|Year : 2021 | Volume
| Issue : 1 | Page : 26-33
Safety and long-term outcomes of repeated dexamethasone intravitreal implant (OZURDEX®) for the management of macular edema: Real-life study
Meriem Abdellaoui1, Meriem El Bahloul2, Ahmed Bennis1, Fouad Chraïbi1, Adil Najdi3, Idriss Andaloussi Benatiya1
1 Department of Ophthalmology, University Hospital Hassan II, Fez; Faculty of Medicine and Pharmacy Fez, Sidi Mohammed Benabdellah University, Morocco
2 Department of Ophthalmology, University Hospital Hassan II, Fez; Faculty of Medicine and Pharmacy Tangier, Abdelmalek Essaâdi University, Morocco
3 Faculty of Medicine and Pharmacy Tangier, Abdelmalek Essaâdi University; Department of Epidemiology, University Hospital of Tangier, Morocco
|Date of Submission||27-Sep-2021|
|Date of Acceptance||26-Nov-2021|
|Date of Web Publication||27-Jan-2022|
Dr. Meriem Abdellaoui
Hopital OMAR Drissi, Batha, 30000 Fez
Source of Support: None, Conflict of Interest: None
Purpose: This study to assess the efficacy and the safety of repeated dexamethasone intravitreal implant (Ozurdex®) in vascular macular edema in real-life practice. Materials and Methods: This was a 22-month prospective study, including eyes with vascular macular edema according to the inclusion criteria. Baseline and follow-up visits included best-corrected visual acuity (BCVA) measurement, slit-lamp biomicroscopy, dilated fundoscopy, intraocular pressure (IOP) measurement, and central macular thickness (CMT) measurement with optical coherence tomography. Main outcomes included changes in BCVA and CMT at the 1st, 2nd, 4th, and 6th months; time to retreatment; and incidence of side effects. Results: A total of 31 eyes of 24 patients were included in the present study. After the first intravitreal injection, BCVA (baseline 0.940 ± 0.463 LogMAR) improved significantly to 0.483 ± 0.323 LogMAR at 2nd month (P = 0.000), 0.657 ± 0.357 at 4th month (P = 0.000), and 0.690 ± 0,448 at 6th month (P = 0.001). Mean CMT (baseline = 582.51 ± 148.20) decreased statistically significantly at 2nd month and 4th month after the first intravitreal injection (245.87 ± 103.86 and 456.68 ± 182.735, respectively, both P < 0.001 vs. baseline). At the 6th month, CMT was 407.93 ± 212.70 for the 16 eyes that had not been reinjected versus baseline CMT 576.93 ± 158.56 (P = 0.008). After other Ozurdex® injections, we had the same visual acuity gain and CMT reduction, an average of 2.03 ± 0.83 injections were done. The most common side effects were cataract development and rise in IOP. Conclusion: Ozurdex® implant is an effective treatment for vascular macular edema with a good safety profile; however, its effectiveness seems to decrease with time requiring repeated injections.
Keywords: Chronic uveitis, dexamethasone implant, diabetes, macular edema, retinal vein occlusion
|How to cite this article:|
Abdellaoui M, El Bahloul M, Bennis A, Chraïbi F, Najdi A, Benatiya IA. Safety and long-term outcomes of repeated dexamethasone intravitreal implant (OZURDEX®) for the management of macular edema: Real-life study. Egypt Retina J 2021;8:26-33
|How to cite this URL:|
Abdellaoui M, El Bahloul M, Bennis A, Chraïbi F, Najdi A, Benatiya IA. Safety and long-term outcomes of repeated dexamethasone intravitreal implant (OZURDEX®) for the management of macular edema: Real-life study. Egypt Retina J [serial online] 2021 [cited 2022 Jul 5];8:26-33. Available from: https://www.egyptretinaj.com/text.asp?2021/8/1/26/336671
| Introduction|| |
The prevalence of vascular macular edema and especially diabetic macular edema is in perpetual increase; in fact, it presents the leading cause of vision loss in diabetic patients.
