Diabetic macular edema (DME) is one of the clinical manifestations of diabetic retinopathy (DR). It is the leading cause of reduced visual acuity and visual impairment in diabetic patients [
The management of DME has changed significantly in recent years. For several decades, laser photocoagulation [
The objective of this work is therefore to synthetize the available observational studies concerning the pharmacological management of DME.
A review of the literature was conducted on the PubMed database on February 1, 2018, to identify all articles investigating the efficacy of anti-VEGF and DEX-implants for treating DME. The key words used were as follows: diabetic macular edema (DME) AND ranibizumab, DME AND Lucentis, DME AND bevacizumab, DME AND Avastin, DME AND aflibercept, DME AND Eylea, DME AND dexamethasone implant, DME AND Ozurdex, DME AND ranibizumab AND aflibercept AND bevacizumab AND dexamethasone implant, and finally DME AND Lucentis AND Avastin AND Eylea AND Ozurdex.
Only articles published in English were selected. Only the ranibizumab, aflibercept, bevacizumab, and dexamethasone implant molecules were retained. Two study designs were found: randomized pivotal studies and observational “real-life” studies. Only the observational studies were selected for this work. Of the studies investigating the efficacy of anti-VEGF and DEX-implant, only series with an initial enrollment of more than 10 patients and follow-up of more than six months were included in the final analysis. For any given study, if different anti-VEGF drugs were used or different types of patients included (for instance naïve versus non-naïve patients), we presented the results separated into different groups of treatment.
The visual acuity (VA) or gain values used for this work were the primary objectives from each study. For the anti-VEGF studies, the VA or gain values used were the end-of-study data, and for the DEX-implant studies, the primary effectiveness endpoints were the maximum mean change in best corrected visual acuity (BCVA) (best improvement) from baseline after each DEX injection. This criterion for DEX-implant was validated by the Food and Drug Administration (FDA) and used in the Reinforce study [
In order to report on functional efficacy, a comparison of VA gains, final VA, and the number of anti-VEGF injections or DEX-implants was initially conducted on the overall study population. Secondary analyses of subgroups, formed according to BVA (less than 50 letters, between 50 and 60 letters, and greater than 60 letters) and the naïve or non-naïve status of the patient at baseline, were also performed. In the case of switching therapy, a minimum wash out time of 1 month was observed in all the studies. The results are presented with the mean gain value and range (minimum and maximum gain observed in studies).
Our PubMed search initially screened 189 studies, 129 studies of anti-VEGF, and 60 studies of DEX-implants. After eliminating the interventional studies and applying our search criteria (follow-up ≥ 6 months and a minimum of 10 patients included), a total of 32 studies (38 groups of treatment) evaluating the efficacy of anti-VEGF [
For the anti-VEGF studies, patients had a mean BVA of 57.3 letters (range 38-72 letters). Mean follow-up was 15.6 months (6-48 months). During follow-up, a mean gain of + 4.7 letters (-5 - +8.5 letters) (median 4.7 letters) was observed for a mean of 5.8 intravitreal injections (IVI) (1.3-17) (Figures
Summary of observational studies investigating the efficacy of anti-VEGF in the treatment of diabetic macular edema.
Final visual acuity as a function of baseline visual acuity in studies evaluating the efficacy of anti-VEGF.
For the DEX-implant studies, patients had a mean BVA of 51.5 letters (range 18.8-72.5 letters). Mean follow-up was 10.3 months (6-36 months). During follow-up, a mean maximum gain of + 9.6 letters (+5.2 - +20.2 letters) was observed for a mean number of 1.6 IVI (1-3.9) (Figures
Summary of observational studies investigating the efficacy of the dexamethasone implant in the treatment of diabetic macular edema.
Final visual acuity as a function of baseline visual acuity in studies evaluating the efficacy of the dexamethasone implant.
Figure
Comparison of mean gain in the different observational studies investigating the efficacy of dexamethasone implant (Figure
By analyzing the results according to the patient’s baseline status, we found, in the anti-VEGF studies, a mean gain of + 5 letters for 5.2 IVI in naïve patients (BVA 56 letters) [
In the DEX-implant studies, there was a mean gain of + 12 letters for 1.9 IVI in naïve patients (BVA 57.9 letters) [
Visual acuity gain in ETDRS letters according to the patients’ naïve or non-naïve status in the different observational studies with dexamethasone implant (a) and anti-VEGF (b).
