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视网膜静脉阻塞抗血管内皮生长因子治疗研究进展

以血管内皮生长因子（VEGF）为特异性靶点的新疗法，较激光光凝、糖皮质激素等传统治疗方法独具优势，有望成为视网膜静脉阻塞继发黄斑水肿（ME）的一线治疗。其代表药物抗VEGF单克隆抗体ranibizumab、bevacizumab、aflibercept均能非特异性阻断VEGF-A全部亚型，通过抗原-抗体结合反应在局部发挥药理作用。已有的大样本、随机对照临床研究初步肯定其兼具疗效性和安全性，但仍存在ME复发、治疗频繁、个体差异、费用高等诸多问题，且治疗相关并发症及风险尚待进一步观察。为此，有关预后研究、联合治疗等方面研究已有展开。

视网膜静脉阻塞继发黄斑水肿的治疗进展

视网膜静脉阻塞（RVO）继发黄斑水肿（ME）传统的治疗方法主要为激光光凝和以曲安奈德、地塞米松为主的糖皮质激素治疗。近年来，雷珠单抗（商品名Lucentis）、贝伐单抗（商品名Avastin）等抗血管内皮生长因子药物玻璃体腔注射以及玻璃体视网膜手术治疗是RVO继发ME治疗探索的主要方向。虽然许多非随机、缺乏对照的临床试验结果表明这些新的治疗方法能明显改善ME并提高视力，但仍需进行大规模、多中心、随机对照临床试验研究，以更加客观地评价这些疗法的治疗效果和安全性。

玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab治疗视网膜静脉阻塞黄斑水肿的研究现状

玻璃体腔注射抗血管内皮生长因子(VEGF)单克隆抗体ranibizumab(商品名Lucetis) (IVR)治疗视网膜静脉阻塞(RVO)继发黄斑水肿的短期疗效已得到广泛肯定。由于ranibizumab半衰期短，黄斑水肿易复发，需多次注射，增加了患者眼内注射潜在并发症的风险。传统激光光凝治疗是目前治疗RVO黄斑水肿的主要方法，其疗效作用较为持久，相对安全，但对视网膜组织具有一定的破坏作用，对视力改善效果不明显。IVR联合黄斑格栅样激光光凝治疗RVO黄斑水肿相比单纯IVR可减少玻璃体腔反复注射次数，降低眼内注射并发症风险，达到更好的治疗效果，可成为将来治疗的发展趋势。但联合治疗时机的选择以及反复注射存在的潜在危险仍需要大样本的长期前瞻性研究进一步观察验证。

副肿瘤性视网膜视神经病变诊疗进展

视网膜和视神经受累的副肿瘤综合征包括癌症相关性视网膜病变（CAR）、癌症相关性视锥细胞功能障碍（CACD）、黑色素瘤相关性视网膜病变（MAR）、副肿瘤性视神经病变（PON）、双眼弥漫性葡萄膜黑色素细胞增生（BDUMP）、自身免疫相关性视网膜病变和视神经病变等。双眼无痛性、亚急性进行性视力下降，视野缺损，伴闪光感，症状与眼底病变程度不一致者应考虑到CAR、CACD、MAR、PON的可能；双眼不明原因的色素播散、色素上皮萎缩，伴或不伴视网膜血管炎、渗出性视网膜脱离者，要考虑BDUMP的可能。视觉生理检查是诊断该病的重要手段。仔细寻找原发或转移病灶是诊断该病所必需。

Effects of retina on macromolecules diffusion after retinal vein occlusion

Objective To observe the change of diffusion upper limit of macromol ecules through pathological retina and the difference between the layers of retina. Methods Retinal edema was emulated by establishing branch retinal vein occlusion (RVO) model in miniature pig eyes under photodynamic method. Two days later, the retinas of both eyeballs were peeled off. The diffusion test apparatus was designed by ourselves. FITC-dextrans of various molecular weights (4.4, 9.3, 19.6, 38.9, 71.2 and 150 kDa) and Carboxyfluorescein (376 Da) were dissolved in RPMI1640 solutions and diffused through inner or outer surface of retina. The rate of transretinal diffusion was determined with a spectrophotometer. Theoretical maximum size of molecule (MSM) was calculated by extrapolating the trend-linear relationship with the diffusion rate. In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluores cence microscope. Results FITC-dextrans applying to inner retinal surface, 4.4 kDa dextrans were largely blocked by inner nuclear layer (INL); 19.6,71.2 kDa dextrans were blocked by the nerve fiber layer (NFL) and inner plexiform layer; 15.0 kDa dextrans were blocked by NFL. FITC-dextrans applying to outer retinal surface, most dextrans with various molecular weights were blocked before outer nuclear layer (ONL). No matter applying to the inner or outer surface, Carboxyfluore scein can diffuse through the whole retina and aggregate at INL and ONL. After RVO, the inner part of retina became edema and cystoid, loosing the barrier function. Compared with the normal retina, the MSM in RVO tissues increased (6.5plusmn;0 39nm Vs 6.18plusmn;0.54nm, t=4.143, P=0.0001). Conclusions A fter RVO, the barrier function of inner part of retinal is destroyed and the upper limit of diffusion macromolecule size increased, which is nevertheless limited. ONL acts as bottle-neck barriers to diffusion, if the outer part of retina is damaged, the change of the diffusion upper limit will be prominent. （Chin J Ocul Fundus Dis，2008，24：197-201）

