Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model

PubMed Central

Horner, Marc; Muralikrishnan, R.

2010-01-01

ABSTRACT Purpose A computational fluid dynamics (CFD) study examined the impact of particle size on dissolution rate and residence of intravitreal suspension depots of Triamcinolone Acetonide (TAC). Methods A model for the rabbit eye was constructed using insights from high-resolution NMR imaging studies (Sawada 2002). The current model was compared to other published simulations in its ability to predict clearance of various intravitreally injected materials. Suspension depots were constructed explicitly rendering individual particles in various configurations: 4 or 16 mg drug confined to a 100 μL spherical depot, or 4 mg exploded to fill the entire vitreous. Particle size was reduced systematically in each configuration. The convective diffusion/dissolution process was simulated using a multiphase model. Results Release rate became independent of particle diameter below a certain value. The size-independent limits occurred for particle diameters ranging from 77 to 428 μM depending upon the depot configuration. Residence time predicted for the spherical depots in the size-independent limit was comparable to that observed in vivo. Conclusions Since the size-independent limit was several-fold greater than the particle size of commercially available pharmaceutical TAC suspensions, differences in particle size amongst such products are predicted to be immaterial to their duration or performance. PMID:20467888

Management of diabetic macular edema with intravitreal dexamethasone implants: Expert recommendations using a Delphi-based approach.

PubMed

Giovannini, Alfonso; Parravano, Mariacristina; Ricci, Federico; Bandello, Francesco

2018-06-01

Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema. A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy. Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti-vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti-vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti-vascular endothelial growth factor therapy. While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.

Intravitreous Bevacizumab in the Treatment of Macuar Edema from Branch Retinal Vein Occlusion and Hemisphere Retinal Vein Occlusion (An AOS Thesis)

PubMed Central

Fish, Gary Edd

2008-01-01

Purpose To compare intravitreous bevacizumab to other current treatments of branch retinal vein occlusion (BRVO) and hemisphere retinal vein occlusion (HRVO) with consideration to visual outcome, cost, convenience, and risk of treatment. Methods This is a retrospective chart review from a large referral retina practice. The data comprise 56 patients with BRVO and HRVO treated by intravitreous bevacizumab, with and without intravitreous triamcinolone acetonide. Initial visual acuities at the time of first bevacizumab injection, best acuities through the follow-up time, final acuity at last visit before review, initial macular thickness, and final macular thickness were measured. Changes in vision and thickness were calculated, as were the percentage of eyes improving, stabilizing, and worsening. Results The data were compared to composite data derived from several current treatments of BRVO. The subgroup of 39 eyes that received only bevacizumab without triamcinolone acetonide had the most improvement in vision. The median change in visual acuity was 1.5 lines (P = .012) over a mean follow-up of 8.8 months. Twenty-three eyes (59%) improved visually, with 20 eyes (51%) improving 2 or more lines. These results are similar to those for eyes that received argon grid laser and chorioretinal anastomosis, but are worse than in eyes that received arteriovenous adventitial sheathotomy, macular decompression surgery, and intravitreous triamcinolone acetonide. Conclusions Visual benefit from intravitreous bevacizumab compares well against laser treatments for BRVO and HRVO but not as well opposed to surgical techniques and intravitreous triamcinolone acetonide. Intravitreous bevacizumab injection has a risk, cost, and convenience profile that is favorable. PMID:19277242

Pharmacokinetic behavior of intravitreal triamcinolone acetonide prepared by a hospital pharmacy.

PubMed

Oishi, Masako; Maeda, Shinichiro; Hashida, Noriyasu; Ohguro, Nobuyuki; Tano, Yasuo; Kurokawa, Nobuo

2008-01-01

We developed a new hospital pharmaceutical preparation of triamcinolone acetonide (TA) for intravitreal injections using sodium hyaluronate as the vehicle. The purpose of this study was to compare the pharmacokinetic behavior of this hospital pharmacy preparation of TA (HPP-TA) to that of a commercial preparation of TA (CP-TA) in rats. We injected the two preparations of TA into the vitreous humor of male Wistar rats. The rats were killed between days 1 and 21, and the concentration of TA in the vitreous was measured by high-performance liquid chromatography to determine the pharmacokinetic parameters. We also examined the microscopic appearance of the TA particles in these preparations. The elimination half-life was 6.08 days for the CP-TA and 5.78 days for the HPP-TA. A two-compartment model was suitable to approximate the pharmacokinetic behavior of HPP-TA in the vitreous body, but this model was not suitable for CP-TA, because its pharmacokinetic behavior was not sufficiently stable. The particle size of CP-TA was largest, followed by TA powder and HPP-TA. Many particles were agglutinated in the CP-TA preparation, whereas the TA particles were fine and dispersed in the HPP-TA medium. The TA particle size and the suspension medium are likely important factors in the preparation of a safe and stable suspension of TA. HPP-TA satisfied these requirements and should be suitable for clinical use.

Suspected bacterial endophthalmitis following sustained-release dexamethasone intravitreal implant: a case report.

PubMed

Arıkan Yorgun, Mücella; Mutlu, Melek; Toklu, Yasin; Cakmak, Hasan Basri; Cağıl, Nurullah

2014-06-01

A 58-year-old man admitted to our opthalmology department with the complaint of branch retinal vein occlusion. He was treated with intravitreal Ozurdex in the right eye. Two days after the injection, the patient presented with ocular pain and the visual acuity was hand movement. A diagnosis of endophthalmitis was made. We performed emergent pars plana vitrectomy (PPV) and the implant was removed from the vitreous cavity using a retinal forceps. A combination of vancomycin 1.0 mg and amikacin 0.4 mg was injected intravitreally. However, because of the blurring in the vitreus one week after the procedure, phacoemulsification and a repeat PPV was performed. Five days after the last procedure the signs and symptoms of endophthalmitis were resolved. Our case demonstrated that endophthalmitis could develop after intravitreal implantation of Ozurdex. Surgical removal of the implant and immediate vitrectomy seems to be a useful treatment option in these cases.

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

PubMed Central

Hunter, Rebecca S; Lobo, Ann-Marie

2011-01-01

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

Effect of an intravitreal cyclosporine implant on experimental uveitis in horses.

PubMed

Gilger, B C; Malok, E; Stewart, T; Horohov, D; Ashton, P; Smith, T; Jaffe, G J; Allen, J B

2000-10-31

The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25 microg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25 microg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFN gamma) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72 h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFN gamma-mRNA were

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty.

PubMed

Zafar, Andleeb; Aslanides, Ioannis M; Selimis, Vasileios; Tsoulnaras, Konstantinos I; Tabibian, David; Kymionis, George D

2018-01-01

We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye.

Real-world experience with 0.2 μg/day fluocinolone acetonide intravitreal implant (ILUVIEN) in the United Kingdom

PubMed Central

Bailey, C; Chakravarthy, U; Lotery, A; Menon, G; Talks, J; Bailey, Clare; Kamal, Aintree; Ghanchi, Faruque; Khan, Calderdale; Johnston, Robert; McKibbin, Martin; Varma, Atul; Mustaq, Bushra; Brand, Christopher; Talks, James; Glover,, Nick

2017-01-01

Aims To compare safety outcomes and visual function data acquired in the real-world setting with FAME study results in eyes treated with 0.2 μg/day fluocinolone acetonide (FAc). Methods Fourteen UK clinical sites contributed to pseudoanonymised data collected using the same electronic medical record system. Data pertaining to eyes treated with FAc implant for diabetic macular oedema (DMO) was extracted. Intraocular pressure (IOP)-related adverse events were defined as use of IOP-lowering medication, any rise in IOP>30 mm Hg, or glaucoma surgery. Other measured outcomes included visual acuity, central subfield thickness (CSFT) changes and use of concomitant medications. Results In total, 345 eyes had a mean follow-up of 428 days. Overall, 13.9% of patients required IOP-lowering drops (included initiation, addition and switching of current drops), 7.2% had IOP elevation >30 mm Hg and 0.3% required glaucoma surgery. In patients with prior steroid exposure and no prior IOP-related event, there were no new IOP-related events. In patients without prior steroid use and without prior IOP-related events, 10.3% of eyes required IOP-lowering medication and 4.3% exhibited IOP >30 mm Hg at some point during follow-up. At 24 months, mean best-recorded visual acuity increased from 51.9 to 57.2 letters and 20.8% achieved ≥15-letter improvement. Mean CSFT reduced from 451.2 to 355.5 μm. Conclusions While overall IOP-related emergent events were observed in similar frequency to FAME, no adverse events were seen in the subgroup with prior steroid exposure and no prior IOP events. Efficacy findings confirm that the FAc implant is a useful treatment option for chronic DMO. PMID:28737758

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty

PubMed Central

Zafar, Andleeb; Aslanides, Ioannis M.; Selimis, Vasileios; Tsoulnaras, Konstantinos I.; Tabibian, David; Kymionis, George D.

2018-01-01

Purpose We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. Methods The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Results Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. Conclusion A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye. PMID:29643797

Management of inadvertent needle penetration resulting in subretinal triamcinolone acetonide and retinal detachment.

PubMed

Tran, Kimberly D; Crane, Ashley M; Flynn, Harry W

2018-06-01

To report management of inadvertent needle penetration during subtenons triamcinolone acetonide administration resulting in retinal detachment. A 71-year-old female with history of diabetes, hypothyroidism, and mild myopia underwent subtenons triamcinolone acetonide (TA) injection in the right eye for nodular scleritis. There was unexpected patient movement concurrent with the injection resulting in needle penetration, subretinal and intravitreal injection of TA, superotemporal retinal break, and macula-involving retinal detachment. The patient underwent partial subretinal TA removal, successful retinal detachment repair, and recovered 20/25 visual acuity. In spite of prominent subretinal TA and retinal detachment, successful repair of retinal detachment and recovery of good visual acuity is possible.

Early Retinal and Choroidal Coat Thickness Changes After Intravitreal Dexamethasone Implant Injection for Diabetic Macular Edema.

PubMed

Horozoğlu, Fatih; Sever, Özkan

2018-06-05

Intravitreal steroid injection is one of the treatment choices in diabetic macular edema (DME). Dexamethasone (Dx) implant is the most novel form of intravitreal steroid therapy. Macular thickness improvement is well known effect of Dx implant however; subfoveal choroidal coat thickness (SFCT) changes need to be investigated. To evaluate the early central macular thickness (CMT) and SFCT alterations after single dose dexamethasone implant injection in DME. Retrospective cross-sectional study. We identified 29 patients with DME (29 eyes) who underwent optical coherence tomography (OCT) and fundus fluoroscein angiography (FFA). All patients received a single dose intravitreal Dx implant and were followed for CMT and SFCT alterations for the post-injection first hour, first day, first week, first month and third month. The preoperative mean CMT and SFCT measurements were 592.3±122.3 (412-879) μm and 264.8±53.7 (165-397) μm, respectively. CMT measurements significantly decreased from the first hour (p<0.050) and kept decreasing till 3 month (p<0.001); while SFCT decrement was just significant at the first day (p<0.05). When we compared the decrease in SFCT and CMT, 1 hour was similar, however not significant, 1.5% SFCT and 5% CMT decrease was, respectively (p>0.050). CMT decrease rate was significantly higher than SFCT at 1 day, 1 week, 1 month and 3 month (p<0.001). Intravitreal Dx implant has got a meaningful effect on CMT in patients with DME while SFCT decreases significantly at first hour and first day.

Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

PubMed

Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

2017-10-03

To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

PubMed

Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

2016-11-08

Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

Quantitative evaluation of reduction of plaque-like hard exudates in diabetic macular edema after intravitreal triamcinolone injection.

PubMed

Cekiç, Osman; Bardak, Yavuz; Tiğ, U Sahin; Yildizoğlu, Uzeyir; Bardak, Handan

2008-04-01

To describe a new method of quantifying the amount of plaque-like hard exudates after intravitreal triamcinolone acetonide injection in diabetic macular edema. This study included 22 eyes of 14 patients (mean age, 63 years) with chronic diabetic macular edema and plaque-like hard exudates. The patients were injected with a single dose of 4 mg intravitreal triamcinolone acetonide. The optic disc size as relative size unit was taken to quantify the hard exudates: Total areas of exudates and the optic nerve head were computed from fundus pictures with a digital analysis program on magnified images. The former was divided by the latter, and the results were expressed as a percentage value. The ratio was used to track improvements in a given eye over 6 months. Average ratio of hard exudates to optic nerve head area reduced to 81% of its initial value at 1 month (P=0.007), to 54% at 3 months (P<0.001) and to 41% at 6 months (P<0.001). The new method allowed detection of a significant reduction of ratio of hard exudates to optic disc area of diabetic plaque-like hard exudates following 4 mg intravitreal triamcinolone.

Comparison between intravitreal bevacizumab and triamcinolone for macular edema secondary to branch retinal vein occlusion.

PubMed

Kim, Jin Young; Park, Sung Pyo

2009-12-01

To compare the effects of intravitreal bevacizumab to those of triamcinolone acetonide injection for the treatment of macular edema secondary to branch retinal vein occlusion. This retrospective study included 50 eyes of 50 patients who received a single injection of intravitreal bevacizumab (1.25 mg/0.05 mL, 22 eyes) or triamcinolone acetonide (4 mg/0.1 mL, 28 eyes) as the only treatment for macular edema secondary to branch retinal vein occlusion; all patients had a post-injection follow-up duration of >24 weeks. Best corrected visual acuity (BCVA), intraocular pressure (IOP), and central macular thickness (CMT) by optical coherence tomography were measured for up to 24 weeks after injection. BCVA was improved at 1, 4, 8,12 weeks post-injection in the bevacizumab group, and at 1, 4, 8 weeks post-injection in the triamcinolone group. No significant difference was found between the two groups except at 12 weeks. CMT decreased significantly within each group, and no significant difference between groups was found. In the bevacizumab group, no elevated IOP was observed, whereas IOP was significantly increased at 4, 8, and 12 weeks after triamcinolone injection; IOP was therefore significantly different between the two groups. Intravitreal bevacizumab is a comparatively simple treatment method that can effectively improve BCVA and reduce CMT without ocular and systemic complications. Consequently, intravitreal bevacizumab injections may be useful as both an alternative and primary treatment for macular edema secondary to branch retinal vein occlusion.

Cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for noninfectious intermediate, posterior, and panuveitis.

PubMed

Sugar, Elizabeth A; Holbrook, Janet T; Kempen, John H; Burke, Alyce E; Drye, Lea T; Thorne, Jennifer E; Louis, Thomas A; Jabs, Douglas A; Altaweel, Michael M; Frick, Kevin D

2014-10-01

To evaluate the 3-year incremental cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for the treatment of noninfectious intermediate, posterior, and panuveitis. Randomized, controlled, clinical trial. Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment Trial. Data on cost and health utility during 3 years after randomization were evaluated at 6-month intervals. Analyses were stratified by disease laterality at randomization (31 unilateral vs 224 bilateral) because of the large upfront cost of the implant. The primary outcome was the incremental cost-effectiveness ratio (ICER) over 3 years: the ratio of the difference in cost (in United States dollars) to the difference in quality-adjusted life-years (QALYs). Costs of medications, surgeries, hospitalizations, and regular procedures (e.g., laboratory monitoring for systemic therapy) were included. We computed QALYs as a weighted average of EQ-5D scores over 3 years of follow-up. The ICER at 3 years was $297,800/QALY for bilateral disease, driven by the high cost of implant therapy (difference implant - systemic [Δ]: $16,900; P < 0.001) and the modest gains in QALYs (Δ = 0.057; P = 0.22). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.003 and 0.04, respectively. The ICER for unilateral disease was more favorable, namely, $41,200/QALY at 3 years, because of a smaller difference in cost between the 2 therapies (Δ = $5300; P = 0.44) and a larger benefit in QALYs with the implant (Δ = 0.130; P = 0.12). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.53 and 0.74, respectively. Fluocinolone acetonide implant therapy was reasonably cost-effective compared with systemic therapy for individuals with unilateral intermediate, posterior, or panuveitis but not for those with bilateral disease. These results do

Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion

PubMed Central

Shahsuvaryan, Marianne L.

2012-01-01

Retinal vein occlusion (RVO) is the most common visually disabling disease affecting the retina after diabetic retinopathy. Although the disease entity has long been known, its management is still controversial. Macular edema is the main reason for decreased visual acuity (VA) in this retinal vascular disorder. Recently the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of macular edema through intravitreal injection route. The most widely injected drugs so far have been triamcinolone acetonide (TA) and bevacizumab. The objective of this review is to evaluate the evidence and discuss the rationale behind the recent suggestions that intravitreal pharmacotherapy by corticosteroids and anti-vascular endothelial growth factors may be useful in the treatment of retinal vein occlusion. PMID:23275914

Treatment of refractory uveitic macular edema: results of a first and second implant of long-acting intravitreal dexamethasone

PubMed Central

Zola, Marta; Briamonte, Cristina; Lorenzi, Umberto; Machetta, Federica; Grignolo, Federico M; Fea, Antonio M

2017-01-01

Purpose The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema. Methods Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA), complete slit-lamp examination, intraocular pressure (IOP), optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p<0.05). BCVA was better after the second implant compared to the first one throughout the follow-up, but without statistical significance. Mean central macular thickness (CMT) was 446.3±129.9 μm at baseline and was significantly reduced until day 135 (p<0.05). CMT reductions after the second injection showed a similar pattern, though differences were not statistically significant. Cataract progression was observed in 4 of 8 phakic eyes (50%) after the first implant, and in 2 of 3 phakic eyes following the second implant, with 1 eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, treated topically. Conclusion Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. PMID:29184384

Ischemic index changes in diabetic retinopathy after intravitreal dexamethasone implant using ultra-widefield fluorescein angiography: a pilot study.

PubMed

Querques, Lea; Parravano, Mariacristina; Sacconi, Riccardo; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-08-01

To investigate the effect of dexamethasone intravitreal implant on peripheral ischemia in patients affected by diabetic macular edema (DME). Patients with treatment-naïve diabetic retinopathy (DR) undergoing intravitreal dexamethasone implant for DME between October 2015 and March 2017 were enrolled. Patients underwent a comprehensive ocular examination at baseline (<2 weeks before treatment) and 10 ± 2 weeks after dexamethasone implant including best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography, ultra-widefield (UWF) retinography and UWF fluorescein angiography (UWFA). Nine eyes of seven consecutive patients (five males; mean age 66.4 ± 6.7 years) were enrolled. Mean duration of DR was 12.3 ± 8.4 years. Mean interval between UWFA acquisitions was 12.1 ± 2.1 weeks, and the mean interval between intravitreal injection and UWFA acquisition was 11.0 ± 1.6 weeks. Mean pre- and post-injection BCVA was 0.30 ± 0.20 and 0.21 ± 0.14 logMAR (p = 0.06), respectively. Mean pre- and post-injection central macular thickness was 449.8 ± 92.5 and 356.3 ± 52.4 μm (p = 0.03), respectively. Mean pre- and post-injection ischemic index was 24.0 ± 25.0 and 9.8 ± 12.1% (p = 0.0427), respectively. Intravitreal dexamethasone implant reduces peripheral retina ischemia in patients with DR.

Real-World Cost Savings Demonstrated by Switching Patients with Refractory Diabetic Macular Edema to Intravitreal Fluocinolone Acetonide (Iluvien): A Retrospective Cost Analysis Study.

PubMed

Ch'ng, Soon W; Brent, Alexander J; Empeslidis, Theodoros; Konidaris, Vasileios; Banerjee, Somnath

2018-06-01

It is hypothesized that using fluocinolone acetonide (FAc) implants such as Iluvien for the treatment of diabetic macular edema (DME) may reduce the total number of intravitreal injections and clinic visits, resulting in an overall treatment cost reduction. The primary aim of this study is to identify the real-world cost savings achievable in a tertiary National Health Service (NHS) hospital. A retrospective cost analysis study was conducted. The inclusion criteria were patients with refractory DME who were switched to Iluvien. The average yearly costs were calculated both before and after the switch to Iluvien. All costs including medicines, investigations, clinics, and management of raised intraocular pressure (IOP) were calculated. The cost differences over the 3 years' worth of Iluvien treatment were calculated and analyzed. To ensure non-inferiority of this treatment intervention, the best corrected visual acuity (BCVA) and central retinal thickness (CRT) were also analyzed. Statistical analysis was conducted with a Student t test where appropriate and statistical significance is identified where p < 0.05. Fourteen eyes of 13 patients met the inclusion criteria. Switching patients to Iluvien achieved on average a saving of £2606.17 per patient (p = 0.33) over the 3 years. However, seven cases (50%) had a rise in IOP after Iluvien that warranted medical treatment and two cases (14.3%) required glaucoma surgery. Incorporating the costs of glaucoma management reduced the overall savings over 3 years to £1064.66 per patient. The BCVA and CRT analysis showed a non-inferiority relationship between Iluvien and any previous treatment. The use of Iluvien in refractory DME patients represents a cost- and time-saving procedure, while showing non-inferiority in terms of efficacy.

Accidental injections of dexamethasone intravitreal implant (Ozurdex) into the crystalline lens.

PubMed

Coca-Robinot, Javier; Casco-Silva, Bruno; Armadá-Maresca, Felix; García-Martínez, Jesús

2014-01-01

To describe the side effects and management after inadvertent injection of a dexamethasone implant (Ozurdex) into the crystalline lens. Two case reports. Two patients with macular edema due to unilateral retinal vein occlusion were scheduled for an intravitreal injection of Ozurdex. During the procedure, the implant was accidentally injected into the crystalline lens. Both patients developed cataracts during the course of several weeks and in both there was an intraocular pressure (IOP) increase, which required treatment with topical hypotensives. Macular edema improved only slightly. Cataract surgery with uneventful removal of the implant was performed 3 (case 1) and 6 months (case 2) after the injection. After inadvertent injection of Ozurdex into the crystalline lens, cataract surgery with removal of the implant should be performed as soon as possible in order to avoid IOP increase and so that the underlying condition may be treated adequately.

In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide.

PubMed

Sheshala, Ravi; Hong, Gan Chew; Yee, Wong Pui; Meka, Venkata Srikanth; Thakur, Raghu Raj Singh

2018-02-26

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

A meta-analysis of the effect of a dexamethasone intravitreal implant versus intravitreal anti-vascular endothelial growth factor treatment for diabetic macular edema.

PubMed

He, Ye; Ren, Xin-Jun; Hu, Bo-Jie; Lam, Wai-Ching; Li, Xiao-Rong

2018-05-21

This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 μm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 μm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.

Fluocinolone acetonide implant (Retisert) for chronic cystoid macular edema in two patients with AIDS and a history of cytomegalovirus retinitis.

PubMed

Hu, Jianmin; Coassin, Marco; Stewart, Jay M

2011-06-01

To report the authors' experience using fluocinolone acetonide (Retisert) to treat cystoid macular edema (CME) resulting from immune recovery uveitis (IRU) in 2 acquired immunodeficiency syndrome (AIDS) patients with a history of cytomegalovirus (CMV) retinitis. Interventional case series. Medical records were reviewed of 2 patients who received Retisert implantation in 3 eyes for IRU-associated inflammation and CME. Suppression of CMV disease was achieved with oral medication in one patient and with simultaneous implantation of a ganciclovir implant in the other patient. After Retisert implantation in 3 eyes in AIDS patients on HAART, improvement in CME was seen in 2 eyes. No CMV reactivation was detected during the several-month follow-up period. Retisert may be an effective treatment for CME in AIDS patients with IRU reactivation and a history of CMV retinitis.

Intravitreal Controlled Release of Dexamethasone from Engineered Microparticles of Porous Silicon Dioxide

PubMed Central

Wang, Chengyun; Hou, Huiyuan; Nan, Kaihui; Sailor, Michael J; Freeman, William R.; Cheng, Lingyun

2014-01-01

Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterificaion Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and

Efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma.

PubMed

Tang, Min; Fu, Yang; Wang, Ying; Zheng, Zhi; Fan, Ying; Sun, Xiaodong; Xu, Xun

2016-01-09

Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma. In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and < = 21 mm Hg, with or without the use of anti-glaucoma medications, and without severe complications or reoperation. Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7% vs. 71.4% at six months and 72.2% vs. 68.4% at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months. Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation. Chinese Clinical Trial Registry ( ChiCTR-OOC-14005709, Trial registration date: 2014-12-01).

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

PubMed

Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P < 0.0001). By Month 6, mean central retinal thickness was 287.3 μm (P = 0.16). Eyes with only intraretinal fluid (13 eyes) achieved a fluid-free macula. Eyes with predominantly subretinal fluid (6 eyes) did not improve central retinal thickness and continued monthly ranibizumab. Mean baseline intraocular pressure was 13.2 mmHg, which peaked at 15.6 mmHg by Month 2 (P = 0.004). Intravitreal dexamethasone implant improved only macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Comparison of the Efficacy Between an Intravitreal and a Posterior Subtenon Injection of Triamcinolone Acetonide for the Treatment of Diffuse Diabetic Macular Edema

PubMed Central

Qamar, Rao Muhammad Rashad; Saleem, Muhammad Imran; Saleem, Muhammad Farhan

2013-01-01

Objective: To compare the efficacy of an intravitreal injection to a posterior subtenon injection of triamcinolone acetonide for the treatment of diffuse diabetic macular edema. Materials and Methods: Sixty patients with diabetes mellitus presenting with diffuse diabetic macular edema were recruited for the study. In each patient, one eye received a 4.0 mg (0.1 mL) intravitreal (IVT) injection of TA and the other eye was treated with a 40 mg (1.0 mL) posterior subtenon (PST) injection of triamcinolone acetonide (TA). We measured the visual acuity, the intraocular pressure (IOP) and the thickness of the macula using optical coherence tomography (OCT) before treatment and at one, three and six months after treatment. Results: Eyes treated with PST showed 1–3 lines of improvement in Snellen’s acuity from their pre-injection baseline visual status. The eyes in the IVT group showed 1–3 lines of improvement in Snellen’s acuity in 80% of the treated eyes, but 20% of the treated eyes did not display any benefit at the end of six months. The difference in acuity between an IVT injection and a PST injection at six months post-treatment was statistically significant (p<0.05). The macular thickness of the eyes treated with an IVT injection was significantly reduced after one (222.7±13.4 μm; p<0.001) and three months (228.1±10.6 μm; p<0.001) of treatment. The eyes treated with a PST injection displayed a slow response and a significant improvement in macular thickness that was observed only after three months (231.3±10.9 μm; p<0.001). The difference between the eyes treated with an IVT injection (385.2±11.3 μm) and those treated with a PST injection (235.4±8.7 μm) was significantly different six months after treatment (p<0.001). The IOP of the eyes treated with an IVT injection was significantly increased after one (17.7±1.1 mm/Hg; p<0.020), three (18.2±1.2 mm/Hg; p<0.003) and six months (18.1±1.320 mm/Hg; p<0.007) when compared to the baseline value (16.1�

Review and update of intraocular therapy in noninfectious uveitis.

PubMed

Sallam, Ahmed; Taylor, Simon R J; Lightman, Sue

2011-11-01

To review new clinically relevant data regarding the intraocular treatment of noninfectious uveitis. Triamcinolone acetonide, the most commonly used intravitreal corticosteroid for treatment of uveitis and uveitic macular oedema has a limited duration of action and is associated with a high risk of corticosteroid-induced intraocular pressure (IOP) rise and cataract. Recent advances have led to the development of sustained-release corticosteroid devices using different corticosteroids such as dexamethasone and fluocinolone acetonide. Treatment options for patients who have previously exhibited corticosteroid hypertensive response have also expanded through the use of new noncorticosteroid intravitreal therapeutics such as methotrexate and antivascular endothelial growth factor (anti-VEGF) agents. Ozurdex dexamethasone implant appears to have a better safety profile, and a slightly long-lasting effect than triamcinolone acetonide. The Retisert implant allows the release of corticosteroids at a constant rate for 2.5 years, but it requires surgical placement and its use is associated with a very high risk of cataract and requirement for IOP-lowering surgery. For patients who are steroid responders, methotrexate may offer a better alternative to corticosteroid treatment than anti-VEGF agents, but controlled trials are required to confirm this.

Incidence, Risk Factors, and Timing of Elevated Intraocular Pressure After Intravitreal Triamcinolone Acetonide Injection for Macular Edema Secondary to Retinal Vein Occlusion: SCORE Study Report 15.

PubMed

Aref, Ahmad A; Scott, Ingrid U; Oden, Neal L; Ip, Michael S; Blodi, Barbara A; VanVeldhuisen, Paul C

2015-09-01

The Standard of Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study showed that intravitreal triamcinolone acetonide (IVTA) is effective at reducing macular edema and improving visual acuity in participants with retinal vein occlusion. Secondary analysis of the incidence, risk factors, and timing of intraocular pressure (IOP) elevation occurring after IVTA provides guidance for clinical decision making and management of patients treated with IVTA. To investigate the incidence, risk factors, and time course of IOP elevation in participants in the SCORE Study. Secondary analysis conducted from August through December 2014 of a prospective, randomized clinical trial featuring an evaluable population conducted at 75 clinical sites. Six hundred eighty-two patients with macular edema secondary to retinal vein occlusion were enrolled in the study. The SCORE Study enrollment period ran from November 4, 2004, to February 29, 2008, with participant follow-up ending February 28, 2009. Study participants were randomized to standard of care, 1 mg of IVTA, or 4 mg of IVTA therapy and followed up for a mean (SD) of 24.7 (10.3) months. Intraocular pressure elevation greater than 10 mm Hg from baseline. Kaplan-Meier incidences of IOP elevation greater than 10 mm Hg from baseline at 36 months were 0.02 (95% CI, 0.01-0.06), 0.09 (95% CI, 0.05-0.14), and 0.45 (95% CI, 0.38-0.53) in the standard of care, 1-mg IVTA, and 4-mg IVTA groups, respectively. The rates of IOP-related events were higher for the 4-mg IVTA group compared with the other groups (P ≤ .001 for main outcome measure). Younger age, 4-mg IVTA vs 1-mg IVTA treatment, and higher baseline IOP were found to confer greater risk for IOP-related events (P < .05 for all). The median number of days from time of first injection to IOP elevation greater than 10 mm Hg from baseline was 34.0 and 52.5 days in participants treated with 1-mg and 4-mg IVTA, respectively. Intravitreal triamcinolone acetonide injection

Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis.

PubMed

Bratton, Monica L; He, Yu-Guang; Weakley, David R

2014-04-01

To report our experience using Ozurdex (Allergan, Irvine, CA), a biodegradable intravitreal implant containing of 0.7 mg of dexamethasone approved for use in adults with noninfectious uveitis in adults, in the treatment of pediatric uveitis. The medical records of consecutive patients with noninfectious posterior uveitis who were unresponsive to standard treatment and subsequently received the Ozurdex implant from March 2011 to March 2013 were retrospectively reviewed. A total of 14 eyes of 11 patients (mean age, 10.1 years; range 4-12) received 22 Ozurdex implants during the study period. Of the 11 patients, 7 had idiopathic intermediate or posterior uveitis, 1 had sympathetic ophthalmia, 2 had juvenile idiopathic arthritis, and 1 had sarcoidosis. All patients were uncontrolled with standard treatment, including topical or sub-Tenon's or systemic corticosteriods and/or immune-modulation. Visual acuity improved after Ozurdex implant in 5 of 8 patients (63%). Intraocular inflammation was controlled or improved after 17 of 22 of implants (12 eyes [77%]). The frequency of topical corticosteroids was decreased and/or discontinued after 18 of 22 implants (12 eyes [82%]). Complications included implant migration into the anterior chamber (4 aphakic eyes), increased intraocular pressure (5 eyes), and progression of a preexisting cataract (1 eye). The uveitis reoccurred in 57% of eyes at 4.3 months (2-7 months) after injection. The Ozurdex implant in combination with systemic immunomodulatory therapy resulted in improved visual acuity, control of intraocular inflammation, and a decrease in corticosteroid use. In the majority of eyes the uveitis reoccurred around 4 months after injection. The adverse events in our study are similar to those identified in adult studies. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial.

PubMed

Bressler, Susan B; Qin, Haijing; Melia, Michele; Bressler, Neil M; Beck, Roy W; Chan, Clement K; Grover, Sandeep; Miller, David G

2013-08-01

The standard care for proliferative diabetic retinopathy (PDR) usually is panretinal photocoagulation, an inherently destructive treatment that can cause iatrogenic vision loss. Therefore, evaluating the effects of therapies for diabetic macular edema on development or worsening of PDR might lead to new therapies for PDR. To evaluate the effects of intravitreal ranibizumab or triamcinolone acetonide, administered to treat diabetic macular edema, on worsening of diabetic retinopathy. Exploratory analysis was performed on worsening of retinopathy, defined as 1 or more of the following: (1) worsening from no PDR to PDR, (2) worsening of 2 or more severity levels on reading center assessment of fundus photographs in eyes without PDR at baseline, (3) having panretinal photocoagulation, (4) experiencing vitreous hemorrhage, or (5) undergoing vitrectomy for the treatment of PDR. Community- and university-based ophthalmology practices. Individuals with central-involved diabetic macular edema causing visual acuity impairment. Eyes were assigned randomly to sham with prompt focal/grid laser, 0.5 mg of intravitreal ranibizumab with prompt or deferred (≥24 weeks) laser, or 4 mg of intravitreal triamcinolone acetonide with prompt laser. Three-year cumulative probabilities for retinopathy worsening. For eyes without PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening (P value comparison with sham with prompt laser) were 23% using sham with prompt laser, 18% with ranibizumab with prompt laser (P = .25), 7% with ranibizumab with deferred laser (P = .001), and 37% with triamcinolone with prompt laser (P = .10). For eyes with PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening were 40%, 21% (P = .05), 18% (P = .02), and 12% (P < .001), respectively. CONCLUSIONS AND RELEVANCE Intravitreal ranibizumab appears to be associated with a reduced risk of diabetic retinopathy worsening in eyes with or without PDR. Intravitreal

Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

PubMed

Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

2011-02-01

Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution

Comparison of grid laser, intravitreal triamcinolone, and intravitreal bevacizumab in the treatment of diffuse diabetic macular edema.

PubMed

Sobaci, Güngör; Ozge, Gökhan; Erdurman, Cüneyt; Durukan, Hakan A; Bayraktar, Zeki M

2012-01-01

To compare the effects of grid laser (GL), intravitreal bevacizumab (IVB), and intravitreal triamcinolone acetonide (IVTA) in diffuse diabetic macular edema (DDME). One hundred and twenty-six patients (126 eyes) treated with GL (modified grid), IVTA (4 mg), and IVB (1.25 mg) injections, matched for best corrected visual acuity (BCVA) and OCT-based central macular thickness at presentation, were enrolled. Primary outcome measure was change in best corrected logMAR visual acuity at 1-year follow-up. Rates of visual stabilization (within ±0.2 logMAR of baseline BCVA) (71.4, 83.3, 78.6%, respectively) were not different between the groups (p = 0.41) at 12-month follow-up. Higher rates of anatomical and functional success, however, were evident in IVB and IVTA groups within 6 months of treatment (p < 0.05 for both). No severe adverse effects except higher intraocular pressure (10 mm Hg from baseline) in one third (14 eyes) of the IVTA cases, who required trabeculectomy in 2 (4.8%) eyes, were observed. Intraocular injections may give favorable results within the first 6 months, and after 6 months, GL results seem to be more favorable in the treatment of treatment-naïve, acute, nonischemic, and center-involving DDME. Copyright © 2011 S. Karger AG, Basel.

Intravitreal injection therapy in the treatment of noninfectious uveitis.

PubMed

Modorati, Giulio; Miserocchi, Elisabetta

2012-01-01

Uveitis is responsible for 5-20% of legal blindness in the United States and in Europe. In noninfectious uveitis, the most frequent uveitic complication that endangers sight is cystoid macular edema. Clinical characteristics, inflammation grading and visual acuity determine the choice of the correct therapy for each patient. We can utilize drugs either alone or in combination using different dosages and routes of administration. Intravitreal injection directly into the vitreous cavity leads to rapid therapeutic drug concentration in the retinal tissue and reduces systemic side effects. Intravitreally injected triamcinolone acetonide is the most powerful drug for the treatment of cystoid macular edema related to intraocular inflammation, but it also causes the most frequent and serious side effects. Due to the numerous side effects associated with the use of corticosteroids, there is a need to identify other anti-inflammatory agents with a better safety profile. Recent studies have demonstrated that intravitreal immunosuppressant injections of methotrexate or anti-VEGF agents may lead to fewer intraocular side effects, but also have a lower therapeutic activity for the reduction of macular edema. At present, intraocular anti-TNF-α drugs do not show promising results. As regards nonsteroidal anti-inflammatory drugs, further data are necessary to fully understand their efficacy and potential side effects. Copyright © 2012 S. Karger AG, Basel.

Postoperative outcomes after fluocinolone acetonide implant surgery in patients with birdshot chorioretinitis and other types of posterior and panuveitis.

PubMed

Burkholder, Bryn M; Wang, Jiangxia; Dunn, James P; Nguyen, Quan D; Thorne, Jennifer E

2013-09-01

To evaluate outcomes after placement of fluocinolone acetonide (FA) implants in eyes with birdshot chorioretinitis and to compare these outcomes with eyes with posterior and panuveitis. This is a retrospective cohort study of 48 eyes from patients with posterior and panuveitis treated with FA implants from 2006 to 2010. Outcome measures include visual acuity, intraocular pressure, need for glaucoma surgery, postoperative complications, and control of inflammation. All eyes treated with FA implants achieved improved control of inflammation and decreased reliance on adjunctive therapy. Birdshot chorioretinitis eyes had a statistically significant increase in intraocular pressure in the first 4 months after FA implantation (P = 0.04) compared with baseline intraocular pressure. A higher percentage of eyes with birdshot chorioretinitis required glaucoma surgery and after a shorter time period after FA implantation than did eyes with other forms of posterior and panuveitis (0.42/eye-year vs. 0.11/eye-year; median time to glaucoma surgery: 15.5 months vs. 31.5 months respectively, hazard ratio, 3.4; 95% confidence interval, 1.0-10.8, P = 0.04). Although the FA implant is effective in controlling inflammation and reducing the need for systemic immunosuppressive therapy, eyes of patients with birdshot chorioretinitis tend to have a more robust intraocular pressure response to the FA implant than eyes with other types of posterior and panuveitis.

Effect of intravitreal triamcinolone acetonide injection at the end of vitrectomy for vitreous haemorrhage related to proliferative diabetic retinopathy.

PubMed

Takamura, Yoshihiro; Shimura, Masahiko; Katome, Takashi; Someya, Hideaki; Sugimoto, Masahiko; Hirano, Takao; Sakamoto, Taiji; Gozawa, Makoto; Matsumura, Takehiro; Inatani, Masaru

2018-01-17

To investigate whether intravitreal injection of triamcinolone acetonide (IVTA) combined with vitrectomy prevents postoperative inflammation in patients with vitreous haemorrhage (VH) due to proliferative diabetic retinopathy (PDR). This prospective, multicentre, randomised study conducted at seven sites in Japan enrolled patients diagnosed as having VH following PDR. Patients underwent vitrectomy with (IVTA+VIT group) or without (VIT group) IVTA at the end of the surgery. Anterior flare intensity (AFI), central retinal thickness (CRT), best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured before and at 3 days, 1 week, 1, 3 and 6 months after surgery and compared. Number of patients who completed 6 months of follow-up was 40 and 41 in VIT group and IVTA+VIT group, respectively. AFI was significantly higher in the VIT group than in the IVTA+VIT group at 3 days (P=0.033), 1 week (P=0.019) and 1 month (P=0.037). There were no significant differences in CRT, BCVA and IOP between the groups through the observational periods. In the cases with macular oedema >350 µm of CRT at 3 days, CRT was significantly lower in the IVTA+VIT group than in the VIT group at 1 month (P=0.041). IVTA combined with vitrectomy and cataract surgery contributed to inhibit the postoperative inflammation in patients with VH due to PDR. The effect of IVTA in the reduction of diabetic macular oedema may be limited to the early stage after surgery. UMIN000020376, Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Combined Glaucoma Tube Shunt (Ahmed) and Fluocinolone Acetonide (Retisert™) Implantation Compared to Ahmed Alone in Uveitic Glaucoma.

PubMed

Zivney, Mark; Lin, Phoebe; Edmunds, Beth; Parikh, Mansi; Takusagawa, Hana; Tehrani, Shandiz

2016-12-01

Glaucoma is a known complication of uveitis, and may require glaucoma tube shunt implantation for intraocular pressure (IOP) control. The success of glaucoma tube shunt implantation in the setting of a local ocular steroid depot in uveitic glaucoma remains unknown. The purpose of this study was to determine whether patients who underwent combined glaucoma tube shunt (Ahmed) and fluocinolone acetonide (Retisert™, Bausch + Lomb, Bridgewater, NJ, USA) implantation have superior outcomes compared to patients with Ahmed implants only in the setting of uveitic glaucoma. All participants were studied retrospectively and underwent Ahmed implantation alone or with existing/concurrent Retisert implantation (combined group) at a single academic institution. The main outcome measures were IOP, visual acuity (VA), number of IOP-lowering medications, and adverse events at 6 months after Ahmed implantation. Secondary outcome measures included adverse events and surgical success at 6 months after Ahmed implantation. Mean IOP at 6 months after Ahmed implantation was 15.3 ± 4.8 and 15.1 ± 4.9 mm Hg in the Ahmed only group (n = 17) and the combined group (n = 17), respectively (p = 0.89). The mean number of IOP-lowering medications at 6 months after Ahmed implantation was 1.7 ± 1.0 and 1.8 ± 1.0 in the Ahmed only group and the combined group, respectively (p = 0.86). Mean VA at 6 months after Ahmed implantation was 0.35 ± 0.29 and 0.42 ± 0.33 log mean angle of resolution in the Ahmed only group and the combined group, respectively (p = 0.50). No significant differences in surgical success or adverse events were noted between the two groups. At 6 months, no significant differences in mean IOP, mean number of IOP-lowering medications, VA, surgical success, or adverse events were noted between Ahmed implantation alone or combined Ahmed and Retisert implantation in patients with uveitic glaucoma.

Combination therapy with dexamethasone intravitreal implant and macular grid laser in patients with branch retinal vein occlusion.

PubMed

Pichi, Francesco; Specchia, Claudia; Vitale, Lucia; Lembo, Andrea; Morara, Mariachiara; Veronese, Chiara; Ciardella, Antonio P; Nucci, Paolo

2014-03-01

To test a combination of dexamethasone intravitreal implant with macular grid laser for macular edema in patients with branch retinal vein occlusion (BRVO). Prospective interventional, randomized, multicenter study. Patients with macular edema secondary to BRVO underwent an Ozurdex intravitreal implant at baseline. After 1 month, patients were randomly assigned to 2 study groups. Patients in Group 1 were followed up monthly and retreated with Ozurdex implant whenever there was a recurrence of macular edema or a decrease in best-corrected visual acuity (BCVA). In Group 2 patients macular grid laser was performed between weeks 6 and 8. After that, patients were followed up and retreated as for Group 1. In Group 1 at 4 months, mean BCVA was 0.49 ± 0.35 logMAR and central retinal thickness (CRT) was 391 ± 172 μm; both improved significantly at 6 months, to 0.32 ± 0.29 logMAR and 322 ± 160 μm, respectively. In Group 2, CRT was reduced significantly to 291 ± 76 μm at 4 months, and BCVA improved to 0.25 ± 0.20 logMAR. At the final visit, BCVA was 0.18 ± 0.14 logMAR and mean CRT was 271 ± 44 μm. The number of Ozurdex implants at 4 months was 12 of 25 (48%) in Group 1 patients vs 3 of 25 (12%) in Group 2 patients (P = .012). At 6 months 3 of 25 patients (12%) in Group 1 vs 0 of 25 (0%) in Group 2 (P = .23) were retreated. The combination of Ozurdex implant and macular grid laser is synergistic in increasing BCVA and lengthening the time between injections. Copyright © 2014 Elsevier Inc. All rights reserved.

Viral retinitis following intraocular or periocular corticosteroid administration: a case series and comprehensive review of the literature.

PubMed

Takakura, Ako; Tessler, Howard H; Goldstein, Debra A; Guex-Crosier, Yan; Chan, Chi-Chao; Brown, Diane M; Thorne, Jennifer E; Wang, Robert; Cunningham, Emmett T

2014-06-01

To describe viral retinitis following intravitreal and periocular corticosteroid administration. Retrospective case series and comprehensive literature review. We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.

Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature

PubMed Central

Takakura, Ako; Tessler, Howard H.; Goldstein, Debra A.; Guex-Crosier, Yan; Chan, Chi-Chao; Brown, Diane M.; Thorne, Jennifer E.; Wang, Robert; Cunningham, Emmett T.

2014-01-01

Purpose To describe viral retinitis following intravitreal and periocular corticosteroid administration. Methods Retrospective case series and comprehensive literature review. Results We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25–13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Conclusions Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy. PMID:24655372

Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.

PubMed

Holbrook, Janet T; Sugar, Elizabeth A; Burke, Alyce E; Vitale, Albert T; Thorne, Jennifer E; Davis, Janet L; Jabs, Douglas A

2016-04-01

To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial. Randomized clinical trial with extended follow-up. Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically related. A total of 250 eyes (146 patients) had at least 1 implant placed. Median follow-up time after implant placement was 6 years (range 0.5-9.2 years). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval [CI]: 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. Thirty-nine implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%-48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, P < .001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or its treatment. There is an increasing risk of dissociation of Retisert implants during follow-up; the risk is greater with removal/exchange surgeries, but the risk of both spontaneous and surgically related events increases with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected. Copyright © 2016 Elsevier Inc. All rights reserved.

Adjunctive triamcinolone acetonide for Ahmed glaucoma valve implantation: a randomized clinical trial.

PubMed

Yazdani, Shahin; Doozandeh, Azadeh; Pakravan, Mohammad; Ownagh, Vahid; Yaseri, Mehdi

2017-06-26

To evaluate the effect of intraoperative sub-Tenon injection of triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. In this triple-blind randomized clinical trial, 104 eyes with refractory glaucoma were randomly assigned to conventional AGV (non-TA group) or AGV with adjunctive triamcinolone (TA group). In the TA group, 10 mg TA was injected in the sub-Tenon space around the AGV plate intraoperatively. Patients were followed for 1 year. The main outcome measure was intraocular pressure (IOP). Other outcome measures included best-corrected visual acuity (BCVA), occurrence of hypertensive phase (HP), peak IOP, number of antiglaucoma medications, and complications. A total of 90 patients were included in the final analysis. Mean IOP was lower in the TA group at most follow-up visits; however, the difference was statistically significant only at the first month (p = 0.004). Linear mixed model showed that mean IOP was 1.5 mm Hg lower in the TA group throughout the study period (p = 0.006). Peak postoperative IOP was significantly lower in the TA group (19.3 ± 4.8 mm Hg versus 29 ± 9.2 mm Hg, p = 0.032). Rates of success (defined as 6 < IOP <21 mm Hg) were similar in both groups at 12 months. There was no difference in the occurrence of the HP between the 2 groups (p = 0.123). Loss of BCVA >2 lines was more common in the non-TA group (p = 0.032). Adjunctive intraoperative TA injection during AGV implantation can blunt peak IOP levels and reduce mean IOP up to 1 year. Visual outcomes also seem to be superior to standard surgery.

Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

PubMed

Arcieri, Enyr S; Paula, Jayter S; Jorge, Rodrigo; Barella, Kleyton A; Arcieri, Rafael S; Secches, Danilo J; Costa, Vital P

2015-02-01

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate.

PubMed

Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

2012-01-01

The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.

SCORE Study Report 7: incidence of intravitreal silicone oil droplets associated with staked-on vs luer cone syringe design.

PubMed

Scott, Ingrid U; Oden, Neal L; VanVeldhuisen, Paul C; Ip, Michael S; Blodi, Barbara A; Antoszyk, Andrew N

2009-11-01

To evaluate the incidence of intravitreal silicone oil (SO) droplets associated with intravitreal injections using a staked-on vs luer cone syringe design in the SCORE (Standard Care vs COrticosteroid in REtinal Vein Occlusion) Study. Prospective, randomized, phase III clinical trial. The incidence of intravitreal SO was compared among participants exposed to the staked-on syringe design, the luer cone syringe design, or both of the syringe designs in the SCORE Study, which evaluated intravitreal triamcinolone acetonide injection(s) for vision loss secondary to macular edema associated with central or branch retinal vein occlusion. Injections were given at baseline and 4-month intervals, based on treatment assignment and study-defined retreatment criteria. Because intravitreal SO was observed following injections in some participants, investigators were instructed, on September 22, 2006, to look for intravitreal SO at all study visits. On November 1, 2007, the luer cone syringe design replaced the staked-on syringe design. A total of 464 participants received a total of 1,205 injections between November 4, 2004 and February 28, 2009. Intravitreal SO was noted in 141 of 319 participants (44%) exposed only to staked-on syringes, 11 of 87 (13%) exposed to both syringe designs, and 0 of 58 exposed only to luer cone syringes (P < .0001). Among participants with first injections after September 22, 2006, intravitreal SO was noted in 65 of 114 (57%) injected only with staked-on syringes compared with 0 of 58 injected only with luer cone syringes. Differential follow-up is unlikely to explain these results. In the SCORE Study, luer cone syringe design is associated with a lower frequency of intravitreal SO droplet occurrence compared with the staked-on syringe design, likely attributable to increased residual space in the needle hub with the luer cone design.

[Viral retinitis following intravitreal triamcinolone injection].

PubMed

Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

2013-09-01

Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis. Copyright © 2013. Published by Elsevier Masson SAS.

Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion.

PubMed

Haller, Julia A; Bandello, Francesco; Belfort, Rubens; Blumenkranz, Mark S; Gillies, Mark; Heier, Jeffrey; Loewenstein, Anat; Yoon, Young-Hee; Jacques, Marie-Louise; Jiao, Jenny; Li, Xiao-Yan; Whitcup, Scott M

2010-06-01

To evaluate the safety and efficacy of dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, CA) compared with sham in eyes with vision loss due to macular edema (ME) associated with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Two identical, multicenter, masked, randomized, 6-month, sham-controlled clinical trials (each of which included patients with BRVO and patients with CRVO). A total of 1267 patients with vision loss due to ME associated with BRVO or CRVO. A single treatment with DEX implant 0.7 mg (n = 427), DEX implant 0.35 mg (n = 414), or sham (n = 426). The primary outcome measure for the pooled data from the 2 studies was time to achieve a > or =15-letter improvement in best-corrected visual acuity (BCVA). Secondary end points included BCVA, central retinal thickness, and safety. After a single administration, the time to achieve a > or =15-letter improvement in BCVA was significantly less in both DEX implant groups compared with sham (P<0.001). The percentage of eyes with a > or =15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (P<0.001). The percentage of eyes with a > or =15-letter loss in BCVA was significantly lower in the DEX implant 0.7-mg group compared with sham at all follow-up visits (P< or =0.036). Improvement in mean BCVA was greater in both DEX implant groups compared with sham at all follow-up visits (P< or =0.006). Improvements in BCVA with DEX implant were seen in patients with BRVO and patients with CRVO, although the patterns of response differed. The percentage of DEX implant-treated eyes with intraocular pressure (IOP) of > or =25 mmHg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. There was no significant between-group difference in the occurrence of cataract or cataract surgery. Dexamethasone intravitreal implant can both reduce the risk of vision loss and improve the

A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Focal/Grid Photocoagulation for Diabetic Macular Edema

PubMed Central

2009-01-01

Objective To evaluate the efficacy and safety of 1 mg and 4 mg doses of preservative-free intravitreal triamcinolone in comparison with focal/grid photocoagulation for the treatment of diabetic macular edema (DME). Design Multi-center randomized clinical trial Participants 840 study eyes of 693 subjects with DME involving the fovea and visual acuity 20/40 to 20/320 Methods Eyes were randomized to focal/grid photocoagulation (N=330), 1 mg intravitreal triamcinolone (N=256), or 4 mg intravitreal triamcinolone (N=254). Retreatment was given for persistent or new edema at 4-month intervals. The primary outcome was at 2 years. Main Outcome Measures Visual acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method (primary), optical coherence tomography (OCT)-measured retinal thickness (secondary), and safety. Results At 4 months, mean visual acuity was better in the 4 mg triamcinolone group than in either the laser group (P<0.001) or the 1 mg triamcinolone group (P=0.001). By 1 year, there were no significant differences among groups in mean visual acuity. At the 16-month visit and extending through the primary outcome visit at 2 years, mean visual acuity was better in the laser group than in the other two groups (at 2 years, P=0.02 comparing the laser and 1 mg groups, P=0.002 comparing the laser and 4 mg groups, and P=0.49 comparing the 1mg and 4 mg groups). Treatment group differences in the visual acuity outcome could not be attributed solely to cataract formation. OCT results generally paralleled the visual acuity results. Intraocular pressure was increased from baseline by ≥10 mm Hg at any visit in 4%, 16%, and 33% of eyes in the three treatment groups, respectively, and cataract surgery was performed in 13%, 23%, and 51% of eyes in the three treatment groups, respectively. Conclusions Over a 2-year period, focal/grid photocoagulation is more effective and has fewer side effects than 1 mg or 4 mg doses of preservative

A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema.

PubMed

2008-09-01

To evaluate the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone in comparison with focal/grid photocoagulation for the treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. Eight hundred forty study eyes of 693 subjects with DME involving the fovea and with visual acuity of 20/40 to 20/320. Eyes were randomized to focal/grid photocoagulation (n = 330), 1 mg intravitreal triamcinolone (n = 256), or 4 mg intravitreal triamcinolone (n = 254). Retreatment was given for persistent or new edema at 4-month intervals. The primary outcome was evaluated at 2 years. Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method (primary), optical coherence tomography-measured retinal thickness (secondary), and safety. At 4 months, mean visual acuity was better in the 4-mg triamcinolone group than in either the laser group (P<0.001) or the 1-mg triamcinolone group (P = 0.001). By 1 year, there were no significant differences among groups in mean visual acuity. At the 16-month visit and extending through the primary outcome visit at 2 years, mean visual acuity was better in the laser group than in the other 2 groups (at 2 years, P = 0.02 comparing the laser and 1-mg groups, P = 0.002 comparing the laser and 4-mg groups, and P = 0.49 comparing the 1-mg and 4-mg groups). Treatment group differences in the visual acuity outcome could not be attributed solely to cataract formation. Optical coherence tomography results generally paralleled the visual acuity results. Intraocular pressure increased from baseline by 10 mmHg or more at any visit in 4%, 16%, and 33% of eyes in the 3 treatment groups, respectively, and cataract surgery was performed in 13%, 23%, and 51% of eyes in the 3 treatment groups, respectively. Over a 2-year period, focal/grid photocoagulation is more effective and has fewer side effects than 1-mg or 4-mg doses of preservative-free intravitreal triamcinolone for

Hemodynamic response to intravitreal triamcinolone in eyes with macular edema: intravitreal triamcinolone and ocular blood flow.

PubMed

Cekiç, Osman; Bardak, Yavuz; Tiğ, Sahin U; Demirkol, Aykut; Ekim, Mustafa M; Altintaş, Onem; Yeşildağ, Ahmet; Oyar, Orhan

2007-10-01

To assess ocular hemodynamic response to intravitreal triamcinolone in patients with macular edema due to diabetes or retinal vein occlusion. Forty-three patients that were injected by intravitreal triamcinolone acetonide (0.1 cc 4 mg) for unilateral macular edema due to diabetes mellitus (n = 17) and occlusion of retinal vein (n = 26) underwent ocular hemodynamic evaluation by color Doppler imaging (CDI) before and one, two and three months after injection. Non-injected fellow eyes as well as 16 healthy volunteers were also evaluated. In patients with diabetic macular edema, there was no hemodynamic difference between eyes to be injected and non-injected at baseline (P > 0.23). Compared to controls, a significant difference existed in the ophthalmic artery resistant index (P = 0.001) and end-diastolic velocity (P < 0.001) in diabetics. At one month, compared to fellow eyes, change in end diastolic velocity from baseline in treated eyes was significantly decreased in posterior ciliary arteries (0.68 +/- 0.34 cm/s [mean +/- SEM] vs. -1.04 +/- 0.81 cm/s, P = 0.012). Throughout the study period, no significant alteration from baseline in the resistant index of any artery was noted in treated diabetic eyes (P > 0.05). In eyes with retinal vein occlusion, baseline CDI evaluation demonstrated reduced posterior ciliary arteries systolic flow velocity compared to fellow and control eyes (13.24 +/- 1.04 cm/s, 16.37 +/- 0.76 cm/s and 14.33 +/- 1.41 cm/s, respectively, P = 0.007). Increased peak systolic velocity in the posterior ciliary arteries at one week (P = 0.02), one month (P = 0.005) and two months (P = 0.04), and increase in central retinal artery resistant index at one month was noted (P = 0.05). Intravitreal triamcinolone temporarily changed central retinal artery blood flow and posterior ciliary arteries' peak systolic blood velocity in eyes with retinal vein occlusion whilst no response of blood flow to triamcinolone injection but only transiently altered end

Influence of the test method on in vitro drug release from intravitreal model implants containing dexamethasone or fluorescein sodium in poly (d,l-lactide-co-glycolide) or polycaprolactone.

