Effect of mitomycin C on ciliary body and intraocular pressure with various application depths: an experimental study

BACKGROUND: To evaluate the effects of mitomycin C (MMC) on intraocular pressure (IOP) and ciliary body via transmission electron microscopy when applied under conjunctiva or different depths of sclera, without performing any filtering surgery. METHODS: Thirty-six eyes of 36 New Zealand albino rabbits were used in this study. MMC was prepared in a concentration of 0.4 mg/mL and 0.05 cc (20 microg) was soaked in preprepared sterile surgical sponges. Six groups each consisting of six eyes were formed and IOP was measured preoperatively. Group 1 was the control group: the superior conjunctiva was opened and only irrigated with balanced salt solution (BSS). In group 2, MMC soaked sponges were applied under the conjunctiva. In groups 3 and 4, a scleral flap of approximately 1/3 scleral thickness was prepared and in groups 5 and 6, and a scleral flap of approximately 2/3 scleral thickness was prepared, all with a standard size of 4 x 4 mm. MMC soaked sponges were applied under these areas for 5 min in eyes in groups 3 and 5 followed by an irrigation of the relevant areas with 10 cc BSS, whereas only irrigation with BSS was done in groups 4 and 6 as control groups. No filtering procedure was performed in any of the eyes. Eyes were enucleated on the 30th day following measurement of IOP and the ciliary body regions were evaluated using transmission electron microscopy. Kruskal-Wallis test was used for the statistical assessment of IOP between groups. RESULTS: The deep scleral flap group (group 5) showed statistically significantly more IOP reduction than both the superficial scleral flap group (group 3; P = 0.004) and the subconjunctival group (group 2; P = 0.002) on postoperative day 30. Electron microscopic evaluation of the surgical groups revealed a wide range of different histopathological effects due to different MMC application methods. The histopathological changes were more evident in the group 5, where MMC was applied under deep scleral flap. CONCLUSIONS: Subscleral application of MMC seems to provide greater IOP decrease than subconjunctival application, possibly caused by a more significant ciliary body toxicity. This may be the beginning of a non-penetrating, easy to perform and safe method to decrease IOP in glaucoma patients, which the authors call 'toxic ciliary ablation surgery'. However, the long-term results and complications must be assessed with further studies.     

The toxicology of mitomycin C on the ciliary body

Over the past few years, the use of mitomycin C (MMC) to reduce surgical failures following filtering procedures has largely increased. After topical application, significant amounts of MMC can be detected intraocularly. In both rabbit and human eyes, a reduction of the normal and elevated intraocular pressures could be achieved with subconjunctival injections of MMC without filtering procedures. Histopathologic examination of the ciliary body in a human eye shortly after surgery with MMC revealed moderate, diffuse toxic changes of the two layers of the ciliary epithelium. By fluorophotometry, eyes after trabeculectomy with MMC had a decreased production of aqueous humor compared with eyes that underwent trabeculectomies without antimetabolites. Independent studies suggest that the toxicity of MMC for the ciliary epithelium may be a significant factor contributing to postoperative hypotony.     

PRK和LASIK对非接触眼压计测量值的影响

目的 :研究PRK和LASIK手术前后非接触眼压计 (NCT)测量值的改变及其与切削深度的相关性。方法 :对不同屈光度患者 673只眼 (PRK 3 2 5眼、LASIK 3 48眼 )术前、术后 3、 6、 12个月的眼压、角膜厚度及切削深度 ,应用统计学方法检验 ,并对眼压改变值与术中角膜切削深度作相关性分析。结果 :术后角膜厚度随屈光度增加而变薄 ,LASIK组大于PRK组 :NCT测量值均明显低于术前 ,差异有显著性 (P <0 0 5 ) ,但LASIK组与PRK组差异无显著性。术后一年眼压下降值与术中角膜切削深度存在统计学上的相关性 :PRK组r =0 2 85 6,LASIK组r =0 2 5 3 8。结论 :PRK和LASIK术后NCT测量结果下降 ,角膜变薄是其主要原因。     

