[Show abstract][Hide abstract] ABSTRACT: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME.
Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34–68 Early Treatment Diabetic Retinopathy Study letters (20/200–20/50 Snellen equivalent), and central retinal thickness (CRT) ≥300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry.
Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had ≥15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was −126.1 μm with DEX 0.7 versus −39.0 μm with sham (P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery.
DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population.
ClinicalTrials.gov NCT00168337 and NCT00168389, registered 12 September 2005
[Show abstract][Hide abstract] ABSTRACT: Bevacizumab (Avastin) is a recombinant humanized monoclonal immunoglobulin antibody that has two antigen-binding domains and blocks all active forms of vascular endothelial growth factor-A. It was originally designed and is still in use as antitumor agent (for colorectal and non-small cell lung cancers). Besides inhibiting vessel growth and neovascularization, the drug promotes the regression of existing microvessels and induces 'normalization' of surviving mature vasculature, stabilizes vessels and prevents leakage. Its molecular weight is 149 kDa and its estimated terminal half-life is approximately 20 days for both men and women. The effectiveness and safety of bevacizumab was proven in retrospective and prospective controlled clinical trials for the treatment of neovascular age-related macular degeneration, neovascularization in proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusion and retinopathy of prematurity, especially for zone I. Uncontrolled trials have shown its effectiveness in various other conditions as myopic and uveitic choroidal neovascularization and neovascular glaucoma. There are no absolute contraindications to intravitreal injection though it is recommended to withhold treatment in patients who have recently suffered from a cardiovascular or cerebrovascular event and during pregnancy. Ocular complications from intravitreal use are usually mild and transient (corneal abrasion, chemosis, subconjunctival hemorrhage and vitreous hemorrhage). Bacterial endophthalmitis is rare (about 0.1%). New or progressive subretinal hemorrhages, tears of the retinal pigment epithelium and an increased incidence of geographic atrophy have also been reported.
No preview · Article · Oct 2015 · Developments in ophthalmology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema.
Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials.
Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.
Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy and safety of intraocular injections of bevacizumab in patients with macular edema (ME) following branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO).
Retrospective, non-comparative case series. Patients ≥18 years of age with ME secondary to BRVO or CRVO who received a minimum of one intravitreal injection of bevacizumab with a follow-up >3 months were included. Primary endpoints were mean change in best corrected visual acuity (BCVA) from baseline to 12 and 24 months, and mean change in central macular thickness (CMT) after 3 injections. Secondary endpoints were mean change in BCVA and CMT from baseline to end of follow-up, number of injections, and ocular adverse events.
Eighty-seven eyes with BRVO and 65 eyes with CRVO were included. Mean follow-up time was 24.4 and 26.1 months in the BRVO and CRVO groups, respectively. The mean change in BCVA was 0.25 LogMAR in the BRVO group and -0.118 LogMAR in the CRVO group.
Visual acuity outcomes in the CRVO group were poorer, especially in patients with low baseline BCVA.
No preview · Article · Aug 2015 · Albrecht von Graæes Archiv für Ophthalmologie
[Show abstract][Hide abstract] ABSTRACT: To investigate the changes over time in optical density (OD) characteristics of subretinal fluid (SRF) in rhegmatogenous retinal detachment (RRD) and their clinical relevance.
The study included patients with first-onset RRD and no history of intraocular illness who underwent optical coherence tomography (OCT) and whose OCT scans showed sufficient SRF for sampling (08/2013-09/2014). The highest quality B-scan (as graded by the OCT image acquisition software) containing SRF was analyzed. Optical density measurements were obtained using ImageJ. Optical density ratios (ODRs) were calculated as SRF OD divided by vitreous OD. Time from onset of RRD was determined by first signs of visual loss as described in the patient's anamnesis. Patients were divided into three groups by RRD duration: acute (≤1 week), subacute (between 1 week and 1 month), and chronic (>1 month).
Thirty-five eyes (34 patients) met the inclusion criteria. The ODR measurement was significantly associated with RRD duration. The ODR had a significant (P < 0.0001) association with the 3-month postoperative visual acuity (VA). Vitreous OD did not differ significantly between the three groups.
The increase over time in the ODR of the SRF in RRD might reflect a change in SRF composition and state of the retina. This, together with a significant association between preoperative ODR values and postoperative VA suggest its potential as a biological prognostic marker.
