One Intravitreal Dexamethasone Implant versus Single or Multiple Intravitreal Triamcinolone Acetonide Injections for Macular Edema due to Central Retinal Vein Occlusion: Efficacy and Safety

2.1. Study Design

This retrospective study involved eyes with macular edema associated with CRVO. Patients received treatment with either ITA or IDI at the Eye and Ear Hospital International in Lebanon, between January 2016 and January 2023. The study included a total of 60 eyes, with 30 eyes receiving ITA and 30 eyes receiving IDI. Inclusion criteria included a follow-up period of 6 months, the presence of CRVO, and treatment with one or multiple ITA injections or a single IDI. Patients with diabetic retinopathy, aphakia, and those treated with subtenon or subconjunctival ITA injections were excluded from the study. Moreover, patients who were given a combination of steroid injections and anti-VEGF injections were excluded from the study. Cataract progression was considered when the cataract reached grade 2 on the Lens Opacities Classification System (LOCS) III. Cataract surgery was performed when the cataract reached grade 3 or higher. IOP spike was considered when an increase of more than 10 mmHg from baseline was observed, or when IOP was more than 21 mmHg.

Ethical approval was granted by the Eye and Ear University Hospital's ethics committee before starting the study. The Declaration of Helsinki's principles were adhered to throughout the study's execution. Prior to using their medical data in our research, all patients were informed and signed a consent form.

2.2. Minimum Sample Size

The G-power software calculated a minimum sample of 20 participants to have enough statistical power based on an alpha error of 5%, a beta error of 20%, and an IOP value of 17.00 ± 1.94 in the dexamethasone group vs 22.2 ± 4.93 in the triamcinolone group according to a previous study (5).

2.3. Patient Data

Patients’ past ocular history included cataract surgery (simple or complicated), prior pars plana vitrectomy, treatment for glaucoma either medically or surgically, presence of rubeosis, retinal detachment, or macular hole. Post-injection complications were observed, along with their corresponding treatment: endophthalmitis, elevated intraocular pressure (IOP) exceeding 21 mm Hg, progression of cataracts, intravitreal hemorrhage, epiretinal membrane, retinal detachment, flare-up of herpetic keratitis, and corneal decompensation.

Outcome measurements were conducted to assess the results, which included best-corrected visual acuity (BCVA) measured using a Snellen chart (converted to logMAR for statistical purposes), central retinal thickness (CRT) measured using spectral domain optical coherence tomography (SD-OCT) in micrometers (µm), and IOP measured with a Goldman applanation tonometer in mmHg. The follow-up protocol was day 1, 1 week, 2 weeks, 1 month, and then monthly until 6 months.

2.4. Intravitreal Injection

All procedures were performed in the minor surgery room under local anesthesia (using topical anesthetic drops) with strict adherence to sterility precautions. A sterile eyelid speculum was used to retract the eyelids before the injection, which was performed 3.5–4 mm from the limbus in the inferotemporal quadrant, as measured with a sterile caliper. Either 0.7 mg of intravitreal dexamethasone implant (IDI) or 0.1 mL of 4 mg intravitreal triamcinolone acetonide (ITA) was administered.

2.5. Anatomical and Functional Success

Anatomical results were considered successful when there was improvement or stabilization of the BCVA and an improvement in the central retinal thickness within the normal range of CRT (below 310 µm) at the final follow-up visit.

2.6. Criteria for Re-injection of ITA

If any of the following criteria were present at least 1 month after the injection, re-injection was considered: residual macular oedema and a decrease in BCVA by 3 or more lines compared to the initial visit.

2.7. Statistical Analysis

IBM SPSS Statistics software version 27 was used for all statistical analyses. Chi-square/Fisher's exact tests were carried out to compare two qualitative variables. The Student's t-test was conducted to compare two means. A repeated-measures ANOVA was used to compare BCVA, CRT, and IOP values at baseline, 1 month, and 6 months. The result was considered statistically significant if the p-value was < 0.05.

3.1. BCVA Results

At the final follow-up, both groups demonstrated improvement in BCVA compared to baseline. In the ITA group, BCVA improved significantly from 0.89 ± 0.55 logMAR at baseline to 0.57 ± 0.60 at 1 month (p < 0.001; 95% CI for the difference [0.19; 0.45]) and remained stable at 6 months with a value of 0.58 ± 0.59 (p = 1; 95% CI for the difference [-0.08; 0.05] vs. 1 month; p < 0.001; 95% CI for the difference [0.18; 0.44] vs. baseline). In the IDI group, BCVA improved significantly from 0.97 ± 0.52 at baseline to 0.86 ± 0.55 at 1 month (p < 0.001; 95% CI for the difference [0.06; 0.16]), and at 6 months, BCVA decreased further (0.76 ± 0.68; 95% CI for the difference [0.06; 0.37]) compared to baseline (p < 0.001), but this change was not significant compared to the 1-month value (p = 0.412; 95% CI for the difference [-0.07; 0.27]) (Fig. 1). Between-group comparisons showed no statistically significant differences in BCVA at baseline (0.89 ± 0.55 vs. 0.97 ± 0.52, the mean difference was -0.82 logMar, 95% CI [-0.60 to 0.44], p=0.556), at 1 month (0.57 ± 0.6 vs. 0.86 ± 0.55, the mean difference was -0.29 logMar, 95% CI [-0.86 to 0.27], p = 0.054), or at 6 months (0.58 ± 0.59 vs. 0.76 ± 0.68, the mean difference was -0.18 logMar, 95% CI [-0.79 to 0.44], p = 0.287).