The therapeutic arsenal of macular edema is rich and includes, in addition to the management of systemic risk factors, the focal laser photocoagulation in focal macular edema not reaching the central region, nevertheless for clinically significant diffuse macular edema, treatment is based on intravitreal (IVT) injection of anti-vascular endothelial growth factor (VEGF) agents or corticosteroid.,
Although currently IVT injections of anti-VEGF have proved their efficacy for the treatment of macular edema in several pilot studies, some patients can have a poor response to it., In addition, the compliance to the treatment is moderate because of the iterative and the high number of injections per year. Hence the interest of the use of corticoid in the management of macular edema.
Corticosteroids act in different ways on macular edema. It has an anti-inflammatory action resulting in a decrease in the recruitment of cells involved in inflammation than in the production of inflammation mediators. They have also an anti-edematous action due to their ability to reduce the breakdown of the blood-retinal barrier, especially by increasing the activity and density of intercellular junctions, by decreasing the synthesis of prostaglandins and VEGF and by their role in the regulation of homeostasis under the influence of microglia and Müller cells. Besides to the two previous actions, corticosteroids have an anti-angiogenic action linked in particular to the inhibition of neovascular growth factors (including VEGF) and metalloproteinases. It has also an anti-angiogenic action linked in particular to the inhibition of neovascular growth factors (including VEGF) and metalloproteinases.
Intravitreal triamcinolone acetonide has been used initially off label to treat macular edema, and it has been shown a good efficacy than placebo in improving vision in patients with refractory macular edema. However, triamcinolone acetonide has several side effects, particularly an increased intraocular pressure (IOP) and cataract development.
Dexamethasone intravitreal implant (Ozurdex®) is a biodegradable implant, containing 0.7 mg dexamethasone with progressive release, its biological activity is maintained for 4–6 months.,
Different studies have reported effectiveness and safety of this dexamethasone intravitreal implant in anatomical and functional improvement of macular edema.,
Although the Ozurdex® implant has been available in Morocco since 2016, it remains nonrefundable by social security schemes outside the medical assistance scheme. Contrary to other countries, no clinical study has provided specific results for our population.
We aimed primarily through this real-life study to evaluate the efficacy of the Ozurdex® implant and secondarily to assess its safety in the treatment of vascular macular edema.
| Materials and Methods|| |
This prospective and observational clinical study included patients with vascular macular edema, followed between January 2017 and October 2018.
It included patients with vascular macular edema; that is to say, macular edema secondary to diabetes or secondary to retinal vein occlusion and chronic uveitic macular edema.
The inclusion criteria were as follows: macular edema with clinically significant vision loss defined by a best-corrected visual acuity (BCVA) <0.2 LogMAR refractory to IVT injections of anti-VEGF or for whom noncorticoid treatment is not suitable, central macular thickness (CMT) ≥300 μm.
Refractory macular edema to IVT injections of anti-VEGF was defined by no increasing in BCVA and/or no decreasing in CMT with a minimum of three intravitreal injections of bevacizumab 1.25 mg, administered 1 month apart. Moreover, treatment with bevacizumab must precede IVT injection of dexamethasone implant by at least 1 month.
Patients were excluded if they had any of the following criteria: poorly controlled diabetes (hemoglobin A glycated >10%), glaucoma unbalanced by monotherapy, proliferative diabetic retinopathy without effective pan-retinal photocoagulation, macular ischemia on fluorescein angiography, and notion of herpes infection of the studied eye.
The data collected were age, sex, general history (diabetes, high blood pressure, dyslipidemia, and sleep apnea syndrome), ophthalmologic history (glaucoma, cataract surgery, and herpes infection), the duration of evolution of symptoms and previous treatment with anti-VEGF as well as the date of the last IVT.
Baseline and follow-up visits included BCVA measurement (BCVA was initially reported as Snellen fraction More Detailss, it was converted to the logarithm of the minimal angle of resolution “log-MAR”), slit-lamp biomicroscopy, dilated fundoscopy, IOP measurement (Goldmann applanation tonometer) corrected by pachymetry, and CMT measurement with optical coherence tomography (SD-OCT). Fluorescein angiography for evaluating the presence of macular ischemia was performed at the baseline evaluation.
