The aim of this study was to better understand the efficacy of various drugs, such as glucocorticoids and anti-vascular endothelial growth factors (VEGF), in the treatment of diabetic macular edema (DME), and to evaluate various clinical treatment regimens consisting of different therapeutic measures.

This study included randomized controlled trials up to February 2023 comparing the efficacy of corticosteroid-related therapy and anti-VEGF therapy. PubMed, the Cochrane Library, and Embase were searched, and the quality of the studies was carefully assessed. Finally, 39 studies were included.

Results at 3-month followup showed that intravitreal injection of bevacizumab (IVB) + triamcinolone acetonide (TA) was the most beneficial in improving best-corrected visual acuity and reducing the thickness of macular edema in the center of the retina in patients with DME. Results at 6-month follow-up showed that intravitreal dexamethasone (DEX) was the most effective in improving patients' bestcorrected visual acuity and reducing the thickness of central macular edema.

Overall, IVB+TA was beneficial in improving best-corrected visual acuity and reducing central macular edema thickness over a 3-month follow-up period, while DEX implants had a better therapeutic effect than anti-VEGF agents at 6 months, especially the patients with severe macular edema and visual acuity impaired.

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=397100, identifier CRD42023397100.

Ophthalmic drug delivery to the posterior segment of the eye has been challenging due to the complex ocular anatomy. Intravitreal injection of drugs was introduced to deliver therapeutic doses in the posterior segment. Different posterior segment diseases including age-related macular degeneration, diabetic macular edema, retinal vein occlusions, uveitis, and cystoid macular edema, among others, have been historically treated with intravitreal corticosteroids injections, and more recently with intravitreal corticosteroids drug implants. Triamcinolone acetonide (TA) is the most frequently used intraocular synthetic corticosteroid. Using nanoparticle-based TA delivery systems has been proposed as an alternative to intravitreal injections in the treatment of posterior segment diseases. From these novel delivery systems, topical liposomes have been the most promising strategy. This review is oriented to exhibit triamcinolone acetonide drug evolution and its results in treating posterior segment diseases using diverse delivery platforms.

Diabetic macular edema (DME) is secondary to leakage from diseased retinal capillaries with thickening of central retina, and is an important cause of poor central visual acuity in people with diabetic retinopathy. Intravitreal steroids have been used to reduce retinal thickness and improve vision in people with DME.

To assess the effectiveness and safety of intravitreal steroid therapy compared with other treatments for DME.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 15 May, 2019. We also searched reference lists, Science Citation Index, conference proceedings, and relevant trial registers. We conducted a top up search on 21 October, 2020.

We included randomized controlled trials that evaluated any type of intravitreal steroids as monotherapy against any other intervention (e.g. observation, laser photocoagulation, anti-vascular endothelial growth factor (antiVEGF) for DME.

Two review authors independently assessed study eligibility and risk of bias and extracted data. Where appropriate, we performed meta-analyses.

