Intravitreal injection of methotrexate in an experimental rabbit model: Determination of ultrastructural changes

Purpose:

To investigate the ultrastructural changes of the rabbit retina induced by intravitreal methotrexate injection.

Materials and Methods:

Ten New Zealand white rabbits were enucleated bilaterally at different time periods after intravitreal methotrexate injection. One rabbit was used as control group and one rabbit was used as intact group. Histopathological examinations were performed under light and electron microscopy. Early (within first three days after injection) and long-term (one month after serial injections) effects of intravitreal methotrexate on the retina were investigated.

Results:

Retinal edema, vacuolization, and disintegration of mitochondria of the retinal cells were observed as early changes. The main long-term effects after serial injections were edema in the photoreceptor, inner nuclear, and ganglionic cell layers. Cellular disorganisation was seen on light microscopy. Electron microscopic examination revealed mitochondrial degeneration and vacuole formation in retinal cells, nuclear degeneration in outer nuclear layer, and membranous whorl formation in photoreceptor and nerve fiber layers.

Conclusions

High dose intravitreal methotrexate injection may cause significant ultrastructural changes in the rabbit retina in varying severity. This finding may highlight the potential side effects of methotrexate on human retina in higher doses.     

网脱术中阿霉素和地塞米松眼内注射的观察

目的应用阿霉素及地塞米松在网脱术中注入玻璃体腔,观察对增生性视网膜玻璃体病变(PVR)的抑制作用.方法对42例视网膜脱离伴PVR的患者施行手术加玻璃体腔药物注射,与单纯手术组30眼视网膜脱离伴PVR作对比分析,并行有关血流动力学观察.结果手术加注药物组与单纯手术组比较,术后3～5月视网膜表面增生膜和网膜下机化膜比术前加重的发生率分别为7.14%和26.67%,x2检验P＜0.05.两组环扎术均可导致眼部血流动力学改变,术后1～2周的视网膜中央动脉和中央静脉的收缩期最大平均流速分别为(6.31±2.5)cm/s和(4.77±1.4)cm/s,比正常值分别下降33.66%和16.66%.结论此方法是防治PVR的一种有价值的方法.     

Intravitreal injection of cidofovir in CMV retinitis

Background: CMV retinitis is the most common opportunistic ocular infection and the main cause of blindness in AIDS patients with a T-helper cell count ≤ 50/μl. Cidofovir is a nucleotide analogue with a long half-life time after phosphorylation intracellularly. It is effective against CMV and can be given intravenously and intravitreally. The aim was to offer an alternative therapy for CMV retinitis to patients who could not receive standard treatment because of contraindications or refused it. The efficacy and tolerance of intravitreal injections of cidofovir should be evaluated. Patients and methods: We treated 16 eyes of 12 patients. The total number of injections with 15 μg of cidofovir each was 49, with an average of 3 injections per eye. The duration of follow-up was 75–295 days (median 170 days). Probenecid was given concomitantly. Injections were repeated after 6–10 weeks. Secondary prophylaxis of CMV organ infection was done with oral ganciclovir. Results: Within a few days all areas with active retinitis turned into scars following the first injection. Under consequent treatment no reactivation was observed. Four eyes developed a mild iritis with hypotony within a mean time of 12 days after injection. All responded rapidly to topical steroids. None had a persisting loss of vision. Two eyes developed cystoid macular edema (CME). Two patients stopped anti-CMV treatment (ganciclovir orally and injections), followed by a recurrence after an average of 64 days. Conclusions: Intravitreal injection therapy with 15 μg cidofovir and concomitant oral probenecid is a valuable and safe alternative treatment for CMV retinitis in AIDS patients. Its main complication is iritis with hypotony, which is effectively treatable with topical steroids. No complications caused by the injection technique itself were noted. The occasional observation of CME in otherwise quiet eyes, however, is probably drug-related.      