In the anti-VEGF studies, the non-naïve patients had received a mean of at least 10.7 treatments (other anti-VEGF, Triamcinolone IVT, DEX IVT, focal laser) prior to inclusion, compared to 5.4 in the DEX-implant studies.
For subgroups with low BVA (<50 letters), there is a mean gain of +4.3 letters in the anti-VEGF studies [
For subgroups with BVA of between 50 and 60 letters, there is a mean gain of + 5.8 letters in the anti-VEGF studies [
Finally, for subgroups with high BVA (>60 letters), there is a mean gain of + 3.1 letters in the anti-VEGF studies [
Summary of BVA, gain, final VA and mean number of injections in the overall population and subgroups for anti-VEGF and DEX-implant observational studies (BVA: baseline visual acuity, IVI: intravitreal injection.
Anti-VEGF | DEX-implant | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Number of eyes | BVA (letters) | Mean gain (letters) | Final VA (letters) | Mean follow-up (months) | Mean IVI | Number of eyes | BVA (letters) | Mean gain (letters) | Max VA (letters) | Mean follow-up (months) | Mean IVI | |
Overall population | 6842 | 57.3 | +4.7 | 62 | 15.6 | 5.8 | 1703 | 51.5 | +9.6 | 61.2 | 10.3 | 1.6 |
BVA | ||||||||||||
≤ 50 letters | 449 | 42.4 | +4.3 | 46.7 | 13 | 3 | 363 | 39.4 | +10.5 | 49.9 | 9 | 1.2 |
50-60 letters | 4773 | 55.7 | +5.8 | 61.7 | 16.3 | 5.8 | 1218 | 54.1 | +9.3 | 63.7 | 11.6 | 1.75 |
≥ 60 letters | 1620 | 65.3 | +3.1 | 68.3 | 13.5 | 6.5 | 122 | 68.4 | +8.8 | 76.5 | 9 | 1.8 |
Initial Status | ||||||||||||
Naive patients | 781 | 56 | +5 | 61 | 12.3 | 5.2 | 176 | 57.9 | + 12 | 69.9 | 10.8 | 1.9 |
Non-naïve patients | 413 | 56.9 | + 4.8 | 61.8 | 12.1 | 6.2 | 801 | 48.7 | +8.6 | 57.3 | 9.2 | 1.4 |
Visual acuity gain (in letters ETDRS) according to the 3 baseline visual acuity subgroups in the observational studies with dexamethasone implant (a) and anti-VEGF (b).
Table
Since anti-VEGF and DEX-implants came onto the market, the therapeutic practices for DME have evolved, and laser photocoagulation treatments have gradually been abandoned in favor of IVI. Indeed, the impressive results obtained in clinical trials have encouraged practitioners to use these pharmacological treatments which offer much higher VA gains [
Indeed, these types of studies have numerous advantages over interventional studies: they provide a more accurate reflection of routine practice; confirm the effectiveness of a treatment under real conditions; include unselected patients under a regimen based on day-to-day practice (actual injection intervals and follow-up); provide complementary data to the interventional studies (notably on the state of practice and possible comparisons between countries); and also provide long-term data. On the other hand, these studies have a number of potential drawbacks, including the possibility of introducing bias (missing data, patients lost to follow-up) and a lower level of evidence. It is therefore essential to analyze a significant number of observational studies and to synthetize their findings, in order to draw scientifically valid conclusions from them.
