Long-term Intraocular Pressure Reduction Research Articles

Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.

Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant.

The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues. MMP gene expression by human trabecular meshwork (TM), scleral fibroblast (SF), and ciliary muscle (CM) cells exposed to 10 to 1000 µM bimatoprost or 0.1 to 10 µM BFA (intraocular concentrations after intracameral bimatoprost implant and topical bimatoprost dosing, respectively) was measured by polymerase chain reaction array. Bimatoprost dose-dependently upregulated MMP1 and MMP14 mRNA in all cell types and MMP10 and MMP11 mRNA in TM and CM cells; in TM cells from normal eyes, mean MMP1 mRNA levels were 62.9-fold control levels at 1000 µM bimatoprost. BFA upregulated MMP1 mRNA only in TM and SF cells, to two- to three-fold control levels. The largest changes in extracellular matrix (ECM)-related gene expression by TM cells derived from normal (n = 6) or primary open-angle glaucoma (n = 3) eyes occurred with 1000 µM bimatoprost (statistically significant, ≥50% change for 9-11 of 84 genes on the array, versus 1 gene with 10 µM BFA). Bimatoprost and BFA had differential effects on MMP/ECM gene expression. Dramatic upregulation in MMP1 and downregulation of fibronectin, which occurred only with bimatoprost at high concentrations observed in bimatoprost implant-treated eyes, may promote sustained outflow tissue remodeling and long-term intraocular pressure reduction beyond the duration of intraocular drug bioavailability. Variability in bimatoprost-stimulated MMP upregulation among cell strains from different donors may help explain differential long-term responses of patients to bimatoprost implant.

Use of Latanoprostene Bunod as Adjunctive Glaucoma Therapy in Refractory Glaucoma.

To investigate the long-term efficacy of adjunctive use of latanoprostene bunod (LBN), a new nitric oxide donating prostaglandin medication, in refractory cases of glaucoma at a tertiary care center. A review for patients who received add-on LBN was conducted from 1st January 2018 to 31st August 2020. A total of 33 patients (53 eyes) met the inclusion criteria of being on ≥3 topical medications, having an intraocular pressure measurement prior to starting LBN, and having adequate follow-up. Baseline demographics, prior treatments, adverse effects, and intraocular pressures measured at baseline, 3, 6, and 12 months were recorded. Mean baseline intraocular pressure (IOP) [mm Hg ± standard deviation (SD)] was 19.9 ± 6.0. At 3 months, 49 eyes had a mean IOP of 17.3 ± 5.5 (p < 0.01) with an absolute reduction of 2.6 ± 6.6 and a percent reduction of 9 ± 28%. At 6 months, 35 eyes had a mean IOP of 17.2 ± 4.7 (p < 0.01) with an absolute reduction of 3.6 ± 7.4 and a percent reduction of 11 ± 30%. At 12 months, 28 eyes had a mean IOP of 16 ± 4.5 (p < 0.01) with an absolute reduction of 5.8 ± 7.4 and a percent reduction of 19 ± 38%. Over the course of the study, 18 eyes were lost to follow-up. Three eyes had a laser trabeculoplasty, and four eyes required incisional surgery. No eyes discontinued the medication due to adverse effects. Adjunctive use of LBN in refractory glaucoma showed clinically and statistically significant IOP reductions at 3, 6, and 12-month time points. IOP reduction in patients was stable throughout the course of the study, with the largest decreases seen at the 12-month interval. LBN was well tolerated by patients and may be useful as an additive agent in providing long-term intraocular pressure reduction for patients with severe glaucoma on maximal therapy. Zhou B, Bekerman VP, Khouri AS. Use of Latanoprostene Bunod as Adjunctive Glaucoma Therapy in Refractory Glaucoma. J Curr Glaucoma Pract 2022;16(3):166-169.

Long-term limitations and complications of trans-scleral diode laser cycloablation for refractory glaucoma.