No preview · Article · Aug 2015 · Investigative ophthalmology & visual science
[Show abstract][Hide abstract] ABSTRACT: Optic disc pit (ODP) is a rare congenital anomaly of the optic disc, which can be complicated by a maculopathy associated with progressive visual loss. Optic disc pits are usually unilateral and sporadic in occurrence, and the development of maculopathy is unpredictable with no known triggers. Optic disc pit maculopathy (ODP-M) is characterized by intraretinal and subretinal fluid at the macula, causing visual deterioration. The source of this fluid is still unclear, and several competing theories have suggested it may be vitreous fluid, cerebrospinal fluid, leakage from blood vessels at the base of the pit or leakage from the choroid. The mechanism of pathogenesis of ODP-M has not been fully elucidated, but vitreous liquefaction and traction and pressure gradients within the eye have been implicated to be involved. There are no clear guidelines on the management of patients with ODP-M, and numerous techniques have been described, including laser photocoagulation, intravitreal gas injection, macular buckling and pars plana vitrectomy with many different modifications. The majority of reports describe small series, and as there are no comparative studies there is no consensus regarding the optimal treatment for ODP-M. This review discusses the literature on the possible sources of fluid and mechanisms of pathogenesis in ODP-M, as well as the wide array of treatment modalities and their results. Based on these, a set of recommended key concepts for the timing and choice of treatment for these challenging are presented.
[Show abstract][Hide abstract] ABSTRACT: Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood-retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (<2%). Dexamethasone intravitreal implant offers a viable treatment option for DME, especially in cases that are persistent or treatment (anti-vascular endothelial growth factor/laser) refractory.
[Show abstract][Hide abstract] ABSTRACT: To validate and evaluate the accuracy of an algorithm for the identification of nonmetallic intraocular foreign body composition based on computed tomography and magnetic resonance imaging.
An algorithm for the identification of 10 nonmetallic materials based on computed tomography and magnetic resonance imaging has been previously determined in an ex vivo porcine model. Materials were classified into 4 groups (plastic, glass, stone, and wood). The algorithm was tested by 40 ophthalmologists, which completed a questionnaire including 10 sets of computed tomography and magnetic resonance images of eyes with intraocular foreign bodies and were asked to use the algorithm to identify their compositions. Rates of exact material identification and group identification were measured.
Exact material identification was achieved in 42.75% of the cases, and correct group identification in 65%. Using the algorithm, 6 of the materials were exactly identified by over 50% of the participants, and 7 were correctly classified according to their groups by over 75% of the materials.
The algorithm was validated and was found to enable correct identification of nonmetallic intraocular foreign body composition in the majority of cases. This is the first study to report and validate a clinical tool allowing intraocular foreign body composition based on their appearance in computed tomography and magnetic resonance imaging, which was previously impossible.
No preview · Article · May 2015 · Retina (Philadelphia, Pa.)
[Show abstract][Hide abstract] ABSTRACT: PurposeTo evaluate the safety and efficacy of 1.5% dexamethasone nanoparticle (DexNP) drops in eyes with non-infectious uveitic macular oedema and vitritis.Methods
In a prospective pilot study, DexNP drops were administered four times a day for 4 weeks followed by drops tapering over a period of another 4 weeks. Follow-up time was 12 weeks.ResultsFive eyes with macular oedema and three eyes with vitritis were included in the study. Best corrected visual acuity (BCVA) significantly improved from a median of 0.2 logMAR to a median of 0.15 logMAR at 4 weeks' time (p < 0.05). Median BCVA was 0.175 logMAR and 0.2 logMAR, at week 8 and 12, respectively (p > 0.05). Macular oedema significantly improved at all time-points as compared to baseline (p < 0.05) and resolved in all eyes during follow-up. One eye had macular oedema relapse at week 12. Vitritis improved in all eyes and resolved completely in two eyes. One eye had intraocular pressure (IOP) elevation which was well controlled with topical antihypertensive treatment, and one eye had cataract progression.Conclusion
This short pilot study demonstrates favourable effect of 1.5% DexNP eye drops on eyes with non-infectious uveitic macular oedema and vitritis. Further comparative long-term studies are warranted to assess this effect.
No preview · Article · May 2015 · Acta ophthalmologica
[Show abstract][Hide abstract] ABSTRACT: PurposeTo compare the efficacy in pupil dilation and degree of discomfort between topical instillation of mydriatic drops and gel.Methods
The study included 60 patients with no previous ocular history of trauma and surgery. One eye was dilated with two drops (tropicamide 0.5% and phenylephrine 10%), and the other with one drop of gel (tropicamide 0.5%+phenylephrine 5%). Pupil size was measured by a Colvard pupillometer at baseline and 5, 15, 30, and 45 min following instillation. Pain upon instillation was measured by visual analog scale (VAS).ResultsThere was no difference in pupil size at baseline. Use of the gel achieved greater mydriasis than drops (P=0.01), and was also associated with lower pain scores (P=0.003). In diabetic patients, pupil size was smaller at baseline and following instillation of drops and gel. Use of the gel achieved an even greater degree of pupil dilation in this subset of patients than drops (P=0.019).Conclusions
Gel formulation achieved significantly greater pupil dilation than drops, despite a lower concentration of phenylephrine, and was also associated with significantly lower patient discomfort. This study is the first report of improved mydriatic efficacy in diabetic patients.Eye advance online publication, 10 April 2015; doi:10.1038/eye.2015.47.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of oral Rifampin in patients with chronic central serous chorioretinoapthy (CSCR).