Therapeutic protocol and follow-up
A single ophthalmologist conducted all intravitreal injections. Drug administration was performed under sterile conditions in the operating room, after applying topical oxybuprocaïne 0.4 %, eyelids and supraorbital area were disinfected with 10% povidone iodine. The conjunctiva was also disinfected with povidone iodine 5% after sterile field was placed and eyelids were opened with a blepharostat.
Dexamethasone intravitreal implant was inserted into the vitreous cavity through the pars plana 3.5 to 4.0 mm from the limbus, depending on the whether the patient was phakic or pseudophakic.
Prophylactic antibiotic treatment (topical azithromycin 15 mg/g eye drop) was given twice a day for 3 days directly thereafter.
The controls, after, the first IVT, were carried out on the 1st and the 7th day; then in the absence of increased IOP noted at the first injection, the controls were performed 2 (M2), 4 (M4), and 6 (M6) months after retreatment with dexamethasone implant.
Our retreatment criteria were as follows: BCVA ≤ 0.3 LogMAR or a decrease in visual acuity after initial improvement that did not exceed 0.2 LogMAR, and recurrence of macular edema defined by an increase in CMT >20% compared to the last assessment and after initial improvement. Patient flow through the study is shown in [Figure 1].
|Figure 1: Patient flow through our study. ME: Macular edema, RVO: Retinal vein occlusion, **Because patients were included at different times after the start of the study|
Click here to view
Study objectives and outcomes assessment
The main objective of the study was to evaluate the efficacy of the Ozurdex® implant, by evaluating the maximum of functional response (visual acuity gain), the maximum of anatomic response (decrease in CMT), and the retreatment interval. The efficacy of the treatment was evaluated for each eye and it was defined by a visual acuity gain of 2 lines with a CMT <300 μm.
The secondary objective was to evaluate the safety of the Ozurdex® implant by the assessment of the rate of cataract surgery, ocular infections, and the rate of increased IOP. Post Ozurdex® IVT IOP increasing was defined by untreated IOP ≥23 mmHg and IOP ≥21 mmHg treated with one antiglaucoma medication.
Data entry and analysis
The input of this data was done on Excel. The quantitative variables were described in terms of mean with standard deviation and the qualitative variables in percentage. The effectiveness of the treatment was calculated at M2 and M4 after the first IVT injection, and we remained descriptive at M6 and after the following Ozurdex® implant injections.
Student's paired sample t-test was used to compare BCVA and CMT before treatment, 2, 4, and 6 months after the first injection.
We also studied the efficacy according to several basic factors including age, sex, indication of dexamethasone intravitreal implant, and the duration of evolution of macular edema before treatment with Ozurdex® implant; the Chi-square test was used to study the qualitative variables and the Student's independent sample t-test was used to study the quantitative variables. P < 0.05 were considered statistically significant, and analyses were performed using SPSS version 21(epidemiology laboratory of the faculty of medicine of tangier).
The ethical aspect
Our patients have been informed that their data will be the subject of a study, so we have obtained their informed consent.
| Results|| |
A total of 31 eyes of 24 patients (13 men, 11 women; mean age = 55.25 ± 10.73 years) were included in the present study. The indication of dexamethasone intravitreal implant was diabetic macular edema in 17 eyes (54.84%), macular edema secondary to retinal vein occlusion in 7 eyes (22.58%), and chronic uveitic macular edema in 7 eyes (22.58%).
About 62.5% of patients were diabetic, all had type II diabetes, and the most of them (70.37%) had a hemoglobin A glycated between 6.5 and 7.5%, and the average duration of diabetes was 9.9 ± 7.07 years. Among diabetic patients, 52.63% have preproliferative diabetic retinopathy. Fourteen patients were treated for high blood pressure and two patients were treated for glaucoma managed with one antiglaucoma medication. Twenty-one eyes were phakic and 10 eyes were pseudophakic; among the phakic patients, four had a beginner cataract.