注气法联合其他术式治疗黄斑裂孔性视网膜脱离

目的：评价玻璃体腔内注气术联合其他术式在黄斑裂孔性视网膜脱离治疗中的价值。方法：对黄斑裂孔性视网膜脱离患者20例（21只眼）施行玻璃体腔内注气（C2F6、C3F8）联合环扎术、激光光凝术、玻璃体切割术。术后俯卧位。全部病例随访4－6月。结果：18例（19只眼）手术成功，痊愈率90．48％％，2只眼失败。结论：玻璃体腔内注气联合其他术式治疗黄斑裂孔性视网膜脱离安全、可靠、方便、有效。     

Intravitreal triamcinolone injection for chronic diabetic macular oedema with severe hard exudates

Background The purpose of the study was to determine the efficacy and safety of intravitreal triamcinolone acetonide (TA) in chronic diabetic macular oedema with severe hard exudates. Methods This prospective, interventional consecutive case series study consisted of 33 eyes of 28 patients with chronic diabetic macular oedema and severe foveal hard exudates who received an intravitreal injection of 4 mg of TA. The patients were divided into two groups according to the type of foveal hard exudates: group I, plaque-like (17 eyes) and group II, dot-like scattered hard exudates (16 eyes). The results of both groups, evaluated by colour fundus photography and fluorescein angiography, were compared and complications were recorded. Results All patients completed at least 6 months of follow-up. In all eyes, the hard exudates were completely resolved (24% in group I and 50% in group II) or decreased (76% in group I and 50% in group II). In group I, the mean diameter of the exudates plaques significantly decreased from 5.5±3.8 mm² in the pre-treatment period to 2.2±2.7 mm² at the end of the follow-up period. There was no recurrence of the hard exudates in either of the groups. The mean ± SD visual acuity (VA) improved from 0.07±2.5 at the baseline to a maximum of 0.09±2.1 lines in group I (P<0.01) and from 0.13±3.9 to a maximum of 0.27±2.7 lines in group II (P<0.01). The mean VA improvement in group II was better than group I (3.2±2.5 vs. 1.4±1.0 lines, P<0.05). Intraocular pressure exceeded 21 mmHg in 10 eyes (30%), which was then controlled by topical medication. Three eyes (9%) exhibited signs of subcapsular cataract progression. Conclusions Intravitreal TA appears to be a valuable treatment in chronic diabetic macular oedema with severe foveal hard exudates. In all eyes in this study the hard exudates were completely resolved or decreased, and the mean VA improved significantly in both groups. However, the VA improvement was significantly worse in eyes with plaque-like exudates suggesting the possible value of earlier treatment. Further studies would enable the assessment of the universal effectiveness of this treatment. This study was presented in part at the 4th European Vitreoretinal Society (EVRS) Meeting, Istanbul, Turkey, 12–15 September 2004     

A Case of CMV Endotheliitis Treated with Intravitreal Ganciclovir Injection

We report a case of CMV corneal endotheliitis that was treated with intravitreal ganciclovir injection. A 56-year-old man who has suffered from uveitis was referred to our clinic due to corneal endothelial abnormality. Slit lamp examination showed a localized sectoral corneal edema and linear keratic precipitates along the boundary of edema. In spite of treatment with oral steroid and acyclovir, the disease progressed and two new coin-like lesions were developed. After topical ganciclovir and intavitreal injection of ganciclovir, the corneal lesions disappeared.     

