DEX Implant Research Articles

Two or more dexamethasone intravitreal implants in treatment-naïve patients with macular edema due to retinal vein occlusion: subgroup analysis of a retrospective chart review study

BackgroundDexamethasone intravitreal implant (DEX implant) is a biodegradable, sustained-release implant that releases dexamethasone for up to 6 months. We evaluated the efficacy and safety of DEX implant in the treatment of macular edema secondary to retinal vein occlusion (RVO) in treatment-naïve patients.MethodsA multicenter, retrospective, open-label chart review study investigated the efficacy and safety of DEX implant treatment in 289 patients with macular edema secondary to branch or central RVO (BRVO, CRVO) who received ≥2 treatments with DEX implant in the study eye. Concomitant adjunctive RVO treatments were permitted. Data collected from the time of the first implant (baseline) to 3–6 months after the last implant included best-corrected visual acuity (BCVA) and central retinal thickness measured with optical coherence tomography. In this subgroup analysis, we evaluated outcomes in patients who had received no previous treatment for RVO complications.ResultsThirty-nine patients were treatment-naïve at the time of their first DEX implant (18 BRVO, 21 CRVO). Before the initial DEX implant, the mean duration of macular edema in treatment-naïve patients was 4.9 months, mean central retinal thickness was 550 μm, and mean Early Treatment Diabetic Retinopathy Study BCVA was 8.5 lines (20/125 Snellen). Treatment-naïve patients received a mean of 2.9 implants, either as monotherapy (n = 12) or with adjunctive RVO treatments (n = 27). The mean interval between implants was 177 days. After the first through sixth implants, mean changes from baseline BCVA ranged from +3.0 − +8.0 lines, and mean decreases from baseline central retinal thickness ranged from 241–459 μm. BCVA improved in both BRVO and CRVO and in both phakic and pseudophakic eyes. Overall, 83.8 % of treatment-naïve patients gained ≥2 lines in BCVA, 70.3 % gained ≥3 lines in BCVA, and 56.4 % achieved central retinal thickness ≤250 μm. The most common adverse event was increased intraocular pressure. Fifteen treatment-naïve patients had intraocular pressure ≥25 mm Hg; none required laser or incisional glaucoma surgery.ConclusionTreatment with 2 or more DEX implants had a favorable safety profile and improved visual acuity and anatomic outcomes when used, either alone or with adjunctive RVO therapy, as initial treatment for RVO-associated macular edema.Trial registrationClinicalTrials.gov NCT01411696, registered on August 5, 2011.

EFFICACY AND SAFETY OF DEXAMETHASONE INTRAVITREAL IMPLANT FOR PERSISTENT UVEITIC CYSTOID MACULAR EDEMA.

To investigate dexamethasone intravitreal implant (DEX Implant 0.7 mg, Ozurdex; Allergan, Inc, Irvine, CA) as a treatment for persistent cystoid macular edema (CME) secondary to uveitis. Treatment and outcomes data were collected retrospectively for 18 eyes from 13 consecutive patients treated with the DEX Implant for persistent, noninfectious uveitic CME. Outcome measures included the cumulative incidence of resolution of CME, visual acuity, central retinal thickness (measured by spectral domain optical coherence tomography), and vitreous haze score. After a single DEX Implant, there was no detectable CME in 89% and 72% of eyes at 1 month and 3 months, respectively. The median time to recurrence of CME (±standard error) was 201 ± 62 days. The percentage of eyes with no recurrence of CME was 35% at 6 months and 30% at 12 months. At 3 months, there was a significant improvement from baseline in mean visual acuity (+2.1 lines, P < 0.01). Eyes with an epiretinal membrane at baseline had shorter time to recurrence of CME and smaller improvements in visual acuity and central retinal thickness than eyes without an epiretinal membrane. At least 1 episode of intraocular pressure >25 mmHg occurred within the first 3 months in 11% (2 of 18) of eyes; all effectively managed with topical hypotensive medications. A single DEX Implant produced sustained improvements in both visual acuity and retinal thickness in the majority of eyes with persistent uveitic CME. Uveitic CME did gradually recur in most eyes; however, close posttreatment monitoring is recommended.

Efficacy and tolerability of bilateral sustained-release dexamethasone intravitreal implants for the treatment of noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion.

