Phase 3 Randomized Clinical Trial of the Safety and Efficacy of Travoprost Intraocular Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial). DESIGN: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial. PARTICIPANTS: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline. METHODS: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193). MAIN OUTCOME MEASURES: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments. RESULTS: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis). CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Qualitative Development of the Allergan Satisfaction with Treatment Experience Questionnaire (ASTEQ) Instrument, a Patient-Reported Outcome Measure in Glaucoma and Ocular Hypertension.

INTRODUCTION: Sustained-release intraocular implants provide a therapeutic option for open-angle glaucoma (OAG) and ocular hypertension (OHT) patients who are non-compliant with eyedrops. Currently, there are no published patient-reported outcome (PRO) measures that assess treatment satisfaction with intraocular implants. To address this gap, a new PRO instrument, the Allergan Satisfaction with Treatment Experience Questionnaire (ASTEQ), has been developed in accordance with Food and Drug Administration guidance. METHODS: Qualitative research interviews were conducted among patients with OAG/OHT who had received three intraocular injections of a sustained-release bimatoprost (10 or 15 µg) implant within the clinical trial setting. A preliminary conceptual framework capturing treatment satisfaction concepts in glaucoma, as identified from the literature, was used to develop a semi-structured interview guide. A concept elicitation (CE) interview to identify aspects of the glaucoma treatment experience pertinent to intraocular implants provided content for a draft instrument. A cognitive debriefing (CD) interview to test the instrument's interpretability, relevance, and validity informed its subsequent refinement. Interview analysis followed a grounded theory approach to identify data patterns and relationships. RESULTS: CE interviews (n = 19) indicated that participants' main considerations in rating satisfaction with implant treatment were physical comfort during preparation for the implant and implant administration, anxiety about the procedure, frequency of implant administration, possible side effects, convenience and accessibility of the implant, relationship with the clinician, and lifestyle fit. Draft ASTEQ revision based on CD interviews (n = 20) and readability tests yielded a nine-item ASTEQ instrument comprising satisfaction with overall implant experience and frequency of administration, occurrence/bother of immediate and long-term side effects, worry about implant administration and possible risks/side effects, and physical discomfort during preparation for the implant and implant administration. CONCLUSION: The ASTEQ instrument has demonstrated content validity in patients with OAG/OHT treated with a sustained-release bimatoprost implant. Further research is necessary to evaluate its psychometric properties.

Intravitreal DEX Implant for the Treatment of Diabetic Macular Edema: A Review of National Consensus.

Diabetic macular edema (DME)'s therapeutic approach can frequently be challenging. The purpose of the review is to propose evidence-based recommendations on the employment of intravitreal dexamethasone implants (DEX) when approaching patients suffering from DME. Seven national consensuses redacted by different groups of retina specialists from Europe and Asia were examined and confronted. Each consensus was redacted utilizing a Delphi approach, in person meetings, or by reviewing the literature. DEX can be studied as a first-line strategy in individuals suffering from DME with inflammatory OCT biomarkers, in vitrectomized eyes, in patients with recent cardiovascular events, in pregnant women, in patients scheduled to undergo cataract surgery or with poor compliance. The other parameters considered were the indications to the DME treatment, when to switch to DEX, the definition of non-responder to anti-VEGFs agents and to the DEX implant, whether to combine DEX with laser photocoagulation, the association between glaucoma and DEX, and the management of DEX and the cataract. Although several years have passed since the introduction of DEX implants in the DME treatment, there is still not a unified agreement among retina specialists. This paper compares the approach in the DME treatment between countries from different continents and provides a broader and worldwide perspective of the topic.

Pathogenesis and current therapies for non-infectious uveitis.

Non-infectious uveitis (NIU) is a disorder with various etiologies and is characterized by eye inflammation, mainly affecting people of working age. An accurate diagnosis of NIU is crucial for appropriate therapy. The aim of therapy is to improve vision, relieve ocular inflammation, prevent relapse, and avoid treatment side effects. At present, corticosteroids are the mainstay of topical or systemic therapy. However, repeated injections are required for the treatment of chronic NIU. Recently, new drug delivery systems that may ensure intraocular delivery of therapeutic drug levels have been highlighted. Furthermore, with the development of immunosuppressants and biologics, specific therapies can be selected based on the needs of each patient. Immunosuppressants used in the treatment of NIU include calcineurin inhibitors and antimetabolites. However, systemic immunosuppressive therapy itself is associated with adverse effects due to the inhibition of immune function. In patients with refractory NIU or those who cannot tolerate corticosteroids and immunosuppressors, biologics have emerged as alternative treatments. Thus, to improve the prognosis of patients with NIU, NIU should be managed with different drugs according to the response to treatment and possible side effects.