3.2. CRT Results

In the ITA group, CRT also decreased significantly from 463.70 ± 106.59 µm at baseline to 369.70 ± 75.83 µm at 1 month (p < 0.001; 95% CI for the difference [62.86; 125.14]) and to 349.80 ± 83.56 µm at 6 months (p = 0.128; 95% CI for the difference [-3.94; 43.74] vs. 1 month; p < 0.001; 95% CI for the difference [-125.14; -62.86] vs. baseline). In the IDI group, CRT decreased significantly from 473.70 ± 98.69 µm at baseline to 452.60 ± 98.04 µm at 1 month (p < 0.001; 95% CI for the difference [12.83; 29.37]), and further to 405.70 ± 106.91 µm at 6 months (p < 0.001; 95% CI for the difference [20.04; 73.76] vs. 1 month; p < 0.001; 95% CI for the difference [40.15; 95.85] vs. baseline) (Fig. 2). Between groups, CRT was comparable at baseline (463.70 ± 106.59 µm vs. 473.70 ± 98.69 µm; mean difference = -10.0 µm, 95% CI [-110.02 to 90.02], p = 0.708). At 1 month, CRT was significantly lower in the ITA group (369.70 ± 75.83 µm vs. 452.60 ± 98.04 µm, the mean difference was -82.90 µm, 95% CI [-168.24 to 2.44], p < 0.001), while at 6 months, the difference was statistically significant in favor of a lower CRT in the ITA group (349.8 ± 83.56 µm vs. 405.70 ± 106.91 µm, the mean difference was -55.90 µm, 95% CI [-149.33 to 37.53], p = 0.028) (Fig. 2).

3.3. IOP Results

In the ITA group, IOP increased from 14.60 ± 1.22 mmHg at baseline to 17.60 ± 6.70 mm Hg at 1 month (p = 0.038; 95% CI for the difference [-5.86; -0.14]), then decreased significantly to 15.30 ± 4.43 mm Hg at 6 months (p < 0.001; 95% CI for the difference [0.97; 3.64] vs. 1 month; p = 1; 95% CI for the difference [-2.60; 1.20] vs baseline). In the IDI group, IOP increased from 15.60 ± 3.19 mmHg at baseline to 18.70 ± 8.46 mmHg at 1 month but this was not significant (p = 0.063; 95% CI for the difference [-6.33; 0.13]), then decreased to 16.10 ± 4.42 mmHg at 6 months (p = 0.377; 95% CI for the difference [-1.59; 6.79] vs. 1 month and p = 1; 95% CI for the difference [-2.10; 1.10] vs baseline) (Fig. 3). Between-group comparisons showed no significant differences in IOP at baseline (14.6 ± 1.22 mmHg vs. 15.60 ± 3.19 mmHg, the mean difference was -1.0 mmHg, 95% CI [-3.35 to 1.35], p = 0.117), at 1 month (17.6 ± 6.7 mmHg vs. 18.70 ± 8.46 mmHg, the mean difference was -1.1 mmHg, 95% CI [-8.53 to 6.33], p = 0.579), or at 6 months (15.3 ± 4.6 mmHg vs. 16.10 ± 4.58 mmHg, the mean difference was -0.8 mmHg, 95% CI [-5.11 to 3.51], p = 0.487) (Fig. 3).

3.4. Between-group Comparison

No significant difference was found between the two groups in terms of all variables, except for the CRT at 1 month and at 6 months, where a higher mean was seen in the IDI group compared to the ITA group (452.60 vs 369.70; p < 0.001 and 405.70 vs 349.80; p = 0.028, respectively) (Table 2).

3.5. Complications

The increase in IOP was treated with topical anti-glaucoma medications, with none requiring surgery. Cataract progression was treated surgically if the cataract reached grade 3 on the Lens Opacities Classification System (LOCS) III. None of the eyes reached grade 3 during the 6-month follow-up period.

4.1. Intravitreal Triamcinolone Acetonide (ITA)

In the ITA group, BCVA improved significantly from 0.89 ± 0.55 to 0.57 ± 0.60 logMAR at 1 month (p < 0.001) and remained stable at 6 months (0.58 ± 0.59, p = 1 vs. 1 month), while CRT decreased significantly from 463.70 ± 106.59 µm to 369.70 ± 75.83 µm at 1 month (p < 0.001) and further to 349.80 ± 83.56 µm at 6 months (p < 0.001 vs. baseline). These findings align with those reported in the SCORE study, which found that 1 mg and 4 mg of ITA, compared with observation, had similar visual acuity outcomes in the treatment of macular edema associated with CRVO over 1 to 2 years. It was found that the odds of reaching the primary outcome in the 1mg and 4mg groups were 5 times greater than in the observation group, with rates of 27%, 26%, and 7%, respectively. This is similar to our study, as a statistically significant improvement was found at 6 months in the ITA group compared with baseline.

