The effect of non-steroidal anti-inflammatory drugs on inflammatory cystoid macular edema

PURPOSE: To assess the role of systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory cystoid macular edema (iCME). DESIGN: Pilot study. METHODS: We included 66 patients with iCME and treated them with naproxen (2 x 250 mg daily; n = 28) or rofecoxib (1 x 25 mg daily; n = 38). After 4 months of therapy, visual acuity and inflammation activity were measured. We evaluated the grade of CME, retinal vasculitis, and papillary leakage with fluorescein angiography. RESULTS: No clear effect of NSAIDs on iCME, visual acuity, and intraocular inflammation was observed. A beneficial effect was noted in less than 8% of the affected eyes. The drop-out rate after 4 months of treatment was 52%, because of adverse effects or inefficacy of the treatment. Improvement of visual acuity was slightly better in patients who were treated with naproxen compared with rofecoxib (P < or = .05). CONCLUSION: Systemic NSAIDs have a limited role (if any) in the treatment of iCME.     

A comparative analysis of topical corticosteroids and non-steroidal anti-inflammatory drugs to control inflammation and macular edema following uneventful phacoemulsification

Purpose:To compare the efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and prednisolone acetate in controlling inflammation and preventing cystoid macular edema (CME) after uneventful phacoemulsification.Methods:All patients who underwent uneventful phacoemulsification from December 2020 to Feb 2021 were included in the study. These were randomly assigned to receive any one anti-inflammatory agent among topical nepafenac (0.1%) [96 eyes], bromfenac (0.07%) [93 eyes], preservative-free ketorolac (0.4%) [94 eyes], nepafenac (0.3%) [96 eyes], or prednisolone acetate (1%) [91 eyes]. The efficacy of the drugs was evaluated by comparing the grade of anterior chamber (AC) cells, conjunctival hyperemia, pain score, visual acuity, intraocular pressure (IOP), and central macular thickness (CMT) at 1 and 6 weeks after surgery.Results:At 1 and 6 weeks, there was no significant difference in pain score, conjunctival hyperemia, AC cells, change in IOP, and visual acuity between the prednisolone and the NSAIDs groups, though nepafenac 0.3% was most effective. At 6 weeks, there was no significant difference in the number of patients developing subclinical CME in the prednisolone versus NSAID group. The mean increase in CMT was significantly lower in nepafenac 0.3% than prednisolone at 1 and 6 weeks (P = 0.003 and 0.004, respectively).Conclusion:NSAIDs used in isolation are comparable to prednisolone in preventing inflammation and pain after uneventful phacoemulsification. However, nepafenac 0.3% is most comparable to prednisolone and more efficacious in reducing the incidence of CME. We recommend that nepafenac 0.3% can be used as a sole anti-inflammatory agent in patients with uneventful phacoemulsification.     

Treatment of pseudophakic cystoid macular edema

Pseudophakic cystoid macular edema (PCME) is the most common complication following cataract surgery. In 1-3% of cases it is associated with a decrease in visual acuity. However, PCME has a good prognosis, persisting in only 10% of the patients beyond 2 years. The prophylactic therapy of eyes without additional disease with non-steroidal antiphlogistic drugs or steroids does not influence the final visual acuity. Under certain circumstances, prophylaxis can be a reasonable option. Risk factors that promote the formation of PCME are discussed. The course of acute or chronic PCME can be influenced by drug treatment, but in general the level of evidence for the treatment of this widespread problem is low. We would therefore like to present the Freiburg treatment scheme for PCME for discussion.     

非甾体抗炎药的不同给药时机对超声乳化吸除术后CME影响的Meta分析

目的：系统评价白内障超声乳化吸除术前加用非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)对术后黄斑囊样水肿(cystoid macular edema,CME)的影响。

方法：计算机检索Cochrane Library、PubMed、BMC、中国期刊全文数据库(CNKI)、维普中文期刊数据库(VIP)。收集NSAIDs的不同给药时机(试验组予以NSAIDs术前及术后局部点眼治疗,对照组予以NSAIDs术后治疗)对白内障超声乳化吸除术后CME及黄斑中心凹厚度影响的临床随机对照试验文献。采用RevMan 5.2软件及Stata12.0软件进行Meta分析。