PurposeTo report our experience with bilateral placement of dexamethasone 0.7 mg (DEX) sustained-release intravitreal implant in the management of noninfectious posterior uveitis or macular edema secondary to retinal vein occlusion.MethodsA retrospective chart review of patients with bilateral noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion who were treated with DEX intravitreal implant was performed. Ocular side effects such as intraocular pressure (IOP), cataract, and tolerability of bilateral injections was reviewed.ResultsTwenty-two eyes of eleven patients treated with a total of 32 DEX implants were included. Ten of eleven patients received bilateral implants due to active noninfectious uveitis while the other demonstrated macular edema in both eyes following separate central retinal vein occlusions. Among the patients with bilateral uveitis, the mean interval between DEX implant in the initial eye and the subsequent DEX in the fellow eye was 15.6 days (range 2–71 days). Seven of the ten patients received the second implant in the fellow eye within 8 days of the initial implantation. None of the patients had bilateral implantations on the same day. Seven eyes required reimplantation for recurrence of inflammation (mean interval between first and repeat implantation was 6.00±2.39 months). Following single or, in the case of the aforementioned seven eyes, repeat DEX implantation, all 20 uveitic eyes demonstrated clinical and/or angiographic evidence of decreased inflammation in the form of reduction in vitreous cells on slit lamp ophthalmoscopy, macular edema on ophthalmoscopy, or optical coherence tomography and/or disc and vascular leakage on fluorescein angiography. The mean follow-up for all eyes after initial implantation was 23.57 months (range 1–48 months). IOP was significantly higher (P=0.028) at 6 months (16.62 mmHg ±5.97) but not (P=0.82) at most recent follow-up (14.9±3.37 mmHg) when compared with baseline (14.68±3.02 mmHg). Four eyes (18.2%) required initiation of IOP-lowering medications. During the follow-up period, no eyes underwent filtration or cataract extraction. No serious ocular adverse effects were noted during the follow-up period.ConclusionIn patients with bilateral noninfectious posterior uveitis and macular edema secondary to vein occlusion, bilateral injection of DEX intravitreal implant was well tolerated and had an acceptable safety profile.

Two or more dexamethasone intravitreal implants as monotherapy or in combination therapy for macular edema in retinal vein occlusion: subgroup analysis of a retrospective chart review study.

BackgroundDexamethasone intravitreal implant (DEX implant) is a sustained-release biodegradable implant approved for treatment of macular edema associated with retinal vein occlusion (RVO). The safety and efficacy of treatment of RVO-associated macular edema with sequential DEX implants in clinical practice was evaluated in patients who received DEX implant as monotherapy compared with patients who received DEX implant in combination with other RVO treatments.MethodsA multicenter, retrospective, open-label chart review study (one study eye/patient) evaluated use of DEX implant and outcomes in 289 patients with branch or central RVO who received at least 2 DEX implant treatments in the study eye. Data were collected from the time of the first implant (baseline) to 3–6 months after the last implant. Subgroup analysis evaluated outcomes in patients receiving only DEX implant during the study versus patients receiving DEX implant plus adjunctive RVO treatments. Endpoints included best-corrected visual acuity (BCVA) and central retinal thickness (CRT) change from baseline.ResultsDEX implant was used as monotherapy in 84 (29.1%) patients and in combination with other therapy in 205 (70.9%) patients. Mean number of DEX implant treatments received was 3.1 in the monotherapy group and 3.3 in the combination therapy group (P = 0.344). Mean time between implants was longer in the combination therapy group (177 vs. 151 days, P < 0.001). Mean change from baseline BCVA after the first through sixth DEX implants ranged from +0.6 to +3.4 lines in the monotherapy group and +1.3 to +2.8 lines in the combination therapy group. Mean decrease from baseline CRT ranged from 165 to 230 μm in the monotherapy group and 136 to 175 μm in the combination therapy group. Increased intraocular pressure was more common in the combination therapy group.ConclusionsTreatment of RVO-associated macular edema with at least 2 sequential DEX implants was safe and effective both when used alone and when combined with other RVO treatments. Improvements in BCVA and CRT were generally similar in the monotherapy and combined therapy groups.Trial registrationClinicalTrials.gov NCT01411696.

Anatomical and functional recurrence after dexamethasone intravitreal implants: a 6-month prospective study.