Trans-scleral diode laser cycloablation (cyclodiode) is effective in the short-term management of refractory glaucoma where alternative treatments are not feasible. Long-term outcomes of 5-years or more are not well-documented, particularly in relation to intraocular pressure (IOP) control, need for further procedures and complications such as hypotony and phthisis. A review was undertaken of patient medical records with refractory glaucoma who underwent cyclodiode at City Eye Centre in Brisbane from 2012 to 2016. Data included sex, age, laterality, type of glaucoma, cyclodiode parameters, number of glaucoma medications, visual acuity and treatment with acetazolamide. Data were analysed using generalised linear modelling and Kaplan-Meier analysis. A total of 54 eyes in 54 patients (29 M:25F) with a mean age of 66 years (range 15-85 years) with a minimum of 5 years follow up were included. The mean number of burns was 23.3 (range 12-40) over 180-270 degrees, mean power per burn was 1967 mW (range 1500-2000 mW), with a mean duration of 1981 ms (1500-2000 ms). The mean pre-treatment IOP was 31.5 mmHg (range 17-56 mmHg) and mean IOP 5 years post-treatment was 16.1 mmHg (2-42 mmHg). The mean number of pre-treatment medications was 3.6 (range 1-6) and 2.7 (range 0-5) 5 years post treatment, including 5 (8.3%) on oral acetazolamide. Complications of cyclodiode were seen in 6 (11.1%) patients, including 3 (5.0%) cases of hypotony, and 2 (3.3%) phthisis. Cyclodiode is often utilised for end-stage glaucoma when the IOP is uncontrolled on medical treatment and drainage surgery is not indicated, resulting in long-term reduction of IOP and the number of medications, including acetazolamide. Hypotony and phthisis can be significant complications.

Surgical Advancement of Tenon's Layer During Trabeculectomy Improves Bleb Morphology.

Trabeculectomy surgery remains the gold standard incisional glaucoma surgical procedure in many practices, particularly for patients requiring intraocular pressure (IOP) in the low teens or below. However, trabeculectomy surgery is associated with complications including leakage, over filtration, or fibrosis of the surgical bleb. Morphology of the surgical bleb is an important predictor of surgical success defined as long-term IOP reduction with minimal to no complications. There have been many, often subtle, variations in the surgical technique in hopes of improving long-term IOP reduction. However, fewer changes have been implemented specifically to modify bleb morphology. In our surgical practice, we began performing a thorough dissection and advancement of Tenon's layer with incorporation into the conjunctival closure in a 2-layered manner. This technique allowed flow of aqueous to a delineated potential space between sclera and Tenon's layer. Our clinical observations were improved bleb morphology characterized by diffuse, low-lying blebs with nonischemic overlying conjunctiva compared with those performed with a more traditional trabeculectomy technique. Since we incorporated this change into our practice at a defined time, we have a small number of patients in our practice that had a more traditional trabeculectomy technique in the fellow eye. Therefore, in our surgical practice, a small number of patients had trabeculectomy in 1 eye before implementation of this new technique, and then had trabeculectomy in the fellow eye after this technique was adopted, providing opportunity for comparison of bleb morphology with and without Tenon advancement. In series we present two representative, index cases and describe our surgical technique.

Influence of pars plana vitrectomy for macular surgery on the medium term intraocular pressure.

PurposeTo evaluate the long-term effect of 20 and 23 gauge pars plana vitrectomy (PPV) on intraocular pressure (IOP).MethodsStudy type: Monocentric retrospective cohort study. 249 eyes of 249 patients undergoing PPV due to epiretinal membrane (EM), idiopathic macular hole (IMH) or vitreoretinal traction (VT) were included. The fellow eye served as control. Exclusion criteria were factors known to influence the IOP, such as cataract surgery during follow-up, extended use of steroids, cryotherapy and silicone oil endotamponade. The relative change of IOP (operated vs. fellow eye) at 6–12 months after surgery was defined as primary endpoint. Secondary endpoints were the relative change of IOP at 3–6 and 12–24 months. Possible influencing cofactors were analysed using ANCOVA.ResultsThe primary endpoint did not show a significant IOP reduction of the operated eye relative to the fellow eye (P = 0.089, n = 84). However, the IOP of the operated eye alone was significantly reduced at 6–12 and 12–24 months after surgery (-0.75 ± 2.80 and -1.22 ± 3.29 mmHg, P = 0.008 and 0.007, respectively). The IOP of the fellow eye was also significantly reduced at the 12–24 months period (-0.75 ± 2.73 mmHg, P = 0.008). In the subgroup analysis, sclerotomy size was a significant influencing cofactor, leading to lower IOP after 20G compared to 23G vitrectomy (P = 0.04).ConclusionPars plana vitrectomy did not induce a significant long-term IOP reduction relative to the contralateral eye. However, we observed a IOP lowering potential in 20G vitrectomy.

