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.

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.

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.

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.

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.

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.

New options for uveitis treatment

Uveitis is one of the most important causes of blindness worldwide.Its etiology and pathogenesis are complicated and have not been well understood.The treatment for uveitis is predominantly based on steroids and immunosuppressants.However,systemic side effects limit their clinical application.With the advancement of molecular biology,some intravitreal implants and biologic agents have been used for the treatment of uveitis.Additionally,novel techniques such as gene therapy and RNA interference are being studied for using as uveitis therapy.This paper reviews recent advances in uveitis treatment.

Clinical trials on corticosteroids for diabetic macular edema

Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.

Treatment of refractory diabetic macular edema with a fluocinolone acetonide implant in vitrectomized and non-vitrectomized eyes

AIM: To report real-life data on the use of an intravitreal fluocinolone acetonide implant in the treatment of refractory diabetic macular edema(DME) in pars plana vitrectomized(PPV) and non-PPV eyes.METHODS: This was a comparative retrospective observational study of 23 eyes with chronic DME. Bestcorrected visual acuity(BCVA) and central macular thickness(CMT) were recorded at baseline, 1, 4 and 12 mo. Descriptive statistics and non-parametric tests were performed to analyze and compare PPV and non-PPV eyes. RESULTS: Seven PPV and 16 non-PPV eyes were included in the study. Median BCVA in the non-PPV group varied from 0.65 logMAR [Interquartile range(IQR): 0.40] at baseline to 0.42 logMAR(IQR: 0.40) at 12 mo. Median CMT varied from 430 μm(IQR: 131.3) at baseline to 317 μm(IQR: 107.5) at 12 mo. Median BCVA in the PPV group varied from 0.60 logMAR(IQR: 0.62) at baseline to 0.74 logMAR(IQR: 0.34) at 12 mo. Median CMT varied from 483 μm(IQR: 146) at baseline to 397 μm(IQR: 132) at 12 mo. Of 0/7 eyes and 1/16 eyes in the PPV and non-PPV eyes respectively had a baseline visual acuity of 6/12 or better(0.3 logMAR). At last follow up, 1/7 and 5/16 eyes in the PPV and non-PPV group respectively achieved a visual acuity of 6/12 or better.CONCLUSION: Visual outcomes are modest following the use of the fluocinolone acetonide implant for chronic DME. The steroid implant is a useful treatment option in the management of refractory DME in vitrectomized and non-vitrectmized eyes.