PubMed

Stein, Sandra; Auel, Tobias; Kempin, Wiebke; Bogdahn, Malte; Weitschies, Werner; Seidlitz, Anne

2018-06-01

Sustained intravitreal dexamethasone (DX) administration with the FDA and EMA approved Ozurdex® implant is indicated for the treatment of macular edema and non-infectious uveitis. Since drug release after intravitreal application cannot be determined in vivo in human eyes, the characterization of drug release in vitro in addition to animal models is of great importance. The aim of this study was to provide information about the influence of the test method on the in vitro drug release from intravitreal model implants. The following test methods were used: a shaking incubator experiment in reagent tubes, the small volume USP apparatus 7, the Vitreous Model (VM) and a system simulating the impact of movement on the VM (Eye Movement System, EyeMoS). Cylindrical model implants composed of DX and PLGA (poly (d,l-lactide-co-glycolide)) and additional polycaprolactone (PCL) implants containing fluorescein sodium (FS) as a model substance were produced by hot melt extrusion and were cut to a length of approximately 6 mm. Drug release was studied in ringer buffer pH 7.4 and in a modified polyacrylamide gel (PAAG) as vitreous substitute. In combination with the VM, the shape, the gel structure and a partial liquefaction (50%) were simulated in vitro. Swelling, disintegration, fragmentation, surface enlargement and changes in shape of the PLGA model implants were observed during the drug release study. We experienced that not each of the test methods and media were suitable for drug release studies of the PLGA implants. Marked differences in the release profiles were observed depending on the employed test method. These results emphasize the necessity to understand the underlying in vivo processes and to transfer the knowledge about the release determining factors into reliable in vitro test systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide.

PubMed

Turalba, Angela V; Pasquale, Louis R

2014-01-01

To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Retrospective comparative case series. Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery.

Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide

PubMed Central

Turalba, Angela V; Pasquale, Louis R

2014-01-01

Objective To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Design Retrospective comparative case series. Participants Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. Methods A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Main outcome measures Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Results Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Conclusions Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery. PMID:25050061

The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

PubMed

Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

2014-08-01

To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

Distribution of Triamcinolone Acetonide after Intravitreal Injection into Silicone Oil-Filled Eye.

PubMed

Da, Ma; Li, Kenneth K W; Chan, Kevin C; Wu, Ed X; Wong, David S H

2016-01-01

There is increasing use of the vitreous cavity as a reservoir for drug delivery. We study the intraocular migration and distribution of triamcinolone acetonide (TA) after injection into silicone oil tamponade agent during and after vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo assessment, intraocular migration of TA was imaged using real-time FLASH MRI scans and high-resolution T2W imaging and the in vitro model was monitored continuously with a video camera. Results of the ex vivo experiment showed that the TA droplet sank to the interface of silicone oil and aqueous almost immediately after injection and remained inside the silicone oil bubble for as long as 16 minutes. The in vitro results showed that, after the shrinkage of the droplet, TA gradually precipitated leaving only a lump of whitish crystalline residue inside the droplet for about 100 minutes. TA then quickly broke the interface and dispersed into the underlying aqueous within 15 seconds, which may result in a momentary increase of local TA concentration in the aqueous portion and potentially toxic to the retina. Our study suggests that silicone oil may not be a good candidate as a drug reservoir for drugs like TA.

Spontaneous Resolution of Intravitreal Steroid-Induced Bilateral Cytomegalovirus Retinitis

PubMed Central

Cho, Won Bin; Kim, Hyung Chan

2012-01-01

A 73-year-old woman underwent vitrectomy and intravitreal triamcinolone acetonide (IVTA) of the right eye and cataract surgery with IVTA of the left eye, for bilateral diabetic macular edema. The patient presented with visual loss in both eyes three-months postoperatively. The fundoscopic examination revealed white-yellow, necrotic peripheral lesions in the superotemporal quadrant of both eyes. Although bilateral acute retinal necrosis was suspected, azotemia resulting from diabetic nephropathy limited the use of acyclovir. Antiviral treatment was not started. A sample of the aqueous humor for polymerase chain reaction (PCR) analysis was obtained. One week later, the PCR results indicated the presence of cytomegalovirus (CMV). Since the retinal lesions did not progress and did not threaten the macula, the patient was followed without treatment for CMV. The retinal lesions progressively regressed and completely resolved in both eyes by six months of follow-up. Patients with IVTA-induced CMV retinitis may not require systemic treatment with ganciclovir. PMID:22511845

Benefits of Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Intraocular Implant for Intermediate, Posterior and Panuveitis: 54 month results of The Multicenter Uveitis Steroid Treatment Trial (MUST) and Follow-up Study

PubMed Central

2015-01-01

Objective To compare the benefits of fluocinolone acetonide implant therapy versus systemic corticosteroid therapy supplemented (when indicated) with immunosuppression for intermediate, posterior, and panuveitis. Design Additional follow-up of a randomized comparative effectiveness trial cohort Participants 255 patients with intermediate, posterior or panuveitis who had been randomized to implant or systemic therapy. Main Outcome Measures Best-corrected visual acuity (BCVA), visual field mean deviation, activity of uveitis, and presence of macular edema (per Reading Center grading) were ascertained prospectively. Methods Trial participants were followed through 54 months from original randomization. Results The trajectory of visual function in uveitic eyes demonstrated a similar (p = 0.73) degree of modest (not statistically significant) improvement from baseline to 54 months in both groups (mean improvement in BCVA at 54 months: 2.4 and 3.1 letters in the implant and systemic group respectively). Many had excellent initial visual acuity, limiting the potential for improvement. The mean automated perimetry mean deviation score remained similar to baseline throughout 48 months’ follow-up in both groups. Overall control of inflammation was superior in the implant group at every time point assessed (p<0.016), although most eyes in the systemic therapy arm also had substantial inflammatory improvement, achieving complete control or low levels of inflammation. While macular edema improved significantly more often with implant treatment within the first six months, the systemic group gradually improved over time thereafter such that the proportions with macular edema converged in the two groups by 36 months and were overlapping thereafter (p=0.41 at 48 months). Conclusions Visual outcomes of fluocinolone acetonide implant and systemic treatment for intermediate, posterior, and panuveitis were similarly favorable through 54 months. The implant maintains a clear

Quantification of fluid resorption from diabetic macular oedema with foveal serous detachment after dexamethasone intravitreal implant (Ozurdex® ) in a pregnant diabetic.

PubMed

Hodzic-Hadzibegovic, Delila; Ba-Ali, Shakoor; Valerius, Marianne; Lund-Andersen, Henrik

2017-05-01

To quantify the fluid resorption from the centre of the fovea in a pregnant woman with diabetic macular oedema by daily optical coherence tomography (OCT) measurements after the administration of intravitreal dexamethasone implant (Ozurdex ® ). A 36-year-old pregnant woman with type 1 diabetes for 33 years presented with diabetic macular oedema with foveal serous detachment and symptomatic vision loss at 16 gestational weeks. Best-corrected visual acuity (BCVA) in Snellen notation and central retinal volume assessed by optical coherence tomography (OCT, Topcon Corporation) were measured almost on a daily basis the first five weeks after implantation and then 2-3 times per month until childbirth. The pretreatment BCVA was 0.6/1.0, and pretreatment central retinal volume was 0.32 mm 3 . Near elimination of the oedema was achieved 3 days after treatment. One week after treatment, BCVA improved to preconception level, and full regression of the oedema was achieved. The rate of fluid resorption from the centre of the fovea was highest 3 days after treatment 0.00139 μL/hr and decreasing to 0.00065 μL/hr 1 week after treatment. Intravitreal dexamethasone implant Ozurdex reduces promptly central retinal volume in diabetic macular oedema involving the centre of the fovea in pregnancy with highest rate of fluid resorption 3 days after treatment initiation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

Single Dexamethasone Intravitreal Implant in the Treatment of Noninfectious Uveitis.

PubMed

Frère, Ariane; Caspers, Laure; Makhoul, Dorine; Judice, Lia; Postelmans, Laurence; Janssens, Xavier; Lefebvre, Pierre; Mélot, Christian; Willermain, François

2017-05-01

To investigate the effect of a single intravitreal dexamethasone implant (IVT-DI; Ozurdex; Allergan, Inc.) on visual acuity, macular thickness, and intraocular pressure (IOP) in active noninfectious uveitis. Medical records of patients with noninfectious active uveitis treated by IVT-DIs were retrospectively reviewed. Uveitis etiologies, treatment indications, best corrected visual acuity (BCVA), central retinal thickness measured by ocular coherence tomography, IOP, and systemic, local, and topical treatments were collected. Parameters were analyzed before the injection of the implant, after 1.5 ± 0.8 months and 4.4 ± 0.9 months for the BCVA, after 2 ± 1.3 months and 4.6 ± 1.3 months for the ocular coherence tomography, and after 1.3 ± 0.7 months and 4.4 ± 1 months for the IOP. We included 14 patients (20 eyes, 20 implant injections) with cystoid macular edema (78%), vasculitis (7%), choroiditis (7%), and vasculitis associated with choroiditis (7%). Before the injection, mean visual acuity was 0.4 ± 0.5 logMAR (logarithm of the minimum angle of resolution) that improved to 0.3 ± 0.5 logMAR (P = 0.0002) after 1.5 ± 0.8 months and to 0.3 ± 0.5 logMAR (P = 0.005) after 4.4 ± 0.9 months. A statistically significant decrease of macular thickness was observed both at 2 ± 1.3 months and at 4.6 ± 1.3 months after IVT-DI. Mean IOP was 16 ± 5 mmHg before injections, 18 ± 6 mmHg (P = 0.13) at 1.3 ± 0.7 months, and 15 ± 4 mmHg (P = 0.65) at 4.4 ± 1 months. By Kaplan-Meier analysis, we found that after 3.3 months, 17% of the eyes still present a BCVA amelioration ≥0.3 logMAR. In our patients with active noninfectious uveitis, injection of a first single dexamethasone implant was found to improve visual acuity and decrease macular thickness without significant increase of IOP, although the effect seems limited in time.

Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.

PubMed

Kempen, John H; Altaweel, Michael M; Drye, Lea T; Holbrook, Janet T; Jabs, Douglas A; Sugar, Elizabeth A; Thorne, Jennifer E

2015-10-01

To compare the benefits of fluocinolone acetonide implant therapy versus systemic corticosteroid therapy supplemented (when indicated) with immunosuppression for intermediate uveitis, posterior uveitis, and panuveitis. Additional follow-up of a randomized comparative effectiveness trial cohort. Two hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis randomized to implant or systemic therapy. Best-corrected visual acuity (BCVA), visual field mean deviation (MD), activity of uveitis, and presence of macular edema (per reading center grading) ascertained prospectively. Trial participants were followed-up for 54 months from original randomization. The visual function trajectory in uveitic eyes demonstrated a similar (P = 0.73) degree of modest (not statistically significant) improvement from baseline to 54 months in both groups (mean improvement in BCVA at 54 months, 2.4 and 3.1 letters in the implant and systemic groups, respectively). Many had excellent initial visual acuity, limiting the potential for improvement. The mean automated perimetry MD score remained similar to baseline throughout 48 months of follow-up in both groups. Overall control of inflammation was superior in the implant group at every time point assessed (P < 0.016), although most eyes in the systemic therapy arm also showed substantial improvement, achieving complete control or low levels of inflammation. Although macular edema improved significantly more often with implant treatment within the first 6 months, the systemic group gradually improved over time such that the proportions with macular edema converged in the 2 groups by 36 months and overlapped thereafter (P = 0.41 at 48 months). Visual outcomes of fluocinolone acetonide implant and systemic treatment for intermediate uveitis, posterior uveitis, and panuveitis were similarly favorable through 54 months. The implant maintained a clear advantage in controlling inflammation through 54 months. Nevertheless

Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.

PubMed

Boyer, David S; Yoon, Young Hee; Belfort, Rubens; Bandello, Francesco; Maturi, Raj K; Augustin, Albert J; Li, Xiao-Yan; Cui, Harry; Hashad, Yehia; Whitcup, Scott M

2014-10-01

To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME). Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis. Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography. Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months. The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP). Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (-111.6 μm) and DEX implant 0.35 mg (-107.9 μm) than sham (-41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy. The DEX implant 0.7 mg and 0.35 mg met the

Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.

PubMed

Iezzi, Raymond; Guru, Bharath R; Glybina, Inna V; Mishra, Manoj K; Kennedy, Alexander; Kannan, Rangaramanujam M

2012-01-01

Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 μg of FA conjugated to 7 μg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Intravitreal steroids for the treatment of retinal diseases.

PubMed

Sarao, Valentina; Veritti, Daniele; Boscia, Francesco; Lanzetta, Paolo

2014-01-01

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Intravitreal Steroids for the Treatment of Retinal Diseases

PubMed Central

Veritti, Daniele; Boscia, Francesco

2014-01-01

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

Evaluation of best corrected visual acuity and central macular thickness after intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome: A retrospective study of six cases.

PubMed

Keilani, Chafik; Halalchi, Aziz; Wakpi Djeugue, Désiré; Regis, Anne; Abada, Samir

2016-10-01

Irvine-Gass syndrome is a macular edema (ME) that specifically occurs after cataract surgery. Its incidence varies from 0.2-2%. The purpose of this study is to evaluate the effectiveness of intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome. Patients with ME secondary to cataract surgery who underwent intravitreal injections of dexamethasone implant between December 2011 to October 2014 at François-Quesnay hospital (Mantes-la-Jolie, France) were retrospectively reviewed. The patients were followed for at least 10 months. All the patients were handled by intravitreal injection of dexamethasone in the eye of study among which some resisted to a preliminary treatment by non-steroidal anti-inflammatory drug (NSAID) and acetazolamide. The patients were examined each month. The patients were again handled by intravitreal injection of dexamethasone if they presented a recurrence. The primary endpoint of the study was determined on best corrected visual acuity (BCVA) using early diabetic retinopathy study (ETDRS) scale and central macular thickness (CMT) [μm] using optical coherence tomography (OCT) 3 and 6 months after the first injection. Secondary endpoints were the number of recurrences, the number of injections, the duration average before the first recurrence, the BCVA 10 months after the first injection and the tolerance. Six eyes of six patients were studied. At baseline, the mean (standard deviation [SD]) of the BCVA was 59.8±11. Three months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72.2±8.6 (P=0.03). Six months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72±11.8 (P=0.03). Concerning the CMT, the mean (SD) was 495.6±135.2 before treatment. Three months after the first injection, the mean (SD) of the CMT showed a statistically significant decrease to 268.6±57.8 (P=0.03). Six months after the first injection, the

Efficacy of intravitreal anti-vascular endothelial growth factor or steroid injection in diabetic macular edema according to fluid turbidity in optical coherence tomography.

PubMed

Lee, Kyungmin; Chung, Heeyoung; Park, Youngsuk; Sohn, Joonhong

2014-08-01

To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initial intravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism.

Ranibizumab versus dexamethasone implant for central retinal vein occlusion: the RANIDEX study.

PubMed

Chatziralli, Irini; Theodossiadis, George; Kabanarou, Stamatina A; Parikakis, Efstratios; Xirou, Tina; Mitropoulos, Panagiotis; Theodossiadis, Panagiotis

2017-10-01

To compare intravitreal ranibizumab and dexamethasone implant in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). Participants were 42 treatment naive patients with ME due to CRVO, who received either intravitreal 0.5 mg ranibizumab (n = 25) or intravitreal 0.7 mg dexamethasone implant (n = 17). The main outcomes included the mean change in best corrected visual acuity (BCVA) and central subfield thickness (CST) at month 12 compared to baseline in the two groups. At month 12, there was no statistically significant difference in BCVA and CST change between the two groups. However, there was recurrence in ME at month 5 in the dexamethasone group. Both ranibizumab and dexamethasone implant were found to be safe and effective at the 12-month follow-up in patients with ME secondary to CRVO. Since there was a recurrence in ME at month 5 in the dexamethasone group, we suggested that intravitreal injection of dexamethasone implant should be potentially administered sooner than 6 months.

The effects of commonly used intravitreal steroids on proliferation index of ciliary body-derived mesenchymal stem cells: an in vitro study.

PubMed

Demir, M Necati; Acar, Ugur; Sobaci, Gungor; Pınarlı, Ferda Alpaslan; Erginturk Acar, Damla; Beyazyıldız, Emrullah; Yesilyurt, Ahmet; Delibasi, Tuncay

2016-03-01

To investigate the effects of commonly used intravitreal steroids on survival and proliferation (namely, proliferation index) of ciliary body-derived mesenchymal stem cells (CB-MSC). CB-MSCs were isolated from newborn rats' eye, and they were expanded in the medium. Commonly used intravitreal steroids such as dexamethasone (Dex) and triamcinolone acetonide (TA) were added into the medium at commonly used concentration in clinical practice (0.1 mg/mL) and at lower concentration (0.01 mg/mL). Proliferation indexes of CB-MSCs were analyzed with the xCELLigence system at nine consecutive times (at 3rd, 6th, 21th, 30th, 45th, 60th, 75th, 90th and 100th h). Both TA and Dex at both 0.01 mg/mL and 0.1 mg/mL concentrations had negative effect on proliferation indexes of CB-MSC. Although negative effect of TA on proliferation index of CB-MSC at both concentrations was not statistically significant, statistically significant negative effect of Dex at 0.01 mg/mL concentration started 60th h (p = 0.017) and 0.1 mg/mL concentration started 30th h (p = 0.014). Even therapeutic doses of intravitreal corticosteroid agents might have negative effects on limited numbers of stem cells. Especially, Dex caused statistically significant toxic effects on CB-MSCs even at lower concentrations of those used clinically. These novel findings deserve further in vivo investigations.

Randomized Comparison of Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Implant for Intermediate, Posterior and Panuveitis: The Multicenter Uveitis Steroid Treatment Trial

PubMed Central

Kempen, John H.; Altaweel, Michael M.; Holbrook, Janet T.; Jabs, Douglas A.; Louis, Thomas A.; Sugar, Elizabeth A.; Thorne, Jennifer E.

2011-01-01

Objective To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for non-infectious intermediate, posterior or panuveitis (uveitis). Design Randomized controlled parallel superiority trial. Participants Patients with active/recently active uveitis. Methods Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (three countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis. Main Outcome Measures Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life (QoL), ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked. Results Among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), evaluating changes from baseline to 24 months, the implant and systemic therapy groups respectively had +6.0 vs. +3.2 letters' improvement in visual acuity (p=0.16, 95% confidence interval on difference in improvement between groups: −1.2 to +6.7 letters, positive values favoring implant), +11.4 vs. +6.8 units' vision-related QoL improvement (p=0.043), +0.02 vs. −0.02 change in EuroQol-EQ5D health utility (p=0.060), and 12% vs. 29% had active uveitis (p=0.001). Over 24 months, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio (HR) = 3.3, p<0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, p<0.0001), and glaucoma (17%, HR = 4.2, p=0.0008). Systemic-assigned patients had more

Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, or Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment Trial and Follow-up Study.

PubMed

2015-10-01

To evaluate the risks and quality-of-life (QoL) outcomes of fluocinolone acetonide implant versus systemic therapy with corticosteroid and immunosuppression when indicated for intermediate uveitis, posterior uveitis, and panuveitis. Additional follow-up of a randomized trial cohort. Two hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis, randomized to implant or systemic therapy. Randomized subjects with intermediate uveitis, posterior uveitis, or panuveitis (479 eyes) were followed up over 54 months, with 79.2% completing the 54-month visit. Local and systemic potential complications of the therapies and self-reported health utility and vision-related and generic health-related QoL were studied prospectively. Among initially phakic eyes, cataract and cataract surgery occurred significantly more often in the implant group (hazard ratio [HR], 3.0; P = 0.0001; and HR, 3.8; P < 0.0001, respectively). In the implant group, most cataract surgery occurred within the first 2 years. Intraocular pressure elevation measures occurred more frequently in the implant group (HR range, 3.7-5.6; all P < 0.0001), and glaucoma (assessed annually) also occurred more frequently (26.3% vs. 10.2% by 48 months; HR, 3.0; P = 0.0002). In contrast, potential complications of systemic therapy, including measures of hypertension, hyperlipidemia, diabetes, bone disease, and hematologic and serum chemistry indicators of immunosuppression toxicity, did not differ between groups through 54 months. Indices of QoL initially favored implant therapy by a modest margin. However, all summary measures of health utility and vision-related or generic health-related QoL were minimally and nonsignificantly different by 54 months, with the exception of the 36-item Short-Form Health Survey physical component summary score, which favored implant by a small margin at 54 months (3.17 on a scale of 100; P = 0.01, not adjusted for multiple comparisons). Mean QoL results were

Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery.

PubMed

McAvoy, Kathryn; Jones, David; Thakur, Raghu Raj Singh

2018-01-16

To investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents. Triamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin. Regardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period. Photocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.

A case of aminoglycosides induced retinal toxicity treated with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex(®)).

PubMed

Hernández Pardines, F; Tapia-Quijada, H; Hueso-Abancens, J R

2016-06-01

The case is described of a patient who had a sudden loss of vision in her right eye after glaucoma surgery. A diagnosis of retinal toxicity due to tobramycin (an aminoglycoside) was reached, which was characterised by retinal whitening with a red cherry stain, macular oedema, and vasculitis that progressed to papillary and macular atrophy with arteriolar sclerosis. Given the severity of symptoms an early attempt was made with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex®, Allergan S.A.), without response. Aminoglycoside toxicity is a rare, idiosyncratic, very serious complication for which there is no effective treatment. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications.

PubMed

Araújo, J; Gonzalez-Mira, E; Egea, M A; Garcia, M L; Souto, E B

2010-06-30

The purpose of this study was to develop a novel nanostructured lipid carrier (NLC) for the intravitreal-targeting delivery of triamcinolone acetonide (TA) by direct ocular instillation. A five-level central composite rotable design was used to study the influence of four different variables on the physicochemical characteristics of NLCs. The analysis of variance (ANOVA) statistical test was used to assess the optimization of NLC production parameters. The systems were produced by high pressure homogenization using Precirol ATO5 and squalene as solid and liquid lipids respectively, and Lutrol F68 as surfactant. Homogenization at 600 bar for 3 cycles of the optimized formulation resulted in the production of small NLC (mean diameter < 200 nm) with a homogeneous particle size distribution (polydispersity index (PI) approximately 0.1), of negatively charged surface (approximately |45| mV) and high entrapment efficiency (approximately 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and FT-IR analyses confirmed that TA was mostly entrapped into the NLC, characterized by an amorphous matrix. In vivo Draize test showed no signs of ocular toxicity. 2010 Elsevier B.V. All rights reserved.

INTRAVITREAL DEXAMETHASONE IMPLANTATION IN PATIENTS WITH DIFFERENT MORPHOLOGICAL DIABETIC MACULAR EDEMA HAVING INSUFFICIENT RESPONSE TO RANIBIZUMAB.

PubMed

Kaldırım, Havva; Yazgan, Serpil; Atalay, Kursat; Gurez, Ceren; Savur, Fatma

2018-05-01

To evaluate the effectiveness of a single intravitreal injection of dexamethasone implant in resistant diabetic macular edema that have different morphological types. In this retrospective study, 31 patients (35 eyes) with persistent diabetic macular edema, who underwent a single injection of dexamethasone implant, were evaluated. Diabetic macular edema was classified into three types: diffuse retinal thickening (n = 10), cystoid macular edema (n = 13), and serous retinal detachment (n = 12). Primary outcome measures were best corrected visual acuity, and central macular thickness. The three subgroups were similar in terms of age and gender (P > 0.05). Total duration of diabetes was significantly less in the serous retinal detachment subgroup (P = 0.01). There were no differences in the best corrected visual acuity between the three subgroups until the sixth month. However, the best corrected visual acuity was significantly better in the diffuse retinal thickness subgroup at the sixth month (P = 0.008). Regarding the central macular thickness values, it was statistically better in serous retinal detachment than in diffuse retinal thickening and cystoid macular edema subgroups till the sixth month (P = 0.001). However, at the sixth month, there was not any statistical difference between subgroups regarding central macular thickness values. Antiglaucomatous agents were required in 4 (11.4%) patients throughout the study. Treatment algorithms should differ according to the morphology of diabetic macular edema; however, more data is needed to give specific recommendations.

Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results.

PubMed

Haller, Julia A; Bandello, Francesco; Belfort, Rubens; Blumenkranz, Mark S; Gillies, Mark; Heier, Jeffrey; Loewenstein, Anat; Yoon, Young Hee; Jiao, Jenny; Li, Xiao-Yan; Whitcup, Scott M; Li, Joanne

2011-12-01

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

Longitudinal Study of Sustained-Release Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema.

PubMed

Aknin, Isabelle; Melki, Laurent

2016-01-01

Observational studies are needed to confirm the long-term efficacy and safety of Ozurdex® intravitreal implant in real life. Among 29 patients with persistent diabetic macular edema (DME), of whom 14 (48%) patients did not have any previous treatments and 22 (76%) any previous antivascular endothelial growth factor (anti-VEGF) injections, significant visual acuity (VA) improvement was observed with a mean gain of 13.8 letters at month 6 (p < 0.0001), 12.7 letters at month 12 (p = 0.0032) and 16.5 letters at month 18 (p = 0.0313). During the follow-up, a total of 17 (59%) patients had a VA improvement of ≥15 letters. Significant central macular thickness decrease was observed with a mean reduction of 159.07 μm at month 6 (p < 0.0001), 181.8 μm at month 12 (p < 0.0001) and 236.17 μm at month 18 (p = 0.0313). No serious adverse events were reported. With a good efficacy and safety, manageable adverse events and an injection rate much lower compared to that of anti-VEGF, this study confirms the use of Ozurdex® for the treatment of persistent DME. © 2016 S. Karger AG, Basel.

Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.

PubMed

Gilger, B C; Wilkie, D A; Davidson, M G; Allen, J B

2001-12-01

To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. 16 horses with recurrent uveitis. Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis.

Anti-Toxoplasma activity and impact evaluation of lyophilization, hot molding process, and gamma-irradiation techniques on CLH-PLGA intravitreal implants.

PubMed

Fernandes-Cunha, Gabriella M; Rezende, Cíntia M F; Mussel, Wagner N; da Silva, Gisele R; de L Gomes, Elionai C; Yoshida, Maria I; Fialho, Sílvia L; Goes, Alfredo M; Gomes, Dawison A; de Almeida Vitor, Ricardo W; Silva-Cunha, Armando

2016-01-01

Intraocular delivery systems have been developed to treat many eye diseases, especially those affecting the posterior segment of the eye. However, ocular toxoplasmosis, the leading cause of infectious posterior uveitis in the world, still lacks an effective treatment. Therefore, our group developed an intravitreal polymeric implant to release clindamycin, a potent anti-Toxoplasma antibiotic. In this work, we used different techniques such as differential scanning calorimetry, thermogravimetry, X-ray diffraction, scanning electron microscopy, and fourier-transform infrared spectroscopy to investigate drug/polymer properties while manufacturing the delivery system. We showed that the lyophilization, hot molding process, and sterilization by gamma irradiation did not change drug/polymer physical-chemistry properties. The drug was found to be homogeneously dispersed into the poly lactic-co-glycolic acid (PLGA) chains and the profile release was characterized by an initial burst followed by prolonged release. The drug profile release was not modified after gamma irradiation and non-covalent interaction was found between the drug and the PLGA. We also observed the preservation of the drug activity by showing the potent anti-Toxoplasma effect of the implant, after 24-72 h in contact with cells infected by the parasite, which highlights this system as an alternative to treat toxoplasmic retinochoroiditis.

Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera.

PubMed

Meyer, Carsten H; Klein, Adrian; Alten, Florian; Liu, Zengping; Stanzel, Boris V; Helb, Hans M; Brinkmann, Christian K

2012-01-01

Ozurdex, a novel dexamethasone (DEX) implant, is released by a drug delivery system into the vitreous cavity. We analyzed the mechanical release aperture of the novel applicator, obtained real-time recordings using a high-speed camera system and performed kinematic analysis of the DEX application. Experimental study. : The application of intravitreal DEX implants (6 mm length, 0.46 mm diameter; 700 μg DEX mass, 0.0012 g total implant mass) was recorded by a high-speed camera (500 frames per second) in water (Group A: n = 7) or vitreous (Group B: n = 7) filled tanks. Kinematic analysis calculated the initial muzzle velocity as well as the impact on the retinal surface at approximately 15 mm of the injected drug delivery system implant in both groups. A series of drug delivery system implant positions was obtained and graphically plotted over time. High-speed real-time recordings revealed that the entire movement of the DEX implant lasted between 28 milliseconds and 55 milliseconds in Group A and 1 millisecond and 7 milliseconds in Group B. The implants moved with a mean muzzle velocity of 820 ± 350 mm/s (±SD, range, 326-1,349 mm/s) in Group A and 817 ± 307 mm/s (±SD, range, 373-1,185 mm/s) in Group B. In both groups, the implant gradually decelerated because of drag force. With greater distances, the velocity of the DEX implant decreased exponentially to a complete stop at 13.9 mm to 24.7 mm in Group A and at 6.4 mm to 8.0 mm in Group B. Five DEX implants in Group A reached a total distance of more than 15 mm, and their calculated mean velocity at a retinal impact of 15 mm was 408 ± 145 mm/s (±SD, range, 322-667 mm/s), and the consecutive normalized energy was 0.55 ± 0.44 J/m (±SD). In Group B, none of the DEX implants reached a total distance of 6 mm or more. An accidental application at an angle of 30 grade and consecutively reduced distance of approximately 6 mm may result in a mean velocity of 844 and mean normalized energy of 0.15 J/m (SD ± 0.47) in a

Assistive Device for Efficient Intravitreal Injections.

PubMed

Ullrich, Franziska; Michels, Stephan; Lehmann, Daniel; Pieters, Roel S; Becker, Matthias; Nelson, Bradley J

2016-08-01

Intravitreal therapy is the most common treatment for many chronic ophthalmic diseases, such as age-related macular degeneration. Due to the increasing worldwide demand for intravitreal injections, there exists a need to render this medical procedure more time- and cost-efficient while increasing patient safety. The authors propose a medical assistive device that injects medication intravitreally. Compared to the manual intravitreal injection procedure, an automated device has the potential to increase safety for patients, decrease procedure times, allow for integrated data storage and documentation, and reduce costs for medical staff and expensive operating rooms. This work demonstrates the development of an assistive injection system that is coarsely positioned over the patient's head by the human operator, followed by automatic fine positioning and intravitreal injection through the pars plana. Several safety features, such as continuous eye tracking and iris recognition, have been implemented. The functioning system is demonstrated through ex vivo experiments with porcine eyes. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:752-762.]. Copyright 2016, SLACK Incorporated.

Corticosteroid implants for chronic non-infectious uveitis

PubMed Central

Brady, Christopher J; Villanti, Andrea C; Law, Hua Andrew; Rahimy, Ehsan; Reddy, Rahul; Sieving, Pamela C; Garg, Sunir J; Tang, Johnny

2016-01-01

Background Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary body, choroid). Uveitis is the fifth most common cause of vision loss in high-income countries, accounting for 5% to 20% of legal blindness, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of acute treatment for all anatomical subtypes of non-infectious uveitis and can be administered orally, topically with drops or ointments, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. Objectives To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com) (last searched 15 April 2013), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform(ICTRP) (www.who.int/ictrp/search/en).We did not use any date or language restrictions in the electronic search for studies. We last searched the electronic databases on 6 November 2015. We also searched reference lists of included study reports, citation databases, and abstracts and clinical study presentations from professional meetings. Selection criteria We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone intravitreal implants with standard

Efficacy of Intravitreal Anti-vascular Endothelial Growth Factor or Steroid Injection in Diabetic Macular Edema According to Fluid Turbidity in Optical Coherence Tomography

PubMed Central

Lee, Kyungmin; Chung, Heeyoung; Park, Youngsuk

2014-01-01

Purpose To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. Methods A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initialintravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Results Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. Conclusions IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism. PMID:25120338

Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation.

PubMed

Googe, Joseph; Brucker, Alexander J; Bressler, Neil M; Qin, Haijing; Aiello, Lloyd P; Antoszyk, Andrew; Beck, Roy W; Bressler, Susan B; Ferris, Frederick L; Glassman, Adam R; Marcus, Dennis; Stockdale, Cynthia R

2011-06-01

To evaluate 14-week effects of intravitreal ranibizumab or triamcinolone in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation. Three hundred and forty-five eyes with a visual acuity of 20/320 or better, center-involved diabetic macular edema receiving focal/grid laser, and diabetic retinopathy receiving prompt panretinal photocoagulation were randomly assigned to sham (n = 123), 0.5-mg ranibizumab (n = 113) at baseline and 4 weeks, and 4-mg triamcinolone at baseline and sham at 4 weeks (n = 109). Treatment was at investigator discretion from 14 weeks to 56 weeks. Mean changes (±SD) in visual acuity letter score from baseline were significantly better in the ranibizumab (+1 ± 11; P < 0.001) and triamcinolone (+2 ± 11; P < 0.001) groups compared with those in the sham group (-4 ± 14) at the 14-week visit, mirroring retinal thickening results. These differences were not maintained when study participants were followed for 56 weeks for safety outcomes. One eye (0.9%; 95% confidence interval, 0.02%-4.7%) developed endophthalmitis after receiving ranibizumab. Cerebrovascular/cardiovascular events occurred in 4%, 7%, and 3% of the sham, ranibizumab, and triamcinolone groups, respectively. The addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study.

Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy.

PubMed

Wykoff, Charles C

2017-05-01

Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself. Phase 3 trials employing ranibizumab, aflibercept, and fluocinolone acetonide enrolling eyes with center-involving DME causing visual acuity loss have demonstrated impressive alteration of the natural history of progressive diabetic retinopathy worsening over time through blunted progression to proliferative diabetic retinopathy, improving diabetic retinopathy severity levels, and slowing progressive retinal nonperfusion, the underlying disease process central to diabetic retinopathy itself. Accumulating data indicate that the threshold to initiate ocular-specific pharmacologic treatment for diabetic retinopathy, previously predominately limited to eyes with visual loss because of center-involved DME or proliferative diabetic retinopathy, is being lowered to earlier stages of diabetic retinopathy. Ongoing clinical trials and secondary analyses continue to further explore the impact and durability of vascular endothelial growth factor blockade and corticosteroids on modification of diabetic retinopathy and the underlying retinal vasculature itself.

Intravitreal flomoxef sodium in rabbits.

PubMed

Mochizuki, K; Torisaki, M; Yamashita, Y; Komatsu, M; Tanahashi, T

1993-01-01

We studied the intraocular concentration of flomoxef sodium in nonvitrectomized and vitrectomized eyes of albino rabbits after intravenous administration of 100 mg/kg flomoxef sodium. The concentration of flomoxef sodium in the vitreous body was undetectable (< 0.1 micrograms/ml) in nonvitrectomized eyes. Retinal toxicity of flomoxef sodium was investigated with ophthalmoscopy, electroretinography (ERG) and light microscopy after intravitreal injection of 200, 500, 1,000 and 2,000 micrograms flomoxef sodium in albino and pigmented rabbits. No ERG changes were induced with 200 micrograms. Other higher doses caused transient ERG changes. After the 200-micrograms injection, the intravitreal concentration decreased exponentially, the half-life being 4.4 h. The antibacterial activity, broad coverage and low intravitreal toxicity of flomoxef sodium suggest that this compound may be used to treat bacterial endophthalmitis.

Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy

NASA Astrophysics Data System (ADS)

Li, Xingyi; Wang, Yuqin; Yang, Chengbiao; Shi, Shuai; Jin, Ling; Luo, Zichao; Yu, Jing; Zhang, Zhaoliang; Yang, Zhimou; Chen, Hao

2014-11-01

Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton®), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases.Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular

Intravitreal clindamycin and dexamethasone for toxoplasmic retinochoroiditis.

PubMed

Kishore, K; Conway, M D; Peyman, G A

2001-01-01

To present a new method for the management of toxoplasmic retinochoroiditis (TRC). The patients were females ranging in age from 10 to 61 years (average 26.5). Four eyes of 4 patients were treated with intravitreal injections of 1.0 mg clindamycin in 0.1 mL and 1.0 mg of dexamethasone in 0.1 mL. The injections were given under general or peribulbar anesthesia. Three patients continued one systemic drug. Follow-up ranged from 11 to 26 months (mean 17.5). A favorable response was noted in each eye within two weeks after the intravitreal injections. All patients required 2 to 4 intravitreal injections in the affected eye for the control of TRC. Visual acuity improved in each eye. The disc and macula were preserved in all eyes. Recurrence was noted in one case, which responded to a repeated intravitreal injection of clindamycin and dexamethasone. Intravitreal injections of clindamycin and dexamethasone are well tolerated and may offer an additional strategy to treat TRC in patients who are unable to afford or tolerate systemic therapy, or whose disease progresses despite systemic therapy.

Clinical Outcomes of Intravitreal Preservative-Free Triamcinolone Preparation (Triesence®) for Cystoid Macular Oedema and Inflammation in Patients with Uveitis.

PubMed

Steeples, Laura R; Anand, Nitin; Moraji, Jiten; Jones, Nicholas P

2017-03-20

To assess the outcomes of intravitreal benzyl alcohol-free triamcinolone acetonide suspension in uveitis-related macular oedema. Single-center retrospective cohort study of 66 injections to 44 eyes of 40 patients. Uveitis diagnosis, systemic and local therapy, intraocular pressure (IOP), central retinal thickness (CRT), number of injections, time to re-injection and side-effects were noted during 6-months minimum follow-up. Sixty eight percent of eyes received a single injection. 18% required 2 injections, and 13% received ≥3 injections with mean time to second and third injections of 25.5 and 52.7 weeks, respectively. 90% of injections were unilateral. Mean CRT reduced, and by 12-weeks visual acuity improvement >0.3logMar was achieved in 46%. Cataract progression (47%) and IOP>21 mmHg (45%) were the commonest adverse events. Preservative-free triamcinolone is an additional option for uveitis-related macular oedema, particularly in unilateral cases, with favorable CRT and visual outcomes. Repeat injections may be necessary, and the period of efficacy varies between eyes.

Case of cytomegalovirus retinitis aggravated by sub-Tenon injection of triamcinolone acetonide with subsequent metastatic liver cancer

PubMed Central

Yamamoto, Yumiko; Kato, Yoshitake; Tabuchi, Hitoshi; Fukushima, Atsuki

2013-01-01

We report a case of cytomegalovirus (CMV) retinitis in an immunocompetent patient who was resistant to antiviral treatment, and in whom fatal metastatic liver cancer was later detected. A 74-year-old Japanese man visited our ophthalmology clinic in May 2011. He had a history of well controlled type 2 diabetes and colon cancer, and underwent successful surgical treatment in 2008. In April 2011, he was diagnosed with uveitis affecting his left eye and received posterior sub-Tenon injection of triamcinolone acetonide. He was referred to us because of aggravation of the retinal lesion. Funduscopic examination of the left eye revealed arcuate, whitish, necrotizing retinitis with hemorrhage along the temporal arcade of the retina. Polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Because of diagnosis of CMV retinitis in his left eye, he was referred to an internist and investigated for systemic CMV infection or any serious disease which could cause immunocompromise, but neither was detected. Despite an intensive course of intravitreous ganciclovir and oral valganciclovir, the retinitis did not resolve. In June 2012, 14 months after the initial ocular symptoms, metastatic liver cancer was found and the patient passed away. When CMV retinitis is resistant to antiviral treatment or recurs in an immunocompetent patient, it is important that ophthalmologists undertake systemic investigation for occult malignancy. PMID:23467884

[Comparison of Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab as a First-Line Treatment of Macular Oedema due to Retinal Vein Occlusion].

PubMed

Mayer, W J; Hadjigoli, A; Wolf, A; Herold, T; Haritoglou, C

2015-11-01

The present study investigated the treatment effect of dexamethasone implant (Ozurdex®, group 1) and anti-VEGF injection (Lucentis®, group 2) in course of macular oedema due to retinal vein occlusion in a retrospective, non-randomised case series. Group 1 comprised 60 patients (31 with CRVO and 29 with BRVO) and group 2 included 52 patients, 27 with CRVO and 25 with BRVO) and both groups were further treated in case of recurrence. Preoperative and in monthly intervals best corrected visual acuity (BCVA), central retinal thickness using SD-OCT (Spectralis, Heidelberg Engineering), intraocular pressure, biomicroscopy status and a fundus photo documentation (Optomap) were evaluated. The primary clinical endpoint was visual acuity 12 months after the first intravitreal therapy, while secondary endpoints included the central retinal thickness change and safety of therapy. In group 1, an increase of BCVA (± standard deviation) of 8.4 (± 1.9) letters was observed in CRVO patients and a gain of 10.7 (± 3.8) letters in BRVO patients after 12 months, while in group 2, an increase of BCVA of 6.9 (± 1.9) letters (CRVO) compared to 12.5 (± 3.7) letters (BRVO) was observed after the same time span. In both groups a significant reduction in retinal thickness was achieved. An increase of intraocular pressure above 5 mmHg was observed in nearly half of the cases In group 1, but was well controlled by conservative antiglaucomatous therapy. We observed a progression of lens opacity in approximately 50 % of the cases in group 1. The treatment with Ozurdex compared to Lucentis appears to provide a trend towards a better although not significant visual acuity increase after 12 months in CRVO patients. A similar trend favouring anti-VEGF treatment with Lucentis was seen in patients with BRVO. However, the lens status and age of the patient should be taken into account when considering a treatment with Ozurdex. Georg Thieme Verlag KG Stuttgart · New York.

Short-term efficacy of intravitreal dobesilate in central serous chorioretinopathy

PubMed Central

2012-01-01

Purpose To report the anatomic and functional outcome of intravitreal dobesilate to treat recurrent central serous chorioretinopathy (CSC). Methods This is an interventional case report in which dobesilate was intravitreally injected in a case of recurrent CSC. Main measures included fundoscopy, Snellen visual acuity (VA) testing, fluorescein angiography and optical coherence tomography (OCT). Results We present anatomical and functional evidences, obtained as early as eleven days after the treatment, of the efficacy of intravitreal dobesilate, in the treatment of chronic CSC condition. The effect after intravitreal dobesilate injection for CSC might be related to the normalization of retinal architecture. Conclusions Intravitreal dobesilate may be an effective treatment option for recurrent CSC. PMID:22788836

Chemical Upcycling of Expired Drugs: Synthesis of Guaifenesin Acetonide

ERIC Educational Resources Information Center

Barcena, Homar; Maziarz, Katarzyna

2017-01-01

In an effort to repurpose expired guaifenesin tablets, experiments devised for practical instruction are reported for the preparation and isolation of the guaifenesin acetonide using a microscale kit. The laboratory experiment successfully utilizes a waste chemical in lieu of a fine chemical to illustrate the principles behind protecting groups in…

Randomized trial of anesthetic methods for intravitreal injections.

PubMed

Blaha, Gregory R; Tilton, Elisha P; Barouch, Fina C; Marx, Jeffrey L

2011-03-01

To compare the effectiveness of four different anesthetic methods for intravitreal injection. Twenty-four patients each received four intravitreal injections using each of four types of anesthesia (proparacaine, tetracaine, lidocaine pledget, and subconjunctival injection of lidocaine) in a prospective, masked, randomized block design. Pain was graded by the patient on a 0 to 10 scale for both the anesthesia and the injection. The average combined pain scores for both the anesthesia and the intravitreal injection were 4.4 for the lidocaine pledget, 3.5 for topical proparacaine, 3.8 for the subconjunctival lidocaine injection, and 4.1 for topical tetracaine. The differences were not significant (P = 0.65). There were also no statistical differences in the individual anesthesia or injection pain scores. Subconjunctival lidocaine injection had the most side effects. Topical anesthesia is an effective method for limiting pain associated with intravitreal injections.

Intralesional Injection of Triamcinolone Acetonide for Subcutaneous Lipoma causing Musculoskeletal and Neurologic Symptoms

PubMed Central

Hayward, William A.; Sibbitt, Randy R.; Muruganandam, Maheswari; Rolle, Noelle A.; Fangtham, Monthida; Suzanne Emil, N.; Kettwich, Scarlett K.

2018-01-01

Objective: Benign subcutaneous lipomas can cause musculoskeletal pain and nerve impingement. We hypothesized that the potent lipolytic and atrophic effect of 40mg/mL triamcinolone acetonide would atrophy symptomatic lipomas so surgical excision could be avoided. Design: This was a cohort study. Setting: This study took place in an ultrasound injection clinic. Participants: Eight subjects with painful symptomatic lipoma were included. Measurements: Preprocedurally, the margins of the lipomas were palpated and marked with ink, then measured in centimeters (cm). Small lipomas (1–3cm) were injected with 40mg triamcinolone acetonide, while large lipomas (4–6cm) were injected with 80mg of triamcinolone acetonide. The subjects were reassessed at a four-month follow-up appointment and then again at one year and two years after the procedure. Results: Pre-injection, all eight subjects had symptoms related to impingement or pain with compression of the lipoma. At four months post-injection, none of the patients had symptoms attributable to the lipoma (p<0.001). The mean lipoma palpable dimension was 5.0±1.2cm prior to the injection and was 2.0±1.1cm at four months after the injection, with a significant mean 3.0±0.3cm (60%) reduction in lipoma dimensions (p<0.001). Two subjects demonstrated some mild hypopigmentation of the skin at four months post-injection. Within two years, three lipomas had symptomatically recurred, one of which was removed surgically and the two of which were reinjected. There were no infections or other serious adverse reactions that occurred. Conclusions: For individuals with painful subcutaneous lipoma, intralesional injection of 40mg/mL of triamcinolone acetonide is an effective and safe alternative to surgical excision or injection of sclerosing agents and should be considered as a reasonable therapeutic alternative in select patients. PMID:29785238

21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a... sensitivity testing, and the use of the appropriate antimicrobial agent. As with any corticosteroid, animals...

21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a... sensitivity testing, and the use of the appropriate antimicrobial agent. As with any corticosteroid, animals...

21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a... sensitivity testing, and the use of the appropriate antimicrobial agent. As with any corticosteroid, animals...

21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a... sensitivity testing, and the use of the appropriate antimicrobial agent. As with any corticosteroid, animals...

Diabetic Macular Edema: Options for Adjunct Therapy.

PubMed

Calvo, Pilar; Abadia, Beatriz; Ferreras, Antonio; Ruiz-Moreno, Oscar; Verdes, Guayente; Pablo, Luis E

2015-09-01

Diabetes mellitus (DM) is a chronic disease that affects 387 million people worldwide. Diabetic retinopathy (DR), a common complication of DM, is the main cause of blindness in the active population. Diabetic macular edema (DME) may occur at any stage of DR, and is characterized by vascular hyperpermeability accompanied by hard exudates within the macula. Medical and surgical therapies have dramatically reduced the progression of DR, and timely intervention can reduce the risk of severe vision loss by more than 90 %. In 2012, intravitreal ranibizumab became the first antivascular endothelial growth factor (anti-VEGF) agent approved for DME and, since then, many reports of the use of ranibizumab for DME have been promising. Randomized, prospective, multicenter clinical trials-most notably, RESOLVE, READ-2, RISE/RIDE, RESTORE, DRCR.net protocol I, and RETAIN-reported improvements in best-corrected visual acuity and decreased central retinal thickness as measured with optical coherence tomography in patients with DME. Similar treatment benefits have also been noted in clinical trials evaluating intravitreal aflibercept and bevacizumab (DAVINCI, VISTA/VIVID, and BOLT) and more recently DRCR.net protocol T. Intravitreal steroids (dexamethasone intravitreal implant and fluocinolone acetonide), particularly in refractory cases, also play a significant role in the management of DME (MEAD/CHAMPLAIN and FAMOUS/FAME studies). In summary, over the last 5 years, blocking VEGF and inflammation has been shown to improve visual outcomes in patients with macular edema due to DM, revolutionizing the treatment of center-involved DME and establishing a new standard of care.

ACTINOMYCES NEUII ENDOPHTHALMITIS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION.

PubMed

Sahni, Sakshi; Watson, Randee Miller; Sheth, Veeral S

2017-01-01

To describe a case of acute endophthalmitis caused by Actinomyces neuii after intravitreal anti-vascular endothelial growth factor injection. Observational case report, review of published literature. A 67-year-old white man with wet age-related macular degeneration developed endophthalmitis secondary to A. neuii on the 10th day after intravitreal anti-vascular endothelial growth factor injection. Both anterior chamber and vitreous cultures were positive for A. neuii. He was treated successfully with intravitreal injection of vancomycin and ceftazidime. This is the first published report of culture-positive endophthalmitis caused by A. neuii after intravitreal injection.

Renal Effects of Long Term Administration of Triamcinolone Acetonide in Normal Dogs

PubMed Central

Osbaldiston, G. W.

1971-01-01

Triamcinolone acetonide was administered in excessive dosage to dogs to study the renal mechanism responsible for polyuria which is a clinically undesirable side effect of long term glucocorticoid therapy. Polyuria occurred coincident with a significant increase in urinary solute output. Although continuous administration of triamcinolone acetonide at 0.1 or 0.2 mg/lb/day caused a small but significant increase in creatinine output, the primary mechanism for the polyuria was increased solute excretion. Associated with the polyuria was pronounced hyperphagia and polydipsia. The cause of the hyperphagia was not established. The increase in electrolyte excretion caused by this synthetic steroid was probably compensated for by the hyperphagia. Because all the dogs showed muscle weakness and loss of body condition, it is likely that alteration in protein and amino acid metabolism was responsible for the hyperphagia. PMID:4251411

Occurrence of intraocular air bubbles during intravitreal injections for retinopathy of prematurity.

PubMed

Sukgen, Emine Alyamac; Gunay, Murat; Kocluk, Yusuf

2017-02-01

This study aims to present five cases with retinopathy of prematurity (ROP) who were found to have intraocular air bubbles after intravitreal injection (IVI) treatment. The medical records of 148 infants who underwent IVI for ROP were retrospectively reviewed and the ones who demonstrated post-injection intraocular air bubble formation were recruited. Of the 148 patients (31 babies received ranibizumab, 20 babies received aflibercept, 97 babies received bevacizumab), five were found to have intraocular air bubbles right after the IVI. Two infants received intravitreal ranibizumab and three received intravitreal bevacizumab injections. Although intraocular pressure increased temporarily, no intraocular sterile or infective reactions were observed in the postoperative period. The air bubble was found to resorb spontaneously within 72 h. The occurrence rate of the intravitreal air bubbles in our series was 3.37 % despite previously not been reported in the literature. Due to the intravitreal air injection risk, it is important to be more careful while preparing the intravitreal medication before treatment in premature babies.

Dystrophic Calcification in the Epidural and Extraforaminal Space Caused by Repetitive Triamcinolone Acetonide Injections

PubMed Central

Chung, Sang-Bong; Kim, Ki-Jeong; Kim, Hyun-Jib

2011-01-01

The authors report a case of epidural and extraforaminal calcification caused by repetitive triamcinolone acetonide injections. A 66-year-old woman was admitted presenting with lower extremity weakness and radiating pain in her left leg. Ten months before admission, the patient was diagnosed as having an L4-5 spinal stenosis and underwent anterior lumbar interbody fusion followed by posterior fixation. Her symptoms had been sustained and she did not respond to transforaminal steroid injections. Repetitive injections (10 times) had been performed on the L4-5 level for six months. She had been taking bisphosphonate as an antiresorptive agent for ten months after surgery. Calcification in the ventral epidural and extraforaminal space was detected. The gritty particles were removed during decompressive surgery and these were proven to be a dystrophic calcification. The patient recovered from weakness and radiating leg pain. Repetitive triamcinolone acetonide injections after discectomy may be the cause of dystrophic calcification not only in the degenerated residual disc, but also in the posterior longitudinal ligament. Possible mechanisms may include the toxicity of preservatives and the insolubility of triamcinolone acetonide. We should consider that repetitive triamcinolone injections in the postdisectomy state may cause intraspinal ossification and calcification. PMID:22053235

Intravitreal Phacoemulsification Using Torsional Handpiece for Retained Lens Fragments

PubMed Central

Kumar, Vinod; Takkar, Brijesh

2016-01-01

Purpose: To evaluate the results of intravitreal phacoemulsification with torsional hand piece in eyes with posteriorly dislocated lens fragments. Methods: In this prospective, interventional case series, 15 eyes with retained lens fragments following phacoemulsification were included. All patients underwent standard three-port pars plana vitrectomy and intravitreal phacoemulsification using sleeveless, torsional hand piece (OZiL™, Alcon's Infiniti Vision System). Patients were followed up for a minimum of six months to evaluate the visual outcomes and complications. Results: The preoperative best-corrected visual acuity (BCVA) ranged from light perception to 0.3. No complications such as thermal burns of the scleral wound, retinal damage due to flying lens fragments, or difficult lens aspiration occurred during intravitreal phacoemulsification. Mean post-operative BCVA at the final follow-up was 0.5. Two eyes developed cystoid macular edema, which was managed medically. No retinal detachment was noted. Conclusion: Intravitreal phacoemulsification using torsional hand piece is a safe and effective alternative to conventional longitudinal phacofragmentation. PMID:27621783

Intravitreal Phacoemulsification Using Torsional Handpiece for Retained Lens Fragments.

PubMed

Kumar, Vinod; Takkar, Brijesh

2016-01-01

To evaluate the results of intravitreal phacoemulsification with torsional hand piece in eyes with posteriorly dislocated lens fragments. In this prospective, interventional case series, 15 eyes with retained lens fragments following phacoemulsification were included. All patients underwent standard three-port pars plana vitrectomy and intravitreal phacoemulsification using sleeveless, torsional hand piece (OZiL™, Alcon's Infiniti Vision System). Patients were followed up for a minimum of six months to evaluate the visual outcomes and complications. The preoperative best-corrected visual acuity (BCVA) ranged from light perception to 0.3. No complications such as thermal burns of the scleral wound, retinal damage due to flying lens fragments, or difficult lens aspiration occurred during intravitreal phacoemulsification. Mean post-operative BCVA at the final follow-up was 0.5. Two eyes developed cystoid macular edema, which was managed medically. No retinal detachment was noted. Intravitreal phacoemulsification using torsional hand piece is a safe and effective alternative to conventional longitudinal phacofragmentation.

Treatment of cytomegalovirus retinitis with intravitreal ganciclovir. Long-term results.

PubMed

Cantrill, H L; Henry, K; Melroe, N H; Knobloch, W H; Ramsay, R C; Balfour, H H

1989-03-01

Long-term management of cytomegalovirus (CMV) retinitis by intravitreal injection of ganciclovir was evaluated in ten patients with acquired immune deficiency syndrome (AIDS). Patients were unable to tolerate systemic ganciclovir because of severe neutropenia (8 cases), catheter-induced sepsis (1 case), or the need to continue therapy for human immunodeficiency virus (HIV) with zidovudine (ZDV) (1 case). All patients had a favorable response to initial treatment. Cytomegalovirus retinitis progressed in four fellow eyes in which treatment was deferred. Vision improved or remained stable in all but one eye. Patients were followed for a mean of 4 months and received an average of 16.6 intravitreal injections in each eye. Relapse occurred late in the course while on maintenance treatment in five eyes (33%). There was no evidence of toxicity from repeated intravitreal injections. Treatment was very well tolerated. The only severe complication in a total of 249 injections was a single case of Staphylococcus epidermidis endophthalmitis which responded to intravitreal antibiotic treatment. Intravitreal ganciclovir is an effective alternative to systemic ganciclovir in those patients with severe neutropenia and in those patients who desire to remain on systemic ZDV.

Acute sterile endophthalmitis following intravitreal bevacizumab: case series

PubMed Central

Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

2014-01-01

Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

[Incidence of endophthalmitis after intravitreal injection: is antibioprophylaxis mandatory?].

PubMed

Ramel, J-C; Bron, A-M; Isaico, R; Meillon, C; Binquet, C; Creuzot-Garcher, C

2014-04-01

Endophthalmitis is the most dreaded complication after intravitreal injection. With the rise of antiangiogenics their rate is getting higher each year. The use of antibioprophylaxis is controversial. We tried to evaluate the impact of antibioprophylaxis on intravitreal injection endophthalmitis incidence. All patients who received intravitreal injections between January 2007 and October 2012 were included in this retrospective study. Until June 2012 all patients had antibiotics the days following the injection. From July 2012 the antibiotic was replaced by an antiseptic immediately after the injection. An overall number of 11,450 injections were performed. The overall rate of endophthalmitis was 6/11,450 (0.052%). The incidence of endophthalmitis in the group with antibiotics was 3/10,144 injections (0.03%), 2 were culture proven (0.02%). The incidence in the group without antibiotics was 3/1306 (0.23%). The difference was significant (P=0.024). The incidence of endophthalmitis post-intravitreal injections seems to be lower when using antibiotics. However, a prospective study is mandatory to draw more robust conclusions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Long-term follow-up of Dupuytren disease after injection of triamcinolone acetonide in Chinese patients in Taiwan.

PubMed

Yin, C-Y; Yu, H-H M; Wang, J-P; Huang, Y-C; Huang, T-F; Chang, M-C

2017-09-01

Injection of triamcinolone acetonide is a non-operative treatment for early-stage Dupuytren disease in Caucasians, but its effectiveness in non-Caucasians is unclear. We report averaged 5-year follow-up results of 37 patients (49 affected hands) with early-stage Dupuytren disease for patients in Taiwan (non-Caucasian) who received a single dose of 5 mg triamcinolone acetonide injection into nodules monthly for 3 months. Using ultrasound, we recorded no progression of sizes of the modules following injection after 6 months. After an average 5-year follow-up, two patients with three hands (6%) experienced reactivation of the treated nodules. None required surgical intervention. Ultrasound examination showed that sizes of the treated Dupuytren nodules decreased significantly by 40% 6 months after injection and 56% at the final follow-up. We conclude that in these Chinese patients in Taiwan with early Dupuytren nodules, triamcinolone acetonide injection was effective in reducing the size of the Dupuytren nodules and maintaining long-term durable control of the nodular growth. III.

A survey of UK practice patterns in the delivery of intravitreal injections.