Real-life observational studies tend to confirm the level of efficacy obtained in interventional studies of pharmaceutical treatments for DME. Indeed, observational studies of anti-VEGF and DEX-implants show VA gains of up to +20 letters. Analysis of the data from these observational studies suggests that the gain in VA is greater with DEX-implant than with anti-VEGF. Indeed, the mean maximum gain obtained after DEX-implant IVI (+9.6 letters) is higher than the mean gain obtained after anti-VEGF (+ 4.7 letters). This increased gain was obtained with a smaller number of IVI in the DEX group compared to the anti-VEGF group. In addition, by setting a gain threshold of 5 letters, the majority of real-life DEX studies achieved increases above this value, in contrast to the majority of anti-VEGF studies (Figure
However, no difference was found in final visual acuity, which is around 62 letters for both groups. This result, which could contradict the observed gains in VA, can be partially explained by the BVA. Indeed, the latter is lower in the DEX studies (BVA 51.5 letters) compared to the anti-VEGF studies (BVA 57.3 letters). This lower level of VA in the DEX studies may relate to the fact that DEX-implant remains a second-line treatment in routine practice [
Thus, in the RELDEX study [
All these data argue in favor of the earlier use of DEX-implant, either as first-line therapy in naïve patients or more quickly as a second-line therapy. Indeed, in the literature, the response to anti-VEGF seems predictable after 3 to 6 injections [
Moreover, our analysis of the observational studies shows that patients with low BVA can potentially gain a substantial number of letters. Indeed, Figure
In the subgroup with low BVA (<50 letters), there is a marked difference between the anti-VEGF (+4.3 letters) and the DEX-implant (+10.5 letters) studies, whereas BVA is relatively similar (42.4 in anti -VEGF versus 39.4 in DEX-implant studies). This difference is also present in the BVA subgroups between 50 and 60 letters with a mean gain of +5.3 letters and +9.3 letters in the anti-VEGF studies (BVA 57.7 letters) and DEX-implant studies (BVA 54.1 letters), respectively. However, the greatest difference is in the subgroups with BVA of more than 60 letters with a mean gain of +3.1 letters (BVA 65.3 letters) and + 8.8 letters (BVA 68.4 letters), respectively.
Therefore, even taking into account the possibility of a ceiling effect, the difference in gain in favor of DEX-implant in this last subgroup shows that the mean VA gain, which seems better in real life with the DEX-implant, is not only due to the lower mean baseline VA for this molecule, as it persists in the high BVA subgroup (greater than 60 letters).
In comparison to the interventional studies, the observational DEX-implant studies appear to yield better results in terms of VA gain. Indeed, the MAGGIORE study reported a gain of + 2.5L for a mean of 2.9 IVI in the first year [
On the other hand, the anti-VEGF studies show precisely the opposite, with better results obtained in the interventional studies compared to the observational studies. Indeed, the interventional studies report a higher gain both for studies using a frequent injection schema, such as RESOLVE (gain of + 10.3L for 10.2 IVI in the first year) [