兔玻璃体腔注射美罗培南治疗细菌性眼内炎

目的评价兔玻璃体腔注射国产美罗培南对敏感菌引起的眼内炎的疗效。方法选取健康成年日本大耳白兔24只，随机分为Ⅰ、Ⅱ两组，每组12只，分别玻璃体腔内接种金黄色葡萄球菌和绿脓杆菌建立相应的眼内炎模型。待出现典型眼内炎体征时，Ⅰ组和Ⅱ组再随机分为A、B组和C、D组。B、D组玻璃体腔均注射美罗培南1．25mg，A、C组分别注射万古霉素1．0mg和复达欣2．0mg作为对照。通过临床炎症评分、细菌培养阳性率、组织学检查病理评分等指标评估药物疗效。结果在两种眼内炎模型中，美罗培南用药后临床炎症评分均有显著下降，用药前后相比有统计学差异，但与万古霉素、复达欣相比无统计学差异；美罗培南用药后细菌培养阳性率在金黄色葡萄球菌和绿脓杆菌眼内炎模型中分别为0和16．7％，均低于万古霉素和复达欣，与万古霉素相比差异有统计学意义；用药2周后组织学检查显示绝大多数标本视网膜组织结构基本完整，层间有不同程度变性和坏死伴炎症细胞浸润，美罗培南与万古霉素、复达欣相比其视网膜病理评分均无统计学差异。结论兔玻璃体腔注射美罗培南治疗敏感金黄色葡萄球菌和绿脓杆菌引起的眼内炎，疗效分别与万古霉素、复达欣基本相当，但当眼内炎体征已明显时单次眼内用药很难完全控制炎症。     

Intravitreal injection of liposome-encapsulated ganciclovir in a rabbit model

The authors determined the intravitreal clearance of liposome-encapsulated ganciclovir. Liposome-encapsulated ganciclovir (84.1 micrograms/0.1 ml) was injected into the vitreous cavity of New Zealand rabbits, which were killed at 24 hours and 7, 14, and 28 days after injection. Total ganciclovir concentrations in the vitreous, up to 28 days, were higher than ID50 (50% inhibitory dose) for different clinical and laboratory strains of viruses belonging to the herpes simplex family.     

Dose Dependent Effects of Intravitreal Triamcinolone Acetonide on Diffuse Diabetic Macular Edema

Purpose

To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular edema.

Methods

In a retrospective study, 44 eyes with diffuse diabetic macular edema were treated with an intravitreal injection of 4 mg (n=12 eyes), 8 mg (n=17) or 25 mg (n=15) of triamcinolone acetonide (TA). Optical coherence tomography, best-corrected logMAR visual acuity and Goldmann tonometry were performed at baseline, 1 week, and 1, 3, 6, 9 and 12 months after treatment. Mean follow-up was 9.8 months (standard deviation=2.3) with a range of 5-12 months.

Results

The duration of intravitreal TA effects on macular thickness and visual acuity increased with increasing dosage. An observed increase in intraocular pressure induced by TA was not significantly associated with dosage.

Conclusions

In patients with diffuse diabetic macular edema who receive intravitreal TA, effects may last longer after a dosage of 25 mg, than after lower doses of 8 mg or 4 mg.     

Intravitreal diclofenac versus intravitreal bevacizumab in persistent diabetic macular edema: Anatomical and functional outcome

Purpose

To compare the efficacy of diclofenac versus bevacizumab following single intravitreal injection in eyes with persistent diabetic macular edema.

Intravitreal Triamcinolone Injection for Uveitic Macular Edema: A Randomized Clinical Study

Abstract

Purpose: To evaluate the additive effect of intravitrial triamcinolone (TA) injection in uveitic macular edema compared to systemic anti-inflammatory treatment only.

Methods: Patients were randomized into the intravitreal TA injection group and the sham group. All patients received systemic anti-inflammatory treatment with follow-up monthly to 6 months, with additional treatment as needed.

Results: Fifty eyes of 50 patients were enrolled. Central foveal thickness decreased significantly from month 1 in the TA group, and from month 3 in the sham group. Parafoveal area thickness significantly decreased in both groups from month 1, with greater decrease in the TA group at months 2 and 3. Leakage area on fluorescein angiography was significantly smaller in the TA group at months 1 to 3. Intraocular pressure increased in the TA group at months 1 and 2.

Conclusions: Intravitreal TA injection showed earlier reduction of leakage and retinal edema compared to systemic anti-inflammatory treatment alone.     