结果：共纳入6项研究。术前是否加用NSAIDs对白内障超声乳化吸除术后CME的发生在术后1wk差异无统计学意义(OR=1.58,95%CI：0.48～5.18,P>0.05)、术后1mo差异无统计学意义(OR=0.78,95%CI：0.30～2.00,P>0.05),术后3mo差异有统计学意义(OR=0.22,95%CI：0.11～0.43,P<0.01); 黄斑中心凹厚度在术后1wk差异无统计学意义(WMD=-7.20,95%CI：-15.17～0.77,P>0.05)、术后1mo差异无统计学意义(WMD=-3.98,95%CI：-14.05～6.08,P>0.05),术后3mo差异有统计学意义(WMD=-18.25,95%CI：-33.80～-2.70,P<0.05)。

结论：术前及术后联合应用NSAIDs治疗可以显著降低白内障超声乳化吸除术后CME的发生,降低术后黄斑中心凹的厚度,提示NSAIDs的术前术后联合应用较单独术后应用更具有优越性。     

Posterior sub-Tenon's injections of corticosteroids in uveitis patients with cystoid macular edema

Cystoid macular edema (CME) is a major cause of visual impairment and is thought to be due to abnormal perifoveal capillary permeability. Posterior sub-Tenon's corticosteroid injections are used to improve the visual acuity in CME, although their mechanism of action is uncertain. In this study, visual acuity, blood retinal barrier (BRB) permeability, and fluorescein angiograms were recorded immediately before and one and four weeks after the administration of steroid injections. Ten patients (12 treated eyes) with CME secondary to uveitis were studied. Visual improvement, defined as an increase in at least two lines of Snellen visual acuity, was seen in half of the treated eyes. In some patients, these improvements were not directly related to changes in the BRB permeability or the amount of macular fluid. Posterior sub-Tenon's corticosteroid injections do not consistently affect blood retinal barrier permeability.     

非甾体类抗炎药预防白内障术后黄斑囊样水肿的Meta分析

目的：系统评价非甾体类抗炎药物对白内障术后黄斑囊样水肿的预防作用。

方法：计算机检索PubMed、EMbase、Cochrane Library、Medline、CNKI、万方、维普及中国生物医学文献数据库收录的,因特网搜索的截止到2015-03有关非甾体类抗炎药物对白内障术后黄斑囊样水肿预防作用研究的随机对照试验(RCT), 同时手工检索相关书籍、期刊和会议论文及其参考文献。按照纳入和排除标准限定研究对象,针对白内障术后黄斑囊样水肿发生率,使用Cochrane协作网提供的RevMan5.2软件进行Meta分析。

结果：7项研究纳入分析(共1422例,其中治疗组712例,对照组710例),白内障手术前后使用非甾体类抗炎药进行治疗,可显著降低术后黄斑水肿发生率(OR=0.31,95%CI：0.18～0.52,P<0.01)。

结论：白内障手术前后使用非甾体类抗炎药进行治疗,可显著降低术后黄斑水肿发生率,预防白内障术后黄斑水肿的发生,由于纳入研究的样本量偏小,且方法学质量中等,致使本系统评价结果论证强度不高,因此还需要开展更多的高质量的临床随机对照研究,以便更客观、准确、全面地评价。     

Pseudophakic cystoid macular edema

Cystoid macular edema (CME) following cataract surgery has been recognized for over 50 years as an important cause of suboptimal post-operative vision. The incidence of CME varies widely, but is likely in the range of 1-2% using modern cataract extraction techniques. The diagnosis of CME can generally be made on clinical examination with evidence of perifoveal cystic spaces and can be confirmed with use of fluorescein angiography to document the classic petaloid pattern of leakage mainly into the outer retina. Leak from perifoveal vessels is induced by inflammatory mediators and results in intraretinal fluid accumulation and corresponding decrease in retinal function. The risk factors most associated with CME; rupture of posterior capsule, vitreous loss, iris incarceration, use of iris fixated lenses, active uveitis and diabetes, may all increase the potency of these mediators and exacerbate post-operative CME. The treatment of CME remains controversial but generally starts with conservative observation in isolated angiographic cases and progresses through topical non-steroidal anti-inflammatory agents (NSAIDs), topical steroids, peri-ocular steroids, systemic steroids and surgical intervention in refractory cases. Even more controversial is the role of NSAID prophylaxis peri-operatively in preventing clinical CME. Though the data is tantalizing in the short term, there is little to support the long-term benefit of such prophylaxis with respect to visual outcomes.     