Concerning side effects, cataract formation and increasing the intraocular pressure (IOP) are considered to be the main side effects of intravitreal corticosteroids and seem to be dose dependent [
Some limitations have been also described with anti-VEGF, including the need for frequent injections, induction of resistance, and tachyphylaxis due to the long-term nature of the treatment [
Concerning the real-life studies evaluated in present analysis, similar side effects have been reported in anti-VEGF and DEX studies (Table
Summary of anti-VEGF and DEX-implant studies (VA: Visual Acuity, CSMT: central subfield macular thickness, ND: nondeclared, IVI: intravitreal injection, IOP: intraocular pressure).
Study | Drugs | Study design | Patient status | Number (eyes) | Follow-up (months) | Mean Number IVI | Baseline VA (letters) | Final VA (letters) | Mean VA gain (letters) | IOP | Cataract progression/extraction | Others complications |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Blinder KJ et al. [ | Anti-VEGF | Retrospective | Mixed | 156 | 36 | 14.2 | 59.0 | 64.5 | 5.5 | 7.7% IOP ≥ 25 mmHg, 1.3% IOP ≥35 mmHg, rise of IOP ≥10 mmHg in 5.1% | 15.4% | No endophthalmitis |
Matsuda S et al. [ | Anti-VEGF | Retrospective | Naïve | 124 | 12 | 5.8 | 57.5 | 64 | 6.5 | ND | ND | ND |
Shah CP et al. [ | Anti-VEGF | Prospective | Non-Naïve | 30 | 29.2 | 17.0 | 63.5 | 67 | 3.5 | ND | ND | ND |
Shimizu N et al. [ | Anti-VEGF | Retrospective | Mixed | 46 | 6 | 2.7 | 65.5 | 70 | 4.5 | ND | ND | ND |
Wecker T, et al. [ | Anti-VEGF | Retrospective | ND | 479 | 12 | 17.0 | 60.5 | 59.2 | -1.3 | ND | ND | ND |
Yiu G et al. [ | Anti-VEGF | Retrospective | Naïve | 33 | 6 | 2.7 | 60 | 64 | 3.85 | ND | ND | ND |
Barhamy B et al. [ | Aflibercept | Prospective | Non-Naïve | 43 | 6 | 5.0 | 67.8 | 71 | 3.2 | 0% (IOP ≥ 25mmHg or a rise of IOP ≥ 10mmHg) | 0% | None |
Herbaut A. et al. [ | Aflibercept | Retrospective | Non-Naïve | 29 | 6 | 3.0 | 57.1 | 65.1 | 8 | ND | ND | ND |
Kaiho T et al. [ | Aflibercept | ND | Non-Naïve | 51 | 12 | 3.8 | 65.5 | 70 | 4.5 | ND | ND | ND |
Klein et al. [ | Aflibercept | Retrospective | Non-Naïve | 11 | 6 | 4.7 | 54.8 | 62.3 | 7.5 | ND | ND | ND |
Aksoy S et al. [ | Bevacizumab | Prospective | Naïve | 20 | 6 | 6.0 | 51.0 | 55.5 | 4.5 | 10% (IOP > 21mmHg) | 2.50% | None |
Fong DS et al. [ | Bevacizumab | Retrospective | Mixed (65% Naïve, 30% Laser, 4% Steroïd) | 309 | 24 | 3.1 | 57 | 62.3 | 5.3 | ND | ND | ND |
Güler E et al. [ | Bevacizumab | Prospective | ND | 20 | 9 | 6.0 | 38 | 42 | 4 | ND | 0% | None |
Hanhart J et al. [ | Bevacizumab | Retrospective | Naïve | 35 | 8 | 3.6 | 60.5 | 64 | 3.5 | ND | ND | ND |
Koc C et al. [ | Bevacizumab | Retrospective | Naïve | 90 | 24 | 4.9 | 45.2 | 48.7 | 3.5 | ND | 13.7% | 1 cerebrovascular accident |
Kook D et al. [ | Bevacizumab | Prospective | Non-Naïve | 126 | 12 | 2.7 | 40.3 | 45.4 | 5.1 | ND | ND | ND |
Riazi-Esfahani M et al. [ | Bevacizumab | ND | Naïve | 46 | 6 | 67.5 | 72.5 | 5 | 6.5% (IOP ≥ 21 mmHg) | 0 | ND | |
Fechter BS et al. [ | Bevacizumab | ND | Non-Naïve | 30 | 12 | 9.3 | 63.5 | 70.35 | 6.9 | ND | ND | None |
Yuksel E et al. [ | Bevacizumab | Retrospective | Non-Naïve | 71 | 9.8 | 2.0 | 41 | 45.5 | 4.5 | ND | ND | ND |
Solaiman KAM et al. [ | Bevacizumab | Prospective | ND | 22 | 14 | 3.3 | 56.3 | 64.3 | 8 | ND | 9.1% | Subconjunctival haemorrhage |