A novel suprachoroidal microinvasive glaucoma implant: in vivo biocompatibility and biointegration

BackgroundA major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium).ResultsIn two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies.ConclusionsThe novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.

Nano-structured glaucoma drainage implant safely and significantly reduces intraocular pressure in rabbits via post-operative outflow modulation

Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040. Intraocular pressure (IOP) reduction prevents development of glaucoma and vision loss from glaucoma. Glaucoma surgeries reduce IOP by facilitating aqueous humor outflow through a vent fashioned from the wall of the eye (trabeculectomy) or a glaucoma drainage implant (GDI), but surgeries lose efficacy overtime, and the five-year failure rates for trabeculectomy and tube shunts are 25–45%. The majority of surgical failures occur due to fibrosis around the vent. Alternatively, surgical procedures can shunt aqueous humor too well, leading to hypotony. Electrospinning is an appealing manufacturing platform for GDIs, as it allows for incorporation of biocompatible polymers into nano- or micro-fibers that can be configured into devices of myriad combinations of dimensions and conformations. Here, small-lumen, nano-structured glaucoma shunts were manufactured with or without a degradable inner core designed to modulate aqueous humor outflow to provide immediate IOP reduction, prevent post-operative hypotony, and potentially offer significant, long-term IOP reduction. Nano-structured shunts were durable, leak-proof, and demonstrated biocompatibility and patency in rabbit eyes. Importantly, both designs prevented hypotony and significantly reduced IOP for 27 days in normotensive rabbits, demonstrating potential for clinical utility.

Baerveldt glaucoma drainage implant surgery for secondary glaucoma in patients with transthyretin-related familial amyloid polyneuropathy.

To investigate outcomes associated with Baerveldt glaucoma drainage implant (BGI) surgery for refractory glaucoma secondary to transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) with TTR Val30Met mutation. Retrospective case series. Medical records of 5 eyes of 4 patients were reviewed. All patients had refractory glaucoma secondary to FAP with a history of unsuccessful intraocular pressure (IOP) control by trabeculectomy with mitomycin C, underwent BGI surgery, and were followed up for at least 1year. The primary outcome was mean postoperative IOP, and secondary outcomes included the number of ocular hypotensive medications and postoperative complications. The mean postoperative follow-up period was 52.4months. The mean preoperative IOP of 37.0mmHg was reduced to 13.4mmHg immediately postoperatively, and respective subsequent means were 15.8, 13.0, 14.4, and 16.8mmHg at 1, 3, 6, 12, and 24months (P < 0.05). The preoperative mean number of ocular hypotensive medications of 5.4 was reduced to respective means of 2.2, 1.6, 2.8, 2.8, and 2.8 at 1, 3, 6, 12, and 24months. One eye suffered from IOP elevation and underwent cyclophotocoagulation at 26months. Another was dropped from further analyses because of deterioration in the patient's general condition due to FAP progression. The remaining 3 eyes exhibited adequate IOP control (13, 13, 13mmHg) at the final visit. BGI surgery may be the current optimal treatment for patients with refractory glaucoma secondary to TTR-FAP with regard to achieving long-term IOP reduction.

Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 Disruption Using CRISPR-Cas9.