PubMed

Samia-Aly, Emma; Cassels-Brown, Andrew; Morris, Daniel S; Stancliffe, Rachel; Somner, John E A

2015-07-01

To assess UK practice patterns related to the prescription of antibiotics before, during and after intravitreal injections, the location where injections are carried out and the qualifications of those administering the injections. Every ophthalmology unit featured in the Royal College of Ophthalmologists (UK) training directory was contacted. A healthcare professional involved in giving intravitreal injections at each institution completed a questionnaire regarding local practice patterns. A response rate of 85% (115/136) was achieved. Seventy four percent of hospitals (85/115) gave take home antibiotics post intravitreal injection. Twenty three percent (26/115) of hospitals employed non-medical healthcare professionals to administer injections and 83% (96/115) administered intravitreal injections in a dedicated clean room as opposed to an operating theatre. Practice patterns for intravitreal injection vary considerably. Guidelines alone do not appear to be effective in reducing practices which are considered wasteful and other approaches need to be developed. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Management of a case of Candida albicans endogenous endophthalmitis with intravitreal caspofungin

PubMed Central

Yadav, Harshali Manish; Thomas, Boben; Thampy, Cherian; Panaknti, Tandava Krishnan

2017-01-01

We report a case of Candida albicans endogenous endophthalmitis treated with intravitreal caspofungin. The patient was a known case of acute lymphoblastic leukemia on chemotherapy and presented to us with features suggestive of endogenous endophthalmitis. He was treated initially with intravenous (IV) caspofungin and intravitreal amphotericin B. Patients condition worsened after IV caspofungin was replaced by amphotericin B necessitating a core vitrectomy. The patient was given the option of off-label caspofungin intravitreal injection for which the patient consented. There was a gradual improvement in the clinical picture. The situation worsened after the injections were stopped necessitating a revitrectomy. The study demonstrates the clinical efficacy of intravitreal caspofungin for the first time in human eyes. PMID:28643723

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

PubMed

Kent, Tiffany L; Glybina, Inna V; Abrams, Gary W; Iezzi, Raymond

2008-01-01

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'.

PubMed

Iglicki, Matias; Zur, Dinah; Busch, Catharina; Okada, Mali; Loewenstein, Anat

2018-06-01

Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24 months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6 months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR ≥ 1 grade and progression to proliferative diabetic retinopathy (PDR). Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P < 0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P < 0.0001). This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24 months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.

Aortoduodenal fistula in a patient on intravitreal bevacizumab injections: a case report.

PubMed

Pepper, Amber N; Valenzuela, Mauricio O; Oller, Kellee L

2015-01-01

An 88-year-old woman on long-term intravitreal bevacizumab presented with acute gastrointestinal hemorrhage. She was stabilized and underwent nonrevealing upper endoscopy. She continued to require intermittent blood transfusions, and resulting computed tomography of the abdomen revealed an aortoduodenal fistula. The patient was undergoing treatment for her macular degeneration with intravitreal bevacizumab, an angiogenesis inhibitor frequently used to treat solid organ malignancies. Systemic administration has been associated with serious adverse events, including gastrointestinal hemorrhage, perforation, and fistula formation. Intravitreal bevacizumab has been used off-label to treat macular degeneration, but data on the safety of this therapy are limited. Given her lack of other risk factors, the authors postulate a potential association between intravitreal bevacizumab and aortoduodenal fistula formation in this patient.

[Systemic safety following intravitreal injections of anti-VEGF].

PubMed

Baillif, S; Levy, B; Girmens, J-F; Dumas, S; Tadayoni, R

2018-03-01

The goal of this manuscript is to assess data suggesting that intravitreal injection of anti-vascular endothelial growth factors (anti-VEGFs) could result in systemic adverse events (AEs). The class-specific systemic AEs should be similar to those encountered in cancer trials. The most frequent AE observed in oncology, hypertension and proteinuria, should thus be the most common expected in ophthalmology, but their severity should be lower because of the much lower doses of anti-VEGFs administered intravitreally. Such AEs have not been frequently reported in ophthalmology trials. In addition, pharmacokinetic and pharmacodynamic data describing systemic diffusion of anti-VEGFs should be interpreted with caution because of significant inconsistencies reported. Thus, safety data reported in ophthalmology trials and pharmacokinetic/pharmacodynamic data provide robust evidence that systemic events after intravitreal injection are very unlikely. Additional studies are needed to explore this issue further, as much remains to be understood about local and systemic side effects of anti-VEGFs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A protocol for the retina surgeon's safe initial intravitreal injections.

PubMed

Frenkel, Ronald E P; Haji, Shamim A; La, Melvin; Frenkel, Max P C; Reyes, Angela

2010-11-10

To determine the safety of a surgeon's initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure. A retrospective chart review. Fifty-nine patients (30 females, 29 males) received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections. The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab) were reviewed. All injections were performed in an office-based setting. Povidone-iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection. Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage. There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections. The incidence of serious complications was very low for the intravitreal injections given. A surgeon's initial intravitreal injections may be performed with a very high degree of safety using this protocol.

Cytomegalovirus retinitis after intravitreal bevacizumab injection in an immunocompetent patient.

PubMed

Bae, So Hyun; Kim, Tae Wan; Chung, Hum; Heo, Jang Won

2013-02-01

We report a case of cytomegalovirus (CMV) retinitis after intravitreal bevacizumab injection. A 61-year-old woman with diabetic macular edema developed dense vitritis and necrotizing retinitis 3 weeks after intravitreal bevacizumab injection. A diagnostic vitrectomy was performed. The undiluted vitreous sample acquired by vitrectomy was analyzed by polymerase chain reaction and culture. Polymerase chain reaction of the vitreous was positive for CMV DNA. Other laboratory results did not show evidence of other infectious retinitis and systemic immune dysfunction. Human immunodeficiency virus antibodies were also negative. After systemic administration of ganciclovir, retinitis has resolved and there has been no recurrence of retinitis during the follow-up period of 12 months. Ophthalmologists should be aware of potential risk for CMV retinitis after intravitreal bevacizumab injection.

[Early efficacy of dexamethasone implant (OZURDEX®) in diabetic macular edema: Real life study].

PubMed

Sarda, V; Fajnkuchen, F; Nghiem-Buffet, S; Grenet, T; Chaine, G; Giocanti-Auregan, A

2017-05-01

To assess early efficacy of dexamethasone intravitreal implant 0.7mg (OZURDEX ® ) at the time of peak efficacy (2 months after injection) in patients with decreased visual acuity secondary to diabetic macular edema (DME). Retrospective monocentric study. Inclusion criteria were best-corrected visual acuity (BCVA)≤70 letters (20/40) due to DME and central retinal thickness (CRT)≥300 microns (Cirrus 2, Carl Zeiss Meditec, Inc, Dublin). Enrolled patients could be treatment naive or not (after failure of laser photocoagulation and/or anti-VEGF therapy). Follow-up was at least 6 months. Our primary endpoint was BCVA gain at M2 after injection. Secondary endpoints were best-corrected visual acuity at 2 and 4 months, central retinal thickness at 2 and 4 months, mean interval between 2 injections, and adverse events. Nineteen eyes of 19 patients were included in this study. The mean age was 67.45 years, sex ratio was 2.17 men/women, and the patients were all type 2 diabetics. Three of 19 patients were treatment naive for anti-VEGF intravitreal injection, and 52.3% were pseudophakic (10/19 patients). The mean gain of BCVA at M2 was +7.7 letters. The mean BCVA was 51.1 ETDRS letters at baseline and 58.8 at M2. Mean CRT was 568.9μm at baseline and 291.2μm at M2. Treatment with dexamethasone implant was mainly a second-line treatment after failure of other treatments (macular laser photocoagulation and/or intravitreal injection of anti-VEGF). Three patients were naive of anti-VEGF treatment. Intraocular pressure≥25mmHg was found in 2 patients, and controlled medically. No glaucoma surgery was performed. The dexamethasone implant (OZURDEX ® ) allows an anatomical and functional improvement in patients suffering from vision loss due to DME. In this series, the implant was well tolerated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Management of iatrogenic crystalline lens injury occurred during intravitreal injection.

PubMed

Erdogan, Gurkan; Gunay, Betul Onal; Unlu, Cihan; Gunay, Murat; Ergin, Ahmet

2016-08-01

To evaluate the approach to management of iatrogenic crystalline lens injury occurred during intravitreal injection (IVI). The patients who were managed operatively or followed-up without intervention after the iatrogenic lens injury due to IVI were included in the study. Capsular breaks remained either quiescent or resulted in cataract formation in the patients with inadvertent crystalline lens capsule damage. Phacoemulsification surgery was performed in patients with cataract formation with lower fluidic settings. A total of 9 cases included in the study. Seven cases underwent phacoemulsification with intraocular lens implantation. Two cases remained as quiescent lens injury during the follow-up. In 2 cases, dislocation of lens fragments occurred during phacoemulsification where pars plana vitrectomy was performed at the same session. After iatrogenic crystalline lens injury, capsular damage could remain quiescent or progress to cataract formation. Although phacoemulsification surgery can be performed with appropriate parameters, lens fragment dislocation can be observed in cases with traumatic lens damage secondary to IVI.

Treatment of acute posterior uveitis in a porcine model by injection of triamcinolone acetonide into the suprachoroidal space using microneedles.

PubMed

Gilger, Brian C; Abarca, Eva M; Salmon, Jacklyn H; Patel, Samirkumar

2013-04-03

To evaluate the effect of triamcinolone acetonide (TA) administered into the suprachoroidal space (SCS) using a microneedle and compare it with intravitreal (IVT) TA injections in a porcine model of acute posterior segment inflammation. An IVT injection of balanced salt solution (BSS) or lipopolysaccharide (LPS) was followed 24 hours later with an injection of 0.2 mg or 2.0 mg of TA into the SCS or IVT. The SCS was accessed using microneedles in a minimally invasive procedure. Ocular inflammatory scores and IOP measurements were collected daily, whereas electroretinography, optical coherence tomography, and wide-field ocular fundus photography was performed on -1, 0, and 3 days after treatment. Aqueous and vitreous humor cell counts and protein levels and histopathology were also compared. Delivery of TA to the SCS using microneedles was simple, effective, and not associated with adverse effects or toxicity. SCS injection of low (0.2 mg) and high doses (2.0 mg) of TA was as effective in reducing acute inflammation in the ocular posterior segment as high-dose IVT injection. Low-dose SCS TA was also effective in reducing inflammation; however, low-dose IVT TA was not. Results from this study suggest that 0.2 mg and 2.0 mg of SCS TA was as effective in reducing inflammation as 2.0 mg IVT TA injection in a model of acute posterior segment inflammation. There were no adverse effects, increased IOP, or evidence of procedural or drug toxicity following injection of TA into the SCS in porcine eyes.

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT.

PubMed

Chhablani, Jay; Narayanan, Raja; Mathai, Annie; Yogi, Rohit; Stewart, Michael

2016-06-01

To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration. Eligible eyes with choroidal neovascularization secondary to age-related macular degeneration each received a single intravitreal injection of ziv-aflibercept. Comprehensive ophthalmic examinations and detailed systemic evaluations were performed at baseline and Days 1, 7, and 30 after injection, and International Society for Clinical Electrophysiology of Vision standard electroretinography was performed at baseline and Day 30. Primary outcome measures were safety parameters that included signs of clinical and electroretinographic toxicity. Secondary outcome measures included changes in best-corrected visual acuity and central subfield thickness. Twelve eyes of 12 patients were treated. None of the patients complained of blurred vision, ocular pain, or bulbar injection at any of the follow-up visits, nor was intraocular inflammation noted. There were no significant differences in implicit times, "a" and "b" wave amplitudes, or b/a ratios at 1 month when compared with baseline (P = 0.4). None of the patients experienced serious ocular or systemic adverse events. Mean best-corrected visual acuity improved only slightly at 30 days (LogMAR 0.45 ± 0.31 [Snellen equivalent: 20/60]) compared with baseline (LogMAR 0.37 ± 0.24 [Snellen equivalent: 20/50]; P = 0.51). Single intravitreal injections of ziv-aflibercept into eyes with neovascular age-related macular degeneration appear to be safe through 1 month. Ziv-aflibercept could become a safe, low-cost therapy for macular diseases in developing countries and in those where intravitreal aflibercept (Eylea) is not available.

Intravitreal memantine retinal toxicity in rabbits.

PubMed

Moreno Páramo, D; Reyna Vielma, S; Rodríguez Reyes, A; Hernández Ayuso, I; Quiroz Mercado, H

2016-02-01

To histologically evaluate whether the intravitreal application of memantine produces retinal toxicity in rabbits. A cross-sectional design, experimental, descriptive study was performed on 16 eyes of 16 New Zealand rabbits of 3 kg, divided in 4 groups of 4 rabbits. A dose of 70 ng/ml of intravitreal memantine was administered in Group A, a dose of 150 ng/ml in Group B, a dose of 400 ng/ml in Group C, and Group D received 1 ml of balanced salt solution. The injected eye of half of each group was enucleated 15 days after the injection, and the rest within 30 days after injection. Following enucleation, each eye was placed in 10% formaldehyde. Histopathological analysis was performed on all enucleated eyes. The animals were treated according to the guidelines of the Association for Research on Vision and Ophthalmology (ARVO). Groups A, B and D did not show any histopathological changes after their enucleation at 15 and 30 days. Group C showed changes in the photoreceptor layer after enucleation at 15 and 30 days. In our study, it was observed that memantine concentrations at 70 ng/ml and 150 ng/ml are safe when administered intravitreally; however, doses of 400 ng/ml produced retinal structural changes. This research should continue to assess its clinical usefulness. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results.

PubMed

Tomkins-Netzer, Oren; Lightman, Susan; Drye, Lea; Kempen, John; Holland, Gary N; Rao, Narsing A; Stawell, Richard J; Vitale, Albert; Jabs, Douglas A

2015-11-01

To evaluate the 2-year outcomes of uveitic macular edema. Longitudinal follow-up of a randomized cohort. At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 μm) on time-domain optical coherence tomography (OCT) of macula. Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003). About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment

Transcleral delivery of triamcinolone acetonide and ranibizumab to retinal tissues using macroesis.

PubMed

Singh, Rishi P; Mathews, Michael Ellen; Kaufman, Michael; Riga, Alan

2010-02-01

To determine the feasibility of macroesis for the delivery of ranibizumab and triamcinolone acetonide via a transcleral route. Macroesis is a non-invasive method of drug delivery that uses alternating current (AC) to deliver drugs to target tissues. Two preclinical models of drug delivery were used for feasibility studies of delivering ranibizumab and triamcinolone acetonide to ocular tissues. In the first model, full-thickness sections of rabbit ocular tissue (conjunctiva to retina) were placed on an interdigitated electrode platform, and the drug was placed on the surface of the tissue. A non-uniform electrical field was applied to the ocular tissue, and electrical conductivity, a measurement of drug delivery, was monitored during the course of the experiment. In a second model, termed a 'simulated vitreous model,' the same full-thickness sections of rabbit ocular tissue were mounted below the electrode device, and the test compounds were placed on the electrodes. The fluid below the tissue, which simulated the vitreous cavity, was analysed using UV spectroscopy at the end of the study for the presence of drug. In the electrical conductivity studies, the electric characteristics of the tissue-drug system clearly showed movement of the drug through the tissue to the dielectric sensor based on changes in the electrical conductivity of the tissue sample with triamcinolone. No change in tissue conductivity was observed when no drug was placed. No heat generation occurred during the course of the study; nor was any gross tissue destruction noted. In the simulated vitreous model, studies using triamcinolone yielded concentrations ranging from 0.280 to 0.970 mg/ml, depending on the voltage, frequency and time applied. In as little as 6.7 min, clinically efficacious doses could be obtained in the preclinical system. Studies using ranibizumab yielded concentrations of 0.070-0.171 mg/ml, depending on the voltage, frequency, and time applied. In as little at 6.7 min, 92

A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

PubMed

Sivaprasad, S; Patra, S; DaCosta, J; Adewoyin, T; Shona, O; Pearce, E; Chong, N V

2011-01-01

To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 μg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 μm. Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 μm (±75). This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD. Copyright © 2011 S. Karger AG, Basel.

Bevacizumab and Panretinal photocoagulation protect against ocular hypertension after posterior subtenon injection of triamcinolone acetonide for diabetic macular edema.

PubMed

Hsieh, Yi-Ting; Yang, Chung-May; Chang, Shu-Hui

2017-08-01

To analyze the prognostic factors for ocular hypertension after posterior subtenon injection of triamcinolone acetonide (PSTA) for the treatment of diabetic macular edema (DME). Patients who received PSTA for DME from January 2006 to December 2011 were enrolled retrospectively and were followed until December 2012 in one hospital. Modified Cox regression models were used to analyze the factors associated with ocular hypertension, which was defined as an intraocular pressure>21 mmHg after PSTA. A total of 180 PSTA injections were given to 114 eyes from 73 adults with DME. During a mean follow-up of 50.4 weeks after each injection, ocular hypertension occurred in 20.6% of injections (28.1% of eyes). Treatment-naïve patients with proliferative diabetic retinopathy (PDR) had a higher risk of ocular hypertension after PSTA than those with nonproliferative diabetic retinopathy (NPDR) [hazard ratio (HR)=3.255, p=0.030]. Intravitreal injection of bevacizumab (IVB) before PSTA had a significant effect in lowering the risk of ocular hypertension after PSTA in patients with PDR who had received panretinal photocoagulation (PRP) (HR=0.107, p=0.035). Both prompt PRP and IVB following PSTA had a protective effect against ocular hypertension in treatment-naïve patients with PDR (HR=0.086, p=0.0002 and HR=0.155, p=0.049, respectively). Treatment-naïve patients with PDR had a higher risk of ocular hypertension after PSTA than those with NPDR. Bevacizumab and prompt PRP both had a protective effect against ocular hypertension after PSTA in patients with PDR. Copyright © 2016. Published by Elsevier B.V.

Short-term outcome after intravitreal ranibizumab injections for the treatment of retinopathy of prematurity.

PubMed

Castellanos, María Ana Martínez; Schwartz, Shulamit; García-Aguirre, Gerardo; Quiroz-Mercado, Hugo

2013-07-01

To evaluate ocular outcome in premature infants treated with intravitreal ranibizumab injections for retinopathy of prematurity (ROP) over a period of 3 years. An interventional case series. Premature infants with high-risk prethreshold or threshold ROP with plus disease received an off label monotherapy with intravitreal injections of ranibizumab. The primary outcome was treatment success defined as regression of neovascularisation (NV) and absence of recurrence. The secondary outcomes were ocular and systemic adverse events and visual acuity. Six eyes were included in the study and treated with intravitreal injections of ranibizumab. All showed complete resolution of NV after a single injection. The anti-angiogenic intravitreal injections allowed for continued normal vessel growth into the peripheral retina, without any signs of disease recurrence or progression during the follow up period. No ocular or systemic adverse effects were observed. Three years of follow up in a small series suggest that intravitreal ranibizumab injections for ROP result in apparently preserved ocular outcome. Further large scale studies are needed to address the long-term safety and efficacy.

Nurse-led ranibizumab intravitreal injections in wet age-related macular degeneration: a literature review.

PubMed

Gregg, Emma

2017-04-12

Aim The aim of this literature review was to explore the development of the role of specialist ophthalmic nurses in delivering ranibizumab intravitreal injections to patients with wet age-related macular degeneration (AMD), and to evaluate their contribution to reducing capacity pressures in medical retina services, while maintaining safe and effective standards of care. Method A systematic literature search was undertaken to identify relevant articles published between January 2000 and June 2015. A search of electronic databases was undertaken, and selected relevant journals were searched manually. A free text and subject heading search strategy was conducted, in which the abstracts of publications identified for review were assessed for relevance. Inclusion criteria were: nurses delivering ranibizumab intravitreal treatment; studies performed in the UK and other countries; and patients with AMD, diabetic macular oedema or central retinal vein occlusion receiving nurse-led ranibizumab (Lucentis) intravitreal treatment. Findings Five studies were identified from the literature search, which audited a total of 31,303 injections delivered by nurse practitioners between January 2007 and November 2013. The visual outcomes and the rate of complications from intravitreal injections delivered by trained ophthalmic nurse practitioners were comparable to intravitreal injections delivered by ophthalmologists. Four of the five studies reported increased patient satisfaction, patients consenting to nurse-delivered intravitreal injections, favourable pain experience, and absence of complaints. Conclusion Practice innovation is an example of a quality, innovation, productivity and prevention process. Role expansion, in which specialist ophthalmic nurses deliver intravitreal injections, has been shown to be economical, safe and effective. It enables timely delivery of the service, thereby preventing irreversible blindness for individuals with wet AMD.

Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes.

PubMed

Manna, Soumyarwit; Banerjee, Rupak K; Augsburger, James J; Al-Rjoub, Marwan F; Donnell, Anna; Correa, Zelia M

2015-08-01

The purpose of this study was to evaluate the pharmacokinetics and toxicity of a chitosan (CS) and polylactic acid (PLA) based methotrexate (MTX) intravitreal micro-implant in an animal model using rabbit eyes. CS- and PLA-based micro-implants containing 400 μg of MTX were fabricated using lyophilization and dip-coating techniques. The micro-implants were surgically implanted in the vitreous of eight New Zealand rabbits employing minimally invasive technique. The PLA-coated CS-MTX micro-implant was inserted in the right eye and the placebo micro-implant in the left eye of each rabbit. Two rabbits were euthanized at each pre-determined time point post-implantation (days 5, 12, 19, and 33) for pharmacokinetics and histopathology evaluation. A therapeutic concentration of MTX (0.1-1.0 μM) in the vitreous was detected in the rabbit eyes studied for 33 days. The MTX release from the coated micro-implants followed a first order kinetics (R (2) ~ 0.88), implying that MTX release depends on the concentration of MTX in the micro-implant. Histopathological analysis of the enucleated eyes failed to show any signs of infection or tissue toxicity in any of the specimens. The PLA-coated CS-MTX micro-implants were able to deliver therapeutic release of MTX for a period of more than 1 month without detectable toxicity in a rabbit model. The micro-implants can be further investigated as a prospective alternative to current treatment protocols of repeated intravitreal MTX injections in intraocular disorders such as primary intraocular lymphoma, and selected cases of non-microbial intraocular inflammation.

Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

PubMed

Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

2013-08-01

To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

Non-physician delivered intravitreal injection service is feasible and safe - a systematic review.

PubMed

Rasul, Asrin; Subhi, Yousif; Sørensen, Torben Lykke; Munch, Inger Christine

2016-05-01

Non-physicians such as nurses are trained to give injections into the vitreous body of the eye to meet the increasing demand for intravitreal therapy with vascular endothelial growth factor inhibitors against common eye diseases, e.g. age-related macular degeneration and diabetic retinopathy. We systematically reviewed the existing literature to provide an overview of the experiences in this transformational process. We searched for literature on 22 September 2015 using PubMed, Embase, the Cochrane Library, CINAHL and the Web of Science. Eligible studies had to address any outcome based on non-physician delivered intravitreal therapy regardless of the study design. Being non-physician was defined as the injecting personnel not being a physician, but no further restrictions were made. Five studies were included with a total of 31,303 injections having been performed by 16 nurses. The studies found that having nurses perform the intravitreal injections produced to a short-term capacity improvement and liberated physicians for other clinical work. Training was provided through courses and direct supervision. The rates of endophthalmitis were 0-0.40‰, which is comparable to reported rates when the intravitreal therapy is given by physicians. Non-physician delivered intravitreal therapy seems feasible and safe.

Safety of intravitreal quinupristin/dalfopristin in an animal model.

PubMed

Giordano, Veronica E; Hernandez-Da Mota, Sergio E; Adabache-Guel, Tania N; Castillejos-Chevez, Armando; Corredor-Casas, Sonia; Salinas-Longoria, Samantha M; Romero-Vera, Rafael; Jimenez-Sierra, Juan M; Guerrero-Naranjo, Jose L; Morales-Canton, Virgilio

2016-01-01

To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. Eighteen New Zealand white rabbits were divided into three treatment groups (groups 1 to 3) and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection (baseline) and after 7, 14, 21 and 28d, followed by enucleation for histological examination. Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 (Kruskall-Wallis test, P=0.000). By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealed no significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/0.1 mL in this rabbit model.

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

PubMed

Del Amo, Eva M; Urtti, Arto

2015-08-01

Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

PubMed

Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice

PubMed Central

Powner, Michael B.; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of “whitening” of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. PMID:26226015

Chronic cystoid macular oedema treated with intravitreal dobesilate

PubMed Central

Cuevas, Pedro; Outeiriño, Luis A; Angulo, Javier; Giménez-Gallego, Guillermo

2012-01-01

Dobesilate is an anti-inflammatory and antipermeability agent. Intravitreal administration of this compound is a therapeutically beneficial agent in the treatment of chronic cystoid macular oedema. PMID:22778475

Survey of intravitreal injection techniques among retina specialists in Israel

PubMed Central

Segal, Ori; Segal-Trivitz, Yael; Nemet, Arie Y; Geffen, Noa; Nesher, Ronit; Mimouni, Michael

2016-01-01

Purpose The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results Overall, 66% (52/79) completed the survey. Most (98%) do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71%) use sterile surgical draping. All respondents apply topical analgesics and a majority (69%) measure the distance from the limbus to the injection site. A minority (21%) displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%). Less than half routinely assess postinjection optic nerve perfusion (44%). A majority (92%) apply prophylactic antibiotics immediately after the injection. Conclusion The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques that combine safety and efficacy while causing as little discomfort to the patients as possible. PMID:27366050

[Intravitreal bevacizumab for choroidal neovascularization associated with Best's disease].

PubMed

Velazquez-Villoria, D; Macià Badia, C; Rigo Quera, J; Velez-Escola, L; Arcos-Algaba, G; Martínez-Castillo, V; García-Arumí, J

2014-10-01

A 27-year old woman presented with loss of vision in the right eye (20/200). Ophthalmoscopic examination showed intrarretinal hemorrhage in the macular region with neurosensory detachment in the right eye, and viteliform deposit on the left eye. Fluorescein angiography and the electrooculogram confirmed the diagnosis of choroidal neovascularization associated with Best's disease. Four weeks after a single bevacizumab intravitreal injection, visual acuity was restored (20/25) and remained stable after a 12 month follow-up. Intravitreal bevacizumab appears to be an effective treatment for choroidal neovascularization associated to Best's disease. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Treatment of cytomegalovirus (CMV) retinitis with intravitreous ganciclovir in HIV-infected children.

PubMed

Surachatkumtonekul, Thammanoon; Chokephaibulkit, Kulkanya; Vanprapar, Nirun; Pamonvaechavan, Pittaya

2008-03-01

To evaluate the efficacy, visual outcomes, and complications of intravitreous ganciclovir treatment in cytomegalovirus (CMV) retinitis in HIV-infected children. The medical records of HIV-infected children who were screened for CMV retinitis from February 2002 to February 2005 were reviewed. The children with CD4+ < 15%, or with clinical category C would have complete ophthalmic examination every 3 months. Ganciclovir (4 mg/0.04 ml) was administered intravitreously to the eye with CMV retinitis every 2 weeks under general anaesthesia. After injection, fundi were examined immediately, 1 day, 14 days and every 2 weeks until the lesions were stable. Six (9 eyes) out of 45 children (13%) aged 2-12 years were found to have CMV retinitis. All CMV retinitis lesions were "cheese and ketchup like" (retinal hemorrhage and exudate) lesions and presented in the posterior pole. Bilateral CMV retinitis were found in 3 children. Intravitreous ganciclovir was injected in 4 children (5 eyes). The average number of intravitreous injections for each patient was 5.6 (3-7) times. All of the children received antiretroviral therapy and 3 children also received intravenous ganciclovir CMV retinitis lesions were improved in every eye. The visual acuity (VA) remained stable in 4 eyes, but endophthalmitis developed in one eye a few days after injection. The average duration of follow-up was 13.5 months (3-23 months). CMV retinitis was not uncommon. The authors found that intravitreous ganciclovir was effective but may cause complications. This treatment should be considered in a resource-limited setting.

Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes

PubMed Central

Dejneka, Nadine S.; Wan, Shanhong; Bond, Ottrina S.; Kornbrust, Douglas J.

2008-01-01

Purpose The primary objective of these investigations was to determine the ocular biodistribution of bevasiranib, a small interfering RNA (siRNA) targeting vascular endothelial growth factor A (VEGF-A), following a single intravitreal injection to rabbit eyes. Methods A tissue distribution and pharmacokinetic study was conducted with 3H-bevasiranib prepared in balanced-salt solution (BSS). Single doses of either 0.5 mg/eye or 2.0 mg/eye of 3H-bevasiranib were given by intravitreal injection to Dutch-Belted rabbits (both eyes were treated). Subgroups of rabbits were serially-sacrificed at various times up to 7 days following dosing for collection of tissue samples. The right eye of each rabbit was collected whole, and the left eye was dissected to isolate five ocular tissues. All samples were analyzed by liquid scintillation counting to determine the concentrations of bevasiranib equivalents. An ocular disposition study was also performed with non-radiolabeled bevasiranib, which was administered to Dutch-Belted rabbit eyes via intravitreal injection at a dose of 2.0 mg/eye. Twenty-four hours post-dose, the eyes were enucleated and dissected into eight individual ocular structures that were analyzed for intact bevasiranib using a locked nuleic acid (LNA) noncompetitive hybridization-ligation enzyme-linked immunosorbent assay. Results Following intravitreal injection of 0.5 mg or 2.0 mg radiolabeled bevasiranib to Dutch-Belted rabbits, bevasiranib was detected in the vitreous, iris, retina, retinal pigment epithelium (RPE), and sclera (+choroid). As expected, the highest concentrations were found in the vitreous, and vitreous levels steadily decreased over time, while concentrations of radioactivity in the other ocular tissues increased to maximum values between 24 h and 72 h after dosing. Of these tissues, the highest concentration of radioactivity was detected in the retina. The LNA assay further confirmed the presence of intact bevasiranib in these tissues 24 h

Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles

PubMed Central

Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

2013-01-01

Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. PMID:24036388

Determination of the toxicity of intravitreal minocycline in rabbit eyes.

PubMed

Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari

2016-09-01

To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.

Repeated intraocular crystallization of ganciclovir in one eye after bilateral intravitreal injections: a case report.

PubMed

Iu, Lawrence P L; Fan, Michelle C Y; Lam, Wai-Ching; Wong, Ian Y H

2018-02-09

Cytomegalovirus (CMV) retinitis is an opportunistic infection that primarily affects immunocompromised individuals. Intravitreal ganciclovir injection monotherapy or in combination with systemic anti-CMV therapy are effective treatments for CMV retinitis. Crystallization of ganciclovir after intravitreal injection is extremely rare. Only two cases had been reported in literature. Crystallization in only one eye after bilateral injections had not been reported before. We hereby report a case of intraocular ganciclovir crystallization in one eye after bilateral intravitreal injections, and repeated crystallization in the same eye after repeated injections. A 79-year-old patient had bilateral cytomegalovirus retinitis and received bilateral intravitreal ganciclovir injections of 2.5 mg in 0.05 ml sterile water. Fundus examination after injection showed formation of needle-shaped, golden-yellow crystals in the vitreous of right eye but not in left eye. The crystals dissolved spontaneously. Repeated bilateral intravitreal ganciclovir injections 4 days later resulted in repeated crystallization of ganciclovir in right eye but not in left eye. The crystals dissolved spontaneously and completely after 5 minutes. Visual acuity remained unchanged and intraocular pressure was normal. Intraocular ganciclovir crystallization could occur after intravitreal injections. It is important to perform fundus examination after injection. The crystals may dissolve rapidly and vitrectomy may not be necessary. Our case suggested intraocular ganciclovir crystallization is an idiosyncratic phenomenon, subjects to distinctive intraocular environment which could be different between two eyes of the same patient. The susceptible intraocular environment could be persistent leading to repeated crystallization.

Effects of Intravitreal Ranibizumab in the Treatment of Retinopathy of Prematurity in Chinese Infants.

PubMed

Yi, Zuohuizi; Su, Yu; Zhou, Yunyun; Zheng, Hongmei; Ye, Meihong; Xu, Yonghong; Chen, Changzheng

2016-08-01

To evaluate the efficacy associated with intravitreal ranibizumab in the treatment of retinopathy of prematurity (ROP). A retrospective case series study. Infants diagnosed with Type 1 ROP, or aggressive posterior ROP (AP-ROP) were enrolled in the study. All infants in the study received intravitreal ranibizumab (0.25 mg/0.025 ml) as the initial treatment. Follow-up examinations were performed the day after treatment, then weekly for 1 month, bi-monthly for two additional months, then monthly until vascularization of zone III occurred. Additional treatments were initiated in cases of disease recurrence. Thirty-three premature infants (a total of 66 eyes) receiving intravitreal ranibizumab were included. The mean birth weight was 1291 ± 211 g (range: 650-1650 g) and the mean gestational age was 29.8 ± 1.6 weeks (range: 27.0-33.6 weeks). The mean gestational age at the time of the first injection was 35.8 ± 1.6 weeks (range: 32.7-38.4 weeks). The mean follow-up time was 12.9 ± 4.9 months (range: 6-22 months). Single injections were administered to 58 eyes (87.9%), whereas eight eyes (12.1%) received additional treatments. Recurrence was observed in eight eyes (12.1%), with a mean time to recurrence of 6.9 ± 1.8 weeks (range: 4-8 weeks). Intravitreal ranibizumab is effective for the treatment of retinopathy of prematurity, although a small amount of patients recurred. Compared with intravitreal bevacizumab, a higher incidence and shorter time to recurrence were observed after intravitreal ranibizumab treatment, thus longer and more frequent follow-ups are needed.

Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection.

PubMed

Huang, Di; Chen, Ying-Shan; Thakur, Sachin S; Rupenthal, Ilva D

2017-10-01

Intravitreal injection is the most common administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient delivery of drugs administered intravitreally. This study aimed to improve the diffusive mobility of nanoparticles (NPs) in the vitreous and enhance their permeation across the retina after intravitreal injection by application of ultrasound (US). Ex vivo posterior bovine eye cups were used and the vitreous was either left intact or removed gently from the neural retina. Hyaluronic acid coated human serum albumin NPs were administered into the eye cups and continuous US with a frequency of 1MHz, an intensity of 0.5W/cm 2 , and a duration of 30s was applied once or repeatedly via the transscleral route. After pre-determined time points, fluorescence intensities in the vitreous and the retina were analyzed. Short pulses of US significantly improved the diffusive mobility of NPs through the vitreous as well as their penetration across the neural retina into the retinal pigment epithelium and choroid without causing any detectable damage to the ocular tissues. Therefore, transscleral US could be a powerful and safe tool to enhance retinal delivery of intravitreally injected NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Reversible bull's-eye maculopathy associated with intravitreal fomivirsen therapy for cytomegalovirus retinitis.

PubMed

Stone, T W; Jaffe, G J

2000-08-01

To report two cases in which a bull's eye maculopathy developed after intravitreal injection of fomivirsen. Case reports. A 50-year-old man with acquired immunodeficiency syndrome (AIDS) and refractory cytomegalovirus retinitis developed bull's-eye pigmentary changes in the macula of the right eye after initiating therapy with fomivirsen (Vitravene; CIBA Vision, Atlanta, Georgia) intravitreal injections. These pigmentary changes resolved upon cessation of treatment. A 36-year-old man with AIDS and refractory bilateral cytomegalovirus retinitis developed bull's-eye pigmentary changes in both eyes during bilateral intravitreal treatment with fomivirsen. Vision was not affected. These changes resolved after treatment with fomivirsen was stopped. Fomivirsen, a new medication for the treatment of refractory cytomegalovirus retinitis, may cause a bull's-eye maculopathy in some patients. The bull's-eye maculopathy is reversible and does not appear to affect vision.

Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization

PubMed Central

Kurup, Shree; Lew, Julie; Byrnes, Gordon; Yeh, Steven; Nussenblatt, Robert; Levy-Clarke, Grace

2010-01-01

Purpose To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis-associated choroidal/retinal neovascularization. Methods Two female patients (40 years, 15 years) with posterior uveitis, (one presumed ocular sarcoidosis, one lupus) were evaluated for neovascularization of the posterior segment. Both patients were given a single dose of 1.25 mg intravitreal bevacizumab. Results Significant anatomical and functional recovery was evident in both patients within a few weeks. Conclusion In selected uveitic patients, bevacizumab may be an option for managing neovascularization. PMID:18513266

Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles.

PubMed

Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

2013-11-01

Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Solution formulation development of a VEGF inhibitor for intravitreal injection.

PubMed

Marra, Michelle T; Khamphavong, Penney; Wisniecki, Peter; Gukasyan, Hovhannes J; Sueda, Katsuhiko

2011-03-01

PF-00337210 is a potent, selective small molecule inhibitor of VEGFRs and has been under consideration for the treatment of age-related macular degeneration. An ophthalmic solution formulation intended for intravitreal injection was developed. This formulation was designed to maximize drug properties such that the formulation would precipitate upon injection into the vitreous for sustained delivery. As a parenteral formulation with additional constraints dictated by this specialized delivery route, multiple features were balanced in order to develop a successful formulation. Some of these considerations included low dosing volumes (≤0.1 mL), a limited repertoire of safe excipients for intravitreal injection, and the unique physical chemical properties of the drug. The aqueous solubility as a function of pH was characterized, buffer stressing studies to select the minimal amount of buffer were conducted, and both chemical and physical stability studies were executed. The selected formulation consisted of an isotonic solution comprised of PF-00337210 free base in a citrate-buffered vehicle containing NaCl for tonicity. The highest strength for regulatory toxicology studies was 60 mg/mL. The selected formulation exhibited sufficient chemical stability upon storage with no precipitation, and acceptable potency and recovery through an intravitreal dosing syringe. Formulation performance was simulated by precipitation experiments using extracted vitreous humor. In simulated injection experiments, PF-00337210 solutions reproducibly precipitated upon introduction to the vitreous so that a depot was formed. To our knowledge, this is the first time that a nonpolymeric in situ-forming depot formulation has been developed for intravitreal delivery, with the active ingredient as the precipitating agent. © 2011 American Association of Pharmaceutical Scientists

An Outbreak of Streptococcus Endophthalmitis after Intravitreal Injection of Bevacizumab

PubMed Central

Goldberg, Roger A.; Flynn, Harry W.; Isom, Ryan F.; Miller, Darlene; Gonzalez, Serafin

2011-01-01

Purpose To report a series of patients with Streptococcus endophthalmitis after injection with intravitreal bevacizumab prepared by the same compounding pharmacy. Design Non-comparative consecutive case series. Methods Medical records and microbiology results of patients who presented with endophthalmitis after injection with intravitreal bevacizumab between July 5 and July 8, 2011, were reviewed. Results Twelve patients were identified with endophthalmitis, presenting 1-6 days after receiving an intravitreal injection of bevacizumab. The injections occurred at four different locations in South Florida. All patients received bevacizumab prepared by the same compounding pharmacy. None of the infections originated at the Bascom Palmer Eye Institute, Miami, FL, although nine patients presented to its tertiary-care ophthalmic emergency room for treatment, and three additional patients were seen in consultation. All patients were treated initially with a vitreous tap and injection; eight patients subsequently received a vitrectomy. Microbiology cultures for ten patients were positive for Streptococcus mitis/oralis. Seven unused syringes of bevacizumab prepared by the compounding pharmacy at the same time as those prepared for the affected patients also were positive for S. mitis/oralis. After four months of follow-up, all but one patient had count-fingers or worse visual acuity, and three required evisceration or enucleation. Local, state and federal health department officials have been investigating the source of the contamination. Conclusions In this outbreak of endophthalmitis after intravitreal bevacizumab injection, Streptococcus mitis/oralis was cultured from the majority of patients and from all unused syringes. Visual outcomes were generally poor. The most likely cause of this outbreak was contamination during syringe preparation by the compounding pharmacy. PMID:22264943

Inhibition of ultraviolet-B epidermal ornithine decarboxylase induction and skin carcinogenesis in hairless mice by topical indomethacin and triamcinolone acetonide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, N.J.; Connor, M.J.; Breeding, J.

1982-10-01

Modulation of ultraviolet-B (UVB) skin carcinogenesis by topical treatment with two antiinflammatory drugs expected to have different mechanisms of action has been studied in the hairless mouse. Indomethacin is a nonsteroidal antiinflammatory agent which may act by inhibiting prostaglandin biosynthesis. Triamcinolone acetonide is a steroidal antiinflammatory agent. Both of these drugs inhibited the induction of epidermal ornithine decarboxylase by UVB when applied topically in a acetone vehicle. A UVB skin tumor study was designed. Groups of mice were irradiated daily with UVB for 20 days, each mouse receiving a total of 17.1 kJ UVB per sq m. Group 1 wasmore » treated with acetone immediately after each irradiation; Group 2 received 700 nmol indomethacin in acetone immediately after each irradiation; Group 3 received 14.4 nmol triamcinolone acetonide in acetone immediately after each irradiation. Mice were killed after 52 weeks, and the tumors were excised and examined histologically. Both topical indomethacin and topical triamcinolone acetonide were effective in reducing the incidence and size of the skin tumors induced by UVB. This evidence supports the hypothesis that the induction of ornithine decarboxylase may be a critical component of UVB skin carcinogenesis and that inhibition of ornithine decarboxylase induction can be used as a screen for agents which will inhibit UVB skin carcinogenesis.« less

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

PubMed Central

Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

2011-01-01

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

Rilonacept in the treatment of subacromial bursitis: A randomized, non-inferiority, unblinded study versus triamcinolone acetonide.

PubMed

Carroll, Matthew B; Motley, Spencer A; Wohlford, Susanna; Ramsey, Bryan C

2015-12-01

Subacromial bursitis is caused by inflammation of the bursa that separates the superior surface of the supraspinatus tendon from the overlying coraco-acromial ligament and acromion. While multiple cytokines are implicated, interleukin-1 beta appears to play a prominent role. Rilonacept, an interleukin-1 trap, may be an alternative to corticosteroid injection for the management of this condition. This single center, randomized, non-inferiority, unblinded study recruited 33 subjects over 9 months. Twenty subjects received 160mg intrabursal injection of rilonacept and 13 received a 6mL mixture of lidocaine, bupivacaine, and 80mg triamcinolone acetonide. QuickDASH, subject reported pain, and adverse events were recorded at time of injection, 2 days later, 2 weeks later, and 4 weeks later. Primary outcome was improvement in QuickDASH 4 weeks post-injection. Secondary outcomes were improvement in subject reported pain and occurrence of adverse events at 4 weeks. Both study groups were equally matched for age, gender, ethnicity, and site of bursa injection. Both medications demonstrated a statistically significant improvement in QuickDASH 4 weeks post-injection, but triamcinolone acetonide injection offered greater improvement (P=0.004). Both medications demonstrated improvement in subject reported pain but between group comparison at 4 weeks showed that triamcinolone was superior (P=0.044). No statistically significant differences in adverse events were noted between groups, but subjects who received rilonacept experienced more episodes of diarrhea and headache. While improvement in QuickDASH and pain was noted with a single intrabursal injection of rilonacept at 4 weeks, injection with triamcinolone acetonide was more efficacious. This trial was registered with www.clinicaltrials.gov (NCT01830699). Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Short-term effects of intravitreal bevacizumab on cornea and anterior chamber.

PubMed

Güler, Mete; Capkın, Musa; Simşek, Ali; Bilak, Semsettin; Bilgin, Burak; Hakim Reyhan, Ali; Fırat, Müge

2014-10-01

To determine the short-term effects of single-dose intravitreal bevacizumab injection on central corneal thickness (CCT), simulated keratometry (Sim K), anterior chamber depth (ACD), iridocorneal angle (ICA) and intraocular pressure (IOP) measurements. Prospective, nonrandomized, interventional clinical trial. Forty-three eyes of 43 patients aged between 41 and 78 years (average 62 ± 13 years) received an intravitreal injection of 2.5 mg/0.1 mL bevacizumab. Patients who had not undergone additional intravitreal anti-vascular endothelial growth factor therapy within 6 months were included in the study. CCT, Sim K, ACD and ICA measurements were obtained with Sirius Topographer. IOP measurements were taken after topographic measurements with Goldmann applanation tonometer. The CCT, ACD, ICA and IOP measurements were taken before and after 3rd, 15th days and 1st month of intravitreal bevacizumab injection. Pre- and postinjection of 3rd, 15th days and 1st month CCT (p = 0.999), Sim K (p = 0.746), ACD (p = 0.996), ICA (p = 0.632) and IOP (p = 0.707) measurements were not statistically different. Mean CCT (p = 1.000), Sim K (0.972), ACD (p = 0.998), ICA (0.667) and IOP (0.951) values were similar before and after 3rd day of bevacizumab injection. Mean CCT (p = 0.999), Sim K (p = 0.994), ACD (p = 1.000), ICA (p = 0.999) and IOP (p = 1.000) measurements were also similar before and after 15th day of injection. Preinjection and 1st month of postinjection CCT (p = 0.999), Sim K (p = 0.932), ACD (p = 0.998), ICA (p = 1.000) and IOP (p = 0.741) measurements did not change significantly. Single-dose intravitreal bevacizumab injection does not affect CCT, Sim K, ACD, ICA and IOP in short-term period.

Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.

1982-11-01

The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C was cortisol during the 40-minmore » period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the /sup 3/H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6.« less

Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.

PubMed

Moisseiev, Elad; Anderson, Johnathon D; Oltjen, Sharon; Goswami, Mayank; Zawadzki, Robert J; Nolta, Jan A; Park, Susanna S

2017-10-01

Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline. Two weeks post-injection, fluorescein angiography (FA) and phase-variance optical coherence tomography angiography (pvOCTA) were used to assess retinal perfusion. Retinal thickness was determined by OCT. The extent of retinal neovascularization was quantitated histologically by counting vascular nuclei on the retinal surface. Among eyes with OIR, intravitreal exosome treatment partially preserved retinal vascular flow in vivo and reduced associated retinal thinning; retinal thickness on OCT was 111.1 ± 7.4µm with saline versus 132.1 ± 11.6µm with exosome, p < 0.001. Retinal neovascularization among OIR eyes was reduced with exosome treatment when compared to saline-treated eyes (7.75 ± 3.68 versus 2.68 ± 1.35 neovascular nuclei per section, p < 0.0001). No immunogenicity or ocular/systemic adverse effect was associated with intravitreal exosome treatment. Intravitreal administration of exosomes derived from hMSCs was well tolerated without immunosuppression and decreased the severity of retinal ischemia in this murine model. This appealing novel non-cellular therapeutic approach warrants further exploration.

Intravitreal bevacizumab and dexamethasone implant for treatment of chronic diabetic macular edema.

PubMed

Güler, Emre; Totan, Yüksel; Betül Güragaç, Fatma

2017-06-01

To evaluate anatomical and functional outcomes of intraviteal bevacizumab (IVB) in patients with chronic diabetic macular edema (DME), and the effectivity and safety of dexamethasone implant in those unresponsive to regular IVB treatment. Thirty-five eyes of 35 patients (16 male and 19 female) with chronic DME (central foveal thickness (CFT)  > 275 μm, duration  > 6 months) received three injections of 2.5 mg IVB with six-week intervals. At 18 weeks, dexamethasone implant was applied to patients unresponsive to IVB. Main outcomes were the change in best corrected visual acuity (BCVA), CFT and ocular and systemic adverse effects for both drugs. The patients responsive to IVB were followed up for 36 weeks and those patients receiving dexamethasone implant were followed up for 24 weeks postoperatively. At 18 weeks, the mean BCVA (0.68 ± 0.40 logMAR, p = 0.45) and CFT (453 ± 169 μm, p = 0.58) did not show any significant change compared to baseline (0.74 ± 0.42 logMAR and 521 ± 151 μm, respectively). In 20 patients (%57.1) responsive to IVB, the CFT was significantly improved from 12 to 36 weeks with the mean value of 295 ± 42 μ (p = 0.01). However, no significant difference was observed for BCVA during this period (p = 0.17). Dexamethasone was implanted in 15 eyes (42.8%) unresponsive to IVB at 18 weeks. Statistically significant improvements were observed in BCVA (at postoperative 4 and 12 weeks) and CFT (at postoperative 4, 12 and 24 weeks). In addition, both parameters significantly worsened at 24 weeks compared to 12 weeks (p < 0.001 and p = 0.01, respectively). Patients with chronic DME should be followed in accordance with a fixed treatment protocol combining anti-VEGF and steroid treatments.

Determination of betamethasone and triamcinolone acetonide by GC-NCI-MS in excreta of treated animals and development of a fast oxidation procedure for derivatisation of corticosteroids.

PubMed

Courtheyn, D; Vercammen, J; Logghe, M; Seghers, H; De Wasch, K; De Brabander, H

1998-12-01

The use of corticosteroids in combination with other hormonal substances has long been known to result in increased mass gain with bovines. Practice has demonstrated, however, that even the single use of a glucocorticoid may result in growth promoting effects. In addition to the popular dexamethasone, more recently other corticosteroids have also been misused for fattening purposes. The first part of this study deals with the detection of two of them, namely betamethasone and triamcinolone acetonide. Betamethasone was administered orally to a cow at a dose of 50 mg d-1 for 5 d, then later the same cow was injected intramuscularly with a dose of 50 mg of betamethasone dipropionate. Excretion in urine and faeces was followed with both HPLC-enzyme immunoassay and a previously described method based on negative chemical ionization mass spectrometry (NCI-MS) after oxidation. For the triamcinolone acetonide study a cow was treated with 50 mg d-1 of the drug during a 7 d period. Excretion in faeces was followed with GC-NCI-MS. As triamcinolone acetonide is resistant to the previously described oxidation procedure, however, a hydrolysis step had to be introduced prior to oxidation. In addition to this specific modification necessary for triamcinolone acetonide, in a subsequent part of this study the original oxidation procedure with pyridinium chlorochromate was re-investigated especially to shorten the procedure. With the introduction of potassium dichromate the reaction time could be decreased from 3 h to 10 min.

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

PubMed Central

Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

2011-01-01

BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

Intravitreal Infliximab Injection to Treat Experimental Endophthalmitis.

PubMed

Ondas, Osman; Ates, Orhan; Keles, Sadullah; Yildirim, Kenan; Baykal, Orhan; Karamese, Selina Aksak; Karamese, Murat; Uslu, Hakan; Yildirim, Mustafa; Naldan, Muhammet Emin; Ates, Irem

2017-10-01

The purpose of this study was to compare the use of an intravitreal injection of infliximab and of dexamethasone combined with vancomycin to treat experimental endophthalmitis induced by Staphylococcus epidermidis. The study was conducted between March 25 and April 13, 2012. Twenty-five six-month-old healthy rabbits were used, each weighing 2.5-3 kg. The rabbits were randomized into five groups with five animals per group. Endophthalmitis was induced by 0.1 mL (103 colony-forming units) S. epidermidis in all groups. In group 1, injection was not implemented after the occurrence of endophthalmitis. In groups 2, 3, and 4, the following intravitreal injections were given 24 h after the occurrence of endophthalmitis: group 2, 0.1 mg/0.1 mL vancomycin; group 3, 1 mg/0.1 mL vancomycin and 1 mg/0.1 mL dexamethasone; and group 4, 1 mg/0.1 mL vancomycin and 2 mg/0.1 mL infliximab. Group 5 was the control/uninfected group. The rabbits were clinically assessed each day for seven days. On day 9, a histopathologic evaluation was performed after enucleation. After a clinical evaluation, no statistically significant difference was found between the vancomycin+infliximab and vancomycin+dexamethasone groups (p>0.05). The difference was significant when both groups were compared with the vancomycin group (p<0.001). After the histopathologic evaluation, no statistically significant difference was found among the three groups (p>0.05). An intravitreal injection of infliximab and of dexamethasone combined with vancomycin have similar clinical and histopathologic effects. To supplement the antibiotic treatment of endophthalmitis, infliximab in a safe dose range can be used as an alternative to dexamethasone to suppress inflammation and prevent ocular damage.

Resolution of macular edema in Coats' disease with intravitreal bevacizumab

PubMed Central

Entezari, Morteza; Ramezani, Alireza; Safavizadeh, Ladan; Bassirnia, Nader

2010-01-01

A 13-year-old boy was referred because of visual deterioration in his right eye. The visual acuity was two meters of counting fingers. Indirect ophthalmoscopy and biomicroscopy revealed exudative macular edema as well as tumor-like telangiectatic vessels and exudation in temporal periphery. With diagnosis of Coats' disease (stage II) confirmed by fluorescein angiography, three intravitreal injections of bevacizumab were performed at 6-week intervals. One year after the last injection, there was a significant resolution of macular edema as well as visual acuity improvement to 20/20. This is the first case report in which a distinct improvement in macular edema was observed with intravitreal bevacizumab in Coats' disease. PMID:20029156

[Subretinal neovascular membrane in angioid streaks treated with intravitreal bevacizumab].

PubMed

García-López, A; González-Castaño, C

2014-05-01

Angioid streaks are breaks in Bruch's membrane that may be associated, among others, with pseudoxanthoma elasticum. Its most common complication is the development of subretinal neovascular membranes (SRNVM) and the decreased vision this entails. A 28 year old woman with angioid streaks and SRNVM in the left eye, who received 3 injections of intravitreal bevacizumab, with rapid improvement in vision and stability during 11 months follow up. The finding of angioid streaks led to the diagnosis of pseudoxanthoma elasticum. Intravitreal bevacizumab should be considered as an effective treatment option for choroidal neovascularization associated with angioid streaks. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up

PubMed Central

FAGHIHI, Hooshang; YAHYAPOUR, Hanif; MAHMOUDZADEH, Raziyeh; FAGHIHI, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration. PMID:29392145

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

PubMed

Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

Retinal and optic nerve atrophy induced by intravitreous vincristine in the primate.

PubMed Central

Green, W R

1975-01-01

Vincristine is known to be toxic to neural tissue, where it is thought to react with microtubules and impair axonal transport. Intravitreous vincristing-induced changes of the retina have been reported to be reversible after 10 micrograms. In the present study, the effects of 0.01 to 100 micrograms of intravitreous vincristine in monkeys were studied ophthalmoscopically and by light microscopy and electron microscopy. Retinal degeneration and optic atrophy were evident ophthalmoscopically in two to three weeks. Morphological changes included swelling of retinal neurons, loss of organelles and microtubules and accumulation of fibrillar-granular material. Progression of effects, with plasma membrane rupture and cell death, was observed with all doses of 0.1 micrograms and higher. The retina and optic nerve of monkeys appear to be more sensitive to intravitreous vincristine than are the same structures in certain lower animals. Images FIGURE 10 FIGURE 18 FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 19 FIGURE 20 PMID:813350

Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits.

PubMed

Labrador Velandia, Sonia; Di Lauro, Salvatore; Alonso-Alonso, Maria Luz; Tabera Bartolomé, Soraya; Srivastava, Girish Kumar; Pastor, José Carlos; Fernandez-Bueno, Ivan

2018-01-01

To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits. Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 10 6 cells/ml. Groups 3 and 6 received a high dose of 30 × 10 6 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs. There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected. MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 10 6 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.

Treatment outcomes of reduced-dose intravitreal ganciclovir for cytomegalovirus retinitis.

PubMed

Choopong, Pitipol; Vivittaworn, Kamolporn; Konlakij, Duanphen; Thoongsuwan, Somanus; Pituksung, Auengporn; Tesavibul, Nattaporn

2016-04-18

Cytomegalovirus retinitis (CMVR) is one of the most common opportunistic infection in immunocompromised individuals. Intravitreal ganciclovir injection has been used successfully but no standard regimen was established. Risks of drug toxicity, endophthalmitis, and injection-related complications increased with number and frequency of injection. The aim of this study is to evaluate the outcomes of reduced-dose intravitreal ganciclovir (2 mg/0.04 mL) for the treatment of CMVR. A prospective observational cohort study involving 67 eyes of 49 patients with CMVR was performed. Induction therapy involved intravenous ganciclovir (10 mg/kg/day) for 2 weeks unless contraindicated or patients refused. Patients were then treated with reduced-dose intravitreal ganciclovir every week for 4 weeks, and then every other week until the lesion healed. The patients' demographic data were recorded, and vision parameters were examined every visit. Twenty eyes (29.9 %) presented with initial visual acuities less than 6/60. The majority of patients were diagnosed with CMVR in zones 1 or 2 (63 eyes, 94 %), and, at least, one quadrant of the retina was involved (56 eyes, 83.6 %). Forty-one eyes (61.2 %) completely resolved after treatment within the 6-month follow-up. There was no significant difference in healing time, whether or not patients received induction treatment with intravenous ganciclovir (111.00 ± 12.96 vs 105.00 ± 28.32 days, p = 0.8). Five eyes (12.2 %) of patients with healed CMVR had visual acuities less than 6/60. Reduced-dose intravitreal ganciclovir is a safe and effective treatment option. It provides comparable results to other weekly regimens. Induction with intravenous ganciclovir is not crucial in a resolution of retinitis, although it may be necessary to reduce systemic cytomegalovirus loads and mortality rates. The trial was registered with Thai Clinical Trials Registry (TCTR) on 16 March 2016 - TCTR20160316001 .

Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection.

PubMed

Wessels, Uwe; Zadak, Markus; Reiser, Astrid; Brockhaus, Janis; Ritter, Mirko; Abdolzade-Bavil, Afsaneh; Heinrich, Julia; Stubenrauch, Kay

2018-04-11

High drug concentrations in ocular fluids after intravitreal administration preclude the use of drug-sensitive immunoassays. A drug-tolerant immunoassay is therefore desirable for immunogenicity testing in ophthalmology. Immune complex (IC) antidrug antibody (ADA) assays were established for two species. The assays were compared with the bridging assay in ocular and plasma samples from two preclinical studies. The IC assays showed high drug tolerance, which enabled a reliable ADA detection in ocular fluids after intravitreal administration. The IC assays were superior to the bridging assay in the analysis of ocular fluids with high drug concentrations. The IC assay allows a reliable ADA detection in matrices with high drug concentrations, such as ocular fluids.

Focal macular electroretinograms after intravitreal injections of bevacizumab for age-related macular degeneration.

