Biocompatibility and feasibility of VisiPlate, a novel ultrathin, multichannel glaucoma drainage device.

BACKGROUND: Glaucoma is the leading cause of blindness worldwide. Glaucoma drainage devices and minimally invasive glaucoma surgeries (MIGS) often present with tradeoffs in safety and durability of efficacy. Using a rabbit model, we examined the biocompatibility and feasibility of VisiPlate, a novel, ultrathin, tubeless subconjunctival shunt comprised of a network of microchannels. METHODS: Six naive female New Zealand White rabbits received implants (three only in the right eye with contralateral eye untreated and three in both eyes) composed of a 400-nm-thick aluminum oxide core coated with 2 µm of parylene-C, manufactured with microelectromechanical systems (MEMS) techniques. Tonometry, slit lamp exam, clinical exam, fluorescein patency testing, and histopathology were performed. RESULTS: VisiPlate demonstrated IOP-lowering of 20-40% compared to baseline at each time point over the course of 3 months in the nine implanted eyes. All eyes developed blebs over the implant, and fluorescein testing demonstrated fluid patency at 22 days post-implantation. Slit lamp and clinical observations showed that VisiPlate was well tolerated, with low levels of conjunctival congestion, conjunctival swelling, aqueous flare, hyphema, and iris involvement from surgery that resolved over time. At sacrifice time points of 93 days and 180 days, the only notable observations were mild levels of conjunctival congestion in implanted eyes. Histopathology showed minimal tissue response and no obvious inflammation, fibrosis, or necrosis around the implant. CONCLUSIONS: The results of this in vivo study demonstrate the biocompatibility and IOP-lowering effect of a multichannel, ultrathin subconjunctival shunt in a rabbit model. The data suggest that VisiPlate may safely enhance aqueous outflow and significantly reduce intraocular pressure.

Development of a biodegradable flow resisting polymer membrane for a novel glaucoma microstent.

Within this paper we analyzed the technical feasibility of a novel microstent for glaucoma therapy. For lowering of intraocular pressure, the flexible polyurethane (PUR) implant is designed to drain aqueous humour from the anterior chamber of the eye into subconjunctival, or alternatively suprachoroidal, space. The microstent includes a biodegradable, flow resisting polymer membrane serving as temporary flow resistance for the prevention of early postoperative hypotony. A biodegradable local drug delivery (LDD)-device was designed to prevent fibrous encapsulation. Biodegradable components were made of flexible, nonwoven membranes of Poly(4-hydroxybutyrate) (P(4HB)). Polymer samples and microstent prototypes were manufactured by means of dip coating, electrospinning and femtosecond-laser micromachining and characterized in vitro with regard to structural and fluid mechanical properties, degradation behavior and drug release. Bending stiffness of PUR-tubing (62.53 ± 7.57 mN mm2) is comparable to conventional glaucoma drainage devices in a tube-plate design. Microstent prototypes yield a flow resistance of 2.4 ± 0.6 mmHg/µl min-1 which is close to the aspired value corresponding to physiological pressure (15 mmHg) and aqueous humour flow (2 µl min-1) conditions inside the eye. Degradation of electrospun P(4HB) specimens was found to be almost completely finished after six months in vitro. Within this time frame, flow capacity of the microstent increases, which is beneficial to compensate potentially increasing flow resistance of fibrous tissue in vivo. Fast drug release of the LDD-device was found. One microstent prototype was implanted into a porcine eye ex vivo. Future preclinical studies will allow further information about Microstent performance.

Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys.

PURPOSE: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. DESIGN: Preclinical efficacy study of 3 treatment arms in a crossover design. PARTICIPANTS: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. METHODS: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05). CONCLUSIONS: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.

Development of brimonidine niosomes laden contact lenses for extended release and promising delivery system in glaucoma treatment.

