Intraocular Pressure In Rabbits Research Articles

A digoxin derivative that potently reduces intraocular pressure: efficacy and mechanism of action in different animal models.

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human α2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the α2 isoform of Na,K-ATPase, which is expressed strongly in nonpigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive nonhuman primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 h) and extended (7-10 days) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. 1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. 2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicate that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.NEW & NOTEWORTHY When applied topically, a cyclobutyl derivative of digoxin (DcB) potently reduces intraocular pressure in an ocular hypertensive nonhuman primate model (Macaca fascicularis), associated with increased aqueous humor (AH) flow rate (AFR). The mechanism of action of DcB involves increased AH outflow facility as detected in enucleated perfused porcine eyes and, in parallel, increased (AH) inflow as detected in isolated porcine ciliary epithelium. DcB might have potential as a drug for the treatment of open-angle human glaucoma.

A Direct Comparison of Peptide Drug Delivery Systems Based on the Use of Hybrid Calcium Phosphate/Chitosan Nanoparticles versus Unmixed Calcium Phosphate or Chitosan Nanoparticles In Vitro and In Vivo.

Nanocarriers provide a number of undeniable advantages that could improve the bioavailability of active agents for human, animal, and plant cells. In this study, we compared hybrid nanoparticles (HNPs) consisting of a calcium phosphate core coated with chitosan with unmixed calcium phosphate (CaP) and chitosan nanoparticles (CSNPs) as carriers of a model substrate, enalaprilat. This tripeptide analog is an inhibitor of angiotensin-converting enzyme and was chosen by its ability to lower intraocular pressure (IOP). In particular, we evaluated the physicochemical characteristics of the particles using dynamic light scattering (DLS) and scanning electron microscopy (SEM) and analyzed their ability to incorporate and release enalaprilat. HNPs exhibited the highest drug loading capacity and both HNPs and CSNPs demonstrated slow drug release. The comparison of the physiological effects of enalaprilat-loaded CaP particles, HNPs, and CSNPs in terms of their impact on IOP in rabbits revealed a clear advantage of hybrid nanoparticles over both inorganic and chitosan nanoparticles. These results could have important mechanistic implications for developing nano-based delivery systems for other medical, veterinary, and agricultural applications.

Modeling experimental glaucoma for screening studies of antiglaucomatous activity

Introduction: In vivo screening studies, in which the efficacy of dozens of drugs is tested to select several applicants for further study of their safety in humans, are the main stage in the study of the pharmacodynamics of promising antiglaucoma drugs. This imposes a number of specific requirements both on experimental models of glaucoma and on laboratory animals used in the experiment.
 Materials and Methods: 32 male rabbits of the Soviet Сhinchilla breed, 6 male albino rabbits weighing 3-3.5 kg, and 20 outbred white rats weighing 220-250 g were used in total in experiments to reproduce the glaucoma process. All manipulations on the rabbit eye were performed by an ophthalmologist under general anesthesia with telazol. Triamcinolone (vitreous injection) was used to simulate glaucoma in rabbits, lauromacrogol 400 or fine kaolin (anterior chamber injection) was used to simulate glaucoma in rabbits; adrenaline hydrochloride (intraperitoneal administration) was used to simulate glaucoma in rats.
 Results and Discussion: Double intravitreal administration of a suspension of triamcinolone at a dose of 4 mg was the most attractive model in terms of the technique of reproducing the pathology and the results obtained in modeling glaucoma in rabbits. However, this model did not produce a stable increase in intraocular pressure (IOP). Doubling the dose of triamcinolone and replacing chinchilla rabbits with albinos did not lead to a positive result. The introduction of the venous sclerosing drug lauromacrogol 400 into the anterior chamber of the eye proved to be ineffective either. The introduction of finely dispersed kaolin into the anterior chamber of the eye of rabbits led to a persistent increase in IOP. The intraperitoneal administration of epinephrine hydrochloride to rats according to the described method gave no stable results. The increase in IOP became stable only after a significant increase in the dose of adrenaline.
 Conclusion: The conducted studies of four models of glaucoma and their three modifications in animals made it possible to select two of them, which contributed to a stable and fairly long-term increase in IOP in rabbits (introduction of finely dispersed kaolin into the anterior chamber of the eye) and rats (adrenaline-induced model).

The Repeatability and Reproducibility of a New Minimally Invasive Method for Orbital Pressure Measurement.