The mean macular edema duration was 10.0 ± 5.41 months. Seven eyes were treatment-naïve, and the other 24 eyes had received intravitreal bevacizumab injections before injection of the dexamethasone implant. The mean interval between bevacizumab treatment and dexamethasone implantation was 3.83 ± 2.64 months. Other baseline characteristics of the patients are shown in [Table 1].
The treatment was effective at M2 for 70% of eyes according to the criteria we defined previously. In univariate analysis, this efficacy was associated with the duration of evolution of macular edema (mean duration was 9.52 months in eyes for which Ozurdex® implant was effective; P = 0.000; versus 13 months in eyes for which treatment was ineffective) and indication of dexamethasone intravitreal implant; indeed, the treatment was effective for 64.7% of eyes treated for DME [Figure 2] and [Figure 3], 50% of eyes treated for edema secondary to retinal vein occlusion [Figure 4], and 100% of eyes treated for chronic uveitic macular edema (P = 0.002) [Figure 5]. At M4, the efficacy rate of the treatment was 20%, which explains the need for reinjection within 6 months. In general, an average of 2.03 ± 0.83 injections were required for all eyes during 22 months of follow-up, with a mean time interval between two successive injections of 5.47 ± 1.27 months. Subgroup analysis showed an average of 2.3 ± 0.83, 2.5 ± 0.57, and 1.28 ± 0.48 injections during the follow-up period, respectively, for eyes with DME, macular edema secondary to retinal vein occlusion, and chronic uveitic macular edema. Interval of reinjection was 5.4 ± 1.27, 4.75 ± 0.86, and 7 ± 0.25 months, respectively, in the previous three groups.
|Figure 2: Optical coherence tomography of the right eye of 50 year-old woman, who had DME refractory to IVT of anti-VEGF. (a) Baseline CMT, BCVA at baseline visit was 0.4 LogMar; (b-d) CMT at months 2, 4, and 6, respectively, after IVT injection of dexamethasone implant. BCVA improved to 0.1 LogMar at M2, M4, and 0.2 LogMar at M6. In this case, we can observe a sustained effect over up 6 months|
Click here to view
|Figure 3: Evolution of CMT during 4 months after Ozurdex implant, in a 55-year-old patient with DME refractory to IVT of anti-VEG. Baseline CMT (a) and BCVA were, respectively, 699 μm and 0.5 LogMar. 2 months after Ozurdex implant (b) CMT decreased to 215μm and BCVA improved to 0.3 LOGMar. At M4 (c), we can see reappearance of macular edema (CMT was 528μm and BCVA was 0.4 LogMAR)|
Click here to view
|Figure 4: Optical coherence tomography showing the evolution of Macular edema secondary to central retinal vein occlusion 4 months after Ozurdex® implant in a 50-year-old patient. (a) Baseline CMT was 796 μm with BCVA of 1.3 LogMar, (b) significant improvement in CMT (204μm) and BCVA (0.2 LogMar) 2 months after the IVT. However, at the 4th month after IVT (c) macular edema subsequently relapsed, CMT increased to 641μm and BCVA decreased to 0.7 LogMar|
Click here to view
|Figure 5: Optical coherence tomography showing the evolution of CMT during 6 months after Ozurdex implant, in a 45-year-old patient with chronic uveitic ME. Baseline CMT (a) and BCVA were, respectively, 527 μm and 1 LogMar. (b-d) CMT was 297μ, 308 μm and 318 μm at M2, M4, and M6, respectively, with stable BCVA (0.5 LogMar) during 6 months after dexamethasone intravitreal implant|
Click here to view
The analysis of other prognostic factors revealed that treatment efficiency was not affected by age, sex, baselines logMAR BCVA, and CMT.
Changes in visual acuity
After the first intravitreal injection, BCVA (baseline 0.940 ± 0.463 LogMAR) improved significantly to 0.483 ± 0.323 LogMAR at 2nd month (P = 0.000), 0.657 ± 0.357 at 4th month (P = 0.000), and 0.690 ± 0,448 at 6th month (P = 0.001).