BACKGROUND: Increased intraocular pressure is a common symptom of glaucoma. In severe circumstances, it may result in loss of eyesight. Glaucoma treatment is difficult due to ocular physiological barriers that prevent medications from reaching the afflicted area. Traditional formulations (eye drops) have a short residence period and are rapidly drained away via the nasolacrimal duct, resulting in increased adverse drug responses and lower efficacy. The usage of nanoparticles such as niosomes could be one potential answer to these problems. While niosomes improve drug penetration, they have little effect on ocular retention of the medication. Contact lenses containing niosomes can assist to overcome this disadvantage. OBJECTIVE: This study aims to prepare and evaluate Brimonidine niosomes laden contact lenses for the treatment of Glaucoma. METHODS: Brimonidine niosomes were prepared using thin film hydration method and evaluated. The contact lenses were soaked in the niosomal formulation at varying intervals (3-10 days). Thereafter, the contact lenses were evaluated for %transmittance, %swelling index, drug quantification and in vitro drug release. The pharmacodynamic studies were conducted to assess the reduction in intraocular pressure (IOP) in albino rabbits. The research compared the results of the reduction in intraocular pressure caused by Brimonidine niosomes laden contact lenses with a marketed preparation of niosomes. RESULTS: Higher concentration of the drug was loaded in contact lenses loaded with Brimonidine niosomes compared to the marketed formulation, by soaking method. The contact lenses exhibited an optimal %transmittance of 98.02 ± 0.36 and %swelling index of 50.35 ± 0.57. Increase in the soaking time up to 7 days led to an increase in the drug concentration in the contact lenses. However, no further increase was observed after the 7th day due to saturation of the contact lenses. Brimonidine niosomes laden contact lenses provided a reduction in intraocular pressure that was similar to the marketed preparation. Further, the contact lenses provided extended release up to 20 h. CONCLUSION: Brimonidine niosomes laden contact lenses exhibited superior drug loading through the soaking method, displaying optimal %transmittance and %swelling index. Soaking for 7 days increased drug concentration in contact lenses with no further increase due to saturation. These lenses reduced intraocular pressure like the marketed formulation, offering extended release for 20 h.

Mesenchymal stem cells differentiate to retinal ganglion-like cells in rat glaucoma model induced by polystyrene microspheres.

AIM: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. MATERIALS AND METHODS: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. RESULTS: Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. CONCLUSION: Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.

TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis.

Retinal ischemia-reperfusion injury (IRI) is one of the main pathogenic mechanisms of glaucoma, which are largely unknown, including neuroinflammation and neuronal death in the pathological process. In our previous studies, mesenchymal stem cells (MSCs) have been reported to play anti-inflammatory and neuroprotective roles. Additionally, conditioned culture medium (CM) of MSCs stimulated by TNF-α have achieved better antiallergic effects in an experimental allergic conjunctivitis mouse model. However, there is an urgent need for cell-free therapy approaches, like exosomes, to reduce the side effects of autoimmunity. The present study aimed to elucidate the pathways involving TNF-α-stimulated gingival MSC (GMSC)-exosomes (TG-exos), in modulating inflammatory microglia and alleviating apoptosis. In this study, exosomes from the CM of GMSCs were isolated by ultracentrifugation and were injected into the vitreous of mice. The results showed that intraocular injection of TG-exos into mice with IRI notably reduced inflammation and cell loss than that with G-exos (GMSC-exosomes). Similar results were observed in vitro. Additionally, with the microRNA (miR) arrays, it was found that miR-21-5p acted as a crucial factor in TG-exos for neuroprotection and anti-inflammation. Following target prediction and dual-luciferase assay suggested that miR-21-5p played a role by combining with programmed cell death 4 (PDCD4), which was regulated by the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) as a competing endogenous RNA (ceRNA). This study demonstrates a new therapeutic pathway for neuroprotection against IRI by delivering miR-21-5p-enriched exosomes through MEG3/miR-21-5p/PDCD4 axis and paves the way for the establishment of a cell-free therapeutic approach for glaucoma.

A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.

Cationic nano-copolymers mediated IKKß targeting siRNA to modulate wound healing in a monkey model of glaucoma filtration surgery.