We included 10 trials (4348 participants, 4505 eyes). These trials compared intravitreal steroid therapies versus other treatments, including intravitreal antiVEGF therapy, laser photocoagulation, and sham injection. Most trials had an overall unclear or high risk of bias. One trial (701 eyes ) compared intravitreal dexamethasone implant 0.7mg with sham. We found moderate-certainty evidence that dexamethasone leads to slightly more improvement of visual acuity than sham at 12 months (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.12 to -0.05 logMAR). Regarding improvement of three or more lines of visual acuity, there was moderate-certainty evidence in favor of dexamethasone at 12 months, but the CI covered the null value (risk ratio (RR) 1.39, 95% CI 0.91 to 2.12). Regarding adverse events, dexamethasone increased by about four times the risk of cataract progression and the risk of using intraocular pressure (IOP)-lowering medications compared to sham (RR 3.89, 95% CI 2.75 to 5.50 and RR 4.54, 95% CI 3.19 to 6.46, respectively; moderate-certainty evidence); about 4 in 10 participants treated with dexamethasone needed IOP-lowering medications. Two trials (451 eyes) compared intravitreal dexamethasone implant 0.7mg with intravitreal antiVEGF (bevacizumab and ranibizumab). There was moderate-certainty evidence that visual acuity improved slightly less with dexamethasone compared with antiVEGF at 12 months (MD 0.07 logMAR, 95% CI 0.04 to 0.09 logMAR; 2 trials; 451 participants/eyes; I² = 0%). The RR of gain of three or more lines of visual acuity was inconsistent between trials, with one trial finding no evidence of a difference between dexamethasone and bevacizumab at 12 months (RR 0.99, 95% CI 0.70 to 1.40; 1 trial; 88 eyes), and the other, larger trial finding the chances of vision gain were half with dexamethasone compared with ranibizumab (RR 0.50, 95% CI 0.32 to 0.79; 1 trial; 432 participants). The certainty of evidence was low. Cataract progression and the need for IOP-lowering medications increased more than 4 times with dexamethasone implant compared to antiVEGF (moderate-certainty evidence). One trial (560 eyes) compared intravitreal fluocinolone implant 0.19mg with sham. There was moderate-certainty evidence that visual acuity improved slightly more with fluocinolone at 12 months (MD -0.04 logMAR, 95% CI -0.06 to -0.01 logMAR). There was moderate-certainty evidence that an improvement in visual acuity of three or more lines was more common with fluocinolone than with sham at 12 months (RR 1.79, 95% CI 1.16 to 2.78). Fluocinolone also increased the risk of cataract progression (RR 1.63, 95% CI 1.35 to 1.97; participants = 335; moderate-certainty evidence), which occurred in about 8 in 10 participants, and the use of IOP-lowering medications (RR 2.72, 95% CI 1.87 to 3.98; participants = 558; moderate-certainty evidence), which were needed in 2 to 3 out of 10 participants. One small trial with 43 participants (69 eyes) compared intravitreal triamcinolone acetonide injection 4 mg with sham. There may be a benefit in visual acuity at 24 months (MD -0.11 logMAR, 95% CI -0.20 to -0.03 logMAR), but the certainty of evidence is low. Differences in adverse effects were poorly reported in this trial. Two trials (615 eyes) compared intravitreal triamcinolone acetonide injection 4mg with laser photocoagulation and reached discordant results. The smaller trial (31 eyes followed up to 9 months) found more visual acuity improvement with triamcinolone (MD -0.18 logMAR, 95% CI -0.29 to -0.07 logMAR), but a larger, multicenter trial (584 eyes, 12-month follow-up) found no evidence of a difference regarding change in visual acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07 logMAR) or gain of three or more lines of visual acuity (RR 0.85, 95% CI 0.55 to 1.30) (overall low-certainty evidence). Cataract progression was about three times more likely (RR 2.68, 95% CI 2.21 to 3.24; moderate-certainty evidence) and the use of IOP-lowering medications was about four times more likely (RR 3.92, 95% CI 2.59 to 5.96; participants = 627; studies = 2; I² = 0%; moderate-certainty evidence) with triamcinolone. About 1 in 3 participants needed IOP-lowering medication. One small trial (30 eyes) compared intravitreal triamcinolone acetonide injection 4mg with intravitreal antiVEGF (bevacizumab or ranibizumab). Visual acuity may be worse with triamcinolone at 12 months (MD 0.18 logMAR, 95% CI 0.10 to 0.26 logMAR); the certainty of evidence is low. Adverse effects were poorly reported in this trial. Four trials reported data on pseudophakic participants, for whom cataract is not a concern. These trials found no decrease in visual acuity in the second treatment year due to cataract progression.

Intravitreal steroids may improve vision in people with DME compared to sham or control. Effects were small, about one line of vision or less in most comparisons. More evidence is available for dexamethasone or fluocinolone implants when compared to sham, and the evidence is limited and inconsistent for the comparison of dexamethasone with antiVEGF treatment. Any benefits should be weighed against IOP elevation, the use of IOP-lowering medication and, in phakic patients, the progression of cataract. The need for glaucoma surgery is also increased, but remains rare.

To report on the follow-up of patients who received an intravitreal high-dosage injection of triamcinolone acetonide (IVTA) as treatment of diffuse diabetic macular edema.

The clinical interventional case-series study included 109 eyes (90 patients) with diffuse diabetic macular edema who consecutively received an IVTA of about 20 mg. Mean follow-up was 11.2 +/- 6.2 months.