Evaluation of orbital pressure is crucial for monitoring various orbital disorders. However, there is currently no reliable technique to accurately measure direct orbital pressure (DOP). This study aimed to establish a new method for the DOP as well as to verify its repeatability and reproducibility in rabbits. The study included 30 normal eyes from fifteen 3-month-old New Zealand white rabbits. After administering inhalation anesthesia, intraocular pressure (IOP) was determined by tonometry (Tonopen). For DOP manometry, a TSD104 pressure transducer was inserted between the disposable injection needle and the syringe, and the output results were displayed on a computer. Two observers independently participated in the experiment to verify its repeatability and reproducibility. The mean IOP of rabbits was significantly higher than the DOP in normal rabbits (11.67 ± 1.08 mm Hg versus 4.91 ± 0.86 mm Hg, P < 0.001). No significant interocular difference was detected for both IOP and DOP ( P > 0.05). A high correlation was found for intraobserver measurements of both IOP (intraclass correlation coefficient = 0.87, P < 0.001) and DOP (intraclass correlation coefficient = 0.89, P < 0.001). A high agreement was also presented for the interobserver reproducibility for the measurements of IOP [Pearson correlation coefficient ( R ) = 0.86, P < 0.001] and DOP ( R = 0.87, P < 0.001). Direct orbital pressure was positively correlated with IOP in both observers ( R 1 = 0.66, R 2 = 0.62, P < 0.001). The Bland-Altman plots revealed that 5.0% (3/60) of the IOP and DOP measurement points were outside of the 95% limits of agreement, respectively. The TSD104 pressure transducer-based manometry may serve as a reliable device for the measurement of DOP, providing real-time measuring results with acceptable reproducibility and repeatability.

Pharmacological Properties of Sulfonamide Derivatives, New Inhibitors of Carbonic Anhydrase.

Selective blocking of individual isoforms of carbonic anhydrase (CA) is now one of the main directions in the development of its inhibitors. The new 1,2,4-oxadiazole-containing sulfonamides B12 and B13 predominantly block CA II and CA IX. The study of acute toxicity of B12 and B13 showed their safety. Substance B13 caused a relatively short-term, but rapid (within 30 min) decrease in the intraocular pressure in rabbits, which indicates the promise of its use for the emergency decrease in the intraocular pressure in medical practice. Analysis of the effects of sulfonamides on the functions of CNS showed that compound B12 probably exhibit tranquilizing activity; B13 is promising for the creation of drugs that have an antidepressant effect and at the same time increase the mental and physical performance.

Injection of New PMMA* Loaded Microspheres into Anterior Chamber to Establish a Rabbit Glaucoma Model

Objective: To develop a novel PMMA material microsphere and characterize it. Named it PMMA*.The microsphere was loaded with drugs, and the intraocular pressure of rabbits was increased by anterior chamber injection, so as to establish a new animal model of ocular hypertension. Methods: PMMA* microspheres with a diameter of 50-80μm were prepared, and the drug loading, release and biosafety of PMMA* microspheres were analyzed. PMMA* microsphere suspension was prepared at 1% dosage of atropine sulfate. Eighteen healthy male New Zealand white rabbits were selected, with the right eye as the experimental eye and the left eye as the control eye. They were randomly divided into blank microsphere group, atropine sulfate group and atropine sulfate loaded microsphere group with 6 rabbits in each group. The chronic ocular hypertension model of the right eye was established. Intraocular pressure was monitored postoperatively and Micro-CT was used to determine the position of the microsphere at the anterior chamber Angle. The pathological changes of chronic glaucoma were studied. Results: PMMA* microspheres have the characteristics of micropore structure, adjustable size, slow release, in situ residence and good biosafety. There was no significant difference in preoperative intraocular pressure in rabbits (P>0.05), which was comparable. At 15 days after surgery, the intraocular pressure in experimental eyes was significantly higher than that in control eyes, with statistical significance (P<0.05), and the increase of intraocular pressure caused by drug-loaded PMMA* microspheres was more significant. Micro-CT determined the position of the microsphere in the anterior chamber Angle of rabbit. The atropine sulfate loaded microspheres showed more obvious ganglion cell - retinal nerve fiber layer damage. Conclusions:The PMMA* microspheres synthesized in this study have good drug loading performance and slow release performance. Intraventral injection of drug-loaded PMMA* microspheres can block the outflow of aqueous solution to establish a better chronic glaucoma model.

