Ophthalmol. 2001;24(6):331-6.
13 Brown JC, Solomon SD, Bressler SB, et al. Detection of diabetic foveal edema: contact lens biomicroscopy compared with optical coherence tomography. Arch Ophthalmol. 2004 Mar;122(3):330-5.
14 Optical Coherence Tomography Scanner Three: Owner's Manual. Dublin, Calif:Zeiss-Humphrey Systems; 2002.
15 Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales.Ophthalmology. 2003 Sep; 110(9): 1677-82.
16 Massin P, Erginay A, Haouchine B, et al. Retinal thickness in healthy and diabetic subjects measured using optical coherence tomography mapping software. Eur J Ophthalmol. 2002 Mar-Apr; 12(2): 102-8.
17 Goebel W, Kretzchmar-Gross T. Retinal thickness in diabetic retinopathy: a study using optical coherence tomography (OCT). Retina. 2002 Dec;22(6):759-67.
18 Lattanzio R, Brancato R, Pierro L, et al. Macular thickness measured by optical coherence tomography (OCT) in diabetic patients. Eur J Ophthalmol. 2002 Nov-Dec;12(6):482-7.
19 Hee MR, Izatt JA, Swanson EA, et al. Optical coherence tomography of the human retina. Arch Ophthalmol. 1995 Mar;113(3):325-32.
20 Shahidi M, Ogura Y, Blair NP, et al. Retinal thickness analysis for quantitative assessment of diabetic macular edema. Arch Ophthalmol. 1991 Aug;109(8):1115-9.
21 Yasukawa T, Kiryu J, Tsujikawa A, et al. Quantitative analysis of foveal retinal thickness in diabetic retinopathy with the scanning retinal thickness analyzer. Retina. 1998;18(2):150-5.
22 Oshima Y, Emi K, Yamanishi S, et al. Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser. Br J Ophthalmol. 1999 Jan;83(1):54-61.
23 Early Treatment Diabetic Retinopathy Study Group. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study Report no. 4. The Early Treatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin. 1987 Winter;27(4):265-72.
24 Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998 Sep 12;317(7160):703-13.
25 Snow V, Weiss KB, Mottur-Pilson C, et al. The evidence base for tight blood pressure control in the management of type 2 diabetes mellitus. Ann Intern Med. 2003 Apr 1;138(7):587-92.
26 Davis MD, Fisher MR, Gangnon RE, et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18. Invest Ophthalmol Vis Sci. 1998 Feb;39(2):233-52.
27 Klein R, Sharrett AR, Klein BE, et al. The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes : the atherosclerosis risk in communities study. Ophthalmology. 2002 Jul; 109(7): 1225-34.
28 Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985 Dec;103(12):1796-806.
29 Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Arch Ophthalmol. 1995 Sep;113(9):1144-55.
30 Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology. 1991 May;98(5 Suppl):786-806.
31 Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology. 1991 May;98(5 Suppl):766-85.
32 Early Treatment Diabetic Retinopathy Study Research Group. Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7. Ophthalmology. 1991 May;98(5 Suppl):741-56.
33 British Multicenter Study Group. Photocoagulation for proliferative diabetic retinopathy: a randomised controlled clinical trial using the xenon-arc. Diabetologia. 1984 Feb;26(2):109-15.
34 McDonald HR, Schatz H. Macular edema following panretinal photocoagulation. Retina. 1985 Winter-Spring;5(1):5-10.
35 Shimura M, Yasuda K, Nakazawa T, et al. Quantifying alterations of macular thickness before and after panretinal photocoagulation in patients with severe diabetic retinopathy and good vision. Ophthalmology. 2003 Dec; 110(12):23 86-94.
36 McDonald HR, Schatz H. Visual loss following panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology. 1985 Mar;92(3):388-93.
37 Higgins KE, Meyers SM, Jaffe MJ, et al. Temporary loss of foveal contrast sensitivity associated with panretinal photocoagulation. Arch Ophthalmol. 1986 Jul;104(7):997-1003.
38 Henricsson M, Heiji A. The effect of panretinal laser photocoagulation on visual acuity, visual fields and on subjective visual impairment in preproliferative and early proliferative diabetic retinopathy. Acta Ophthalmol (Copenh). 1994 Oct;72(5):570-5.
39 Shimura M, Yasuda K, Shiono T. Posterior sub-Tenon's capsule injection of triamcinolone acetonide prevents panretinal photocoagulation-induced visual dysfunction in patients with severe diabetic retinopathy and good vision. Ophthalmology. 2006 Mar;113(3):381-7. Epub 2006 Feb 3.
40 Bandello F, Polito A, Del Borrello M, et al. "Light" versus "classic" laser treatment for clinically significant diabetic macular oedema. Br J Ophthalmol. 2005 Jul;89(7):864-70.
41 Laursen ML, Moeller F, Sander B, et al. Subthreshold micropulse diode laser treatment in diabetic macular oedema. Br J Ophthalmol. 2004 Sep;88(9):1173-9.