PRK与LASIK术后角膜表面形态改变对NCT眼压读数的影响

目的：探讨ＰＲＫ和ＬＡＳＩＫ术后眼压明显低于术前的相关因素。方法：对不同屈光度患者８０４只眼术前、术后的眼压、角膜厚度及切削深度，应用统计学方法检验对眼压测量的影响。结果：角膜厚度随屈光度增加而变薄，术前眼压与屈光度和角膜厚度无关，所有患者术后６个月眼压明显低于术前，且高度近视组低于中低度组，有显著性差异（Ｐ＜０．０１）。结论：患者术后眼压降低的原因可能主要由于手术导致角膜中央变薄，前弹力层被破坏，使角膜形态学改变，由此引发气体动力学的变化，使得气体压平眼压计读数发生误差，眼压值变低。故应对气体眼压计读数进行修定，防止屈光性手术后激素性青光眼的漏诊造成的视功能损害。     

外伤性白内障摘出后房型人工晶状体植入术后虹膜和睫状体病理形态学实验研究

动态观察兔眼外伤性白内障摘出及后房型人工晶状体植入术后虹膜和睫状体的病变特征，发现眼内炎症反应的早期为急性炎症和渗出性改变，中期为亚急性炎症和肉芽组织形成，后期炎症趋向慢性化，出现纤维化改变。测定结果表明，外伤性白内障摘出及人工晶状体植入术后在虹膜和睫状体内的炎症细胞数增高，术后第1和14天嗜中性粒细胞和巨噬细胞，术后第7和14天嗜酸性粒细胞高于单纯晶状体囊外摘除组，差异有显著性。     

Effects of topical anaesthetics and repeated tonometry on intraocular pressure

Purpose: To investigate the effects of repeated measurements of intraocular pressure (IOP) using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) to identify mechanisms contributing to the expected IOP reduction. Methods: A prospective, single‐centre study with six healthy volunteers. Consecutive repeated series (six measurements/serie/method) were made alternately on both eyes for 1 hr with oxybuprocaine/fluorescein in the right eye and tetracaine in the left. The left eye was Pentacam^® photographed before and repeatedly for 20 min after the IOP measurements. On a separate occasion, the same volunteers received the same amount of anaesthetic drops for 1 hr but without repeated IOP measurements. Results: A significant IOP reduction occurred with both ART and GAT in the oxybuprocaine‐treated eye, ?4.4 mmHg and ?3.8 mmHg, respectively and with ART in the tetracaine eye, ?2.1 mmHg. There was a significant difference in IOP reduction between the oxybuprocaine and tetracaine eyes with ART. There was a significant drop in anterior chamber volume (ACV) immediately after the IOP measurements, ?12.6 μl that returned to pretrial level after 2 min. After 1 hr of receiving anaesthetic eye drops (without IOP measurements), the IOP decreased significantly in the oxybuprocaine eye for both ART and GAT, ?3.1 and ?1.7 mmHg, respectively, but not in the tetracaine eye (p = 0.72). Conclusion: The IOP reduction cannot be explained solely by aqueous humor being pressed out of the anterior chamber. While significant IOP reduction occurred with both tetracaine and oxybuprocaine after repeated mechanical applanation, the IOP reduction was significantly greater with oxybuprocaine.     

丝裂霉素C对青光眼小梁切除术后眼内压和眼血流的影响

目的：：分析丝裂霉素C对青光眼小梁切除术后眼内压和眼血流的影响,探讨其有效性和安全性。方法：将103例青光眼患者随机分为两组,均给予青光眼小梁切除术,观察组在术中行丝裂霉素C抗瘢痕治疗;术后完成6~12 mo随访,对比两组患者的临床眼压控制疗效、并发症发生率及视网膜中央动脉血流动力学指标。结果：观察组临床疗效优于对照组(P<0.05);两组患者的总并发症发生率无统计学差异(P>0.05),但并发症类型有所区别,观察组多发生低眼压和畏光症状,对照组多发生瘢痕性阻塞。治疗前,两组患者的眼压动力学指标无统计学差异(P>0.05);治疗后1mo,观察组收缩期峰速( peak systolic velocity,PSV)与舒张末期血流速度( end diastolic velocity, EDV )明显低于对照组,阻力指数( resistance index,RI)与搏动指数( pulsatility index,PI)明显高于对照组,差异有统计学意义(P<0.05);治疗后6mo,观察组PSV与EDV明显高于对照组,RI与PI明显低于对照组,差异有统计学意义(P<0.05)。结论：丝裂霉素C对青光眼小梁切除术患者的术后不良影响时间较短,其长期疗效安全、可靠。     