Visual acuity improved significantly (p<0.001) from 0.89 +/- 0.33 logMAR to a best minimum of 0.65 +/- 0.35 logMAR. An increase in best visual acuity by at least 1 Snellen line, 2 lines, and 3 lines was found in 91 (83%) eyes, 68 (62%) eyes, and 45 (41%) eyes, respectively. Differences in visual acuity between baseline and follow-up examinations were significant for measurements performed at 1 month (p<0.001), 2 months (p<0.001), 3 months (p<0.001), and at 6 months (p=0.001) after the injection. At 9 months after the injection, mean visual acuity regressed significantly so that visual acuity at 9 months (p=0.83) and at 12 months after the injection (p=0.58) compared with baseline values did not differ significantly. Forty-seven (43%) eyes developed a rise in intraocular pressure (pressure >21 mmHg) for 6 to 8 months after the injection. No other severe complications were detected.

The duration of a visual acuity increase and intraocular pressure rise after high-dosage IVTA in diffuse diabetic macular edema is about 6 to 8 months. Compared with data in the literature, the high-dosage IVTA may not have a markedly higher profile of side effects than low-dosage IVTA.

To compare therapeutic effects of intravitreal triamcinolone acetonide (IVTA) versus intravitreal bevacizumab (IVB) injections for bilateral diffuse diabetic macular edema (DDME).

Forty eyes of 20 patients with bilateral DDME participated in this study. For each patient, 4 mg/0.1 mL IVTA was injected to one eye and 2.5 mg/0.1 mL IVB was injected to the other eye. The effects of injection for diabetic macular edema (DME) were evaluated using best-corrected visual acuity (BCVA), central macular thickness (CMT) by optical coherence tomography (OCT) and intraocular pressure (IOP) by applanation tonometer. Patients underwent eye examinations, including BCVA, CMT, and IOP at pre-injection, 1, 4, 8, 12 and 24wk after injection. During the follow-up, second injections were performed to eyes which have CMT greater than 400 µm at 12wk for salvage therapy.

BCVA (logarithm of the minimum angle of resolution) at pre-injection, 1, 4, 8, 12 and 24wk after injection was 0.71±0.19, 0.62±0.23, 0.63±0.12, 0.63±0.13, 0.63±0.14 and 0.61±0.24 in the IVTA group and 0.68±0.25, 0.61±0.22, 0.60±0.24, 0.62±0.25, 0.65±0.26 and 0.59±0.25 in the IVB group, respectively. CMT (µm) at pre-injection, 1, 4, 8, 12 and 24wk after injection was 544±125, 383±96, 335±87, 323±87, 333±92, 335±61 in the IVTA group and 514±100, 431±86, 428±107, 442±106, 478±112, 430±88 in the IVB group respectively. Reduction ratios of mean CMT were 29% at 1wk, 38% at 4wk, 40% at 8wk, 38% at 12wk, and 38% at 24wk in the IVTA group. Second IVTA injections were performed to the 6 eyes (30%) at 12wk. Reduction ratios of mean CMT were 16% at 1wk, 17% at 4wk, 14% at 8wk, 7% at 12wk, and 16% at 24wk in the IVB group. Second IVB injections were performed to the 15 eyes (75%) at 12wk.

This study showed earlier and more frequent macular edema recurrences in the eyes treated with bevacizumab compared with the ones treated with triamcinolone acetonide. Triamcinolone acetonide was found to provide more efficient and long-standing effect in terms of reducing CMT compared with the bevacizumab.

The aim of the study was to compare intravitreal bevacizumab (IVB) and posterior subtenon triamcinolone (PST) as an adjunct to laser treatment in diffuse diabetic macular edema (Diffuse DME). Prospective-randomized control trial of 30 eyes of 30 diabetic patients having Diffuse DME with maximum retinal thickness (MRT) was more than or equal to 350 µm. The subjects were randomly allocated into two groups. Group A (12 eyes) received IVB and group B received PST (18 patients) before laser treatment. Grid laser treatment was done when the MRT decreased to less than 350 µm. OCT thickness-guided repeat injections were given if required. The patients had minimum follow-up of 6 months. At 6-month follow-up, the two groups were compared for (1) Maximum change in visual acuity letter score using logMAR chart (2) Reduction in MRT on OCT. The mean logMAR visual acuity at baseline was 0.63 ± 0.45 (0-1.6) in group A and was 0.76 ± 0.38 (0.2-1.3) in group B. The mean logMAR visual acuity at 6 month in group A was 0.34 ± 0.21 (0-0.6) and in group B was 0.64 ± 0.37 (0.3-1.3). The mean visual acuity at last follow-up was significantly better in group A than group B (p = 0.02). The mean change in MRT in Group A and Group B was 177.8 ± 85.64 and 156.07 ± 102.86, respectively, which was significantly better than the baseline in both the groups and was comparable in both groups. The study provides evidence to support the use of IVB over PST in diffuse diabetic macular edema.