PubMed

Iwata, Eiji; Ueno, Shinji; Ishikawa, Kohei; Ito, Yasuki; Uetani, Ruka; Piao, Chang-Hua; Kondo, Mineo; Terasaki, Hiroko

2012-06-28

To evaluate the changes in the best-corrected visual acuity (BCVA), macular thickness, and focal macular electroretinograms (FMERGs) after three intravitreal injections of bevacizumab for a choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). The medical records of 18 eyes of 18 patients who had received three consecutive monthly intravitreal injections of bevacizumab were retrospectively studied. The BCVA, macular thickness determined by optical coherence tomography (OCT), and FMERGs were measured before the first injection, and 10 days after each of the intravitreal bevacizumab injections. The number of eyes with improvement in BCVA after the first injection was one (6%), after the second injection was four (22%), and after the third injection was five (28%). The number of eyes with reduction in macular thickness was 4 (33%), 8 (44%), and 10 (56%) after each of the three injections. The number of eyes with increase in b-wave amplitude of the FMERGs was 7 (38%), 6 (33%), and 10 (56%) after each of the three each injections. The mean macular thickness was significantly thinner after the first injection, and the mean BCVA was significantly improved after the second injection. The mean amplitude and implicit time of the b-wave of the FMERGs were significantly improved only after the third injection (P<0.05). All parameters improved but the best was after the third injection, indicating that three monthly intravitreous injections with bevacizumab may be an effective treatment regimen for AMD.

Effect of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy on the Risk of Arterial Thromboembolic Events: A Meta-Analysis

PubMed Central

Lu, Guo-Cai; Wei, Rui-Li

2012-01-01

Background Intravitreal anti-vascular endothelial growth factor (VEGF) monoclonal antibodies are used in ocular neovascular diseases. A consensus has emerged that intravenous anti-VEGF can increase the risk of arterial thromboembolic events. However, the role of intravitreal anti-VEGF in arterial thromboembolism is controversial. Therefore, we did a systematic review and meta-analysis to investigate the effects of intravitreal anti-VEGF on the risk of arterial thromboembolic events. Methods Electronic databases were searched to identify relevant randomized clinical trials comparing intravitreal anti-VEGF with controls. Criteria for inclusion in our meta-analysis included a study duration of no less than 12 months, the use of a randomized control group not receiving any intravitreal active agent, and the availability of outcome data for arterial thromboembolic events, myocardial infarction, cerebrovascular accidents, and vascular death. The risk ratios and 95% CIs were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Results A total of 4942 patients with a variety of ocular neovascular diseases from 13 randomized controlled trials were identified and included for analysis. There was no significant difference between intravitreal anti-VEGF and control in the risk of all events, with risk ratios of 0.87 (95% CI, 0.64 to 1.19) for arterial thromboembolic events, 0.96 (95% CI, 0.55–1.68) for cerebrovascular accidents, 0.69 (95% CI 0.40–1.21) for myocardial infarctions, and 0.68 (95% CI, 0.37–1.27) for vascular death. Conclusions The strength evidence suggests that the intravitreal use of anti-VEGF antibodies is not associated with an increased risk of arterial thromboembolic events. PMID:22829940

High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

PubMed

Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

2016-10-01

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m 2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Intravitreal injections: what do patients prefer? Analysis of patient's satisfaction and preferences about where to perform intravitreal injections.

PubMed

Rodríguez Ramírez, M; del Barrio Manso, M I; Martín Sánchez, M D

2014-12-01

To analyse satisfaction and patient preferences on the location where they receive an intravitreal injection. A survey was conducted with the intention of analysing these patients who attended the macula clinic and have been intervened using an intravitreal injection at least once in the day hospital or in the theatre setting, comparing both locations. The majority of the interviewed patients preferred the day hospital (50.0 versus 37.5%), mostly because of the comfort and the quick service. In patients with severe age-related macular degeneration (AMD) the option is reversed. The overall satisfaction level was positive in both cases (with 87.5% of patients satisfied or very satisfied in the day hospital and 91.1% in the theatre setting). Through the analysis of different aspects of clinical care the assessment was the same or superior for 75.0% of these patients, except in the waiting time. There were no cases of endophthalmitis. In general, patients prefer the clinical intervention in the consulting room than in the theatre setting because of the quicker service. There are several characteristics that can influence this choice and should be taken into account. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Evaluation of Pharmacologic Agents to Suppress Intraocular Cellular Proliferation Following Trauma

DTIC Science & Technology

1986-07-01

Tracttonal Detachment* aniawl op uVeitis agent-- -- 1 (1-4) or control 1 wk 2 wk 4 wk 6 wk 12 wk Gross Lama* Imadi to Injaetica or drug 61 1 D S L C R F...BIBLIOGRAPHY 1. Mimura Y: The effect of colchicine treatment on ocular lesions in Behcet’s disease. Ophthalmol Jpn 26:902-908, 1985. 2. Brown W O... Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 90:810, 1980. 9. Trese MT, Spitznas M

Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging.

PubMed

Kim, Hyuncheol; Lizak, Martin J; Tansey, Ginger; Csaky, Karl G; Robinson, Michael R; Yuan, Peng; Wang, Nam Sun; Lutz, Robert J

2005-02-01

Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.

Accelerated ischemic vascular retinopathy after intravitreally injected bevacizumab for central retinal vein occlusion in elderly patients

PubMed Central

Isola, Vincenzo; Pece, Alfredo; Massironi, Claudio; Reposi, Simone; Dimastrogiovanni, Fabio

2013-01-01

Background: Ischemic changes in the retinal circulation are an uncommon but severe adverse vascular reaction to intravitreal bevacizumab (Avastin®, Genentech, San Francisco, CA, USA/Roche, Basel, Switzerland) for central retinal vein occlusion (CRVO). In the two cases reported here, ischemic changes in the retina vasculature following intravitreal bevacizumab for CRVO were observed with the aim of describing the clinical and angiographic features of these changes. Methods: Two elderly patients with recent-onset CRVO received one off-label intravitreal injection of bevacizumab 0.05 mL/1.25 mg. Results: In Case 1, the patient’s pre-treatment visual acuity was 20/400. At 3 weeks post injection, the patient could count fingers at a distance of 1 ft (30 cm) and fluorescein angiography showed reduction in intraretinal hemorrhages and areas of retinal non-perfusion. However, at 6 weeks these were markedly increased compared with those seen in the photograph taken 3 weeks after treatment. In Case 2, the patient’s pre-treatment visual acuity was 20/200. At 1 month post injection, vision had decreased to 20/400 and fluorescein angiography showed severe macular ischemia with a remarkable capillary dropout throughout the macula. Conclusion: Ischemic retinal injury may be an uncommon but severe adverse vascular reaction to intravitreal bevacizumab for CRVO. Although progression of retinal ischemia in CRVO could be observed shortly after intravitreal bevacizumab, whether this is a drug- or procedure-related effect or part of the natural history of the condition remains uncertain. PMID:23467497

Intravitreal properties of porous silicon photonic crystals

PubMed Central

Cheng, L; Anglin, E; Cunin, F; Kim, D; Sailor, M J; Falkenstein, I; Tammewar, A; Freeman, W R

2009-01-01

Aim To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery. Methods A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology. Results No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases. PMID:18441177

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review.

PubMed

Smith, Stephen J; Smith, Brian D; Mohney, Brian G

2014-03-01

To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma. PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans. Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments. Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Zhang, Wei; Lanza, Robert; Lu, Shi-Jiang; Jonas, Jost B; Xu, Liang

2017-09-01

To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate-buffered saline (PBS). We examined the vasculature integrity in the mice with OIR, the blood-retina barrier in the rats with induced DR, and retinal thickness and retinal ganglion cell density in retina flat mounts of the rats with the retinal ischaemic-reperfusion retinopathy. In the OIR model, the study group versus control groups showed a significantly (p < 0.001) smaller retinal avascular area [5.1 ± 2.7%;n = 18 animals versus 12.2 ± 2.8% (PBS group; n = 10 animals) and versus 11.8 ± 3.7% (EC group; n = 8 animals)] and less retinal neovascularization [6.3 ± 2.5%;n = 18 versus 15.2 ± 6.3% (n = 10; PBS group) and versus 15.8 ± 3.3% (n = 8; EC group)]. On retinal flat mounts, hESC-HBs were integrated into damaged retinal vessels and stained positive for PECAM (CD31) as EC marker. In the DR model, the study group versus the EC control group showed a significantly (p = 0.001) better blood-retina barrier function as measured at 2 days after the intravitreal injections [study group: 20.2 ± 12.8 μl/(g × hr); n = 6; versus EC control group: 52.9 ± 9.9 μl/(g × hr; n = 6)]. In the retinal ischaemia-reperfusion model, the groups did not differ significantly in retinal thickness and retinal ganglion cell density at 2, 5 and 7 days after baseline. By integrating into

BEVACIZUMAB LEVELS IN BREAST MILK AFTER LONG-TERM INTRAVITREAL INJECTIONS.

PubMed

McFarland, Trevor J; Rhoads, Andrew D; Hartzell, Matthew; Emerson, Geoffrey G; Bhavsar, Abdhish R; Stout, J Timothy

2015-08-01

The purpose of this study is to determine whether bevacizumab is detectable in the breast milk of nursing mothers. Breast milk samples were collected from 2 patients receiving monthly intravitreal bevacizumab injections for choroidal neovascularization over the course of 16 months. Enzyme-linked immunosorbent assay and Western blot analysis was used to determine the levels of bevacizumab in the milk samples. An enzyme-linked immunosorbent assay was developed using antibodies specific to bevacizumab in which the sensitivity threshold was 3 ng/mL. All breast milk samples assayed from the two patients actively undergoing treatment did not have detectable levels of bevacizumab. Samples collected 1.5 hours and 7 hours after an injection and 2 randomly chosen samples were negative by Western blot analysis. A sensitive assay to detect bevacizumab in breast milk samples assayed suggests that intravitreal injections do not result in detectable bevacizumab in breast milk.

Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study.

PubMed

Ogura, Yuichiro; Roider, Johann; Korobelnik, Jean-François; Holz, Frank G; Simader, Christian; Schmidt-Erfurth, Ursula; Vitti, Robert; Berliner, Alyson J; Hiemeyer, Florian; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert

2014-11-01

To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). Randomized, double-masked, phase 3 study. A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of Intravitreal Bevacizumab on Vascular Endothelial Growth Factor Expression in Patients with Proliferative Diabetic Retinopathy

PubMed Central

Chung, Eun Jee; Kang, Shin Jeong; Koo, Ja Seung; Choi, Yoon Jung; Grossniklaus, Hans E.

2011-01-01

Purpose To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco, CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). Materials and Methods Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done. Results The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043). Conclusion Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug. PMID:21155048

Determination of physicochemical properties and degradation kinetics of triamcinolone acetonide palmitate in vitro.

PubMed

Peng, Cuilian; Liu, Cong; Tang, Xing

2010-12-01

Triamcinolone acetonide palmitate (TAP) is a lipophilic prodrug of triamcinolone acetonide (TAA) to improve the insoluble TAA physicochemical properties for the preparation of emulsions. This investigation has focused on the preformulation study of TAP, including its physicochemical properties and hydrolysis kinetics in vitro. The solubility of TAP in medium-chain triglyceride is about twice greater than that in soybean oil (long-chain triglyceride) (19.17 versus 9.55 mg/g) at 25°C, and in all investigated cases, lecithin (80, 160, and 240 mg/g) as solubilizer provided increased solubility of drugs in medium-chain triglyceride and long-chain triglyceride, whereas the maximum water solubility of TAP was 0.10 μg/mL. The partition coefficient (log P) of TAP was 5.79 irrespective of the pH conditions. The hydrolysis of TAP followed pseudo-first-order kinetics in aqueous solutions, and the stable pH range was from pH 5.0 to 9.0. The in vitro enzymolysis kinetics of TAP in rat plasma and liver homogenate was evaluated by measuring the decrease of TAP as well as the increase of TAA at 37°C for 96 hours. The results demonstrated that the TAP may be hydrolyzed mainly by rat plasma esterase and, to a minor extent, by liver esterase, and the hydrolysis half-life of TAP in 100% rat plasma was 17.53 ± 6.85 hours at pH 7.4. All these results indicated that TAP had successfully obtained higher lipid-soluble property for the preparation of intravenous emulsion and may be an effective prodrug for sustained release of TAA in vivo.

Ocular inflammatory effects of intravitreally-injected tumor necrosis factor.

PubMed Central

Rosenbaum, J. T.; Howes, E. L.; Rubin, R. M.; Samples, J. R.

1988-01-01

Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3263050

Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

PubMed

Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

2015-03-01

Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

Effects of music therapy on intravitreal injections: a randomized clinical trial.

PubMed

Chen, Xuejing; Seth, Rajeev K; Rao, Veena S; Huang, John J; Adelman, Ron A

2012-08-01

To investigate the effects of music therapy on anxiety, perceived pain, and satisfaction in patients undergoing intravitreal injections in the outpatient setting. This is a randomized clinical trial. Seventy-three patients were recruited from the retina clinic at 1 institution and randomized into a music therapy (n=37) or control (n=36) group. Prior to injection, patients completed the state portion of the Spielberger State Trait Anxiety Inventory (STAI-S). The music therapy group listened to classical music through computer speakers while waiting for and during the injection. The control group underwent the injection in the same setting without music. Afterward, all patients completed another STAI-S and a satisfaction and pain questionnaire. The main outcome measures were objective anxiety derived from STAI-S scores and subjective pain and anxiety from the post procedure questionnaire. The music therapy group had a greater decrease in anxiety than the control group (P=0.0480). Overall, 73% of all patients requested music for future injections (P=0.0001). The music therapy group (84%) requested music in future injections more frequently than the control group (61%) (P=0.0377). Both groups reported similar levels of pain (P=0.5879). Classical music before and during intravitreal injections decreases anxiety in patients without decreasing pain. Most patients desire to have music during future injections. Music therapy is a low-cost, easy, safe intervention that reduces anxiety during intravitreal injections in the outpatient setting.

Characteristics of patients with neovascular age-related macular degeneration who are non-responders to intravitreal aflibercept.

PubMed

Hara, Chikako; Wakabayashi, Taku; Toyama, Hiroshi; Fukushima, Yoko; Sayanagi, Kaori; Sato, Shigeru; Sakaguchi, Hirokazu; Nishida, Kohji

2018-06-15

To investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD). Retrospective, interventional, consecutive case series. Three hundred and sixty-five eyes of 365 patients with AMD who underwent 3 monthly intravitreal aflibercept treatments with follow-up for at least 12 months were investigated. Treatment response was evaluated as follows. Responders were defined as those with complete resolution of exudation, including intraretinal oedema, subretinal fluid and pigment epithelial detachment, or more than a 100 µm decrease of central retinal thickness at 3 months compared with baseline. Non-responders were defined as patients exhibiting an increase in exudation or a decreased central retinal thickness of less than 100 µm. Nineteen (5.2%) of 365 eyes were identified as non-responders. The remaining were responders to intravitreal aflibercept. The non-responders group was significantly associated with choroidal vascular hyperpermeability on indocyanine green angiography and lower frequency of subretinal hyper-reflective materials on optical coherence tomography. The central choroidal thickness at baseline and after 3 monthly injections tended to be thicker in the non-responder group than the responder group, although the differences did not meet statistical significance (p=0.066 and p=0.051, respectively). Additional treatments with either intravitreal ranibizumab or PDT in combination with aflibercept were effective in 15 (79%) of 19 non-responders. Intravitreal aflibercept is effective for treating eye pathology in most naïve AMD cases. However, non-responsiveness may occur in small subgroup of patients with choroidal vascular hyperpermeability. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly

Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep

PubMed Central

Cakmak Argun, Tugba; Yalcin Tok, Ozlem; Tok, Levent; Yilmaz, Gulsen; Meric Yilmaz, Fatma; Gunes, Alime; Argun, Mehmet; Butuner, Osman

2017-01-01

AIM To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period. PMID:28730108

Intravitreal bevacizumab (Avastin) treatment of diffuse diabetic macular edema in an Indian population

PubMed Central

Sinha, Subijay

2007-01-01

Background: To report the anatomic and visual acuity response after intravitreal bevacizumab (Avastin) in patients with diffuse diabetic macular edema. Design: Prospective, interventional case series study. Materials and Methods: This study included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic macular edema with a mean age of 59 years who were treated with two intravitreal injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome measures were 1) early treatment diabetic retinopathy study visual acuity, 2) central macular thickness by optical coherence tomography imaging. Each was evaluated at baseline and follow-up visits. Results: All the eyes had received some form of laser photocoagulation before (not less than six months ago), but all of these patients had persistent diffuse macular edema with no improvement in visual acuity. All the patients received two injections of bevacizumab at an interval of six weeks per eye. No adverse events were observed, including endophthalmitis, inflammation and increased intraocular pressure or thromboembolic events in any patient. The mean baseline acuity was 20/494 (log Mar=1.338±0.455) and the mean acuity at three months following the second intravitreal injection was 20/295 (log Mar=1.094±0.254), a difference that was highly significant ( P =0.008). The mean central macular thickness at baseline was 492 µm which decreased to 369 µm ( P =0.001) at the end of six months. Conclusions: Initial treatment results of patients with diffuse diabetic macular edema not responding to previous photocoagulation did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular thickness and improvement in visual acuity at three months but the effect was somewhat blunted, though still statistically significant at the end of six months. PMID:17951903

Immediate effect of intravitreal injection of bevacizumab on intraocular pressure

PubMed Central

Lemos-Reis, Ricardo; Moreira-Gonçalves, Nuno; Melo, António B; Carneiro, Ângela M; Falcão-Reis, Fernando M

2014-01-01

Purpose To investigate the immediate effect of intravitreal injection of bevacizumab on intraocular pressure (IOP). Methods This was a prospective and nonrandomized study. A total of 291 eyes with macular edema or active choroidal neovascularization were submitted to a single 1.25 mg (0.05 mL) bevacizumab intravitreal injection. Intraocular pressure was measured with an Icare® tonometer immediately before and after injection in a seated position. The presence of subconjunctival reflux was recorded. The fellow eye served as the control. Results Mean preoperative IOP was 18.0±5.9 mmHg in the treated eye versus 16.9±6.0 mmHg in the fellow eye. Mean postoperative IOP was 42.1±14.5 mmHg in the treated eye versus 17.5±6.0 mmHg in the fellow eye. The IOP variation was statistically significant in both cases and controls (P<0.001 and P=0.003, respectively), and this increase was higher in cases than in controls (P<0.001). Postoperative IOPs higher than 50 mmHg were achieved in 32.0% of the eyes. Subconjunctival reflux was present in 21.3% and determined a lower IOP rise (P<0.001). Tested variables (glaucoma, phakic status, and sex) did not have a statistically significant effect on IOP rise or subconjunctival reflux. Conclusion IOP increases with intravitreal bevacizumab injection, reaching 50 mmHg or more in about one third of patients. A higher IOP is expected if no subconjunctival reflux occurs. The baseline IOP does not influence the incidence of subconjunctival reflux. The clinical relevance of these facts has yet to be clarified. PMID:25092962

Fundus spectroscopy and studies in retinal oximetry using intravitreal illumination

NASA Astrophysics Data System (ADS)

Salyer, David Alan

This dissertation documents the development of a new illumination technique for use in the studies of retinal oximetry and fundus spectroscopy. Intravitreal illumination is a technique where the back of the eye is illuminated trans-sclerally using a scanning monochromator coupled into a fiber optic illuminator. Retinal oximetry is the process of measuring the oxygen saturation of blood contained in retinal vessels by quantitative measurement of the characteristic color shift seen as blood oxygen saturation changes from oxygenated blood (reddish) to deoxygenated blood (bluish). Retinal oximetry was first attempted in 1963 but due to a variety of problems with accuracy and difficulty of measurement, has not matured to the point of clinical acceptability or commercial viability. Accurate retinal oximetry relies in part on an adequate understanding of the spectral reflectance characteristics of the fundus. The use of intravitreal illumination allows new investigations into the spectral reflectance properties of the fundus. The results of much research in fundus reflectance and retinal oximetry is detailed in this document, providing new insight into both of these related fields of study. Intravitreal illumination has been used to study retinal vessel oximetry and fundus reflectometry resulting in several important findings that are presented in this document. Studies on enucleated swine eyes have provided new insight into the bidirectional reflectance distribution function of the fundus. Research on live swine has shown accurate measurement of retinal vessel oxygen saturation and provided the first in vivo spectral transmittance measurement of the sensory retina. A secondary discovery during this research suggests that vitrectomy alters the retinal vasculature, an finding that should spawn new research in its own right.

Outcome of cytomegalovirus retinitis in immunocompromised patients without Human Immunodeficiency Virus treated with intravitreal ganciclovir injection.

PubMed

Agarwal, Aniruddha; Kumari, Neha; Trehan, Amita; Khadwal, Alka; Dogra, Mangat R; Gupta, Vishali; Sharma, Aman; Gupta, Amod; Singh, Ramandeep

2014-09-01

To study the outcomes of treatment with intravitreal ganciclovir injection for cytomegalovirus (CMV) retinitis in patients without Human Immunodeficiency Virus (HIV) infection. In this retrospective cohort study, demographic and clinical characteristics of patients with CMV retinitis without HIV were noted. Patients received intravitreal ganciclovir injection (2 mg/0.1 ml) alone until quiescence. The outcome measures were time taken for the lesions to heal, number of injections, change in best-corrected visual acuity (BCVA), recurrence of retinitis, occurrence of immune recovery uveitis (IRU) or injection-related complications and retinal detachment (RD). 18 eyes of ten patients (six males) with mean age of 33.7 years from June 2004 to March 2013 were included. Thirteen eyes with active lesions (mean BCVA of 0.51 ± 0.41) received 5.54 ± 3.36 intravitreal ganciclovir injections with complete healing within 1.81 ± 1.25 months. The final BCVA was 0.43 ± 0.52. IRU was observed in six eyes (33.33%) and RD developed in one eye. One eye had recurrence 1 month after stopping ganciclovir injections. The rest of the patients had recurrence-free follow-up at 9.46 ± 12.42 months. Non-HIV patients with CMV retinitis can be successfully treated with intravitreal ganciclovir injection alone, avoiding the systemic side effects of systemic anti-CMV therapy.

Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.

PubMed

Li, Huiling; Palamoor, Mallika; Jablonski, Monica M

2016-10-01

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.

Endophthalmitis after intravitreal injections. Incidence, management and prognosis.

PubMed

Tarragó, R; Olea, J L; Ramírez, C; Escudero, L

2017-03-01

To assess the rate of endophthalmitis after intravitreal injection (IVI) in a «clean room» of a single health centre, following the guidelines of the Spanish Vitreo-Retinal Society (SERV). An analysis was performed on the culture specimens, response to treatment, and final outcomes (guidelines). A retrospective, observational study was conducted on a consecutive case series of patients diagnosed with infectious endophthalmitis after IVI in a single health centre between 2010 and 2015. Intravitreal and systemic treatment was given following the SERV guidelines. The patients were followed up the case was resolved. There were 5 cases of endophthalmitis out of 9467 IVI (incidence 0.053%). Positive cultures were obtained in aqueous and/or vitreous fluid in all cases, with Staphylococcus epidermidis being involved in 4 out of 5 cases. In 2 cases, final visual acuity was non-light perception due to intractable retinal detachments after resolution of the infectious process. IVI performed in a «clean room» have a low incidence of endophthalmitis. The most common infectious agent was Staphylococcus species. In 2 cases the functional prognosis was poor. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Randomized Comparison of Topical Betamethasone Valerate Foam, Intralesional Triamcinolone Acetonide and Tacrolimus Ointment in Management of Localized Alopecia Areata

PubMed Central

Kuldeep, CM; Singhal, Himanshu; Khare, Ashok Kumar; Mittal, Asit; Gupta, Lalit K; Garg, Anubhav

2011-01-01

Background: Alopecia areata (AA) is a common, non-scarring, patchy loss of hair at scalp and elsewhere. Its pathogenesis is uncertain; however, auto-immunity has been exemplified in various studies. Familial incidence of AA is 10-42%, but in monozygotic twins is 50%. Local steroids (topical / intra-lesional) are very effective in treatment of localized AA. Aim: To compare hair regrowth and side effects of topical betamethasone valerate foam, intralesional triamcinolone acetonide and tacrolimus ointment in management of localized AA. Materials and Methods: 105 patients of localized AA were initially registered but 27 were drop out. So, 78 patients allocated at random in group A (28), B (25) and C (25) were prescribed topical betamethasone valerate foam (0.1%) twice daily, intralesional triamcinolone acetonide (10mg/ml) every 3 weeks and tacrolimus ointment (0.1%) twice daily, respectively, for 12 weeks. They were followed for next12 weeks. Hair re-growth was calculated using “HRG Scale”; scale I- (0-25%), S II-(26-50%), S III - (51-75%) and S IV- (75-100%). Results: Hair re-growth started by 3 weeks in group B (Scale I: P<0.03), turned satisfactory at 6 weeks in group A and B (Scale I: P<0.005, Scale IV: P<0.001)), good at 9 weeks (Scale I: P<0.0005, Scale IV: P<0.00015), and better by 12 weeks of treatment (Scale I: P<0.000021, Scale IV: P<0.000009) in both A and B groups. At the end of 12 weeks follow-up hair re-growth (>75%, HRG IV) was the best in group B (15 of 25, 60%), followed by A (15 of 28, 53.6%) and lastly group-C (Nil of 25, 0%) patients. Few patients reported mild pain and atrophy at injection sites, pruritus and burning with betamethasone valerate foam and tacrolimus. Conclusion: Intralesional triamcinolone acetonide is the best, betamethasone valerate foam is better than tacrolimus in management of localized AA. PMID:21769231

Intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases.

PubMed

HodjatJalali, Kamran; Mehravaran, Shiva; Faghihi, Hooshang; Hashemi, Hassan; Kazemi, Pegah; Rastad, Hadith

2017-09-01

To investigate the short-term outcomes after intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases. Thirty-four eyes of 29 patients with age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion (RVO) received a single dose intravitreal injection of 0.05 ml ziv-aflibercept (1.25 mg). Visual acuity, spectral domain optical coherence tomography (SD-OCT) activity, and possible side effects were assessed before and at 1 week and 1 month after the intervention. At 1 month after treatment, mean central macular thickness (CMT) significantly decreased from 531.09 μm to 339.5 μm ( P  < 0.001), and no signs of side effects were observed in any subject. All patients responded to treatment in terms of reduction in CMT. The improvement in visual acuity was statistically non-significant. Our findings suggest that a single dose intravitreal injection of ziv-aflibercept may have acceptable relative safety and efficacy in the treatment of patients with intraocular vascular disease. The trial was registered in the Iranian Registry of Clinical Trials (IRCT2015081723651N1).

Humoral Immune Response After Intravitreal But Not After Subretinal AAV8 in Primates and Patients.

PubMed

Reichel, Felix F; Peters, Tobias; Wilhelm, Barbara; Biel, Martin; Ueffing, Marius; Wissinger, Bernd; Bartz-Schmidt, Karl U; Klein, Reinhild; Michalakis, Stylianos; Fischer, M Dominik

2018-04-01

To study longitudinal changes of anti-drug antibody (ADA) titers to recombinant adeno-associated virus serotype 8 (rAAV8) capsid epitopes in nonhuman primates (NHP) and patients. Three groups of six NHP each received subretinal injections (high dose: 1 × 1012 vector genomes [vg], low dose: 1 × 1011 vg, or vehicle only). Four additional animals received intravitreal injections of the high dose (1 × 1012 vg). Three patients received 1 × 1010 vg as subretinal injections. ELISA quantified ADA levels at baseline and 1, 2, 3, 7, 28, and 90 days after surgery in NHP and at baseline and 1, 3, and 6 months after surgery in patients. Two out of 22 animals lacked ADA titers at baseline and developed low ADA titers toward the end of the study. Titers in the low-dose group stayed constant, while two of six animals from the high-dose group developed titers that rose beyond the range of the assay. All animals from the intravitreal control group showed a rise in ADA titer by day 7 that peaked at day 28. Preliminary data from the clinical trial (NCT02610582) show no humoral immune response in patients following subretinal delivery of 1 × 1010 vg. No significant induction of ADA occurred in NHP when mimicking the clinical scenario of subretinal delivery with a clinical-grade rAAV8 and concomitant immunosuppression. Likewise, clinical data showed no humoral immune response in patients. In contrast, intravitreal delivery was associated with a substantial humoral immune response. Subretinal delivery might be superior to an intravitreal application regarding immunologic aspects.

Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.

PubMed

Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2013-11-15

To investigate the potential therapeutic benefit of intravitreally implanted dental pulp stem cells (DPSCs) on axotomized adult rat retinal ganglion cells (RGCs) using in vitro and in vivo neural injury models. Conditioned media collected from cultured rat DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were assayed for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) secretion using ELISA. DPSCs or BMSCs were cocultured with retinal cells, with or without Fc-TrK inhibitors, in a Transwell system, and the number of surviving βIII-tubulin⁺ retinal cells and length/number of βIII-tubulin⁺ neurites were quantified. For the in vivo study, DPSCs or BMSCs were transplanted into the vitreous body of the eye after a surgically induced optic nerve crush injury. At 7, 14, and 21 days postlesion (dpl), optical coherence tomography (OCT) was used to measure the retinal nerve fiber layer thickness as a measure of axonal atrophy. At 21 dpl, numbers of Brn-3a⁺ RGCs in parasagittal retinal sections and growth-associated protein-43⁺ axons in longitudinal optic nerve sections were quantified as measures of RGC survival and axon regeneration, respectively. Both DPSCs and BMSCs secreted NGF, BDNF, and NT-3, with DPSCs secreting significantly higher titers of NGF and BDNF than BMSCs. DPSCs, and to a lesser extent BMSCs, promoted statistically significant survival and neuritogenesis/axogenesis of βIII-tubulin⁺ retinal cells in vitro and in vivo where the effects were abolished after TrK receptor blockade. Intravitreal transplants of DPSCs promoted significant neurotrophin-mediated RGC survival and axon regeneration after optic nerve injury.

Dexamethasone implant in silicone oil: in vitro behavior.

PubMed

Flores-Villalobos, Erick Omar; Ramírez-Estudillo, J Abel; Robles-Contreras, Atzin; Oliva-Ramírez, Jacqueline L

2018-01-01

To determine the effect of the silicone on the dexamethasone intravitreal implant. Basic, experimental, prospective and transversal study performed at the hospital "Nuestra Señora de la Luz" in Mexico City. One dexamethasone implant was placed in a test tube with 4 mL of each tamponade medium: 1000cS, 5000cS and heavy silicone oil; basic saline solution was used as the control medium. Photographs were taken weekly for 12 months. 200 µL samples were taken from each medium at 24 h, 1, 2 weeks and monthly for 12 months. ELISA test was performed to quantify dexamethasone release in every sample. An inflammatory stimulus was created and later exposed it to every sample in order to test their anti-inflammatory capacity by cytokine analysis using cytometric bead array. Statistically significant results were obtained with p < 0.05. Photographic follow-up showed disintegration of the implant in control medium. Implants in silicone oil suffered no changes during follow-up. Dexamethasone levels in control medium showed stability from month 2 to 12. Silicone oil mediums showed irregular dexamethasone release during the 1 year period. Dexamethasone in control medium had inhibitory effects on TNF-α starting at 24 h (p < 0.001) and remained stable. Dexamethasone in 1000cS silicone oil showed inhibitory effects from month 2 (p < 0.001) until month 6 (p < 0.001). Implants in denser silicone oils showed no inhibitory effects in any of the samples. Denser mediums altered the implant pharmacokinetics and showed no anti-inflammatory effects even when concentrations were quantified at levels similar to control medium in vitro.

[Neurodevelopment in patients with retinopathy of prematurity treated with intravitreal bevacizumab. Case series].

PubMed

Martínez-García, Sarah Melania; Hernández-Da Mota, Sergio Eustolio; Rubio-Rangel, Araceli; Rojas-Flores, Ignacio; Vieyra-López, Mayra Edith; Martínez-Castellanos, María Ana; Zavala-Martínez, María Teresa; Gómez García, Anel

Retinopathy of prematurity (ROP) is an eye disease caused by an alteration in retinal vasculogenesis that may lead to partial or complete vision loss with a harmful impact in terms of neurodevelopment. The purpose of the present study was to determine the neurodevelopment in patients with type i retinopathy of prematurity treated with intravitreal bevacizumab. Case series. The inclusion criteria were: patients with type I ROP treated with a dose of 0.625mg/0.025ml of intravitreal bevacizumab. Demographic data and comorbidities were documented. Neurodevelopment was evaluated with the screening test of the Bayley Scale of Infant Development (BSID) in all patients between 11 and 28 weeks of age. Seven patients were included in the study. Four patients showed normal neurodevelopment according to the overall scores of the BSID scale. The distribution of high risk for neurodevelopmental delay in the different areas evaluated were as follows: 3 patients presented it in the cognitive area, one in the receptive communication area, one in the expressive area, one in the fine motor skills and 3 patients in the gross motor skills area. In these case series, the majority of patients treated with intravitreal bevacizumab for ROP showed normal neurodevelopment scores. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Retinoblastoma Vitreous Seed Clouds (Class 3): A Comparison of Treatment with Ophthalmic Artery Chemosurgery with or without Intravitreous and Periocular Chemotherapy.

PubMed

Francis, Jasmine H; Iyer, Saipriya; Gobin, Y Pierre; Brodie, Scott E; Abramson, David H

2017-10-01

To compare the efficacy and toxicity of treating class 3 retinoblastoma vitreous seeds with ophthalmic artery chemosurgery (OAC) alone versus OAC with intravitreous chemotherapy. Retrospective cohort study. Forty eyes containing clouds (class 3 vitreous seeds) of 40 retinoblastoma patients (19 treated with OAC alone and 21 treated with OAC plus intravitreous and periocular chemotherapy). Ocular survival, disease-free survival and time to regression of seeds were estimated with Kaplan-Meier estimates. Ocular toxicity was evaluated by clinical findings and electroretinography: 30-Hz flicker responses were compared at baseline and last follow-up visit. Continuous variables were compared with Student t test, and categorical variables were compared with the Fisher exact test. Ocular survival, disease-free survival, and time to regression of seeds. There were no disease- or treatment-related deaths and no patient demonstrated externalization of tumor or metastatic disease. There was no significant difference in the age, laterality, disease, or disease status (treatment naïve vs. previously treated) between the 2 groups. The time to regression of seeds was significantly shorter for eyes treated with OAC plus intravitreous chemotherapy (5.7 months) compared with eyes treated with OAC alone (14.6 months; P < 0.001). The 18-month Kaplan-Meier estimates of disease-free survival were significantly worse for the OAC alone group: 67.1% (95% confidence interval, 40.9%-83.6%) versus 94.1% (95% confidence interval, 65%-99.1%) for the OAC plus intravitreous chemotherapy group (P = 0.05). The 36-month Kaplan-Meier estimates of ocular survival were 83.3% (95% confidence interval, 56.7%-94.3%) for the OAC alone group and 100% for the OAC plus intravitreous chemotherapy group (P = 0.16). The mean change in electroretinography responses was not significantly different between groups, decreasing by 11 μV for the OAC alone group and 22 μV for the OAC plus intravitreous chemotherapy

Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

PubMed Central

Jeon, Sohee; Lee, Won Ki

2014-01-01

Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months. PMID:25143708

Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration.

PubMed

Reis, Gustavo Msm; Grigg, John; Chua, Brian; Lee, Anne; Lim, Ridia; Higgins, Ralph; Martins, Alessandra; Goldberg, Ivan; Clement, Colin I

2017-01-01

The aim of this article is to evaluate the rate of patients developing sustained elevated intraocular pressure (IOP) after ranibizumab (Lucentis) intravitreal (IVT) injections. This is a retrospective study. Charts of 192 consecutive patients receiving Lucentis for age-related macular degeneration (AMD) were retrospectively reviewed. We enrolled patients with at least two IOP measurements between injections. Elevated IOP was defined as >21 mm Hg with an increase of at least 20% from baseline. Noninjected contralateral eyes of the same patient cohort were used as control. Primary outcome was defined as elevated IOP. Secondary outcomes were presence and type of glaucoma, number of injections, and time to IOP elevation. Elevated IOP occurred at a significantly higher rate in eyes receiving IVT ranibizumab (7.47%; n = 9) compared with control (0.93%; n = 1). Patients with preexisting glaucoma or ocular hypertension (OHT) were more likely to develop elevated IOP after IVT ranibizumab injection. Intravitreal ranibizumab injections are associated with sustained IOP elevation in some eyes. Reis GMSM, Grigg J, Chua B, Lee A, Lim R, Higgins R, Martins A, Goldberg I, Clement CI. The Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration. J Curr Glaucoma Pract 2017;11(1):3-7.

Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study.

PubMed

Brown, David M; Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Sandbrink, Rupert; Zhu, Xiaoping; Haller, Julia A

2013-03-01

To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO). Randomized controlled trial. This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52. At week 24, 56.1% of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1% of sham + IAI PRN patients (P < .001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure. Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

Incidence of Endophthalmitis after Intravitreal Bevacizumab using Aliquots Prepared On-site in 2 Operating Rooms in Kuwait

PubMed Central

Wani, Vivek B.; Al-Kandari, Jamal; Sabti, Khalid; Aljassar, Faisal; Qali, Hussain; Kumar, Niranjan; Uboweja, Anilkumar; Al-Sabah, Khalid; Diab, Fahad A.; Al-Rashidi, Saleh

2016-01-01

Purpose: To report the incidence of endophthalmitis after intravitreal injection of bevacizumab and the outcomes of treatment of endophthalmitis at two centers in Kuwait. Subjects and Methods: The aliquots of bevacizumab were prepared under aseptic precautions and administered in the operating theater on the same day at both centers. All patients received antibiotic drops after injection of bevacizumab. Data were collected on the number of cases that received intravitreal bevacizumab (IVB) and those that developed endophthalmitis were identified at the two centers. All cases of endophthalmitis received an intravitreal antibiotic injection and additional treatments as warranted. Data were collected on the outcomes of endophthalmitis treatment. Results: There were 5 cases of endophthalmitis among a total of 5429 injections (0.09%: Confidence interval: 0.084–0.1). The incidence was 3 cases among 4690 (0.06%) and 2 cases among 739 injections (0.027%) at each center, respectively (P = 0.08). Four cases of endophthalmitis were culture-positive and organisms isolated were, coagulase negative Staphylococcus in 2 cases, Staphylococcus lugdunensis and Streptococcus pneumoniae in 1 case each. The final visual acuity was better than pre-IVB in 3 cases, same as pre-IVB in 1 case and worse in 1 case with streptococcal infection. No eyes developed phthisis bulbi or required enucleation. Conclusions: The incidence of endophthalmitis after intravitreal injection of bevacizumab using aliquots prepared in the operating room is comparable to other studies. There were no clusters of endophthalmitis cases. PMID:26957841

Intravitreal Aflibercept Injection in Eyes With Substantial Vision Loss After Laser Photocoagulation for Diabetic Macular Edema: Subanalysis of the VISTA and VIVID Randomized Clinical Trials.

PubMed

Wykoff, Charles C; Marcus, Dennis M; Midena, Edoardo; Korobelnik, Jean-François; Saroj, Namrata; Gibson, Andrea; Vitti, Robert; Berliner, Alyson J; Williams Liu, Zinaria; Zeitz, Oliver; Metzig, Carola; Schmelter, Thomas; Heier, Jeffrey S

2016-12-22

Information on the effect of anti-vascular endothelial growth factor therapy in eyes with diabetic macular edema (DME) with vision loss after macular laser photocoagulation is clinically valuable. To evaluate visual and anatomic outcomes in a subgroup of macular laser photocoagulation treatment control (hereafter laser control) eyes with substantial vision loss receiving treatment with intravitreal aflibercept injection. This investigation was a post hoc analysis of a subgroup of laser control eyes in 2 phase 3 trials-VISTA (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) and VIVID (Intravitreal Aflibercept Injection in Vision Impairment Due to DME)-in a multicenter setting. One hundred nine laser control eyes with center-involving DME were included. Treatment with intravitreal aflibercept injection (2 mg) every 8 weeks after 5 monthly doses with sham injections on nontreatment visits starting at week 24 was initiated on meeting prespecified criteria of at least a 10-letter visual acuity loss at 2 consecutive visits or at least a 15-letter visual acuity loss from the best previous measurement at 1 visit and vision not better than at baseline. Visual and anatomic outcomes in a subgroup of laser control eyes receiving treatment with intravitreal aflibercept injection. Through week 100, a total of 63 of 154 eyes (40.9%) in VISTA and 46 of 133 eyes (34.6%) in VIVID initially randomized to laser control received treatment with intravitreal aflibercept injection. The median time from week 24 to the first intravitreal aflibercept injection treatment was 34.0 (VISTA) and 83.5 (VIVID) days. In this subgroup, the mean (SD) visual gain from baseline to week 100 was 2.2 (12.5) (VISTA) and 3.8 (10.1) (VIVID) letters. At the time of intravitreal aflibercept injection initiation, these eyes had a mean (SD) loss of 11.0 (10.1) (VISTA) and 10.0 (6.5) (VIVID) letters from baseline, and they subsequently gained a mean (SD) of 17.4 (9.7) (VISTA

Treatment of unilateral zone I cytomegalovirus retinitis in acute lymphoblastic leukemia with oral valganciclovir and intravitreal ganciclovir

PubMed Central

Tripathy, Koushik; Mittal, Kanhaiya; Venkatesh, Pradeep; Bakhshi, Sameer; Chawla, Rohan

2017-01-01

Cytomegalovirus retinitis (CMVR) is an opportunistic infection seen in immunocompromised patients, especially suffering from acquired immune deficiency syndrome. It is uncommonly seen in hematological malignancies and in patients on immunosuppressants. The authors present a 12-year-old girl with unilateral CMVR who was on maintenance phase therapy for mixed phenotype (B/myeloid) leukemia. Serology for human immunodeficiency virus was negative. The child was successfully treated with oral valganciclovir and repeated intravitreal ganciclovir injections. CMVR in pediatric population with leukemia can be successfully treated with oral valganciclovir and intravitreal ganciclovir injections. PMID:29118508

Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration.

PubMed

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2009-06-01

To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval. Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments). Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

Intravitreal foscarnet for recurring CMV retinitis in a congenitally infected premature infant.

PubMed

Tawse, Kirstin L; Baumal, Caroline R

2014-02-01

A girl born at 32 weeks' gestational age was diagnosed at birth with congenital cytomegalovirus (CMV) infection without ocular involvement. On day 19 of life, retinal examination requested for retinopathy of prematurity (ROP) identified bilateral CMV retinitis and stage 1 ROP. Treatment of macular threatening CMV infection with intravitreal foscarnet injections and intravenous ganciclovir for 6 weeks led to quiescence of retinitis. Bilateral recurrence of CMV retinitis occurred on day 89 of life, requiring a second course of intravitreal foscarnet injections and intravenous ganciclovir. Both the initial presentation and reactivation of CMV retinitis were identified on examination for ROP and would have gone unrecognized had the infant not met ROP screening criteria. This case demonstrates delayed presentation of CMV retinitis after initial negative retinal examination in a premature infant with congenital infection and concurrent ROP. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Longitudinal Vision-Related Quality of Life for Patients with Noninfectious Uveitis Treated with Fluocinolone Acetonide Implant or Systemic Corticosteroid Therapy.

PubMed

Sugar, Elizabeth A; Venugopal, Vidya; Thorne, Jennifer E; Frick, Kevin D; Holland, Gary N; Wang, Robert C; Almanzor, Robert; Jabs, Douglas A; Holbrook, Janet T

2017-11-01

To evaluate longitudinal vision-related quality of life (VRQoL) in patients with noninfectious uveitis. Cohort study using randomized controlled trial data. Patients with active or recently active intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Steroid Treatment Trial and Follow-up Study. Data from the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) for the first 3 years after randomization were evaluated semiannually. Analyses were stratified by assigned treatment (129 implants vs. 126 systemic therapies) because of substantial differences in the trajectories of VRQoL. The impact of baseline measurements of visual function (visual acuity and visual field), demographics, and disease characteristics was assessed using generalized estimating equations. Primary outcome was the NEI-VFQ-25 composite score over 3 years after randomization. Individuals in both treatment groups showed similar improvement in NEI-VFQ-25 scores after 3 years of follow-up (implant: 11.9 points; 95% confidence interval [CI], 8.6-15.2; P < 0.001; systemic: 9.0 points; 95% CI, 5.6-12.3; P < 0.001; P = 0.21 for interaction). Individuals in the implant group showed a substantial improvement during the first 6 months followed by stable scores, whereas individuals in the systemic group showed a steady improvement over the course of follow-up. Worse initial visual acuity and visual fields were associated with lower initial NEI-VFQ-25 scores for both treatment groups. In the systemic group, these differences were maintained throughout follow-up. In the implant group, individuals with initial visual acuity worse than 20/40 showed additional improvement in NEI-VFQ-25 score to come within -7 points (95% CI, -15.0 to 0.9) of those with visual acuity 20/40 or better initially, a clinically meaningful but not statistically significant difference (P = 0.081). Results based on sensitivity analyses showed similar patterns. Both treatment

Intravitreal bevacizumab monotherapy for retinopathy of prematurity.

PubMed

Şahin, Alparslan; Şahin, Muhammed; Cingü, Abdullah Kürşat; Çınar, Yasin; Türkcü, Fatih Mehmet; Yüksel, Harun; Kaya, Savaş; Arı, Şeyhmus; Caça, İhsan

2013-10-01

The aim of this study was to evaluate the treatment outcomes of intravitreal bevacizumab (IVB) injections, used as a monotherapy in type 1 retinopathy of prematurity (ROP). A retrospective chart review was performed for 17 type 1 ROP patients (34 eyes), who had IVB injection between July 2011 and June 2012. Birthweight, gestational age at birth, stage and location of ROP, IVB injection time, time of complete retinal vascularization, and additional treatments if needed, were noted. A total of 0.625 mg (0.025 mL) bevacizumab was injected intravitreally. Thirty eyes of 17 patients with type 1 ROP enrolled in the study were treated with IVB injection. Of them seven had aggressive posterior-ROP, six had stage 2 ROP, and four had stage 3 ROP. The mean gestational age was 28.44 weeks (range, 26-31 weeks); and the mean birthweight was 1151.88 g (range, 600-1600 g). The mean age for IVB injection was 35.47 weeks. The mean full retinal vascularization time was 136.6 ± 26.6 days. The mean follow-up time was 285.3 ± 70 days. ROP was regressed and retinal vascularization was completed in all cases except one eye, which had threshold disease. IVB injection, used as a monotherapy, is an effective treatment approach in patients with type 1 ROP. Timely treatment of stage 2 and early stage 3 ROP in which disease progression was observed, prevents vitreoretinal membrane formation in posterior disease. Further studies need to be performed to determine the safety of IVB injection. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

The therapeutic efficacy of sacroiliac joint blocks with triamcinolone acetonide in the treatment of sacroiliac joint dysfunction without spondyloarthropathy.

PubMed

Liliang, Po-Chou; Lu, Kang; Weng, Hui-Ching; Liang, Cheng-Loong; Tsai, Yu-Duan; Chen, Han-Jung

2009-04-20

Prospective case series. The study aimed to investigate the therapeutic efficacy of sacroiliac joint (SIJ) blocks with triamcinolone acetonide in patients with SIJ pain without spondyloarthropathy. Numerous studies have demonstrated that SIJ blocks with corticosteroid/anesthetic provide long-term pain relief in seronegative spondyloarthropathy. However, only one report on SIJ dysfunction patients without spondyloarthropathy shows promising results. We conducted a prospective observational study of patients at a University Spine Center from March 2005 to May 2006. The above mentioned SIJ blocks were performed in 150 patients, and dual SIJ blocks confirmed SIJ pain in 39 patients (26%). Twenty-six patients (66.7%) experienced significant pain reduction for more than 6 weeks; the overall mean duration of pain reduction in these responders was 36.8 +/- 9.9 weeks. SIJ blocks were ineffective in 13 patients (33.3%); the mean duration of pain reduction in these patients was 4.4 +/- 1.8 weeks. Univariate analysis revealed that treatment failure was significantly associated with a history of lumbar/lumbosacral fusion (P = 0.03). SIJ blocks with triamcinolone acetonide are beneficial for some patients with SIJ pain without spondyloarthropathy. The SIJ blocks showed a long-lasting efficacy in two-thirds of the patients; however, the duration of its efficacy was shorter in patients with a history of lumbar/lumbosacral fusion. These findings suggest the need for further studies.

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.

PubMed

Witkin, Andre J; Rayess, Nadim; Garg, Sunir J; Maguire, Joseph I; Storey, Philip; Kaiser, Richard S; Hsu, Jason; Vander, James F; Ho, Allen C

2017-01-01

To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Retrospective, consecutive, interventional case series. Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks' follow-up. Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

The role of intravitreal bevacizumab in experimental posterior penetrating eye injury.

PubMed

Mehdizadeh, Morteza; Fattahi, Fariba; Eghtedari, Masoumeh; Nowroozzadeh, Mohammad H; Toosi, Foroogh

2011-01-01

The purpose of this study was to investigate the effect of intravitreal bevacizumab on an experimental rabbit model of penetrating posterior ocular injury. The right eyes of 40 white New Zealand rabbits were included in a penetrating posterior ocular injury model that was consisted of a 5-mm circumferential incision placed 8 mm behind the limbus at the supratemporal quadrant. They were randomly divided into two groups. The rabbits in Group 1 (n = 20) received 1.25 mg (0.05 mL) of intravitreal bevacizumab via pars plana injection and those in Group 2 (control group, n = 20) received 0.05 mL of intravitreal balanced salt solution. On Day 28, the eyes were enucleated and evaluated by gross inspection and light microscopy. Clearance time of vitreous hemorrhage, presence of fibrous proliferation or retinal detachment, greatest linear dimension of fibrosis, and grade of fibrous extension were regarded as outcome measures. Nominal variables were evaluated by the chi-square or the Fisher's exact test; continuous variables were evaluated using the Mann-Whitney U test. At the end of the surgery, all the eyes had moderate (n = 9 and 7 in the case and control groups, respectively) or severe vitreous hemorrhage (n = 11 and 13 in the case and control groups, respectively) (P = 0.52). Average clearance time of vitreous hemorrhage was 3.42 ± 2.71 and 6.47 ± 3.58 days in bevacizumab and control groups, respectively (P = 0.01). The incidence of ophthalmoscopically visible fibrous proliferation was 31.6% in the bevacizumab group and 63.2% in the control group (P = 0.05). The greatest linear dimension of fibrosis was 0.91 ± 1.14 mm in the bevacizumab group and 2.00 ± 1.58 mm in the control group (P = 0.02). Retinal detachment rate was 11% (n = 2, all rhegmatogenous) and 21% (n = 4, 2 rhegmatogenous and 2 tractional) in the bevacizumab and control groups, respectively (P = 0.66). Choroidal congestion, optic disk edema, and macular edema were seen in 1 eye (5.5%) of the bevacizumab

Minimizing the endophthalmitis rate following intravitreal injections using 0.25% povidone-iodine irrigation and surgical mask.

PubMed

Shimada, Hiroyuki; Hattori, Takayuki; Mori, Ryusaburo; Nakashizuka, Hiroyuki; Fujita, Kyoko; Yuzawa, Mitsuko

2013-08-01

To examine the efficacy of complying with an infection control manual for intravitreal injection of anti-vascular endothelial growth factor (VEGF) preparations in reducing the rate of endophthalmitis. We retrospectively reviewed intravitreal anti-VEGF injections conducted by vitreoretinal specialists at the outpatient injection room of a single university hospital between July 2009 and July 2012. The injections were conducted following an infection control manual established by our department. Doctors and nurses wore surgical masks, and disinfected the patient's eyelid skin with 10% povidone-iodine and then the conjunctiva with 0.25% povidone-iodine. After putting a drape on the patient's face, a lid speculum was placed. The conjunctival surface was again washed with 5 ml of 0.25% povidone-iodine. After waiting at least 30 seconds, intravitreal injection was performed through povidone-iodine. Following injection, the injection site was again washed with 5 ml of 0.25% povidone-iodine. Patients were treated with topical levofloxacin 4 times a day for 3 days before and after the injection. A total of 15,144 injections comprising 548 injections of pegaptanib sodium, 846 injections of bevacizumab, and 13,750 injections of ranibizumab were performed. During this period, no case of suspected or proven infectious endophthalmitis occurred. The endophthalmitis rate was 0 per 15,144 injections, (95% confidence interval, 0.0-0.0%). The results suggest that endophthalmitis can be reduced to a minimum by preventing normal flora of the conjunctiva and bacteria in the oral cavity from entering the vitreous. For this purpose, an infection control manual that requires nurses and doctors to wear surgical mask and drape the patient's face, irrigate the conjunctiva with 0.25% povidone-iodine and wait at least 30 seconds before performing intravitreal injection is useful.

EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT AND RANIBIZUMAB IN ASIAN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Subgroup Analyses From the View Trials.

PubMed

Wong, Tien Yin; Cheung, Chui Ming Gemmy; Lai, Timothy Y Y; Chen, Shih-Jen; Lee, Won Ki; Yoon, Young Hee; Iida, Tomohiro; Tueckmantel, Claudia; Sowade, Olaf; Ogura, Yuichiro

2017-12-26

To assess the treatment effect of intravitreal aflibercept and ranibizumab in Asian patients with neovascular age-related macular degeneration. We evaluated data from VIEW 1 and VIEW 2, comparing functional and morphologic outcomes at Week 96 between intravitreal aflibercept 2 mg monthly (2q4) or 2 mg bimonthly after 3 initial monthly doses (2q8) versus ranibizumab 0.5 mg monthly among Asian patients (n = 269) and between Asian and white patients (n = 2044). In Asian patients, there were no significant differences between intravitreal aflibercept 2q4 and 2q8 compared with ranibizumab in mean gain in best-corrected visual acuity (10.23 and 8.35 vs. 8.51 letters). Reduction in central retinal thickness was greater for intravitreal aflibercept 2q4 (150.43 μm, P = 0.0075) and 2q8 (148.15 μm, P = 0.0126) than ranibizumab (119.46 μm). The proportion of dry retinas was greater for intravitreal aflibercept 2q4 (65.7%, P < 0.01) than ranibizumab (41.7%). There were no differences in outcomes between Asian and white patients. Serious treatment-emergent ocular adverse events occurred in <8% of treated eyes, evenly distributed across subgroups. In Asian patients with neovascular age-related macular degeneration, functional and morphologic outcomes were largely similar between intravitreal aflibercept and ranibizumab groups, and to results seen in white patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration

PubMed Central

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2009-01-01

Purpose To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). Methods We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14 month period, and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28±7 days after administration in an eye which had previously demonstrated a therapeutic response in the same time interval. Results Five patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10). Conclusion Tachyphylaxis can occur following long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved. PMID:19516114

[Incidence of endophthalmitis after intravitreal Avastin injection with and without postoperative topical antibiotic application].

PubMed

Meyer, C H; Mennel, S; Eter, N

2007-11-01

Intravitreal injection of vascular endothelial growth factor inhibitors is safe as a standardized procedure. In a retrospective study, we examined the incidence of intraocular inflammation and endophthalmitis when intravitreal Avastin was given on both an outpatient and an inpatient basis. Two centers treated a total of 1844 patients with intravitreal Avastin injection (IVA), 1.25 mg/0.05 ml. The medication was given under aseptic conditions with a sterile drape and lid speculum and after an incubation of 5% povidone-iodine for 60 s in the conjunctival fornix. Center A performed all applications as an outpatient procedure with no postoperative topical antibiotics. Center B performed all IVAs prior to a 1-day hospital admission and gave topical antibiotics for 3 days. In both centers the patients were told to return to the hospital immediately if visual disturbance, pain, or redness of the eyes was noticed. Center A did 984 IVAs. Postoperatively no patients had endophthalmitis. On the 2nd postoperative day, two patients developed a mild intraocular uveitis, which was treated with local steroid ointments. Center B did 860 IVAs. Five days after discharge from the hospital, two patients presented with endophthalmitis and underwent vitrectomy when their vision dropped to counting fingers. There was no positive microbiological result of either vitreous probe. Although equal treatment guidelines were established, the perioperative hospital admission and postoperative application of topical antibiotic ointment could not reduce the occurrence of mild to severe intraocular endophthalmitis.

High Variation of Intravitreal Injection Rates and Medicare Anti-Vascular Endothelial Growth Factor Payments per Injection in the United States.

PubMed

Erie, Jay C; Barkmeier, Andrew J; Hodge, David O; Mahr, Michael A

2016-06-01

To estimate geographic variation of intravitreal injection rates and Medicare anti-vascular endothelial growth factor (VEGF) drug costs per injection in aging Americans. Observational cohort study using 2013 Medicare claims database. United States fee-for-service (FFS) Part B Medicare beneficiaries and their providers. Medicare Provider Utilization and Payment Data furnished by the Centers for Medicare and Medicaid Services was used to identify all intravitreal injection claims and anti-VEGF drug claims among FFS Medicare beneficiaries in all 50 states and the District of Columbia in 2013. The rate of FFS Medicare beneficiaries receiving intravitreal injections and the mean Medicare-allowed drug payment per anti-VEGF injection was calculated nationally and for each state. Geographic variations were evaluated by using extremal quotient, coefficient of variation, and systematic component of variance (SCV). Rate of FFS Medicare Part B beneficiaries receiving intravitreal injections (Current Procedural Terminology [CPT] code, 67028), nationally and by state; mean Medicare-allowed drug payment per anti-VEGF injection (CPT code, 67028; and treatment-specific J-codes, J0178, J2778, J9035, J3490, and J3590) nationally and by state. In 2013, the rate of FFS Medicare beneficiaries receiving intravitreal injections varied widely by 7-fold across states (range by state, 4 per 1000 [Wyoming]-28 per 1000 [Utah]), averaging 19 per 1000 beneficiaries. The mean SCV was 8.5, confirming high nonrandom geographic variation. There were more than 2.1 million anti-VEGF drug claims, totaling more than $2.3 billion in Medicare payments for anti-VEGF agents in 2013. The mean national Medicare drug payment per anti-VEGF injection varied widely by 6.2-fold across states (range by state, $242 [South Carolina]-$1509 [Maine]), averaging $1078 per injection. Nationally, 94% of injections were office based and 6% were facility based. High variation was observed in intravitreal injection rates and

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.