Toxic effects of subconjunctival 5-fluorouracil and mitomycin C on ciliary body of rats

Purpose: The effects of subconjunctival injection of mitomycin C and different concentrations of 5-fluorouracil on the epithelium of the ciliary body of twenty Sprague Dawley SD rats was studied.Methods: Twenty rats were divided into four treatment groups.The first three groups received 0.2 ml of 5, 10, and 30 mg of 5-fluorouracil subconjunctivally respectively, and the fourth group 0.2 ml of 0.4 mg/ml mitomycin C subconjunctivally. The right eye received 0.2 ml of the antimetabolite,while the left eye was injected with 0.2 ml of saline subconjunctivally, as a control.The eyes were examined histologically, in a masked fashion, by light and bytransmission electron microscopy. In each treatment group, two eyes were examined after one week, and three eyes were examined one month after the subconjunctival injection. Results: Electron microscopy revealed toxic effects in the epitheliumof the ciliary body of all treatment groups. The 5-fluorouracil group revealed focal mitochondrial edema, enlargement of intercellular spaces, and dilatation of intracellular spaces. The mitomycin C group showed pyknotic nuclei,enlargement of intercellular spaces, and irregular flattened epithelial cells. Theseverity of changes correlated with concentration and length of exposure. No pathology was found by light microscopy in all groups.Conclusions: This study demonstrates that subconjunctival antimetabolites mitomycin C and 5-fluorouracil can penetrate the sclera and exert toxiceffects on the epithelium of the ciliary body, even in low doses. These changeswere only apparent by electron microscopy and were still present one month after theinjection. These findings may contribute to the theory that the application ofantimetabolites during or after surgery has a direct effect on the epithelium of the ciliary body, besides its known effect on the conjunctiva. Further studies are needed to evaluate its effect on intraocular pressure.     

丝裂霉素C对兔眼睫状体无色素上皮细胞的毒性作用

目的 观察兔眼巩膜咬切术中应用０．２ｍｇ／ｍｌ丝裂霉素Ｃ（ＭＭＣ）后,睫状体无色素上皮细胞的病理形态学的改变,探讨ＭＭＣ对睫状体的毒性作用。方法 在兔眼巩膜咬切术中用含０．２ｍｇ／ｍｌ的ＭＭＣ０．１ｍｌ的海绵块,置于Ｔｅｎｏｎ囊和巩膜之间共５分钟,并用２０ｍｌ生理盐水冲洗,术后第７天及２８天,采用光镜观察睫状体,透射电镜观察其无色素上皮细胞。结果 术后第７天睫状体无色素上皮细胞水肿,线粒体丰富、肿     

丝裂霉素C与地塞米松治疗PRK后角膜上皮下雾状混浊的对比实验研究

目的　探讨滴用丝裂霉素 C溶液治疗准分子激光屈光性角膜切削术 (excim erlaser photorefractive keratectom y,PRK)后角膜上皮下雾状混浊 (haze)的作用 ,并与地塞米松溶液对比。方法　对 4 1只新西兰白兔双眼行 PRK,术后分别给予 0 .2 g· L- 1丝裂霉素 C和 1.0 g· L- 1地塞米松滴眼治疗及平衡盐液滴眼作为对照 ,并行裂隙灯、角膜内皮镜、光镜、电镜检查。结果　术后 4、8周 ,丝裂霉素 C组与地塞米松组 haze程度相同 (P>0 .0 5 ) ,均较对照组为轻 (P<0 .0 5 )。光镜及电镜检查表明 :对照组术区角膜上皮细胞过度增生 ,前基质成纤维细胞增生活跃 ,纤维排列明显紊乱 ;而丝裂霉素 C组与地塞米松组角膜上皮细胞和前基质成纤维细胞的增生以及胶原纤维合成均受抑制 ,纤维排列较整齐。结论　丝裂霉素 C能减轻 PRK后 haze,且无明显副作用 ,可望成为防治 haze的一种新药     