To evaluate the efficacy, safety, and delay of anatomical and functional recurrence after a first intravitreal injection of dexamethasone implant in eyes with cystoid macular edema (CME) secondary to retinal vein occlusion (RVO). A 6-month prospective, monocentric and noncomparative case-series of 26 eyes of 26 patients. Best-corrected visual acuity (BCVA) and central subfield thickness (CST) were measured at baseline and each visit at 1 week, and months 1, 2, 3, 4, 5, and 6 after a first treatment. Primary efficacy outcome was the proportion of eyes with a minimum three-line improvement from baseline BCVA at each visit and at 6 months. We also defined different patterns of recurrence: qualitative anatomical recurrence, quantitative anatomical recurrence and functional recurrence. A P-value <5% was considered statistically significant. Mean population age was 69.3 years (SD=12.2; range=42-94 years). Mean ME duration before treatment was ~9.2 months (SD=11.43; range=0.4-40 months). Eighty eight percent of eyes achieved a three-line improvement from baseline at 2 months (P=0.02). The mean delay from baseline until qualitative anatomical, functional, or quantitative anatomical recurrence was 4.11 months (±0.86), 4.31 months (±1.33), and 4.40 months (±1.14), respectively. Qualitative anatomical recurrence occurred on average 14.4 days (SD=42.18) before a minimum of one-line BCVA impairment (functional recurrence). Dexamethasone intravitreal treatment seems to be effective for ME after RVO even with long-duration ME or poor visual acuity before treatment. Other longer studies should assess the delay of recurrence after second and further treatments with DEX implants or combined therapies for ME after RVO.

Sustained-release dexamethasone intravitreal implant for persistent macular edema after vitrectomy for epiretinal membrane.

Persistent macular edema (ME) after surgical removal of epiretinal membrane (ERM) may impair postoperative visual recovery. Sustained-release dexamethasone intravitreal implant (DEX) was used to treat recalcitrant ME after vitrectomy for ERM. Retrospective chart review of eyes treated with DEX for ME after ERM removal. Visual and anatomic outcomes were evaluated. Five eyes with refractory ME on optical coherence tomography (OCT) after ERM surgery were treated with DEX. Four of five eyes demonstrated reduction in macular thickness on OCT (mean: 106 μm), with mean percentage reduction in central foveal thickness of 25%. Visual acuity improved by one or more Snellen lines in four of five eyes. DEX effect duration was 3 to 9 months. Two eyes with OCT and visual improvement after initial DEX received multiple DEX implants for maintenance therapy. Inflammatory factors may contribute to persistent ME after vitrectomy for ERM. DEX may be a treatment option in such cases.

Monthly microperimetry (MP1) measurement of macular sensitivity after dexamethasone implantation (Ozurdex) in retinal vein occlusions.

To evaluate changes in macular sensitivity as measured via microperimetry (MP) in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) after dexamethasone implantation (DEX implantation, Ozurdex), in comparison to distance visual acuity, reading ability, and spectral domain optical coherence tomography (SD-OCT). Twenty-three patients with ME secondary to RVO were treated with a DEX implantation in this prospective, observational case study. Patients were controlled at baseline and then monthly with microperimetry and assessment of distance visual acuity, reading ability, and SD- OCT. Side effects of the DEX implant were monitored by measuring the intraocular pressure (IOP) and lens grading with Lens Opacities Classification System (LOCS) charts. The 23 patients with RVO included 16 patients with branch retinal vein occlusion (BRVO) and 7 patients with central retinal vein occlusion (CRVO). Improvement in distance visual acuity, reading ability, and in central 8-points microperimetry showed statistical significance from month 1 to 3, whereas the 40-points microperimetry improved with statistical significance from month 1 to 2. The reduction of central retinal thickness measured with SD-OCT remained statistically significant until month 4. Subgroup analysis of patients with BRVO and CRVO confirmed the best test results observed at month two after DEX implantation. The highest macular sensitivity was measured two months after DEX implantation. This corresponds to the best test results for distance visual acuity, reading ability, and SD-OCT observed two months after treatment.

Dexamethasone intravitreal implant for pseudophakic cystoid macular edema in patients with diabetes.