Capsulotomía Nd-Yag Láser en Pseudofáquicos con OCP

Una de las causas de la disminución de la visión es la catarata. El tratamiento es la extracción del cristalino opaco con reemplazo por un lente intraocular (LIO). La opacidad de cápsula posterior (OCP) es una complicación frecuente a largo plazo. Las modificaciones en el diseño del LIO tanto del material y la forma tienen mayor importancia para prevenir la OCP. Como tratamiento está la capsulotomía neodimio YAG láser. Objetivo: identificar la OCP relacionado con el tipo de LIO implantado en pacientes pseudofáquicos en la FBO, entre el periodo de marzo del 2019 hasta febrero del 2022. Métodos: estudio observacional, tipo analítico, subtipo cohorte histórica, retro- prospectiva y longitudinal, con enfoque de análisis estadístico de tipo cuantitativo. Resultados: predominó el género femenino con un 60 % y un 40 % representaba al masculino; un 60,3 % del total tenían entre 65 a 80 años. La OCP en los 3 tipos de lentes intraoculares (acrílico y PMMA) ocasionó una disminución en la agudeza visual: el 37 %, predominó, por el LIO hidrofóbico, 36 % por el LIO PMMA y destacamos que el 27 % fue por el LIO hidrofílico. La incidencia de OCP a 5 años fue del 32 %. No se registró ningún efecto adverso en nuestro estudio. Conclusiones: la OCP provoca una baja de agudeza visual leve a moderada en los 3 tipos de LIOs; con un mínimo predominio de BAV leve para el tipo de LIO hidrofóbico comparado con el hidrofílico. Además después de la capsulotomía un gran porcentaje tiene entre 20/20 a 20/25 de AV mejor corregida.

One of the causes of decreased vision is cataract. Treatment is removal of the cloudy lens with replacement by an intraocular lens (IOL). Posterior capsule opacity (PCO) is a common long-term complication. Modifications in the design of the IOL both in terms of material and shape are of greater importance in preventing PCO. Treatment is neodymium YAG laser capsulotomy. Objective: to identify the PCO related to the type of IOL implanted in pseudophakic patients in the FBO, from March 2019 to February 2022. Methods: observational study, analytical type, historical cohort subtype, retro-prospective and longitudinal, with a quantitative statistical analysis approach. Results: the female gender predominated with 60% and 41% represented the male; 60.3% of the total was between 65 and 80 years old. PCO in the 3 types of intraocular lenses (acrylic and PMMA) caused a decrease in visual acuity: 37%, predominated, due to the hydrophobic IOL, 36% due to the PMMA IOL and we highlight that 27% was due to the hydrophilic IOL. The incidence of PCO at 5 years was 32%. No adverse effect was recorded in our study. Conclusion: PCO causes mild to moderate visual acuity loss in all 3 types of IOLs; with a minimal predominance of mild AVB for the hydrophobic IOL type compared to the hydrophilic one. In addition, after capsulotomy, a large percentage has between 20/20 and 20/25 better corrected visual acuity.

An overview of the influence and design of biomaterial of the intraocular implant of the posterior capsule opacification.

Posterior capsule opacification remains till nowadays one of the most hypothetical problems concerning the cataract surgery. When it comes in preventing PCO, this complication is made in multiple ways that concern, along with the surgery steps, the choice for the biomaterial of the intraocular implant lens. The concern of influence of the type of the used material (hydro-phob/ hydro-philic), of the design of the implant (1-piece IOL = monobloc vs. 3 - piece IOL - multipiece) and with the design at the edge, they all have been considered in multiple studies. This article performs a synthesis of those studies and establishes conclusions regarding possible choices. Abbreviations: PCO = Posterior capsule opacification, IOL = intraocular lens; LEC = lens epithelial cells.

[Recurrence of capsular pseudoexfoliation on intraocular implant]. / Récidive d'une pseudo-exfoliation capsulaire sur implant intraoculaire.

We here report the case of a 79-year old patient who underwent cataract by phacoemulsification associated with preoperative left and right eyes pseudo-capsular exfoliation in 2000. He had pseudo-exfoliative glaucoma with recurrence on the implant.

A new endocapsular open ring for prevention of anterior and posterior capsule opacification.