PURPOSE: To investigate the efficacy and safety of cationic nano-copolymers CS-g-(PEI-b-mPEG) mediated IκB kinase beta (IKKß) targeting siRNA in modulating wound healing in a monkey model of glaucoma filtration surgery. METHODS: The IKKß targeting siRNAs were chemically synthesized and screened in cultured monkey Tenon's fibroblasts in vitro. Fourteen monkeys underwent trabeculectomy and were randomly allocated to one of three treatment regimens: subconjunctival injection of either CS-g-(PEI-b-mPEG)/IKKß-siRNA (six eyes, 50nM, at the time of surgery and 7 days post surgery) or phosphate buffered saline (four eyes), or treated with mitomycin C (MMC; four eyes, 0.2 mg/ml). Bleb survival and characteristics, and intraocular pressure, were evaluated over a 60-day period. Histology of the surgical eyes was performed to evaluate ocular scarring and fibrosis in each group. RESULTS: Subconjunctival injection of CS-g-(PEI-b-mPEG)/IKKß-siRNA was well tolerated in this model. Both siRNA and MMC significantly prolonged bleb survival compared with the PBS group (the medians for survival days were 45.5, 60, and 29.5 in the siRNA, MMC, and PBS groups, respectively, p<0.01). Higher blebs were observed in the siRNA group than in the PBS group (p<0.01), while the MMC group showed the highest blebs among three groups (p<0.01). The surgical eyes in both the siRNA and MMC groups had significantly larger bleb area compared with the PBS group (p<0.01), but there was no significant difference between the siRNA and MMC groups (p=0.214). There were no significant differences in IOP readings among the three groups on the designated days after surgery (all p>0.05). The histologic examination demonstrated that the eyes treated with siRNA showed a marked reduction in subconjunctival scar tissue compared with the eyes in the PBS group. The conjunctival epithelium appeared healthy without the acellularity that was present in the MMC group. CONCLUSIONS: Subconjunctival injection of cationic nano-copolymers mediated IKKß targeting siRNA is associated with improved surgical outcome in a monkey model of trabeculectomy. This novel approach may potentially be a more controlled alternative as an anti-scarring agent in glaucoma filtration surgery.

Retinal Tissue Bioengineering, Materials and Methods for the Treatment of Glaucoma.

BACKGROUND: Glaucoma, a characteristic type of optic nerve degeneration in the posterior pole of the eye, is a common cause of irreversible vision loss and the second leading cause of blindness worldwide. As an optic neuropathy, glaucoma is identified by increasing degeneration of retinal ganglion cells (RGCs), with consequential vision loss. Current treatments only postpone the development of retinal degeneration, and there are as yet no treatments available for this disability. Recent studies have shown that replacing lost or damaged RGCs with healthy RGCs or RGC precursors, supported by appropriately designed bio-material scaffolds, could facilitate the development and enhancement of connections to ganglion cells and optic nerve axons. The consequence may be an improved retinal regeneration. This technique could also offer the possibility for retinal regeneration in treating other forms of optic nerve ailments through RGC replacement. METHODS: In this brief review, we describe the innovations and recent developments in retinal regenerative medicine such as retinal organoids and gene therapy which are specific to glaucoma treatment and focus on the selection of appropriate bio-engineering principles, biomaterials and cell therapies that are presently employed in this growing research area. RESULTS: Identification of optimal sources of cells, improving cell survival, functional integration upon transplantation, and developing techniques to deliver cells into the retinal space without provoking immune responses are the main challenges in retinal cell replacement therapies. CONCLUSION: The restoration of visual function in glaucoma patients by the RGC replacement therapies requires appropriate protocols and biotechnology methods. Tissue-engineered scaffolds, the generation of retinal organoids, and gene therapy may help to overcome some of the challenges in the generation of clinically safe RGCs.

Brinzolamide loaded core-shell nanoparticles for enhanced coronial penetration in the treatment of glaucoma.

A neurodegenerative disorder, glaucoma is a leading cause of blindness in the world. The conventional treatment strategies do not allow the significant penetration of the drug in the cornea. Therefore, we prepare a brinzolamide (Brz) loaded core-shell nanoparticles (NPs) to enhance the coronial penetration of the drug and thus treating the glaucoma. The shell of the NPs was composed of phosphatidylserine (PS; 1,2-diacyl-sn-glycero-3-phospho-L-serine), whereas the core of the NPs contains the Brz encapsulated in brinzolamide-phosphatidylserine-polymer poly-(DL-lactic acid-co-glycolic acid)-phosphatidylserine (Brz-PS-PLGA). The synthesis of Brz-PS-PLGA was achieved by using a coaxial electrospray process (CEP), which allows the preparation of the particles in a single step. The size of Brz-PS-PLGA with PS shell and brinzolamide-poly (lactic-co-glycolic) acid (Brz-PLGA) without shell was 571 ± 27.02 nm and 456 ± 19.17 nm, respectively. The charges on the surface of Brz-PS-PLGA and Brz-PLGA were (-) 27.45 ± 2.98 mV and (-) 19.47 ± 2.83 mV. The transmission electron microscopy images clearly reveal the PS shell as a light black layer over the dark black PLGA core. The CEP allows the high encapsulation of Brz in Brz-PS-PLGA where percentage of entrapment efficiency for Brz-PS-PLGA was 88.13 ± 6.43%. The release study conducted in a simulated tear fluid revealed the sustained release patterns of Brz from Brz-PS-PLGA and these were nontoxic to the cells as revealed by the cytotoxicity studies. Further, the Brz-PS-PLGA enhanced the coronial penetration of Brz and was capable of significantly reducing the intraocular pressure (IOP) after administration to the rabbit eye in comparison to the Brz-PLGA and free Brz. The results clearly suggest that the PS coating significantly enhances the capability of the particles in reducing IOP.