This corresponded to a mean gain from baseline of 4.5 lines at 2nd month (P = 0.000), 2.8 lines at 4th month (P = 0.000), and 2.5 lines at 6th month (P = 0.002). Results of the following injections are shown in [Table 2].
|Table 2: Change in best-corrected visual acuity and central macular thickness after repeat Ozurdex® intravitreal implants|
Click here to view
Mean CMT (baseline = 582.51 ± 148.20) decreased statistically significantly at 2nd month and 4th month after the first intravitreal injection (245.87 ± 103.86 and 456.68 ± 182.735, respectively, both P < 0.001 vs. baseline). At the 6th month, CMT 407.93 ± 212.70 for the 16 eyes that had not been reinjected versus baseline CMT 576.93 ± 158.56 (P = 0.008). Details of results of the others IVT are shown in [Table 2].
Cataract surgery was performed in 58% of the phakic eyes (n = 12/21) during the study period. About 15% of cataracts were diagnosed after the first injection, 24% after the second injection, and 19% after the third injection.
Increasing in IOP was observed at the 1st month after the first dexamethasone intravitreal injection, the mean IOP (baseline = 15.13 mmHg ± 2.34) was raised to 18 mmHg ± 5.28 at 2nd month and 17.31 mmHg ± 2.94 at 4th month and returned to baseline value 15.06 mmHg ± 1.61 at 6th month.
IOP ≥23 mmHg was diagnosed in 41.94% (n = 13) of eyes of which two had an IOP ≥30 mmHg. IOP Increasing required one topical antiglaucoma medication in 69.23% (n = 9) of eyes, two and three topical antiglaucoma medication was used in 15.38% (n = 2) of eyes, without any additional procedures (laser or surgery) to normalize IOP. No progression of IOP elevation or other adverse effects, such as endophtalmitis, was noted due to repeated dexamethasone intravitreal injections.
| Discussion|| |
The goal of our study was to assess long-term real-life effectiveness and safety of intravitreal dexamethasone implant (Ozurdex®) in patients with vascular macular edema. We have demonstrated through this study an efficiency rate of around 70% at the 2nd month after the first IVT injection, with a mean visual gain of 4.5 lines and a reduction of CMT between baseline and 2nd month post treatment of 336.64 (both P = 0.000 vs. baseline). This corresponds to the peak effectiveness of intravitreal dexamethasone implant, which is consistent with results published in the majority of studies, especially Sarda et al. and Yucel et al. who reported a maximum efficiency of the treatment at 2nd and 3rd months, respectively.,
At the 4th month after the first IVT injection, the efficiency rate was around 20%, thus requiring a reinjection. Statistical analysis was carried out only after the first injection; for subsequent injections, we stayed observational because of the small size and the heterogeneity of the sample. We found the same efficiency rate and the same improvement of BCVA and CMT after the following Ozurdex® injections.
Our results confirm those of other studies previously published; indeed, Bonfiglio et al. showed in a prospective study about 44 eyes with DME refractory to three previous ranibizumab IVT, a maximum improvement of BCVA at 1 month after treatment (from baseline 51.5 ± 8.3 letters to 56.9 ± 8.8 letters, P = 0.017) and a significantly reduction of CMT at the 1st and 3rd months (from 618 ± 94 μm to 417 ± 149 μm and 469 ± 128 μm, respectively, both P < 0.001); however at the 6th months, BCVA and CMT were returned to baseline value (51.3 ± 7.9 letters and 590 ± 97 μm respectively).
Moreover, Khan et al. reported in a recent metanalysis of 15 studies, including 3859 patients presenting with DME resistant to IVT injections of anti-VEGF and treated with intravitreal dexamethasone implant; overall, Moreover, Khan et al. reported in a recent metanalysis of 15 studies, including 3859 patients presenting with DME resistant to IVT injections of anti-VEGF and treated with intravitreal dexamethasone implant; overall, a mean improvement in vision of 0.47 LogMAR with a mean gain of 4 lines during mean follow-up period of 6 months” This sentence is complete.