Effects of topical mitomycin C on primary trabeculectomies and combined procedures.

The charts were reviewed of all patients who underwent primary trabeculectomies (group 1) or combined procedures (phacoemulsification + intraocular lens implantation + trabeculectomy--group 2) and received intraoperative mitomycin C (0.4 mg/ml) between 1991 and 1992 at Wills Eye Hospital. A total of 54 eyes of 54 patients were included: 39 in group 1 and 15 in group 2. Intraocular pressure was controlled successfully in 97.4% of eyes in group 1 (mean follow up 6.7 months), and in 93.3% in group 2 (mean follow up 6.8 months). Main complications included choroidal detachment (n = 15), shallow anterior chamber (n = 9), cataract formation (n = 8), and hypotony maculopathy (n = 3). The use of mitomycin C in primary trabeculectomies and combined procedures is associated with high success rates. However, it may be associated with unacceptable risks of vision threatening complications related to excessive filtration.     

Pigment dispersion with elevated intraocular pressure after AcrySof intraocular lens implantation in the ciliary sulcus

A 45-year-old white woman had phacoemulsification with intraocular lens (IOL) implantation. The surgery was routine except for a linear tear in the posterior capsule; there was no disruption of the anterior vitreous face. After residual soft lens matter was removed, an AcrySof IOL was placed in the ciliary sulcus. One month postoperatively, the patient presented with an intraocular pressure (IOP) of 30 mm Hg and signs of pigment dispersion with 360 degrees of heavy pigmentation of the trabecular meshwork and iris transillumination defects. Intraocular pressure was controlled with a topical beta-blocker. The optic disc appearance and visual field remained normal, but the uniocular hyperpigmentation of the trabecular meshwork was still present. We hypothesize that the sharp square edge of the AcrySof IOL increases the risk of a chafing effect on the posterior iris pigment and advocate that this IOL be placed in the capsular bag and ideally have 360 degrees of protective overlapping of the anterior capsule over the edge of the optic.     

Effect of topical mitomycin C on corneal endothelium

PURPOSE: To evaluate patients with ocular surface squamous neoplasia (OSSN) on treatment with topical mitomycin C (MMC) with regard to changes in corneal thickness and endothelial count. DESIGN: Prospective, nonrandomized, interventional series. METHODS: In this prospective evaluation, 25 patients with OSSN with different clock hours of involvement (range, one to eight), age varying from 19 to 76 years, were treated with topical MMC 0.04% in a cyclic manner. Preoperative corneal thickness measurement and endothelial cell density were obtained, and the tests were repeated after one, three, and six months of complete resolution. The fellow eyes of the same patients served as controls. RESULTS: Mean +/- standard deviation (SD) pachymetry and endothelial cell counts before and after instillation were 504.48 +/- 5.45 microm and 2325.76 +/- 192.52 cells/mm2 and 503.52 +/- 5.75 microm and 2297.60 +/- 192.08 cells/mm2, respectively, suggesting no significant difference in the above two parameters. Similarly, in the fellow control eyes, mean +/- SD pachymetry and endothelial cell counts before and after instillation were 502.80 +/- 4.34 microm and 2326.72 +/- 191.93 cells/mm2 and 504.64 +/- 5.19 microm and 2313.60 +/- 192.03 cells/mm2, respectively. CONCLUSIONS: Topical 0.04% MMC drops do not significantly affect the corneal endothelium. However, its judicious use and long-term follow-up are mandatory.