To evaluate the role of central green-light fundus autofluorescence (FAF) in diabetic macular edema (DME).

A consecutive series of 92 study eyes with diabetic retinopathy were included. Out of those, 51 diabetic eyes had DME and were compared to 41 diabetic eyes without DME. In all subjects, green-light FAF images were obtained, quantified and classified into various FAF patterns. Cross-sectional optical coherence tomography (OCT) scans were obtained for evaluation of Inner/Outer segment (IS/OS) layer integrity, measurements of central RPE-IS/OS layer thickness as well as classification of DME into various subtypes.

Mean central green-light FAF intensity of eyes with DME (1.289±0.140)log did not significantly differ from diabetic patients without DME (1.317±0.137)log. Most classifiable FAF patterns were seen in patients with cystoid DME. Mean central retinal thickness (CRT) of all study eyes with DME was (501.9±112.4)µm compared to (328.2±27.0)µm in diabetic patients without DME. Patients with DME had significantly more disrupted photoreceptor IS/OS layers than diabetic patients without DME (28/51 vs 5/41, P<0.001). Mean RPE-IS/OS thickness of patients with DME (60.7±14.1)µm was significantly (P<0.001) lower than in diabetic eyes without DME (73.5±9.4)µm. Correlation analys1s revealed non-significant correlations of green-light FAF intensity and OCT parameters in all subtypes of DME.

Our results indicate a poor correlation of central green-light FAF intensity with CRT, IS/OS layer integrity or RPE-IS/OS layer thickness in diabetic patients with or without DME and its various subtypes. Thus, central green-light FAF is not suitable for detection of retinal thickening in DME.

To evaluate the effectiveness of combined treatment with posterior sub-Tenon's triamcinolone injection and focal laser photocoagulation, compared with laser treatment alone, in diffuse diabetic macular edema.

This was a nonrandomized, prospective, controlled study that involved 20 eyes with diffuse diabetic macular edema. The patients were divided into 2 groups: group I (10 eyes) received focal laser photocoagulation alone; and group II (10 eyes) received combined focal laser photocoagulation and posterior sub-Tenon's triamcinolone injection. All patients were followed for 6 months. Main outcome measures were final visual outcome and fluorescein leakage and retreatment rates at the end of the follow-up period.

Combined therapy showed better visual and angiographic outcome at 6 months. The retreatment rate was significantly lower in the combined-therapy group compared with the laser-therapy-alone group, with more stable visual acuity.

Improvement of visual acuity and decreased fluorescein leakage suggest that combination therapy with posterior sub-Tenon's triamcinolone injection and focal laser photocoagulation, particularly when used as a first-line therapy, is advantageous and merits further investigation.

Diabetic macular edema (DME) causes visual loss in diabetic patients. Multifocal electroretinograms (mfERGs) have been used to assess macular function pre- and postvitrectomy for DME.

A standard three-port pars plana vitrectomy with peeling of inner limiting membrane was performed in 25 eyes of 21 patients (13 male, 8 female) with DME. For each patient, visual acuity examination, measure of retinal thickness (using optical coherence tomography), and mfERGs were performed before and 1 week, 1 month, 3 months, and 6 months after vitrectomy.

Mean postoperative visual acuity was significantly improved (p<0.05, t test), with mean increase of 0.17 logMAR units; mean retinal thickness was significantly (p<0.001) decreased after surgery (from 537 microm to 298 microm). The increase of normalized amplitude of central ring was not significant; the mean P1 wave-amplitude increased from 0.33 to 0.40 mV; mean P1 wave-implicit time decreased 2.88 ms. We divided the patients into two groups: Group 1 (13 eyes), in which the visual recovery was less than 0.20 logMAR, and Group 2 (12 eyes), in which the visual recovery was greater than 0.20 logMAR. ERG results were statistically significantly different between the groups (p<0.025), when we consider the response recorded from the central ring. In Group 2 there is a marked reduction in implicit time of both ERGs waves, which was statistically significant for N1 wave (p=0.01). The changes of parameters of mfERG observed 6 months after surgery were consistent with those recorded just 1 week after surgery.