两种非甾体抗炎药对白内障术后黄斑水肿影响的对比研究

目的比较0.1%溴芬酸钠水合物滴眼液和普拉洛芬滴眼液对白内障超声乳化术后黄斑水肿的影响。方法采用前瞻性临床随机对照试验。将行白内障超声乳化吸除联合人工晶状体植入术的年龄相关性白内障患者随机分为两组,每组118只眼。A组:术前2 d和术后4周应用0.1%溴芬酸钠水合物滴眼液,联合术后2周应用妥布霉素地塞米松滴眼液;B组:术前2 d和术后4周应用普拉洛芬滴眼液,联合术后2周应用妥布霉素地塞米松滴眼液。分别在术前2 d内,术后1 d、1、4、12周测定黄斑中心亚区域平均厚度(CSMT),并计算术后黄斑水肿发生率。结果术前、术后1 d、1周、12周A组与B组CSMT比较,差异均无统计学意义(P>0.05);术后4周A组CSMT为(251.57±6.814)μm,低于B组的(254.40±12.004)μm,差异有统计学意义(P<0.05);术后1 d、1、4、12个月试验组黄斑水肿发生率分别为0、0、0.85%、0.85%,对照组分别为0、0.85%、1.69%、1.69%,术后各时间点两组黄斑水肿发生率比较,差异均无统计学意义(P>0.05)。结论白内障超声乳化术前和术后应用0.1%溴芬酸钠水合物滴眼液或普拉洛芬滴眼液,术后黄斑水肿发生率均较低,前者比后者可能会更大程度地抑制术后黄斑中心亚区域增厚。     

Inflammatory cystoid macular edema

PURPOSE OF REVIEW: The aim of this article is to update our current understanding and management of inflammatory cystoid macular edema. RECENT FINDINGS: Cystoid macular edema is a common cause of visual loss in uveitis, which occurs predominantly in older patients with chronic uveitis forms and might be heralded by subclinical changes on optic coherence tomography. Cystoid macular edema is emerging as a major cause of visual loss in HIV-infected patients with immune recovery uveitis. Elevated levels of proinflammatory cytokines and vascular endothelial growth factor were found in all types of cystoid macular edema. Treatment with anti-inflammatory and anti-vascular endothelial growth factor drugs is widely applied for all forms of cystoid macular edema and usually has a beneficial, but temporary effect. So far, there are no clear guidelines for the treatment of subclinical cystoid macular edema in uveitis. The effect of vitrectomy in inflammatory cystoid macular edema is not yet clear and might become more important in the future. Recent advances in management include intravitreal drug delivery systems of cystoid macular edema-modifying drugs. SUMMARY: This review summarizes current thoughts on inflammatory cystoid macular edema focusing on the new, clinically relevant findings. Upcoming data on aqueous constituents in cystoid macular edema and imaging with the new generation of optic coherence tomography offer the hope that a better treatment strategy will soon be established.     

Pseudophakic cystoid macular edema

Cystoid macular edema (CME) following cataract surgery has been recognized for over 50 years as an important cause of suboptimal post-operative vision. The incidence of CME varies widely, but is likely in the range of 1-2% using modern cataract extraction techniques. The diagnosis of CME can generally be made on clinical examination with evidence of perifoveal cystic spaces and can be confirmed with use of fluorescein angiography to document the classic petaloid pattern of leakage mainly into the outer retina. Leak from perifoveal vessels is induced by inflammatory mediators and results in intraretinal fluid accumulation and corresponding decrease in retinal function. The risk factors most associated with CME; rupture of posterior capsule, vitreous loss, iris incarceration, use of iris fixated lenses, active uveitis and diabetes, may all increase the potency of these mediators and exacerbate post-operative CME. The treatment of CME remains controversial but generally starts with conservative observation in isolated angiographic cases and progresses through topical non-steroidal anti-inflammatory agents (NSAIDs), topical steroids, peri-ocular steroids, systemic steroids and surgical intervention in refractory cases. Even more controversial is the role of NSAID prophylaxis peri-operatively in preventing clinical CME. Though the data is tantalizing in the short term, there is little to support the long-term benefit of such prophylaxis with respect to visual outcomes.     

