Vitreous Implants Research Articles

Meropenem loaded 4-arm-polyethylene-succinimidyl-carboxymethyl ester and hyaluronic acid based bacterial resistant hydrogel

Developing an ideal vitreous substitute/implant is a current challenge. Moreover, implants (e.g., heart valves and vitreous substitutes), are associated with a high risk of bacterial infection when it comes in contact with cells at implant site. Due to infection, many implants fail, and the patient requires immediate surgery and suffers from post-operative problems. To overcome these problems in vitreous implants, we developed a bacterial resistant vitreous implant, where meropenem (Mer), an antibiotic, has been incorporated in a hydrogel prepared by crosslinking HA (deacetylated sodium hyaluronate) with 4-arm-polyethylene-succinimidyl-carboxymethyl-ester (PESCE). The HA-PESCE hydrogel may serve as a suitable artificial vitreous substitute (AVS). The pre-gel solutions of HA-PESCE without drug and with the drug are injectable through a 22 G needle, and the gel formation occurred in approx. 3 min: it indicates its suitability for in-situ gelation through vitrectomy surgery. The HA-PESCE hydrogel depicted desired biocompatibility, transparency (>90 %), water content (96 %) and sufficient viscoelasticity (G′ >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. The HA-Mer-PESCE hydrogel showed improved biocompatibility, suitable transparency (>90 %), high water content (96 %), and suitable viscoelasticity (G′ >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. Further, hydrogel strongly inhibits the growth of bacteria E.coli and S.aureus. The drug loaded hydrogel showed sustained in-vitro drug release by the Fickian diffusion-mediated process (by Korsmeyer-Peppas and Peppas Sahlin model). Thus, the developed hydrogel may be used as a potential bacterial resistant AVS.

Personalized Nano Delivery Strategy in Treating Uveitis

Uveitis is an inflammatory disease causes the damage of eye tissues and leads to the loss of vision once kept untreated. Early detection and identification of the disease are necessary for the prevention of the progressing inflammation and tissue damage. Existing treatment comprise of the administration of oral steroids, immunosuppressant, biological and adjuvant therapy. Even though topical, intravitreal and subconjunctival administration routes have been chosen for the drug administration, they fail to achieve the drug concentration to elicit a better therapeutic action due to the presence of ocular barriers such as tear, cornea conjunctiva, sclera, choroid membrane, retina, and blood-retinal barrier. Design of delivery systems that can prolong the precorneal habitation time increase the drug release as well as reduce the side effects such as methods to achieve prolonged can promise effective ocular drug delivery. Delivery systems such as hydrogels, liposomes, micro carrier systems, vitreous implants, medicated lenses, nanotechnology approaches such as nanocrystals, nanoemulsions, nanosuspensions, dendrimers, microneedles etc. exist as current research and the future research perspectives to achieve effective ocular drug delivery.

Intraocular silicone implant to treat chronic ocular hypotony-preliminary feasibility data.

Ocular hypotony secondary to proliferative vitreoretinopathy-related retinal detachment, trauma or inflammation is difficult to treat. Besides endotamponades such as silicone oil, vitreous implants such as iris diaphragms or balloons have been developed to stabilize the eye and to prevent phthisis of the globe. Vitreous implants tested thus far exhibit a seam at the attachment site of the hemispheres, or micropores. This manuscript reports the development of a seamless silicone balloon implant without micropores, which can be filled with silicone oil and surface-modified to improve its biocompatibility. Developed for intraocular placement in the management of chronic hypotony and phthisis prevention, it may also be suitable for tamponading retinal detachments. Silicone was used as the basic structure for the fabrication of a seamless balloon-shaped intraocular implant, which was coated by employing a six-arm star-shaped (sP) macromer of a copolymer of 80% ethylene oxide (EO) and 20% propylene oxide (PO) with conjugated functional terminal isocyanate groups, NCO-sP(EO-stat-PO), with and without heparin. Three variants of implants, which differ in their surfaces, were manufactured: uncoated silicone, NCO-sP (EO-stat-PO) coated silicone and heparin-NCO-sP (EO-stat-PO) coated silicone implants. To exert a tamponade effect, the implant was filled with silicone oil and its properties were studied. Seamless thin balloon implants made of silicone, which are considered biocompatible and intrinsically resistant to biological attacks in vivo, could be fabricated in different sizes. The silicone oil-filled implant can mimic the mechanism of buoyant force and high surface tension of silicone oil, which is the only long-term vitreous substitute currently available. The silicone oil-filled implant can also mimic the natural vitreous body by occupying the entire posterior segment. The intraocular silicone implant as an alternative long-term treatment of chronic ocular hypotony might offer a new option for clinical ophthalmological practice. In vivo studies need to be performed to collect more data on the implant's long-term mechanical and optical properties, as well as long-term biocompatibility.

Quantitative Assessment of Optic Nerve Changes in Patients With Diabetic Macular Edema Treated With Fluocinolone Acetonide Vitreous Implants.

