Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion

AIM:To evaluate the efficacy,timing of retreatment and safety of dexamethasone(DEX)implant on macular edema(ME)secondary to diabetic retinopathy(DME)and retinal vein occlusion(RVO-ME)patients who were refractory to anti-vascular endothelial growth factor(VEGF)treatment.METHODS:This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1,2019,and January 1,2023.These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness(CRT).The best corrected visual acuity(BCVA)and CRT were measured at baseline,and at 1,3,4 and 6mo post-DEX implant injection.Adverse events such as elevated intraocular pressure(IOP)and cataract were recorded.RESULTS:For RVO cases(n=22),there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection(P<0.05)and CRT decreased from 472.1±90.6 to 240.5±39.0μm at 6mo(P<0.0001).DME cases(n=15)experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection(P=0.0098),with CRT reducing from 445.7±55.7 to 271.7±34.1μm at 6mo(P<0.0001).Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications.No cases of cataract or other adverse events were reported.CONCLUSION:DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME.Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

Dexamethasone implant in naive versus refractory patients with diabetic macular edema:a Meta-analysis

AIM:To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema(DME).METHODS:PubMed,Embase,Web of Science,and Medline databases were searched.The main outcomes were best-corrected visual acuity(BCVA)and central retinal thickness(CRT).The secondary outcomes included mean number of injections,intraoperative or postoperative complications including intraocular pressure(IOP)elevation and cataract.RESULTS:Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected.The postoperative BCVA in the naive group was significantly better than in the refractory group[mean difference(MD)-0.11,95% confidence interval(CI)-0.17 to-0.05,P=0.0003;MD 8.69,95%CI 5.08 to 12.30,P<0.00001].Additionally,the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group[MD 7.71,95%CI 2.02 to 13.40,P=0.008;odds ratio(OR)2.99,95%CI 2.05 to 4.37,P<0.00001].The subgroup analysis revealed that the naive group had significantly higher BCVA gains of≥5,≥10,and≥15 letters compared to the refractory group(P=0.002,0.0001,0.003,respectively).No significant difference was detected between the two groups in either postoperative CRT(MD-22.36,95%CI-46.39 to 1.66,P=0.07)or the overall mean number of injections(MD-0.08,95%CI-0.38 to 0.22,P=0.61).Intraoperative and postoperative complications including the elevation of IOP(OR 0.47,95%CI 0.20 to 1.13,P=0.09)and cataract(OR 1.78,95%CI 0.97 to 3.24,P=0.06)showed no significant differences between the two groups during the follow-up time.CONCLUSION:Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety profile.Moreover,naive eyes maintain better visual outcomes than refractory eyes.It provides further evidence of better visual response when used for naive eyes as firstline therapy.

Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema

Diabetic macular edema(DME)is a very important and well-known cause of visual loss in diabetics.Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME.Even though it is not clearly understood,current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME.Clinical trials are continuously shaping our treatment approaches for the eyes with DME.Today,vascular endothelial growth factor(VEGF)inhibitor and steroid administrations are the main alternatives in DME treatment.Dexamethasone(DEX)implant(Ozurdex®;Allergan,Inc.,Irvine,CA,United States)was approved by the United States Food&Drug Administration in 2014 for DME treatment.The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time.Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile.DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents.Thus,DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy.However,it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes.Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event,pregnancy and noncompliant to frequent visits.This mini-review briefly overviews the efficacy,safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Intravitreal dexamethasone implant in naive and previously treated patients with diabetic macular edema:a retrospective study