Cheema HR et al. [ | Bevacizumab (Diffuse) | Retrospective | ND | 28 | 6 | 1.3 | 44.0 | 45 | 1 | ND | ND | ND |
Cheema HR et al. [ | Bevacizumab (Focal) | Prospective | ND | 20 | 6 | 2.1 | 69.0 | 73.5 | 4.5 | ND | ND | ND |
Cheema HR et al. [ | Bevacizumab (NSD) | Retrospective | ND | 13 | 6 | 2.6 | 38.5 | 45.5 | 7 | ND | ND | ND |
Mushtaq B et al. [ | Bevacizumab CSMT<400 | ND | ND | 81 | 12 | 3.3 | 56 | 62.5 | 6 | ND | ND | ND |
Mushtaq B et al. [ | Bevacizumab CSMT>400 | ND | ND | 94 | 12 | 4.0 | 51.5 | 57.5 | 6 | ND | ND | ND |
Crosson JN et al. [ | Bevacizumab | Retrospective | ND | 102 | 60 | 5.5 | 50 | 55 | 5 | ND | ND | ND |
Solaiman et al. [ | Bevacizumab | Prospective | ND | 22 | 14 | 2.4 | 54.5 | 59.1 | 4.6 | ND | 9.1% | ND |
Chatziralli I et al. [ | Ranibizumab | Retrospective | Naïve | 332 | 12 | 6.7 | 56.4 | 64.4 | 8 | ND | ND | ND |
Ciulla TA et al. [ | Ranibizumab | Retrospective | Non-Naïve | 33 | 12 | 6.0 | 59.0 | 63 | 4 | ND | ND | ND |
Egan C, et al. [ | Ranibizumab | Retrospective | Mixed (49,6% Naïve) | 3103 | 24 | 5.4 | 51.1 | 52.5 | 1.4 | ND | ND | 1 endophthalmitis |
Granstrom T et al. [ | Ranibizumab | Retrospective | ND | 59 | 12 | 5.0 | 65 | 70.2 | 5.2 | ND | ND | ND |
Hadzibegovic DH et al. [ | Ranibizumab | Retrospective | Mixed (97% Naïve) | 566 | 48 | 13.5 | 64.8 | 67.1 | 2.3 | ND | 9.9% | 1 traumatic cataract |
Katz G et al. [ | Ranibizumab | ND | Non-Naïve | 40 | 16 | 8.4 | 65 | 66.5 | 1.5 | ND | 0 | None |
Koc C et al. [ | Ranibizumab | Retrospective | Naïve | 101 | 24 | 6.9 | 49.8 | 54.8 | 5 | ND | 7.1% | None |
Koyanagi Y et al. [ | Ranibizumab | Retrospective | Non-Naïve | 25 | 12 | 7.4 | 60 | 68.5 | 8.5 | ND | 0 | None |
Mori Y et al. [ | Ranibizumab | Retrospective | Non-Naïve | 68 | 12 | 6.4 | 72 | 77.5 | 5.5 | ND | ND | ND |
Wilke RGH et al. [ | Ranibizumab | Retrospective | ND | 335 | 36 | 10.0 | 59 | 63.8 | 4.8 | ND | ND | ND |
Akincioglu D et al. [ | DEX Implant | Retrospective | Non-Naïve | 57 | 12 | 1.3 | 51 | 58 | 7 | 28% (rise of IOP > 10 mmHg) | 21.5% | ND |
Alshahrani ST et al. [ | DEX Implant | Retrospective | Non-Naïve | 26 | 6 | 1.0 | 52 | 59 | 7 | 26% IOP > 21mmHg | 1.8% | ND |
Bansal P et al. [ | DEX Implant | Retrospective | Mixed | 67 | 6 | 1.0 | 44 | 56 | 12 | 12% (IOP > 21 mmHg) | 4.5% | Subconjunctival haemorrhage |
Chatziral.li I et al. [ | DEX Implant | Prospective | Non-Naïve | 54 | 12 | 2.1 | 52 | 5.2 | 5.6% (IOP > 20mmHg) | 4.3% | ND | |
Chhablani J et al. [ | DEX Implant | Retrospective | Non-Naïve | 64 | 7.67 | 1.3 | 52.5 | 61 | 8.5 | 7.6% (rise of IOP > 10 mmHg) | 2.5% | ND |
Chhablani J et al. [ | DEX Implant | Retrospective | Naïve | 15 | 11 | 1.3 | 56 | 63 | 7 | 7.6% (rise of IOP > 10 mmHg) | 2.5% | ND |
Cicinelli MV et al. [ | DEX Implant | Retrospective | Non-Naïve | 45 | 12 | 1.9 | 64.2 | 70 | 5.8 | 18.4% (IOP ≥ 20 mmHg) | 20% | ND |
Degoumois A et al. [ | DEX Implant | Retrospective | Non-Naïve | 42 | 20.6 | 1.6 | 55 | 61.4 | 6.4 | 8% (IOP > 25 mmHg), 2 % (IOP> 30 mmHg) | 4.8% | ND |
Dutra Medeiros M et al. [ | DEX Implant | Retrospective | Non-Naïve | 58 | 6 | 1.0 | 52 | 63 | 11 | No anecdotal IOP elevation | ND | None |
Escobar-Barranco JJ et al. [ | DEX Implant | Prospective | Non-Naïve | 40 | 6 | 1.9 | 51.3 | 59.4 | 8.1 | 7.9% (rise of IOP > 10 mmHg) | 2.6% | 3.9% Intravitreal haemorrhage |
