A biodegradable drug delivery system for the treatment of postoperative inflammation

Cataract surgery is often performed in patients suffering from associated pathologies. Our goal is to develop a biodegradable drug delivery system (DDS) combined with the artificial intraocular lens (IOL). DDS were manufactured using poly(D,L-lactide-co-glycolide), or PLGA, and were loaded with triamcinolone acetonide (TA). The loading capacity was approximately 1050 microg of TA per DDS. The higher the molecular weight of PLGA (34,000, 48,000 and 80,000Da), the slower was the release of TA in vitro. Cataract surgery was performed on the right eye of rabbits. IOL was inserted with (i) no DDS, (ii) unloaded DDS PLGA48000, (iii) one loaded DDS PLGA48000, (iv) two loaded DDS. The number of inflammatory cells and the protein concentration were measured in the aqueous humor (AH). Unloaded DDS showed good ocular biocompatibility. One DDS PLGA48000 loaded with TA significantly reduced postoperative ocular inflammation. Two loaded DDS PLGA48000 was even more effective in inhibiting such inflammation. On long-term observation (days 63 and 84), reduction of inflammation could be obtained by insertion of one DDS PLGA48000 and a second DDS PLGA80000. Therefore, our "all in one" system is very promising since it could replace oral treatment and reduce the number of intraocular injections

Propionibacterium acnes: An Underestimated Pathogen in Implant-Associated Infections.

The role of Propionibacterium acnes in acne and in a wide range of inflammatory diseases is well established. However, P. acnes is also responsible for infections involving implants. Prolonged aerobic and anaerobic agar cultures for 14 days and broth cultures increase the detection rate. In this paper, we review the pathogenic role of P. acnes in implant-associated infections such as prosthetic joints, cardiac devices, breast implants, intraocular lenses, neurosurgical devices, and spine implants. The management of severe infections caused by P. acnes involves a combination of antimicrobial and surgical treatment (often removal of the device). Intravenous penicillin G and ceftriaxone are the first choice for serious infections, with vancomycin and daptomycin as alternatives, and amoxicillin, rifampicin, clindamycin, tetracycline, and levofloxacin for oral treatment. Sonication of explanted prosthetic material improves the diagnosis of implant-associated infections. Molecular methods may further increase the sensitivity of P. acnes detection. Coating of implants with antimicrobial substances could avoid or limit colonization of the surface and thereby reduce the risk of biofilm formation during severe infections. Our understanding of the role of P. acnes in human diseases will likely continue to increase as new associations and pathogenic mechanisms are discovered.

Ophtalmologie. Nouvelles tendances dans la chirurgie de la cataracte [Ophthalmology. New trends in cataract surgery].

Cataract surgery is the most frequent surgery performed in the world. Modernization of cataract surgery is a continuous process and recent technological progress have enlarged the spectrum of treatable refractive errors, improved safety of surgery, speed of visual recovery and reduction of complications rate. Thus, during the last years, refractive intraocular lenses such as toric and multifocal IOLS have been introduced in practice, as well as torsional phacoemulsification and corneal microincision. For endophthalmitis prophylaxis, modern management includes intracameral injection of antibiotics. The future of cataract surgery is probably to replace phacoemulsification surgery by laser surgery, which is safer and more reproducible.

Cytotoxic effects of FGF2-saporin on bovine epithelial lens cells in vitro.

PURPOSE: To test the ability of two preparations of FGF2-saporin, either FGF2 chemically conjugated to saporin (FGF2-SAP) or genetically engineered FGF2-saporin (rFGF2-SAP) to inhibit the growth of bovine epithelial lens (BEL) cells in vitro when in solution and when immobilized on heparin surface-modified (HSM) polymethylmethacrylate (PMMA) intraocular lenses (IOLs). METHOD: Bovine epithelial lens cells were incubated with various concentrations FGF2-saporin for as long as 4 days. The number of surviving cells was determined by counting the number of nuclei. Because FGF2 binds to heparin, FGF2-saporin was incubated with HSM PMMA IOLs; excess toxin was washed off, and the BEL cells were grown on the FGF2-saporin-treated IOLs (HSM and non-HSM) for 4 days. Cell density was determined by image analysis. RESULTS: Both FGF2-SAP and rFGF2-SAP were highly cytotoxic (nM range), with rFGF2-SAP 10 times less active than FGF2-SAP. FGF2-saporin bound to the surface of HSM IOLs and eluted by 2M NaCl retained its activity. Toxin bound to HSM IOLs killed more than 90% of the BEL cells placed on the IOL surface within 4 days. The ability of FGF2-saporin to prevent the growth of cells on the IOL surface was strictly dependent on the presence of heparin on the IOL. CONCLUSIONS: FGF2-saporin is bound to HSM PMMA IOLs and prevents the growth of epithelial cells on the surface of the lens.