正常兔眼玻璃体微泡注射联合超声辐照干预中最适超声参数的筛选

背景 微泡可作为药物和基因的转染载体,经超声照射后转染效率提高,从而在多种眼科疾病的治疗方面发挥重要作用.然而,不同超声辐照强度发挥的生物学效应有所不同. 目的 筛选适用于正常兔视网膜组织的超声辐照强度和时间,为超声联合微泡治疗眼底疾病的研究提供实验依据.方法 选取18只清洁级新西兰大白兔,按照随机数字表法分为空白对照组、单纯超声辐照组、单纯玻璃体腔注射组及玻璃体腔注射+低、中、高强超声辐照组.空白对照组未给予任何处理,单纯超声辐照组和单纯玻璃体腔注射组分别给予2.0 W/cm2的超声强度照射实验眼60 s或单纯玻璃体腔注射0.1ml微泡,玻璃体腔注射+低、中、高强超声辐照组兔眼在玻璃体腔注射0.1ml微泡后分别用0.5、1.0和2.0 W/cm2超声强度照射实验眼60 s.各组于术前、术后即刻、术后第1天、第7天分别行眼前节照相、直接检眼镜检查和彩色眼底照相观察眼前节和眼底情况,于术后第7天处死实验兔并分离视网膜,行苏木精-伊红染色,光学显微镜下观察实验眼视网膜形态学改变,透射电子显微镜观察兔视网膜超微结构变化.结果 空白对照组、单纯超声辐照组、单纯玻璃体腔注射组及玻璃体腔注射+低、中、高强超声辐照组兔手术前后不同时间点眼前后节均未见明显异常.术后7d,光学显微镜下可见空白对照组、单纯超声辐照组、单纯玻璃体腔注射组和玻璃体腔注射+低超声辐照组兔10层视网膜组织结构清晰,未见炎症、变性及细胞坏死等改变,而玻璃体腔注射+中强超声辐照组和玻璃体腔注射+高强超声辐照组兔眼视网膜各层组织结构疏松,视细胞层排列紊乱,内核层和外核层不同程度变薄,视网膜神经节细胞(RGCs)数量减少,可见细胞的空泡样变性.透射电子显微镜下可见空白对照组、单纯超声辐照组、单纯玻璃体腔注射组及玻璃体腔注射+低强超声辐照组兔视网膜超微结构未见明显异常改变,而玻璃体腔注射+中强超声辐照组和玻璃体腔注射+高强超声辐照组兔眼视细胞排列紊乱,内核层和外核层细胞数目减少,细胞排列紊乱,细胞核染色质不均匀,RGCs数目减少.结论 适用于正常兔视网膜组织的理想超声参数为超声强度0.5 W/era2辐照60 s,这一结果为超声联合微泡治疗眼底疾病的研究提供了实验依据.     

Presumed necrotizing viral retinitis after intravitreal triamcinolone injection: case report

A 56-year-old man presented with anterior chamber inflammation, increased intraocular pressure, peripheral retinal infiltration, and generalized retinal arterial obstruction suggesting acute retinal necrosis five months after intravitreal triamcinolone acetonide injection (IVTA). He was treated with intravenous antiviral agents and aspirin. Shortly after treatment, retinal infiltrations were resolved, and partial recanalization of the obstructed vessel was observed. Viral retinitis may occur as an opportunistic infection following IVTA due to the local immune modulatory effect of the steroid; hence, close observation following IVTA is necessary.     

外伤性眼内炎玻璃体切除联合注药的临床观察

目的 探讨玻璃体切除联合玻璃体腔内注药治疗外伤性眼内炎的临床效果。方法 回顾性分析我院1998年10月－1999年10月收治的16例外伤性眼内炎的临床资料。结果 16眼术后炎症均得到控制,眼球得以保留,视力均有提高,半年后7例行人工晶状体植入术,最好视力达0.8。结论 玻璃体切除联合玻璃体腔内注药是治疗外伤性眼内炎的最佳选择。     

Intravitreal injection of bevacizumab and gas for diabetic premacular hemorrhage with active fibrovascular proliferation