Formulation and evaluation of polymer-coated bimatoprost-chitosan matrix ocular inserts for sustained lowering of IOP in rabbits

Bimatoprost (BIM), a prostaglandin analog is a promising drug for treating glaucomic symptoms. However, Bimatoprost has short elimination half life in addition, the eye drops that are most prevalently sold on the market have a shorter ocular residence time; as a result, the drug has a poor bioavailability. The current study's goal was to create and test a promising sustained-release ocular insert for bimatoprost. By the solvent casting method BIM-chitosan matrix was prepared and the dried film was coated with Polycaprolactone (PCL)/PCL-PVA solution. Studies on swelling index, ATR-FTIR, drug content uniformity were used to characterise the inserts. SEM was used to observe surface morphology of uncoated insert, and PCL and PVP K 30 coated inserts. And thickness of the ocular insert (51 μm). In vitro studies were carried out using Franz diffusion cells. In vivo studies were conducted on healthy rabbits to examine changes in intraocular pressure (IOP), showed IOP of 15.9 mmHg for BIM-PCL insert and 14.6 mmHg for BIM-PVP insert at 120 h. This confirmed that the BIM inserts were able to have sustained reduction of IOP for a period of six days.

Novel Metoprolol-Loaded Chitosan-Coated Deformable Liposomes in Thermosensitive In Situ Gels for the Management of Glaucoma: A Repurposing Approach.

Glaucoma is a long-term eye disease associated with high intraocular pressure (IOP), which seriously damages the eyes, causing blindness. For successful therapy, potent drugs and delivery systems are required. Metoprolol (MT) is believed to help reduce elevated IOP. The paradigm of ocular therapeutics may be changed by the integration of chitosan-coated liposomes (CLPs) with thermosensitive in situ gel (ISG). Therefore, MT-CLPs were developed and characterized and compared to uncoated ones (MT-LPs). Furthermore, MT-LP- and MT-CLP-loaded ISGs were prepared and characterized in in vitro, ex vivo, and in vivo studies. MT-LPs and MT-CLPs displayed spherical shapes with nanosize range, reasonable EE%, and significant bioadhesion. The zeta potential changed from negative to positive after CS coating. The extended in vitro drug release of MT-CLPs showed significant mucin mucoadhesion. The formed ISGs were homogeneous with a pH range of 7.34 to 7.08 and a rapid sol–gel transition at physiological temperature. MT-ISG1 (MT-LP) and MT-ISG2 (MT-CLPs-0.5) could increase ocular permeability by 2-fold and 4.4-fold compared to MT-ISG (pure MT). MT-ISG2 demonstrated significantly reduced IOP in rabbits without causing any irritation. In conclusion, MT-ISG2 markedly enhanced corneal permeability and reduced IOP. They would be promising carriers for MT for glaucoma management.

Variation of intraocular pressure comparing rebound (TONOVET Plus®) and applanation (TONO-PEN VET®) tonometry in New Zealand rabbits treated with Amlodipine®

Rabbits have played an important role in ophthalmological research processes, however in the environment there has been a deficiency of sensitive equipment in measurement of intraocular pressure for this species. To compare intraocular pressure (IOP) measured with rebound (TONOVET Plus®) and applanation (TONO-PEN VET®) tonometry in healthy New Zealand rabbits treated with Amlodipine. Twelve healthy male New Zealand white rabbits, 5 months old; two groups with 6 individuals were used in this study. The experimental group was given Amlodipine® at a dose of 5 mg/kg, once a day for a month. Blood pressure and intraocular pressure were measurement before treatment and 6 h after treatment in a period of one month. A trend is noted where the group of animals treated with amlodipine® presents lower values than the control group, both in systolic and diastolic pressure. The systolic pressure of the control group showed an average of 116.5 ± 7.9 mmHg and 117.4 ± 8.9 mmHg and the treatment group showed an average of 113.6 ± 7.9 mmHg and 111.8 ± 10.0 mmHg (pretreatment and posttreatment respectively). Tonometry: the values obtained using the TONOVET Plus® (19 ± 3 mmHg) are on average higher than the values obtained using the TONO-PEN VET® (17 ± 3 mmHg). It was possible to demonstrate the relationship between systemic blood pressure and intraocular pressure in New Zealand white rabbits. Rebound tonometry showed less variability in results than applanation tonometry. This study confirmed that both tonometers are reliable for measuring IOP in rabbits.