AIM:To assess the effect of the intravitreal dexamethasone implant(DEX)Ozurdex on the best corrected visual acuity(BCVA)and central retinal thickness(CRT)in patients with diabetic macular edema(DME).METHODS:Totally 43 eyes(24 naive and 19 previously treated)were included in the study.Retrospective and single-center study involved patients with a clinical diagnosed of DME,who received treatment with DEX implant and had a follow-up of at least 12 mo.Primary endpoints included changes in BCVA and CRT.RESULTS:At month 12,mean improvement in BCVA from baseline was 20.4±20.8 letters and 6.8±6.9 letters in naive and previously treated patients,respectively(P=0.0132).The naive patients achieved the BCVA improvement significantly faster(2.4±1.5 mo)than the previously treated ones(3.5±2.4 mo,P=0.0298;MannWhitney test).The proportion of eyes gaining≥15 letters was 54.2%and 21.1%in the non-previously treated and previously treated groups,respectively(P=0.0293).CRT was significantly reduced from 484.0±119.8 and 487.5±159.9μm to 272.0±39.2 and 233.5±65.7μm in the naive and previously treated patients,respectively;P<0.0001 each,respectively.The presence of subretinal fluid was significantly associated with the proportion of patients achieving a BCVA improvement≥5 letters[HR(95%CI),1.23(1.04 to 1.45),P=0.0145];≥10 letters[HR(95%CI),1.75(1.10 to 2.77),P=0.0182];and≥15 letters[HR(95%CI),2.04(1.03 to 4.02),P=0.0407].Naive patients received less DEX implants throughout the study than the previously treated ones(1.8±0.6 vs 2.3±0.6,P=0.0172,respectively).Totally 9 patients(20.9%)have developed ocular hypertension,which was successfully controlled with topical hypotensive drugs.Of the 23 phakic eyes at baseline,5 eyes(21.7%)either had new onset lens opacity or progression of an existing opacity during the study follow-up.Four of them(2 in the naive group and 2 in the previously treated one)required cataract surgery at months 4,6,6,and 6,respectively.CONCLUSION:The results obtained in this study may support the early use of DEX Ozurdex as first line therapy in naive patients.

Intravitreal dexamethasone implant — a new treatment for idiopathic posterior scleritis: A case report

BACKGROUND Posterior scleritis is one of the most easily missed and misdiagnosed diseases in ophthalmology.In this case we treated a patient with intravitreal dexamethasone implant that has not been extensively studied before.CASE SUMMARY A 40-year-old female patient who had anxiety,palpitation,and insomnia presented with eye pain and decreased vision in the left eye.An eye examination indicated that her visual acuity(VA)was 40/100.Her left eye presented conjunctival edema,mild exophthalmos,clear cornea,KP(-),and clear aqueous humor.In the fundus,there was a cinerous retinal protuberance.Ultrasonography showed“T-sign”and no systemic association was detected in laboratory examination.One month after injection of dexamethasone implant,the patient exhibited VA of 20/20,fundus serous retinal detachment disappeared,and intraocular pressure of both eyes was at the normal level.CONCLUSION Intravitreal injection of dexamethasone implant may be a safe and effective treatment for patients with idiopathic posterior scleritis.

Simultaneous Intravitreal Ranibizumab and Dexamethasone Implant Administration at the Same Setting in Eyes with Severe Diabetic Macular Edema

Aim: To share our experience in eyes with severe DME (exhibiting serous retinal detachment or large cysts) treated with simultaneous intravitreal ranibizumab and dexamethasone implant administration at the same setting as the first treatment step. Subjects and Results: Five eyes of three patients with DME who were either treatment naive or relatively undertreated were presented in this report. As optical coherence tomography exhibited serous retinal detachment or severe cystoid edema with large cysts, intravitreal ranibizumab and dexamethasone implant were simultaneously employed at the same setting as the first treatment step in those eyes. Panretinal photocoagulation was also commenced bilaterally a week after the start of injections when at least one eye had retinal neovascularization. Subsequent treatments of intravitreal ranibizumab and/or dexamethasone implant were administered. Patients were followed up for seven, eight and 13 months respectively. All five eyes achieved a relative anatomic stability and experienced visual improvement at the end of follow-up. Conclusion: In some cases with severe DME with or without proliferative diabetic retinopathy, simultaneous intravitreal ranibizumab and dexamethasone implant administration at the same setting may be a better option to initiate the treatment over mono ranibizumab treatment. A randomized study comparing the mono anti-VEGF therapy and mono dexamethasone implant administration with simultaneous treatment may outline the place of this type of therapy in the treatment armamentarium of severe DME.

Complications of dexamethasone implants:risk factors,prevention,and clinical management