Background  To report the effect of intravitreal injection of bevacizumab and gas for the treatment of diabetic premacular hemorrhage with active fibrovascular proliferation. Methods  Six eyes of six consecutive patients with acute diabetic premacular hemorrhage and active fibrovascular proliferation received intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) and C3F8 (0.2–0.3 mL) during the same setting. All six cases had panretinal photocoagulation prior to the procedure. After treatment, patients maintained a prone position for 3 days and were followed for an average of 8 months (range, 4–13 months). Results  All six eyes had complete reabsorption of the hemorrhage and reduction of fibrovascular proliferation. Transient vitreous opacification from breakthrough of the blood were observed in all eyes. An average of 3.8 weeks (range, 1–6 weeks) was required for the clearing of preretinal hemorrhage. Visual acuity improved in all six eyes. No recurrent bleeding or other adverse events were encountered in all cases. Conclusions  Intravitreal injection of bevacizumab and gas may be an effective method for treating acute diabetic premacular hemorrhage with active fibrovascular proliferation. The authors do not have any proprietary interests in the material used in this study. The authors have full control of all primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review the data upon request. ClinicalTrials.gov ID: NCT00673296. The study was approved by the institutional research board of National Taiwan University Hospital (NTUH-REC No. 200711050R).     

Comparison of Injection of Intravitreal Drugs with Standard Care in Macular Edema Secondary to Branch Retinal Vein Occlusion

Purpose

To compare the long-term efficacy and safety of intravitreal triamcinolon with or without rescue laser therapy (intravitreal triamcinolone injection [IVTA] group), bevacizumab with or without rescue laser treatment (intravitreal bevacizumab injection [IVB] group), or a combination of both with or without rescue laser therapy (IVTA + IVB group), with standard care for patients with macular edema secondary to branch retinal vein occlusion (BRVO).

Methods

We reviewed the medical records of 151 patients treated with intravitreal injection with or without rescue laser for treatment of macular edema caused by BRVO, and who were followed up at 1, 3, 6, 12, and 24 months. During the observation period, rescue grid laser or repeated intravitreal injection with initial drug was performed if recurrence of macular edema was confirmed. Visual acuity, change in visual acuity, and intraocular pressure were compared in each phase.

Results

Totals of 16%, 5.6%, and 0% of participants in the three groups showed significant visual loss of more than three lines of the Snellen chart at last follow-up. The IVTA group was the least effective treatment modality, with statistical significance. The development rates of elevated intraocular pressure were similar among the groups.

Conclusions

Although IVTA yielded effects similar to those of standard grid photocoagulation based on the Standard Care vs Corticosteroid for Retinal Vein Occlusion study, IVB or IVTA + IVB with or without rescue laser treatment resulted in improvement in visual acuity at 24 months after the start of treatment and was associated with few serious adverse side effects. Thus, these approaches could be useful for treating macular edema arising secondary to BRVO.     

Intravitreal triamcinolone acetonide for the management of papillophlebitis and associated macular edema

Background To investigate the efficacy of intravitreal injection of triamcinolone acetonide in the management of papillophlebitis and associated cystoid macular edema. Methods This study was a retrospective medical records review of four eyes of four patients (three males and one female) who had approximately 2-4 months history of papillophlebitis and associated persistent cystoid macular edema. These patients were treated with a single intravitreal injection of 4 mg triamcinolone acetonide. Mean follow-up time was 15 +/- 4 months. The outcome measures included best corrected visual acuity (BCVA), intraocular pressure (IOP), and central retinal thickness by optical coherence tomography (OCT). Results The BCVA ranged from 20/100 to 20/60 pre-operation. The mean gain in BCVA was 7 +/- 1 Snellen lines. All eyes had BCVA of 20/20 at the last visit. The mean baseline central retinal thickness as measured by OCT was 529 +/- 53 mum. The mean central retinal thickness by OCT was 235 +/- 15 mum at 1-week follow-up examination. At the last visit the mean central retinal thickness by OCT was 161 +/- 7 mum. One patient experienced an increase in IOP after the first injection and another patient had IOP elevation after the second injection. Both were well controlled with single topical anti-glaucoma medication. Conclusion Intravitreal injection of triamcinolone acetonide appears to be an effective treatment for patients with papillophlebitis and associated cystoid macular edema.     