Formulation and evaluation of brinzolamide encapsulated niosomal in-situ gel for sustained reduction of IOP in rabbits

Glaucoma, the multifactorial disease of the eye, is characterized by many biological risk factors as well as genetic factors which lead to degeneration of optic nerves. The major factor which is associated with glaucoma is increase in intraocular pressure (IOP). Treatment for glaucoma should be such that to reduce the IOP either by decreasing the production of aqueous humor or by enhancing its drainage. Currently, the most commonly used approach is the use of conventional ophthalmic eye drops, which accounts for approximately more than 90% of the available marketed ophthalmic dosage forms. Brinzolamide, the carbonic anhydrase inhibitor, in the present study has been formulated as niosomes to provide a sustained action and compared with niosomal in-situ gel loading Brinzolamide. Brinzolamide loaded niosomes had vesicle size of 236.2 ± 3.1 nm and a high zeta potential of −46.2 ± 3.1 mV. A high Encapsulation efficiency of 79.99 ± 2.2% and a sustained release profile in vitro for 24 h. The Niosomal in-situ gel system showed good gelation capacity and adequate spreadability. In-vivo studies conducted on healthy New Zealand white rabbits showed maximum IOP reduction at 8 h and maintained IOP reduction effect till 24 h. The study showed a sustained release of Brinzolamide from the niosomal in-situ gel and a sustained reduction in IOP in rabbits for 24 h with a single administration.

Chitosan-covered calcium phosphate particles as a drug vehicle for delivery to the eye

Formulations on the base of an inhibitor of angiotensin-converting enzyme, enalaprilat, were prepared by the inclusion of the drug into calcium phosphate (CaP)-particles in situ, followed by the covering of the particles with 5 kDa chitosan or 72 kDa glycol chitosan and cross-linking with sodium tripolyphosphate. Physicochemical characterization of the resulted hybrid particles was conducted using dynamic light scattering, as well as scanning and transmission electron microscopy. Enalaprilat-containing particles had a mean hydrodynamic diameter 180 nm and 260 nm and ζ-potential +7 mV and +16 mV for 5 kDa and 72 kDa chitosans, respectively. In vivo studies showed that enalaprilat within particles stayed longer in the tear fluid after single instillation and caused a significantly pronounced and prolonged decrease of intraocular pressure in rabbits, especially in the case of CaP-particles, covered by glycol chitosan. Thus, such formulations demonstrate potential as prospective therapeutic agents for the treatment of eye diseases.

Repeatability, reproducibility, and agreement of three tonometers for measuring intraocular pressure in rabbits

The aim of this study was to evaluate repeatability, reproducibility, and agreement of three commonly used tonometers in animal research (TonoLab, TonoVet, and TonoPEN AVIA) in a cohort of 24 rabbits. Additionally, the impact of sedation on IOP was investigated in 21 New Zealand White rabbits with the TonoVet tonometer. Repeatability was determined using the coefficient of variation (CoV) for two observers. For the TonoLab (6.55%) and TonoVet (6.38%) the CoV was lower than for the TonoPEN AVIA (10.88%). The reproducibility was highest for the TonoVet (0.2 ± 3.3 mmHg), followed by the TonoLab (0 ± 12.89 mmHg) and lowest for the TonoPEN AVIA (− 1.48 ± 10.3 mmHg). The TonoLab and TonoVet showed the highest agreement (r = 0.85, R2 = 0.73). After sedation, a significant IOP reduction (often > 25%) was observed. Our results show that among the three tonometers tested, the TonoVet tonometer is best for use in rabbits while the TonoLab should be avoided. The impact of sedation on IOP was substantial and should be taken into account during experimentation.

Edward S Perkins, MD, PhD (1919-2015): In the vanguard of ophthalmic physician-scientists.

British-American ophthalmologist Edward Perkins, MD, PhD (1919-2015) held wide-ranging research interests during his career at the Institute of Ophthalmology in London, the University of Iowa, and as a military doctor stationed in Kenya. With his PhD and a medical degree, Perkins was in the vanguard of clinician-scientists who possessed such dual credentials, enabling him to perform noteworthy experimental and clinical research. Perkins' glaucoma research included early work on acetazolamide and prostaglandins, laser iridotomy, and large-scale glaucoma surveys such as the Bedford Glaucoma Survey. In 1957, Perkins earned a PhD with a thesis on cranial nerve influences on rabbit intraocular pressure. Perkins also invented a handheld applanation tonometer; wrote an entire volume on uveitis for Duke-Elder's system of Ophthalmology; co-founded the Association for Eye Research (the European Association for Vision and Eye Research forerunner); and was a charter member of the Glaucoma Research Society. In 1961, Perkins became the first Professor of Experimental Ophthalmology at the Institute of Ophthalmology in London. In 1979, Perkins and his family emigrated to the United States, where he became a Professor of Ophthalmology at the University of Iowa. Perkins' understated personality masked a legacy of extensive contributions to the field of ophthalmology.