Co-delivery of brinzolamide and miRNA-124 by biodegradable nanoparticles as a strategy for glaucoma therapy.

Co-delivery nanoparticles with characteristics of intracellular precision release drug have been generally accepted as an effective therapeutic strategy for eye diseases. In this study, we designed a new co-delivery system (miRNA/NP-BRZ) as a lasting therapeutic approach to prevent the neuro-destructive after the long-term treatment of glaucoma. Neuroprotective and intraocular pressure (IOP) response were assessed in in vivo and in vitro models of glaucoma. At the meaning time, we describe the preparation of miRNA/NP-BRZ, drug release characteristics, intraocular tracing, pharmacokinetic and pharmacodynamics study and toxicity test. We found that miRNA/NP-BRZ could remarkably decrease IOP and significantly prevent retinal ganglion cell (RGC) damages. The new formula of miRNA-124 encapsulated in PEG-PSA-BRZ nanoparticles exhibits high encapsulation efficiency (EE), drug-loading capacity (DC), and stable controlled-release efficacy (EC). Moreover, we also verified that the miRNA/NP-BRZ system is significantly neuroprotective and nontoxic as well as lowering IOP. This study shows our co-delivery drug system would have a wide potential on social and economic benefits for glaucoma.

Glaucoma: Current treatment and impact of advanced drug delivery systems.

The human eye being a complex and a very sensitive organ makes the drug delivery task challenging. An increase in the intra-ocular pressure at the aqueous humour leads to glaucoma which is not only indecipherable but can also be the reason of blindness for many. The presently available marketed formulations using anti-glaucoma drugs have issues of either difficulty in crossing the blood- retinal barrier or lower systemic bioavailability. Hence, the drugs having lower therapeutic index would need to be administered frequently, which eventually lead to deposition of concentrated solutions at ocular site, producing toxic effects and cellular damage to the eye. To overcome these drawbacks the novel drug delivery systems like In-situ gels, liposomes, niosomes, hydrogel, dendrimers, nanoparticles, solid lipid nanoparticles, Microneedles or ocular inserts play an important role to enhance the therapeutic efficacy of the anti-glaucomic drugs. The present review briefs the current treatments in terms of drugs used and in detail the impact of utilizing the above mentioned novel drug delivery systems in the treatment of glaucoma.

Transfixion technique for the treatment of silicone oil pupillary block glaucoma refractory to Nd-YAG iridotomy.

BACKGROUND: Pupillary block induced by silicon oil in vitrectomized patients is a common condition usually treated with Nd-YAG laser iridotomy or with surgical removal of silicon oil. CASE REPORT: A case of silicone oil pupillary block glaucoma successfully treated with a 30 G needle transfixion technique is described. We performed a non-complicated vitrectomy surgery for retinal detachment with proliferative vitreoretinopathy that included lensectomy, inferior peripheral iridectomy, and silicone oil injection. After surgery, the iridectomy became occluded with fibrous tissue and the intraocular pressure raised to 50 mmHg. After an initial Nd-YAG iridotomy was unsuccessful, we passed a 30 Ga needle through the sclerocorneal limbus and cut the fibrous tissue that blocked the iridectomy. This procedure restored the aqueous humor flow through the iridectomy, pushed back the silicone oil bubble into the vitreous cavity and lowered the intraocular pressure to normal levels. CONCLUSIONS: 30 Ga needle transfixion technique could be an effective, low cost, simple alternative for the treatment of silicone oil pupillary block in aphakic patients.