兔眼玻璃体腔注射替考拉宁眼内药代动力学研究

背景 眼内炎是严重的感染性眼病,早期有效的药物治疗至关重要.替考拉宁眼内用药治疗眼内炎及眼内药代动力学方面的研究文献报道较少.目的 探讨兔眼玻璃体腔注射替考拉宁眼内药代动力学过程及特点.方法 取日本大耳白兔33只,右眼玻璃体腔注射替考拉宁0.5 mg后,分别于15 min、30 min和1、2、4、6、12、24、48、96、192 h抽取玻璃体及房水各0.1ml,采用微生物检定法测定替考拉宁的质量浓度.结果 替考拉宁标准品质量浓度的对数值随着抑菌圈直径的增加而增加,其标准品回归曲线方程:Y=0.174X-0.813(R2 =0.999),在替考拉宁质量浓度为1.0-80.0 mg/L范围内线性关系良好.替考拉宁玻璃体腔单次注射符合开放性二室模型,玻璃体腔分布相Tα1/2与消除相Tβ1/2分别为1.68 h、152.15 h,房水中分布相T1/2与消除相Tβ1/2分别为2.83 h、70.56h.替考拉宁在玻璃体、房水中的峰质量浓度分别为(358.47±21.53)mg/L、(102.17±9.54)mg/L,达峰时间分别为1h;在192 h时,玻璃体、房水中替考拉宁质量浓度分别为(4.38±0.68)mg/L、(2.38±0.38)mg/L.结论 替考拉宁0.50 mg玻璃体腔注射后能在玻璃体、房水中维持较长时间的药物治疗质量浓度.     

玻璃体腔注射甲氨蝶呤治疗原发性眼内淋巴瘤的临床研究

目的观察玻璃体腔注射甲氨蝶呤(MTX)个体化治疗原发性眼内淋巴瘤(PIOL)的疗效和安全性。 方法收集2013年4月至2019年12月于首都医科大学附属北京朝阳医院眼科就诊的PIOL患者20例(30只眼)的临床资料进行研究。其中，男性6例(6只眼)，女性14例(24只眼)。患者年龄34~81岁，平均年龄(55.9±12.4)岁。所有患者肿瘤性质均为弥漫性大B细胞淋巴瘤。治疗方案为"根据淋巴瘤临床表现"的个体化治疗，所有患眼均接受单次玻璃体腔注射MTX(400 μg：0.1ml)治疗。如出现玻璃体混浊加重、眼底病灶范围扩大或IL-10/IL-6比值增高行再次注射。自治疗开始随访12~30个月。所有患眼均行最佳矫正视力(BCVA)、眼压、裂隙灯显微镜、彩色眼底照相、光学相干断层扫描(OCT)及荧光素眼底血管造影(FFA)检查并行房水或玻璃体IL-10/IL-6浓度检测。BCVA转换为LogMAR视力和眼压的检查数据先行正态性检验。眼压符合正态分布采用±s表示，治疗前后眼压的比较采用配对t检验；BCVA不符合正态分布，采用中位数和上下四分位数表示，治疗前后BCVA的比较采用Wilcoxon配对秩和检验。裂隙灯显微镜检查、彩色眼底照相、OCT、FFA及IL-10/IL-6的比值采用文字形式进行描述。 结果治疗前后LogMAR视力中位数为0.75(0.47，1.43)和0.4(0.2，0.57)，差异具有统计学意义(Z＝3.43，P<0.05)。治疗前后眼压分别为(16.56±4.31)mmHg(1 mmHg＝0.133 kPa)和(16.13±3.87)mmHg，差异无统计学意义(t＝0.40，P>0.05)。所有患者经玻璃体腔注射MTX治疗后玻璃体混浊程度较治疗前好转者有12例(19只眼)，占63%(19/30)；视网膜下黄白色奶油样浸润灶减轻或消失者有15例(20只眼)，占66%(20/30)；视网膜色素上皮下的高反射病灶减轻或消失的为13例(18只眼)，占60%(18/30)。注射次数为1~8次，平均(3.00±2.37)次。 结论"根据淋巴瘤临床表现"进行个体化玻璃体腔注射MTX治疗PIOL安全有效，可达到临床缓解。