In the current study, a gain of 2 lines with a CMT <300 μm was seen in 64.7% of eyes treated for DME; to maintain this efficiency, an average of 2.3 ± 0.83 injections during 22 months of follow-up with a time interval between two successive injections of 5.4 ± 1.27 months were necessary. Scaramuzzi et al. observed in a retrospective study about 15 eyes of 12 patients with DME, an improvement of 2 lines or more in BCVA in 33% of patients, and the mean retreatment time was 7.8 ± 4.1 months after the first intravitreal dexamethasone injection. Another study conducted by Querques et al. reported an average of 2.4 injections per year and 4.9 months between treatments in patients treated for DME.
Regarding eyes treated for macular edema secondary to retinal vein occlusion, the efficacy rate was 50% with a mean IVT number of 2.5 ± 0.57 during the follow-up period and an interval of reinjection of 4.75 ± 0.86 months; here also, the maximum efficiency was seen at 2 months. In a retrospective study about 33 eyes with glaucoma or treated ocular hypertension with macular edema due to retinal vein occlusion, Theodoropoulou et al. reported a significant improvement in BCVA 2 months after intravitreal dexamethasone implant (P = 0.049), increasing in BCVA at months 4, 6, and 12 which was not significant. CMT reduction was significant in the first 4 months after dexamethasone injection; mean CMT decreased from 530 ± 25 μm at baseline visit to 323 ± 27 μm and 445 ± 32 μm, respectively, at the 2nd month and the 4th month after intravitreal injection. Blanc et al. conducted a retrospective multicenter study including 66 patients with macular edema secondary to retinal vein occlusion; after 3 years of follow-up, patients had received a median of 5 dexamethasone implant injections and the median time of reinjection was 4.8 months.
Ozurdex® seems to produce a sustained effect over up to 6 months in chronic uveitic macular edema; a retrospective case series conducted by Garweg et al. including 36 eyes with uveitic macular edema showed that complete resolution of central macular edema was achieved in 94% by 1 month and in 80% by 3 months after injection. Compared with baseline, CMT decreased from 519 ± 43 μm to 297 ± 23 μm and 356 ± 49 μm in the 1st and 3rd month visit control (P = 0.02) and to 429 ± 57 μm before reimplantation of Ozurdex®; similarly, BCVA improved from 0.47 ± 0.06 LogMAR at baseline visit to 0.34 ± 0.09 LogMAR, 0.26 ± 0.07 LogMAR, and 0.29 ± 0.08 LogMAR at the first and 3rd months of follow-up and before reinjection of dexamethasone implant, respectively. Always in the same study, mean time to reimplantation of dexamethasone implant was 6.6 ± 3.4 months. Likewise, we demonstrated that the duration of the dexamethasone-induced effect persists longer in cases of uveitic macular edema. In our study, ozurdex® implant had an excellent efficiency rate. in fact, it was around of 100%, with an average of 1.28 ± 0.48 injections during the follow-up period and a time interval between 2 successive injections of 7± 0.25 months.
Overall, after the 2nd and 3rd intravitreal dexamethasone implant, we had a visual acuity gain and a CMT reduction comparable with those after the first intravitreal Ozurdex® injection. Despite the anatomical improvement after the 4th Ozurdex® IVT, BCVA changes were not so important, this could be explained by steroid-related cataract progression. The efficacy results from our study compare favorably with those reported in the Mead trial by Boyer et al., but unlike the Mead study protocol that defined 6 months as the minimum interval time for retreatment, the mean interval of reinjection was 5.4 ± 1.27 months for eyes with DME in our study. In the Louvre study; conducted by Korobelnik et al, including 375 patients with macular edema due to retinal vein occlusion and followed in 48 randomly selected sites in metropolitan France; the mean change at the end of follow up from baseline BCVA was +20.7 letters in patients treated with a single dexamethasone implant only, and +4.9 letters in patients treated with ≥ 2 dexamethasone implants, in this case patients received a mean of 2.6 dexamethasone implant over 24 months, mean time between injections was 6.6 months.