Multifocal electroretinogram can be useful to predict functional prognosis in patients with diabetes who underwent vitrectomy for diabetic macular edema.

To compare the efficacy and safety of different doses of intravitreal triamcinolone (IVTA) in treating eyes with refractory diffuse diabetic macular edema (DME) with cystic changes.

Forty-five eyes of 45 patients with diffuse DME were randomized to receive 1, 2, or 4 mg IVTA. Patients were observed for 6 months and changes in best-corrected visual acuity (VA) in Early Treatment Diabetic Retinopathy Study (ETDRS) scores, retinal thickness analyzer (RTA) central macular thickness (CMT), intraocular pressure, and cataract progression were compared among the three groups.

Forty-two patients completed 6 months of follow-up and were included in the analysis. Following IVTA injection, the ETDRS score improved similarly, eight to nine letters, in all three groups at 4 weeks. The standardized CMT improved in all three groups at 4 weeks. This improvement was maintained through 12 and 24 weeks in the 1 and 2 mg groups, but not in the 4 mg group, which was significantly worse than the 1 and 2 mg groups at 12 and 24 weeks (P = 0.01, 0.03, 0.01, and 0.05).

Regarding eyes with refractory diffuse DME with cystic changes, 4 mg IVTA does not appear to be more effective than 1 or 2 mg IVTA.

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.

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

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

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

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

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.

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.

The use of intravitreal corticosteroids in the management of macular oedema has recently gained widespread acceptance. New long-acting steroid preparations and methods of delivery have facilitated the use of these new modalities. This review describes the various types of macular oedema for which this therapeutic option is used and the results.

To evaluate prospectively the efficacy and safety of one intravitreal injection of 4 mg triamcinolone acetonide for refractory diffuse diabetic macular edema.

Seventeen patients with bilateral diabetic macular edema unresponsive to laser photocoagulation. In all patients, one eye was injected, and the other served as a control. The intervention consisted in intravitreal injection of 4 mg triamcinolone acetonide. The main outcome measure was central macular thickness (CMT) at 4, 12 and 24 weeks, measured by Optical Coherence Tomography. Secondary outcomes were Early Treatment Diabetic Rentinopathy Study (ETDRS) scores, intraocular pressure and cataract PROGRESSION.

Before injection, mean +/- SD CMT was 566.4 +/- 182.4 mum in injected eyes. Four, 12, and 24 weeks after injection, it was 228.4 +/- 47.5 mum, 210.9 +/- 87.2 mum and 358.5 +/- 160.5 mum respectively. CMT was significantly lower in injected eyes vs. control eyes except 24 weeks after injection because of a recurrence of macular edema in 9/17 injected eyes. Mean +/- SD gain in ETDRS score was significantly better in injected eyes vs. control eyes 4, 12 and 24 weeks after TA injection. In 9 of the 17 injected eyes, intraocular pressure exceeded 24 mmHg and was controlled by topical medication.

In the short-term, intravitreal injection of triamcinolone effectively reduces macular thickening due to diffuse diabetic macular edema and improves visual acuity in most cases. The long-term effect of this treatment and predictive factors of visual recovery remain to be elucidated.

To prospectively compare the efficacy and safety of 4 vs 2 mg intravitreal triamcinolone acetonide (TA) injection for diabetic macular edema.

Interventional case series.

Thirty-two patients with diabetic macular edema unresponsive to laser photocoagulation.

Patients were randomly assigned to receive 4 or 2 mg intravitreal TA in one eye (16 patients in each group).

The main outcome was central macular thickness (CMT) measured by optical coherence tomography (OCT) at four, 12, and 24 weeks. Secondary outcomes were gain in Early Treatment Diabetic Retinopathy Study (ETDRS) scores, intraocular pressure (IOP), cataract progression, and duration of effect.