This issue of ACTA

This issue of ACTA

Ингибиторы ангиотензин-превращающего фермента в составе кальций-фосфатных наночастиц как перспективные препараты для снижения внутриглазного давления

Purpose. To find out the possibility of using angiotensin-converting enzyme (ACE) inhibitors included in calcium-phosphate nanoparticles (CFPs) to reduce intraocular pressure (IOP). Material and methods. Preparation of calcium-phosphate nanoparticles, introduction of ACEI in them, comparative evaluation of the action of enalaprilat, lisinopril and the beta-blocker timolol in the composition of CPF by determining their effect on intraocular pressure in rabbits. Results. Enalaprilat, lisinopril and the beta-blocker timolol in the composition of CPF statistically more significantly reduce intraocular pressure compared to simple solutions of these drugs. Conclusion. The introduction of drugs that reduce IOP into the CPF increases their bioavailability with the instillation method of administration, while their biological activity is preserved, and the effectiveness of the therapeutic effect increases. The results indicates the prospects of using CFPs to include ocular antihypertensive drugs used in the form of eye drops. Key words: calcium-phosphate nanoparticles, angiotensin-converting enzyme inhibitor, intraocular pressure.

NCX 667, a Novel Nitric Oxide Donor, Lowers Intraocular Pressure in Rabbits, Dogs, and Non-Human Primates and Enhances TGFβ2-Induced Outflow in HTM/HSC Constructs.

PurposeNCX 667, a novel nitric oxide (NO) donor with an isomannide core, was characterized for its IOP-lowering ability in animal models of ocular hypertension and glaucoma. Bioengineered human trabecular meshwork/Schlemm's canal (HTM/HSC) constructs were used to explore the mode of action.MethodsOcular normotensive New Zealand white (NZW) rabbits (ONT-rabbits), spontaneously ocular hypertensive pigmented Dutch-belted rabbits (sOHT-rabbits), hypertonic saline (5%)–induced transient ocular hypertensive NZW rabbits (tOHT-rabbits), ocular normotensive Beagle dogs (ONT-dogs), and laser-induced ocular hypertensive cynomolgus monkeys (OHT-monkeys) were used. NCX 667 or vehicle (30 µL) was instilled in a crossover, masked fashion and intraocular pressure (IOP) measured before dosing (baseline) and for several hours thereafter. The ONT-rabbits were used for cyclic guanosine monophosphate (cGMP) determination in ocular tissues after ocular dosing with NCX 667. Transforming growth factor-beta2 (TGFβ2) (2.5 ng/mL, six days)–treated HTM/HSC constructs were used to address changes in outflow facility.ResultsNCX 667 resulted in robust and dose-dependent IOP decrease in all models used. Maximal IOP-lowering efficacy at 1% was −4.1 ± 0.6, −12.2 ± 2.7, −10.5 ± 2.0, −5.3 ± 0.8, and −6.6 ± 1.9 mmHg, respectively, in ONT-dogs, sOHT-rabbits, tOHT-rabbits, ONT-rabbits, and OHT-monkeys. In ONT-rabbits NCX 667 (1%) increased cGMP in aqueous humor (AH) but not in retina and iris/ciliary body. NCX 667 concentration-dependently increased outflow facility in TGFβ2-treated HTM/HSC constructs (outflow facility, 0.10 ± 0.06 and 0.30 ± 0.10 µL/min/mmHg/mm2, respectively, in vehicle- and NCX 667–treated constructs).ConclusionsNCX 667 leads to robust IOP lowering in several animal models. Evidence in HTM/HSC constructs indicate that the IOP reduction likely results from NO-mediated increase of the conventional outflow pathway. Other mechanisms including changes in AH production and episcleral vein pressure may not be excluded at this time.

Effects of General Anesthesia on Intraocular Pressure in Rabbits.