PubMed

Chao, An- Ning; Kao, Ling-Yuh; Liu, Laura; Wang, Nan-Kai

2016-03-15

Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection. A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 μg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection. Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the

Intravitreal bevacizumab injections for treatment of central retinal vein occlusion: six-month results of a prospective trial.

PubMed

Priglinger, Siegfried G; Wolf, Armin H; Kreutzer, Thomas C; Kook, Daniel; Hofer, Anja; Strauss, Rupert W; Alge, Claudia S; Kunze, Christian; Haritoglou, Christos; Kampik, Anselm

2007-10-01

To evaluate the effect of intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injections on visual acuity and foveal retinal thickness in patients with central retinal vein occlusion (CRVO). In this prospective, noncomparative, consecutive, interventional case series, 46 patients received repeated intravitreal injections (1.25 mg) of bevacizumab. Main outcome measures were visual acuity (Snellen and ETDRS charts) and optical coherence tomography measurements in a 6-month follow-up period. Mean visual acuity improved from 20/250 at baseline to 20/80 at the 6-month follow-up (P < 0.001). ETDRS chart findings revealed a mean letter gain +/-SD from baseline to 6 months of 13.9 +/- 14.4 letters. Mean central retinal thickness +/-SD decreased from 535 +/- 148 microm at baseline to 323 +/- 116 microm at the 6-month follow-up. Ischemic CRVO was associated with significantly lower visual acuity than nonischemic CRVO (P < 0.001). However, visual acuity gain was similar in both groups. Independent of duration of symptoms, CRVO was associated with a similar gain in visual acuity. Intravitreal injection of bevacizumab appears to be a new treatment option for patients with macular edema secondary to CRVO.

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.

PubMed

Prieto, Esther; Vispe, Eugenio; De Martino, Alba; Idoipe, Miriam; Rodrigo, María J; Garcia-Martin, Elena; Fraile, José M; Polo-Llorens, Vicente; Mayoral, José A

2018-03-01

To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration in rabbit eyes. Thirty-two New Zealand albino rabbits were divided into two experimental groups to test intravitreal (IVT group) and suprachoroidal (SCS group) administration of a 100-μl and 50-μl Laponite suspension respectively. Following injection, the eyes were monitored by ocular tonometry, slit-lamp eye examination and indirect ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post administration. Histological examination was also performed to determine whether any ocular pathological change had occurred. Throughout the study, LAP presence in vitreous was estimated by complexometric titration with ethylenediaminetetraacetic acid (EDTA), taking advantage of the Laponite high content of magnesium ions. Neither significant differences in the intraocular pressure, nor relevant ocular complications were found in the two experimental groups after LAP administration. The histology of the retina remained unchanged. LAP presence in vitreous could be indirectly confirmed by complexometric titration until 14 weeks post administration in eyes of IVT group. Laponite could be considered as a vehicle for potential clinical use in ocular drug administration, due to its proven ocular biocompatibility and its transparency in gel state.

CLINICAL EVALUATION OF THE RAPID ACCESS VITREAL INJECTION GUIDE: A Handheld Instrument for Assisting Intravitreal Injections.

PubMed

Han, Dennis P; McKenney, Kaitlin C; Kim, Judy E; Weinberg, David V; Musch, David C; Singh, Ravi S J

2017-04-01

The Rapid Access Vitreal Injection (RAVI) guide combines the function of an eyelid speculum and measuring caliper into a single instrument for assisting intravitreal injections. This study clinically evaluated the RAVI guide with respect to patient acceptance, complication rates, and operative goals. A prospective study was performed on 54 patients undergoing intravitreal injections using the RAVI guide (n = 32) or the speculum/caliper (n = 22). Device-related pain was assessed using the Wong-Baker scoring system, scaled from 0 (no pain) to 10 (agonizing pain). Mean device-related pain score did not differ significantly between the 2 groups, with scores of 0.6 and 0.7 for the RAVI guide and speculum groups, respectively. The rate of significant pain (score of ≥2) was twice as high in the speculum group (7 of 22, 32%) compared with the RAVI guide group (5 of 32, 16%), but this difference was not statistically significant (P = 0.19, Fisher's exact test). Operative goals of avoiding needle touch to lashes/lids and guiding needle insertion to the intended site were achieved in all patients. The RAVI guide appeared equivalent to the eyelid speculum in achieving operative goals, with similarly low pain scores. It has the potential for facilitating efficient, accurate, and safe intravitreal injections.

Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

PubMed

Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami

2018-01-01

Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.

PubMed

Munier, Francis L; Soliman, Sameh; Moulin, Alexandre P; Gaillard, Marie-Claire; Balmer, Aubin; Beck-Popovic, Maja

2012-08-01

The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited. A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread. 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135). This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

On the retinal toxicity of intraocular glucocorticoids.

PubMed

Torriglia, Alicia; Valamanesh, Fatemeh; Behar-Cohen, Francine

2010-12-15

Corticosteroids are hormones involved in many physiological responses such as stress, immune modulation, protein catabolism and water homeostasis. The subfamily of glucocorticoids is used systemically in the treatment of inflammatory diseases or allergic reactions. In the eye, glucocorticoides are used to treat macular edema, inflammation and neovascularization. The most commonly used glucocorticoid is triamcinolone acetonide (TA). The pharmaceutical formulation of TA is not adapted for intravitreal administration but has been selected by ophthalmologists because its very low intraocular solubility provides sustained effect. Visual benefits of intraocular TA do not clearly correlate with morpho-anatomical improvements, suggesting potential toxicity. We therefore studied, non-common, but deleterious effects of glucocorticoids on the retina. We found that the intravitreal administration of TA is beneficial in the treatment of neovascularization because it triggers cell death of endothelial cells of neovessels by a caspase-independent mechanism. However, this treatment is toxic for the retina because it induces a non-apoptotic, caspase-independent cell death related to paraptosis, mostly in the retinal pigmented epithelium cells and the Müller cells. Copyright © 2010 Elsevier Inc. All rights reserved.

Intravitreal bevacizumab (Avastin) as treatment for subfoveal choroidal neovascularisation secondary to pathological myopia

PubMed Central

Yamamoto, Izumi; Rogers, Adam H; Reichel, Elias; Yates, Paul A; Duker, Jay S

2007-01-01

Objective To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin) as treatment for subfoveal choroidal neovascularisation (CNV) due to pathological myopia. Methods Consecutive series of primary or recurrent subfoveal CNV secondary to myopia treated with intravitreal bevacizumab 1.25 mg between August 2005 and January 2006 at the New England Eye Center, Boston, Massachusetts, USA, were reviewed retrospectively. Data from clinical examination, fundus photography, fluorescein angiography, optical coherence tomography and visual acuity were collected. Results There were 11 eyes of 9 patients. 5 of 11 eyes had been treated previously with photodynamic therapy. Pre‐injection visual acuity measured 20/50 to 20/100 in 6 eyes and 20/200 or worse in 5 eyes. After a mean follow‐up of 153 (range 35–224) days, post‐injection visual acuity measured 20/20 to 20/40 in 7 eyes, 20/50 to 20/100 in 1 eye and 20/200 or worse in 3 eyes. Three eyes received two bevacizumab injections and eight eyes received one injection. Visual acuity improved by a mean of +3.5 (range −1 to +8 lines) lines, and 8 of 11 eyes achieved 20/50 or better at the last follow‐up. Central foveal thickness improved from 340 (range 253–664) μm to 234 (range 142–308) μm, representing an average reduction of 103 (range +4 to −356) μm. No injection complications or drug‐related side effects were observed. Conclusions In this small series of eyes with limited follow‐up, intravitreal bevacizumab seems to be safe and potentially efficacious in eyes with subfoveal CNV secondary to pathological myopia. PMID:16870653

Intravitreal erythropoietin injection in late-stage optic neuropathy: a safety study on human.

PubMed

Acar, Ugur; Kucuk, Bekir; Sevinc, Mehmet Koray; Aykas, Seckin; Erdurmus, Mesut; Sobaci, Gungor

2018-06-01

To evaluate the whether intravitreal erythropoietin (EPO) administration has any beneficial or adverse effect in patients with late-stage optic neuropathy (ON) or not. The study examined 16 eyes of 16 patients who had late-stage ON and ≥1/20 best-corrected visual acuity (BCVA) in their affected eye. There were nonarteritic ischemic ON in 10 (62.5%) eyes, traumatic ON in 4 (25.0%) eyes and methanol-induced ON in 2 (12.5%) eyes. Using pars plana approach, 2000 IU/0.2 ml EPO was administered intravitreally with a 30-gauge needle. Injections were administered three times with 6-week intervals. We compared the differences in the BCVA, intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, pattern visual evoked potentials (p-VEP) and pattern electroretinography (p-ERG) parameters performed at initial examination and final visits. The mean age of the patients was 52.38 ± 12.00 years; 2 (12.50%) of them were female, and 14 (87.50%) of them were male. The mean BCVA levels of 16 patients with optic atrophy were 1.12 ± 0.25 logMAR at the initial examination and 1.08 ± 0.26 logMAR at the final visit (p = 0.102). There was no statistically significant difference between the initial and final RNFL thicknesses, IOP values, p-ERG or p-VEP responses. Intravitreal EPO injections have no beneficial or detrimental effect on the late stage of ON. Further studies are necessary to compare our results in patients with ON in earlier stages.

An application of second-order UV-derivative spectrophotometry for study of solvolysis of a novel fluocinolone acetonide ester

NASA Astrophysics Data System (ADS)

Markovic, Bojan; Vladimirov, Sote; Cudina, Olivera; Savic, Vladimir; Karljikovic-Rajic, Katarina

2010-02-01

A novel topical corticosteroid FA-21-PhP, 2-phenoxypropionate ester of fluocinolone acetonide, has been synthesized in order to investigate the possibility of decreasing systemic side effects. In this study model system for in vitro solvolytic reaction of FA-21-PhP has been analyzed in ethanol/water (90:10, v/v) with excess of sodium hydrogen carbonate. The selected conditions have been used as in vitro model for activation of corticosteroid C-21 ester prodrug. The second-order derivative spectrophotometric method (DS) using zero-crossing technique was developed for monitoring ternary mixture of solvolysis. Fluocinolone acetonide (FA) as a solvolyte was determined in the mixture in the concentration range 0.062-0.312 mM using amplitude 2D 274.96. Experimentally determined LOD value was 0.0295 mM. The accuracy of proposed DS method was confirmed with HPLC referent method. Peak area of parent ester FA-21-PhP was used for solvolysis monitoring to ensure the initial stage of changes. Linear relationship in HPLC assay for parent ester was obtained in the concentration range 0.054-0.54 mM, with experimentally determined LOD value of 0.0041 mM. Investigated solvolytic reaction in the presence of excess of NaHCO 3 proceeded via a pseudo-first-order kinetic with significant correlation coefficients 0.9891 and 0.9997 for DS and HPLC, respectively. The values of solvolysis rate constant calculated according to DS and HPLC methods are in good accordance 0.038 and 0.043 h -1, respectively.

Long-term follow-up of patients with retinitis pigmentosa (RP) receiving intraocular ciliary neurotrophic factor implants

PubMed Central

Birch, David G.; Bennett, Lea D.; Duncan, Jacque L.; Weleber, Richard G.; Pennesi, Mark E.

2016-01-01

Purpose To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Design Long-term follow up of a multicenter, sham-controlled study. Methods Thirty-six patients at three CNTF4 sites were randomly assigned to receive a high- or low- dose implant in one eye and sham surgery in the fellow eye. The primary endpoint (change in visual field sensitivity at 12 months) has been reported previously.1 Here we report long-term visual acuity, visual field and optical coherence tomography (OCT) outcomes in 24 patients either retaining or explanting the device at 24 months relative to sham-treated eyes. Results Eyes retaining the implant showed significantly greater visual field loss from baseline than either explanted eyes or sham eyes through 42 months. By 60 months and continuing through 96 months, visual field loss was comparable among sham-treated eyes, eyes retaining the implant and explanted eyes, as was visual acuity and OCT macular volume. Conclusions Over the short term, ciliary neurotrophic factor released continuously from an intra-vitreal implant lead to loss of total visual field sensitivity that was greater than the natural progression in the sham-treated eye. This additional loss of sensitivity related to the active implant was reversible when the implant was removed. Over the long term (60 – 96 months), there was no evidence of efficacy for visual acuity, visual field sensitivity or OCT measures of retinal structure. PMID:27457255

Intravitreal aflibercept versus intravitreal ranibizumab in patients with age-related macular degeneration: a comparative effectiveness study.

PubMed

Smit, Cornelis; Wiertz-Arts, Karin; van de Garde, Ewoudt Mw

2018-06-01

A hospital-wide, unselected switch of ranibizumab to aflibercept in treatment of age-related macular degeneration (AMD) allowed us to compare the clinical effectiveness of these agents. In a single-center before-after, observational study design new AMD-patients started with aflibercept treatment in 2013-2014 were compared with a control group of AMD-patients on ranibizumab before the switch. The mean difference in visual acuity (in logMAR units) after 1 year was comparable (+0.012 [aflibercept, n = 37] vs +0.17 [ranibizumab, n = 30], p = 0.154). However, the aflibercept-group did receive more intravitreal injections (5.8 vs 4.7 injections, p = 0.004) and were treated longer (265.7 vs 197.7 days; p = 0.011). With no difference in clinical effectiveness, longer treatment intervals for aflibercept should be investigated.

Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA).

PubMed

Nguyen, Quan Dong; Merrill, Pauline T; Clark, W Lloyd; Banker, Alay S; Fardeau, Christine; Franco, Pablo; LeHoang, Phuc; Ohno, Shigeaki; Rathinam, Sivakumar R; Thurau, Stephan; Abraham, Abu; Wilson, Laura; Yang, Yang; Shams, Naveed

2016-11-01

To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Intravitreal sirolimus 440 μg demonstrated a significant

Determination of a No-Observable Effect Level for Endotoxin Following a Single Intravitreal Administration to Dutch Belted Rabbits.

PubMed

Bantseev, Vladimir; Miller, Paul E; Bentley, Ellison; Schuetz, Chris; Streit, Tim M; Christian, Brian J; Farman, Cindy; Booler, Helen; Thackaberry, Evan A

2017-03-01

The purpose of this study was to characterize the inflammatory response and determine a no-observable effect level (NOEL) in rabbit eyes after endotoxin intravitreal (ITV) injection. Fifty-three naïve male Dutch Belted rabbits were treated with a single 50-μL ITV injection ranging from 0.01 to 0.75 endotoxin units/eye (EU/eye) and monitored for up to 42 days post treatment. Ophthalmic examination included slit-lamp biomicroscopy and indirect ophthalmoscopy. Laser flare photometry was performed in a subset of animals. On days 2, 8, 16, and 43, a subset of animals was necropsied and eyes processed for histopathological evaluation. Intravitreal injection of endotoxin at ≥0.05 EU/eye resulted in a dose-related anterior segment inflammation response. No aqueous flare or cell response was noted in the 0.01 EU/eye dose group. A more delayed posterior segment response characterized by vitreal cell response was observed beginning on day 5, peaking on day 9, and decreasing starting on day 16 that persisted at trace to a level of 1+ on day 43. Microscopy findings of infiltrates of minimal mixed inflammatory cells in the vitreous and subconjunctiva and proteinaceous fluid in the anterior chamber and/or vitreous were observed in eyes given ≥0.1 EU/eye. We defined the NOEL for ITV endotoxin to be 0.01 EU/eye, suggesting that the vitreal cavity is more sensitive to the effects of endotoxin than the anterior segment and aqueous chamber. These data highlight the importance of assessing endotoxin level in intravitreal formulations, as levels as low as 0.05 EU/eye may confound the safety evaluations of intravitreal therapeutics in rabbits.

Mobile ultra-clean unidirectional airflow screen reduces air contamination in a simulated setting for intra-vitreal injection.

PubMed

Lapid-Gortzak, Ruth; Traversari, Roberto; van der Linden, Jan Willem; Lesnik Oberstein, Sarit Y; Lapid, Oren; Schlingemann, Reinier O

2017-02-01

The aim of this study is to determine whether the use of a mobile ultra-clean laminar airflow screen reduces the air-borne particle counts in the setting of a simulated procedure of an intra-vitreal injection. A mobile ultra-clean unidirectional airflow (UDF) screen was tested in a simulated procedure for intra-vitreal injections in a treatment room without mechanical ventilation. One UDF was passed over the instrument tray and the surgical area. The concentration of particles was measured in the background, over the instrument table, and next to the ocular area. The degree of protection was calculated at the instrument table and at the surgical site. Use of the UDF mobile screen reduced the mean particle concentration (particles > 0.3 microns) on the instrument table by a factor of at least 100.000 (p < 0.05), and over the patient's eye by at least a factor of 436 (p < 0.05), which in clinical practice translates into significantly reduced air contamination. Mobile UDF screen reduces the mean particle concentration substantially. The mobile UDF screen may therefore allow for a safer procedural environment for ambulatory care procedures such as intra-vitreal injections in treatment rooms.

Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract.

PubMed

Akinci, Arsen; Batman, Cosar; Ozkilic, Ersel; Altinsoy, Ali

2009-01-01

The purpose of this study was to evaluate the results of phacoemulsification with intravitreal bevacizumab injection in patients with diabetic clinically significant macular edema and cataract. The records of 31 patients with diabetic clinically significant macular edema and cataract, which would interfere with macular laser photocoagulation, who have undergone phacoemulsification with intravitreal injection of 1.25 mg bevacizumab were retrospectively evaluated. All patients had undergone focal or modified grid laser photocoagulation 1 month after the surgery. All patients were evaluated by spectral optical coherence tomography/optical coherence tomography SLO before and 1 and 3 months after the surgery beyond complete ophthalmologic examination. The best-corrected visual acuity (BCVA) levels and central macular thickness (CMT) recorded at the first and third months after the surgery were compared with the initial values. Paired samples t test was used for statistical analysis. The mean initial BCVA was 0.10 +/- 0.04 (range, 0.05-0.2). The mean BCVA at the first and third months after the surgery were 0.47 +/- 0.16 (standard deviation) (range, 0.2-0.5) and 0.51 +/- 0.12 (standard deviation) (range, 0.3-0.6), respectively. The BCVA level recorded at the first and third months after the surgery were significantly higher than the initial BCVA (P = 0.004). The mean initial CMT was 387.5 +/- 109.5 microm. The mean CMT at the first and third months after the surgery were 292.7 +/- 57.2 and 275.5 +/- 40.3. The CMT recorded at the first and third months after the surgery were significantly lower than the initial CMT (P < 0.001, P < 0.001). Phacoemulsification with intravitreal injection of bevacizumab provides improvement in clinically significant macular edema with a gain in BCVA in patients with diabetes with clinically significant macular edema and cataract.

Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections.

PubMed

Levin, Ariana M; Rusu, Irene; Orlin, Anton; Gupta, Mrinali P; Coombs, Peter; D'Amico, Donald J; Kiss, Szilárd

2017-01-01

The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA.

Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

PubMed

Shoeibi, Nasser; Hosseini, Seyedeh Maryam; Banaee, Touka; Ansari-Astaneh, Mohammad-Reza; Abrishami, Majid; Ahmadieh, Hamid

2018-01-01

Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study.

PubMed

de Jong, Jan H; van Zeeburg, Elsbeth J T; Cereda, Matteo G; van Velthoven, Mirjam E J; Faridpooya, Koorosh; Vermeer, Koenraad A; van Meurs, Jan C

2016-05-01

Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ≤14 days at time of surgery and SMH thickness had to be between 250 μm and 1,250 μm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91-99%) in the intravitreal rtPA group and 100% (95-100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PubMed

de Oliveira Dias, João Rafael; de Andrade, Gabriel Costa; Kniggendorf, Vinicius Ferreira; Novais, Eduardo Amorim; Maia, André; Meyer, Carsten; Watanabe, Sung Eun Song; Farah, Michel Eid; Rodrigues, Eduardo Büchele

2017-08-01

To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm to 8.08 ± 1.34 mm, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

Elimination of Topical Antibiotics for Intravitreous Injections and the Importance of Using Povidone-Iodine: Update From the Diabetic Retinopathy Clinical Research Network.

PubMed

Bhavsar, Abdhish R; Glassman, Adam R; Stockdale, Cynthia R; Jampol, Lee M

2016-10-01

This report provides updated endophthalmitis rates for eyes receiving intravitreous injections with and without povidone-iodine and rates with and without topical antibiotics from Diabetic Retinopathy Clinical Research Network clinical trials. Among 8 Diabetic Retinopathy Clinical Research Network clinical trials conducted from 2006 to 2015, 28 786 intravitreous injections were administered (3123 eyes), and 20 617 of those (2264 eyes) were administered between 2012 and 2015. Eleven cases of endophthalmitis occurred; 4 occurred between 2012 and 2015. Thirteen injections in 3 eyes from 2 participants were administered without povidone-iodine; both participants developed endophthalmitis in 1 eye. Of the remaining 28 773 injections (3120 eyes) performed with povidone-iodine, 9 cases of endophthalmitis occurred: 6 cases (0.05% of 11 565 injections) in eyes receiving topical antibiotics and 3 cases (0.02% of 17 208 injections) in eyes not receiving topical antibiotics (P = .17). While only a small number of eyes did not receive povidone-iodine just prior to an intravitreous injection, this report provides further evidence regarding the risk of endophthalmitis when povidone-iodine is not used before intravitreous injections. Exclusion of topical antibiotics was not associated with a higher risk of endophthalmitis. Continued use of povidone-iodine and consideration to eliminate topical antibiotics from injection procedures seems warranted.

Combined intravitreal bevacizumab and photodynamic therapy with vertiporfin for management of choroidal neovascularization secondary to age-related macular degeneration

PubMed Central

Kabeel, Mamdouh M; El-Batarny, Ashraf M; Tameesh, Mohamed K; Abou El Enein, Moustafa A

2008-01-01

Purpose To test the results for patients treated with combined photodynamic therapy (PDT) with vertiporfin (Visudyne, Novartis AG) and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Patients and methods This is a prospective study including 18 eyes with subfoveal or juxtafoveal CNV secondary to AMD. Patients were treated with intravitreal bevacizumab 2.5 mg in the morning then PDT with vertiporfin in the evening of the same day. All patients were followed up for 6 months. The main outcome measures were stabilization (no change) or improvement of best corrected visual acuity (BCVA) with no leakage in fluorescein angiography (FLA) and reduction of central retinal thickness, and retreatment rate. Results At the end of 6 months follow up, all cases had either stabilization or improved BCVA. Fifteen eyes (80%) showed improved BCVA. The overall mean improvement in BCVA (n = 18) was 2.17 lines. Fifteen eyes (80%) required single combined treatment. Only 3 eyes (20%) required retreatment with the same protocol. No systemic or ocular complications were reported. Conclusion Combined intravitreal bevacizumab and PDT as a treatment of CNV secondary to AMD either for predominantly classic or occult subtypes has a positive therapeutic effect with stabilization or improvement of final BCVA and also might reduce the need for retreatment compared with literature retreatment rates of either modality alone. Summary Eighteen patients receiving combined therapy with PDT and intravitreal bevacizumab for CNV secondary to AMD, showed not only significant visual improvement but also reduction in the frequency of retreatment when compared to the results of monotherapy with each modality. PMID:19668400

Characterization of uveitis induced by use of a single intravitreal injection of bacterial lipopolysaccharide in cats.

PubMed

Del Sole, María J; Sande, Pablo H; Felipe, Antonio E; Fernandez, Diego C; Keller Sarmiento, María I; Aba, Marcelo A; Rosenstein, Ruth E

2008-11-01

To investigate the use of a single intravitreal injection of bacterial lipopolysaccharide (LPS) to experimentally induce uveitis in cats. 7 young male European shorthair cats that were considered physically and ophthalmologically healthy. In each cat, LPS was injected intravitreally into 1 eye; the contralateral eye was injected with the preparation vehicle. During a period of 45 days, both eyes were evaluated by means of clinical evaluation; assessment of the integrity of the blood-aqueous humor barrier (determined via measurement of protein concentration and cell content in samples of aqueous humor); functional analysis (via electroretinography); and following euthanasia, histologic examination of the retinas. In LPS-treated eyes, several clinical signs were observed until day 45 after injection. Compared with vehicle-treated eyes, intraocular pressure was significantly lower and protein concentration and the number of infiltrating cells were significantly higher in LPS-treated eyes. Mean amplitudes of scotopic electroretinographic a- and b-waves were significantly reduced in eyes injected with LPS, compared with findings in eyes injected with vehicle. At 45 days after injection, LPS-induced alterations in photoreceptors and the middle portion of the retina were detected histologically. Results indicated that a single intravitreal injection of LPS in eyes of cats induced clinical, biochemical, functional, and histologic changes that were consistent with the main features of naturally occurring uveitis. This technique may be a useful tool in the investigation of new treatment strategies for uveitis in cats.

Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

PubMed

Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

2014-01-01

Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

Glaucoma filtration surgery following sustained elevation of intraocular pressure secondary to intravitreal anti-VEGF injections.

PubMed

Skalicky, Simon E; Ho, Ivan; Agar, Ashish; Bank, Allan

2012-07-01

To document cases of sustained elevation of intraocular pressure (IOP) while receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents and subsequent management. A retrospective series of all cases managed by the authors and colleagues was performed. Six patients developed sustained elevated IOP; five received ranibizumab and one bevacizumab. Four received unilateral and two received bilateral injections. Two had preexisting primary open-angle glaucoma and one had pseudoexfoliative glaucoma, all with stable IOP prior to anti-VEGF treatment. Angles were open in all cases. Peak IOP averaged 43 mm Hg (range: 34 to 60 mm Hg). The mean number of injections preceding the IOP increase was 10 (range: 1 to 20). Four patients required trabeculectomy, one selective laser trabeculoplasty, and one multiple topical medications. A sustained increase in IOP requiring glaucoma filtering surgery is a rare but important treatment complication for patients receiving intravitreal anti-VEGF therapy, especially those with preexisting glaucoma or glaucoma risk factors. Copyright 2012, SLACK Incorporated.

Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.

PubMed

Tode, Jan; Richert, Elisabeth; Koinzer, Stefan; Klettner, Alexa; Pickhinke, Ute; Garbers, Christoph; Rose-John, Stefan; Nölle, Bernhard; Roider, Johann

2017-08-01

To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU). EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R). Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (p<0.01) and IL-17 (p=0.01) levels in treated eyes compared to the fellow control eyes. This difference was not seen in non-responding mice. Intravitreal anti-IL-6 treatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

PubMed

Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

2015-07-01

This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

Treatment of Geographic Atrophy with Intravitreal Sirolimus: The Age-Related Eye Disease Study 2 Ancillary Study.

PubMed

Gensler, Gary; Clemons, Traci E; Domalpally, Amitha; Danis, Ronald P; Blodi, Barbara; Wells, Jack; Rauser, Michael; Hoskins, John; Hubbard, G Baker; Elman, Michael J; Fish, Gary E; Brucker, Alexander; Margherio, Alan; Chew, Emily Y

2018-05-01

To evaluate efficacy and safety of monthly intravitreal injections of sirolimus, an immunosuppressive drug, for the treatment of age-related macular degeneration associated geographic atrophy (GA). Randomized, controlled, single-masked multi-center phase 2 clinical trial of intravitreal sirolimus vs. sham therapy in AREDS2 clinical centers. Participants with GA. Participants eligible in one eye were randomly assigned to a monthly intravitreal injection of sirolimus (20 µL [440 µg]) or sham treatment while participants with two study eyes were assigned to a monthly intravitreal injection in a randomly-selected eye. Best-corrected visual acuities (BVCA), spectral domain optical coherence tomography (OCT), fundus color photography and fundus autofluorescence (FAF) images were obtained at baseline and every 6 months until visit month 24. Rate of progression of GA (mm 2 /year) measured on color fundus photograph from baseline to 24 months. Secondary outcome measures include change in BVCA, worsening of vision by ≥3 lines, and changes in area of GA measured on FAF and OCT. 52 participants (mean age 79 years) were enrolled with 27 study eyes assigned to sirolimus from May 2012 to March 2014. The baseline median area of GA was 4.73 DA (12.01 mm 2 ). The mean (standard deviation) growth rates of GA detected on color fundus photographs were 2.27 (2.17) mm 2 and 1.91 (2.27) mm 2 at month 12, and 4.94 (2.96) mm 2 and 5.72 (3.97) mm 2 at month 24, for the sirolimus and sham groups, respectively. There was no statistically significant difference in the GA growth rates between the two treatment groups (P=0.33). Median visual acuity changes and incidence of 15-letter loss from baseline were not different between the 2 treatment groups (p=0.19). The intervention was stopped early because of sterile endophthalmitis that occurred in 3 participants in the sirolimus group. Participants were followed for safety until the study was closed in May 2015 due to lack of efficacy

Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration.

PubMed

Guthoff, Rainer; Guthoff, Tanja; Meigen, Thomas; Goebel, Winfried

2011-01-01

To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration. Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months. The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P < 0.05). Also, after 7 months, best-corrected visual acuity was significantly higher in the bevacizumab/rTPA/gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P < 0.05). Reading vision could be restored in 0% (rTPA/gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas). From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

Effect of Photodynamic Therapy with Posterior Sub-Tenon Triamcinolone Acetonide on Predominantly Classic Choroidal Neovascularization: One-Year Results

PubMed Central

Sertoz, Ayzin Deniz; Ates, Orhan; Keles, Sadullah; Kocer, Ibrahim; Kulacoglu, Destan Nil; Baykal, Orhan

2008-01-01

Objective: The aim of this study was to compare the results of monotherapy (photodynamic therapy) and combined therapy (photo-dynamic therapy with posterior sub-Tenon triamcinolone acetonide) in age-related macular degeneration (AMD). Materials and Methods: Forty eyes from forty patients with diagnosed neovascular AMD were enrolled in this study during March-2005 – October-2008. All patients were grouped in either the study or the control group. Both the study and control groups consisted of 20 eyes from 20 patients. The study group was treated with posterior sub-Tenon triamcinolone acetonide (PSTA) along with their initial photodynamic therapy (PDT) treatment. The control group members were treated with PDT alone. All patients were examined at 1, 3, 6 and 12 months. Visual acuity (VA), lesion size and number of treatment sessions were recorded during each examination. Results: The mean difference between pre- and post-treatment VA using the Snellen chart was +0.6 ± 1.7 in study group and −1.4 ± 1.7 in control. The difference for VA was significant in the study group as compared to control (p<0.05). The decrease in lesion size in the study group was 680±1195.2 µm, and the decrease was 32.75 ± 809.9 µm in the control. The difference with regard to the decrease in lesion sizes was significant in the study group as compared to the control (p<0.05). Total PDT treatment sessions were applied 1.2 times per patient in the study group and 1.9 times per patient in the control group. The difference was not significant (p>0.05). Conclusion: Our study showed that PSTA with PDT significantly reduces CNV growth, and improves VA at the 12-month follow-up in patients with AMD. PMID:25610041

EFFICACY OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN THE TREATMENT OF VITREOUS HEMORRHAGE RELATED TO PROLIFERATIVE DIABETIC RETINOPATHY.

PubMed

Chelala, Elias; Nehme, Joseph; El Rami, Hala; Aoun, Roni; Dirani, Ali; Fadlallah, Ali; Jalkh, Alex

2018-06-01

To investigate the efficacy of intravitreal ranibizumab injections in proliferative diabetic retinopathy associated with vitreous hemorrhage (VH). A prospective study including patients with proliferative diabetic retinopathy who presented with persistent VH. Vitreous hemorrhage was graded into mild, moderate, and severe. Patients were randomized into two groups: the ranibizumab group was treated with intravitreal injections of ranibizumab and the control group was assigned to observation alone. Vitrectomy was performed if there was any aggravation of the VH in patients with mild, moderate, and severe VH or in the absence of improvement by 16 weeks in patients with moderate and severe VH. The ranibizumab group included 71 patients and the control group included 62 patients. There was a statistically significant difference in the vitrectomy rate in patients with mild-to-moderate VH (5 patients [7.04%] and 12 patients [19.35%], respectively; P = 0.04). However, there was no statistically significant difference in the overall vitrectomy rate, and in the vitrectomy rate in severe VH (17 [23.94%] and 12 [16.90%] patients in the ranibizumab group vs. 22 [35.48%] and 10 [16.13%] patients in the control group, P = 0.14 and P = 0.83, respectively). Recurrence of the VH occurred in 22 patients in the ranibizumab group and 29 patients in the control group (P = 0.06). Better visual acuity measurements were recorded on all follow-up visits in the ranibizumab group (P ≤ 0.04). Intravitreal ranibizumab injections could be considered in proliferative diabetic retinopathy patients with mild and moderate VH.

Short-term clinical evaluation of intralesional triamcinolone acetonide injection for ulcerative oral lichen planus.

PubMed

Xia, Juan; Li, Chunyang; Hong, Yun; Yang, Linglan; Huang, Yulei; Cheng, Bin

2006-07-01

Efforts are made in a continued searching for novel therapies for symptomatic oral lichen planus (OLP). This study aimed to evaluate the efficacy and safety of intralesional triamcinolone acetonide (TA) injection for ulcerative OLP. Forty-five patients with clinical and histologically confirmed ulcerative OLP on bilateral buccal mucosa, one for treatment and the other for control, were studied. All participants received 0.5 ml TA (40 mg/ml) on experimental sites. Visual analogue scale score and lesion areas were recorded at the time of injection and 1-week interval. After 2 weeks, if the treated ulceration reduced < 81% in size, a second injection was given. The treated group gave rapid relief of signs and symptoms, while the control group showed minimal decrease. 38 (84.4%) patients demonstrated complete response in ulceration size. No complications were noted with TA injections. Intralesional TA injection in ulcerative OLP is effective and safe in achieving lesion and pain regression.

Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial.

PubMed

Toy, Brian C; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2012-05-01

To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2. Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography. The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 ± 7.0% for study eyes and -2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes. Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

The clinical outcomes of surgical management of anterior chamber migration of a dexamethasone implant (Ozurdex®).

PubMed

Kang, Hyunseung; Lee, Min Woo; Byeon, Suk Ho; Koh, Hyoung Jun; Lee, Sung Chul; Kim, Min

2017-09-01

Our purpose was to describe the clinical course, and individualized management approaches, of patients with migration of a dexamethasone implant into the anterior chamber. This was a retrospective review of four patients with seven episodes of anterior chamber migration of a dexamethasone implant. After 924 intravitreal dexamethasone injections, anterior migration of the implant occurred in four eyes of four patients (0.43%). All four eyes were pseudophakic: one eye had a posterior chamber intraocular lens in the capsular bag but in a post-laser posterior capsulotomy state, two eyes had a sulcus intraocular lens (IOL), and one eye had an iris-fixated retropupillary IOL. All eyes had a prior vitrectomy and no lens capsule. The time interval from injection to detection of the implant migration ranged from 2 to 6 weeks. Of the four eyes with corneal edema, only one eye required a corneal transplantation, although it was unclear whether the implant migration was the direct cause of the corneal decompensation because the patient had a history of bullous keratopathy resulting from an extended history of uveitis. All patients underwent surgical intervention: two patients with a repositioning procedure, and the other two patients with removal due to repeated episodes, although surgical removal was not always necessary to reverse the corneal complications. In our study, not all patients required surgical removal of the implants. Repositioning the implant back into the vitreous cavity may be considered as an option in cases involving the first episode with no significant corneal endothelial decompensation. Considering potential anterior segment complications and the loss of drug effectiveness together, an individualized approach is recommended to obtain the best treatment outcomes and to minimize the risk of corneal complications.

[Managment of subretinal heamorrhages within the macular area using intravitreal injections of recombined tissue plasminogen activator, sulphur hexafluoride and ranihizumab--preliminary report].

PubMed

Miniewicz, Joanna; Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Boźena

2015-01-01

Submacular hemorrhages cause serious vision impairment. Patient observation, waiting for the spontaneous blood reabsorption and resolution of the haemorrhage leads to the severe damage to retinal tissue as a result of scar formation. The paper presents 7 cases of patients with submacular haemorrhages treated with intravitreal injections of recombined tissue plasminogen activator (rtPA) and sulphur hexafluoride (SFG). In 4 cases, the haemorrhage was secondary to AMD, in two cases to trauma, and it was idiopathic in one case. All patients were treated with intravitreal injections of rtPA and SF6 for thrombolysis and pneumatic displacement of haemorrhage outside macular structures. Ranibizumab was additionally administered to patients with age-related macular degeneration. Such treatment improved visual acuity in all patients, reducing the central retinal thickness as shown in follow-up optical coherence tomography. The presented treatment of submacular hemorrhages with intravitreal injections of rtPA and SF6 provided good results, but in order to develop a standard management algorithm for this disease, the analysis of larger patient sample is required.

Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635

PubMed Central

Agurto-Rivera, Ricardo; Diaz-Rubio, Jose; Torres-Bernal, Luis; Macky, Tamer A; Colina-Luquez, Juner; Papa-Oliva, Gabriela; Jager, Rama D; Martinez-Jardon, Susana; Fromow-Guerra, Jans; Quiroz-Mercado, Hugo

2005-01-01

Background To assess the effect of intravitreal triamcinolone acetonide (iTA) as an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD). Methods This prospective randomized controlled pilot study comprised 26 patients scheduled to receive TTT, due to either absent indications for photodynamic therapy or financial issues. Patients were assigned into; Group A (n = 14) received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for; best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by optical coherence tomography (OCT). Results All 26 patients completed 6 months of follow ups. The average age for both groups was 74 years. Occult CNV formed 64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic 15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045 for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and 2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six months the proportion of patients gained ≥ 1 lines was 14% and 25% (P = 0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P = 0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P = 0.341), for group A and B respectively. Conclusion The use of iTA as an adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better functional results. However due to the small sample size of the study a statistically significant results could not be reached. PMID:16309554

Comparative toxicity of 4 commonly used intravitreal corticosteroids on rat retina.

PubMed

Citirik, Mehmet; Dilsiz, Nihat; Batman, Cosar; Zilelioglu, Orhan

2009-06-01

To investigate the effects of 4 commonly used steroids (dexamethasone, triamcinolone, betamethasone, and methylprednisolone) on 50 retinas of 25 adult pigmented rats. Experimental animal study. Twenty-five pigmented Long-Evans male rats. Each steroid drug with 2 different doses (0.025 mL and 0.050 mL) was injected into the vitreous of each eye of 5 rats. The low drug dose was injected into the right eye and the high dose was injected into the left eye. Ten eyes of 5 randomly selected rats were used as a control group and intravitreal saline was injected into these eyes. Oxidative damage and intrinsic antioxidative capacity were determined by measuring retinal malondialdehyde (MDA) and glutathione (GSH) levels, respectively. No statistically meaningful difference was observed in retinal GSH and MDA measurements in the low- and high-dose triamcinolone (1 and 2 mg), low-dose betamethasone (0.075 mg), and low-dose dexamethasone (0.1 mg) groups, compared with the control group. Both doses of methylprednisolone (1.6 mg and 3.2 mg), high-dose betamethasone (0.15 mg), and high-dose dexamethasone (0.2 mg) markedly altered retinal GSH and MDA levels. The results of our study show that the toxicity of triamcinolone is not evident even in high doses. It may be used safely. We also suggest that intravitreal use of low doses of betamethasone and dexamethasone is safer than higher doses of these drugs and both doses of methylprednisolone.

A Novel Method Combining Vitreous Aspiration and Intravitreal AAV2/8 Injection Results in Retina-Wide Transduction in Adult Mice.

PubMed

Da Costa, Romain; Röger, Carsten; Segelken, Jasmin; Barben, Maya; Grimm, Christian; Neidhardt, John

2016-10-01

Gene therapies to treat eye disorders have been extensively studied in the past 20 years. Frequently, adeno-associated viruses were applied to the subretinal or intravitreal space of the eye to transduce retinal cells with nucleotide sequences of therapeutic potential. In this study we describe a novel intravitreal injection procedure that leads to a reproducible adeno-associated virus (AAV)2/8-mediated transduction of more than 70% of the retina. Prior to a single intravitreal injection of a enhanced green fluorescent protien (GFP)-expressing viral suspension, we performed an aspiration of vitreous tissue from wild-type C57Bl/6J mice. One and one-half microliters of AAV2/8 suspension was injected. Funduscopy, optical coherence tomography (OCT), laser scanning microscopy of retinal flat mounts, cryosections of eye cups, and ERG recordings verified the efficacy and safety of the method. The combination of vitreous aspiration and intravitreal injection resulted in an almost complete transduction of the retina in approximately 60% of the eyes and showed transduced cells in all retinal layers. Photoreceptors and RPE cells were predominantly transduced. Eyes presented with well-preserved retinal morphology. Electroretinographic recordings suggested that the new combination of techniques did not cause significant alterations of the retinal physiology. We show a novel application technique of AAV2/8 to the vitreous of mice that leads to widespread transduction of the retina. The results of this study have implications for virus-based gene therapies and basic science; for example, they might provide an approach to apply gene replacement strategies or clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in vivo. It may further help to develop similar techniques for larger animal models or humans.

POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

PubMed

Reibaldi, Michele; Pulvirenti, Alfredo; Avitabile, Teresio; Bonfiglio, Vincenza; Russo, Andrea; Mariotti, Cesare; Bucolo, Claudio; Mastropasqua, Rodolfo; Parisi, Guglielmo; Longo, Antonio

2018-01-01

To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

Comparison of Intravitreal Bevacizumab, Intravitreal Ranibizumab and Laser Photocoagulation for Treatment of Type 1 Retinopathy of Prematurity in Turkish Preterm Children.

PubMed

Kabataş, Emrah Utku; Kurtul, Bengi Ece; Altıaylık Özer, Pınar; Kabataş, Naciye

2017-07-01

To evaluate effectiveness of treatment modalities, major complications and refractive errors in children who were treated with intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP). Premature infants who underwent IVB monotherapy (Group 1), IVR monotherapy (Group 2) or LP (Group 3) for type 1 ROP and infants with spontaneously regressed ROP (Group 4) were included for the study. Major complications, recurrence rate, recurrence time, total retinal vascularization time and refractive errors at 18 months of corrected age (CA) were determined. Groups 1, 2, 3 and 4 included 24 eyes of 12 patients, 12 eyes of six patients, 72 eyes of 36 patients and 148 eyes of 74 patients, respectively. Recurrence of the disease occurred in two eyes of one patient in Group 1 at 52 weeks of postmenstrual age (PMA) and two eyes of one patient at 48 weeks of PMA in Group 2. In Group 3, disease did not regress after the first treatment in 10 eyes of five patients. The mean vascularization time in Group 1 was 73 ± 10.1 weeks of PMA and 61.8 ± 6.6 weeks of PMA in Group 2 (p = 0.027). Macular ectopia was seen in two eyes of one patient and exudative retinal detachment (ERD) occurred in two eyes of one patient in Group 3. Mean spherical equivalent was 1.49 ± 3.04 diopters (D) in Group 1, -1.79 ± 2.87D in Group 2, -1.27 ± 2.8 D in Group 3 and 1.52 ± 1.07 D in Group 4 at 18 months of CA. There was no significant difference in astigmatism values in all groups. IVB, IVR and LP are options that can successfully treat ROP. Myopia was observed to be the main refractive error in all treatment groups. Vascularization of the retina was completed later in the IVB group than in the IVR group.

Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

PubMed

Petrou, Philip A; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y; Wong, Wai T

2014-12-18

To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

PubMed

Cheng, Hui-Chen; Lee, Shui-Mei; Hsieh, Yi-Ting; Lin, Po-Kang

2015-04-01

To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

[Intravitreal Ranibizumab Injection for the Treatment of Occult and Classic CNV in Exsudative AMD].

PubMed

Maier, M M; Feucht, N; Fegert, C; Fiore, B; Winkler von Mohrenfels, C; Lohmann, C

2011-02-01

Double-blind, randomised, placebo-controlled and multicentre studies have proven an increase in visual acuity in one-third of the patients receiving Ranibizumab (0.5 mg) injections, who suffer from exsudative AMD. The purpose of this study was to evaluate the early effects of intravitreal Ranibizumab therapy in patients with mainly occult neovascular AMD in clinical applications. In a retrospective cohort study, 91 eyes with occult and classic neovascular AMD were treated with intravitreal injections of Ranibizumab (0.5 mg) at 30-day intervals. The treatment effects were evaluated according to best corrected visual acuity, optical coherence tomography (OCT) and intraocular pressure at baseline as well as 1, 3 and 6 months after the beginning of therapy. Furthermore, fluorescein angiography (FLA) was performed at baseline as well as 3 and 6 months after therapy. 74 % of the patients lost fewer than 15 letters on the EDTRS-scale 6 months after the beginning of therapy. Visual acuity improved by more than 15 letters in 11 % of the patients. Central retinal thickness, measured by OCT, decreased statistically significantly in each control compared to baseline (1 month: p = 0.045; 3 months: p = 0.001; 6 months: p = 0.006). Leakage and membranes, evaluated in FA, worsened in 31 % of the patients; in 67 % the findings were stable. No increase in intraocular pressure was detected. Intravitreal application of Ranibizumab was safe and well tolerated. In the clinical situation, visual acuity was stabilised in the short term. As opposed to phase-III studies, no improvement in visual acuity could be accomplished. Cental retinal thickness decreased and findings in fluorescein angiography were stable within a 6-month follow-up period. It is necessary to perform monthly controls and proceed with VA- and OCT-based injections in order to maintain the therapeutic effect. Futher clinical evaluations of Ranibizumab will be necessary to evaluate its long-term treatment effects. �

Streptococcus endophthalmitis outbreak after intravitreal injection of bevacizumab: one-year outcomes and investigative results.

PubMed

Goldberg, Roger A; Flynn, Harry W; Miller, Darlene; Gonzalez, Serafin; Isom, Ryan F

2013-07-01

To report the 1-year clinical outcomes of an outbreak of Streptococcus endophthalmitis after intravitreal injection of bevacizumab, including visual acuity outcomes, microbiological testing, and compound pharmacy investigations by the Food and Drug Administration (FDA). Retrospective consecutive case series. Twelve eyes of 12 patients who developed endophthalmitis after receiving intravitreal bevacizumab prepared by a single compounding pharmacy. Medical records of patients were reviewed; phenotypic and DNA analyses were performed on microbes cultured from patients and from unused syringes. An inspection report by the FDA based on site visits to the pharmacy that prepared the bevacizumab syringes was summarized. Visual acuity, interventions received, time to intervention, microbiological consistency, and FDA inspection findings. Between July 5 and 8, 2011, 12 patients developed endophthalmitis after intravitreal bevacizumab from syringes prepared by a single compounding pharmacy. All patients received initial vitreous tap and injection, and 8 patients (67%) subsequently underwent pars plana vitrectomy (PPV). After 12 months follow-up, outcomes have been poor. Seven patients (58%) required evisceration or enucleation, and only 1 patient regained pre-injection visual acuity. Molecular testing using real-time polymerase chain reaction, partial sequencing of the groEL gene, and multilocus sequencing of 7 housekeeping genes confirmed the presence of a common strain of Streptococcus mitis/oralis in vitreous specimens and 7 unused syringes prepared by the compounding pharmacy at the same time. An FDA investigation of the compounding pharmacy noted deviations from standard sterile technique, inconsistent documentation, and inadequate testing of equipment required for safe preparation of medications. In this outbreak of endophthalmitis, outcomes have been generally poor, and PPV did not improve visual results at 1-year follow-up. Molecular testing confirmed a common strain

Streptococcus Endophthalmitis Outbreak after Intravitreal Injection of Bevacizumab: One-year Outcomes and Investigative Results

PubMed Central

Goldberg, Roger A.; Flynn, Harry W.; Miller, Darlene; Gonzalez, Serafin; Isom, Ryan F.

2013-01-01

Purpose To report the one-year clinical outcomes of an outbreak of Streptococcus endophthalmitis after intravitreal injection of bevacizumab, including visual acuity outcomes, microbiological testing and compound pharmacy investigations by the Food and Drug Administration (FDA). Design Retrospective consecutive case series. Participants 12 eyes of 12 patients who developed endophthalmitis after receiving intravitreal bevacizumab prepared by a single compounding pharmacy. Methods Medical records of patients were reviewed; phenotypic and DNA analyses were performed on microbes cultured from patients and from unused syringes. An inspection report by the FDA based on site-visits to the pharmacy that prepared the bevacizumab syringes was summarized. Main Outcome Measures Visual acuity, interventions received, time-to-intervention; microbiological consistency; FDA inspection findings. Results Between July 5 and July 8, 2011, 12 patients developed endophthalmitis after intravitreal bevacizumab from syringes prepared by a single compounding pharmacy. All patients received initial vitreous tap and injection, and eight (67%) subsequently underwent pars plana vitrectomy (PPV). After twelve months follow-up, outcomes have been poor: 7 patients (58%) required evisceration or enucleation, and only one patient regained pre-injection visual acuity. Molecular testing using real time polymerase chain reaction, partial sequencing of the groEL gene, and multilocus sequencing of 7 housekeeping genes confirmed the presence of a common strain of Streptococcus mitis/oralis in vitreous specimens and seven unused syringes prepared by the compounding pharmacy at the same time. An FDA investigation of the compounding pharmacy noted deviations from standard sterile technique, inconsistent documentation, and inadequate testing of equipment required for safe preparation of medications. Conclusions In this outbreak of endophthalmitis, outcomes have been generally poor and PPV did not improve

Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR.

PubMed

Yin, Philip D; Kurup, Shree K; Fischer, Steven H; Rhee, Henry H; Byrnes, Gordon A; Levy-Clarke, Grace A; Buggage, Ronald R; Nussenblatt, Robert B; Mican, JoAnn M; Wright, Mary E

2007-03-01

Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes.

A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema.

PubMed

Daull, Philippe; Paterson, Christopher A; Kuppermann, Baruch D; Garrigue, Jean-Sébastien

2013-03-01

Dexamethasone palmitate (DXP) is a lipophilic prodrug of dexamethasone (DXM), a potent corticosteroid used to treat a variety of ophthalmic diseases. The aim of the study was to characterize the sustained release capacity (in rabbit), efficacy (in rat and rabbit), and safety (in rabbit, cat, and minipig) of intravitreal (IVT) DXP emulsions in preclinical models. Oil-in-water emulsions of DXP were administered by IVT injections in rats, rabbits, cats, or minipigs. Efficacy was assessed in rabbits by the inhibition of VEGF-induced vascular leakage and in rats by inhibition of laser-induced choroidal neovascularization. Concentrations of DXP and DXM in aqueous humor, vitreous, retina, choroid, and blood were determined to characterize the ocular and systemic pharmacokinetic (PK) profile. Complete ophthalmic examinations (indirect ophthalmoscopy, slit-lamp biomacroscopy, electroretinography, tonometry) were performed to assess the ocular safety of IVT DXP doses up to 2,600 μg in minipig, followed by histopathologic examinations. A validated feline model of DXM-induced elevated intraocular pressure (IOP) was used to assess the ocular hypertensive impact (i.e., the safety) of an IVT injection of DXP emulsion. Rat and rabbit efficacy data demonstrated that IVT injections of DXP emulsions were effective. Rabbit PK data demonstrated that following a single 1,280 μg IVT injection resulted in sustained DXM levels in the retina and choroid (1,179.6 and 577.7 ng/g with a half-life of 189 and 103 days, respectively) sufficient to inhibit VEGF-induced vascular hyper-permeability for up to 9 months. No adverse ocular findings were observed in the rabbit at the 1,280 μg DXP dose. Plasma levels of DXP and DXM were close to the lower limit of quantification (0.5 ng/mL). In minipigs, no systemic effects were observed at a dose up to 2,600 μg DXP. In steroid responsive cats, IVT DXP emulsions increased IOP to a lesser extent than triamcinolone acetonide with a more rapid return to

Intravitreal ranibizumab as an adjunct for Ahmed valve surgery in open-angle glaucoma: a pilot study.

PubMed

Desai, Rajen U; Singh, Kuldev; Lin, Shan C

2013-03-01

To determine the safety and efficacy of intravitreal ranibizumab therapy before and after Ahmed tube insertion for open-angle glaucoma as a means of optimizing postoperative intraocular pressure control. Randomized, controlled trial. Open-angle glaucoma patients scheduled for Ahmed tube insertion, randomized to ranibizumab or control groups. Ranibizumab (0.5 mg in 0.05 mL) was administered intravitreally at three time points: 9 days prior to surgery, 1 month post-surgery and 2 months post-surgery. Control patients underwent the same procedure without ranibizumab. Success at 6 months postoperatively was defined as intraocular pressure <18 mmHg with no adjunctive medications or intraocular pressure <15 mmHg with one adjunctive medication. The study and control arms included six and five subjects, respectively, with four in each arm undergoing combined cataract surgery. In the ranibizumab arm, the preoperative and postoperative intraocular pressure/medication usage was 21.0 ± 6.7 mmHg on 3.2 ± 1.5 medications and 14.7 ± 1.9 mmHg on 0.5 ± 0.8 medications, respectively. In the control arm, preoperative and postoperative intraocular pressure/medication usage was 18.8 ± 3.8 mmHg on 2.8 ± 1.3 medications and 16.2 ± 3.6 mmHg with 1.8 ± 1.6 medications, respectively. Success was achieved in 83% of subjects in the ranibizumab group compared with 40% in the control group (two-tailed Fisher's exact test, P = 0.24). The findings from this small pilot comparative study suggest that intravitreal ranibizumab use may be a safe and potentially effective adjunctive treatment modality in improving success after Ahmed tube placement. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

A 9 year-old girl with herpes simplex virus type 2 acute retinal necrosis treated with intravitreal foscarnet.

PubMed

King, John; Chung, Mina; DiLoreto, David A

2007-01-01

A 9-year-old girl presented with a 2-week history of redness in the left eye. Examination revealed vitritis, retinal whitening, vasculitis, and optic nerve head edema. Polymerase chain reaction testing of the aqueous fluid revealed herpes simplex virus type 2. The retinitis was controlled with intravenous acyclovir and intravitreal foscarnet. The clinical course was complicated by retinal neovascularization and vitreous hemorrhage, which was treated by pars plana vitrectomy and endolaser. While there are few case reports of herpes simplex virus type 2 retinitis in children, this one is unique for the following reasons: it is the first reported case of herpes simplex virus type 2 retinitis in a child less than 10 years old without a previous history of neonatal infection or central nervous system involvement; no other children have been reported to have been treated with intravitreal foscarnet; and retinal neovascularization complicated the recovery.

Treatment of Non-neovascular Idiopathic Macular Telangiectasia Type 2 with Intravitreal Ranibizumab: Results of a Phase II Clinical Trial

PubMed Central

Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2015-01-01

Purpose To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for non-neovascular idiopathic macular telangiectasia, type 2 (IMT2). Methods Single-center, open-label phase II clinical trial enrolling 5 participants with bilateral non-neovascular IMT2. Intravitreal ranibizumab (0.5mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in: best corrected visual acuity (BCVA), area of late-phase leakage on fluorescein angiography (FA), and retinal thickness on optical coherence tomography (OCT). Results The study treatment was well-tolerated and associated with few adverse events. Change in BCVA at 12 months was not significantly different between treated study eyes (0.0±7.5 letters) and control fellow eyes (+2.2±1.9 letters). However, decreases in the area of late-phase FA leakage (−33±20% for study eyes, +1±8% for fellow eyes) and in OCT central subfield retinal thickness (−11.7±7.0% for study eyes and −2.9±3.5% for fellow eyes) were greater in study eyes compared to fellow eyes. Conclusions Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with non-neovascular IMT2. PMID:22266930

Efficacy of Intravitreal injection of 2-Methoxyestradiol in regression of neovascularization of a retinopathy of prematurity rat model.

PubMed

Said, Azza Mohamed Ahmed; Zaki, Rania Gamal Eldin; Salah Eldin, Rania A; Nasr, Maha; Azab, Samar Saad; Elzankalony, Yaser Abdelmageuid

2017-04-04

Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat. ROP was induced in 21 rats then two concentrations of 2-ME nanoparticles were injected in right eyes of 14 rats (low dose; study group I, high dose; study group II). A blank nanoemulsion was injected in the right eyes of seven rats (control positive group I). No injections performed in contralateral left eyes (control positive group II). Seven rats (14 eyes) were kept in room air (control negative group). On postnatal day 17, eyeballs were enucleated. Histological structure of the retina was examined using Hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP) expressions were detected by immunohistochemical studies. Intravitreal injection of 2-ME (in the two concentrations) caused marked regression of the new vascular tufts on the vitreal side with normal organization and thickness of the retina especially in study group II, which also show negative VEGF immunoreaction. Positive GFAP expression was detected in the control positive groups and study group (I). Intravitreal injection of 2-Methoxyestradiol nanoemulsion is a promising effective method in reduction of neovascularization of a ROP rat model.

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PubMed

Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

2017-12-01

To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P < 0.001). Similarly, subfoveal choroidal thickness had decreased from 157.0 μm (interquartile range 116.0-244.5) at baseline to 139.0 μm (interquartile range 102.5-212.0) at the final examination (P < 0.001). Both parameters macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

Pneumatic Displacement with Perfluoropropane Gas and Intravitreal Tissue Plasminogen Activator for Subretinal Subfoveal Hemorrhage after Focal Laser Photocoagulation in Central Serous Chorioretinopathy

PubMed Central

Espinoza, Juan V.; Lasave, Andres F.; Savino-Zari, Dario; Arevalo, Fernando A.