Escobar-Barranco JJ et al. [ | DEX Implant | Prospective | Naïve | 36 | 6 | 1.9 | 59.6 | 73.6 | 14.1 | 7.9% (rise of IOP > 10 mmHg) | 2.6% | 3.9% Intravitreal haemorrhage |
Esen E et al. [ | DEX Implant | Retrospective | Non-Naïve | 25 | 6 | 1.0 | 36.5 | 46.5 | 10 | 16% (IOP > 21 mmHg) | 4% | None |
Güler E et al. [ | DEX Implant | Prospective | Non-Naïve | 15 | 6 | 49 | 62 | 13 | 20% | 0 | None | |
Iglicki et al. [ | DEX Implant | Retrospective | Non-Naïve | 59 | 24 | 3.1 | 54.5 | 63 | 8.5 | 7.1% | ND | ND |
Iglicki et al. [ | DEX Implant | Retrospective | Naïve | 71 | 24 | 3.9 | 55.5 | 66.8 | 11.3 | 11.4% | ND | ND |
Kaldirim H et al. [ | DEX Implant | Retrospective | Non-Naïve | 35 | 6 | 1.0 | 58 | 69.5 | 11.5 | 11.4% | 0% | ND |
Lozano Lopez V et al. [ | DEX Implant | Retrospective | ND | 36 | 6 | 10.9 | 29.5% (IOP > 23 mmHg) 1.1% filtering surgery | ND | None | |||
Mastropasqua R et al. [ | DEX Implant | Prospective | Naïve | 27 | 6 | 1.7 | 68.5 | 79.5 | 11 | 0% | 0% | ND |
Matonti F et al. [ | DEX Implant | Retrospective | Mixed | 23 | 12 | 2.1 | 49.6 | 60 | 10.4 | 11.7% (IOP> 25 mmHg) | 0% | 26% Subconjunctival haemorrhage |
Moon BG et al. [ | DEX Implant | Retrospective | Mixed | 186 | 6 | >1 | 55 | 60.5 | 5.5 | 4.3% (IOP > 30mmHg) | 23.2% | 1 Infectious endophthalmitis |
Guigou S et al. [ | DEX Implant | Retrospective | Naïve | 16 | 6 | 1.2 | 51.1 | 71.3 | 20.2 | 11.7% (IOP > 25 mmHg), 13.3% (rise of IOP > 10 mmHg) | 0% | 26% Subconjunctival haemorrhage, 8.6% Intravitreal haemorrhage |
Guigou S et al. [ | DEX Implant | Retrospective | Mixed (20,5% De Naïve) | 78 | 6 | 1.2 | 53.9 | 61.92 | 8 | 11.7% (IOP > 25 mmHg), 13.3% (rise of IOP > 10 mmHg) | 0% | 27% Subconjunctival haemorrhage, 2.6% Intravitreal haemorrhage |
Aknin I et al. [ | DEX Implant | Retrospective | Mixed | 29 | 18 | 1.5 | 51.7 | 68.2 | 16.5 | 6.9% (IOP > 25 mmHg) | 13.8% | None |
Pacella E et al [ | DEX Implant | ND | Non-Naïve | 20 | 6 | 1.0 | 18.8 | 28.15 | 9.4 | 5.8% (IOP >26 mmHg) | 0% | None |
Pareja-Rios et al. [ | DEX Implant | Retrospective | Naïve | 113 | 12 | 1.4 | 43.5 | 53.2 | 9.7 | 4% (rise of IOP > 10mmHg) | ND | None |
Pareja-Rios et al. [ | DEX Implant | Retrospective | Naïve | 11 | 12 | 1.4 | 56.5 | 65.3 | 8.8 | 4% (rise of IOP > 10mmHg) | ND | ND |
Bellocq D et al. [ | DEX Implant | Prospective | Mixed (73% Naïve) | 37 | 6 | 1.5 | 58.7 | 68.7 | 10.1 | 14% (IOP > 25 mmHg), 3% (IOP > 35mmHg) 8% (rise of IOP > 10 mmHg) | ND | Subconjunctival haemorrhage |
Fine et al. [ | DEX Implant | Prospective | Non-Naïve | 101 | 12 | 2.0 | 57.2 | 65.9 | 8.7 | 12.2% (IOP > 25 mmHg), 2.8% (IOP > 35mmHg) 12.8% (rise of IOP > 10 mmHg) | ND | Vitreous floaters (4.3%) |
Mal.clès A et al. [ | DEX Implant | Retrospective | Mixed (27% Naïve) | 128 | 36 | 3.6 | 50.5 | 60.6 | 9.5 | 10.2% (IOP > 25 mmHg), 2.3% (IOP > 35mmHg) 19% (rise of IOP > 10 mmHg) | ND | ND |
Sacconi R et al. [ | DEX Implant | Prospective | Mixed | 14 | 12 | 1.7 | 72.5 | 80 | 7.5 | 21% (IOP > 21 mmHg) | 0% | ND |
Scaramuzzi M et al. [ | DEX Implant | Retrospective | Mixed (7% Naïve) | 15 | 12 | 2.0 | 51.5 | 60 | 8.5 | 20% | 8.3% | ND |
Totan Y et al. [ | DEX Implant | Prospective | Non-Naïve | 30 | 6 | >1 | 57 | 64.5 | 7.5 | 13.3% (IOP > 21 mmHg) | 0% | ND |
Unsal. E et al. [ | DEX Implant | Retrospective | Non-Naïve | 46 | 6 | 1.1 | 41 | 57.5 | 16.5 | 17.4% (IOP > 25 mmHg) | 8.7% | 12% Subconjunctival haemorrhage |