Before injection, mean (+/- SD) CMT was 564.5 +/- 119 microm and 522.9 +/- 148.5 microm in the 4- and 2-mg groups, respectively. At four, 12, and 24 weeks after injection, it was 275.0 +/- 79.8, 271.4 +/- 128.7, and 448.7 +/- 146.4 microm, respectively, in the 4-mg group, and 267.3 +/- 82.4, 289.8 +/- 111.4, and 394.7 +/- 178.9 microm, respectively, in the 2-mg group. At no time was the difference in CMT between both groups statistically significant (P> 0.3). The between-group differences in the gain in the ETDRS score and in IOP were not statistically significant either. Diabetic macular edema recurred after a median period of 20 weeks vs 16 weeks in the 4- and 2-mg groups, respectively (P = 0.11).

In the short term, intravitreal injection of 4 or 2 mg TA does not have different effects on CMT, visual acuity, or IOP.

Based on experimental studies and clinical observations by Robert Machemer, Gholam Peyman and others, the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of intraocular diseases.

The most widely injected drug so far has been triamcinolone acetonide for various intraocular neovascular and edematous diseases. Comparing the various diseases with respect to effect and side effects of the treatment, the best response in terms of gain in visual acuity has been achieved for intraretinal edematous diseases such as diffuse diabetic macular edema, branch retinal vein occlusion, central retinal vein occlusion, and pseudophakic cystoid macular edema. In eyes with various types of noninfectious uveitis including acute or chronic sympathetic ophthalmia and Adamantiadis-Behçet's disease, visual acuity increased and the degree of intraocular inflammation decreased. Some studies have suggested that intra- vitreal triamcinolone may be useful as an angiostatic agent in eyes with iris neovascularization and proliferative ischemic retinopathies. Intravitreal triamcinolone may possibly be helpful as adjunct therapy for exudative age-related macular degeneration, particularly in combination with photodynamic therapy. In eyes with chronic, therapy-resistant ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure and may stabilize the eye. The complications of intravitreal triamcinolone therapy include secondary ocular hypertension in about 40% of the eyes injected; medically uncontrollable high intraocular pressure leading to antiglaucomatous surgery in about 1-2% of the eyes; posterior subcapsular cataract and nuclear cataract leading to cataract surgery in about 15-20% in elderly patients within 1 year after injection; postoperative infectious endophthalmitis with a rate of about 1:1,000; noninfectious endophthalmitis, perhaps due to a reaction to the solvent agent, and pseudoendophthalmitis with triamcinolone acetonide crystals appearing in the anterior chamber. Intravitreal triamcinolone injection can be combined with other types of intraocular surgery including cataract surgery, particularly in eyes with iris neovascularization. Cataract surgery performed some months after the injection does not show a markedly elevated complication rate. The injection may be repeated, if vision redecreases. In nonvitrectomized eyes, the duration of the effect and side effects of a single intravitreal injection of triamcinolone is about 6-9 months for a dosage of about 20 mg, and about 2-4 months for a dosage of 4 mg. It has remained unclear so far, whether and how to remove the solvent agent. In the future, intravitreal triamcinolone may be combined with other antiangiogenic drugs for the treatment of exudative age-related macular degeneration or with neuroprotective drugs for treatment of diabetic retinopathy.

Despite an exponentially increasing number of mostly case-series studies, the intravitreal injection of triamcinolone may still be considered an experimental procedure until randomized studies have been presented.

The aim of this study was to examine the visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide (TA) as treatment of diffuse diabetic macular edema (DDME).

This prospective, placebo-controlled, randomized, clinical interventional study included 40 eyes (38 patients) with DDME, with 28 (70%) eyes randomized to treatment and 12 (30%) eyes randomized to receive a placebo injection. Thirty-six (36) (90%) eyes completed the 3-month study visit, and 32 (80%) eyes completed the 6-month study visit. The treatment group received an intravitreal injection of approximately 20 mg of TA.

Visual acuity increased significantly (P < 0.001) in the study group by 3.4 +/- 2.5 Snellen lines. In the control group, visual acuity did not change significantly (P = 0.07) during follow-up. Difference in change of best visual acuity was significant (P < 0.001) between both groups. At 3 months after baseline, 11 (11/26; 42%) eyes and 10 (10/26; 39%) eyes, respectively, improved by at least 2 and 3 lines, respectively, in the study group, versus 2 (2/10; 20%) eyes and 1 (1/10; 10%) eye in the control group. At 6 months after baseline, 11 (11/23; 48%) eyes and 9 (9/23; 39%) eyes, respectively, improved by at least 2 and 3 lines, respectively, in the study group, versus 0 (0%) eyes and 0 (0%) eyes in the control group. The difference was significant for the 2-line improvement (P = 0.01) and 3-line improvement (P = 0.03).