Iris varix as a cause of late-onset inflammation after implantation of a phakic iris claw lens [Irisvarize als Ursache einer verzögerten Entzündung nach Implantation einer Iris-Clip-Linse ins phake Auge]

Implantation of a phakic iris claw intraocular lens is a common, effective and safe procedure to correct high myopia, hyperopia and astigmatism [2]. Due to the nature of its fixation on the iris using claws, chronic irritation and inflammation have remained a major concern with the Artisan® lens since its market introduction in 1998. Following iris claw implantation, monitoring of postoperative inflammation is mandatory [4][7]. Usually, signs of inflammation can be detected in the anterior chamber during the early postoperative period. We present here the first case of late-onset inflammation after implantation of an iris claw lens triggered by an iris varix. The iris varix is a rare benign iris vascular abnormality, with a low prevalence as a solitary primary lesion in the general population and little is known about its clinical characteristics [1][5][6]. This report shows that an iris varix could be a cause of a late onset and chronic inflammation after phakic Artisan® lens implantation.

In vivo inhibition of lens regrowth by fibroblast growth factor 2-saporin.

PURPOSE: To investigate the ability of fibroblast growth factor (FGF) 2-saporin to prevent lens regrowth in the rabbit. METHODS: Chemically conjugated and genetically fused FGF2-saporin (made in Escherichia coli) were used. Extracapsular extraction of the lens was performed on the rabbit, and the cytotoxin either was injected directly into the capsule bag or was administered by FGF2-saporin-coated, heparin surface-modified (HSM) polymethylmethacrylate intraocular lenses. The potential of the conjugate was checked by slit lamp evaluation of capsular opacification and by measuring crystallin synthesis. Toxin diffusion and sites of toxin binding were assessed by immunohistochemistry. Possible toxicity was determined by histologic analysis of ocular tissues. RESULTS: FGF2-saporin effectively inhibited lens regrowth when it was injected directly into the capsular bag. However, high concentration of the toxin induced transient corneal edema and loss of pigment in the iris. Intraocular lenses coated with FGF2-saporin reduced lens regrowth and crystallin synthesis without any detectable clinical side effect. After implantation, FGF2-saporin was shown to have bound to the capsules and, to a lesser extent, to the iris; no histologic damage was found on ocular tissues as a result of implantation of drug-loaded HSM intraocular lenses. CONCLUSIONS: Chemically conjugated (FGF2-SAP) and genetically fused FGF2-saporin (rFGF2-SAP) bound to HSM intraocular lenses can prevent lens regrowth in the rabbit.

Correcting Interdevice Bias of Horizontal White-to-White and Sulcus-to-Sulcus Measures Used for Implantable Collamer Lens Sizing.

PURPOSE: To assess the agreement and repeatability of horizontal white-to-white (WTW) and horizontal sulcus-to-sulcus (STS) diameter measurements and use these data in combination with available literature to correct for interdevice bias in preoperative implantable collamer lens (ICL) size selection. DESIGN: Interinstrument reliability and bias assessment study. METHODS: A total of 107 eyes from 56 patients assessed for ICL implantation at our institution were included in the study. This was a consecutive series of all patients with suitable available data. The agreement and bias between WTW (measured with the Pentacam and BioGraph devices) and STS (measured with the HiScan device) were estimated. RESULTS: The mean spherical equivalent was -8.93 ± 5.69 diopters. The BioGraph measures of WTW were wider than those taken with the Pentacam (bias = 0.26 mm, P < .01), and both horizontal WTW measures were wider than the horizontal STS measures (bias >0.91 mm, P < .01). The repeatability (Sr) of STS measured with the HiScan was 0.39 mm, which was significantly reduced (Sr = 0.15 mm) when the average of 2 measures was used. Agreement between the horizontal WTW measures and horizontal STS estimates when bias was accounted for was г = 0.54 with the Pentacam and г = 0.64 with the BioGraph. CONCLUSIONS: Large interdevice bias was observed for WTW and STS measures. STS measures demonstrated poor repeatability, but the average of repeated measures significantly improved repeatability. In order to conform to the US Food and Drug Administration's accepted guidelines for ICL sizing, clinicians should be aware of and account for the inconsistencies between devices.