2014-01-01

Objective. To report the visual and anatomic outcomes of pneumatic displacement with perfluoropropane (C3F8) gas and intravitreal tissue plasminogen activator (IVTPA) for subretinal subfoveal hemorrhage after focal laser photocoagulation in central serous chorioretinopathy (CSCR). Method. Interventional, retrospective case report of one eye (one patient). Outcome measures included visual acuity (VA), central macular thickness (CMT), and size of the lesion at two weeks of followup. Fluorescein angiography (FA) and optical coherent tomography (OCT) were used to measure anatomic outcomes. Results. A 35-year-old man with history of chronic CSCR received focal laser photocoagulation in the right eye two days before presentation. At initial examination, VA was 20/200 (ETDRS chart), CMT was 398 μ, and a subretinal subfoveal hemorrhage was seen. Tissue plasminogen activator (tPA) at a dose of 25 µg/0.1 mL was injected intravitreally before intravitreal C3F8 injection, and prone positioning was indicated postoperatively. At 24 hours, the hemorrhage had been displaced inferiorly and VA improved to 20/100. Two weeks later, VA improved to 20/80, CMT decreased to 225 μ, and the hemorrhage decreased without foveal involvement. Conclusions. The technique seems safe and effective in treating visually significant subretinal subfoveal hemorrhage. PMID:25485161

Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

PubMed

Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

2018-03-01

Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals

FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

PubMed

Onishi, Yuka; Yokoi, Tae; Kasahara, Kaori; Yoshida, Takeshi; Nagaoka, Natsuko; Shinohara, Kosei; Kaneko, Yuichiro; Suga, Mitsuki; Uramoto, Kengo; Ohno-Tanaka, Akiko; Ohno-Matsui, Kyoko

2018-05-03

To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV). We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis. The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy. Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.

High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration.

PubMed

Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung; Kwon, Oh Woong

2016-08-01

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Increasing the dose of bevacizumab in refractory PED may be a possible treatment option.

Intravitreal injection of rapamycin-loaded polymeric micelles for inhibition of ocular inflammation in rat model.

PubMed

Wu, Wei; He, Zhifen; Zhang, Zhaoliang; Yu, Xinxin; Song, Zongming; Li, Xingyi

2016-11-20

The therapeutic efficacy of rapamycin conjugated monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles (rapamycin micelles) was evaluated in a rat experimental autoimmune uveitis (EAU) model. Rapamycin micelles exhibited spherical morphology and had a mean particle size of 40nm and a zeta-potential of -0.89mv. The water solubility of rapamycin improved by more than 1000-fold in a micellar formulation. Intravitreal injection of MPEG-PCL micelles did not result in vitreous hemorrhage or retinal detachment. Fluorescence microscopy demonstrated that labeled micelles localized to the retinal pigment epithelium for at least 14 days following injection and the drug concentration of rapamycin micelles in the retinal tissue was significantly higher than unconjugated rapamycin over this period. At the optimal concentration of rapamycin micelles (9μg/eye), clinical signs of EAU were abolished via the downregulation of the Th1 and Th17 response. There were no significant difference in T cell proliferation and delayed-type hypersensitivity between the treatment and control groups, suggesting that the therapeutic effect of rapamycin manifested locally in the eye and not systemically. These results indicate that intravitreal injection of rapamycin micelles is a promising therapy for controlling sterile intraocular inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.

PubMed

Lai, Kunbei; Jin, Chenjin; Tu, Shu; Xiong, Yunfan; Huang, Rui; Ge, Jian

2014-07-01

The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136 ± 0.0283 mm(2), p <0.01; n = 6) and 0.01 μg/mL (0.4351 ± 0.0349 mm(2), p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm(2); n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the (99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in

Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats.

PubMed

Peters, Tobias; Kim, Seong-Woo; Castro, Vinicius; Stingl, Krunoslav; Strasser, Torsten; Bolz, Sylvia; Schraermeyer, Ulrich; Mihov, George; Zong, MengMeng; Andres-Guerrero, Vanessa; Herrero Vanrell, Rocio; Dias, Aylvin A; Cameron, Neil R; Zrenner, Eberhart

2017-04-01

To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated. Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8). Electroretinography (ERG), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (sdOCT) were performed at baseline, weeks 1 and 2, and months 1, 2, and 3 after intravitreal injection. Eyes were histologically examined using light microscopy and transmission electron microscopy at the end of the in vivo study. There were no statistically significant changes in ERG among the groups. Abnormal FAF pattern and abnormal deposits in OCT were observed after injection but almost completely disappeared between week 2 and month 3 in all injected groups. GFAP staining showed that Müller glia cell activation was most pronounced in PLGA-injected eyes. Increased cell death was not observed by TUNEL staining at month 1. In electron microscopy at month 3, the remnants of microparticles were found in the retinal cells of all injected groups, and loss of plasma membrane was seen in the PLGA group. Although morphological changes such as mild glial activation and material remnants were observed histologically 1 month and 3 months after injection in all injected groups, minor cell damage was noted only in the PLGA group at 3 months after injection. No evidence of functional abnormality relative to untreated eyes could be detected by ERG 3 months after injection in all groups. Changes observed in in vivo imaging such as OCT and FAF disappeared after 3 months in almost all cases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

PubMed Central

Koocheki, Saeid; Madaeni, Sayed Siavash; Niroomandi, Parisa

2011-01-01

We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly(d,l-lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement. PMID:21589650

Vitreomacular Changes after Intravitreal Gas Injection for Idiopathic Impending or Early Macular Hole: An Optical Coherence Tomography Study.

PubMed

Tew, Teck-Boon; Chen, Ta-Ching; Yang, Chang-Hao; Yang, Chung-May

2018-01-01

To study the early changes of vitreomacular microstructure by optical coherence tomography (OCT) after intravitreal gas injection for the treatment of idiopathic impending or early full-thickness macular hole (FTMH). A retrospective, interventional case series. A total of 21 eyes were included. In the impending macular hole, 8/8 achieved vitreomacular traction (VMT) release, while a macular hole developed in 1 case. On postoperative day 1, the vitreomacular configuration by OCT showed either a flattening (n = 3) or elevation (n = 1) pattern. In early FTMH, vitreomacular separation was achieved in 10/13 cases, but macular hole closure was only observed in 3 cases. On postoperative day 1, only flattening of the vitreomacular configuration was observed (n = 5). Enlargement of the macular hole was found in 4 cases. VMT separation can be achieved with intravitreal gas injection by mechanically stretching the posterior vitreous cortex, causing either flattening or steepening of the vitreomacular configuration. However, it did not always result in macular hole closure. © 2017 S. Karger AG, Basel.

Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres.

PubMed

Doty, Amy C; Hirota, Keiji; Olsen, Karl F; Sakamoto, Naoya; Ackermann, Rose; Feng, Meihua R; Wang, Yan; Choi, Stephanie; Qu, Wen; Schwendeman, Anna; Schwendeman, Steven P

2016-12-01

Here we describe development of a silicone rubber/stainless steel mesh cage implant system, much like that used to assess biocompatibility of biomaterials [1], for easy removal of injectable polymer microspheres in vivo. The sterile cage has a type 316 stainless steel mesh size (38 μm) large enough for cell penetration and free fluid flow in vivo but small enough for microsphere retention, and a silicone rubber shell for injection of the microspheres. Two model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist, leuprolide, were encapsulated in PLGA microspheres large enough (63-90 μm) to be restrained by the cage implant in vivo. The in vitro release from both formulations was followed by ultra-performance liquid chromatography (UPLC) with and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 + 0.05% sodium azide, at 37 °C. Pharmacokinetics (PK) in rats was assessed after SC injection or SC in-cage implantation of microspheres with plasma analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely unaffected after the initial burst irrespective of the cage or test tube incubation vessel and release was much slower than observed in vivo for both drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage were highly similar during the 2-3 week release duration before a significant inflammatory response was caused by the cage implant. Hence, the PK-validated cage implant provides a simple means to recover and evaluate the microsphere drug carriers in vivo during a time window of at least a few weeks in order to characterize the polymer microsphere release and erosion behavior in vivo. This approach may facilitate development of mechanism-based in vitro/in vivo correlations and enable development of more accurate and useful in vitro release tests. Copyright © 2016 Elsevier Ltd. All

Intravitreal Adalimumab in Active Noninfectious Uveitis: A Pilot Study.

PubMed

Hamam, Rola N; Barikian, Anita W; Antonios, Rafic S; Abdulaal, Marwan R; Alameddine, Ramzi M; El Mollayess, Georges; Mansour, Ahmad M

2016-06-01

To evaluate the short-term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis. Consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2, then every 4 weeks for total of 26 weeks. Six out of 7 patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Seven out of 12 eyes had improvement of ≥2 ETDRS lines. Three out of three eyes had resolution of anterior chamber cells. And 9 of 10 eyes with vitreous haze had zero haze at 26 weeks. Five out of 8 eyes with macular edema had complete resolution. Median fluorescein angiography score improved from 14 to 4 on last follow-up. IVA was effective in controlling the inflammation, decreasing the macular edema, and improving the best corrected visual acuity in the majority of eyes in this series.

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

PubMed

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

INFECTIOUS ENDOPHTHALMITIS AFTER GLAUCOMA DRAINAGE IMPLANT SURGERY: Clinical Features, Microbial Spectrum, and Outcomes.

PubMed

Zheng, Cindy X; Moster, Marlene R; Khan, M Ali; Chiang, Allen; Garg, Sunir J; Dai, Yang; Waisbourd, Michael

2017-06-01

To report the clinical features, microbial spectrum, and treatment outcomes of endophthalmitis after glaucoma drainage implant (GDI) surgery. Records of patients diagnosed with endophthalmitis after GDI surgery were reviewed. Data on clinical course, microbiological laboratory results, and treatment were analyzed. Of 1,891 eyes that underwent GDI surgery, 14 eyes (0.7%) developed endophthalmitis. The mean time interval between GDI surgery and diagnosis of endophthalmitis was 2.6 ± 3.2 years (median, 1.3 years; range, 11 days-11.4 years). For initial treatment, 13/14 eyes underwent vitreous tap and injection of intravitreal antibiotics and 1/14 eyes underwent primary pars plana vitrectomy. Three additional eyes underwent pars plana vitrectomy because of deteriorating clinical course. Glaucoma drainage implant erosion was present in 9/14 eyes. All 9 eroded GDIs were surgically removed within a mean of 9 ± 5 days (range 2-29 days) after diagnosis of endophthalmitis. Overall, mean logarithm of the minimum angle of resolution best-corrected visual acuity worsened from 0.7 ± 0.7 (Snellen equivalent 20/100) at baseline to 1.6 ± 1.1 (Snellen equivalent 20/800) at final follow-up (P = 0.005). Mean duration between the onset of symptoms and presentation was significantly longer in patients with decreased final best-corrected visual acuity (>2 Snellen lines) compared to patients with stable final best-corrected visual acuity (6.8 vs. 1.0 days; P = 0.005). Glaucoma drainage implant-related endophthalmitis is rare and often associated with GDI erosion. Patients who presented earlier after the onset of symptoms had better final visual outcomes. Prompt evaluation and treatment is required, often with removal of the eroded GDI.

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley

Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study.

PubMed

Korobelnik, Jean-François; Holz, Frank G; Roider, Johann; Ogura, Yuichiro; Simader, Christian; Schmidt-Erfurth, Ursula; Lorenz, Katrin; Honda, Miki; Vitti, Robert; Berliner, Alyson J; Hiemeyer, Florian; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert

2014-01-01

To evaluate the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO). A randomized, multicenter, double-masked phase 3 study. A total of 177 treatment-naive patients with macular edema secondary to CRVO were randomized in a 3:2 ratio. Patients received either 2-mg intravitreal aflibercept or sham injections every 4 weeks for 20 weeks. From week 24 to 48, the aflibercept group received aflibercept as needed (pro re nata [PRN]), and the sham group continued receiving sham injections. The primary efficacy end point was the proportion of patients who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24. This study reports week 52 results including the proportion of patients who gained 15 letters or more in BCVA and the mean change from baseline BCVA and central retinal thickness. Efficacy end points at week 52 were all exploratory. At week 52, the mean percentage of patients gaining 15 letters or more was 60.2% in the aflibercept group and 32.4% in the sham group (P = 0.0004). Aflibercept patients, compared with sham patients, had a significantly higher mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and reduction in central retinal thickness (-423.5 μm vs. -219.3 μm, respectively) at week 52 (P < 0.0001 for both). Aflibercept patients received a mean of 2.5 injections (standard deviation, 1.7 injections) during PRN dosing. The most common ocular adverse events in the aflibercept group were related to the injection procedure or the underlying disease, and included macular edema (33.7%), increased intraocular pressure (17.3%), and eye pain (14.4%). Treatment with intravitreal aflibercept provided significant functional and anatomic benefits after 52 weeks as compared with sham. The improvements achieved after 6 monthly doses at week 24 largely were maintained until week 52 with as-needed dosing. Intravitreal aflibercept

Triamcinolone Acetonide Decreases Outflow Facility in C57BL/6 Mouse Eyes

PubMed Central

Kumar, Sandeep; Shah, Shaily; Deutsch, Emily Rose; Tang, Hai Michael; Danias, John

2013-01-01

Purpose. To determine the effect of triamcinolone acetonide (TA) on outflow facility in mice. Methods. Animals received 20 μL of TA (40 mg/mL) suspension subconjunctivally either bilaterally or unilaterally and were euthanized after either 1 week or 3 weeks. Before mice were killed, IOP was measured with a rebound tonometer. Outflow facility was determined using simultaneous pressure and flow measurements. Another set of animals received bilateral injection of anecortave acetate (AA) with or without bilateral TA injection and their outflow facility was also determined. Myocilin expression was investigated in a subset of eyes using quantitative PCR (qPCR). Results. Outflow facility of eyes in animals receiving bilateral TA injection (TABL) and TA-treated eyes of animals receiving unilateral injection (TAUL) was significantly decreased compared to naïve control eyes (Cnaive) after 1 week and 3 weeks of TA treatment (ANOVA P < 0.01, P < 0.001, respectively). Eyes treated with AA (with or without TA) had higher outflow facility than animals treated with TA (P < 0.05). IOP data did not show any significant difference between groups. qPCR analysis revealed significant decrease in myocilin expression in eyes receiving AA compared to naïve control and TA-treated eyes (ANOVA P < 0.001). Conclusions. Steroid treatment significantly decreases outflow facility in C57BL/6 mice despite having small effect on IOP. This animal model can be useful for studying the pathogenesis of steroid-induced glaucoma. PMID:23322580

Safety and Effectiveness of Cataract Surgery with Simultaneous Intravitreal Anti-VEGF in Patients with Previously Treated Exudative Age-Related Macular Degeneration.

PubMed

Falcão, Manuel Sousa; Freitas-Costa, Paulo; Beato, João Nuno; Pinheiro-Costa, João; Rocha-Sousa, Amândio; Carneiro, Ângela; Brandão, Elisete Maria; Falcão-Reis, Fernando

2017-02-27

To evaluate the safety and impact on visual acuity, retinal and choroidal morphology of simultaneous cataract surgery and intravitreal anti-vascular endothelial growth factor on patients with visually significant cataracts and previously treated exudative age-related macular degeneration. Prospective study, which included 21 eyes of 20 patients with exudative age-related macular degeneration submitted to simultaneous phacoemulsification and intravitreal ranibizumab or bevacizumab. The patients were followed for 12 months after surgery using a pro re nata strategy. Visual acuity, foveal and choroidal thickness changes were evaluated 1, 6 and 12 months post-operatively. There was a statistically significant increase in mean visual acuity at one (13.4 letters, p < 0.05), six (11.5 letters, p < 0.05) and twelve months (11.3 letters, p < 0.05) without significant changes in retinal or choroidal morphology. At 12 months, 86% of eyes were able to maintain visual acuity improvement. There were no significant differences between the two anti-vascular endothelial growth factor drugs and no complications developed during follow-up. Simultaneous phacoemulsification and intravitreal anti- vascular endothelial growth factor is safe and allows improvement in visual acuity in patients with visually significant cataracts and exudative age-related macular degeneration. Visual acuity gains were maintained with a pro re nata strategy showing that in this subset of patients, phacoemulsification may be beneficial. Cataract surgery and simultaneous anti-vascular endothelial growth factor therapy improves visual acuity in patients with exudative age-related macular degeneration.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study.

PubMed

Sobacı, Güngör; Güngör, Rıza; Ozge, Gökhan

2013-01-01

To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus™); IOP measurements were taken 30 minutes and 24 hours after each injection. The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups. Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration.

PubMed

Inoue, Maiko; Kadonosono, Kazuaki; Arakawa, Akira; Yamane, Shin; Ishibashi, Tatsuro

2015-05-01

To evaluate the results of a 3-year follow-up of intravitreal pegaptanib sodium injection as maintenance therapy for the treatment of neovascular age-related macular degeneration (AMD) in Japanese patients. In this prospective, uncontrolled interventional study, 20 eyes of 19 patients with treatment-naïve AMD who had received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as the induction treatment and had shown clinical/anatomical improvement were enrolled. An intravitreal injection of 0.3 mg/0.09 mL pegaptanib sodium was administered as the maintenance therapy every 6 weeks. Booster treatments using ranibizumab were allowed if clinical deterioration was judged to be present. The primary outcome measures were the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) as evaluated using spectral-domain optical coherence tomography. Sixteen of the 20 eyes (80 %) were assessed at the 3-year follow-up. The mean logMAR BCVA improved significantly from 0.56 ± 0.31 before the induction treatment to 0.24 ± 0.25 at baseline (P < 0.001) and was well maintained at 156 weeks (0.25 ± 0.28, P = 0.938). Moreover, the mean CFT also decreased significantly from 346 ± 111 μm before the induction treatment to 232 ± 54 μm at baseline (P < 0.001) and was well preserved at 156 weeks (210 ± 59 μm, P = 0.278). Thirteen eyes (81.3 %) received an unscheduled booster treatment, and no severe systemic or ocular side effects occurred during follow-up. Intravitreal pegaptanib sodium injection as the maintenance therapy was effective in stabilizing the vision of patients with AMD in whom induction treatment led to improved BCVA, as evaluated at the 3-year follow-up.

Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis.

PubMed

Zulian, F; Martini, G; Gobber, D; Agosto, C; Gigante, C; Zacchello, F

2003-10-01

To compare the efficacy and safety of intra-articular triamcinolone hexacetonide (TH) and triamcinolone acetonide (TA) in children with oligoarticular juvenile idiopathic arthritis (JIA). One hundred and thirty joints of 85 patients undergoing intra-articular injections were randomly treated with either TH or TA depending on the availability of the drug. The efficacy of both treatments was evaluated prospectively in a blinded fashion. A good response was defined as a decrease in the articular score of > or =60% from baseline. Clinical, laboratory and immunological variables were noted in order to examine possible factors, other than treatment, predictive of the result. Seventy injections were performed using TH and 60 with TA. The two groups were comparable for clinical, immunological and laboratory characteristics. The rate of response was significantly higher with TH than with TA: 81.4% vs 53.3% (P = 0.001) at 6 months, 67.1 vs 43.3% (P = 0.006) at 12 months, and 60 vs 33.3% (P = 0.002) at 24 months. At comparable doses TH appeared to be much more effective than TA for intra-articular use, in both short- and long-term follow-up. This result was not affected by disease duration or degree of local and systemic inflammation.

[Extemporaneous withdrawal with a mini-spike filter: A low infection risk technique for drawing up bevacizumab for intravitreal injection].

PubMed

Le Rouic, J F; Breger, D; Peronnet, P; Hermouet-Leclair, E; Alphandari, A; Pousset-Decré, C; Badat, I; Becquet, F

2016-05-01

To describe a technique for extemporaneously drawing up bevacizumab for intravitreal injection (IVT) and report the rate of post-injection endophthtalmitis. Retrospective monocentric analysis (January 2010-December 2014) of all IVT of bevacizumab drawn up with the following technique: in the operating room (class ISO 7) through a mini-spike with an integrated bacteria retentive air filter. The surgeon was wearing sterile gloves and a mask. The assisting nurse wore a mask. The bevacizumab vial was discarded at the end of each session. Six thousand two hundred and thirty-six bevacizumab injections were performed. One case of endophthalmitis was noted (0.016%). During the same period, 4 cases of endophthalmitis were found after IVT of other drugs (4/32,992; 0.012%. P=0.8). Intravitreal injection of bevacizumab after extemporaneous withdrawal through a mini-spike filter is a simple and safe technique. The risk of postoperative endophthalmitis is very low. This simple technique facilitates access to compounded bevacizumab. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Intravitreal injection anesthesia--comparison of different topical agents: a prospective randomized controlled trial.

PubMed

Yau, Gary L; Jackman, Christopher S; Hooper, Philip L; Sheidow, Tom G

2011-02-01

To compare the anesthetic effectiveness of 3 topical agents used for intravitreal injections. Randomized, triple-armed, double-blinded, prospective, single-centered trial in patients receiving intravitreal ranibizumab for neovascular age-related macular degeneration. Patients were randomized 1:1:1 to receive 0.5% tetracaine hydrochloride drops and a 4% lidocaine pledget (n = 31), 0.5% tetracaine hydrochloride drops alone (n = 31), or 4% cocaine (+ epinephrine 1/100,000) drops alone (n = 31). Patients were asked to score their pain experience using a visual analogue scale (VAS) immediately following and 15 minutes after their injection. The average of these scores was used as the primary outcome. The physician performing the procedure separately scored his perception of the patients' pain using the Wong-Baker FACES scale. Means of the averaged VAS pain score for Groups 1, 2, and 3 were: 19 (95% confidence interval [CI] 12-26), 21 (95% CI 13-29), and 21 (95% CI 16-27) respectively. Mean Wong-Baker pain scores for Groups 1, 2, and 3 were 1.9 (95% CI 1.3-2.6), 2.1 (95% CI 1.4-2.7), and 2.3 (95% CI 1.6-3.1) respectively. There was no significant difference (P = .549) between groups for average VAS pain score. Similarly, there was no significant difference (P = .790) for the physician-perceived pain score between groups. There was no clinical difference in patient pain experience between the 3 anesthetic options tested. The addition of a 4% lidocaine pledget offered no clinical advantage in pain relief compared to 0.5% tetracaine or 4% cocaine (+ epinephrine 1/100,000) drops alone. Copyright © 2011 Elsevier Inc. All rights reserved.

A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Steven L.

2015-01-01

Purpose Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). Methods We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. Results A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. Conclusions A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION. PMID:26624498

A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Steven L

2015-12-01

Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION.

Dual Intravitreal Injections With Foscarnet and Ganciclovir for Ganciclovir-Resistant Recurrent Cytomegalovirus Retinitis in a Congenitally Infected Infant.

PubMed

Boss, Joseph D; Rosenberg, Kevin; Shah, Rajiv

2016-10-22

Resistant strains of cytomegalovirus can be difficult to treat in cases of congenital cytomegalovirus retinitis. The authors describe a case of recurrent bilateral congenital cytomegalovirus retinitis in an immunocompetent newborn with ganciclovir resistance successfully treated uniquely with dual therapy of intravenous ganciclovir and foscarnet and dual intravitreal injections with ganciclovir and foscarnet. [J Pediatr Ophthalmol Strabismus. 2016;53:e58-e60.]. Copyright 2016, SLACK Incorporated.

Intravitreal silicon-based quantum dots as neuroprotective factors in a model of retinal photoreceptor degeneration.

PubMed

Olson, Jeffrey L; Velez-Montoya, Raul; Mandava, Naresh; Stoldt, Conrad R

2012-08-17

To study the intravitreal application of silicon quantum dots (QDs) and their capabilities to deliver electrical stimulation to the retinal cells and to assess the potential effect on retinal electrophysiology and anatomy. A Royal College of Surgeon rat model of retinal degeneration was used in this study. A total of 32 eyes were used, divided in four groups of 8 eyes each; the first group received the silicon-based QD, the second group received an inactive gold-based QD, the third group received a sham injection, and the fourth group was used as a control. An electroretinogram (ERG) was done at baseline and thereafter every week for 9 weeks. At the end of the follow-up, eyes were collected for further pathologic analysis and nuclei cell counts. Eyes within the silicon-based QD group showed a definite but transient increase in the waves of the ERG, especially in the rod response compared with the sham and control groups (P < 0.05). The pathologic examination demonstrated a higher nuclei count in the QD group, consistent with a higher cell survival rate than that in the sham and control groups in which cells degenerated as expected. Intravitreal injection of silicon-based QD seems to be safe and well tolerated, with no evident toxic reaction and demonstrates a beneficial effect by prolonging cell survival rate and improving ERG patterns in a well-established model of retinal degeneration. (ClinicalTrials.gov numbers NCT00407602, NCT01490827.).

Effect of Intravitreal Injection of Bevacizumab on Acute Central Serous Chorioretinopathy Patients Who Visited Feiz Hospital during 2014–2015 Period

PubMed Central

Akhlaghi, Mohamad Reza; Nasrollahi, Cobra; Namgar, Seyed Mohamad; Kianersi, Farzan; Dehghani, Ali Reza; Arefpour, Reza

2017-01-01

Background: Aim of this clinical trial is the evaluation of the effect of intravitreal injection of bevacizumab on acute central serous chorioretinopathy (CSC). Materials and Methods: In a nonrandomized clinical trial, 36 CSC eyes (with <1-month disease history) were examined. Initially, all the patients underwent posterior and anterior segment examinations as well as complete eye examination to evaluate the best spectacle-corrected visual acuity (BSCVA). Then, optical coherence tomography was performed to confirm the diagnosis. The patients were divided to the two groups each of 18 subjects, which 18 patients received intravitreal injection of bevacizumab (1.25 mg) and the rest of them did not receive any treatment (control group). The patients were health checked by the end of the 1st and 3rd months. Significance level was considered as P < 0.05. Results: In the BSCVA, no significant difference in visual improvement was observed in baseline vision compared to each other (P = 0.481). There was also no significant difference in the vision of intervention and control groups 1 and 3 months after injection (P = 0.379 and P = 0.557). A significant decrement existed in the intervention group compared with the control group in the maximum central macular thickness at 1 month after injection (P = 0.001); however, the difference was not significant when comparing the two groups at baseline and 3 months after injection (P = 0.925 and P = 0.338). Conclusion: In general, according to the results of this study, intravitreal injection of bevacizumab was not effective in improvement of patients with acute CSC, although it had no side effects. PMID:29142888

Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

PubMed Central

Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

2015-01-01

Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model.

PubMed

Emre, Esra; Yüksel, Nurşen; Duruksu, Gökhan; Pirhan, Dilara; Subaşi, Cansu; Erman, Gülay; Karaöz, Erdal

2015-05-01

The purpose of this study was to investigate the neuroprotective effects of bone marrow bone marrow-derived and adipose tissue-derived mesenchymal stromal cells (MSCs) that were intravitreally transplanted in an experimental ocular hypertension (OHT) model. An OHT rat model was generated by means of intracameral injection of hyaluronic acid into the anterior chamber. MSCs labeled with green fluorescence protein were transplanted intravitreally 1 week after OHT induction. At the end of the second and fourth weeks, retinal ganglion cells were visualized with the use of a flat-mount retina method and were evaluated by means of immunofluorescence staining against green fluorescence protein, vimentin, CD105, and cytokines (interleukin [IL]-1Ra, prostaglandin E2 receptor, IL-6, transforming growth factor-β1, interferon-γ and tumor necrosis factor-α). The retinal ganglion cell numbers per area were significantly improved in stem cell-treated OHT groups compared with that in the non-treated OHT group (P < 0.05). The results of immunohistochemical analyses indicated that a limited number of stem cells had integrated into the ganglion cell layer and the inner nuclear layer. The number of cells expressing proinflammatory cytokines (interferon-γ and tumor necrosis factor-α) decreased in the MSC-transferred group compared with that in the OHT group after 4 weeks (P < 0.01). On the other hand, IL-1Ra and prostaglandin E2 receptor expressions were increased in the rat bone marrow-derived MSC group but were more significant in the rat adipose tissue-derived MSC group (P < 0.01). After intravitreal transplantation, MSCs showed a neuroprotective effect in the rat OHT model. Therefore, MSCs promise an alternative therapy approach for functional recovery in the treatment of glaucoma. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Pain relief in the rheumatoid knee after steroid injection. A single-blind comparison of hydrocortisone succinate, and triamcinolone acetonide or hexacetonide.

PubMed

Blyth, T; Hunter, J A; Stirling, A

1994-05-01

Since the introduction of intra-articular steroid therapy 40 yr ago there have been many changes in the treatment of rheumatoid patients. Previous studies suggest differing times of response for the same agents. This study reports the response, measured by a five-point pain chart, of 300 patients with painful rheumatoid knees. Sixty received hydrocortisone succinate (HC), 150 received triamcinolone acetonide (TA), and 120 triamcinolone hexacetonide (TH). Results demonstrated little effect with HC, but good responses with TA and TH. More patients were rendered painfree for a longer time with TH; 18% at 12 weeks, as against 9% with TA (chi 2 test P < 0.005). At 12 weeks 59% showed continued improvement with TH as against 44% with TA (chi 2 test P < 0.05). TH is the preferred preparation for injection of the rheumatoid knee.

Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases

PubMed Central

Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

2012-01-01

This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement. PMID:22948997

The Effect of Different Dosing Schedules of Intravitreal Sirolimus, a Mammalian Target of Rapamycin (mTOR) Inhibitor, in the Treatment of Non-Infectious Uveitis (An American Ophthalmological Society Thesis).

PubMed

Nguyen, Quan Dong; Sadiq, Mohammad Ali; Soliman, Mohamed Kamel; Agarwal, Aniruddha; Do, Diana V; Sepah, Yasir J

2016-08-01

To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6). 24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42µm in group 1 and +81.5µm in group 2 at M6. Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months.

Comparison of Two Anesthetic Methods for Intravitreal Ozurdex Injection

PubMed Central

Karabaş, V. Levent; Özkan, Berna; Koçer, Çiğdem Akdağ; Altıntaş, Özgül; Pirhan, Dilara; Yüksel, Nurşen

2015-01-01

Purpose. To determine whether subconjunctival lidocaine injection maintains additional anesthetic effect during intravitreal Ozurdex injection. Methods. 63 patients who were diagnosed as central or branch retinal vein occlusion and planned to receive Ozurdex injection for macular edema were prospectively included in the study. The patients were randomized into one of the two anesthetic groups. The first group received topical proparacaine drop and lidocaine applied pledget. The second group received subconjunctival lidocaine injection in addition to the anesthetics in group 1. Results. Mean pain score was 1.90 ± 2.39 in group 1 and 1.71 ± 2.09 in group 2 (p = 0.746). Mean subconjunctival hemorrhage grade was 1.67 ± 0.17 in group 1 and 0.90 ± 0.14 in group 2 (p = 0.001). There was no relationship between the amount of subconjunctival hemorrhage and pain score of the patients. Conclusions. There was no difference in pain scores between the two anesthetic methods. The addition of subconjunctival lidocaine injection offered no advantage in pain relief compared to lidocaine-applied pledgets. PMID:25949822

Comparison of two anesthetic methods for intravitreal ozurdex injection.

PubMed

Karabaş, V Levent; Özkan, Berna; Koçer, Çiğdem Akdağ; Altıntaş, Özgül; Pirhan, Dilara; Yüksel, Nurşen

2015-01-01

Purpose. To determine whether subconjunctival lidocaine injection maintains additional anesthetic effect during intravitreal Ozurdex injection. Methods. 63 patients who were diagnosed as central or branch retinal vein occlusion and planned to receive Ozurdex injection for macular edema were prospectively included in the study. The patients were randomized into one of the two anesthetic groups. The first group received topical proparacaine drop and lidocaine applied pledget. The second group received subconjunctival lidocaine injection in addition to the anesthetics in group 1. Results. Mean pain score was 1.90 ± 2.39 in group 1 and 1.71 ± 2.09 in group 2 (p = 0.746). Mean subconjunctival hemorrhage grade was 1.67 ± 0.17 in group 1 and 0.90 ± 0.14 in group 2 (p = 0.001). There was no relationship between the amount of subconjunctival hemorrhage and pain score of the patients. Conclusions. There was no difference in pain scores between the two anesthetic methods. The addition of subconjunctival lidocaine injection offered no advantage in pain relief compared to lidocaine-applied pledgets.

Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

PubMed

Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

2017-11-15

A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

PubMed Central

Sobacı, Güngör; Güngör, Rıza; Özge, Gökhan

2013-01-01

AIM To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). METHODS This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus™); IOP measurements were taken 30 minutes and 24 hours after each injection. RESULTS The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups. CONCLUSION Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients. PMID:23638426

COMBINATION THERAPY OF INTRAVITREAL RANIBIZUMAB AND SUBTHRESHOLD MICROPULSE PHOTOCOAGULATION FOR MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION: 6-MONTH RESULT.

PubMed

Terashima, Hiroko; Hasebe, Hiruma; Okamoto, Fumiki; Matsuoka, Naoki; Sato, Yayoi; Fukuchi, Takeo

2018-04-23

To determine the efficacy of the combination therapy of intravitreal ranibizumab (IVR) and 577-nm yellow laser subthreshold micropulse laser photocoagulation (SMLP) for macular edema secondary to branch retinal vein occlusion cystoid macular edema. Retrospective, consecutive, case-control study. Forty-six eyes of 46 patients with treatment-naive branch retinal vein occlusion cystoid macular edema were enrolled. The IVR + SMLP group consisted of 22 patients who had undergone both SMLP and IVR. Intravitreal ranibizumab group consisted of 24 patients who had undergone IVR monotherapy. Intravitreal ranibizumab therapy was one initial injection and on a pro re nata in both groups, and SMLP was performed at 1 month after IVR in the IVR + SMLP group. Preoperatively and monthly, best-corrected visual acuity and central retinal thickness were evaluated using swept source optical coherence tomography. Best-corrected visual acuity and central retinal thickness significantly improved at 6 months in IVR + SMLP and IVR groups. Best-corrected visual acuity and central retinal thickness were not significantly different between the two groups at any time points. The number of IVR injections during initial 6 months in IVR group (2.3 ± 0.9) was significantly greater (P = 0.034) than that in IVR + SMLP group (1.9 ± 0.8). The combination therapy of IVR and SMLP can treat branch retinal vein occlusion cystoid macular edema effectively, by decreasing the frequency of IVR injections while maintaining good visual acuity.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PubMed

Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

2014-11-01

To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis.

PubMed

Afarid, Mehrdad; Lashkarizadeh, Hamid; Ashraf, Mohammad J; Nowroozzadeh, Mohammad Hossein; Shafiee, Sayed M

2016-05-01

To study the efficacy of intravitreal interferon alpha-2b for endotoxin-induced uveitis. A total of 36 rabbits were randomly allocated to one of the three groups: (1) received interferon plus balanced-salt solution; (2) received lipopolysaccharide (LPS) plus interferon; and (3) received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit-lamp biomicroscopy (standardization of uveitis nomenclature grading), binocular indirect ophthalmoscopy (BIO) score, and histopathology. Group 2 showed significantly lower mean (±standard deviation) anterior chamber reaction than Group 3 (3.1 ± 0.9 vs. 3.8 ± 0.4) on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 ± 0.9 vs. 3.8 ± 0.4; day 3: 2.1 ± 1.6 vs. 3.8 ± 0.4; day 7: 1.9 ± 1.3 vs. 3.6 ± 0.7), and lower BIO score on days 1-7 (day 1: 3.3 ± 1.2 vs. 4.4 ± 0.7; day 3: 3.0 ± 1.4 vs. 4.3 ± 0.9; day 7: 2.4 ± 1.4 vs. 3.7 ± 1.2). The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 ± 411.4 vs. 2567.3 ± 330.8 and 2157.0 ± 283.3 vs. 3204.6 ± 259.5, respectively). Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis.

Surface Engineering of Porous Silicon Microparticles for Intravitreal Sustained Delivery of Rapamycin

PubMed Central

Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

2015-01-01

Purpose. To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Methods. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. Results. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Conclusions. Porous silicon–based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. PMID:25613937

Surface engineering of porous silicon microparticles for intravitreal sustained delivery of rapamycin.

PubMed

Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

2015-01-22

To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Porous silicon-based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

The Effect of Different Dosing Schedules of Intravitreal Sirolimus, a Mammalian Target of Rapamycin (mTOR) Inhibitor, in the Treatment of Non-Infectious Uveitis (An American Ophthalmological Society Thesis)

PubMed Central

Nguyen, Quan Dong; Sadiq, Mohammad Ali; Soliman, Mohamed Kamel; Agarwal, Aniruddha; Do, Diana V.; Sepah, Yasir J.

2016-01-01

Purpose: To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. Methods: SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6). Results: 24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and −2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was −89.42µm in group 1 and +81.5µm in group 2 at M6. Conclusions: Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months. PMID:27630374

Posterior subtenon triamcinolone acetonide in gas-filled eyes as an adjunctive treatment for complicated proliferative diabetic retinopathy.

PubMed

Lee, Yongeun; Kang, Seungbum; Park, Young-Hoon

2013-02-01

To evaluate the effect of adjunctive subtenon injection of triamcinolone acetonide (TA) in gas-filled eyes after vitrectomy for complicated proliferative diabetic retinopathy (PDR). This nonrandomized comparative study included 27 patients (27 eyes) who underwent pars plana vitrectomy and gas tamponade for treatment of PDR with tractional or combined tractional-rhegmatogenous retinal detachment and who received subtenon injection of TA (40 mg) at the end of surgery. The study group was compared with the control group (29 eyes), which was matched with the study group for preoperative and intraoperative parameters, but underwent pars plana vitrectomy and gas tamponade without a subtenon injection of TA. Retinal reattachments without reoperation were achieved in 25 eyes (92.6%) and 26 eyes (89.7%) at 6 months (p = 1.000) in the study and control groups, respectively. The study group and the control group did not differ significantly in the frequency of postoperative proliferative vitreoretinopathy, retinal redetachment rate, reoperation rate, macular pucker formation, postoperative vitreous hemorrhage, gain in visual acuity, intraocular pressure, and intraocular inflammation (p > 0.05). The clinical results of pars plana vitrectomy for complicated PDR are not improved significantly by an adjunctive subtenon TA injection in gas-filled eyes.

INTRAVITREOUS CHEMOTHERAPY FOR ACTIVE VITREOUS SEEDING FROM RETINOBLASTOMA: Outcomes After 192 Consecutive Injections. The 2015 Howard Naquin Lecture.

PubMed

Shields, Carol L; Douglass, Alexzandra M; Beggache, Meriem; Say, Emil Anthony T; Shields, Jerry A

2016-06-01

To investigate on the safety and efficacy of intravitreous chemotherapy for retinoblastoma seeding in a relatively large cohort and provide information on the necessary number of injections and long-term control. Retrospective interventional case series of 40 consecutive eyes with viable vitreous seeding after standard treatment of retinoblastoma. All eyes received intravitreal melphalan injection (20-30 μg) and additional topotecan (20 μg) as needed using the trans pars plana route with triple freeze-thaw cryotherapy at needle withdrawal for prevention of extraocular seeding for planned six cycles. The mean patient age at presentation was 36 months, and interval to need for vitreous injection was 14 months. Viable vitreous (n = 40 eyes) and additional subretinal (n = 2 eyes) seeds were documented. There was a total of 192 injections using melphalan (n = 148) and/or topotecan (n = 44) with mean number of injections per eye of melphalan at 4 (median, 4; range, 1-6) and topotecan at 3 (median, 3; range, 1-5). Fewer than six planned melphalan injections (n = 31 cases, 78%) were necessary because of rapid and complete vitreous seed control (n = 30 eyes) or melphalan allergy (n = 1 eye). Fewer than six planned topotecan injections (n = 14 cases, 100%) were necessary because of rapid and complete vitreous seed control in all cases. At median 3-year follow-up, therapeutic success with continued seed regression was observed in all 40 eyes (100%). Globe salvage was attained in 35 cases (88%), and enucleation (n = 5) was necessary for extensive recurrent subretinal seeds (n = 2), neovascular glaucoma with vitreous hemorrhage (n = 2), and hemorrhagic retinal necrosis (n = 1). Side effects included focal retinal pigment epithelial mottling at the site of injection (n = 12), minor focal paraxial lens opacity (not requiring cataract surgery) (n = 11), transient focal vitreous hemorrhage (n = 5), transient hypotony (n = 3), transient retinal hemorrhage (n = 2), optic disc edema

Ocular tissue distribution and pharmacokinetic study of a small 13kDa domain antibody after intravitreal, subconjuctival and eye drop administration in rabbits.

PubMed

Gough, Gerald; Szapacs, Matthew; Shah, Tejash; Clements, Peter; Struble, Craig; Wilson, Robert

2018-02-01

Domain antibodies (dAb's) comprise the smallest functional unit of human IgG and can be targeted to a range of different soluble cytokine and receptor targets in the eye. In particular their small size may offer advantage for ocular tissue penetration and distribution. To investigate this we used a 13kDa tool molecule to undertake a preliminary short term ocular tissue distribution and pharmacokinetic study in the rabbit eye. The dAb was administered by the intravitreal or subconjunctival route or, as topical eye drops for up to five days and dAb concentrations measured in vitreous, aqueous, conjunctiva, choroid-RPE, retina, iris, sclera, and ciliary body. The observed elimination half-live of the dAb (~3 days) in vitreous showed a similar elimination rate to that of a much larger (∼50kDa) Fab fragment whilst the half-life following subconjunctival administration was ∼24 h and, after eye drop dosing the dAb was detectable in aqueous and conjunctiva. These preliminary data show that the intravitreal half-life of dAb's are similar to much larger antibody fragments, offering the potential to deliver significantly more drug to target on a molar basis with a single intravitreal injection potentially enabling dosing frequencies of once a month or less. Subconjunctival injection may provide short duration therapeutic levels of dAb to the anterior and posterior chamber whilst topical eye drop delivery of dAbs may be useful in front-of-eye disease. These data indicate that small domain antibodies may have utility in ophthalmology. Further studies are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of Intralesional Triamcinolone Acetonide, 5-Fluorouracil, and Their Combination for the Treatment of Keloids

PubMed Central

Srivastava, Sunil; Patil, Aditya Nanasaheb; Prakash, Chaitra; Kumari, Hiranmayi

2017-01-01

Objective: Despite the myriad options available, there is no universally accepted treatment for keloids. Our objective was to compare three regimens and establish superiority in terms of objective and subjective outcomes. Approach: In this randomized parallel group study, 60 patients were enrolled and randomly allocated to three groups. Patients received intralesional injections of triamcinolone acetonide (TAC) in Group TAC, 5-fluorouracil (5FU) in Group 5FU, and a combination in Group T + F every 3 weeks till 24 weeks or till the keloid resolved. Results: There was a reduction in all parameters at every successive assessment in all three groups. Improvement in terms of height, vascularity, and pliability was fastest with 5FU, TAC, and T + F group, respectively, which was statistically significant. Decrease in pigmentation was significantly faster with T+F. Reduction in pruritus, however, was significantly faster with 5FU than the other groups, but the difference in reduction of pain among the three groups was not significant. Telangiectasias and skin atrophy were seen most commonly in TAC group, while skin ulceration was a common problem in 5FU group. Conclusion: TAC, 5FU, and their combination are all effective in keloid scars. A combination of TAC +5FU seems to offer the balanced benefit of faster and more efficacious response with lesser adverse effects when compared to individual drugs. PMID:29098115

Short Implants: New Horizon in Implant Dentistry.

PubMed

Jain, Neha; Gulati, Manisha; Garg, Meenu; Pathak, Chetan

2016-09-01

The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark; Dunn, JP; Yeh, Steven

2012-01-01

Purpose To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Design Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. Participants 250 patients with CMV retinitis and CD4+ T cells <100 cells/µL (n=221) at enrollment or incident retinitis (n=29) during cohort follow-up. Methods The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Main Outcome Measures Mortality, CMV dissemination, retinitis progression, treatment side effects. Results Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR]=0.5; 95% confidence interval [CI] = 0.3, 0.7; P=0.006), 90% reduction in new visceral CMV disease (adjusted HR=0.1; 95% CI = 0.04, 0.4;P=0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR=0.2; 95% CI= 0.1, 0.5; P=0.0005) when compared to those using only intraocular therapy (implants or injections). Compared to systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR=3.4, P=0.004) and greater visual field loss (for loss of ½ of the normal field, adjusted HR=5.5, P<0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression =0.5, P=0.26, and for loss ½ visual field =0.5, P=0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis among those treated with intravitreal injections was 0.017/EY (95% CI =0.006, 0.05) and among those treated with an implant 0.01/EY (95% CI =0.002, 0.04). Conclusions In the HAART era

Influence of Palatal Coverage and Implant Distribution on Implant Strain in Maxillary Implant Overdentures.

PubMed

Takahashi, Toshihito; Gonda, Tomoya; Mizuno, Yoko; Fujinami, Yozo; Maeda, Yoshinobu

2016-01-01

Maxillary implant overdentures are often used in clinical practice. However, there is no agreement or established guidelines regarding prosthetic design or optimal implant placement configuration. The purpose of this study was to examine the influence of palatal coverage and implant number and distribution in relation to impact strain under maxillary implant overdentures. A maxillary edentulous model with implants and experimental overdentures with and without palatal coverage was fabricated. Four strain gauges were attached to each implant, and they were positioned in the anterior, premolar, and molar areas. A vertical occlusal load of 98 N was applied through a mandibular complete denture, and the implant strains were compared using one-way analysis of variance (P = .05). The palatolabial strain was much higher on anterior implants than on other implants in both denture types. Although there was no significant difference between the strain under dentures with and without palatal coverage, palateless dentures tended to result in higher implant strain than dentures with palatal coverage. Dentures supported by only two implants registered higher strain than those supported by four or six implants. Implants under palateless dentures registered higher strain than those under dentures with palatal coverage. Anterior implants exhibited higher palatolabial strain than other implants regardless of palatal coverage and implant configuration; it is therefore recommended that maxillary implant overdentures should be supported by six implants with support extending to the distal end of the arch.

Posterior Vitreous Detachment With Microplasmin Alters the Retinal Penetration of Intravitreal Bevacizumab (Avastin) in Rabbit Eyes

PubMed Central

Goldenberg, David T.; Giblin, Frank J.; Cheng, Mei; Chintala, Shravan K.; Trese, Michael T.; Drenser, Kimberly A.; Ruby, Alan J.

2010-01-01

Purpose Intravitreal bevacizumab (Avastin) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare bevacizumab (BV) retinal penetration in rabbit eyes with and without a MP-induced PVD. Methods Twelve adult rabbits were injected with 0.1 ml (0.4 mg) of MP into the vitreous cavity of one eye. One week later, the rabbits were injected with 0.05 ml (1.25 mg) of BV into both eyes. Both eyes of three rabbits each were harvested at 6, 12, 24, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intra-retinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 ml of MP in one eye. One week later, both eyes from each rabbit were enucleated and frozen retinal sections were prepared and analyzed with light microscopy to evaluate for histologic damage. Results Full thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All of the MP-injected eyes exhibited increased antibody labeling in retinas evaluated 6, 12, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By three days after BV injection, all eyes demonstrated decreased antibody labeling compared to earlier time periods

Short Implants: New Horizon in Implant Dentistry

PubMed Central

Gulati, Manisha; Garg, Meenu; Pathak, Chetan

2016-01-01

The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration. PMID:27790598

An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

PubMed

Wu, Lihteh; Evans, Teodoro

2011-01-01

The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

Chronic post-operative iris prosthesis endophthalmitis in a patient with traumatic aniridia: a case report.

PubMed

Firl, Kevin C; Montezuma, Sandra R

2016-11-09

Post-operative endophthalmitis is a serious complication of intraocular surgery which may present acutely or chronically. Chronic post-operative endophthalmitis is characterized by decreased visual acuity, mild pain, and low-grade uveitis several weeks or months after intraocular surgery which may be responsive to corticosteroids, but recur upon tapering. Low virulence organisms such as Propionibacterium acnes are the most common culprit organisms, and treatment most often consists of both intravitreal antibiotic injections and surgery. Aniridia is a condition defined by total or partial loss of the iris and leads to decreased visual quality marked by glare and photophobia. Treatment of complex or severe cases of traumatic aniridia in which surgical repair is difficult may consist of implantation of iris prostheses, devices designed to reduce symptoms of aniridia. Though chronic, post-operative endophthalmitis has been associated with most intraocular surgeries including intraocular lens implantation after cataract removal, it has never been described in a patient with an iris prosthesis. In this case report, we describe the case of a 49 year old, male construction worker with traumatic aniridia who experienced chronic, recurrent low-grade intraocular inflammation and irritation for months after implantation of the Ophtec 311 prosthetic iris. Symptoms and signs of inflammation improved temporarily with sub-Tenon's capsule triamcinolone injections. Ultimately after more than 2 post-operative years, the iris prosthesis was explanted, and intravitreal cultures showed P. acnes growth after 5 days. Intravitreal antibiotics treated the infection successfully. To our knowledge, this is the first reported case of chronic, post-operative endophthalmitis in a patient with an iris prosthesis. Chronic, post-operative endophthalmitis may be a difficult to identify in the context of traumatic aniridia and iris prosthesis implantation due to other potential etiologies of

Glioprotection of Retinal Astrocytes After Intravitreal Administration of Memantine in the Mouse Optic Nerve Crush Model.

PubMed

Maciulaitiene, Ruta; Pakuliene, Giedre; Kaja, Simon; Pauza, Dainius Haroldas; Kalesnykas, Giedrius; Januleviciene, Ingrida

2017-03-07

BACKGROUND In glaucoma, non-intraocular pressure (IOP)-related risk factors can result in increased levels of extracellular glutamate, which triggers a cascade of neurodegeneration characterized by the excessive activation of N-methyl-D-aspartate (NMDA). The purpose of our study was to evaluate the glioprotective effects of memantine as a prototypic uncompetitive NMDA blocker on retinal astrocytes in the optic nerve crush (ONC) mouse model for glaucoma. MATERIAL AND METHODS Optic nerve crush was performed on all of the right eyes (n=8), whereas left eyes served as contralateral healthy controls (n=8) in Balb/c/Sca mice. Four randomly assigned mice received 2-µl intravitreal injections of memantine (1 mg/ml) after ONC in the experimental eye. One week after the experiment, optic nerves were dissec-ted and stained with methylene blue. Retinae were detached from the sclera. The tissue was immunostained. Whole-mount retinae were investigated by fluorescent microscopy. Astrocyte counts for each image were performed manually. RESULTS Histological sections of crushed optic nerves showed consistently moderate tissue damage in experimental groups. The mean number of astrocytes per image in the ONC group was significantly lower than in the healthy control group (7.13±1.5 and 10.47±1.9, respectively). Loss of astrocytes in the memantine-treated group was significantly lower (8.83±2.2) than in the ONC group. Assessment of inter-observer reliability showed excellent agreement among observations in control, ONC, and memantine groups. CONCLUSIONS The ONC is an effective method for investigation of astrocytic changes in mouse retina. Intravitreally administered memantine shows a promising glioprotective effect on mouse retinal astrocytes by preserving astrocyte count after ONC.

Peri-implantitis.

PubMed

Schwarz, Frank; Derks, Jan; Monje, Alberto; Wang, Hom-Lay

2018-06-01

This narrative review provides an evidence-based overview on peri-implantitis for the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. A literature review was conducted addressing the following topics: 1) definition of peri-implantitis; 2) conversion from peri-implant mucositis to peri-implantitis, 3) onset and pattern of disease progression, 4) characteristics of peri-implantitis, 5) risk factors/indicators for peri-implantitis, and 6) progressive crestal bone loss in the absence of soft tissue inflammation. 1)Peri-implantitis is a pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant connective tissue and progressive loss of supporting bone. 2)The histopathologic and clinical conditions leading to the conversion from peri-implant mucositis to peri-implantitis are not completely understood. 3)The onset of peri-implantitis may occur early during follow-up and the disease progresses in a non-linear and accelerating pattern. 4a)Peri-implantitis sites exhibit clinical signs of inflammation and increased probing depths compared to baseline measurements. 4b)At the histologic level, compared to periodontitis sites, peri-implantitis sites often have larger inflammatory lesions. 4c)Surgical entry at peri-implantitis sites often reveals a circumferential pattern of bone loss. 5a)There is strong evidence that there is an increased risk of developing peri-implantitis in patients who have a history of chronic periodontitis, poor plaque control skills, and no regular maintenance care after implant therapy. Data identifying "smoking" and "diabetes" as potential risk factors/indicators for peri-implantitis are inconclusive. 5b)There is some limited evidence linking peri-implantitis to other factors such as: post-restorative presence of submucosal cement, lack of peri-implant keratinized mucosa and positioning of implants that make it difficult to perform oral hygiene

Short-term intraocular pressure trends following intravitreal ranibizumab injections for neovascular age-related macular degeneration-the role of oral acetazolamide in protecting glaucoma patients.

PubMed

Murray, C D; Wood, D; Allgar, V; Walters, G; Gale, R P

2014-10-01

To determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure (IOP) rise in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for neovascular age-related macular degeneration. The study was an open-label, parallel, randomised, controlled trial (EudraCT Number: 2010-023037-35). Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60-90 min before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection (T0) and 5, 10, and 30 min following injection. ANCOVA was used to compare groups, adjusting for baseline IOP. The study was powered to detect a 9-mm Hg difference at T0. The IOP at T0 was 2.3 mm Hg higher in the non-treated group (mean 44.5 mm Hg, range (19-86 mm Hg)) compared with the treated group (mean 42.2 mm Hg, range (25-58 mm Hg)), but was not statistically significant after adjusting for baseline IOP (P=0.440). At 30 min, IOP was 4.9 mm Hg higher in the non-treated group (mean 20.6 mm Hg, range (11-46 mm Hg)) compared with the treated group (mean 15.7 mm Hg, range (8-21 mm Hg)). This was statistically significant after adjusting for baseline IOP (P=0.013). Although the primary end points were not reached, 500 mg oral acetazolamide, 60-90 min before intravitreal injection, results in a statistically significant reduction in IOP at 3O min post injection. Prophylactic treatment may be considered as an option to minimise neuro-retinal rim damage in high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections of ranibizumab.

CHANGES IN CENTRAL CHOROIDAL THICKNESS AFTER TREATMENT OF DIABETIC MACULAR EDEMA WITH INTRAVITREAL BEVACIZUMAB CORRELATION WITH CENTRAL MACULAR THICKNESS AND BEST-CORRECTED VISUAL ACUITY.

PubMed

Nourinia, Ramin; Ahmadieh, Hamid; Nekoei, Elnaz; Malekifar, Parviz; Tofighi, Zahra

2018-05-01

To assess the effect of intravitreal injection of bevacizumab on central choroidal thickness (CCT) and its relationship with central macular thickness (CMT) and best-corrected visual acuity (BCVA) changes in eyes with center-involving diabetic macular edema. This prospective interventional case series included 20 eyes of 20 patients with center-involving diabetic macular edema naive to treatment. The BCVA assessment, complete eye examination, enhanced depth optical coherence tomography, and fluorescein angiography were performed at baseline followed by 3 monthly intravitreal injection of bevacizumab. The treated eyes underwent BCVA evaluation and enhanced depth optical coherence tomography at Months 1, 2, 3, and 6 after the first injection. Change of the CCT was the primary outcome measure. Secondary outcome measures included BCVA and CMT changes and their relationship with CCT changes. Mean age of patients was 63.1 ± 8.0 (range, 52-75) years. Mean baseline CCT was 265 ± 79 μm, which reduced to 251 ± 81 μm and 232 ± 82 μm at Months 3 and 6, respectively (P < 0.001). Corresponding values for CMT were 470 ± 107 μm, 392 ± 104 μm, and 324 ± 122 μm, respectively (P < 0.001). The BCVA improved from 20/60 at baseline to 20/50 at Month 3 and 20/40 at Month 6 (P = 0.007). Each 1 μm decrease in CCT was associated with 2.74 μm reduction in CMT and 0.1 Early Treatment Diabetic Retinopathy Study letter score improvement in BCVA (P < 0.001 and P = 0.001, respectively). After treatment of diabetic macular edema with intravitreal injection of bevacizumab, CCT decreased and this reduction significantly correlated with CMT reduction and vision improvement.

Long-term Results of Intravitreal Anti-VEGF Injections in Wet AMD: A Meta-Analysis.

PubMed

Gerding, H

2016-04-01

Although intravitreal anti-VEGF medications are widely used in age-related macular degeneration, no systematic data analysis is available on the long-term prognosis of this relatively new therapeutic approach. A meta-analysis was performed on available Medline literature. 13 relevant clinical studies (14 case series) could be identified, covering 10 247 treated eyes. The majority of available reports originate from single centre retrospective real-life environments. The mean improvement in average visual gain was 0.9 ± 0.5 (mean ± 1 standard deviation, median; 0.8 lines) at year 1, 1.2 ± 1.1 (median: 1.1) letters at year 2, 0.7 ± 1.0 (median: 0.7) letters at year 3, and 0.2 ± 0.8 (median: 0.5), 0.4 ± 0.4 (median: 0.5) at years 4 and 5. The drop-out rates in these studies was relatively high. At the end of year 3, the average percentage of observed eyes was 44.3 ± 18.4 % (mean ± 1 standard deviation), at the end of year 4 23.5 ± 23.9 % and after years 6 and 7 below 10 % (8.2 and 7.9 %). The mean treatment frequency of injections in all available studies was highest in year 1 (6.4 ± 1.2, 6.1 - mean ± SD; median), followed by relatively consistent mean values of 4.1 and 5.1 (year (Y)2: 4.4, Y3: 4.3, Y4: 4.7, Y5: 4.1, Y6: 5.1, Y7: 4.7) injections per year. The results of this meta-analysis clearly indicate that intravitreal anti-VEGF injection therapy is capable of maintaining visual acuity on a long-term basis of at least 4-5 years. Georg Thieme Verlag KG Stuttgart · New York.

Comparison of intravitreal bevacizumab treatment between phakic and pseudophakic neovascular age-related macular degeneration.