Glaucoma is a common cause of blindness, yet current therapeutic options are imperfect. Clinical trials have invariably shown that reduction in intraocular pressure (IOP) regardless of disease subtype prevents visual loss. Reducing ciliary body aqueous humor production can lower IOP, and the adeno-associated virus ShH10 serotype was identified as able to transduce mouse ciliary body epithelium following intravitreal injection. Using ShH10 to deliver a single vector CRISPR-Cas9 system disrupting Aquaporin 1 resulted in reduced IOP in treated eyes (10.4 ± 2.4 mmHg) compared with control (13.2 ± 2.0 mmHg) or non-injected eyes (13.1 ± 2.8 mmHg; p < 0.001; n = 12). Editing in the aquaporin 1 gene could be detected in ciliary body, and no off-target increases in corneal or retinal thickness were identified. In experimental mouse models of corticosteroid and microbead-induced ocular hypertension, IOP could be reduced to prevent ganglion cell loss (32 ± 4 /mm2) compared with untreated eyes (25 ± 5/mm2; p < 0.01). ShH10 could transduce human ciliary body from post-mortem donor eyes in ex vivo culture with indel formation detectable in the Aquaporin 1 locus. Clinical translation of this approach to patients with glaucoma may permit long-term reduction of IOP following a single injection.

C3 Transferase-Expressing scAAV2 Transduces Ocular Anterior Segment Tissues and Lowers Intraocular Pressure in Mouse and Monkey

Glaucoma is a lifelong disease with elevated intraocular pressure (IOP) as the main risk factor, and reduction of IOP remains the major treatment for this disease. However, current IOP-lowering therapies are far from being satisfactory. We have demonstrated that the lentivirus-mediated exoenzyme C3 transferase (C3) expression in rat and monkey eyes induced relatively long-term IOP reduction. We now show that intracameral injection of self-complementary AAV2 containing a C3 gene into mouse and monkey eyes resulted in morphological changes in trabecular meshwork and IOP reduction. The vector-transduced corneal endothelium and the C3 transgene expression, not vector itself, induced corneal edema as a result of actin-associated endothelial barrier disruption. There was a positive (quadratic) correlation between measured IOP and grade of corneal edema. This is the first report of using an AAV to transduce the trabecular meshwork of monkeys with a gene capable of altering cellular structure and physiology, indicating a potential gene therapy for glaucoma.

Micropulse Transscleral Cyclophotocoagulation: A Look at Long-Term Effectiveness and Outcomes

To investigate the long-term effectiveness of intraocular pressure (IOP) and medication reduction in patients who have undergone micropulse transscleral cyclophotocoagulation (mTS-CPC). Retrospective chart review. A total of 73 eyes of 62 patients treated no more than 1 time with mTS-CPC in a practice in New York City with at least 1 year of follow-up. Treatment was 100 seconds of mTS-CPC with energy titrated on the basis of visual acuity. Paired t test and multivariable analysis were performed with SAS (SAS Institute Inc, Cary, NC). Visual acuity, IOP, medication burden, phthisis, and development of macular edema were followed. Average initial IOP was 25.5±9.4, and average number of initial medications was 3.1±1.1. At 1 year, average IOP was 13.8±7.0 (46% reduction) and average number of medications was 2.5±1.0 (19% reduction). A total of 11 of 15 patients (73.3%) initially taking an oral carbonic anhydrase inhibitor before CPC did not require the oral carbonic anhydrase inhibitor 1 year after treatment. Seventy-six percent of patients obtained at least 20% IOP reduction. Multivariate analysis found IOP reduction was associated with power used and preoperative IOP, whereas medication reduction was associated with initial medication burden. Notably, there was a 57% reduction in IOP at 2500 mW power and a 30% reduction at 2000 mW power. No patients developed macular edema or phthisis from the procedure. Some 18.8% of patients with 20/400 vision or better experienced persistent vision loss of ≥2 lines after the procedure, and 10% of patients with light perception to count finger vision progressed to no light perception (NLP) after the procedure. Of patients with 20/400 vision or better, 12.5% gained ≥2 lines of visual acuity on the Snellen chart at the postoperative year 1 visit. In addition, 15.4% of patients with count fingers to NLP vision improved at the postoperative year 1 visit after treatment. One of 6 patients (16.7%) with NLP gained vision at the postoperative year 1 visit. This study provides evidence that mTS-CPC is a clinically useful procedure associated with good long-term medication burden reduction and IOP reduction that follows a dose-response pattern related to power used.

Trabeculectomy With Mitomycin-C: Outcomes and Risk Factors for Failure in Primary Angle-closure Glaucoma.