ANTECEDENTES: El bloqueo pupilar secundario a aceite de silicón en pacientes vitrectomizados es una condición frecuente que normalmente se trata con apertura de la iridectomía con láser Nd-YAG o con el retiro del aceite de silicón. CASO CLÍNICO: Se describe un caso de glaucoma secundario a bloqueo pupilar por aceite de silicón tratado satisfactoriamente con técnica de transfixión con aguja de calibre 30. Realizamos una cirugía de vitrectomía sin complicaciones para el tratamiento de un desprendimiento de retina con vitreorretinopatía proliferativa, que incluyó lensectomía, iridectomía periférica inferior e inyección de aceite de silicón. Después de la cirugía, la iridectomía se ocluyó con tejido fibroso y la presión intraocular se incrementó a 50 mmHg. Después de que una iridotomía inicial con láser Nd-YAG no tuvo éxito, pasamos una aguja de calibre 30 a través del limbo esclerocorneal y cortamos el tejido fibroso que bloqueaba la iridectomía. Este procedimiento restauró el flujo de humor acuoso a través de la iridectomía, desplazando la burbuja de aceite de silicón a la cavidad vítrea, y la presión intraocular descendió a valores normales. CONCLUSIONES: La técnica de transfixión con aguja de calibre 30 puede ser una alternativa efectiva, simple y de bajo costo para el tratamiento del bloqueo pupilar con aceite de silicón en pacientes con afaquia.

Iridogoniodysgenesis: A Challenging Case.

Iridogoniodysgenesis is a rare autosomal dominant disorder affecting anterior segment of the eye. Fifty percent cases of iridogoniodysgenesis have glaucoma, which is particularly difficult to manage. We report here a case of 40 years old man with this rare disorder, presenting to our glaucoma department. It was characterised by iris hypoplasia and juvenile glaucoma. To stop fluctuation in his intraocular pressure (IOP) and to save his vision from glaucomatous damage, our team had to do three different surgical procedures, i.e. trabeculectomy with F5U, diode laser cycloablation and aqueous shunt procedure, over a period of 10 months. This case report discusses management of glaucoma in this particular patient and challenges faced during the treatment. Regular follow-up and timely intervention can save such patients from complete blindness. To authors' knowledge, this is the first reported case of iridogoniodysgenesis in Pakistan.

Incidence and management of elevated intraocular pressure after silicone oil injection.

PURPOSE: To determine the incidence and clinical features of chronic elevated intraocular pressure after pars plana vitrectomy and silicone oil injection for complicated retinal detachments, and to evaluate the clinical management of eyes with secondary glaucoma. METHODS: This was an observational consecutive case series of 450 eyes in 447 patients who were treated with pars plana vitrectomy and silicone oil injection. Patients who developed secondary glaucoma were treated medically with antiglaucoma medications and surgically with glaucoma drainage implants placed in an inferior quadrant. Main outcome measures were intraocular pressure, number of glaucoma medications, surgical success, and complications. RESULTS: Fifty-one of 450 eyes (11%) developed elevated intraocular pressure after pars plana vitrectomy and silicone oil injection whereas 399 eyes (89%) did not have a rise in intraocular pressure. Of the 51 eyes that developed elevated intraocular pressure, 40 (78%) were treated only with glaucoma medicines. Medical therapy reduced the intraocular pressure from a mean +/- SD of 26 +/- 13.4 mm Hg before treatment to 18 +/- 9.1 mm Hg after medical treatment (P = 0.002). The 11 of 51 eyes (22%) with elevated intraocular pressure that failed medical therapy were treated surgically with Ahmed Glaucoma Valve implantation within 12 months of silicone oil injection. In the surgical group, intraocular pressure was reduced from a mean +/- SD of 44 +/- 11.8 mm Hg before surgery to 14 +/- 4.2 mm Hg at the most recent follow-up after surgery (P < 0.001). The number of antiglaucoma medications was reduced from 3.5 +/- 0.7 before surgery to 1.2 +/- 0.5 at the most recent follow-up after surgery (P < 0.001). CONCLUSION: Chronic intraocular pressure elevation occurs in a minority (11%) of patients who are treated with silicone oil. Most of these eyes are effectively treated with antiglaucoma medications. Eyes that do not respond to medical therapy may be effectively managed with glaucoma drainage implant placement in an inferior quadrant.