42 Catier A, Tadayoni R, Paques M, et al. Characterization of macular edema from various etiologies by optical coherence tomography. Am J Ophthalmol. 2005 Aug;140(2):200-6.
43 Ozdemir H, Karacorlu M, Karacorlu SA. Regression of serous macular detachment after intravitreal triamcinolone acetonide in patients with diabetic macular edema. Am J Ophthalmol. 2005 Aug; 140(2):251-5.
44 Goebel W, Kretzchmar-Gross T. Retinal thickness in diabetic retinopathy: a study using optical coherence tomography (OCT). Retina. 2002 Dec;22(6):759-67.
45 Alkuraya H, Kangave D, Abu El-Asrar AM. The correlation between optical coherence tomographic features and severity of retinopathy, macular thickness and visual acuity in diabetic macular edema. Int Ophthalmol. 2005 Jun;26(3):93-9. Epub 2006 Oct 25.
46 Ozdek SC, Erdinc MA, Gurelik G, et al. Optical coherence tomographic assessment of diabetic macular edema: comparison with fluorescein angiographic and clinical findings. Ophthalmologica. 2005 Mar-Apr;219(2):86-92.
47 Catier A, Tadayoni R, Paques M, et al. Characterization of macular edema from various etiologies by optical coherence tomography. Am J Ophthalmol. 2005 Aug;140(2):200-6.
48 Hussain A, Hussain N, Nutheti R. Comparison of mean macular thickness using optical coherence tomography and visual acuity in diabetic retinopathy. Clin Experiment Ophthalmol. 2005 Jun;33(3):240-5.
1 Aiello LP, Cahill MT, Cavallerano JD. Growth factors and protein kinase C inhibitors as novel therapies for the medical management diabetic retinopathy. Eye, 2004, 18:117-125.
2 Tolentino MJ,McLeod DS,Taomoto M,et al.Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate.AM J Ophthalmol,2002,133:373-385.
3 Ishida S, Usui T, Yamashiro K,et al. VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci, 2003,44:2155-2162.
4 Frank RN. Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol, 2002,133:693-698.
5 Campochiaro PA;C99-PKC412-003 Study Group. Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412.Invest Ophthalmol Vis Sci, 2004,45:922-931.
6 The Effect of Ruboxistaurin on Visual Loss in Patients With Moderately Severe to Very Severe Nonproliferative Diabetic Retinopathy: Initial Results of the Protein Kinase C {beta} Inhibitor Diabetic Retinopathy Study (PKC-DRS) Multicenter Randomized Clinical Trial. Diabetes, 2005,54:2188-2197.
7 Hang JZ, Gao L, Widness M,et al. Captopril inhibits glucose accumulation in retinal cells in diabetes. Invest Ophthalmol Vis Sci, 2003,44:4001-4005.
8 Nagai N, Noda K, Urano T,et al. Selective suppression of pathologic, but not physiologic, retinal neovascularization by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci, 2005,46: 1078-1084.
9 Growth Hormone Antagonist for Proliferative Diabetic Retinopathy Study Group. The effect of a growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology, 2001,108: 2266-2272.
10 Grant MB, Mames RN, Fitzgerald C,et al. The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Diabetes Care, 2000, 23: 504-509.
11 Jonas J, Heatley G, Spaide R, Varma R. Intravitreal triamcinolone acetonide and secondary ocular hypertension. J Glaucoma, 2005, 14: 168-171.
12 Martidis A, Duker JS, Greenberg PB,et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology, 2002,109:920-927.
13 Jonas JB, Kreissig I, Softer A, Degenring RE Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol, 2003, 121:57-61.
14 Dagher Z, Park YS, Asnaghi V, et al.Studies of rat and human retinas predict a role for thepolyol pathway in human diabetic retinopathy. Diabetes, 2004, 53: 2404-2411.
15 Obrosova IG, Minchenko AG, Vasupuram R, et al. Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats. Diabetes, 2003, 52: 864-871.
16 Usick M, Chew EY, Ferris F 3rd, et al. Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein angiographic lesions in galactose-fed dogs. Arch Ophthalmol, 2003,121:1745-1751.
17 Itt AW. Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol, 2001, 85: 746-753.
18 Kern TS, Engerman RL. Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin. Diabetes, 2001, 50:1636-1642.
19 Pta A, Gupta V, Thapar S, et al. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am J Ophthalmol, 2004,137:675-682.
20 Gordon B, Chang S, Kavanagh M,et al. The effects of lipid lowering on diabetic retinopathy. Am J Ophthalmol, 1991,112: 385-391.
21 The DAMAD Study Group.Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. The DAMAD Study Group. Diabetes, 1989, 38: 491-498.
22 Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology, 1991, 98(5 Suppl):757-765.
23 Renu A. Kowluru, Anjaneyulu Kowluru, Subrata Chakrabarti,et al. Potential contributory role of H-Ras,a small G-protein,in the development of retinopathy in diabetic rat. Diabetes, 2004, 53: 775-783.