Yucel OE et al. [ | DEX Implant | Retrospective | Non-Naïve | 30 | BVA (letters) | 1.0 | 51 | 57 | 6 | 16.7% (IOP > 23 mmHg) | 13% | None |
Zhioua I et al. [ | DEX Implant | Retrospective | Non-Naïve | 13 | 9 | 1.1 | 29.6 | 35 | 5.4 | 15.4% (IOP > 21 mmHg) | 7.9% | None |
Yorgun MA et al. [ | DEX Implant | Retrospective | Non-Naïve | 41 | 6 | 1.0 | 42.5 | 50.5 | 8 | 12% (IOP> 21 mmHg) | 0% | None |
Lastly, only one endophthalmitis has been reported in the 31 articles among 2897 injections that have been realized (0.03%).
Our analysis has several limitations including the fact that study data searches on PubMed are not always capable of identifying all relevant material. Moreover, it is methodologically imperfect to make indirect comparisons between studies with different numbers, even if this provides an overall vision of the real-life data. 6,842 eyes were included in the anti-VEGF studies versus 1,703 eyes with the dexamethasone implant. Moreover, we report definitions of gain in VA for anti-VEGF studies different from those reported for DEX-implant studies. Indeed, for the anti-VEGF studies, the VA or gain values used were the end-of-study data, but for the DEX-implant studies, the VA or gain values used were the maximum mean change in BCVA (best improvement) from baseline after each DEX injection. This criterion for DEX-implant was validated by the FDA [
By definition, observational real-life studies have limitations with patients lost to follow-up and missing data. However, the way that missing data are handled is not always reported in real-life studies and is variable and heterogeneous across the different articles. Nevertheless, these studies are primordial because they complete the pivotal studies because the patients included in “real-life” studies are not subject to selection and correspond to the patients seen in our daily routine practice and the treatment regimen corresponds to “real-life” injection intervals and “real-life” follow-up.
An additional potential bias is the difference in the proportion of naïve and non-naïve eyes: one-fifth of the Ozurdex eyes were treatment naïve versus two-thirds of the anti-VEGF eyes.
In conclusion, pharmacological treatment with anti-VEGF and DEX-implant shows significant VA gains in observational studies. The DEX-implant results report clinically VA gains that appear to be better than real-life gains from anti-VEGF. This impression of greater efficacy may be due to the lighter treatment regimen for this molecule and also to its specific mode of action. The choice of treatment must, however, take into account each individual patient’s characteristic in order to offer them personalized treatment.
Laurent Kodjikian is the Principal Investigator for trials sponsored by Novartis, Allergan, Bayer, Théa, and Alcon; has sat on advisory boards for Alcon, Alimera, Allergan, Bayer, Roche, and Novartis; and has received lecture fees from Alcon, Alimera, Allergan, Bayer, Horus, Novartis, and Théa. David Bellocq and Thibaud Mathis declared no conflicts of interest.
Laurent Kodjikian, David Bellocq, and Thibaud Mathis were the principal investigators who conceived and designed the study. This manuscript was drafted by David Bellocq, revised by Laurent Kodjikian and Thibaud Mathis, and approved by all living authors.