玻璃体腔注射抗血管内皮生长因子单克隆抗体Ranibizumab治疗视网膜静脉阻塞继发黄斑水肿

Intravitreous injection with triamcinolone acetonide for cystoid macular edema due to central retinal vein occlusion

ObjectiveTo investigate the efficacy and safety of intravitreous injection with triamcinolone acetonide (TA) for cystoid macular edema (CME) due to central retinal vein occlusion (CRVO).MethodsFourteen eyes of 14 patients with CME due to CRVO underwent intravitreous injection with 0.1 ml TA (40 mg/ml). Best-corrected visual acuity, intraocular pressure (IOP), slitlamp examinaion, fundus fluorescein angiography, and optical coherence tomography (OCT) were performed on the patients before and after the injection. The follow-up period was 10-22.4 months, with the mean of 15.9 months.ResultsThe average visual acuity was 0.1 before the treatment; while 1 month and 3 months after the injection, the visual acuity of all of the patients improved, including ≥0.2 in 71.43% and 63.6% of the patients, respectively, and ≥0.5 in 429% and 27.3%, respectively. After then, the visual acuity of some patients decreased, and in the final visit, 4 eyes (28.6%) had a visual acuity of ≥0.2, and 1 eye (7.1%) of ≥0.5. Compared with that before the treatment, the visual acuity of 10 (71.4%) eyes improved and 4 (28.6%) eyes declined. One month after the treatment, the macular edema disappeared in 10 eyes (71.4%) and alleviated in 4 (28.6%). In the final visit, macular edema disappeared in 4 eyes, alleviated in 9, and aggravated in 1. In the follow-up duration, high IOP［22.3-40.1 mm Hg (1 mm Hg=0.133 kPa)］. In the final visit, posterior subcapsular cataract was found in 7 eyes.ConclusionIntravitreous injection with TA may be effective in reducing CME and enhancing the visual acuity in a short term with high IOP in some eyes. In the long-term follow-up period, the rate of recurrence of CME and incidence of posterior subcapsular cataract is high. (Chin J Ocul Fundus Dis, 2005,21:213-216)

葛根素注射液对视网膜静脉阻塞患眼视力和血液流变学指标的影响

Short-tern efficacy of conbercept versus ranibizumab for macular edema in central retinal vein occlusion

