Intravitreal steroids for macular edema in diabetes

 

Abstract

Background

Macular edema is secondary to leakage from diseased retinal capillaries and is an important cause of poor central visual acuity in patients with diabetic retinopathy.

Objectives

This review evaluated the effectiveness and safety of intraocular steroids in treating diabetic macular edema (DME).

Search methods

We searched CENTRAL, MEDLINE, EMBASE in June 2007, reference lists, Science Citation Index and conference proceedings.

Selection criteria

We included randomized clinical trials (RCTs) evaluating any form of intravitreal steroids for treating DME.

Data collection and analysis

Two authors independently assessed eligibility, methodological quality and extracted data. We performed meta-analyses when appropriate.

Main results

Seven studies, involving 632 DME eyes were included. Four examined the effectiveness of intravitreal triamcinolone acetate injection (IVTA), three examined intravitreal steroids implantation (fluocinolone acetonide implant (FAI) or dexamethasone drug delivery system (DDS)). Two trials were at low risk of bias, one was at median risk of bias, two were at high risk of bias and the remaining two were at unclear risk of bias.
The preponderance of data suggest a beneficial effect from IVTA. Comparing IVTA with controls, the mean difference in visual acuity was -0.15 LogMAR (95% CI -0.21 to -0.09) at 3 months (based on three trials), -0.23 LogMAR (95% CI -0.33 to -0.13) at 6 months (two trials), -0.29 LogMAR (95% CI -0.47 to -0.11) at 9 months (one trial), and -0.11 LogMAR (95% CI -0.20 to -0.03) at 24 months (one trial), all in favor of IVTA. The relative risk (RR) for one or more lines improvement in visual acuity was 2.85 (95% CI 1.59 to 5.10) at 3 months (two trials), 1.25 (95% CI 0.66 to 2.38) at 6 months (one trial), and 2.17 (95% CI 1.15 to 4.11) at 24 months (one trial), all in favor of IVTA. We did not find evidence for three or more lines improvement in visual acuity. The mean difference in retinal thickness was -131.97 um (95% CI -169.08 to -94.86) at 3 months (two trials), -135.00 um (95% CI -194.50 to -75.50) at 6 months (one trial), -133.00 um (95% CI -199.86 to -66.14) at 9 months (one trial), and -59.00 um (95% CI -103.50 to -14.50) at 24 months (one trial), all in favor of IVTA. The RR for at least one grade macular edema resolution was 5.15 (95% CI 2.23 to 11.88) at 3 months in favor of IVTA (one trial).
Two trials reported improved clinical outcome when FAI was compared to standard of care. Beneficial effect was also observed in one dexamethasone DDS trial.
Increased intraocular pressure and cataract formation were side effects requiring monitoring and management.

Authors' conclusions

RCTs included in this review suggest that steroids placed inside the eye by either intravitreal injection or surgical implantation may improve visual outcomes in eyes with persistent or refractory DME. Since the studies in our report focused on chronic or refractory DME, the question arises whether intravitreal steroids therapy could be of value in other stages of DME, especially the earlier stages either as standalone therapy or in combination with other therapies, such as laser photocoagulation.

 

Plain language summary

Intravitreal steroids for macular edema in people with diabetes

Macular edema, swelling of the center of the retina (the part of the eye responsible for our sharpest vision), is an important cause of poor vision in patients with diabetes. New forms of therapy are desirable because the current treatment including laser photocoagulation does not control all cases of diabetic macular edema (DME) and because laser therapy may destroy normal retinal tissue. Intraocular steroids in the form of intravitreal triamcinolone acetate injection (IVTA) and surgical implantation of fluocinolone acetonide (FAI) or dexamethasone drug delivery system (DDS) are promising new therapies. This systematic review included seven randomized clinical trials involving 632 eyes from five countries evaluating the effectiveness and safety of intravitreal steroids for treating DME. Two trials were at low risk of bias, one was at median risk of bias, two were at high risk of bias, and the remaining two had an unclear risk of bias. In this systematic review, the preponderance of data suggest a beneficial effect from IVTA. The average improvement in visual acuity was 7.5 letters more (-0.15 LogMAR; 95% CI -0.21 to -0.09) in the IVTA treated eyes than in those treated with other therapies at three months (based on three trials), 11.5 letters more (-0.23 LogMAR; 95% CI -0.33 to -0.13) at six months (two trials), 14.5 letters more (-0.29 LogMAR; 95% CI -0.47 to -0.11) at nine months (one trial), and 5.7 letters more (-0.11 LogMAR; 95% CI -0.20 to -0.03) at 24 months (one trial). Improved clinical outcomes were also reported in FAI and dexamethasone DDS trials. Elevation of intraocular pressure and cataract progression occur in both IVTA and implants treated eyes but appear manageable.