AIM:To evaluate major complications after intravitreal injection of dexamethasone implants(Ozurdex)and their clinical management.METHODS:In a retrospective observational study between 2014 and 2016 at two university hospitals,we reviewed the clinical records of 1241 consecutive macular edema patients treated with the dexamethasone implant,and separated severe adverse events in the injection procedure from those that were post-injection complications.We evaluated the cause and the outcomes in each case.RESULTS:In twenty-one procedures(1.69%)we noticed significant complications during and after intravitreal injection of the dexamethasone implant.Complications related to the injection procedure were in one case,that a second implant was injected by mistake in the same eye on the same day.In another case,the implant lodged in the sclera during retraction of the injector needle.Leaking scleral tunnel at the injection site led to hypotony in another case.There were 10 cases of post-injection displacement of the implant into the anterior chamber and one case with a migrated and trapped device between the intraocular lens and an artificial iris.Displacement typically occurred in patients with preexisting risk factors:eyes with complicated intraocular lens implantation,iris reconstruction or iris defects or pseudophakic eyes after vitrectomy were prone to develop this complication.Displacement led to secondary corneal decompensation with pseudohypopyon.One case developed an endophthalmitis,and we observed four cases of retinal detachment.Two eyes presented with long-lasting hypotony due to ciliary insufficiency.CONCLUSION:Treatment with the dexamethasone implant may cause various expected or unexpected complications that may have serious consequences for the patient and require further surgery.To reduce complications,clinicians should evaluate certain risk factors before scheduling patients for dexamethasone implant treatment and use proper injection techniques.

Retinal injury following intravitreal injection of a dexamethasone implant in a vitrectomized eye

Lee SM, Jung JW, Park SW, Lee JE, Byon IS. Retinal injury following intravitreal injection of a dexamethasone implant in a vitrectomized eye. Int J Ophthalmo12017; 10（6）： 1019-1020

Optical Coherence Tomography (OCT) Feature Identifying Niche for Dexamethasone (FIND) Intravitreal Implant in the Treatment of Anti-VEGF Slow Responders with Diabetic Macular Edema

This paper raises the question if intravitreal dexamethasone implant deserves to be utilized more effectively in a select subset of eyes with diabetic macular edema (DME). If so, what is the OCT morphology of such eyes? A retrospective consecutive case series is employed to answer these questions. Twenty consecutive eyes were studied: ten that have been treated with intravitreal anti-VEGF (Group A) injections and ten which have been treated with the steroidal implant (Group O) because they failed or were slow to respond to multiple injections of anti-VEGF medications. Specifically, 1) macular edema in the eyes were categorized for the type of OCT morphology and 2) their response to the respective treatments in terms of the resolution of the OCT morphology was determined. Results show that the OCT morphology of eyes that were in Group O predominantly (7/10) had the feature of posterior retinal leakage (subretinal fluid and large outer retinal cysts);this feature was rare in Group A (2/10). Further, each of these eyes (7/7) in Group O had a complete resolution of the macular edema after a single treatment with the dexamethasone intravitreal implant whereas neither eye with this feature (0/2) responded to the (anti-VEGF) treatment in Group A. This leads to the conclusion that there exists an OCT Feature that Identifies a Niche for Dexamethasone Intravitreal implant (FIND) in the treatment of anti-VEGF slow responders in DME. The clinical significance of the study is that selecting eyes with a priori FIND morphology on the OCT for treatment with dexamethasone implant prior to, or at the outset of, a series of anti-VEGF treatment may resolve DME promptly and lower the treatment burden for patients and cost to society.

Combination of cataract surgery with intravitreal injection of dexamethasone intravitreal implant(Ozurdex)for uveitis-induced cataract

AIM:To evaluate the long-term results of patients with chronic uveitis-induced cataract by phacoemulsification with IOL implantation and intravitreal injection of dexamethasone(DEX)intravitreal implant(Ozurdex).METHODS:The study included 32 eyes of 26 patients treated with DEX implant due to chronic uveitis-induced cataract and followed up for at least a year.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),anterior chamber reaction,central macular thickness(CMT),intraoperative and postoperative complications and uveitis recurrence were analyzed retrospectively.RESULTS:A successful surgery was performed in all patients.The average follow-up period was 12mo.The female/male ratio was 13/13.Mean age was 45.65±3.83y(range 26 to 65y).Etiologically,rheumatic arthritis occurred in 6 patients(18.75%),ankylosing spondylitis in 4(12.50%),HLA-B27 associated uveitis in 3(9.38%),Vogt-KoyanagiHarada-associated uveitis in 4(12.50%),Behcet’s disease in 2(6.25%),and 7(21.88%)suffered from unknown diseases.All 32 eyes had varying degrees of improvement at 12mo after surgery,with 2 eyes showing BCVA of 0.1 or below(6.25%),6 having 0.1-0.5(18.75%),18 of 0.5-1.0(56.25%),and 6 of 1.0 or above(18.75%).No cases with increased IOP were observed.The values of mean CMT was increased at day 1,decreased at 1,3mo after surgery and increased at 6,12mo after surgery.No severe uveitis reactions,such as fibrinous exudates in the anterior chamber and exudative membrane formation on the anterior surface of the IOL,were observed after surgery.CONCLUSION:The present studies show that intravitreal injection of Ozudex during cataract operation can provide a new option for the clinical treatment of uveitis-induced cataract.