PURPOSE: The aim of this study is to demonstrate the functionality of a new design of a thick endocapsular open ring for prevention of anterior capsule opacification (ACO) and posterior capsule opacification (PCO). SETTING: The Institute of Vision and Optics, University of Crete and University Hospital of Heraklion, Crete, Greece. DESIGN: Prospective, interventional pilot study. METHODS: Fifteen patients (17 eyes) underwent cataract surgery with phacoemulsification. During surgery, a thick endocapsular open ring (peripheral capsule reconstructor) was inserted into the capsular bag, prior to intraocular lens (IOL) implantation. Six different models of IOL were implanted. Postoperatively, the degree of ACO and PCO was evaluated and described as none, mild, moderate, or severe. RESULTS: The mean follow-up period was 30±8.06 months (range: 12-36 months). At the last follow-up, mild PCO was observed in only three eyes and mild ACO in three patients. The centration of IOLs was good in all but one eye, which had a tilted IOL. CONCLUSION: The results of this pilot study suggest that the implantation of a new design of thick endocapsular open ring is feasible and may contribute to the prevention of PCO and ACO after cataract surgery.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Laser-triggered intraocular implant to induce photodynamic therapy for posterior capsule opacification prevention.

Posterior capsule opacification (PCO) is one of the main reasons for loss of vision again after cataract surgery. In this study, intraocular lenses were modified with indocyanine green (ICG) and sealed up with PLGA to form long-term intraocular implants (ICG-IOL). When triggered by laser, ICG-IOL would induce photodynamic therapy (PDT). In-vitro cell viability assay and scratch wound healing assay demonstrated that ICG-IOL could effectively inhibit HLEpiC proliferation and migration without causing damage to the cells far away from it. Laser attenuation test indicated that ICG-IOL could be applied in vivo. In-vivo pharmacodynamics and safety study showed that ICG-IOL could significantly prevent the occurrence of PCO and was safe for intraocular normal tissue. All these results suggested that ICG-IOL would be a very promising candidate for PCO prevention.

Intraocular Implants for the Treatment of Autoimmune Uveitis.

Uveitis is the third leading cause of blindness in developed countries. Currently, the most widely used treatment of non-infectious uveitis is corticosteroids. Posterior uveitis and macular edema can be treated with intraocular injection of corticosteroids, however, this is problematic in chronic cases because of the need for repeat injections. Another option is systemic immunosuppressive therapies that have their own undesirable side effects. These systemic therapies result in a widespread suppression of the entire immune system, leaving the patient susceptible to infection. Therefore, an effective localized treatment option is preferred. With the recent advances in bioengineering, biodegradable polymers that allow for a slow sustained-release of a medication. These advances have culminated in drug delivery implants that are food and drug administration (FDA) approved for the treatment of non-infectious uveitis. In this review, we discuss the types of ocular implants available and some of the polymers used, implants used for the treatment of non-infectious uveitis, and bioengineered alternatives that are on the horizon.

Design and development of intraocular polymeric implant systems for long-term controlled-release of clindamycin phosphate for toxoplasmic retinochoroiditis.

BACKGROUND: The release of the anti-toxoplasmosis drug, clindamycin phosphate, from intraocular implants of the biodegradable polymers poly (D, L-lactic acid) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) has been studied in vitro. MATERIALS AND METHODS: The preparation of the implants was performed by a melt-extrusion method. The developed extrudates were characterized and compared in in-vitro release profiles for elucidating the drug release mechanism. The formulations containing up to 40% w/w of drug were prepared. Release data in phosphate buffer (pH 7.4) were analyzed by high performance liquid chromatography. The release kinetics were fitted to the zero-order, Higuchi's square-root, first order and the Korsmeyer-Peppas empirical equations for the estimation of various parameters of the drug release curves. Degradation of implants was also investigated morphologically with time (Scanning Electron Microscopy). RESULTS: It was observed that, the release profiles for the formulations exhibit a typical biphasic profile for bulk-eroding systems, characterized by a first phase of burst release (in first 24 hrs), followed by a phase of slower release. The duration of the secondary phase was found to be proportional to the molecular weight and monomer ratio of copolymers and also polymer-to-drug ratios. It was confirmed that Higuchi and first-order kinetics were the predominant release mechanisms than zero order kinetic. The Korsmeyer-Peppas exponent (n) ranged between 0.10 and 0.96. This value, confirmed fickian as the dominant mechanism for PLA formulations (n ≤ 0.45) and the anomalous mechanism, for PLGAs (0.45 < n < 0.90). CONCLUSION: The implant of PLA (I.V. 0.2) containing 20% w/w of clindamycin, was identified as the optimum formulation in providing continuous efficient in-vitro release of clindamycin for about 5 weeks.

Premium IOLs in Glaucoma.

Advanced technology or premium intraocular lenses have been developed to meet the patient expectations of perfect distance and near vision without the need for spectacles. Careful patient selection is critical when implanting these implants. This brief review focusses mainly on multifocal and toric IOLs and their application and limitations in patients with glaucoma. How to cite this article: Ichhpujani P, Bhartiya S, Sharma A. Premium IOLs in Glaucoma. J Current Glau Prac 2013;7(2): 54-57.