Pseudophakic cystoid macular edema

Cataract surgery is an efficient procedure, and is generally associated with good visual results. Nevertheless, cystoid macular edema (CME) may develop, and this can result in suboptimal postoperative vision. Many factors are considered to contribute to its development, and although the treatment options depend upon the underlying cause of CME, the usual therapeutic approach for prophylaxis and treatment of CME is directed towards blocking the inflammatory mediators. This article provides a review of possible risk factors, pathogeneses, incidence rates, and methods of diagnosis, as well as the current guidelines for managing CME.     

Prostaglandins and cystoid macular edema

This review discusses the roles and interactions of prostaglandins and other possible chemical mediators in cystoid macular edema. Prostaglandins have been studied as a potential causative factor of cystoid macular edema following cataract/intraocular lens surgery. The authors' hypothesis and data with regard to the mechanisms of postoperative cystoid macular edema and other inflammatory conditions are presented. The effects of nonsteroidal anti-inflammatory drugs, which are antagonists of prostaglandin biosynthesis, on postoperative inflammatory conditions including cystoid macular edema are also reviewed. Lastly, a mechanism for the induction of cystoid macular edema by anti-glaucoma eyedrops, including prostaglandin analogs is proposed. The results from two clinical trials recently conducted by the authors suggest that the preservative rather than the active ingredient is the causative factor.     

Pathomechanisms of cystoid macular edema

Cystoid macular edema (CME) is a well-known endpoint of various ocular diseases, but the relative pathogenic impact of extra- and intracellular fluid accumulation within the retinal tissue still remains uncertain. While most authors favor an extracellular fluid accumulation as the main causative factor of cyst formation, there are indications that Müller cell swelling may also contribute to CME development (particularly in cases without significant angiographic vascular leakage). Vascular leakage occurs after a breakdown of the blood-retinal barrier during traumatic, vascular, and inflammatory ocular diseases, and allows the serum to get into the retinal interstitium. Since intraretinal fluid distribution is restricted by two diffusion barriers, the inner and outer plexiform layers, serum leakage from intraretinal vessels causes cysts mainly in the inner nuclear layer while leakage from choroid/pigment epithelium generates (in addition to subretinal fluid accumulation) cyst formation in the Henle fiber layer. In the normal healthy retina, the transretinal water fluxes are mediated by glial and pigment epithelial cells. These water fluxes are inevitably coupled to fluxes of osmolytes; in the case of glial (Müller) cells, to K(+) clearance currents. For this purpose, the cells express a complex, microtopographically optimized pattern of transporters and channels for osmolytes and water in their plasma membrane. Ischemic/hypoxic alterations of the retinal microvasculature result in gliotic responses which involve down-regulation of K(+) channels in the perivascular Müller cell end-feet. This means a closure of the main pathway which normally generates the osmotic drive for the redistribution of water from the inner retina into the blood. The result is an intracellular K(+) accumulation which, then, osmotically drives water from the blood into the glial cells (i.e., in the opposite direction) and causes glial cell swelling, edema, and cyst formation. While the underlying mechanisms await further research, it is expected that their improved knowledge will stimulate the development of novel therapeutic approaches to resolve edema in retinal tissue.     

Antiretinal antibodies associated with cystoid macular edema

AIM: Recently, anti-Enolase and anti-carbonic anhydrase antibodies have been observed in over 60% of patients with retinitis pigmentosa (RP) and cystoid macular oedema (CME). We investigated the presence of these antibodies in a series of patients with CME due to different pathologies. METHODS: In 10 patients with CME serum antibodies against Carbonic anhydrase (CA) II (30 kD) and Enolase (46 kD) were sought using Western Blots, Dot Blots as well as ELISA. RESULTS: Western and dot blotting showed anti-CA II antibodies in all and anti-Enolase antibodies in six of the 10 patients. The average titer measured with ELISA was 0.9 +/- 0.08 OD Units (0.35-1.4) with a dilution of 1:400. CONCLUSION: The presence of anti-retinal antibodies in the serum of all patients confirms the high prevalence of these antibodies in patients with CME. This may suggest that a dysfunction of CA and enolase activity in the retinal pigment epithelium may lie at the root of oedema formation, whereas other mechanisms may be responsible in the absence of these antibodies.