24 Mayer-Davis EJ, Bell RA,Reboussin BA,et al. Antioxidant nutrient intake and diabetic retinopathy: the San Luis Valley Diabetes Study. Ophthalmology, 1998, 105:2264-2270.
25 Bhisitkul RB. Anticipation for enzymatic vitreolysis. Br J Ophthalmol, 2001, 85: 1-2.
1 Ko TH, Fujimoto JG, Schuman JS,et al. Comparison of ultrahigh-and standard-resolution optical coherence tomography for imaging macular pathology. Ophthalmology. 2005 Nov; 112(11): 1922. Epub 2005 Sep 23.
2 Wojtkowski M,Srinivasan V, Fujimoto JG, et al. Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology. 2005 Oct;112(10):1734-46.
3 Witkin AJ,Ko TH,Fujimoto JG,et al. Redefining lamellar holes and the vitreomacular interface: an ultrahigh-resolution optical coherence tomography study. Ophthalmology. 2006 Mar;113(3):388-97.
4 Gloesmann M,Hermann B,Schubert C,et al. Histologic correlation of pig retina radial stratification with ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1696-703.
5 Anger EM,Unterhuber A,Hermann B,et al. Ultrahigh resolution optical coherence tomography of the monkey fovea. Identification of retinal sublayers by correlation with semithin histology sections. Exp Eye Res. 2004 Jun;78(6):1117-25.
6 Van Velthoven ME,Verbraak FD. Comment on 'Ultrahigh resolution optical coherence tomography of the monkey fovea. Identification of retinal sublayers by correlation with semithin histology sections' by E.M. Anger et al. [Exp. Eye Res. 78 (2004) 1117-1125]. Exp Eye Res. 2005 Mar;80(3):447-8; author reply 449-50.
7 Ko TH,Fujimoto JG,Duker JS,et al. Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair. Ophthalmology. 2004 Nov;111(11):2033-43.
8 Drexler W,Sattmann H,Hermann B,et al. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch Ophthalmol. 2003 May;121(5):695-706.
9 Pieroni CG,Witkin AJ,KO TH,et al. Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration. Br J Ophthalmol. 2006 Feb;90(2):191-7.
10 Chen TC,Cense B,Pierce MC,et al. Spectral domain optical coherence tomography: ultra-high speed, ultra-high resolution ophthalmic imaging. Arch Ophthalmol. 2005 Dec;123(12):1715-20.
11 Lynda Charters.High-resolution, cross-sectional images offer clearer distinction of retinal layers, expert asserts.Ophthalmology Times.Mar 15, 2006.
12 Ergun E,Hermann B,Wirtitsch M,et al. Assessment of central visual function in Stargardt's disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2005 Jan;46(1):310-6.
13 Chan A,Duker JS,Ko TH,et al.Ultra-high resolution optical coherence tomography of retinal pigment epithelial tear following blunt trauma.Arch Ophthalmol. 2006 Feb; 124(2):281-3.
14 Chan A, Ko TH, Duker JS.Ultrahigh-resolution optical coherence tomography of canthaxanthine retinal crystals.Ophthalmic Surg Lasers Imaging. 2006 Mar-Apr;37(2): 138-9.
15 Paunescu LA,Ko TH,Duker JS,et al. Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahigh-resolution optical coherence tomography. Ophthalmology. 2006 Jan;113(1):48-57. Epub 2005 Dec 15.
16 Witkin AJ,Duker JS,Ko TH,et al. Ultrahigh resolution optical coherence tomography of birdshot retinochoroidopathy. Br J Ophthalmol. 2005 Dec;89(12): 1660-1.
17 Schocket LS, Witkin AJ, Fujimoto JG,et al. Ultrahigh-resolution optical coherence tomography in patients with decreased visual acuity after retinal detachment repair. Ophthalmology.2006 Apr;113(4):666-72.
18 Wollstein G,Paunescu LA,Ko TH,et al. Ultrahigh-resolution optical coherence tomography in glaucoma. Ophthalmology. 2005 Feb;112(2):229-37.
19 Burgoyne CF. Image analysis of optic nerve disease. Eye. 2004 Nov;18(11):1207-13.
20 Linnola RJ,Findl O,Hermann B,et al. Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography Pseudophakic human autopsy eyes. J Cataract Refract Surg. 2005 Apr;31(4):818-23.
21 Linnola RJ,Findl O,Hermann B,et al. Reply: Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography: pseudophakic human autopsy eyes. J Cataract Refract Surg. 2006 Feb;32(2):187.
22 Liu DT,Lee VY,Lam DS. Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography: pseudophakic human autopsy eyes. J Cataract Refract Surg. 2006 Feb;32(2): 186-7.
23 Schmidt-Erfurth U,Leitgeb RA,Michels S,et al. Three-dimensional ultrahigh-resolution optical coherence tomography of macular diseases. Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3393-402.