There are no reported large series of trabeculectomy with mitomycin-C (MMC) in Western patients with primary angle-closure glaucoma (PACG). Our study evaluates long-term tonometric outcomes of trabeculectomy in PACG. This is a retrospective cohort study. The primary outcomes were the Kaplan-Meier success rates on survival analyses using 3 criteria, with or without adjunctive medication: (A) intraocular pressure (IOP) ≤18 mm Hg and IOP reduction of 20%; (B) IOP≤15 mm Hg and IOP reduction 25%; and (C) IOP≤12 mm Hg and IOP reduction 30%. In total, 136 eyes (102 patients) with PACG who underwent trabeculectomy MMC were included. The Cox proportional hazard regression analysis was used to identify risk factors for failure with multivariate analysis (P<0.05). The qualified success rates (±SD) after 1, 3, and 5 years of follow-up for criterion A were 92% (±2.2%), 78% (±3.8%), and 72% (±4.3%); for criterion B, 86% (±3.0%), 65% (±4.4%), and 59% (±4.7%); and for criterion C, 62% (±4.2%), 40% (±4.5%), and 32% (±4.4%). Baseline factors associated with failure were: family history, absence of laser peripheral iridotomy, higher IOP, and presence of a crystalline lens. Trabeculectomy with MMC effectively reduces IOP in PACG. Long-term IOP reduction is achieved for target IOP levels in the mid-teens. Presence of a crystalline lens, lack of iridotomy and higher preoperative IOP were associated with higher risks of failure.

The STARflo glaucoma implant: preliminary 12months results.

The STARflo glaucoma implant is a drainage-free system designed for the operative treatment of refractory open-angle glaucoma. The purpose of this study is to investigate the safety and efficacy of the STARflo implant. The results of 12months follow-up are presented in patients with open-angle glaucoma, PEX-glaucoma, and congenital glaucoma. A prospective study with a total of over 29 patients (36 eyes), in which the suprachoroidal implantation of the STARflo was indicated for long-term intraocular pressure reduction, is still in process and evaluation. The reduction of intraocular pressure was satisfying after 12months with an average intraocular pressure of 15.0 (± 2.5)mmHg in comparison to 21.08 (± 7.29)mmHg preoperatively. There was a significant 66.7% reduction in local glaucoma drops 12months postoperatively (p< 0.001). Twenty-five percent of the eyes needed further surgery to regulate the intraocular pressure. No intraoperative complications have been reported after the implantation of STARflo. Postoperative complications include hyphema and fibrin formation in the anterior chamber, which were completely resorbed after the first postoperative month. A postoperative intraocular pressure (IOP) elevation was the most common complication after the first 3months. The STARflo implant appears to be a safe and effective alternative treatment method for patients with refractory open-angle glaucoma compared to conventional glaucoma surgery.

Comparison of polypropylene and silicone Ahmed® glaucoma valves in the treatment of neovascular glaucoma: A 2-year follow-up.

Inflammation associated with biomaterials of Ahmed® glaucoma drainage devices may cause the formation of a capsule around the device and can thus have a significant influence on the level of intraocular pressure reduction. The objective of this study was to compare the clinical outcomes after the implantation of a polypropylene or silicone Ahmed® glaucoma valve in patients with neovascular glaucoma. In the study, 27 eyes with neovascular glaucoma (group 1) received silicon Ahmed® valves and 23 eyes (group 2) received polypropylene valves. The best corrected distance visual acuity (BCDVA), intraocular pressure (IOP) and number of anti-glaucomatous drugs were recorded preoperatively and during a follow-up period of 24 months after surgery. Success was defined by the following criteria: 1) intraocular pressure in the rage of 6-21 mm Hg; 2) IOP reduction of at least 30% relative to preoperative values. All complications were registered. One month postoperatively, the mean BCDVA increased significantly in both groups compared to preoperative values (p < 0.001). These values did not change during the 24 months of follow-up examinations. The probability of success defined by criterion 1 at 24 months of observation was 66.7% for silicone and 27.3% for propylene valves group (p < 0.007). According to criterion 2, the difference in success between the groups was not statistically significant. The total number of complications that occurred in both groups during the 24 months of follow-up examinations was similar, except for a higher occurrence of Tenon's cyst formation in the group with a polypropylene valve (18% vs 35%; p < 0.04). In patients with neovascular glaucoma, the implantation of a silicone valve is associated with a significantly higher probability of long-term reduction of IOP below 21 mm Hg and with a lower risk of valve encapsulation in comparison to polypropylene valves. The obtained results suggest that silicone Ahmed® valves are more effective in the treatment of patients with neovascular glaucoma.