Using a dosage of approximately 20 mg of intravitreal TA, visual acuity temporarily increases for 6 months after injection.

To evaluate complications and results of intravitreal triamcinolone acetonide for treatment of macular edema.

Interventional, consecutive, retrospective case series.

Ninety-three eyes with macular edema arising from retinovascular etiologies were treated with 4 mg intravitreal triamcinolone. Eyes were monitored after injection for visual acuity changes and complications, including cataract formation and increase in intraocular pressure (IOP). Cataract progression was analyzed by linear regression analysis of lens scores from lens opacity standards.

The mean visual acuity improved from 20/125 to -1 to 20/100 + 2 by one to two months after injection (P < .001) and was 20/100 at the final examination (P = .006) at a mean of 1.2 years after injection. Complications included a severe, culture-negative inflammatory reaction in one eye (1.1%). IOP increased to 30 mm Hg or more in nine (9.7%) of 93 eyes between 1 and 140 days after injection and was more frequent in eyes receiving one or more preinjection glaucoma drops (two of 13 eyes, 15.4%, vs seven of 80 eyes, 8.75%, without preinjection glaucoma drops). Nuclear sclerosis increased at a rate of 0.175 U per year, posterior subcapsular cataracts at 0.423 U per year, and cortical cataracts at 0.045 U per year. Posterior subcapsular cataract increased by > or = 1 U or required cataract surgery in 45.2% of eyes followed at least one year.

Intravitreal triamcinolone improves visual acuity in most eyes but eyes must be monitored carefully for increase in IOP. Posterior subcapsular cataract formation becomes visually significant in almost half of eyes by one year after injection.

To report the results of repeated intravitreal injections of triamcinolone acetonide for treatment of diffuse diabetic macular edema.

Retrospective interventional comparative study.

The investigation included a study group (the responders) of 19 patients (22 eyes) with diffuse diabetic macular edema, who showed an improvement in visual acuity after an intravitreal injection of approximately 20 mg triamcinolone acetonide, and who received a second intravitreal injection 10.0+/-3.8 months after the first injection. A control group consisted of 31 patients with diffuse diabetic macular edema without treatment during follow-up.

Intravitreal injection of approximately 20 mg triamcinolone acetonide.

Visual acuity and intraocular pressure.

Follow-up after the second injection was 9.1+/-4.9 months. Four patients received a third injection at 9.7+/-3.7 months after the second injection, with a follow-up after the third injection that was at 7.9+/-11.5 months. After the second and third injections, visual acuity increased significantly (P = 0.002 and P = 0.068, respectively) by 1.8+/-2.1 and 4.0+/-2.6 Snellen lines, respectively. Eleven eyes (50%) showed an improvement in visual acuity by at least 2 Snellen lines after the second injection, and 3 patients (75%) experienced a gain in visual acuity by at least 2 Snellen lines after the third injection. Intraocular pressure increased significantly (P<0.01) after each injection, and returned to baseline values before each reinjection. Visual acuity improvement (P>0.05) and intraocular pressure rise did not differ significantly (P>0.55) between the various injections. Improvement in visual acuity and rise of intraocular pressure lasted approximately 6 to 8 months after each injection.

Intravitreal injection of approximately 20 mg triamcinolone acetonide may repeatedly lead to an improvement in visual acuity and a rise of intraocular pressure in patients with diffuse diabetic macular edema. The duration of the effect after each injection is approximately 6 to 8 months. Tachyphylaxis in visual acuity or intraocular pressure outcomes were not observed.