 

摘要

背景

玻璃體腔內類固醇用於治療糖尿病患者的黃斑水腫

黃斑水腫是因為視網膜微血管病變造成之續發性滲漏，而且是糖尿病視網膜病變患者其中央視力變差的重要原因。

目標

這篇回顧評估眼內類固醇用以治療糖尿病黃斑水腫(diabetic macular edema (DME))的效果及安全性。

搜尋策略

我們檢索CENTRAL, MEDLINE, EMBASE於2007年6月，參考文獻，Science Citation Index及會議論文。

選擇標準

我們蒐集任何類型玻璃體腔內類固醇以治療糖尿病黃斑水腫的隨機臨床試驗(randomized clinical trials (RCTs))。

資料收集與分析

兩名作者分別評估合格性，方法學品質並摘錄資料。我們用統合分析這些合適的研究。

主要結論

共納入七篇研究，包含632隻糖尿病黃斑水腫眼睛。四篇評估intravitreal triamcinolone acetate(IVTA)的效果，三篇評估intravitreal steroids implantation (fluocinolone acetonide implant (FAI)或dexamethasone drug delivery system (DDS))。兩項試驗有低度的偏差風險，一項試驗有中度的偏差風險，兩篇有高度的偏差風險，其餘兩篇之偏差風險不明。資料認為IVTA具有有利的效果。相較於對照組，在三個月時視覺敏銳度的平均差為−0.15 LogMAR(依據三項試驗)，六個月時為−0.23 LogMAR (95% CI −0.33 to −0.13)(兩項試驗)，九個月時為−0.29 LogMAR (95% CI −0.47 to −0.11)(一項試驗)，24個月時為 −0.11 LogMAR (95% CI −0.20 to −0.03)(一項試驗)，所有的試驗結果皆偏好IVTA。在3個月時改善視覺敏銳度1行以上的相對危險性為2.85(95% CI 1.59 to 5.10)(二項試驗)，6個月時為1.25(95% CI 0.66 to 2.38)(一項試驗)，24個月時為2.17(95% CI 1.15 to 4.11)(一項試驗)，所有的試驗結果皆偏好IVTA。我們並未發現任何可以改善視覺敏銳度3行以上的證據。三個月時視網膜厚度的平均差為−131.97 um (95% CI −169.08 to −94.86)(兩項試驗)，六個月時為−135.00 um (95% CI −194.50 to −75.50)(一項試驗)，九個月時為−133.00 um (95% CI −199.86 to −66.14)(一項試驗)，24個月時為−59.00 um (95% CI −103.50 to −14.50)(一項試驗)，所有的試驗結果皆偏好IVTA。三個月時至少為一級黃斑水腫之相對危險性(RR)為5.15(95% CI 2.23 to 11.88)，結果偏好IVTA(一項試驗)。兩項試驗報告當FAI對照於標準的照護方式時，其臨床結果會獲得改善。有利的效果也同樣在一篇dexamethasone DDS試驗中觀察到。眼壓增加及白內障形成等副作用需要監測及管理。

作者結論

這篇回顧蒐集的隨機對照試驗認為，類固醇經由玻璃體腔內注射或手術植入於眼內，也許可以改善持續性或難治性糖尿病黃斑水腫患者的視覺。由於在我們報告的研究中著重於慢性或難治之糖尿病黃斑水腫，因此問題是，玻璃體腔內注射類固醇療法是否對於其他階段的糖尿病黃斑水腫也具有價值，尤其是早期階段作為單獨治療或合併其他療法，如雷射光凝療法(laser photocoagulation)。

翻譯人

本摘要由高雄榮民總醫院金沁琳翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

玻璃體腔內類固醇用以治療糖尿病患者之黃斑水腫，視網膜中央水腫(該部分負責我們眼睛的最大視野)，是造成糖尿病患者視覺較差的重要因素。由於目前的治療方式包括雷射激光凝療法無法控制所有的糖尿病黃斑水腫病例，且因為雷射激光凝療法也許會破壞正常的視網膜組織，因此期待新型的療法。眼內類固醇以intravitreal triamcinolone acetate(IVTA)注射及手術植入fluocinolone acetonide (FAI)或dexamethasone藥物供給系統(drug delivery system (DDS))是令人期待的新型療法。這篇系統性回顧蒐集了七篇隨機臨床試驗，共包括來自五個國家的632隻眼睛，評估玻璃體腔內類固醇用來治療糖尿病黃斑水腫之效果及安全性。兩項試驗具有低度的偏差風險，一項有中度的偏差風險，兩項有高度的偏差風險，而其餘兩篇偏差風險不明。在這篇系統性回顧中，資料認為IVTA具有有利的效果。相較於那些使用其他療法的眼睛(依據三項試驗)，使用IVTA治療的眼睛其視覺敏銳度在三個月時平均改善7.5條以上(−0.15 LogMAR; 95% CI −0.21 to −0.09)，在六個月時改善11.5條以上(−0.23 LogMAR; 95% CI −0.33 to −0.13)(兩項試驗)，九個月時改善14.5條以上(−0.29 LogMAR; 95% CI −0.47 to −0.11)(一項試驗)，24個月時改善5.7條以上(−0.11 LogMAR; 95% CI −0.20 to −0.03)(一項試驗)。在FAI及dexamethasone DDS的試驗中也有改善的效果。眼壓增加及白內障形成會發生在IVTA及手術植入治療的眼睛，但這類副作用似乎是可管理的。