Our results at the 6th month after each IVT appear better than those at the 4th month post-IVT because patients who have BCVA ≤0.3 LogMAR or a decrease in visual acuity after initial improvement that did not exceed 0.2 LogMAR and an increase in CMT >20% compared to the last assessment were reinjected before the 6th month control visit.
In this study, the analysis of prognostic factors revealed that treatment efficiency was related to the short duration of evolution of macular edema and indication of dexamethasone intravitreal implant, but it is not affected by age, sex, baselines logMAR BCVA, CMT, and lens status. We can notice a light discrepancy with Lee's study, including 32 eyes with DME treated with intravitreal injection of dexamethasone implant, which showed that functional and anatomical improvement was predicted by baselines BCVA, intraretinal fluid morphology, and the short duration of DME. This can be explained by the fact that we only did univariate analysis because of the variability and small size of our sample. However, likewise in Lee's and Zur's studies, we observed that improvement in BCVA at months 2–4 after Ozurdex® implantation was correlated with poor baseline LogMar BCVA., Furthermore, our baseline LogMar BCVA was very low (0.94 ± 0.46) compared to Lee's study (0.58 ± 0.37) and Zur's one (0.68 ± 0.32 for naïve eyes and 0.58 ± 0.27 for eyes with DME refractory to IVT of anti-VEGF).
The most common side effects in our study were cataract development and rise in IOP. Cataract surgery was performed in 58% of our phakic eyes compared to 47% and 73% of baseline phakic eyes in the Reldex study and the subgroup analysis of the Mead study.,
We observed raised IOP in 41.94% of eyes, which appears to be similar with results reported by Theodoropoulou et al.(42% of eyes had an IOP of 21 mmHg or higher). IOP of ≥23 mmHg was seen in 10.2% and in 16.7% of eyes by Malclès et al. and by Yucel et al., respectively., Inversely, Blanc et al. reported that increase of IOP was more frequent in their series (54.5% of eyes) than in literature. As in the most major studies,,,, IOP elevation was managed in all cases by IOP-lowering medication.
The main limitation of our study is the small size and heterogeneity of our sample; not all patients were included at the same time, and the Ozurdex® implant is still not reimbursed by social security in our country, which limits its use. On the other hand, the strengths of this study include its prospective nature, the wide variation in patient and ocular characteristics, the relatively long history of DME, and the use of prior anti-VEGF injections for majority of our patients, which corresponds to real-life situations.
| Conclusion|| |
Dexamethasone intravitreal implant (Ozurdex®) appears to be effective for the treatment of vascular macular edema, whether for treatment-naïve or previously treated eyes with a maximum efficiency observed during the first 3 months. However, to sustain its effectiveness, repeated injections are required; the time interval between two successive injections is variable depending on the therapeutic indication, it is 5 months on average. Despite iterative injections, Ozurdex® implant has a good safety profile.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Unsal E, Eltutar K, Sultan P, Erkul SO, Osmanbasoglu OA. Efficacy and safety of intravitreal dexamethasone implants for treatment of refractory diabetic macular edema. Korean J Ophthalmol 2017;31:115-22.
Sarda V, Fajnkuchen F, Nghiem-Buffet S, Grenet T, Chaine G, Giocanti-Auregan A. Early efficacy of dexamethasone implant (OZURDEX®
) in diabetic macular edema: Real life study. J Fr Ophtalmol 2017;40:408-13.
Creuzot-Garcher C, French Society of Ophthalmology. Macular edema: 2016 SFO report. ELSEVIER MASSON, ISBN: 2016:978-2-294-74949-0.
Bonfiglio V, Reibaldi M, Pizzo A, Russo A, Macchi I, Faro G, et al.
Dexamethasone for unresponsive diabetic macular oedema: Optical coherence tomography biomarkers. Acta Ophthalmol 2019;97:e540-4.
Yucel OE, Can E, Ozturk HE, Birinci H, Sullu Y. Dexamethasone implant in chronic diabetic macular edema resistant to intravitreal ranibizumab treatment. Ophthalmic Res 2017;57:161-5.