To evaluate glaucomatous changes in patients with diabetic macular edema (DME) treated with intravitreal implants releasing 0.2 µg/day or 0.5 µg/day fluocinolone acetonide (FAc) (Iluvien 0.2 µg/day; Alimera Sciences, Alpharetta, GA) or sham control. Fundus photographs were assessed to determine clinically significant changes in glaucomatous indicators. The mean cup-to-disc ratio (CDR) change was similar with all three treatments. Compared with sham control, a significantly greater proportion of patients treated with 0.5 µg/day but not 0.2 µg/day FAc experienced a CDR increase of greater than 0.1. There was no significant increase in the proportion of patients experiencing a CDR increase of greater than 0.2 with either dose of implant versus sham control. Other indicators of glaucomatous change did not differ significantly with treatment. Subgroup analyses showed no differences in cupping based on ocular or baseline characteristics. Treatment with FAc for 36 months was not associated with significant glaucomatous optic nerve head changes in patients with DME with or without increased intraocular pressure. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:418-425.].

Sustained Delivery Fluocinolone Acetonide Vitreous Implants: Long-Term Benefit in Patients with Chronic Diabetic Macular Edema

To present the safety and efficacy of intravitreal implants releasing 0.2 μg/day fluocinolone acetonide (FAc) in patients with chronic versus nonchronic diabetic macular edema (DME). To assess ocular characteristics, anatomic changes, and re-treatment and ancillary therapies that may explain the differential treatment effect seen with intravitreal implants releasing FAc 0.2 μg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk assessment for the FAc 0.2-μg/day and FAc 0.5-μg/day doses has been reported previously. Preplanned subgroup analysis of chronic (duration of diagnosis, ≥3 years) and nonchronic (duration of diagnosis, <3 years) DME in patients from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials. Patients with persistent DME despite 1 or more macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc 0.2 μg/day (n = 375), or FAc 0.5 μg/day (n = 393). Patients received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on re-treatment criteria, additional masked study drug could be given after 1 year. Percentage of patients with improvement of 15 letters or more from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. At month 36, the difference between FAc 0.2 μg/day and sham control in the percentage of patients who gained 15 letters or more was significantly greater in chronic DME patients (FAc 0.2 μg/day, 34.0% vs. sham, 13.4%; P<0.001), compared with patients with nonchronic DME (FAc 0.2 μg/day, 22.3% vs. sham, 27.8%; P = 0.275). The greater response in patients with chronic DME was not associated with baseline ocular characteristics, changes in anatomic features, or differences in re-treatment or ancillary therapies. The ocular adverse event profile for FAc 0.2 μg/day was similar regardless of DME duration. This is the first published analysis correlating duration of diagnosis of DME with treatment effect. In patients with chronic DME, FAc 0.2 μg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy.

Newer Approaches for Optimal Bioavailability of Ocularly Delivered Drugs: Review

Eye diseases can cause discomfort and anxiety in patients, with the ultimate fear of loss of vision and facial disfigurement. Many regions of the eye are relatively inaccessible to systemically administered drugs and, as a result, topical drug delivery remains the preferred route in most cases. Drugs may be delivered to treat the precorneal region for conjunctivitis and blepharitis, or to provide intraocular diseases such as glaucoma, uveitis, and cytomegalovirus retinitis. Most of the ophthalmic formulation strategies aim at maximizing ocular drug permeability through prolongation of the drug residence time in the cornea and conjunctival sac, as well as minimizing precorneal drug loss. The conventional topical ocular drug delivery systems show drawbacks such as increased precorneal elimination and high variability in efficacy. Attempts have been made to overcome these problems and enhance ocular bioavailability by the development of newer drug delivery systems. This review is concerned with classification, recent findings and applications and biocompatibility of newer drug delivery systems for the treatment of ocular diseases.

Intraocular Response to Cotton, Collagen and Cellulose in the Rabbit

Cotton, cellulose and collagen were each implanted into the anterior chamber and anterior vitreous of rabbit eyes. The ocular inflammatory response was studied clinically over a 28-day period and histologically at seven and 28 days. In general, cotton was the least reactive, with collagen and cellulose moderately reactive. Cellulose was associated with progressive inflammation and marked granulomatous response. Vitreous implants showed minimal inflammation, with virtually no response to cotton. These findings support current literature suggesting that the use of cellulose in ophthalmic surgery may increase the risk of postoperative granulomatous inflammation.

Vitreous implants in retinal detachment.

Vitreous implants in retinal detachment.

Further experience with vitreous implants in old retinal detachments.

The vitreous implant is not to be confused with the vitreous transplant. The implant is a technique for adding new vitreous to cases of retinal detachment, while the vitreous transplant is an exchange of clear vitreous for cloudy or bloody vitreous. The basic premise of the use of vitreous in retinal detachment was that it hydraulically could pump the retina back in place, but so could air or saline. The second premise for its use was that vitreous seemed to be what kept the retina normally attached in the first place, for the retina has no attachments between its two extremities—the ora serrata and the disc. The final premise is that vitreous is the normal inhabitant of the vitreous chamber. Therefore, replacement by more vitreous seemed the logical procedure. This has been well expressed by Dr. Graham Clark, who feels that the retina is a membrane in the midst