A New Imaging Software To Evaluate The Centration Of Capsulorhexis And Intraocular Lens (IOL) After Cataract Surgery

Purpose: IOL centration and stability after cataract surgery is of high interest for cataract surgeons and IOL-producing companies. We present a new imaging software to evaluate the centration of the rhexis and the centration of the IOL after cataract surgery.Methods: We developed, in collaboration with the Biomedical Imaging Group (BIG), EPFL, Lausanne, a new working tool in order to assess precisely outcomes after IOL-implantation, such as ideal capsulorhexis and IOL-centration. The software is a plug-in of ImageJ, a general-purpose image processing and image-analysis package. The specifications of this software are: evaluation of the rhexis-centration and evaluation the position of the IOL in the posterior chamber. The end points are to analyze the quality of the centration of a rhexis after cataract surgery, the deformation of the rhexis with capsular bag retraction and the centration of the IOL after implantation.Results: This software delivers tools to interactively measure the distances between limbus, IOL and capsulorhexis and its changes over time. The user is invited to adjust nodes of three radial curves for the limbus, rhexis and the optic of the IOL. The radial distances of the curves are computed to evaluate the IOL implantation. The user is also able to define patterns for ideal capsulorhexis and optimal IOL-centration. We are going to present examples of calculations after cataract surgery.Conclusions: Evaluation of the centration of the rhexis and of the IOL after cataract surgery is an important end point for optimal IOL implantation after cataract surgery. Especially multifocal or accommodative lenses need a precise position in the bag with a good stability over time. This software is able to evaluate these parameters just after the surgery but also its changes over time. The results of these evaluations can lead to an optimizing of surgical procedures and materials.

First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of first-line chemotherapy (CT) in preventing external-beam radiotherapy (EBR) and/or enucleation in patients with retinoblastoma (Rbl). PATIENTS AND METHODS: Twenty-four patients with newly diagnosed unilateral or bilateral Rbl received CT associated with local treatment (LT). Two to five courses of etoposide and carboplatin were administered at 3- to 4-week intervals, depending on tumor response, and were completed each time by LT. RESULTS: Tumor response was observed in all eyes. Twenty-one of 24 patients showed a complete response (CR) that persisted at a median follow-up (FU) of 31 months (range, 4 to 41 months). Among the three patients who relapsed, two were lost to FU and one died of progressive disease. CR was achieved by CT and LT alone in 15 (71.4%) of 21 patients with less advanced disease (groups I to III). Six other patients with advanced disease (groups IV and V) experienced treatment failure and needed salvage treatment by EBR and/or enucleation. The difference between the two patient groups with regard to disease stage was statistically significant (P <.0001). EBR could be avoided in 13 (68.4%) of 19 patients, who presented with groups I to III (15 eyes) and group V (one eye) disease, whereas enucleation could be avoided in only two (40%) of five. CONCLUSION: CT combined with intensive LT is effective in patients with groups I to III Rbl, permitting the avoidance of EBR in the majority of these young children and, thus, reducing the risk of long-term sequelae. This is in contrast with the disappointing results for patients with groups IV and V Rbl, in whom EBR and/or enucleation was needed.

Long-term stability of retinal function despite retained intraocular metallic foreign body.

BACKGROUND: Persisting metallic intraocular foreign bodies (IOFB) with a ferrous content have been associated with ocular siderosis and retinal degeneration. We describe two patients in whom a metallic IOFB containing iron was left embedded for many years in the choroid and sclera after having penetrated through the vitreous and the retina. HISTORY AND SIGNS: Two male patients, aged 41 and 48 years, presented with a metallic IOFB sustained during a work accident involving metal tools. THERAPY AND OUTCOME: For the first patient it was deemed unwise to operate, as the IOFB was also lodged very deeply in the choroid and sclera in the inferior temporal quadrant. The second patient underwent pars plana vitrectomy, but the IOFB could not be removed surgically as it was too deeply embedded in the sclera and choroid. After a period of 6 years (Case 1) and 4 years (Case 2) of follow-up, visual acuity remained at 1.0 and the IOFB was encased in a fibrotic capsule in both cases. Full-field and multifocal electroretinograms showed an inter-ocular asymmetry at baseline, which remained stable during the follow-up. CONCLUSIONS: Ocular siderosis may not develop in patients with a deeply embedded metallic IOFB. Regular monitoring of both visual function and the electroretinogram is mandatory when the IOFB is left inside the eye.

Expansion of intraocular gas bubbles due to altitude: do meteorological factors play a role?