Castro-Navarro V, Cervera-Taulet E, Navarro-Palop C, Monferrer-Adsuara C, Hernández-Bel L, Montero-Hernández J. Intravitreal dexamethasone implant Ozurdex® in naïve and refractory patients with different subtypes of diabetic macular edema. BMC Ophthalmol 2019;19:15.
Theodoropoulou S, Ellabban AA, Johnston RL, Cilliers H, Mohamed Q, Sallam AB. Short-term safety of dexamethasone implant for treatment of macular edema due to retinal vein occlusion, in eyes with glaucoma or treated ocular hypertension. Graefes Arch Clin Exp Ophthalmol 2017;255:725-32.
Korobelnik JF, Kodjikian L, Delcourt C, Gualino V, Leaback R, Pinchinat S, et al.
Two-year, prospective, multicenter study of the use of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in the clinical setting in France. Graefes Arch Clin Exp Ophthalmol 2016;254:2307-18.
Mello Filho P, Andrade G, Maia A, Maia M, Biccas Neto L, Muralha Neto A, et al.
Effectiveness and safety of intravitreal dexamethasone implant (Ozurdex) in patients with diabetic macular edema: A real-world experience. Ophthalmologica 2019;241:9-16.
Augustin AJ, Kuppermann BD, Lanzetta P, Loewenstein A, Li XY, Cui H, et al.
Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: Subgroup analysis of the MEAD study. BMC Ophthalmol 2015;15:150.
Khan Z, Kuriakose RK, Khan M, Chin EK, Almeida DR. Efficacy of the intravitreal sustained-release dexamethasone implant for diabetic macular edema refractory to anti-vascular endothelial growth factor therapy: Meta-analysis and clinical implications. Ophthalmic Surg Lasers Imaging Retina 2017;48:160-6.
Scaramuzzi M, Querques G, Spina CL, Lattanzio R, Bandello F. Repeated intravitreal dexamethasone implant (Ozurdex) for diabetic macular edema. Retina 2015;35:1216-22.
Querques G, Darvizeh F, Querques L, Capuano V, Bandello F, Souied EH. Assessment of the real-life usage of intravitreal dexamethasone implant in the treatment of chronic diabetic macular edema in France. J Ocul Pharmacol Ther 2016;32:383-9.
Blanc J, Deschasse C, Kodjikian L, Dot C, Bron AM, Creuzot-Garcher C. Safety and long-term efficacy of repeated dexamethasone intravitreal implants for the treatment of cystoid macular edema secondary to retinal vein occlusion with or without a switch to anti-VEGF agents: A 3-year experience. Graefes Arch Clin Exp Ophthalmol 2018;256:1441-8.
Garweg JG, Baglivo E, Freiberg FJ, Pfau M, Pfister IB, Michels S, et al.
Response of postoperative and chronic uveitic cystoid macular edema to a dexamethasone-based intravitreal implant (Ozurdex). J Ocul Pharmacol Ther 2016;32:442-50.
Boyer DS, Yoon YH, Belfort R Jr., Bandello F, Maturi RK, Augustin AJ, et al.
Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 2014;121:1904-14.
Lee H, Kang KE, Chung H, Kim HC. Prognostic factors for functional and anatomic outcomes in patients with diabetic macular edema treated with dexamethasone implant. Korean J Ophthalmol 2018;32:116-25.
Zur D, Iglicki M, Busch C, Invernizzi A, Mariussi M, Loewenstein A, et al.
OCT biomarkers as functional outcome predictors in diabetic macular edema treated with dexamethasone implant. Ophthalmology 2018;125:267-75.
Malclès A, Dot C, Voirin N, Agard É, Vié AL, Bellocq D, et al.
Real-life study in diabetic macular edema treated with dexamethasone implant: The reldex study. Retina 2017;37:753-60.
Ramu J, Yang Y, Menon G, Bailey C, Narendran N, Bunce C, et al.
A randomized clinical trial comparing fixed vs pro-re-nata dosing of Ozurdex in refractory diabetic macular oedema (OZDRY study). Eye (Lond) 2015;29:1603-12.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]