PubMed

Ozkaya, Abdullah; Alkin, Zeynep; Perente, Irfan; Yuksel, Kemal; Baz, Okkes; Alagoz, Cengiz; Yazici, Ahmet Taylan; Demirok, Ahmet

2014-01-01

Before the era of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment, only prevention for visual loss might have been achieved in a limited number of neovascular age-related macular generation (nAMD) patients with different treatment options. To compare the efficacy of intravitreal bevacizumab (IVB) for the treatment of nAMD between phakic and pseudophakic eyes. The newly diagnosed nAMD patients were included in this retrospective study. The patients were divided into the phakic and pseudophakic groups. Initially, the patients received three consecutive, monthly, IVB injections, and then the treatment was continued on an as-needed regimen. The patients were examined monthly, and the data at the baseline, at 3, 6, 9, and 12 months and at the last follow-up were evaluated. The changes in the visual acuity (VA), central retinal thickness (CRT) and the number of injections were compared between the two groups. The study included 62 eyes of 62 patients (39 phakic, and 23 pseudophakic patients). The mean follow-up time was 19.7 and 17.2 months in the phakic and pseudophakic groups, respectively (p=0.06). The mean Log MAR VA at the baseline, 12 months and the last follow-up was 0.82, 0.72 and 0.75 in the phakic group and 0.77, 0.67, and 0.68 in the pseudophakic group, respectively. The change in the mean BCVA from the baseline to 12 months and at the last follow-up was not statistically different between the two groups (p=0.9 and p=0.7, respectively). The mean injection number at 12 months was 4.5 and 4.9 in the phakic and pseudophakic group, respectively (p=0.2). The beneficial effect of IVB is equal in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment and the number of injections were similar in the two groups. © NEPjOPH.

Biomechanical behavior of 2-implant-and single-implant-retained mandibular overdentures with conventional or mini implants.

PubMed

Pisani, Marina Xavier; Presotto, Anna Gabriella Camacho; Mesquita, Marcelo Ferraz; Barão, Valentim Adelino Ricardo; Kemmoku, Daniel Takanori; Del Bel Cury, Altair Antoninha

2018-04-24

The use of single or mini dental implants to retain mandibular overdentures is still questionable. The purpose of this finite element analysis (FEA) study was to investigate the biomechanical behavior of 2- and single-implant-retained mandibular overdentures with conventional or mini implants. Four 3-dimensional (3D) finite element models were constructed with the following designs of mandibular overdentures: 2 (group 2-C) and single (group 1-C) conventional external hexagon implants with ball or O-ring attachment and 2 (group 2-M) and single (group 1-M) 1-piece mini implants. A 150-N axial load was applied bilaterally and simultaneously on the first molar. Overdenture displacement, von Mises equivalent stress (implants and/or prosthetic components), and maximum principal stresses (peri-implant bone) were recorded numerically and then color-coded and compared among the groups. The overdenture displacement (in mm) was higher for the 1-M (0.16) and 2-M (0.17) groups when compared with 1-C (0.09) and 2-C (0.08). Irrespective of the type of implant, the single-implant groups presented higher values of stress (in MPa) on the implants than did the 2-implant groups (1-C=52.53; 1-M=2.95; 2-C=34.66; 2-M=2.37), ball attachment (1-C=201.33; 2-C=159.06), housing or O-ring (1-C=125.01; 1-M=1.96; 2-C=88.84; 2-M=1.27), and peri-implant cortical bone (1-C=19.37; 1-M=1.47; 2-C=15.70; 2-M=1.06). The mini implant overdentures presented lower stress values on the implants, housing or O-ring, and peri-implant bone than did the conventional implant overdentures, regardless of the number of implants. The 2-implant-retained overdentures exhibited lower stresses than the single- implant-retained overdentures, irrespective of the type of implant. The mini implants demonstrated higher overdenture displacement and lower stresses than did conventional implant overdentures for single- and 2-implant-retained overdentures. Copyright © 2018 Editorial Council for the Journal of Prosthetic

Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick

PubMed Central

Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank

2012-01-01

Purpose Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Methods Chicks were treated with either +7 D, −7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-AktThr308, and anti-phospho-Erk1/2(Thr202/Tyr204) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Results Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens–treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor

Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick.

PubMed

Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank; Feldkaemper, Marita P

2012-01-01

Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Chicks were treated with either +7 D, -7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-Akt(Thr308), and anti-phospho-Erk1/2((Thr202/Tyr204)) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens-treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor suppressed the effects of

Intravitreal Stanniocalcin-1 Enhances New Blood Vessel Growth in a Rat Model of Laser-Induced Choroidal Neovascularization

PubMed Central

Zhao, Min; Xie, Wankun; Tsai, Shu-Huai; Hein, Travis W.; Rocke, Brent A.; Kuo, Lih; Rosa, Robert H.

2018-01-01

Purpose The purpose of this study was to investigate the impact of stanniocalcin-1 (STC-1), a photoreceptor-protective glycoprotein, on the development of choroidal neovascularization (CNV) in relation to VEGF and its main receptor (VEGFR2) expression after laser injury. Methods In rats, CNV was induced by laser photocoagulation in both eyes, followed by intravitreal injection of STC-1 in the right eye and vehicle or denatured STC-1 injection in the left eye as control. Two weeks after laser injury, fundus autofluorescence (FAF) imaging and fundus fluorescein angiography (FFA) were performed. Fluorescein leakage from CNV was graded using a defined scale system. The size of CNV was quantified with spectral domain optical coherence tomography (SD-OCT), fluorescein-labeled choroid-sclera flat mounts, and hematoxylin-eosin staining. Protein expressions were evaluated by Western blot. Results Photocoagulation produced a well-circumscribed area of CNV. With STC-1 treatment, CNV lesions assessed by FAF were increased by 50% in both intensity and area. The CNV lesions were also increased with SD-OCT, flat-mount, and histologic analyses. FFA disclosed enhanced fluorescein leakage in CNV lesions in STC-1 treated eyes. The STC-1 protein was detected in the choroidal tissue and its level was increased with CNV lesions in correlation with VEGF and VEGFR2 expressions. Intravitreal administration of STC-1 significantly increased choroidal expression of both VEGF and VEGFR2 proteins. Conclusions Chorodial tissue expresses STC-1, which seemingly acts as a stress response protein by enhancing pathological new blood vessel growth in laser-induced CNV. It is likely that STC-1 promotes CNV development via VEGF signaling. PMID:29490350

Efficacy of intravitreal bevacizumab for macular edema following branch retinal vein occlusion stratified by baseline visual acuity.

PubMed

Kim, Mirae; Jeong, Seongyong; Sagong, Min

2017-04-01

To compare the clinical features and bevacizumab efficacy for macular edema (ME) following branch retinal vein occlusion (BRVO) stratified by baseline visual acuity. This retrospective study included a total 117 eyes from 117 consecutive patients with ME following BRVO, who received PRN intravitreal bevacizumab injection and were followed for more than 6 months. The eyes were categorized into three groups according to baseline best-corrected visual acuity (BCVA) (group A, BCVA <20/200; group B, BCVA ≥20/200 and ≤20/40; group C, BCVA >20/40). Baseline demographics, clinical features, BCVA, and central retinal thickness (CRT) at 1, 3, 6, and 12 months after injection and the number of injections were compared. Groups A-C included 11, 83, and 23 eyes, respectively. The mean baseline CRT was thickest in group A (810.1, 580.8, and 473.5 μm in groups A-C, respectively; p < 0.001) and the percentage of eyes with macular ischemia increased in the worst BCVA group (45.5, 25.0, and 4.3 % in groups A-C, respectively; p = 0.005). The mean BCVA and CRT improved at 1, 3, 6, and 12 months after treatment compared to baseline values in all groups (all, p < 0.001). The number of injections for 6 months was greater in the worst BCVA group (3.2, 2.3, and 1.9 injections in groups A-C, respectively; p = 0.009). In ME following BRVO, baseline visual acuity correlates with macular ischemia and baseline CRT. Intravitreal bevacizumab treatment results in significant anatomical and functional improvement regardless of baseline visual acuity.

Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews.

PubMed

Ward, Alexander H; Siegwart, John T; Frost, Michael R; Norton, Thomas T

2017-01-01

We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.

Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews

PubMed Central

Ward, Alexander H.; Siegwart, John T.; Frost, Michael R.; Norton, Thomas T.

2017-01-01

We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 μL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development. PMID:28304244

Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

PubMed Central

Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

2013-01-01

Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

Short dental implants: an emerging concept in implant treatment.

PubMed

Al-Hashedi, Ashwaq Ali; Taiyeb Ali, Tara Bai; Yunus, Norsiah

2014-06-01

Short implants have been advocated as a treatment option in many clinical situations where the use of conventional implants is limited. This review outlines the effectiveness and clinical outcomes of using short implants as a valid treatment option in the rehabilitation of edentulous atrophic alveolar ridges. Initially, an electronic search was performed on the following databases: Medline, PubMed, Embase, Cochrane Database of Systematic Reviews, and DARE using key words from January 1990 until May 2012. An additional hand search was included for the relevant articles in the following journals: International Journal of Oral and Maxillofacial Implants, Clinical Oral Implants Research, Journal of Clinical Periodontology, International Journal of Periodontics, Journal of Periodontology, and Clinical Implant Dentistry and Related Research. Any relevant papers from the journals' references were hand searched. Articles were included if they provided detailed data on implant length, reported survival rates, mentioned measures for implant failure, were in the English language, involved human subjects, and researched implants inserted in healed atrophic ridges with a follow-up period of at least 1 year after implant-prosthesis loading. Short implants demonstrated a high rate of success in the replacement of missing teeth in especially atrophic alveolar ridges. The advanced technology and improvement of the implant surfaces have encouraged the success of short implants to a comparable level to that of standard implants. However, further randomized controlled clinical trials and prospective studies with longer follow-up periods are needed.

Number of implants for mandibular implant overdentures: a systematic review

PubMed Central

Lee, Jeong-Yol; Kim, Ha-Young; Bryant, S. Ross

2012-01-01

PURPOSE The aim of this systematic review is to address treatment outcomes of Mandibular implant overdentures relative to implant survival rate, maintenance and complications, and patient satisfaction. MATERIALS AND METHODS A systematic literature search was conducted by a PubMed search strategy and hand-searching of relevant journals from included studies. Randomized Clinical Trials (RCT) and comparative clinical trial studies on mandibular implant overdentures until August, 2010 were selected. Eleven studies from 1098 studies were finally selected and data were analyzed relative to number of implants. RESULTS Six studies presented the data of the implant survival rate which ranged from 95% to 100% for 2 and 4 implant group and from 81.8% to 96.1% for 1 and 2 implant group. One study, which statistically compared implant survival rate showed no significant differences relative to the number of implants. The most common type of prosthetic maintenance and complications were replacement or reattaching of loose clips for 2 and 4 implant group, and denture repair due to the fracture around an implant for 1 and 2 implant groups. Most studies showed no significant differences in the rate of prosthetic maintenance and complication, and patient satisfaction regardless the number of implants. CONCLUSION The implant survival rate of mandibular overdentures is high regardless of the number of implants. Denture maintenance is likely not inflenced substantially by the number of implants and patient satisfaction is typically high again regardless os the number of implants. PMID:23236572

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

PubMed

Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark; Dunn, J P; Yeh, Steven

2013-06-01

To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Mortality, CMV dissemination, retinitis progression, and treatment side effects. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. In the

Cochlear Implants.

ERIC Educational Resources Information Center

Clark, Catherine; Scott, Larry

This brochure explains what a cochlear implant is, lists the types of individuals with deafness who may be helped by a cochlear implant, describes the process of evaluating people for cochlear implants, discusses the surgical process for implanting the aid, traces the path of sound through the cochlear implant to the brain, notes the costs of…

Rupture of poly implant prothèse silicone breast implants: an implant retrieval study.

PubMed

Swarts, Eric; Kop, Alan M; Nilasaroya, Anastasia; Keogh, Catherine V; Cooper, Timothy

2013-04-01

Poly Implant Prothèse implants were recalled in Australia in April of 2010 following concerns of higher than expected rupture rates and the use of unauthorized industrial grade silicone as a filler material. Although subsequent investigations found that the gel filler material does not pose a threat to human health, the important question of what caused a relatively modern breast implant to have such a poor outcome compared with contemporary silicone breast implants is yet to be addressed. From a cohort of 27 patients, 19 ruptured Poly Implant Prothèse breast implants were subjected to a range of mechanical tests and microscopic/macroscopic investigations to evaluate possible changes in properties as a result of implantation. New Poly Implant Prothèse implants were used as controls. All samples, explanted and controls, complied with the requirements for shell integrity as specified in the International Organization for Standardization 14607. Compression testing revealed rupture rates similar to those reported in the literature. Shell thickness was highly variable, with most shells having regions below the minimum thickness of 0.57 mm that was specified by the manufacturer. Potential regions of stress concentration were observed on the smooth inner surfaces and outer textured surfaces. The high incidence of Poly Implant Prothèse shell rupture is most likely a result of inadequate quality control, with contributory factors being shell thickness variation and manufacturing defects on both inner and outer surfaces of the shell. No evidence of shell degradation with implantation time was determined.

Primary prevention of peri-implantitis: managing peri-implant mucositis.

PubMed

Jepsen, Søren; Berglundh, Tord; Genco, Robert; Aass, Anne Merete; Demirel, Korkud; Derks, Jan; Figuero, Elena; Giovannoli, Jean Louis; Goldstein, Moshe; Lambert, France; Ortiz-Vigon, Alberto; Polyzois, Ioannis; Salvi, Giovanni E; Schwarz, Frank; Serino, Giovanni; Tomasi, Cristiano; Zitzmann, Nicola U

2015-04-01

Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention

Successful displacement of a traumatic submacular hemorrhage in a 13-year-old boy treated by vitrectomy, subretinal injection of tissue plasminogen activator and intravitreal air tamponade: a case report.

PubMed

Doi, Shinichiro; Kimura, Shuhei; Morizane, Yuki; Shiode, Yusuke; Hosokawa, Mio; Hirano, Masayuki; Hosogi, Mika; Fujiwara, Atsushi; Miyamoto, Kazuhisa; Shiraga, Fumio

2015-08-07

The natural course of submacular hemorrhage resulting from traumatic choroidal rupture generally has a poor outcome unless treated. The intravitreal injection of gas only or gas with recombinant tissue plasminogen activator (rt-PA) has been reported to be effective, but has also been reported to induce severe complications such as retinal detachment and vitreous hemorrhage. Recently, we reported a safe and effective procedure for treating submacular hemorrhage due to polypoidal choroidal vasculopathy (PCV) with a low dose of rt-PA. Here we report the application of this procedure to a case of traumatic submacular hemorrhage in a 13-year-old boy, which achieved a good visual outcome. A 13-year-old Japanese boy presented with a thick submacular hemorrhage in his left eye as a result of blunt trauma from being hit by a sinker. Best-corrected visual acuity (BCVA) was assessed as only able to perceive hand motions. We carried out a vitrectomy, subretinal injection of 4,000 IU rt-PA (6.9 μg) and air tamponade. The day after surgery, most of the submacular hemorrhage had moved to the inferior periphery. One month after the surgery, we observed cataract formation, thin remnants of the submacular hemorrhage and juxtafoveal choroidal rupture. We carried out cataract surgery and injected bevacizumab intravitreally to prevent the development of choroidal neovascularization. Two months after the second surgery, the submacular hemorrhage had totally disappeared and the patient had a BCVA of 20/40. Vitrectomy, subretinal injection of rt-PA, and intravitreal air tamponade may be a promising strategy for treating traumatic submacular hemorrhage in young patients.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared

Short Implants Versus Standard Implants: Midterm Outcomes of a Clinical Study.

PubMed

Benlidayi, M Emre; Ucar, Yurdanur; Tatli, Ufuk; Ekren, Orhun; Evlice, Burcu; Kisa, Halil Ibrahim; Baksi, Uygar

2018-02-01

The aim of this study was to evaluate the midterm survival rate, marginal bone resorption (MBR), and stability of short implants and to compare the results with standard length implants. A total of 38 patients were included. In total, 147 implants (Nucleoss Implants, Izmir, Turkey) were placed (86 short implants and 61 standard implants). Cement-retained metal-ceramic prostheses were fabricated. MBR was evaluated on periapical radiographs taken at implant placement, at the time of crown insertion and annually thereafter. The stability of the implants was evaluated by resonance frequency analysis. The 3- and 5-year cumulative survival rates for standard implants was 98.4% and for short implants was 96.5% (P = 0.644). The MBR of the short implants was significantly lower than that of the standard implants after 1, 2, and 3 years of loading (P < 0.05). No significant differences were found between 2 groups after 6 and 12 months of loading in terms of implant stability (implant stability quotient values) (P > 0.05). Within the limits of this study, it is concluded that short implants achieved similar results as standard implants after 3 to 5 years of loading.

Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.

PubMed

Langouet-Astrie, Christophe J; Yang, Zhiyong; Polisetti, Sraavya M; Welsbie, Derek S; Hauswirth, William W; Zack, Donald J; Merbs, Shannath L; Enke, Raymond A

2016-10-01

Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant.

PubMed

Winterhalter, Sibylle; Vom Brocke, Gerrit Alexander; Pilger, Daniel; Eckert, Annabelle; Schlomberg, Juliane; Rübsam, Anne; Klamann, Matthias Karl; Gundlach, Enken; Dietrich-Ntoukas, Tina; Joussen, Antonia Maria

2016-10-27

Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 μm (1 month; p = 0.003,) to 361 μm (2 months; p = 0,002) and to 415 μm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 μm (1 month; p < 0,001) and to 343 μm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity.

A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion

PubMed Central

Ip, Michael S.; Scott, Ingrid U.; VanVeldhuisen, Paul C.; Oden, Neal L.; Blodi, Barbara A.; Fisher, Marian; Singerman, Lawrence J.; Tolentino, Michael; Chan, Clement K.; Gonzalez, Victor H.

2009-01-01

Objective: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). Methods: Multicenter, randomized, clinical trial of 271 participants. Main Outcome Measure: Gain in visual acuity letter score of 15 or more from baseline to month 12. Results: Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR],5.0; 95% confidence interval [CI], 1.8-14.1; P=.001) and 5.0 times greater in 4-mg group than the observation group (OR,5.0; 95% CI, 1.8-14.4; P=.001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P=.97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. Conclusions: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice: Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. Trial Registration: clinicaltrials.gov Identifier: NCT00105027 PMID:19752419

Why are mini-implants lost: the value of the implantation technique!

PubMed

Romano, Fabio Lourenço; Consolaro, Alberto

2015-01-01

The use of mini-implants have made a major contribution to orthodontic treatment. Demand has aroused scientific curiosity about implant placement procedures and techniques. However, the reasons for instability have not yet been made totally clear. The aim of this article is to establish a relationship between implant placement technique and mini-implant success rates by means of examining the following hypotheses: 1) Sites of poor alveolar bone and little space between roots lead to inadequate implant placement; 2) Different sites require mini-implants of different sizes! Implant size should respect alveolar bone diameter; 3) Properly determining mini-implant placement site provides ease for implant placement and contributes to stability; 4) The more precise the lancing procedures, the better the implant placement technique; 5) Self-drilling does not mean higher pressures; 6) Knowing where implant placement should end decreases the risk of complications and mini-implant loss.

Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: Host-microbe interactions in intraocular infection

PubMed Central

Sadaka, Ama; Durand, Marlene L; Gilmore, Michael S

2012-01-01

Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular degeneration raises yet additional risks. Compounding the problem is the continuing progression of antibiotic resistance. Visual prognosis for endophthalmitis depends on the virulence of the causative organism, the severity of intraocular inflammation, and the timeliness of effective therapy. We review the current understanding of the pathogenesis of bacterial endophthalmitis, highlighting opportunities for the development of improved therapeutics and preventive strategies. PMID:22521570

Hydroxyapatite ocular implant and non-integrated implants in eviscerated patients

PubMed Central

Gradinaru, S; Popescu, V; Leasu, C; Pricopie, S; Yasin, S; Ciuluvica, R; Ungureanu, E

2015-01-01

Introduction: This study compares the outcomes and complications of hydroxyapatite ocular implant and non-integrated ocular implants following evisceration. Materials and Methods: This is a retrospective study of 90 patients who underwent evisceration for different ocular affections, in the Ophthalmology Department of the University Emergency Hospital Bucharest, between January 2009 and December 2013. The outcomes measured were conjunctival dehiscence, socket infection, implant exposure and extrusion rate. Results: Forty-three patients had the hydroxyapatite implant (coralline–Integrated Ocular Implants, USA or synthetic–FCI, France) and forty-seven received non-integrated ocular implants (24 acrylic and 23 silicone). Five cases of socket infection, thirteen cases of extrusion and two cases of conjunctival dehiscence were encountered. Conclusions: There was a higher rate of conjunctival dehiscence with hydroxyapatite ocular implant, but implant extrusion and socket infection were found in non-integrated ocular implants. PMID:25914747

Immediate direct-to-implant breast reconstruction using anatomical implants.

PubMed

Kim, Sung-Eun; Jung, Dong-Woo; Chung, Kyu-Jin; Lee, Jun Ho; Kim, Tae Gon; Kim, Yong-Ha; Lee, Soo Jung; Kang, Su Hwan; Choi, Jung Eun

2014-09-01

In 2012, a new anatomic breast implant of form-stable silicone gel was introduced onto the Korean market. The intended use of this implant is in the area of aesthetic breast surgery, and many reports are promising. Thus far, however, there have been no reports on the use of this implant for breast reconstruction in Korea. We used this breast implant in breast reconstruction surgery and report our early experience. From November 2012 to April 2013, the Natrelle Style 410 form-stable anatomically shaped cohesive silicone gel-filled breast implant was used in 31 breasts of 30 patients for implant breast reconstruction with an acellular dermal matrix. Patients were treated with skin-sparing mastectomies followed by immediate breast reconstruction. The mean breast resection volume was 240 mL (range, 83-540 mL). The mean size of the breast implants was 217 mL (range, 125-395 mL). Breast shape outcomes were considered acceptable. Infection and skin thinning occurred in one patient each, and hematoma and seroma did not occur. Three cases of wound dehiscence occurred, one requiring surgical intervention, while the others healed with conservative treatment in one month. Rippling did not occur. So far, complications such as capsular contracture and malrotation of breast implant have not yet arisen. By using anatomic breast implants in breast reconstruction, we achieved satisfactory results with aesthetics better than those obtained with round breast implants. Therefore, we concluded that the anatomical implant is suitable for breast reconstruction.

Survival of dental implants placed in sites of previously failed implants.

PubMed

Chrcanovic, Bruno R; Kisch, Jenö; Albrektsson, Tomas; Wennerberg, Ann

2017-11-01

To assess the survival of dental implants placed in sites of previously failed implants and to explore the possible factors that might affect the outcome of this reimplantation procedure. Patients that had failed dental implants, which were replaced with the same implant type at the same site, were included. Descriptive statistics were used to describe the patients and implants; survival analysis was also performed. The effect of systemic, environmental, and local factors on the survival of the reoperated implants was evaluated. 175 of 10,096 implants in 98 patients were replaced by another implant at the same location (159, 14, and 2 implants at second, third, and fourth surgeries, respectively). Newly replaced implants were generally of similar diameter but of shorter length compared to the previously placed fixtures. A statistically significant greater percentage of lost implants were placed in sites with low bone quantity. There was a statistically significant difference (P = 0.032) in the survival rates between implants that were inserted for the first time (94%) and implants that replaced the ones lost (73%). There was a statistically higher failure rate of the reoperated implants for patients taking antidepressants and antithrombotic agents. Dental implants replacing failed implants had lower survival rates than the rates reported for the previous attempts of implant placement. It is suggested that a site-specific negative effect may possibly be associated with this phenomenon, as well as the intake of antidepressants and antithrombotic agents. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sub-meninges implantation reduces immune response to neural implants.

PubMed

Markwardt, Neil T; Stokol, Jodi; Rennaker, Robert L

2013-04-15

Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. Published by Elsevier B.V.

Sub-meninges Implantation Reduces Immune Response to Neural Implants

PubMed Central

Markwardt, Neil T.; Stokol, Jodi; Rennaker, Robert L.

2013-01-01

Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. PMID:23370311

Imaging of common breast implants and implant-related complications: A pictorial essay.

PubMed

Shah, Amisha T; Jankharia, Bijal B

2016-01-01

The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer.

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and

Evidence-based review of diabetic macular edema management: Consensus statement on Indian treatment guidelines

PubMed Central

Das, Taraprasad; Aurora, Ajay; Chhablani, Jay; Giridhar, Anantharaman; Kumar, Atul; Raman, Rajiv; Nagpal, Manish; Narayanan, Raja; Natarajan, Sundaram; Ramasamay, Kim; Tyagi, Mudit; Verma, Lalit

2016-01-01

The purpose of the study was to review the current evidence and design a diabetic macular edema (DME) management guideline specific for India. The published DME guidelines from different organizations and publications were weighed against the practice trends in India. This included the recently approved drugs. DME management consisted of control of diabetes and other associated systemic conditions, such as hypertension and hyperlipidemia, and specific therapy to reduce macular edema. Quantification of macular edema is precisely made with the optical coherence tomography and treatment options include retinal laser, intravitreal anti-vascular endothelial growth factors (VEGF), and implantable dexamethasone. Specific use of these modalities depends on the presenting vision and extent of macular involvement. Invariable eyes with center-involving macular edema benefit from intravitreal anti-VEGF or dexamethasone implant therapy, and eyes with macular edema not involving the macula center benefit from retinal laser. The results are illustrated with adequate case studies and frequently asked questions. This guideline prepared on the current published evidence is meant as a guideline for the treating physicians. PMID:26953019

Imaging of common breast implants and implant-related complications: A pictorial essay

PubMed Central

Shah, Amisha T; Jankharia, Bijal B

2016-01-01

The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer. PMID:27413269

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Cochlear implants in children implanted in Jordan: A parental overview.

PubMed

Alkhamra, Rana A

2015-07-01

Exploring the perspective of parents on the cochlear implant process in Jordan. Sixty parents of deaf children were surveyed on the information gathering process prior to cochlear implant surgery, and their implant outcome expectations post-surgery. Whether child or parent characteristics may impact parents' post-surgical expectations was explored. Although parents used a variety of information sources when considering a cochlear implant, the ear, nose and throat doctor comprised their major source of information (60%). Parents received a range of information prior to cochlear implant but agreed (93.3%) on the need for a multidisciplinary team approach. Post-surgically, parents' expected major developments in the areas of spoken language (97%), and auditory skills (100%). Receiving education in mainstream schools (92%) was expected too. Parents perceived the cochlear implant decision as the best decision they can make for their child (98.3%). A significant correlation was found between parents contentment with the cochlear implant decision and expecting developments in the area of reading and writing (r=0.7). Child's age at implantation and age at hearing loss diagnosis significantly affected parents' post-implant outcome expectations (p<0.05). Despite the general satisfaction from the information quantity and quality prior to cochlear implant, parents agree on the need for a comprehensive multidisciplinary team approach during the different stages of the cochlear implant process. Parents' education about cochlear implants prior to the surgery can affect their post-surgical outcome expectations. The parental perspective presented in this study can help professionals develop better understanding of parents' needs and expectations and henceforth improve their services and support during the different stages of the cochlear implant process. Copyright © 2015. Published by Elsevier Ireland Ltd.

Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury

PubMed Central

Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2015-01-01

Purpose Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Methods Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. Results A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. Conclusions A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection. PMID:26167113

Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury.

PubMed

Russo, Rossella; Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2015-01-01

Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection.

Breast reconstruction - implants

MedlinePlus

Breast implants surgery; Mastectomy - breast reconstruction with implants; Breast cancer - breast reconstruction with implants ... it harder to find a tumor if your breast cancer comes back. Getting breast implants does not take ...

Intravitreal aflibercept for diabetic macular edema.

PubMed

Korobelnik, Jean-François; Do, Diana V; Schmidt-Erfurth, Ursula; Boyer, David S; Holz, Frank G; Heier, Jeffrey S; Midena, Edoardo; Kaiser, Peter K; Terasaki, Hiroko; Marcus, Dennis M; Nguyen, Quan D; Jaffe, Glenn J; Slakter, Jason S; Simader, Christian; Soo, Yuhwen; Schmelter, Thomas; Yancopoulos, George D; Stahl, Neil; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Metzig, Carola; Brown, David M

2014-11-01

A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME). Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(DME) and VIVID(DME). We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement. Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation. The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography. Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups. At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated. Copyright © 2014

International classification of reliability for implanted cochlear implant receiver stimulators.

PubMed

Battmer, Rolf-Dieter; Backous, Douglas D; Balkany, Thomas J; Briggs, Robert J S; Gantz, Bruce J; van Hasselt, Andrew; Kim, Chong Sun; Kubo, Takeshi; Lenarz, Thomas; Pillsbury, Harold C; O'Donoghue, Gerard M

2010-10-01

To design an international standard to be used when reporting reliability of the implanted components of cochlear implant systems to appropriate governmental authorities, cochlear implant (CI) centers, and for journal editors in evaluating manuscripts involving cochlear implant reliability. The International Consensus Group for Cochlear Implant Reliability Reporting was assembled to unify ongoing efforts in the United States, Europe, Asia, and Australia to create a consistent and comprehensive classification system for the implanted components of CI systems across manufacturers. All members of the consensus group are from tertiary referral cochlear implant centers. None. A clinically relevant classification scheme adapted from principles of ISO standard 5841-2:2000 originally designed for reporting reliability of cardiac pacemakers, pulse generators, or leads. Standard definitions for device failure, survival time, clinical benefit, reduced clinical benefit, and specification were generated. Time intervals for reporting back to implant centers for devices tested to be "out of specification," categorization of explanted devices, the method of cumulative survival reporting, and content of reliability reports to be issued by manufacturers was agreed upon by all members. The methodology for calculating Cumulative survival was adapted from ISO standard 5841-2:2000. The International Consensus Group on Cochlear Implant Device Reliability Reporting recommends compliance to this new standard in reporting reliability of implanted CI components by all manufacturers of CIs and the adoption of this standard as a minimal reporting guideline for editors of journals publishing cochlear implant research results.

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

2017-07-01

To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

Images of intravitreal objects projected onto posterior surface of model eye.

PubMed

Kawamura, Ryosuke; Shinoda, Kei; Inoue, Makoto; Noda, Toru; Ohnuma, Kazuhiko; Hirakata, Akito

2013-11-01

To try to recreate the images reported by patients during vitreous surgery in a model eye. A fluid-filled model eye with a posterior frosted translucent surface which corresponded to the retina was used. Three holes were made in the model eye through which an endoillumination pipe and intraocular forceps could be inserted. A thin plastic sheet simulating an epiretinal membrane and an intraocular lens (IOL) simulating a dislocated IOL were placed on the retina. The images falling on the posterior surface were photographed from the rear. The images seen through the surgical microscope were also recorded. The images from the rear were mirror images of those seen through the surgical microscope. Intraocular instruments were seen as black shafts from the rear. When the plastic sheet was picked up, the tip of the forceps was seen more sharply on the posterior surface. The images of the dislocated IOL from the posterior were similar to that seen through the surgical microscope, including the yellow optics and blue haptics. Intravitreal objects can form images on the surface of a model eye. Objects located closer to the surface are seen more sharply, and the colour of the objects can be identified. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Precision of fit between implant impression coping and implant replica pairs for three implant systems.

PubMed

Nicoll, Roxanna J; Sun, Albert; Haney, Stephan; Turkyilmaz, Ilser

2013-01-01

The fabrication of an accurately fitting implant-supported fixed prosthesis requires multiple steps, the first of which is assembling the impression coping on the implant. An imprecise fit of the impression coping on the implant will cause errors that will be magnified in subsequent steps of prosthesis fabrication. The purpose of this study was to characterize the 3-dimensional (3D) precision of fit between impression coping and implant replica pairs for 3 implant systems. The selected implant systems represent the 3 main joint types used in implant dentistry: external hexagonal, internal trilobe, and internal conical. Ten impression copings and 10 implant replicas from each of the 3 systems, B (Brånemark System), R (NobelReplace Select), and A (NobelActive) were paired. A standardized aluminum test body was luted to each impression coping, and the corresponding implant replica was embedded in a stone base. A coordinate measuring machine was used to quantify the maximum range of displacement in a vertical direction as a function of the tightening force applied to the guide pin. Maximum angular displacement in a horizontal plane was measured as a function of manual clockwise or counterclockwise rotation. Vertical and rotational positioning was analyzed by using 1-way analysis of variance (ANOVA). The Fisher protected least significant difference (PLSD) multiple comparisons test of the means was applied when the F-test in the ANOVA was significant (α=.05). The mean and standard deviation for change in the vertical positioning of impression copings was 4.3 ±2.1 μm for implant system B, 2.8 ±4.2 μm for implant system R, and 20.6 ±8.8 μm for implant system A. The mean and standard deviation for rotational positioning was 3.21 ±0.98 degrees for system B, 2.58 ±1.03 degrees for system R, and 5.30 ±0.79 degrees for system A. The P-value for vertical positioning between groups A and B and between groups A and R was <.001. No significant differences were found for

The effectiveness and reliability of posterior sub-Tenon triamcinolone acetonide injection in branch retinal vein occlusion-related macular edema.

PubMed

Kola, Mehmet; Hacioglu, Dilek; Turk, Adem; Erdol, Hidayet

2016-09-01

To investigate the effectiveness and reliability of posterior sub-Tenon triamcinolone acetonide (PSTA) application in branch retinal vein occlusion (BRVO)-related macular edema. Patients with confirmed BRVO-related macular edema were enrolled in the study. Patients were injected with a single, therapeutic dose of 40 mg PSTA. Detailed ophthalmic examination was performed at baseline and at 1, 3 and 6 months after the treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), cataractogenic change (CC) and macular optical coherence tomography (OCT) analysis results were evaluated. The results were compared statistically. Forty-one eyes of 41 patients with a mean age of 63.49 ± 10.99 (55-86) years, 15 (36.6%) females, were included in the study. BCVA in LogMAR values at 1 and 3 months were significantly better than at baseline, while no significant difference from baseline was observed in sixth month values (p < 0.001, p < 0.001 and p = 0.846, respectively). Central macular thickness values obtained using OCT were significantly lower at the first, third and sixth months compared to baseline (p < 0.001 for all). IOP elevation was determined in only two eyes (4.8%) at the end of the study period, and no CC was detected in any case. PSTA application is an effective and safe option in BRVO-related macular edema.

Cushing's syndrome after intralesional triamcinolone acetonide: a systematic review of the literature and multinational survey.

PubMed

Fredman, Rafi; Tenenhaus, Mayer

2013-06-01

Intralesional triamcinolone acetonide (TAC) is a well-established treatment for keloids and hypertrophic scars. The present text provides a systematic review of all previously reported cases of Cushing's syndrome resulting from intralesional TAC in an effort to discover whether an association exists between dosage or frequency of injection and the subsequent development of Cushing's syndrome. Data collected from a multinational survey of plastic surgeons is presented and discussed to understand current trends in the use of TAC. Recommendations for early recognition of Cushing's syndrome, TAC dosages in children, and follow up guidelines are presented. A systematic review of the literature from 1950 to 2012 was performed to evaluate outcomes following intralesional TAC used for the treatment of scars. A confidential survey was sent to 4125 plastic surgeons, 102 responses from 9 countries were received. A total of 18 cases of Cushing's syndrome after intralesional TAC have been reported in the English world literature. Survey data reveals that at least 30% (25/84) of plastic surgeons exceed the recommended dosage of TAC and 47% (46/97) are not aware of Cushing's syndrome as a possible complication of intralesional TAC. Cushing's syndrome resulting from intralesional TAC has been reported multiple times in the literature. Published literature suggests that TAC administered within the most recent recommendations does not appear to place adult patients at increased risk for developing Cushing's syndrome. Children appear to be most at risk for developing Cushing's syndrome and yet insufficient recommendations currently exist with regard to their safe dosage. Intralesional dosage should not exceed 30 mg per month in children while noting that at least one reported case of Cushing's syndrome resulted from a smaller dose. Diligent follow up and patient education is advised for any patient treated with TAC so that complications can be recognized and addressed promptly

Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes.

PubMed

Abd-El-Barr, Muhammad M; Albini, Thomas A; Carvounis, Petros E; He, Feng; Manzano, Roberta P A; Chevez-Barrios, Patricia; Wensel, Theodore G; Wu, Samuel M; Holz, Eric R

2008-04-01

The aim of this study was to evaluate whether intravitreal triamcinolone hexacetonide (TH) is a safe, longer lasting alternative to intravitreal triamcinolone acetonide (TA) in the rabbit eye. Three groups, each comprising of 15 Dutch-belted rabbits, received a unilateral injection of 0.1 mL of drug and 0.1 mL of physiologic salt solution in the fellow eye. Group I received TA, group II received commercially available TH, and group III received reformulated iso-osmolar triamcinolone hexacetonide (rTH). Simultaneous bilateral dark-adapted electroretinography was performed following the injection. Retinal morphology was assessed by using histopathology in each group enucleated 12 weeks after injection. High-performance liquid chromatography of vitreous isolated from the enucleated eyes was used to determine drug concentrations. A significant reduction in saturated a-wave and maximal scotopic b-wave was observed in the group II eyes relative to the fellow control eyes at both 2 and 12 weeks postinjection (P < 0.001 for each comparison) but not in the other groups. Histopathology showed no differences between drug-injected eyes and fellow control eyes in groups I and III, but in group II there was severe degeneration of all retina layers. In group I, the drug half-life was 17.7 +/- 1.7 days, group II 44 +/- 13 days, and group III 12.8 +/- 2.3 days. The half-life of commercially available TH in the vitreous is double that of TA, but the former is toxic to the retina in this rabbit model. Reformulated iso-osmolar TH showed no evidence of deleterious effects to retina function or structure but had a similar half-life to TA.

[Application of plasma sprayed zirconia coating in dental implant: study in implant].

PubMed

Huang, Z F; Wang, Z F; Li, C H; Hao, D; Lan, J

2018-04-09

Objective: To investigate the osseointegration of a novel coating-plasma-sprayed zirconia in dental implant. Methods: Zirconia coating on non-thread titanium implant was prepared using plasma spraying, the implant surface morphology, surface roughness and wettability were measured. In vivo , zirconia coated implants were inserted in rabbit tibia and animals were respectively sacrificed at 2, 4, 8 and 12 weeks after implantation. The bond strength between implant and bone was measured by push-out test. The osseointegration was observed by scanning electron microscopy (SEM), micro CT and histological analyses. Quantified parameters including removal torque, and bone-implant contact (BIC) percentage were calculated. Results: The surface roughness (1.6 µm) and wettability (54.6°) of zirconia coated implant was more suitable than those of titanium implant (0.6 µm and 74.4°) for osseointegration. At 12 weeks, the push-out value of zirconia coated implant and titanium implant were (64.9±3.0) and (50.4±2.9) N, and BIC value of these two groups were (54.7±3.6)% and (41.5±3.6)%. All these differences had statistical significance. Conclusions: The surface characters of zirconia coated implant were more suitable for osseointegration and present better osseointegration than smooth titanium implant in vivo , especially at early stage.

Physicochemical characterization and in vivo evaluation of triamcinolone acetonide-loaded hydroxyapatite nanocomposites for treatment of rheumatoid arthritis.

PubMed

Jafari, Samira; Maleki-Dizaji, Nasrin; Barar, Jaleh; Barzegar-Jalali, Mohammad; Rameshrad, Maryam; Adibkia, Khosro

2016-04-01

The current study was aimed to investigate the anti-inflammatory effect of triamcinolone acetonide-loaded hydroxyapatite (TA-loaded HAp) nanocomposites in the arthritic rat model. The HAp nanocomposites were synthesized through a chemical precipitation method and the drug was subsequently incorporated into the nanocomposites using an impregnation method. The physicochemical properties as well as cytotoxicity of the prepared nanoformulation were examined as well. To evaluate the therapeutic efficacy of the prepared nanoformulation, the various parameters such as paw volume, haematological parameters and histological studies were assessed in the arthritic rats. The nanocomposites with the particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 41.94% were obtained in this study. The specific surface area (aBET) as well as the volume of nitrogen adsorbed on one gram of HAp to complete the monolayer adsorption (Vm) were decreased after the drug loading process. The prepared nanoformulation revealed the slower drug release profile compared to the pure drug. Furthermore, the obtained data from MTT assay showed that the TA-loaded nanocomposites had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines as compared to the pure drug. Furthermore, TA-loaded HAp nanocomposites demonstrated favorable effects on the paw volume as well as the haematological and histopathological abnormalities in the adjuvant-induced arthritic rats. Therefore, TA-loaded HAp nanocomposites are potentially suggested for treatment of rheumatoid arthritis after further required evaluations. Copyright © 2015 Elsevier B.V. All rights reserved.

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment

PubMed Central

Xie, Z; Chen, F; Wu, X; Zhuang, C; Zhu, J; Wang, J; Ji, H; Wang, Y; Hua, X

2012-01-01

Purpose To elucidate the safety and efficacy of exogenous erythropoietin (EPO) for the protection of photoreceptor cells in a rat model of retinal detachment (RD). Methods Recombinant rat EPO (400 ng) was injected into the vitreous cavity of normal rats to observe the eye manifestations. Retinal function was assessed by flash electroretinograms. Histopathological examination of retinal tissue was performed at 14 days and 2 months after injection, respectively. To investigate the inhibitory effect of EPO on photoreceptor cell apoptosis in RD rats, 100, 200, or 400 ng EPO was injected into the vitreous cavity immediately after RD model establishment. Apoptosis of photoreceptor cells was determined at 3 days after injection. Caspase-3 activation was measured by western blot analysis and immunofluorescence, respectively, and the level of Bcl-XL expression was analyzed by western blot. Results Intravitreal injection of EPO 400 ng into normal rats had no significant impact on retinal function, morphology, or structure. Apoptosis of retinal photoreceptor cells apparently increased after RD and was significantly reduced following EPO treatment. The thickness of the outer nuclear layer in the RD+400 ng group was significantly thicker than that in other experimental RD groups both at 14 days and at 2 months after RD (P<0.05). Western blot and immunofluorescence analyses showed decreased caspase-3 activation and increased Bcl-XL expression following EPO treatment. Conclusion Intravitreal injection of EPO 400 ng is safe, and EPO may suppress caspase-3 activation and enhance Bcl-XL expression, resulting in inhibition of apoptosis and protection of photoreceptor cells. PMID:22020175

Cochlear implantation in late-implanted adults with prelingual deafness.

PubMed

Most, Tova; Shrem, Hadas; Duvdevani, Ilana

2010-01-01

The purpose of this study was to examine the effect of cochlear implantation (CI) on prelingually deafened participants who were implanted as adults. The effect of the CI was examined with regard to the following variables: communication, family, social skills, education, and work satisfaction with one's life, loneliness, and self-esteem. Thirty-eight adults participated. Four self-report questionnaires were used at 2 points in time: before and after CI. The research findings show significant differences in the reports of most variables before and after implantation. The participants felt better with regard to communication, social skills, education, and work and satisfaction with one's life after implantation in comparison to their feelings before implantation. Furthermore, they felt less lonely after implantation. However, there were no significant differences before and after implantation regarding their feelings within the family and regarding their self-esteem. The results demonstrated the need to evaluate the benefits resulting from the CI not only with traditional clinical measures but with additional measures as well. Furthermore, they demonstrated the benefit of the CI on the positive psychosociological implications of prelingually deafened adults. Copyright © 2010 Elsevier Inc. All rights reserved.

Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial.

PubMed

Sen, H Nida; Abreu, Francis M; Louis, Thomas A; Sugar, Elizabeth A; Altaweel, Michael M; Elner, Susan G; Holbrook, Janet T; Jabs, Douglas A; Kim, Rosa Y; Kempen, John H

2016-01-01

To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis Steroid Treatment (MUST) Trial. Nested prospective cohort study of patients enrolled in a randomized clinical trial. Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial. Visual outcomes of cataract surgery were evaluated 3, 6, and 9 months after surgery using logarithmic visual acuity charts. Change in visual acuity over time was assessed using a mixed-effects model. Best-corrected visual acuity. After excluding eyes that underwent cataract surgery simultaneously with implant surgery, among the 479 eyes in the MUST Trial, 117 eyes (28 eyes in the systemic, 89 in the implant group) in 82 patients underwent cataract surgery during the first 2 years of follow-up. Overall, visual acuity increased by 23 letters from the preoperative visit to the 3-month visit (95% confidence interval [CI], 17-29 letters; P < 0.001) and was stable through 9 months of follow-up. Eyes presumed to have a more severe cataract, as measured by inability to grade vitreous haze, gained an additional 42 letters (95% CI, 34-56 letters; P < 0.001) beyond the 13-letter gain in eyes that had gradable vitreous haze before surgery (95% CI, 9-18 letters; P < 0.001) 3 months after surgery, making up for an initial difference of -45 letters at the preoperative visit (95% CI, -56 to -34 letters; P < 0.001). Black race, longer time from uveitis onset, and hypotony were associated with worse preoperative visual acuity (P < 0.05), but did not affect postsurgical recovery (P > 0.05, test of interaction). After adjusting for other risk factors, there was no significant difference in the improvement in visual acuity between the 2 treatment groups (implant vs. systemic therapy, 2 letters; 95% CI, -10 to 15 letters; P = 0.70). Cataract surgery resulted in substantial

Prevalence of peri-implantitis in patients with implant-supported fixed prostheses.

PubMed

Schuldt Filho, Guenther; Dalago, Haline Renata; Oliveira de Souza, João Gustavo; Stanley, Kyle; Jovanovic, Sascha; Bianchini, Marco Aurélio

2014-01-01

The purpose of this study was to evaluate periimplantitis prevalence in patients using implant-supported fixed prostheses that did not have any routine maintenance care. A total of 161 implants (27 patients) were evaluated in patients using implant-supported fixed prostheses. Collected data included information related to patient general health and local factors such as characteristics of implants, time in function, type of loading, positioning, Modified Bleeding Index, bacterial plaque, bleeding on probing (BOP), marginal recession, probing depth (PD), keratinized mucosa, and radiographic bone loss (BL). Factors related to the prostheses were also evaluated. The exclusion criteria were patients that have had any follow-up visit for plaque control of the prosthesis and/or the implants. From a total of 161 implants, 116 (72%) presented without peri-implantitis (PD > 4 mm + BOP + BL > 2 mm) while 45 (28%) had some sign of the disease. Implants placed in the maxilla were 2.98 times more likely to develop the disease (P < .05). Moreover, patients aged ≤ 60 years old were 3.24 times more likely to develop peri-implantitis (P < .05). Another analysis with statistical relevance (P < .05) was that implants with less than 3 mm interimplant distance were three times more likely to have peri-implantitis. There was no statistical relevance considering other analyses. It can be concluded that patients aged ≤ 60 years have a greater chance of presenting periimplantitis, as well as for implants positioned in the maxilla and those placed with an interimplant distance < 3 mm.

Prevalences of peri-implantitis and peri-implant mucositis: systematic review and meta-analysis.

PubMed

Lee, Chun-Teh; Huang, Yen-Wen; Zhu, Liang; Weltman, Robin

2017-07-01

Due to the inconsistent definitions, reporting methods and study characteristics, prevalences of peri-implant diseases significantly varied in studies. This study aimed to systematically analyze implant-based and subject-based prevalences of peri-implant diseases and assess clinical variables potentially affecting the prevalence. Electronic search of studies was conducted using MEDLINE (PubMed), EMBASE and Web of Science. Publication screening, data extraction, and quality assessment were performed. Clinical studies having an at least average three-year follow-up period were selected. The numbers of subjects and implants in the studies had to be equal to or more than thirty. Forty seven studies were selected and prevalences of peri-implant diseases were analyzed. Since heterogeneity existed in each outcome (I 2 =94.7, 95.7, 95.3, and 99.3 for implant-based and subject-based peri-implantitis and peri-implant mucositis, respectively), the random-effects model based on the DerSimonian and Laird method, which incorporate an estimate of heterogeneity in the weighting, was applied to obtain the pooled prevalence. Weighted mean implant-based and subject-based peri-implantitis prevalences were 9.25% (95% Confidence Interval (CI): [7.57, 10.93]) and 19.83% (CI [15.38, 24.27) respectively. Weighted mean implant-based and subject-based peri-implant mucositis prevalences were 29.48% (CI: [22.65, 36.32]) and 46.83% (CI: [38.30, 55.36]) respectively. Functional time and implant to subject ratio were associated with subject-based peri-implantitis prevalence, but not peri-implant mucositis prevalences. Peri-implant diseases were prevalent and prevalence of peri-implantitis increased over time. Prevalences of peri-implantitis and peri-implant mucositis might not be highly associated since the prevalences were influenced by distinct variables. The results should be carefully interpreted because of data heterogeneity. Peri-implant diseases affect a significant number of dental

Decontamination of dental implant surface in peri-implantitis treatment: A literature review

PubMed Central

Buitrago-Vera, Pedro; Solá-Ruiz, María F.; Ferrer-García, Juan C.

2013-01-01

Etiological treatment of peri-implantitis aims to reduce the bacterial load within the peri-implant pocket and decontaminate the implant surface in order to promote osseointegration. The aim of this literature review was to evaluate the efficacy of different methods of implant surface decontamination. A search was conducted using the PubMed (Medline) database, which identified 36 articles including in vivo and in vitro studies, and reviews of different decontamination systems (chemical, mechanical, laser and photodynamic therapies). There is sufficient consensus that, for the treatment of peri-implant infections, the mechanical removal of biofilm from the implant surface should be supplemented by chemical decontamination with surgical access. However, more long-term research is needed to confirm this and to establish treatment protocols responding to different implant characterics. Key words:Peri-implantitis, treatment, decontamination, implant surface, laser. PMID:23986023

Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats.

PubMed

Zhang, Yu; Zhang, Jingfa; Wang, Qingping; Lei, Xia; Chu, Qing; Xu, Guo-Tong; Ye, Wen

2011-01-05

To evaluate the protective effect of intravitreal injection of exendin-4 analogue (E4a) in early diabetic retinopathy (DR) and to explore its possible mechanism. Forty Sprague-Dawley rats were divided into three groups: normal (N), diabetic (D), and E4a-treated diabetic rats (E4a). Diabetes was induced by streptozotocin. Rats in the E4a group were treated with E4a (0.1 μg/2μL/eye), whereas the N and D groups were treated with the equivalent volume of normal saline. Electroretinography was performed at 1 month and 3 months after diabetes onset. Thicknesses and cell counts in each layer of the retina were evaluated. The concentration of glutamate was measured by high-performance liquid chromatography (HPLC). Expressions of glucagon-like peptide-1 receptor (GLP-1R) and GLAST (excitatory amino acid transporter) were detected at mRNA and protein levels and verified by immunohistochemistry in vitro and in vivo. The rMc-1 cells were cultured under high-glucose medium (25 mM), which mimicked diabetic conditions. Effects of E4a (10 μg/mL) were also tested in the rMc-1 culture system. E4a prevented the reduction in b-wave amplitude and oscillatory potential amplitude caused by diabetes. It also prevented the cell loss of outer nuclear layer and inner nuclear layer; the thickness and cell count in the outer nuclear layer were decreased in 1-month diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats and was significantly reduced in the E4a-treated group. Consistent with such changes, retinal GLP-1R and GLAST expression were reduced in the diabetic retina but upregulated in E4a-treated rats. No improvement was found in the retina in both functional and morphologic parameters 3 months after treatment. Intravitreal administration of E4a can prevent the retina, functionally and morphologically, from the insults of diabetes in rats. GLP-1R and GLAST were proved to exist in the rat retina, and their lowered expressions in the diabetic retina

Two-stage implant systems.

PubMed

Fritz, M E

1999-06-01

Since the advent of osseointegration approximately 20 years ago, there has been a great deal of scientific data developed on two-stage integrated implant systems. Although these implants were originally designed primarily for fixed prostheses in the mandibular arch, they have been used in partially dentate patients, in patients needing overdentures, and in single-tooth restorations. In addition, this implant system has been placed in extraction sites, in bone-grafted areas, and in maxillary sinus elevations. Often, the documentation of these procedures has lagged. In addition, most of the reports use survival criteria to describe results, often providing overly optimistic data. It can be said that the literature describes a true adhesion of the epithelium to the implant similar to adhesion to teeth, that two-stage implants appear to have direct contact somewhere between 50% and 70% of the implant surface, that the microbial flora of the two-stage implant system closely resembles that of the natural tooth, and that the microbiology of periodontitis appears to be closely related to peri-implantitis. In evaluations of the data from implant placement in all of the above-noted situations by means of meta-analysis, it appears that there is a strong case that two-stage dental implants are successful, usually showing a confidence interval of over 90%. It also appears that the mandibular implants are more successful than maxillary implants. Studies also show that overdenture therapy is valid, and that single-tooth implants and implants placed in partially dentate mouths have a success rate that is quite good, although not quite as high as in the fully edentulous dentition. It would also appear that the potential causes of failure in the two-stage dental implant systems are peri-implantitis, placement of implants in poor-quality bone, and improper loading of implants. There are now data addressing modifications of the implant surface to alter the percentage of

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.

PubMed

Biagi, C; Conti, V; Montanaro, N; Melis, M; Buccellato, E; Donati, M; Covezzoli, A; Amato, R; Pazzi, L; Venegoni, M; Vaccheri, A; Motola, D

2014-12-01

The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.

Simultaneous determination of triamcinolone hexacetonide and triamcinolone acetonide in rabbit plasma using a highly sensitive and selective UPLC-MS/MS method.

PubMed

Sun, Wei; Ho, Stacy; Fang, Xiaojun Rick; O'Shea, Thomas; Liu, Hanlan

2018-05-10

An ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was successfully developed and qualified for the simultaneous determination of triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TAA, the active metabolite of TAH) in rabbit plasma. To prevent the hydrolysis of TAH to TAA ex vivo during sample collection and processing, we evaluated the effectiveness of several esterase inhibitors to stabilize TAH in plasma. Phenylmethanesulfonyl fluoride (PMSF) at 2.0 mM was chosen to stabilize TAH in rabbit plasma. The developed method is highly sensitive with a lower limit of quantitation of 10.0 pg/mL for both TAA and TAH using a 300 μL plasma aliquot. The method demonstrated good linearity, accuracy, precision, sensitivity, selectivity, recovery, matrix effects, dilution integrity, carryover, and stability. Linearity was obtained over the range of 10-2500 pg/mL. Both intra- and inter-run coefficients of variation were less than 9.1% and accuracies across the assay range were all within 100 ± 8.4%. The run time is under 5 minutes. The method was successfully implemented to support a rabbit pharmacokinetic study of TAH and TAA following a single intra-articular administration of TAH (Aristospan ® ). Copyright © 2018 Elsevier B.V. All rights reserved.

Intravitreal ranibizumab injection combined trabeculectomy versus Ahmed valve surgery in the treatment of neovascular glaucoma: assessment of efficacy and complications.

PubMed

Liu, Lan; Xu, Yongfeng; Huang, Zhu; Wang, Xiaoyu

2016-05-26

Researches have shown anti-vascular endothelial growth factor (VEGF) agent is effective in treating neovascular eye diseases. The purpose of this study is to evaluate the efficacy and safety of intravitreal ranibizumab (IVR) injection combined trabeculectomy in the treatment of neovascular glaucoma (NVG), and compared it with Ahmed valve surgery. Thirty-six NVG patients (37 eyes) from the First Affiliated Hospital of Zhejiang medical college, between January 1, 2014 and January 31, 2015, were included in this prospective, interventional clinical study. Eighteen NVG eyes were given IVR injection one week before trabeculectomy. Ahmed valve implantation surgery was performed in nineteen eyes. Ocular pain, best corrected visual acuity (BCVA), intraocular pressure (IOP) and surgical complications were evaluated before and after the surgery. IOP was significantly decreased following IVR injection combined trabeculectomy treatment (baseline 57.1 ± 8.9 mmHg; week 1, 15.2 ± 4.3 mmHg p = 0.000; month 1, 16.9 ± 2.1 mmHg p = 0.000; month 3, 20.3 ± 7.7 mmHg p = 0.000; month 6, 19.7 ± 7.3 mmHg p = 0.000). There was a significant, though modest, BCVA improvement in sighted eyes of IVR group (baseline 2.42 ± 0.68, W1 1.80 ± 0.91, P = 0.013; M1 1.77 ± 0.93, p = 0.011). IVR injection combined trabeculectomy had less postoperative complications and lower failure ratio than Ahmed surgery (IVR 5.6 %, Ahmed 31.6 %). The study revealed that IVR injection combined trabeculectomy was an effective and safe treatment for NVG. Compared with Ahmed surgery, IVR injection combined trabeculectomy had less complications and higher success ratio. (Chinese Clinical Registry, TRN ChiCTR-OPN-16008147, 3/24/2016, retrospectively registered).

Implant decontamination with phosphoric acid during surgical peri-implantitis treatment: a RCT.

PubMed

Hentenaar, Diederik F M; De Waal, Yvonne C M; Strooker, Hans; Meijer, Henny J A; Van Winkelhoff, Arie-Jan; Raghoebar, Gerry M

2017-12-01

Peri-implantitis is known as an infectious disease that affects the peri-implant soft and hard tissue. Today, scientific literature provides very little evidence for an effective intervention protocol for treatment of peri-implantitis. The aim of the present randomized controlled trial is to evaluate the microbiological and clinical effectiveness of phosphoric acid as a decontaminating agent of the implant surface during surgical peri-implantitis treatment. Peri-implantitis lesions were treated with resective surgical treatment aimed at peri-implant granulation tissue removal, bone recontouring, and pocket elimination. Fifty-three implant surfaces in 28 patients were mechanically cleaned and treated with either 35% phosphoric etching gel (test group) or sterile saline (control group). Microbiological samples were obtained during surgery; clinical parameters were recorded at baseline and at 3 months after treatment. Data were analyzed using multi-variable linear regression analysis and multilevel statistics. Significant immediate reductions in total anaerobic bacterial counts on the implant surface were found in both groups. Immediate reduction was greater when phosphoric acid was used. The difference in log-transformed mean anaerobic counts between both procedures was not statistical significant (p = 0.108), but there were significantly less culture-positive implants after the decontamination procedure in the phosphoric acid group (p = 0.042). At 3 months post-surgery, 75% of the implants in the control group and 63.3% of the implants in the test group showed disease resolution. However, no significant differences in clinical and microbiological outcomes between both groups were found. The application of 35% phosphoric acid after mechanical debridement is superior to mechanical debridement combined with sterile saline rinsing for decontamination of the implant surface during surgical peri-implantitis treatment. However, phosphoric acid as implant surface

Chemical, corrosion and topographical analysis of stainless steel implants after different implantation periods.