Long-term intraocular pressure reduction with intracameral polycaprolactone glaucoma devices that deliver a novel anti-glaucoma agent

Long-term treatment of glaucoma, a major leading cause of blindness, is challenging due to poor patient compliance. Therefore, a drug delivery device that can achieve drug release over several months can be highly beneficial for glaucoma management. Here, we evaluate the long-term pharmacokinetics and therapeutic efficacy of polycaprolactone intracameral drug delivery devices in rabbit eyes. Our study showed that a single drug delivery device loaded with a proprietary hypotensive agent, DE-117, reduced intraocular pressure in normotensive rabbits significantly for 23weeks. In addition, we demonstrated that concentration of DE-117 and its hydrolyzed active form (hDE-117) was maintained in the aqueous humor and the target tissue (iris-ciliary body) up to 24weeks. Our proof-of-concept glaucoma implant shows potential as a long-term treatment that circumvents patient compliance barriers compared to current treatment via eye drops.

Long-Term Subconjunctival Delivery of Brimonidine Tartrate for Glaucoma Treatment Using a Microspheres/Carrier System.

Core-shell polymer microspheres with poly(d,l-lactic-co-glycolic acid) core and poly(l-lactic acid) (PLLA) shell are developed for the long-term subconjunctival release of brimonidine tartrate (BT) in order to reduce intraocular pressure (IOP) in the treatment of glaucoma. The PLLA-rich shell acts as a diffusion barrier, enabling linear release of BT over an extended period of 40 d. The microspheres are encased in a porous non-degradable methacrylate-based carrier for ease of subconjunctival implantation in a glaucoma-induced rabbit model. In vivo release of BT from the microspheres/carrier system has enabled a significant, immediate IOP reduction of 20 mmHg, which is sustained for 55 d. Long-term IOP reduction may be maintained by periodic replacement of the microspheres/carrier system.

Transconjunctival Revision With Mitomycin-C Following Failed Trabeculectomy

To evaluate the efficacy of transconjunctival revision (TCR) with mitomycin-C (MMC) following failed trabeculectomy. The medical records of 27 patients (27 eyes) who underwent TCR with subconjunctival injection of MMC by a single surgeon between September 2001 and August 2013 were retrospectively reviewed. The same surgical protocol was followed for all patients. Revision was performed using a microvitreoretinal blade through a small conjunctival incision. Main outcome measures included visual acuity, intraocular pressure (IOP), and number of glaucoma medications. Failure was defined as an IOP<5 or >14 mm Hg, loss of light perception, or need for additional glaucoma surgery. Mean interval between trabeculectomy and TCR was 56.4±57.2 months. Mean preoperative IOP was 21.9±6.8 mm Hg using 4.0±1.2 glaucoma medications. Fifteen (55.6%) patients met success criteria. At most recent follow-up, mean IOP and number of glaucoma medications for successful patients were 9.7±3.8 mm Hg and 0.6±1.1, respectively. Kaplan-Meier analysis revealed 1-, 2-, and 3-year success rates of 62%, 58%, and 53%, respectively. Three additional patients achieved success after undergoing a second TCR, and 1 patient achieved success after a third TCR. Postoperative complications included transient choroidal effusion (n=8), shallow anterior chamber requiring reformation (n=5), 5-fluorouracil-related corneal epitheliopathy (n=10), and bleb leak (n=1). TCR with adjunctive MMC is a safe and effective procedure following failure of a trabeculectomy. More than 1 revision may be necessary to achieve long-term IOP reduction.