BACKGROUND: Intraocular gas bubbles expand as patients move up to higher altitude. This may cause an acute intraocular pressure (IOP) rise with associated vascular obstructions and visual loss. MATERIALS AND METHODS: Two pseudophakic patients underwent a pars plana vitrectomy and 23% SF6 gas tamponade for a pseudophakic retinal detachment. During the immediate post-operative phase, the patients travelled daily up to their domicile, which was situated approximately 600 m higher than the level where they had been operated on. These travels were always without any pain or visual loss. However 1 week after surgery both patients developed severe ocular pain, and one patient had complete temporary loss of vision after ascending to altitude levels, which had previously presented no problem. Both episodes occurred in parallel with a change in barometric pressure. RESULTS: Treatment with acetazolamide reduced the increased IOP to normal levels, and visual acuity recovered. CONCLUSIONS: Although the post-operative size of an intraocular gas bubble decreases progressively over time, problems with bubble expansion may still occur even at a late stage if meteorological factors, that may increase the bubble size, change.

Hypertonie oculaire dans l'orbitopathie dysthyroidienne: considerations physiopathologiques, diagnostiques et therapeutiques. A propos de trois cas significatifs. [Intraocular high pressure in thyroid-associated orbitopathy: physiopathological mechanisms, diagnosis, and management. Three case reports]

PURPOSE: To determine the mechanisms and treatment of ocular hypertension in patients with thyroid-associated orbitopathy and to differenciate it from glaucomatous damage. DESIGN: Three case reports. METHODS: Retrospective review of clinical findings, course, and treatment of the three patients. RESULTS: Elevated intraocular pressure in thyroid-associated orbitopathy observed in the three cases may involve different physiopathological abnormalities such as disturbances of venous circulation, compression by infiltrative muscles, and long corticosteroid use. In the first two cases, defects demonstrated in the perimetry are in consistent with glaucomatous damage. In the third case, visual field abnormalities may be compatible with a glaucomatous disease, but all defects resolved after therapy. Treatement was of the greatest difficulty for the three cases, associating antiglaucomatous medication, steroids, orbital radiotherapy, orbital decompression and extraocular muscle surgery. Intraocular pressure was controlled in all cases. CONCLUSIONS: Elevated intraocular pressure in thyroid-associated orbitopathy is distinguished from glaucomatous disease by its physiopathological mechanisms, clinical course, visual field defects, and treatment. The management of this hypertension is closely related to the treatment of dysthyroid orbitopathy.

New-Generation Multifocal Intraocular Lens for Pediatric Cataract.

Background/Aims: To evaluate multifocal intraocular lens (MIOL) implantation in children. Methods: This is a retrospective study evaluating refractive, visual and safety results of MIOL in pediatric cataract surgery. Average follow-up was 25.73 ± 10.5 months. Surgery included 12 o'clock clear corneal incision, anterior capsulorhexis, lens material aspiration and MIOL implantation (SN6AD3; Alcon). Results: We included 34 cataract eyes of 26 pediatric patients aged 2-15 years, of which 14 (54%) were unilateral. Best near visual acuity (BNVA) and best distance visual acuity (BDVA) improved significantly in 100% of eyes (p = 0.0001). BDVA was above 0.8 in 31.25% (5/16) of bilateral cases. Significant stereopsis improvement was observed postoperatively in bilateral cases only (p = 0.01). Conclusion: MIOL implantation is a safe alternative to monofocal pseudophakia for pediatric cataract with a very low complication rate. Significant BNVA, BDVA and stereopsis improvement can be achieved, particularly in bilateral cases. Message: This study shows significant BDVA, BNVA and stereopsis improvement, especially in bilateral cases, after MIOL implantation for pediatric cataracts. © 2013 S. Karger AG, Basel.

A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application.

The biocompatibility of a viscous, hydrophobic, bioerodible poly(ortho ester) (POE) intended for intraocular application was investigated. POE was evaluated as a blank carrier and as containing modulators of degradation. Each formulation was injected intracamerally and intravitreally in rabbit eyes, and clinical and histological examinations were performed postoperatively for 2 weeks. In the case of intracameral injections, polymer biocompatibility appeared to depend on the amount injected in the anterior chamber. When 50 microL was administered, the polymer degraded within 2 weeks, and clinical observations showed good biocompatibility of POE with no toxicity to the ocular tissues or increase in intraocular pressure. The injection of a larger volume, 100 microL, of POE, appeared inappropriate because of direct contact of polymeric material with the corneal endothelium, and triggered reversible edema and inflammation in the anterior chamber of the eye that regressed after a few days. After intravitreal administration, POE was well tolerated and no inflammatory reaction developed during the observation period. The polymer degraded slowly, appearing as a round whitish bubble in the vitreous cavity. The presence of modulators of degradation both improved POE biocompatibility and prolonged polymer lifetime in the eye. POE appears to be a promising biomaterial for clinical intraocular application.