Intravitreal triamcinolone acetonide (IVTA) has increasingly been applied as treatment for various intraocular neovascular and oedematous diseases. Comparing the various diseases with respect to effect and side-effects of the treatment, the best response in terms of gain in visual acuity (VA) has been achieved for intraretinal oedematous diseases such as diffuse diabetic macular oedema, branch retinal vein occlusion, central retinal vein occlusion and pseudophakic cystoid macular oedema. In eyes with various types of non-infectious uveitis, including acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease, VA increased and the degree of intraocular inflammation decreased. Some studies have suggested that intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischaemic retinopathies. Intravitreal triamcinolone may possibly be helpful as adjunct therapy for exudative age-related macular degeneration (AMD), particularly in combination with photodynamic therapy. In eyes with chronic, therapy-resistant ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure (IOP) and may stabilize the eye. The complications of intravitreal triamcinolone therapy include: secondary ocular hypertension in about 40% of the eyes injected; medically uncontrollable high IOP leading to antiglaucomatous surgery in about 1-2% of the eyes; posterior subcapsular cataract and nuclear cataract leading to cataract surgery in about 15-20% of elderly patients within 1 year of injection; postoperative infectious endophthalmitis occurring at a rate of about one per 1000; non-infectious endophthalmitis, perhaps due to a reaction to the solvent agent, and pseudo-endophthalmitis with triamcinolone acetonide crystals appearing in the anterior chamber. Intravitreal triamcinolone injection can be combined with other intraocular surgeries, including cataract surgery, particularly in eyes with iris neovascularization. Cataract surgery performed some months after the injection does not show a markedly elevated complication rate. The injection may be repeated if the resultant benefits decrease after the initial IVTA injection. In non-vitrectomized eyes, the duration of the effect and side-effects of a single intravitreal injection of triamcinolone is about 6-9 months for a dosage of about 20 mg, and about 2-4 months for a dosage of 4 mg. So far, it has remained unclear whether the solvent agent should be removed, and if so, how.

To describe the changes in retinal thickness (RT) and visual acuity over time in patients with clinically significant diffuse diabetic macular edema (DME) after intravitreal injection of triamcinolone acetonide (IVTA) and to compare patients with and without previous laser treatment.

A total of 23 eyes with clinically significant DME received a 4-mg IVTA injection. Twelve eyes were refractory to macular laser treatment (group 1), and 11 eyes received IVTA as primary therapy (group 2). Visual acuity and changes in macular thickening shown by optical coherence tomography were evaluated 48 hours after injection, every 7 days for 1 month, and at 3 months and 6 months of follow-up.

RT decreased in all eyes in both groups. The reduction of edema was maximal in the first 7 days after IVTA and tended to remain stable for 3 months. The decrease in RT over time was significant in both groups (P < 0.001). At 6 months, RT had increased in almost all eyes. Visual acuity improved quickly, to a maximum at 2 weeks in both groups, after which it remained stable for 3 months and then decreased. Improvement in visual acuity over time was significant in both groups (P < 0.001). The temporal characteristics of the changes in RT and visual acuity were similar in the two groups (P < 0.05).

IVTA was effective in reducing clinically significant DME and improving visual acuity in eyes with and without previous laser treatment. Its action was maximal in the first week and lasted approximately 3 months in this study.

Within the last three years, triamcinolone acetonide has increasingly been applied intravitreally as treatment option for various intraocular neovascular edematous and proliferative disorders. The best response in terms of gain in visual acuity after the intravitreal injection of triamcinolone acetonide was found in eyes with intraretinal edematous diseases such as diffuse diabetic macular edema, branch retinal vein occlusion, central retinal vein occlusion, and pseudophakic cystoid macular edema. Visual acuity increased and degree of intraocular inflammation decreased in eyes with various types of non-infectious uveitis including acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease. Intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischemic retinopathies. Possibly, intravitreal triamcinolone may be helpful as adjunct therapy for exudative age-related macular degeneration, possibly in combination with photodynamic therapy. In eyes with chronic, therapy resistant, ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure and may stabilize the eye. The complications of intravitreal triamcinolone therapy include secondary ocular hypertension in about 40% of the eyes injected, cataractogenesis, postoperative infectious and non-infectious endophthalmitis, and pseudo-endophthalmitis. Intravitreal triamcinolone injection can be combined with other intraocular surgeries including cataract surgery. Cataract surgery performed some months after the injection does not show a markedly elevated rate of complications. If vision increases and eventually decreases again after an intravitreal triamcinolone acetonide injection, the injection can be repeated. The duration of the effect of a single intravitreal injection of triamcinolone depended on the dosage given. Given in a dosage of about 20mg to non-vitrectomized eyes, the duration of the effect and of the side-effects was 6-9 months. Intravitreal triamcinolone acetonide may offer a possibility for adjunctive treatment of intraocular edematous and neovascular disorders. One has to take into account the side-effects and the lack of long-term follow-up observations.

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

The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3-12 months). Main outcome measures were visual acuity and intraocular pressure.

Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77).

In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used.