Design, Fabrication, and In Vitro Testing of an Anti-biofouling Glaucoma Micro-shunt.

Glaucoma, one of the leading causes of irreversible blindness, is a progressive neurodegenerative disease. Chronic elevated intraocular pressure (IOP), a prime risk factor for glaucoma, can be treated by aqueous shunts, implantable devices, which reduce IOP in glaucoma patients by providing alternative aqueous outflow pathways. Although initially effective at delaying glaucoma progression, contemporary aqueous shunts often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. In this work, we introduce a novel micro-device which provides an innovative platform for IOP reduction in glaucoma patients. The device design features an array of parallel micro-channels to provide precision aqueous outflow resistance control. Additionally, the device's microfluidic channels are composed of a unique combination of polyethylene glycol materials in order to provide enhanced biocompatibility and resistance to problematic channel clogging from biofouling of aqueous proteins. The microfabrication process employed to produce the devices results in additional advantages such as enhanced device uniformity and increased manufacturing throughput. Surface characterization experimental results show the device's surfaces exhibit significantly less non-specific protein adsorption compared to traditional implant materials. Results of in vitro flow experiments verify the device's ability to provide aqueous resistance control, continuous long-term stability through 10-day protein flow testing, and safety from risk of infection due to bacterial ingression.

Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 µg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

[Glaucoma secondary to surgery of the posterior eye segment]. / Les glaucomes secondaires à la chirurgie du segment postérieur de l'oeil.

Whether associated with panretinal photocoagulation, scleral buckling, pars plana vitrectomy, intraocular gases or silicone oil injection, transient or sustained elevation of IOP is a frequent complication following vitreoretinal procedures and may be produced by numerous mechanisms. Among the different primary and secondary glaucomas of both closed and open angle type which may occur, silicone oil glaucoma probably raises the most difficult concerns and frequently requires aggressive medical and surgical management with most often modest chances of success. This presentation will focus on the different mechanisms, the risk factors, the clinical diagnosis and the treatment of ocular hypertension and glaucoma resulting from the different vitreoretinal procedures.

[Ultrasonic treatment of hypertonia caused by intraocular silicone oil]. / Traitement par ultra-sons des hypertonies provoquées par l'huile de silicone intra-oculaire.

The authors treated 53 patients with uncontrolled glaucoma in silicone oil filled eyes with high intensity focused ultrasound. The silicone oil filled eyes present unusually difficult problems in glaucoma management, since the silicone oil rapidly obstructs filtration openings, and laser techniques have not been effective. The mean pretreatment pressure was 34.2 mmHg. The patients were followed for a mean of 17 months. Seventy-five per cent of ultrasound treated eyes had successful reduction of intraocular pressure to below 20 mmHg with or without concomitant medical treatment at two years after treatment. The complication rate was low in this group of eyes. Five eyes developed hypotonia and three eyes had full thickness scleral perforations but were effectively controlled and developed no other complications during two years of follow-up. This technique appears more effective than cyclo-destructive techniques alone.

Experimentally designed glaucoma implant surgery with mitomycin C in rabbit.

An attempt was made to observe the possibility of controlling intraocular pressure (IOP) without hypotony and ocular motility disorder by installing an experimentally designed glaucoma implant through a small conjunctival incision with the aid of a stylet and maintaining the aqueous reservoir using mitomycin C (MMC). The implant was made of silicone tube, of which one end was occluded by glue and on the same end 4 check-valve-like slits were made. Thirty-five healthy white rabbits were used and subdivided into 4 groups. In groups I to III, implants having 2.0, 2.5, 3.0 mm slit lengths, respectively, were installed with MMC application in one eye of each of the 10 rabbits. In group IV, a 2 mm slit-length implant was installed without MMC in one eye of each of the 5 rabbits. Pneumatonometry and ultrasonography were performed to check the IOP and the formation of aqueous reservoir in the implanted eyes for 8 weeks. In group I through III, there was a statistically significant 4-5 mmHg pressure-lowering effect in the implanted eyes compared to the contralateral control eyes for 8 weeks. The aqueous reservoirs were observed throughout the follow-up period. In group IV, we could observe neither a pressure-lowering effect nor aqueous reservoir formation in the implanted eyes after 2 weeks postoperatively. Hypotony did not occur in implanted eyes in any of the groups. This study shows the possibility of IOP control by installing a specially designed glaucoma implant with application of MMC.