Phaco-Trabeculectomy Equals Trabeculectomy in Lowering IOP-A 4 Years Follow-Up Study

Objective: The aim of this study was to compare the long-term efficacy and safety of combined phacotrabeculectomy (phaco-trab) and trabeculectomy (trab) alone. Methods: Retrospective, non-randomized, interventional case series of phaco-trab and trab. Inclusion criteria were diagnosis of glaucoma for both plus vision impairing coexisting cataracts for phaco-trab. Primary outcome measures were change in intraocular pressure (IOP) and number of anti-glaucoma drugs (AGD) at 1 y and 4 ys after surgery, and postoperative interventions (i.e. laser suture lysis, 5-Fluorouracil injection, needling). Secondary outcome measures were visual acuity and complications. Success was defined based on the criteria from the tubeversus- trabeculectomy study. Results: Mean age was 73.6 ± 8.7 years (28% males; 51% right eyes). Median preoperative IOP was reduced from 22.8 mmHg to postoperative 13.0 mmHg at 1 y and to 14.0 mmHg at 4 ys after phaco-trab (n=62), or in trab alone (n=72) from 21.8 mmHg to 12.0 mmHg at 1 y and 4 ys. AGD were reduced from 2.5 ± 0.8 to 0.1 ± 0.3 1 y and 0.2 ± 0.6 4 ys after phaco-trab, and from 2.6 ± 1.0 to 0.2 ± 0.5 AGD 1 y and 4 ys after trab alone. Both IOP and AGD reduction were statistically indifferent between the groups at all-time points. Mean number of postoperative interventions was 2.1 for phaco-trab and 1.8 for trab (p=0.64). 75% of phaco-trab and 74% of trab eyes fulfilled the criteria for complete success after 4 ys (p=0.844). Conclusion: Both procedures resulted in an equally successful and stable long-term reduction of IOP to the lower teens and AGD requirement, together with a good safety profile. The high number of postoperative interventions in both groups emphasizes the importance of a close follow-up. We therefore conclude that if a close and careful postoperative follow-up can be guaranteed, phaco-trabeculectomy should be the treatment of choice for patients with coexisting cataract and otherwise uncontrolled IOP.

Long-term results of up to 12 years of over 700 cases of viscocanalostomy for open-angle glaucoma.

To study the safety and long-term efficacy of classic viscocanalostomy in patients with open-angle glaucoma (OAG) in different populations. A total of 726 eyes of 726 patients from Europe or South Africa with primary OAG (POAG) and pseudoexfoliative glaucoma (PXFG) were included in this retrospective multicentre study. Complete (qualified) success was defined as an intraocular pressure (IOP) equal to or lower than 21, 18 and 16 mmHg without (with or without) medications, respectively. A failed procedure was defined if IOP was above 21 mmHg, not controllable by laser goniopuncture or medications. The mean IOP before surgery was 42.6 ± 14.2 mmHg for all patients, 29.6 ± 6.6 mmHg for European patients and 48.1 ± 12.9 mmHg for African patients. The follow-up time was 86.2 ± 43.1 months. Mean IOP was 15.4 ± 3.6 mmHg at 5 years, 15.5 ± 4.4 mmHg at 10 years and 16.8 ± 4.2 mmHg at 15 years. The qualified success rate for an IOP of 21, 18 or 16 mmHg or less after 5 years was 92% [95% confidence interval (CI) 0.88-0.96], 70% (95% CI 0.63-0.77) and 43% (95% CI 0.36-0.51) in European patients, and 90% (95% CI 0.87-0.93), 77% (95% CI 0.74-0.81) and 67% (95% CI 0.63-0.72) in African patients, respectively. There was no difference between the success rate for POAG and PXFG for an IOP of 21, 18 or 16 mmHg or less at 5 years (p = 0.64, p = 0.20, p = 0.22, respectively). Laser goniopuncture was performed postoperatively on a total of 127 eyes (17.7%), lowering the pressure from 23.1 ± 1.9 mmHg to 15.0 ± 2.2 mmHg. There were no significant complications, in particular, no blebitis or endophthalmitis. Viscocanalostomy produced a sustained long-term reduction of IOP with a low-risk profile in European and African patients with OAG over 12 years.