PubMed

Chrzanowski, Wojciech; Armitage, David Andrew; Knowles, Jonathan Campbell; Szade, Jacek; Korlacki, Wojciech; Marciniak, Jan

2008-07-01

The aim of this work is to examine the corrosion properties, chemical composition, and material-implant interaction after different periods of implantation of plates used to correct funnel chest. The implants are made of 316L stainless steel. Examinations are carried out on three implants: new (nonimplanted) and two implanted for 29 and 35 months. The corrosion study reveals that in the potential range that could occur in the physiological condition the new bar has the lowest current density and the highest corrosion potential. This indicates that the new plate has the highest corrosion resistance and the corrosion resistance could be reduced during implantation by the instruments used during the operation. XPS analysis reveals changes in the surface chemistry. The longer the implantation time the more carbon and oxygen are observed and only trace of elements such as Cr, Mo are detected indicating that surface is covered by an organic layer. On some parts of the implants whitish tissue is observed: the thickness of which increased with the time of implantation. This tissue was identified as an organic layer; mainly attached to the surface on the areas close to where the implant was bent to attain anatomical fit and thus where the implant has higher surface roughness. The study indicates that the chest plates are impaired by the implantation procedure and contact with biological environment. The organic layer on the surface shows that the implant did not stay passive but some reactions at the tissue-implant interface occurred. These reactions should be seen as positive, as it indicates that the implants were accepted by the tissues. Nevertheless, if the implants react, they may continue to release chromium, nickel, and other harmful ions long term as indicated by lower corrosion resistance of the implants following implantation.

Impact of implant design on primary stability of orthodontic mini-implants.

PubMed

Wilmes, Benedict; Ottenstreuer, Stephanie; Su, Yu-Yu; Drescher, Dieter

2008-01-01

Skeletal anchorage with mini-implants has greatly broadened the treatment possibilities in orthodontics over the last few years. To reduce implant failure rates, it is advisable to obtain adequate primary stability. The aim of this study was to quantitatively analyze the impact of implant design and dimension on primary stability. Forty-two porcine iliac bone segments were prepared and embedded in resin. To evaluate the primary stability, we documented insertion torques of the following mini-implants: Aarhus Screw, AbsoAnchor, LOMAS, Micro-Anchorage-System, ORLUS and Spider Screw. In each bone, five Dual Top Screws were inserted for reference purposes to achieve comparability among the specimens. We observed wide variation in insertion torques and hence primary stability, depending on mini-implant design and dimension; the great impact that mini-implant diameter has on insertion torques was particularly conspicuous. Conical mini-implants achieved higher primary stabilities than cylindrical designs. The diameter and design of the mini-implant thread have a distinctive impact on primary stability. Depending on the region of insertion and local bone quality, the choice of the mini-implant design and size is crucial to establish sufficient primary stability.

Effect of implant position, angulation, and attachment height on peri-implant bone stress associated with mandibular two-implant overdentures: a finite element analysis.

PubMed

Hong, Hae Ryong; Pae, Ahran; Kim, Yooseok; Paek, Janghyun; Kim, Hyeong-Seob; Kwon, Kung-Rock

2012-01-01

The aim of this study was to analyze and compare the level and distribution of peri-implant bone stresses associated with mandibular two-implant overdentures with different implant positions. Mathematical models of mandibles and overdentures were designed using finite element analysis software. Two intraosseous implants and ball attachment systems were placed in the interforaminal region. The overdenture, which was supported by the two implants, was designed to withstand bilateral and unilateral vertical masticatory loads (total 100 N). In all, eight types of models, which differed according to assigned implant positions, height of attachments, and angulation, were tested: MI (model with implants positioned in the lateral incisor sites), MC (implants in canine sites), MP (implants in premolar sites), MI-Hi (greater height of attachments), MC-M (canine implants placed with mesial inclination), MC-D (canine implants placed with distal inclination), MC-B (canine implants placed with buccal inclination), and MC-L (canine implants placed with lingual inclination). Peri-implant bone stress levels associated with overdentures retained by lateral incisor implants resulted in the lowest stress levels and the highest efficiency in distributing peri-implant stress. MI-Hi showed increased stress levels and decreased efficiency in stress distribution. As the implants were inclined, stress levels increased and the efficiency of stress distribution decreased. Among the inclined models, MC-B showed the lowest stress level and best efficiency in stress distribution. The lowest stress and the best stability of implants in mandibular two-implant overdentures were obtained when implants were inserted in lateral incisor areas with shorter attachments and were placed parallel to the long axes of the teeth.

Implant Insertion Torque: Its Role in Achieving Primary Stability of Restorable Dental Implants.

PubMed

Greenstein, Gary; Cavallaro, John

2017-02-01

A literature review was conducted to determine the role of insertion torque in attaining primary stability of dental implants. The review is comprised of articles that discussed the amount of torque needed to achieve primary implant stability in healed ridges and fresh extraction sockets prior to immediate implant loading. Studies were appraised that addressed the effects of minimum and maximum forces that can be used to successfully place implants. The minimum torque that can be employed to attain primary stability is undefined. Forces ≥30 Ncm are routinely used to place implants into healed ridges and fresh extraction sockets prior to immediate loading of implants. Increased insertion torque (≥50 Ncm) reduces micromotion and does not appear to damage bone. In general, the healing process after implant insertion provides a degree of biologic stability that is similar whether implants are placed with high or low initial insertion torque. Primary stability is desirable when placing implants, but the absence of micromotion is what facilitates predictable implant osseointegration. Increased insertion torque helps achieve primary stability by reducing implant micromotion. Furthermore, tactile information provided by the first surgical twist drill can aid in selecting the initial insertion torque to achieve predictable stability of inserted dental implants.

Osseointegration of zirconia implants: an SEM observation of the bone-implant interface.

PubMed

Depprich, Rita; Zipprich, Holger; Ommerborn, Michelle; Mahn, Eduardo; Lammers, Lydia; Handschel, Jörg; Naujoks, Christian; Wiesmann, Hans-Peter; Kübler, Norbert R; Meyer, Ulrich

2008-11-06

The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Göttinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.

Scedosporium apiospermum infectious scleritis following posterior subtenon triamcinolone acetonide injection: a case report and literature review.

PubMed

Todokoro, Daisuke; Hoshino, Junki; Yo, Ayaka; Makimura, Koichi; Hirato, Junko; Akiyama, Hideo

2018-02-13

Ubiquitous fungi of the Scedosporium apiospermum species complex (SASC) cause various opportunistic infections. Posterior subtenon triamcinolone acetonide (STTA) injection is a standard therapy for intraocular inflammation and macular edema. We report a case of Scedosporium apiospermum infectious scleritis after a posterior STTA injection. A 75-year-old man received a posterior STTA injection to treat macular edema in his left eye. After 3 months, he complained of ocular pain and hyperemia in his left eye. Examination showed a subtenon abscess in the site corresponding with the STTA injection. After incising the abscess, the smear revealed numerous conidia-like structures. Although we suspected fungal infection and started topical voriconazole (VRCZ) and levofloxacin, the inflammation of the eye worsened. Fungal culture revealed filamentous fungus growth. Subsequently, we added systemic VRCZ and performed surgical debridement of the infected sclera and Tenon's capsule. Pathology of the sclera showed fungal hyphae. The antifungal susceptibility test revealed low minimum inhibitory concentrations for micafungin, VRCZ and miconazole (0.06, 0.25 and 0.5 μg/mL, respectively). After 2 months, the ciliary injection subsided and VRCZ therapy was stopped. However, subtenon abscess recurred 1 month after discontinuation of topical VRCZ. Surgical debridement and topical VRCZ were resumed, with the eye finally improving after 5 months of management. The fungal species was identified as Scedosporium apiospermum sensu stricto morphologically and by DNA sequencing. This case was successfully treated by topical and systemic VRCZ and repeated surgical debridement. Infectious scleritis caused by SASC rarely develops after posterior STTA. SASC can produce conidia in the enclosed subtenon space. Late-onset infectious scleritis after a posterior STTA injection suggests the presence of a fungal infection, including SASC, thereby requiring extensive and prolonged medical and

Immediate Administration of Intraarticular Triamcinolone Acetonide after Joint Injury Modulates Molecular Outcomes Associated with Early Synovitis

PubMed Central

Sieker, Jakob T.; Ayturk, Ugur M.; Proffen, Benedikt L.; Weissenberger, Manuela H.; Kiapour, Ata M.; Murray, Martha M.

2016-01-01

Objective To test if intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament (ACL) transection and characterize the synovial response using a functional genomics approach in a preclinical model of post- traumatic osteoarthritis. Methods Yorkshire pigs received untreated unilateral ACL transection (ACLT, n=6) or transection with immediate injection of 20mg triamcinolone acetonide (STEROID, n=6). Total synovial membrane cellularity and synovial fluid concentration of COL-2 3/4C short neoepitope bearing collagen fragments at 14 days post-injury were primary endpoints and compared between ACLT, STEROID and INTACT (n=6 uninjured knees). Cells were differentiated by histological phenotype and counted, while RNA-seq was used to quantify transcriptome-wide gene expression, monocyte, macrophage and lymphocyte markers. Results Total cellularity of 13% (95% confidence interval of 9–16) and COL-2 3/4C short levels of 0.24 Kg/ml (0.08–0.39) were determined in INTACT. Significant increases in total cellularity to 21% (16–27) and COL-2 3/4C short to 0.49 Kg/ml (0.39–0.59) were observed in ACLT. Compared to ACLT, total cellularity was non-significantly and COL-2 3/4C short was significantly decreased in STEROID to 17% (15–18, p=0.26) and 0.29 Kg/ml (0.23–0.35). Between ACLT and INTACT, 255 genes were differentially expressed and enriched pathways related to cellular immune response and proteolysis. Mononuclear leukocytes were the dominant cell type in cell dense areas. MARCO, SOCS3, CCR1, IL4R and MMP2 expression was significantly associated with COL-2 3/4C short levels. Conclusions Early intraarticular immunosuppression mitigated the injury-induced increase of collagen fragments, an outcome better predicted by specific marker expression than histological measures of synovitis. PMID:26866935

Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration.

PubMed

Yun, Cheolmin; Oh, Jaeryung; Ahn, Jaemoon; Hwang, Soon-Young; Lee, Boram; Kim, Seong-Woo; Huh, Kuhl

2016-09-01

We aimed to compare changes in subfoveal and peripapillary choroidal thickness (CT) after intravitreal aflibercept or ranibizumab injections for neovascular age-related macular degeneration (AMD). Medical records of 54 treatment-naïve, consecutive patients (54 eyes) who were diagnosed with neovascular AMD and received three monthly injections of aflibercept (21 eyes) or ranibizumab (33 eyes) were reviewed. Subfoveal and peripapillary CT were measured with images obtained using spectral domain optical coherence tomography at baseline and at three months. Subfoveal CT decreased from 232.2 ± 94.4 μm at baseline to 207.1 ± 89.3 μm at three months in the aflibercept group (p < 0.001) and from 231.5 ± 102.9 μm to 220.0 ± 98.0 μm in the ranibizumab group (p = 0.006). The reduction was greater in the aflibercept group than in the ranibizumab group (p = 0.024). Peripapillary CT decreased from 157.2 ± 62.2 μm at baseline to 147.4 ± 62.2 μm at three months in the aflibercept group (p < 0.001). However, the change in peripapillary CT from 154.9 ± 46.5 μm at baseline to 152.3 ± 50.0 μm at three months was not significant in the ranibizumab group (p = 0.123). Intravitreally injected aflibercept significantly decreased subfoveal CT more than ranibizumab. Choroidal thinning after aflibercept injection was not limited to the subfoveal area, but extended beyond the macula as well.

Observation of curative effect of intravitreal injection of conbercept in wet age-related macular degeneration: Optical coherence tomography analysis after injection.

PubMed

Yang, Wen; Tan, Ying; Li, Chaowei; Liu, Yi; Lu, Guohua

2018-04-01

To observe the clinical efficacy of intravitreal injection of conbercept in the treatment of wet age-related macular degeneration (wAMD), optical coherence tomography (OCT) and the best corrected visual acuity (BCVA) was observed to measure the changes of anatomical changes of central macular thickness (CMT) and the area and volume of retinal pigment epithelium (RPE) uplift. Fifteen patients (15 eyes) with wet AMD were enrolled in this study. All patients underwent intravitreal injection of conbercept of 0.05 mL once. After 1 week, 1 month, and 3 months, OCT and BCVA were used to examine and to compare with the preoperative and postoperative central macular thickness and RPE uplift area. BCVA (median) increased respectively from 0.12 ± 0.13 to 0.21 ± 0.15 at 1 week, to 0.90 ± 0.25 at 1 month, to 0.38 ± 0.17 at 3 months (p < .001). The thickness of central macular decreased from 500 ± 25 μm to 256 ± 19 μm, 221 ± 29 μm, and 215 ± 14 μm, respectively. The normal physiological structure and stratification of the macular area were clear gradually. Conbercept treatment of wet AMD can significantly improve visual acuity, after 1 month up to the plateau, 3 months of continuous drug injection can make the vision maintained at a high stage, and macular retinal normal structural morphology recovery is good, the treatment has no obvious adverse reactions, and with good security. © 2018 Wiley Periodicals, Inc.

Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial.

PubMed

Zulian, F; Martini, G; Gobber, D; Plebani, M; Zacchello, F; Manners, P

2004-10-01

Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide (TA) is equivalent to that of triamcinolone hexacetonide (TH), if used at double the dosage. In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints, in children with juvenile idiopathic arthritis (JIA). Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study. The symmetry was assessed by both clinical examination and synovial fluid analysis. The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA. The identity of injected compound was blinded to the patient and to the physician. Thirty-seven patients, 30 female, seven male, with JIA, entered the study. A total of 86 joints were injected. Twenty-one (53.8%) of the joints injected with TA relapsed first compared with only six (15.4%) of the joints injected with TH. In three (7.7%) relapse occurred simultaneously. Nine (23%) were still in remission after 24-month follow-up. The percentage of joints with lasting remission was higher with TH than with TA (80 vs 47.5% after 12 months and 63.6 vs 32.4% after 24 months, respectively; log rank test P = 0.003). Even when TA is given at higher doses, TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA.

Influence of controlled immediate loading and implant design on peri-implant bone formation.

PubMed

Vandamme, Katleen; Naert, Ignace; Geris, Liesbet; Vander Sloten, Jozef; Puers, Robert; Duyck, Joke

2007-02-01

Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study

PubMed Central

Gill, Sudeep S; Bronskill, Susan E; Paterson, J Michael; Whitehead, Marlo

2012-01-01

Objective To assess the risk of systemic adverse events associated with intravitreal injections of vascular endothelial growth factor inhibiting drugs. Design Population based nested case-control study. Setting Ontario, Canada. Participants 91 378 older adults with a history of physician diagnosed retinal disease identified between 1 April 2006 and 31 March 2011. Cases were 1477 patients admitted to hospital for ischaemic stroke, 2229 admitted for an acute myocardial infarction, 1059 admitted or assessed in an emergency department for venous thromboembolism, and 2623 admitted for congestive heart failure. Event-free controls (at a ratio of 5:1) were matched to cases on the basis of year of birth, sex, history of the outcome in the previous 5 years, and diabetes. Main exposure measure Exposure to vascular endothelial growth factor inhibiting drugs identified within 180 days before the index date. Results After adjustment for potential confounders, participants who had ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism were not more likely than control participants to have been exposed to either bevacizumab (adjusted odds ratios of 0.95 (95% confidence interval 0.68 to 1.34) for ischaemic stroke, 1.04 (0.77 to 1.39) for acute myocardial infarction, 0.81 (0.49 to 1.34) for venous thromboembolism, and 1.21 (0.91 to 1.62) for congestive heart failure) or ranibizumab (adjusted odds ratios 0.87 (0.68 to 1.10) for ischaemic stroke, 0.90 (0.72 to 1.11) for acute myocardial infarction, 0.88 (0.67 to 1.16) for venous thromboembolism, and 0.87 (0.70 to 1.07) for congestive heart failure). Similarly, a secondary analysis of exclusive users of bevacizumab or ranibizumab showed no differences in risk between the two drugs (adjusted odds ratios for bevacizumab relative to ranibizumab of 1.03 (0.67 to 1.60) for ischaemic stroke, 1.23 (0.85 to 1.77) for acute myocardial infarction, 0.92 (0.51 to 1.69) for venous thromboembolism, and

Intravitreal invading cells contribute to vitreal cytokine milieu in proliferative vitreoretinopathy

PubMed Central

El-Ghrably, I; Dua, H.; Orr, G.; Fischer, D.; Tighe, P.

2001-01-01

AIM—To examine the contribution of infiltrating cells in the local production of cytokines within the vitreous of patients with proliferative vitreoretinopathy (PVR).
METHODS—The presence of mRNA coding for IL-6, IL-8, IL-1β, IL-1α, TNFα, IFNγ, IL-12, and HPRT was investigated in 25 vitreous samples from patients with PVR, 11 vitreous samples from patients with retinal detachment (RD) not complicated by PVR, and 10 vitreous samples from patients with macular hole (MH). A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using an internal competitor was used to investigate these samples. From these samples, 15 PVR, 8 RD, and 8 MH were analysed for the protein levels of the same cytokines using enzyme linked immunosorbent assay (ELISA). Spearman correlation was used to test any association between mRNA and cytokine protein levels, as an indicator of the contribution these cells make to the intravitreal cytokine milieu.
RESULTS—A strong correlation was found between mRNA and their respective cytokine levels (protein products) for IL-6, IL-8, IL-1β, IL-1α, TNFα, IFNγ (Spearman r = 0.83, 0.73, 0.67, 0.91, 0.73, and 0.73 respectively), but not for IL-12. The median levels of IL-6, IL-8, IL-1β, and IFNγ mRNA and their respective cytokines were significantly higher (p <0.05) in patients with PVR than in those with macular hole. There was no statistically significant difference in the median levels of IL-1α mRNA between PVR and MH but the cytokine IL-1α was detected at a significantly higher level in PVR compared with MH patients. Between PVR and RD patients, there was no statistically significant difference in mRNA levels for all the investigated cytokines (p >0.05) except for IL-6 where there was a statistical significance (p= 0.038). In contrast, the median levels of IL-6, IL-8, and IL-1β cytokines were significantly higher (p <0.05) in patients with PVR than in those with RD, whereas for IL-1α and IFNγ no

Influence of Implant Positions and Occlusal Forces on Peri-Implant Bone Stress in Mandibular Two-Implant Overdentures: A 3-Dimensional Finite Element Analysis.

PubMed

Alvarez-Arenal, Angel; Gonzalez-Gonzalez, Ignacio; deLlanos-Lanchares, Hector; Brizuela-Velasco, Aritza; Dds, Elena Martin-Fernandez; Ellacuria-Echebarria, Joseba

2017-12-01

The aim of this study was to evaluate and compare the bone stress around implants in mandibular 2-implant overdentures depending on the implant location and different loading conditions. Four 3-dimensional finite element models simulating a mandibular 2-implant overdenture and a Locator attachment system were designed. The implants were located at the lateral incisor, canine, second premolar, and crossed-implant levels. A 150 N unilateral and bilateral vertical load of different location was applied, as was 40 N when combined with midline load. Data for von Mises stress were produced numerically, color coded, and compared between the models for peri-implant bone and loading conditions. With unilateral loading, in all 4 models much higher peri-implant bone stress values were recorded on the load side compared with the no-load side, while with bilateral occlusal loading, the stress distribution was similar on both sides. In all models, the posterior unilateral load showed the highest stress, which decreased as the load was applied more mesially. In general, the best biomechanical environment in the peri-implant bone was found in the model with implants at premolar level. In the crossed-implant model, the load side greatly altered the biomechanical environment. Overall, the overdenture with implants at second premolar level should be the chosen design, regardless of where the load is applied. The occlusal loading application site influences the bone stress around the implant. Bilateral occlusal loading distributes the peri-implant bone stress symmetrically, while unilateral loading increases it greatly on the load side, no matter where the implants are located.

Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PubMed

Mimura, Kensuke; Matsumoto, Hidetaka; Morimoto, Masahiro; Akiyama, Hideo

2018-01-01

To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended. © 2017 S. Karger AG, Basel.

[Late endophthalmitis following Ahmed valve].

PubMed

del-Hierro-Zarzuelo, A; Vico-Ruiz, E; Martínez-de-la-Casa, J M; García-Feijoó, J; Castillo-Martín, A; García-Sánchez, J

2005-11-01

A 71-year-old woman with a history of aphakic glaucoma underwent implantation of an Ahmed valve and scleral grafting in her right eye. Postoperative visual acuity was 0.5 and intraocular pressure was 12 mmHg during treatment with brimonidine tartrate (0.2%). Nine months after implantation she suffered a conjunctival infection which was treated with hygienic measures and topical antibiotic therapy. Four days later, she developed an endophthalmitis which was treated with topical, intravitreous and intravenous vancomycin and ceftazidime. The Ahmed drainage implant was replaced at 72 hours. Laboratory culture yielded Haemophilus influenzae. Four days later, the eye was enucleated. Endophthalmitis is an uncommon complication of glaucoma drainage implant surgery. Exposure of the drainage tube represents the greatest risk factor for this condition. Removal of the implant in the first 24 hours is recommended if a good visual prognosis is to be achieved.

Peri-implant bone formation and implant integration strength of peptide-modified p(AAM-co-EG/AAC) interpenetrating polymer network-coated titanium implants.

PubMed

Barber, Thomas A; Ho, James E; De Ranieri, Aladino; Virdi, Amarjit S; Sumner, Dale R; Healy, Kevin E

2007-02-01

Interpenetrating polymer networks (IPNs) of poly (acrylamide-co-ethylene glycol/acrylic acid) functionalized with an -Arg-Gly-Asp- (RGD) containing 15 amino acid peptides, derived from rat bone sialoprotein (bsp-RGD(15), were grafted to titanium implants in an effort to modulate bone formation in the peri-implant region in the rat femoral ablation model. Bone-implant contact (BIC) and bone formation within the medullary canal were determined using microcomputed tomography at 2 and 4 weeks postimplantation. BIC for bsp-RGD(15)-IPN implants was enhanced relative to hydroxyapatite tricalcium phosphate (HA-TCP) coated implants, but was similar to all other groups. Aggregate bone formation neither indicated a dose-dependent effect of bsp-RGD(15) nor a meaningful trend. Mechanical testing of implant fixation revealed that only the HA-TCP coated implants supported significant (>1 MPa) interfacial shear strength, despite exhibiting lower overall BIC, an indication that bone ingrowth into the rougher coating was the primary mode of implant fixation. While no evidence was found to support the hypothesis that bsp-RGD(15)-modified IPN coated implants significantly impacted bone-implant bonding, these results point to the lack of correlation between in vitro studies employing primary osteoblasts and in vivo wound healing in the peri-implant region. Copyright 2006 Wiley Periodicals, Inc.

Diameter of retinal vessels in patients with diabetic macular edema is not altered by intravitreal ranibizumab (lucentis).

PubMed

Terai, Naim; Haustein, Michael; Siegel, Anastasia; Stodtmeister, Richard; Pillunat, Lutz E; Sandner, Dirk

2014-07-01

To investigate the effect(s) of intravitreally injected ranibizumab on retinal vessel diameter in patients with diabetic macular edema. Participants of this prospective study were 14 men and 16 women (30 eyes) aged 60 ± 11 years (mean ± standard deviation), all with clinically significant diabetic macular edema. Treatment comprised 3 intravitreal injections of ranibizumab given at 4-week intervals. Examinations were conducted before the first (baseline), before the second (Month 1), before the third (Month 2) injections, and 3 months after baseline (Month 3). Measured parameters included systemic blood pressure, static retinal vessel analysis (central retinal artery equivalent and central retinal vein equivalent), and dynamic retinal vessel analysis, as measured by the change in vessel diameter in response to flicker stimulation during three measurement cycles. Flicker stimulation was accomplished using a 50-second baseline recording, followed by an online measurement during 20-second flicker stimulation and 80-second online measurements in both arteriolar and venular vessel segments. Static retinal vessel analysis showed a reduction of central retinal artery equivalent from 186.25 ± 51.40 μm (baseline) to 173.20 ± 22.2 μm (Month 1), to 174.30 ± 27.30 μm (Month 2), and to 170.56 ± 22.89 μm (Month 3), none of which was statistically significant (P = 0.23, 0.12, and 0.14, respectively). Central retinal vein equivalent was reduced from 216.21 ± 25.0 μm (baseline) to 214.48 ± 25.4 μm (Month 1), to 214.80 ± 24.30 μm (Month 2), and to 211.41 ± 24.30 μm (Month 3), revealing no statistically significant differences between examination time points (P = 0.54, 0.06, and 0.24, respectively). Dynamic vessel analysis yielded a mean retinal arterial diameter change of +1.47% ± 2.3 (baseline), +1.91% ± 2.5 (Month 1), +1.76% ± 2.2 (Month 2), and +1.66% ± 2.1 (Month 3), none of which showed statistically significant differences (P = 0.32, 0.49, and 0

A new system of implant abutment connection: how to improve a two piece implant system sealing.

PubMed

Grecchi, F; DI Girolamo, M; Cura, F; Candotto, V; Carinci, F

2017-01-01

Implant dentistry has become one of the most successful dentistry techniques for replacing missing teeth. The success rate of implant dentistry is above 80%. However, peri-implantitis is a later complication of implant dentistry that if untreated, can lead to implant loss. One of the hypotized causes of peri-implantis is the bacterial leakage at the level of implant-abutment connection. Bacterial leakage is favored to the presence of a micro gap at the implant-abutment interface, allowing microorganisms to penetrate and colonize the inner part of the implant leading to biofilm accumulation and consequently to peri-implantitis development. To identify the capability of the implant to protect the internal space from the external environment, the passage of genetically modified Escherichia coli across implant-abutment interface was evaluated. Implants were immerged in a bacterial culture for twenty-four hours and then bacteria amount was measured inside implant-abutment interface with Real-time PCR. Bacteria were detected inside all studied implants, with a median percentage of 9%. The reported results are better to those of previous studies carried out on different implant systems. Until now, none implant-abutment system has been proven to seal the gap between implant and abutment.

Poly Implants Prosthèse Breast Implants: A Case Series and Review of the Literature.

PubMed

Klein, Doron; Hadad, Eran; Wiser, Itay; Wolf, Omer; Itzhaki Shapira, Ortal; Fucks, Shir; Heller, Lior

2018-01-01

Silicone breast implants from the French manufacturer Poly Implants Prosthèse (PIP) were recalled from the European market after the French regulator has revealed the implants contain non-medical-grade silicone filler. In December 2011, following a large increase in reported rupture rate and a possible cancer risk, the French Ministry of Health recommended consideration of the PIP explantation, regardless of their condition. In 2012, the Israel Ministry of Health recommended to replace the implants only upon suspected implant rupture. The aims of this study were to characterize breast-augmented Israeli patients with PIP implants, compare their outcomes with those of breast-augmented patients with different implant types, and review the current PIP literature. Breast-augmented patients who underwent an elective breast implant exchange in Israel between January 2011 and January 2017 were included in the study. Data were collected from electronic and physical medical files. There were 73 breast-augmented female patients with 146 PIP breast implants included in this study. Average implant age was 6.7 ± 2.79 years. Mean implant size was 342.8 ± 52.9 mL. Fourteen women (19 implants [16%]) had a high-grade capsular contracture (Baker grade 3-4). During exchange, 28 implants were found to be ruptured (19.2%). Less than 10 years following breast augmentation, PIP implants demonstrated higher rupture rate compared with other implants. Our data are comparable to overall available rupture rate. Among patients with definitive rupture diagnosis, an elective implant removal should be recommended. In cases of undamaged implants, plastic surgeons should also seriously consider PIP implant explantation. When the patient does not desire to remove the implant, an annual physical examination and breast ultrasound are recommended, beginning a year after augmentation.

Sacroiliac joint stability: Finite element analysis of implant number, orientation, and superior implant length.

PubMed

Lindsey, Derek P; Kiapour, Ali; Yerby, Scott A; Goel, Vijay K

2018-03-18

To analyze how various implants placement variables affect sacroiliac (SI) joint range of motion. An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the SI joint using various placement configurations of triangular implants (iFuse Implant System ® ). Placement configurations were varied by changing implant orientation, superior implant length, and number of implants. The range of motion of the SI joint was calculated using a constant moment of 10 N-m with a follower load of 400 N. The changes in motion were compared between the treatment groups to assess how the different variables affected the overall motion of the SI joint. Transarticular placement of 3 implants with superior implants that end in the middle of the sacrum resulted in the greatest reduction in range of motion (flexion/extension = 73%, lateral bending = 42%, axial rotation = 72%). The range of motions of the SI joints were reduced with use of transarticular orientation (9%-18%) when compared with an inline orientation. The use of a superior implant that ended mid-sacrum resulted in median reductions of (8%-14%) when compared with a superior implant that ended in the middle of the ala. Reducing the number of implants, resulted in increased SI joint range of motions for the 1 and 2 implant models of 29%-133% and 2%-39%, respectively, when compared with the 3 implant model. Using a validated finite element model we demonstrated that placement of 3 implants across the SI joint using a transarticular orientation with superior implant reaching the sacral midline resulted in the most stable construct. Additional clinical studies may be required to confirm these results.

Strategy for the management of macular edema in retinal vein occlusion: the European VitreoRetinal Society macular edema study.

PubMed

Adelman, Ron A; Parnes, Aaron J; Bopp, Silvia; Saad Othman, Ihab; Ducournau, Didier

2015-01-01

To compare the efficacy of different therapies in the treatment of macular edema associated with retinal vein occlusion (RVO). This is a nonrandomized, multicenter collaborative study. 86 retina specialists from 29 countries provided clinical information, including choice of treatment and outcome, on 2,603 patients with macular edema including 738 cases of RVO. Reported data included the type and number of treatments performed, visual acuities, and other clinical and diagnostic findings. The mean increase in visual acuity and mean number of treatments performed. 358 cases of central retinal vein occlusion (CRVO) and 380 cases of branch retinal vein occlusion (BRVO) were included in this investigation. Taking all RVO cases together, pars plana vitrectomy with internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than other therapies. Those treated with intravitreal antivascular endothelial growth factor (anti-VEGF) injection alone showed the second greatest improvement in vision. Dexamethasone intravitreal implant alone and intravitreal triamcinolone alone both resulted in modest visual gains. In the treatment of macular edema in RVO, vitrectomy with ILM peeling may achieve visual improvement and may be a good option for certain cases. Anti-VEGF injection is the most effective of the nonsurgical treatments.

Metals for bone implants. Part 1. Powder metallurgy and implant rendering.

PubMed

Andani, Mohsen Taheri; Shayesteh Moghaddam, Narges; Haberland, Christoph; Dean, David; Miller, Michael J; Elahinia, Mohammad

2014-10-01

New metal alloys and metal fabrication strategies are likely to benefit future skeletal implant strategies. These metals and fabrication strategies were looked at from the point of view of standard-of-care implants for the mandible. These implants are used as part of the treatment for segmental resection due to oropharyngeal cancer, injury or correction of deformity due to pathology or congenital defect. The focus of this two-part review is the issues associated with the failure of existing mandibular implants that are due to mismatched material properties. Potential directions for future research are also studied. To mitigate these issues, the use of low-stiffness metallic alloys has been highlighted. To this end, the development, processing and biocompatibility of superelastic NiTi as well as resorbable magnesium-based alloys are discussed. Additionally, engineered porosity is reviewed as it can be an effective way of matching the stiffness of an implant with the surrounding tissue. These porosities and the overall geometry of the implant can be optimized for strain transduction and with a tailored stiffness profile. Rendering patient-specific, site-specific, morphology-specific and function-specific implants can now be achieved using these and other metals with bone-like material properties by additive manufacturing. The biocompatibility of implants prepared from superelastic and resorbable alloys is also reviewed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in Japanese Patients: The APOLLO Study.

PubMed

Oshima, Yuji; Kimoto, Kenichi; Yoshida, Noriko; Fujisawa, Kimihiko; Sonoda, Shozo; Kubota, Toshiaki; Murata, Toshinori; Sakamoto, Taiji; Yoshida, Shigeo; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2017-01-01

To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 μm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients. © 2017 S. Karger AG, Basel.

Group D. Initiator paper. Implants--peri-implant (hard and soft tissue) interactions in health and disease: the impact of explosion of implant manufacturers.

PubMed

Ivanovski, Saso

2015-01-01

1. The best-documented implants have a threaded solid screw-type design and are manufactured from commercially pure (grade IV) titanium. There is good evidence to support implants ≥ 6 mm in length, and ≥ 3 mm in diameter. 2. Integrity of the seal between the abutment and the implant is important for several reasons, including minimization of mechanical and biological complications and maintaining marginal bone levels. Although the ideal design features of the implant-abutment connection have not been determined, an internal connection, micro-grooves at the implant collar, and horizontal offset of the implant-abutment junction (platform switch) appear to impart favorable properties. 3. Implants with moderately rough implant surfaces provide advantages over machined surfaces in terms of the speed and extent of osseointegration. While the favorable performances of both minimally and moderately rough surfaces are supported by long-term data, moderately rough surfaces provide superior outcomes in compromised sites, such as the posterior maxilla. 4. Although plaque is critical in the progression of peri-implantitis, the disease has a multi-factorial aetiology, and may be influenced by poor integrity of the abutment/implant connection. Iatrogenic factors, such as the introduction of a foreign body. (e.g., cement) below the mucosal margin, can be important contributors. 5. Clinicians should exercise caution when using a particular implant system, ensuring that the implant design is appropriate and supported by scientific evidence. Central to this is access to and participation in quality education on the impact that implant characteristics can have on clinical outcomes. Caution should be exercised in utilizing non-genuine restorative componentry that may lead to a poor implant-abutment fit and subsequent technical and biological complications.

Cochlear Implants

MedlinePlus

... newsroom@entnet.org . A cochlear implant is an electronic device that restores partial hearing to individuals with ... An internal component that consists of a small electronic device that is surgically implanted under the skin ...

Goserelin Implant

MedlinePlus

Goserelin implant is used in combination with radiation therapy and other medications to treat localized prostate cancer ... and other symptoms) and to help with the treatment of abnormal bleeding of the uterus. Goserelin implant ...

New orthopaedic implant management tool for computer-assisted planning, navigation, and simulation: from implant CAD files to a standardized XML-based implant database.

PubMed

Sagbo, S; Blochaou, F; Langlotz, F; Vangenot, C; Nolte, L-P; Zheng, G

2005-01-01

Computer-Assisted Orthopaedic Surgery (CAOS) has made much progress over the last 10 years. Navigation systems have been recognized as important tools that help surgeons, and various such systems have been developed. A disadvantage of these systems is that they use non-standard formalisms and techniques. As a result, there are no standard concepts for implant and tool management or data formats to store information for use in 3D planning and navigation. We addressed these limitations and developed a practical and generic solution that offers benefits for surgeons, implant manufacturers, and CAS application developers. We developed a virtual implant database containing geometrical as well as calibration information for orthopedic implants and instruments, with a focus on trauma. This database has been successfully tested for various applications in the client/server mode. The implant information is not static, however, because manufacturers periodically revise their implants, resulting in the deletion of some implants and the introduction of new ones. Tracking these continuous changes and keeping CAS systems up to date is a tedious task if done manually. This leads to additional costs for system development, and some errors are inevitably generated due to the huge amount of information that has to be processed. To ease management with respect to implant life cycle, we developed a tool to assist end-users (surgeons, hospitals, CAS system providers, and implant manufacturers) in managing their implants. Our system can be used for pre-operative planning and intra-operative navigation, and also for any surgical simulation involving orthopedic implants. Currently, this tool allows addition of new implants, modification of existing ones, deletion of obsolete implants, export of a given implant, and also creation of backups. Our implant management system has been successfully tested in the laboratory with very promising results. It makes it possible to fill the current gap

Development of an ultra high performance liquid chromatography method for determining triamcinolone acetonide in hydrogels using the design of experiments/design space strategy in combination with process capability index.

PubMed

Oliva, Alexis; Monzón, Cecilia; Santoveña, Ana; Fariña, José B; Llabrés, Matías

2016-07-01

An ultra high performance liquid chromatography method was developed and validated for the quantitation of triamcinolone acetonide in an injectable ophthalmic hydrogel to determine the contribution of analytical method error in the content uniformity measurement. During the development phase, the design of experiments/design space strategy was used. For this, the free R-program was used as a commercial software alternative, a fast efficient tool for data analysis. The process capability index was used to find the permitted level of variation for each factor and to define the design space. All these aspects were analyzed and discussed under different experimental conditions by the Monte Carlo simulation method. Second, a pre-study validation procedure was performed in accordance with the International Conference on Harmonization guidelines. The validated method was applied for the determination of uniformity of dosage units and the reasons for variability (inhomogeneity and the analytical method error) were analyzed based on the overall uncertainty. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peri-implant bone density in senile osteoporosis-changes from implant placement to osseointegration.

PubMed

Beppu, Kensuke; Kido, Hirofumi; Watazu, Akira; Teraoka, Kay; Matsuura, Masaro

2013-04-01

The aim of this study was to examine healing over time after implant body placement in a senile osteoporosis model and a control group. In this study, 16-week-old male mice were used. The senile osteoporosis model consisted of senescence-accelerated prone 6 mice and the control group consisted of senescence-accelerated resistant 1 mice. Titanium-coated plastic implants were used as experimental implants whose dimensions were 3.0 mm in length, 1.1 mm in apical diameter, and 1.2 mm in coronal diameter. Bone samples were collected at 5, 7, 14, 21, and 28 days after implant placement. A micro-quantitative computed tomography (QCT) system was used to scan these samples and a phantom in order to quantitate bone mineral measurements. Bone mineral density (BMD) of each sample was measured. Each sample was also examined by light microscopy after QCT imaging. At 14 and 28 days after implant placement, the bone-implant contact (BIC) ratios were calculated from light microscopy images and were divided into cortical bone and bone marrow regions. When BMD was compared between the osteoporosis and control groups using micro-QCT, the osteoporosis group had a significantly lower BMD in the region 0-20 µm from the implant surface in the bone marrow region at 14 days onward after implant placement. Compared with the control group, the osteoporosis model also had significantly lower BMD in all regions 0-100 µm from the implant surface in the bone marrow region at 14 days after placement. However, in the cortical bone region, no statistically significant difference was observed in the regions at the bone-implant interface. Light microscopy revealed osseointegration for all implants 28 days after implant placement. The osteoporosis model tended to have lower BICs compared with that of the control group, although this did not reach statistical significance. Our results showed that osseointegration was achieved in the osteoporosis model. However, the BMD was 30-40% lower than that of

Sacroiliac joint stability: Finite element analysis of implant number, orientation, and superior implant length

PubMed Central

Lindsey, Derek P; Kiapour, Ali; Yerby, Scott A; Goel, Vijay K

2018-01-01

AIM To analyze how various implants placement variables affect sacroiliac (SI) joint range of motion. METHODS An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the SI joint using various placement configurations of triangular implants (iFuse Implant System®). Placement configurations were varied by changing implant orientation, superior implant length, and number of implants. The range of motion of the SI joint was calculated using a constant moment of 10 N-m with a follower load of 400 N. The changes in motion were compared between the treatment groups to assess how the different variables affected the overall motion of the SI joint. RESULTS Transarticular placement of 3 implants with superior implants that end in the middle of the sacrum resulted in the greatest reduction in range of motion (flexion/extension = 73%, lateral bending = 42%, axial rotation = 72%). The range of motions of the SI joints were reduced with use of transarticular orientation (9%-18%) when compared with an inline orientation. The use of a superior implant that ended mid-sacrum resulted in median reductions of (8%-14%) when compared with a superior implant that ended in the middle of the ala. Reducing the number of implants, resulted in increased SI joint range of motions for the 1 and 2 implant models of 29%-133% and 2%-39%, respectively, when compared with the 3 implant model. CONCLUSION Using a validated finite element model we demonstrated that placement of 3 implants across the SI joint using a transarticular orientation with superior implant reaching the sacral midline resulted in the most stable construct. Additional clinical studies may be required to confirm these results. PMID:29564210

Individual titanium zygomatic implant

NASA Astrophysics Data System (ADS)

Nekhoroshev, M. V.; Ryabov, K. N.; Avdeev, E. V.

2018-03-01

Custom individual implants for the reconstruction of craniofacial defects have gained importance due to better qualitative characteristics over their generic counterparts – plates, which should be bent according to patient needs. The Additive Manufacturing of individual implants allows reducing cost and improving quality of implants. In this paper, the authors describe design of zygomatic implant models based on computed tomography (CT) data. The fabrication of the implants will be carried out with 3D printing by selective laser melting machine SLM 280HL.

Intravitreal, Subretinal, and Suprachoroidal Injections: Evolution of Microneedles for Drug Delivery.

PubMed

Hartman, Rachel R; Kompella, Uday B

Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With the introduction of new therapeutic agents, this number is expected to increase. In addition, drug products that are injectable in ocular compartments other than the vitreous humor are expected to enter the back of the eye market in the not so distant future. Besides the IVT route, some of the most actively investigated routes of invasive administration to the eye include periocular, subretinal, and suprachoroidal (SC) routes. While clinical efficacy is the driving force behind new injectable drug product development for the eye, safety is also being improved with time. In the case of IVT injections, the procedural guidelines have evolved over the years to improve patient comfort and reduce injection-related injury and infection. Similar advances are anticipated for other routes of administration of injectable products to the eye. In addition to procedural improvements, the design of needles, particularly those with smaller diameters, length, and controlled bevel angles are expected to improve overall safety and acceptance of injected ophthalmic drug products. A key development in this area is the introduction of microneedles of a length less than a millimeter that can target the SC space. In the future, needles with smaller diameters and lengths, potentially approaching nanodimensions, are expected to revolutionize ophthalmic disease management.

The effects of implant angulation on the resonance frequency of a dental implant.

PubMed

Harirforoush, R; Arzanpour, S; Chehroudi, B

2014-08-01

Dental implants are ideally placed in an orientation that allows vertical transfer of occlusal forces along their long axis. Nevertheless, optimal situations for implant placement are seldom encountered resulting in implants placement in angulated positions, which may affect their long-term success. The resonance frequency (RF) is an objective tool used to monitor stability of the implant tissue integration; however, little is known of the effect of the implant orientation in bone on the RF and its potential significance. The purpose of this research was to determine the relation between the dental implant orientation and the corresponding RF of implant. Three-dimensional (3D) modelling software was used to construct a 3D model of a pig mandible from computed tomography (CT) images. The RF of the implant was analysed using finite element (FE) modal analysis in software ANSYS (v.12). In addition, a cubical model was also developed in MIMICS to investigate the parameters affecting the relationship between RF and implant orientation in a simplified environment. The orientation angle was increased from 0 to 10 degrees in 1 degree increments and the resulting RF was analysed using correlation analysis and one-way ANOVA. Our analysis illustrated that the RF fluctuation following altering implant orientation was strongly correlated (r=0.97) with the contacting cortical to cancellous bone ratio (CCBR) at the implant interface. The most extreme RF change (from 9.81kHz to 10.07kHz) occurred when the implant was moved 0.5mm in positive z-direction, which resulted in the maximum change of CCBR from 52.9 to 54.8. Copyright © 2014. Published by Elsevier Ltd.

DEALING WITH DENTAL IMPLANT FAILURES

PubMed Central

Levin, Liran

2008-01-01

An implant-supported restoration offers a predictable treatment for tooth replacement. Reported success rates for dental implants are high. Nevertheless, failures that mandate immediate implant removal do occur. The consequences of implant removal jeopardize the clinician's efforts to accomplish satisfactory function and esthetics. For the patient, this usually involves further cost and additional procedures. The aim of this paper is to describe different methods and treatment modalities to deal with dental implant failure. The main topics for discussion include identifying the failing implant, implants replacing failed implants at the exact site, and the use of other restorative options. When an implant fails, a tailor made treatment plan should be provided to each patient according to all relevant variables. Patients should be informed regarding all possible treatment modalities following implant failure and give their consent to the most appropriate treatment option for them. PMID:19089213

Discoloration of the Peri-implant Mucosa Caused by Zirconia and Titanium Implants.

PubMed

Thoma, Daniel S; Ioannidis, Alexis; Cathomen, Elena; Hämmerle, Christoph H F; Hüsler, Jürg; Jung, Ronald E

2016-01-01

The aim of the present study was to assess the discoloration of the peri-implant mucosa caused by zirconia (Zr) and titanium (Ti) dental implants with and without soft tissue grafting (STG). Zr and Ti implants were inserted in edentulous areas in pig maxillae. Spectrophotometric measurements were performed prior to and after the insertion of the implants, and following the placement of a STG on the buccal side. A significant discoloration of the mucosa was observed with a mean ΔE of 8.05 (± 2.51) (Ti) and 4.93 (± 3.18) (Zr). In conjunction with a STG, ΔE values amounted to 5.31 ± 3.50 (Ti) and 5.95 (± 3.68) (Zr). The placement of Zr implants led to less discoloration of the mucosa than Ti implants without STG.

Dental Implant Systems

PubMed Central

Oshida, Yoshiki; Tuna, Elif B.; Aktören, Oya; Gençay, Koray

2010-01-01

Among various dental materials and their successful applications, a dental implant is a good example of the integrated system of science and technology involved in multiple disciplines including surface chemistry and physics, biomechanics, from macro-scale to nano-scale manufacturing technologies and surface engineering. As many other dental materials and devices, there are crucial requirements taken upon on dental implants systems, since surface of dental implants is directly in contact with vital hard/soft tissue and is subjected to chemical as well as mechanical bio-environments. Such requirements should, at least, include biological compatibility, mechanical compatibility, and morphological compatibility to surrounding vital tissues. In this review, based on carefully selected about 500 published articles, these requirements plus MRI compatibility are firstly reviewed, followed by surface texturing methods in details. Normally dental implants are placed to lost tooth/teeth location(s) in adult patients whose skeleton and bony growth have already completed. However, there are some controversial issues for placing dental implants in growing patients. This point has been, in most of dental articles, overlooked. This review, therefore, throws a deliberate sight on this point. Concluding this review, we are proposing a novel implant system that integrates materials science and up-dated surface technology to improve dental implant systems exhibiting bio- and mechano-functionalities. PMID:20480036

Comparison of Reconstructive Outcomes in Breast Cancer Patients With Preexisting Subpectoral Implants: Implant-Sparing Mastectomy With Delayed Implant Exchange Versus Immediate Tissue Expander Reconstruction.

PubMed

Parabkaharan, Sangeetha; Melody, Megan; Trotta, Rose; Lleshi, Amina; Sun, Weihong; Smith, Paul D; Khakpour, Nazanin; Dayicioglu, Deniz

2016-06-01

Women who have undergone prior augmentation mammoplasty represent a unique subset of breast cancer patients with several options available for breast reconstruction. We performed a single institution review of surgical outcomes of breast reconstruction performed in patients with breast cancer with prior history of subpectoral breast augmentation. Institutional review board-approved retrospective review was conducted among patients with previously mentioned criteria treated at our institution between 2000 and 2014. Reconstructions were grouped into 2 categories as follows: (1) removal of preexisting subpectoral implant during mastectomy with immediate tissue expander placement and (2) implant-sparing mastectomy followed by delayed exchange to a larger implant. We reviewed demographics, tumor features, and reconstruction outcomes of these groups. Fifty-three patients had preexisting subpectoral implants. Of the 63 breast reconstructions performed, 18 (28.6%) had immediate tissue expander placed and 45 (71.4%) had implant-sparing mastectomy followed by delayed implant exchange. The groups were comparable based on age, body mass index, cancer type, tumor grade, TNM stage at presentation, and hormonal receptor status. No significant difference was noted between tumor margins or subsequent recurrence, mastectomy specimen weight, removed implant volume, volume of implant placed during reconstruction, or time from mastectomy to final implant placement. Rates of complications were significantly higher in the tissue expander group compared to the implant-sparing mastectomy group 7 (38.9%) versus 4 (8.9%) (P = 0.005). Implant-sparing mastectomy with delayed implant exchange in patients with preexisting subpectoral implants is safe and has fewer complications compared to tissue expander placement. There was no difference noted in the final volume of implant placed, time interval for final implant placement, or tumor margins.

Implant ethics

PubMed Central

Hansson, S

2005-01-01

Implant ethics is defined here as the study of ethical aspects of the lasting introduction of technological devices into the human body. Whereas technological implants relieve us of some of the ethical problems connected with transplantation, other difficulties arise that are in need of careful analysis. A systematic approach to implant ethics is proposed. The major specific problems are identified as those concerning end of life issues (turning off devices), enhancement of human capabilities beyond normal levels, mental changes and personal identity, and cultural effects. PMID:16131553

Effect of implant design and bioactive glass coating on biomechanical properties of fiber-reinforced composite implants.

PubMed

Ballo, Ahmed M; Akca, Eralp; Ozen, Tuncer; Moritz, Niko; Lassila, Lippo; Vallittu, Pekka; Närhi, Timo

2014-08-01

This study aimed to evaluate the influence of implant design and bioactive glass (BAG) coating on the response of bone to fiber-reinforced composite (FRC) implants. Three different FRC implant types were manufactured for the study: non-threaded implants with a BAG coating; threaded implants with a BAG coating; and threaded implants with a grit-blasted surface. Thirty-six implants (six implants for each group per time point) were installed in the tibiae of six pigs. After an implantation period of 4 and 12 wk, the implants were retrieved and prepared for micro-computed tomography (micro-CT), push-out testing, and scanning electron microscopy analysis. Micro-CT demonstrated that the screw-threads and implant structure remained undamaged during the installation. The threaded FRC/BAG implants had the highest bone volume after 12 wk of implantation. The push-out strengths of the threaded FRC/BAG implants after 4 and 12 wk (463°N and 676°N, respectively) were significantly higher than those of the threaded FRC implants (416°N and 549°N, respectively) and the nonthreaded FRC/BAG implants (219°N and 430°N, respectively). Statistically significant correlation was found between bone volume and push-out strength values. This study showed that osseointegrated FRC implants can withstand the static loading up to failure without fracture, and that the addition of BAG significantly improves the push-out strength of FRC implants. © 2014 Eur J Oral Sci.

Peri-implant plastic surgery techniques to hard and soft tissue augmentation in implant rehabilitation

PubMed Central

Baltacioğlu, Esra; Korkmaz, Yavuz Tolga; Korkmaz, Fatih Mehmet; Aydin, Güven; Sukuroglu, Erkan

2017-01-01

This report presents the clinical results of peri-implant plastic surgical approaches for hard and soft tissues before and during the implant placement in a patient with vertical ridge deformation and a shallow vestibule sulcus, and the subsequently performed prosthetic rehabilitation. The surgical approaches used in this case reduced the crown-height space and crown-to-implant ratio and ensured that the implants were placed in their ideal positions, and peri-implant tissue health was maintained. In conclusion, developments in the peri-implant plastic surgery enable the successful augmentation of hard and soft tissue defects and provide the implant-supported fixed prosthetic rehabilitation. PMID:29386805

The clinical implications of poly implant prothèse breast implants: an overview.

PubMed

Wazir, Umar; Kasem, Abdul; Mokbel, Kefah

2015-01-01

Mammary implants marketed by Poly Implant Prothèse (PIP) were found to contain industrial grade silicone and this caused heightened anxiety and extensive publicity regarding their safety in humans. These implants were used in a large number of patients worldwide for augmentation or breast reconstruction. We reviewed articles identified by searches of Medline, PubMed, Embase, and Google Scholar databases up to May 2014 using the terms: "PIP", "Poly Implant Prothèse", "breast implants" and "augmentation mammoplasty" "siloxanes" or "silicone". In addition the websites of regulating bodies in Europe, USA, and Australia were searched for reports related to PIP mammary implants. PIP mammary implants are more likely to rupture than other implants and can cause adverse effects in the short to the medium term related to the symptoms of rupture such as pain, lumps in the breast and axilla and anxiety. Based on peer-reviewed published studies we have calculated an overall rupture rate of 14.5% (383/2,635) for PIP implants. However, there is no evidence that PIP implant rupture causes long-term adverse health effects in humans so far. Silicone lymphadenopathy represents a foreign body reaction and should be treated conservatively. The long-term adverse effects usually arise from inappropriate extensive surgery, such as axillary lymph node dissection or extensive resection of breast tissue due to silicone leakage.

The Clinical Implications of Poly Implant Prothèse Breast Implants: An Overview

PubMed Central

Wazir, Umar; Kasem, Abdul

2015-01-01

Mammary implants marketed by Poly Implant Prothèse (PIP) were found to contain industrial grade silicone and this caused heightened anxiety and extensive publicity regarding their safety in humans. These implants were used in a large number of patients worldwide for augmentation or breast reconstruction. We reviewed articles identified by searches of Medline, PubMed, Embase, and Google Scholar databases up to May 2014 using the terms: "PIP", "Poly Implant Prothèse", "breast implants" and "augmentation mammoplasty" "siloxanes" or "silicone". In addition the websites of regulating bodies in Europe, USA, and Australia were searched for reports related to PIP mammary implants. PIP mammary implants are more likely to rupture than other implants and can cause adverse effects in the short to the medium term related to the symptoms of rupture such as pain, lumps in the breast and axilla and anxiety. Based on peer-reviewed published studies we have calculated an overall rupture rate of 14.5% (383/2,635) for PIP implants. However, there is no evidence that PIP implant rupture causes long-term adverse health effects in humans so far. Silicone lymphadenopathy represents a foreign body reaction and should be treated conservatively. The long-term adverse effects usually arise from inappropriate extensive surgery, such as axillary lymph node dissection or extensive resection of breast tissue due to silicone leakage. PMID:25606483

CO2 laser surface treatment of failed dental implants for re-implantation: an animal study.

PubMed

Kasraei, Shahin; Torkzaban, Parviz; Shams, Bahar; Hosseinipanah, Seyed Mohammad; Farhadian, Maryam

2016-07-01

The aim of the present study was to evaluate the success rate of failed implants re-implanted after surface treatment with CO2 laser. Despite the widespread use of dental implants, there are many incidents of failures. It is believed that lasers can be applied to decontaminate the implant surface without damaging the implant. Ten dental implants that had failed for various reasons other than fracture or surface abrasion were subjected to CO2 laser surface treatment and randomly placed in the maxillae of dogs. Three failed implants were also placed as the negative controls after irrigation with saline solution without laser surface treatment. The stability of the implants was evaluated by the use of the Periotest values (PTVs) on the first day after surgery and at 1, 3, and 6 months post-operatively. The mean PTVs of treated implants increased at the first month interval, indicating a decrease in implant stability due to inflammation followed by healing of the tissue. At 3 and 6 months, the mean PTVs decreased compared to the 1-month interval (P < 0.05), indicating improved implant stability. The mean PTVs increased in the negative control group compared to baseline (P < 0.05). Independent t-test showed that the mean PTVs of treated implants were significantly lower than control group at 3 and 6 months after implant placement (P < 0.05). Based on the PTVs, re-implantation of failed implants in Jack Russell Terrier dogs after CO2 laser surface debridement is associated with a high success rate in terms of implant stability.

An in vivo assessment of the effects of using different implant abutment occluding materials on implant microleakage and the peri-implant microbiome

NASA Astrophysics Data System (ADS)

Rubino, Caroline

Microleakage may be a factor in the progression of peri-implant pathology. Microleakage in implant dentistry refers to the passage of bacteria, fluids, molecules or ions between the abutment-implant interface to and from the surrounding periodontal tissues. This creates a zone of inflammation and reservoir of bacteria at the implant-abutment interface. Bone loss typically occurs within the first year of abutment connection and then stabilizes. It has not yet been definitively proven that the occurrence of microleakage cannot contribute to future bone loss or impede the treatment of peri-implant disease. Therefore, strategies to reduce or eliminate microleakage are sought out. Recent evidence demonstrates that the type of implant abutment channel occluding material can affect the amount of microleakage in an in vitro study environment. Thus, we hypothesize that different abutment screw channel occluding materials will affect the amount of observed microleakage, vis-a-vis the correlation between the microflora found on the abutment screw channel occluding material those found in the peri-implant sulcus. Additional objectives include confirming the presence of microleakage in vivo and assessing any impact that different abutment screw channel occluding materials may have on the peri-implant microbiome. Finally, the present study provides an opportunity to further characterize the peri-implant microbiome. Eight fully edentulous patients restored with at dental implants supporting screw-retained fixed hybrid prostheses were included in the study. At the initial appointment (T1), the prostheses were removed and the implants and prostheses were cleaned. The prostheses were then inserted with polytetrafluoroethylene tape (PTFE, TeflonRTM), cotton, polyvinyl siloxane (PVS), or synthetic foam as the implant abutment channel occluding material and sealed over with composite resin. About six months later (T2), the prostheses were removed and the materials collected. Paper

Trends in Cochlear Implants

PubMed Central

Zeng, Fan-Gang

2004-01-01

More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic aspects of cochlear implants, focusing on their psychophysical, speech, music, and cognitive performance. This report also forecasts clinical and research trends related to presurgical evaluation, fitting protocols, signal processing, and postsurgical rehabilitation in cochlear implants. Finally, a future landscape in amplification is presented that requires a unique, yet complementary, contribution from hearing aids, middle ear implants, and cochlear implants to achieve a total solution to the entire spectrum of hearing loss treatment and management. PMID:15247993