Measurement of intraocular pressure (IOP) is a standard procedure in ophthalmic research in animals, specifically in glaucoma research, and the control of IOP is essential during certain veterinary ophthalmic surgeries. We evaluated the effect of isoflurane on IOP in the clinically healthy laboratory rabbits and tested a way to minimize the alteration of IOP during isoflurane anesthesia. After measurement of the baseline IOP in each eye of 9 awake New Zealand white rabbits, animals were anesthetized by using either: (1) isoflurane without premedication, (2) a combination of ketamine and xylazine, or (3) isoflurane inhalation after an injection of ketamine-xylazine premedication. Isoflurane led to a sustained increase in IOP of approximately 12 mm Hg. In contrast, ketamine and xylazine decreased IOP by nearly 5 mm Hg (all values compared with baseline measurements in awake, unrestrained animals). The observed decrease in IOP after ketamine-xylazine anesthesia is consistent with anesthetic effects generally seen during anesthesia in other studies. The increased IOP after isoflurane anesthesia in rabbits in this study was an unexpected result that appears to be specific to this combination of anesthetic and animal species. Premedication with ketamine-xylazine diminished the effect of isoflurane inhalation on IOP. These results should be considered in the design of ophthalmic research studies using rabbits and in intraocular surgery where IOP stability is desired.

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.

Morphological Changes and Potential Mechanisms of Intraocular Pressure Reduction after Micropulse Transscleral Cyclophotocoagulation in Rabbits

Introduction: Micropulse transscleral cyclophotocoagulation (MP-TSCPC) is a method for intraocular pressure (IOP) reduction in patients with glaucoma; however, the specific mechanisms underlying its ability to reduce IOP remain unclear. We therefore investigated the morphological changes and mechanisms of IOP reduction after MP-TSCPC. Methods: The right eyes of 4 pigmented rabbits were treated with MP-TSCPC with power setting corresponding to those used in glaucoma patients (1 power: 2,000 mW; time: 160 s; duty cycle: 31.3%). Power settings of 1, 1/8, 1/16, and 1/32 power were applied to the right eyes. The left eyes were used as controls. A light microscope and electron microscope were used to observe morphological findings after 1 week of MP-TSCPC. IOP and IOP reduction rate were compared before and after MP-TSCPC application on days 1, 3, and 5, and at 1 week. Results: In the pre-MP-TSCPC, IOP was 16.7 ± 0.6 mm Hg. The IOP of rabbit treated with the 1 power was 3 mm Hg, with an IOP reduction rate of 80%; however, the eyes developed phthisis bulbi. The IOP was 7.0 ± 0.0 mm Hg 1 week after MP-TSCPC (IOP reduction rate: 59%) in rabbit treated with the 1/8 power. Reduction in IOP was observed, but there was significant tissue invasion to the ciliary body. The IOP was 10.3 ± 0.6 mm Hg (IOP reduction rate: 40%) 1 week after MP-TSCPC in rabbit treated with the 1/16 power, which was more effective to reduce IOP than that with the 1/8 power. Tissue invasion to the ciliary body was negligible, nonpigmented epithelial cells of the pars plicata were damaged, basal infoldings were destroyed, and repair was accompanied by proliferating tissue. No IOP reduction or tissue change was observed in rabbit treated with the 1/32 power. Conclusion: A potential mechanism for IOP reduction in pigmented rabbits is aqueous humor transport dysfunction due to damage to the nonpigmented epithelial cells of the pars plicata and destruction of basal infoldings. The power of MP-TSCPC was consistent with both morphological changes and IOP reduction.

A Wireless Handheld Pressure Measurement System for In Vivo Monitoring of Intraocular Pressure in Rabbits

Intraocular pressure (IOP) is the leading modifiable risk factor for preventing vision loss in glaucoma patients. Direct and frequent IOP measurements are highly desirable to assess adequacy of treatment and prevent further vision loss. In this study, we report on successful in vivo measurements of intraocular pressure in rabbits using an optical IOP measurement system. The sensor was implanted during cataract surgery in two New Zealand white (NZW) rabbits and tested in vivo for ten weeks. Prior to implantation, the sensors were characterized in vitro in the physiologically relevant pressure range of 0-60 mmHg. A portable wireless handheld reader consisting of an internal beam splitter, a monochromatic light source, and a digital single-lens reflex (DSLR) camera was also designed and implemented to capture interference patterns from the sensor. The sensitivity and accuracy of the sensor was 30 nm/mmHg and ±0.2 mmHg, respectively. Ten weeks post-implantation, the two NZW rabbits continued to respond well to the implant with no observable inflammation, signs of infection, or biofouling. All IOP measurements were obtained using the portable DSLR handheld reader. Successful in vivo studies demonstrate biocompatibility of the IOP sensor and prove feasibility of the IOP measurement system. The system has the potential to be used in both clinical and patient point-of-care (home) settings to frequently and accurately measure pressure.