ObjectiveTo compare the short-term efficacy of conbercept and ranibizumab for macular edema in central retinal vein occlusion (CRVO)and explore the relationship between the integrity of ellipsoidal zone and visual acuity. MethodsForty-four eyes of 44 patients with macular edema in CRVO were enrolled into this retrospective and comparative study. There were 15 eyes of 15 males, 29 eyes of 29 females; age ranged from 49-61 years old,with an average age of (54.65±3.10) years. All patients were examined with best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit lamp, fundus photograph, fundus fluorescein angiography (FFA), optical coherence tomography(OCT). BCVA were examined with interactional visual chart and recorded with logarithm of the minimum angle of resolution acuity. Twenty-three eyes were intravitreal injected with conbercept 0.5 mg (group A) and 21 eyes were intravitreal injected with ranibizumab 0.5 mg (group B). There was no statistical difference of age (t=-1.41), gender (χ2= 0.55),the percentage of hypertension patients (χ2=0.27), average BCVA (t=-2.06), IOP (t=-2.52), central macular thickness (CMT) (t=-1.96), number of different integrity of ellipsoidal zone patients (χ2=1.00) and number of different types of macular edema patients (χ2=1.03) among the two groups (P > 0.05). The change in BCVA and CMT at 3, 6 months between the two groups were compared. The relationship between BCVA at 6 months and BCVA, CMT at baseline were explored. The relationship between three groups of ellipsoidal zone and BCVA at baseline were evaluated. The change of BCVA after treatment between the three groups of ellipsoidal zone were Compared. The number of intravitreal injections between two groups was compared. ResultsDuring the 3, 6 months after treatment, the mean BCVA were all improved with statistically difference in group A (t=5.13, 7.39; P < 0.05) and group B (t=6.60, 11.52; P < 0.05). There was no significant difference of BCVA at 3, 6 moths between group A and group B (t=-0.99, -0.40; P > 0.05). During the 3, 6 months after treatment, the mean CMT were all decreased with statistically difference in group A (t=11.58, 15.96; P < 0.05) and group B (t=18.77, 35.16; P < 0.05). There was no significant difference of CMT at 3, 6 months between group A and group B (t=-1.52, -1.63; P > 0.05). In both groups,BCVA at 6 months was related to BCVA at baseline (r= 0.44, 0.62; P < 0.05), but not related to CMT at baseline (r=0.19, 0.01; P > 0.05). In the two groups, BCVA at baseline was related to the integrity of ellipsoidal zone (r=0.97, 0.70; P < 0.05). There was statistical difference of the number of intravitreal injections in the two groups (t=-6.88, P < 0.05). There was no systemic or ocular serious side effects during the follow up. ConclusionsComparing to ranibizumab, conbercept has the same effective to the treatment of macular edema in CRVO, but the number of intravitreal injections is less. The integrity of ellipsoidal zone is related to BCVA.

The efficacy of intravitreal conbercept for macular edema secondary to retinal vein occlusion

ObjectiveTo investigate the effects of intravitreous injection of conbercept for macular edema secondary to retina1vein occlusion(RVO) during 6 months period. MethodsA retrospective clinical study. 34 patients (34 eyes) were included in this study,who were diagnosed with macular edema due to retinal vein occlusion by ophthalmologic examination, fundus photography, optical coherence tomography (OCT), fundus fluorescein angiography and other methods. The best corrected visual acuity (BCVA) was examined using the international standard visual acuity chart, and the results were converted to the logMAR visual acuity. The average logMAR BCVA was 0.90±0.68, and the mean macular central retinal thickness (CMT) was (672.27±227.51) μm before treatment. All subjects received intravitreal injection of 0.5 mg conbercept (0.05 ml) at the first visit. Injections were repeated based on the visual acuity changes and the OCT findings. 34 eyes received 69 times of injection, the average number of injections was 2.03±1.03. BCVA, OCT were examined before and after treatment using the same method. BCVA and CMT changes, drugs and treatments associated cardiac and cerebral vascular accident, intraocular pressure elevation, retinal tears, retinal detachment, endophthalmitis and other complications after treatment were observed. Linear correlation analysis was used to analyze the correlation between prognosis BCVA and baseline BCVA, correlation between prognosis BCVA and baseline CMT, and also correlation between BCVA and CMT at different time points before and after treatment. ResultsAt 1 week and 1, 2,3, 6 months after treatment, the average logMAR BCVA was 0.65±0.61, 0.56±0.61, 0.46±0.55, 0.56±0.71, 0.44±0.48 respectively. During 1, 2, 3, 6 months after treatment, the mean logMAR BCVA were improved with statistically significant difference (Z=34.029, 47.294, 41.338, 43.603;P < 0.05), while 1 week after treatment showed no obvious improvement (Z=21.941,P > 0.05). At 1 week and 1, 2, 3, 6 months after treatment, the average CMT was (285.89±96.69), (256.65±143.39), (278.68±156.92), (290.11±188.17), (217.15±48.04) μm respectively. At 1 week and 1,2,3,6 months after treatment, the mean CMT were all decreased with statistically significant difference (Z=68.500, 98.735, 93.235, 91.132, 109.162; P < 0.05). There was a positive correlation between the prognosis visual acuity and preoperative visual acuity (r=0.682,P < 0.05). However,there was no correlation between the prognosis vision and the degree of macular edema before treatment (r=0.078,P > 0.05). Before and 3, 6 months after treatment, BCVA was negatively correlated with CMT (r=0.491, 0.416, 0.386; P < 0.05), while there was no correlation in other time points (r=0.145, 0.217, 0.177; P > 0.05). Systemic adverse reactions and persistent intraocular pressure elevation, iatrogenic cataract, retinal detachment, retinal tear, endophthalmitis and ocular complications were never found in the follow-up period. ConclusionIntravitreal conbercept is a safe and effective approach for RVO,which can significantly improve visual acuity and reduce CMT.