Dexamethasone intravitreal implant(Ozurdex) in diabetic macular edema: real-world data versus clinical trials outcomes

AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants(Ozurdex?/DEX) in patients with diabetic macular edema(DME) either na?ve or nonna?ve to anti-VEGF therapies who switched to DEX implant independent of response to anti-vascular endothelial growth factors(anti-VEGFs).METHODS: This was an audit retrospective review of medical records of patients with DME who switched to the DEX intravitreal implant. Patients were divided into 2 groups: patients na?ve to antiangiogenic therapy and patients who were previously treated with anti-VEGFs. Data regarding demographics, changes in mean best-corrected visual acuity(BCVA), central macular thickness(CMT), and intraocular pressure(IOP) was collected over 6 mo. The demographic data mean changes in BCVA, CMT, and IOP were compared. Six-month follow-up data of 47 patients(57 eyes), who either switched to DEX implant irrespective of response to previous treatments or were treatment na?ve before receiving DEX implant, was collected.RESULTS: Improvement in mean BCVA was observed from 1-4 mo after injection with a decreased effect at month 6 as expected, with better outcomes in na?ve compared to non-na?ve patients. A statistically relevant decrease in mean CMT was observed during the follow-up period. An increase in mean IOP was observed in the first 2 mo after DEX therapy. The mean number of injections of the overall population during the 6 mo was 1.3. A subgroup analysis showed no relevant difference between phakic versus pseudophakic patients relative to measured outcomes. There was no cataract progression during the follow-up period and no adverse events reported.CONCLUSION: This real-life setting study shows that intravitreal DEX implant is effective and safe. The timings of greater therapeutic impact are concordant with previous studies and suggest that earlier treatment with corticosteroids may have an additional benefit in na?ve patients.

Utilizing dexamethasone intravitreal implant to control postoperative inflammation in refractory uveitis undergoing cataract surgery

AIM:To report the effectiveness of intravitreal implantation of dexamethasone implant(Ozurdex)after phacoemulsification and intraocular lens implantation in refractory uveitis patients.METHODS:This single-center retrospective study conducted for refractory pan-uveitis patients who underwent cataract surgery combined with intravitreal Ozurdex implantation.The main outcome measurements were bestcorrected visual acuity(BCVA),central retinal thickness(CRT),grade of anterior chamber cell(AAC),intraocular pressure(IOP),and systemic/ocular adverse events.RESULTS:Ten eyes of 7 patients were included.BCVA showed significant improvement at 1 mo(P=0.004),3 mo(P=0.0004),and 6 mo(P=0.001)post operation.There were no statistically significant differences in the postoperative CRT among follow-up groups(P>0.05).No significant differences were observed in the baseline IOP when compared to 1,3,and 6 mo(all P>0.05)post operation.One patient developed a transient elevated IOP post injection.Two eyes(20%)developed posterior capsular opacifications and underwent neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy.In six patients(8 eyes,71.4%),the systemic steroid usage was reduced to below 10 mg/d.The patients experienced a mean of 1.4±0.52 recurrences of inflammation in the 6 mo before operation and 0.7±0.48 in the 6 mon post operation.The mean recurrence time was 13±0.58 wk(range 12-14 wk)post operation.In five of seven patients(7 out of 10 eyes),inflammation relapse was developed postoperatively.Only one patient(2 eyes)needed increased amounts of oral corticosteroids.Intraocular inflammation recurrence in the remaining patients was controlled by topical steroids.CONCLUSION:Ozurdex is considered a safe and effective approach to control postoperative inflammation in cataract surgery for patients with refractory uveitis in our study.After the disappearance of Ozurdex’s antiinflammatory effects over time,in most cases the recurrent inflammation can be controlled by topical steroids.

Dexamethasone intravitreal implant for diabetic macular edema in a pregnant patient

Dear Editor,We present a case of dexamethasone（DEX）intravitreal implantation（Ozurdex~;Allergan,Irvine,CA,USA）to treat diabetic macular edema（DME）during pregnancy.According to Pescosolido et al,pregnancy may promote the onset of diabetic retinopathy in about 10%of cases and may contribute to its worsening when already present,causing macular edema.Although one report has indicated that DME during pregnancy spontaneously regresses after delivery,others have reported that DME can persist and be associated with severe and persistent visual dysfunction.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.