This was a prospective pilot study of patients with chronic CSCR with persistent subretinal fluid (SRF) for at least 3 months, who were treated with oral Rifampin 300 mg twice per day for 3 months and had 6 months of follow-up. All patients underwent a complete ocular examination and a spectral domain optical coherence tomography (SD-OCT) scan monthly from baseline until month 4, and then at month 6. Fluorescein angiography (FA) was performed at baseline and at the end of the study.
Fourteen eyes of 12 patients were included in the study, nine men and three women. Mean age was 58.5 years (range 32-80). Mean duration of SRF prior to study entry was 28.4 months. Forty-two percent of eyes were treated previously for CSR with thermal laser, PDT, or intravitreal bevacizumab. Mean best corrected visual acuity (BCVA) at presentation was 20/60 and improved to a mean of 20/50 at month 3 (P > 0.05). Retinal thickness was reduced by 25.3 %, 21.2 %, and 21 % on months 1, 2, 3, respectively (P < 0.05). Mean choroidal thickness at presentation was 476 μ (SD 188 μ) decreasing to 427 μ (SD 125 μ) after 3 months of treatment (P > 0.05). SRF was reduced in nine eyes (64 %) and completely resolved in six eyes (42.8 %) at month 3 following 3 months of treatment, and four out of these six eyes remained fluid free at month 6. Two patients stopped the treatment after 2 months due to adverse events.
Oral Rifampin may be a therapeutic option in patients with longstanding chronic CSCR.
No preview · Article · Mar 2015 · Albrecht von Graæes Archiv für Ophthalmologie
[Show abstract][Hide abstract] ABSTRACT: To evaluate clinical feasibility, safety, and efficacy of epiretinal strontium-90 brachytherapy in subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) in eyes unresponsive to repeated anti-VEGF injections.
A retrospective, single-center study on patients treated with strontium-90 brachytherapy for CNV secondary to neovascular AMD. Patients underwent pars plana vitrectomy with a single 24 Gy dose brachytherapy. They were re-treated with anti-VEGF injections on an as-needed basis if subretinal or intraretinal fluid was detected on optical coherence tomography imaging.
Twenty-two patients were treated, and 20 completed 12 months of follow-up. Ten patients maintained stable vision, eight gained vision, and two lost more than three Snellen lines. The mean best corrected visual acuity change from baseline was -8 ± 5.7 letters. A mean of 5.5 ± 4.4 anti-VEGF injections were administered throughout 12 months.
Epimacular brachytherapy is feasible in clinical practice. While some patients benefit from the treatment and need significantly fewer as-needed injections, others appear not to react to irradiation treatment after 1 year of follow-up. Larger numbers of patients are needed to evaluate therapeutic efficacy and to determine which patients can benefit from combined radiation and anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:338-343.].
Copyright 2015, SLACK Incorporated.
No preview · Article · Mar 2015 · Ophthalmic Surgery Lasers and Imaging Retina
[Show abstract][Hide abstract] ABSTRACT: To evaluate the safety and efficacy of switching from bevacizumab to ranibizumab in patients with neovascular age-related macular degeneration.
Retrospective study of patients with neovascular age-related macular degeneration initially treated with bevacizumab and switched to ranibizumab. Visual acuity and central retinal thickness (CRT) were retrieved at four time points: before the last three bevacizumab injections, at the switch, after the first three ranibizumab injections, and at the end of follow-up.
One hundred and fourteen eyes of 110 patients were included. Switching from bevacizumab to ranibizumab did not achieve a significant change in visual acuity, and a significant reduction in CRT was achieved after the first three injections but was not maintained by the end of follow-up. Eyes that lost ≥0.1 logMAR before the switch were more likely to improve in visual acuity (P = 0.013), and eyes with ≥10% increase in CRT before the switch were more likely to improve anatomically (P = 0.0003). In 47.3% of the eyes, the CRT was reduced by ≥10% after the first 3 ranibizumab injections, and the reduction was maintained with additional injections.
Switching to ranibizumab should be considered in patients with visual acuity decrease or CRT increase, despite monthly bevacizumab injections. The response should be evaluated after the first three injections to guide future treatment.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To describe a new method for training residents in ophthalmology in performing laser retinopexy around retinal breaks, and its practicality.
The simulator consists of a model eye that can be adjusted to fit any laser instrument, with a retinal break created in it. The retinal breaks are made of paper strips and can simulate tears and holes. The simulator is used with a three-mirror lens and real laser instrument.
The simulator creates conditions simulating near-real laser retinopexy and has been used successfully in training 3 novice residents who have never performed this procedure before.
This simulator is simple, reusable and inexpensive. We believe it may be a valuable instructional tool in training residents in performing laser retinopexy, shorten their learning curve and improve their efficiency it in.