Another study, conducted on 13 eyes, tested the efficacy of 4 mg ITA in the setting of macular edema associated with CRVO and showed that patients achieved improvement in BCVA and CRT. However, between 3 and 6 months, 4 of 13 enrolled eyes developed recurrent macular edema that was treated with a second injection, and 3 of the 4 eyes responded to the treatment [7]. This is consistent with our results, where 50% of patients required more than one injection, highlighting the often-transient nature of corticosteroid effects and the potential need for re-administration to maintain therapeutic benefit. Our study reinforces the role of ITA in achieving both anatomical and functional improvements in macular edema due to CRVO, while also emphasizing the importance of individualized retreatment strategies in the context of recurrent edema.

4.2. Intravitreal Dexamethasone Implant (IDI)

In the IDI group, BCVA improved significantly from 0.97 ± 0.52 to 0.86 ± 0.55 at 1 month (p < 0.001) and to 0.76 ± 0.68 at 6 months (p < 0.001 vs. baseline, p = 0.412 vs. 1 month), while CRT decreased significantly from 473.70 ± 98.69 µm to 452.60 ± 98.04 µm at 1 month (p < 0.001) and to 405.70 ± 106.91 µm at 6 months (p < 0.001 vs. both 1 month and baseline). Our results partially align with those of the GENEVA study, which evaluated the efficacy of dexamethasone implants in macular edema secondary to CRVO and BRVO compared to a sham group [8]. The study showed that patients who received the IDI had a significant improvement in BCVA and CRT at 90 days compared with the sham group. However, improvement at 6 months was statistically insignificant. This differs from our results, in which CRT continued to improve significantly at 6 months, suggesting a longer-lasting effect on retinal thickness. However, the gain in BCVA did not remain significant after the first month, as in the GENEVA study, which found that visual improvement tends to decrease over time.

Similarly, a clinical trial found that the effect of IDI does not last 6 months, and a retreatment protocol should be used [9]. Our findings partially support this pattern, as improvement in CRT was significant at 6 months, whereas that in BCVA was not. Moreover, a meta-analysis of 4 studies with a total of 99 patients evaluating the efficacy of switching from anti-VEGF to IDI for refractory macular edema in the setting of RVO reported that IDI improved BCVA and CRT, with efficacy lasting for 6 months [4].

Similarly, a study comparing IDI to anti-VEGF showed that IDI was more effective; however, its efficacy peaked at 2 months post-injection and then declined rapidly [10]. This is similar to our study, as at 1 month, patients showed significant improvement in CRT and BCVA. This improvement was maintained in CRT but not in BCVA at 6 months. Additionally, the transient improvement in BCVA observed in the IDI group at 1 month, followed by a non-significant change at 6 months, may be an indication of waning efficacy.

Our study demonstrated that IDI is effective in achieving a sustained reduction in CRT over a 6-month period. However, the absence of continued improvement in visual acuity beyond the first month may be attributed to the limited duration of action of the dexamethasone implant, emphasizing the potential need for timely retreatment in clinical practice.

4.3. ITA versus IDI

Between-group comparisons showed no significant differences in BCVA at baseline, 1 month, or 6 months, while CRT was similar at baseline but significantly lower in the ITA group at both 1 month and 6 months. These findings are consistent with those of another study that aimed at assessing the effectiveness and safety of ITA and IDI in treating macular edema associated with CRVO over a period of 6 months. No significant difference was found in terms of CRT and BCVA between IDI and ITA injections at any follow-up visit up to 6 months (5). In our study, eyes receiving IDI showed improvement at 1 month, which was not observed at 6 months; this suggests that IDI’s effect lasts for less than 6 months.

4.4. Clinical Implications

The findings of this study have valuable clinical implications for ophthalmologists worldwide, particularly those practicing in low-resource settings or serving underserved populations. It provides evidence-based guidance on cost-effective therapeutic strategies. ITA demonstrated comparable visual outcomes and even superior anatomical results compared to IDI, without increasing the risk of complications. Therefore, ophthalmologists may confidently consider ITA as a viable alternative in situations where access to IDI is limited by financial constraints. This is especially relevant in regions affected by economic hardship, humanitarian crises, or disruptions in the pharmaceutical supply chain.

4.5. Limitations

Our study has several limitations that should be acknowledged. It is a retrospective, non-randomized design, with a relatively small sample size (n=60 eyes, 30 per group), which may limit statistical power, particularly for detecting less frequent complications. The follow-up duration was limited to 6 months, which may not be sufficient to evaluate long-term outcomes, such as recurrence rates, cataract progression, and sustained efficacy. Furthermore, potential confounding factors may have influenced the results, including prior anti-VEGF treatment in 70% of patients and differences in treatment frequency between groups, both of which should be taken into account in later studies. A selection bias is also possible, as patients were recruited from a single hospital.