Diabetic patients are at a higher risk of developing pseudophakic cystoid macular edema (PCME) after cataract surgery. This study evaluated the effect of dexamethasone intravitreal implant (DEX Implant 0.7 mg, Ozurdex; Allergan, Irvine, CA) in diabetic patients with PCME. In this prospective case series, six patients with diabetes who developed PCME despite topical anti-inflammatory therapy were treated with a single dexamethasone implant. Outcome measures included best corrected visual acuity (BCVA) and central subfoveal thickness. The mean increase in BCVA from baseline to day 180 was 14 letters (P = .03); four of six patients (67%) achieved greater than 10-letter improvement in BCVA. The mean decrease in central subfoveal thickness was 100 µm (P < .01 vs baseline) by day 30 and 72 µm by day 180 (P = .004). A dexamethasone implant may be an effective treatment for diabetic patients who develop pseudophakic cystoid macular edema after cataract surgery.

Comparison of the release profile and pharmacokinetics of intact and fragmented dexamethasone intravitreal implants in rabbit eyes.

Dexamethasone intravitreal implant (DEX implant, Ozurdex(®); Allergan, Inc.) is used to treat noninfectious posterior uveitis and macular edema associated with retinal vein occlusion and diabetic retinopathy. Two recently published reports of DEX implant fragmentation shortly after injection have raised concerns about the potential for faster implant dissolution and elevated ocular dexamethasone concentrations. This study compared the in vivo release profile and pharmacokinetic behavior of intact and fragmented DEX implants. DEX implant was surgically implanted as a single unit or fragmented into 3 pieces in the posterior segment of opposing eyes of 36 New Zealand white rabbits. The release of dexamethasone over time from 1-piece and 3-piece fragmented implants dissolved in solution in vitro was compared with that from the 1-piece and 3-piece fragmented implants placed in the rabbit eyes. In addition, dexamethasone concentrations in the vitreous and aqueous humors of each eye were measured at 3 h and days 1, 7, 14, 21, and 28. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used for assays. Dexamethasone release from the 1-piece and 3-piece DEX implants in vivo was not different and was consistent with the in vitro release pattern. Moreover, the concentration profile of dexamethasone in the vitreous and aqueous humors was similar for the 1-piece and 3-piece DEX implants at each time point measured. DEX implant fragmentation neither accelerated its dissolution nor increased the dexamethasone concentration delivered at a given time. Accordingly, DEX implant fragmentation is unlikely to have clinically significant effects in patients.

EFFICACY AND SAFETY OF TWO OR MORE DEXAMETHASONE INTRAVITREAL IMPLANT INJECTIONS FOR TREATMENT OF MACULAR EDEMA RELATED TO RETINAL VEIN OCCLUSION (SHASTA STUDY)

To evaluate the efficacy, safety, and reinjection interval of dexamethasone intravitreal implant (DEX implant) in branch retinal vein occlusion and central retinal vein occlusion patients receiving ≥ 2 DEX implant treatments. Multicenter (26-site), retrospective chart review study. Data were collected from baseline (at first DEX implant) through 3 months to 6 months after last DEX implant. Patients (n = 289) received 2 to 9 (mean, 3.2) DEX implants as monotherapy (29.1% of patients) or with adjunctive treatments/procedures. Mean duration of macular edema before first DEX implant was 18.4 months. Mean reinjection interval was 5.6 months. Mean peak change in best-corrected visual acuity from baseline through 4 weeks to 20 weeks after final DEX implant was +1.0 line (P < 0.001). Best-corrected visual acuity and central retinal thickness improved significantly from baseline after each of the first 6 DEX implant injections (P ≤ 0.037); 59.7% of branch retinal vein occlusion and 66.7% of central retinal vein occlusion patients achieved ≥ 2-line best-corrected visual acuity improvement. Intraocular pressure increase (≥ 10 mmHg) occurred in 32.6% of patients; 29.1% used intraocular pressure-lowering medication to treat increases associated with DEX implant. Only 1.7% of patients required incisional glaucoma surgery. Retinal vein occlusion patients treated with multiple DEX implant injections, either alone or combined with other therapies, had improved central retinal thickness and visual acuity with each subsequent injection. No new safety concerns developed with multiple implants.

Dexamethasone Intravitreal Implant in Patients with Macular Edema Related to Branch or Central Retinal Vein Occlusion: Twelve-Month Study Results

To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO). Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension. We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO. At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm. The primary outcome for the open-label extension was safety; BCVA was also evaluated. At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively. Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression. Proprietary or commercial disclosure may be found after the references.