OBJECTIVE: This study comparatively analyzed the morphology of eye tissues after laser exposure using the latest generation of transscleral laser techniques - micropulse transscleral cyclophotocoagulation (MP-TSCPC) and laser activation of scleral hydropermeability (LASH) - in an anatomical experiment.
METHODS: The study used pulsed-periodic radiation of an Er-glass fiber laser (λ=1.56 μm) and radiation of a diode laser (λ=0.81 μm) in the micropulse mode. A comparative morphological evaluation of histological preparations of target scleral and ciliary body (CB) tissues was performed with the study of laser-induced changes occurring after LASH and MP-TSCPC.
RESULTS: The study of histological preparations obtained after MP-TSCPC and LASH did not reveal any noticeable signs of an inflammatory reaction or significant destructive changes. There were no signs of pronounced coagulative changes in the form of disorganization of connective and muscle tissue in the exposure area. At the same time, MP-TSCPC was accompanied by thinning and discontinuity of the CB pigment epithelium in the projection of its flat part and expansion of the gaps between the anterior connective tissue fibers fixing the CB to the sclera, which is likely a factor contributing to uveoscleral outflow. After LASH, in the irradiated areas at the level of the outer layers of the sclera (¾ of its thickness) located in the projection of the flat part of the ciliary body, multiple slit-like cavities and enlargements (stretching) of interfiber spaces were revealed with simultaneous compaction of the inner part of the sclera (¼ of its thickness).
CONCLUSIONS: The identified morphological changes may indicate certain differences in the mechanisms of intraocular pressure (IOP) reduction after MP-TSCPC and LASH. The results of this study suggest that the enhancement of uveoscleral outflow of intraocular fluid and the hypotensive effect after MP-TSCPC may be associated with laser-induced expansion of the interspaces between the anterior connective tissue fibers of the CB in the suprachoroidal space. With LASH, the possible mechanism of lowering IOP may be related rather to an increase in transscleral filtration due to the appearance of slit-like interfiber spaces in the sclera, caused by local contraction of scleral fibers in the area of laser exposure. The absence of pronounced destructive changes at the histological level indicates the gentle nature of both laser techniques and the possibility of expanding the indications for the use of LASH in the treatment of glaucoma, including at its earlier stages.
UNASSIGNED: Провести сравнительный морфологический анализ глазных тканей после лазерного воздействия с использованием транссклеральных технологий последнего поколения — циклофотокоагуляции в микроимпульсном режиме (мЦФК) и лазерной активации гидропроницаемости склеры (ЛАГС) — в условиях анатомического эксперимента.
UNASSIGNED: В работе использовали импульсно-периодическое излучение Er-glass волоконного лазера (λ = 1,56 мкм) и излучение диодного лазера (λ = 0,81 мкм) в микроимпульсном режиме. Проводили сравнительную морфологическую оценку срезов гистологических препаратов тканей-мишеней — склеры и цилиарного тела (ЦТ) — с изучением лазериндуцированных изменений, возникающих после проведения ЛАГС и мЦФК.
UNASSIGNED: Изучение гистологических препаратов, полученных после проведения мЦФК и ЛАГС, не выявило заметных проявлений воспалительной реакции и значительных деструктивных изменений. В зоне воздействия отсутствовали признаки выраженных коагуляционных изменений в виде дезорганизации соединительной и мышечной ткани. При этом проведение мЦФК сопровождалось истончением и прерывистостью пигментного эпителия ЦТ в проекции плоской части и расширением промежутков между передними соединительнотканными волокнами, фиксирующими ЦТ к склере, что, вероятно, является фактором, способствующим усилению увеосклерального оттока. После ЛАГС в облученных участках на уровне наружных слоев склеры (¾ толщины), расположенных в проекции плоской части цилиарного тела, выявлялись множественные щелевидные полости и расширения (растяжения) межволоконных пространств с одновременной компактизацией внутренней части склеры (¼ толщины).
UNASSIGNED: Выявленные морфологические изменения могут указывать на определенные отличия в механизмах снижения уровня внутриглазного давления (ВГД) после мЦФК и ЛАГС. Предполагается, что усиление увеосклерального оттока внутриглазной жидкости и гипотензивный эффект после проведения мЦФК могут быть связаны с лазериндуцированным расширением промежутков между передними соединительнотканными волокнами ЦТ в супрахориоидальном пространстве. При ЛАГС возможный механизм снижения уровня ВГД в большей степени может быть связан с усилением транссклеральной фильтрации за счет появления в склере щелевидных межволоконных пространств, обусловленного локальным стягиванием склеральных волокон в зоне лазерного воздействия. Отсутствие выраженных деструктивных изменений на гистологическом уровне свидетельствует о щадящем характере обеих лазерных технологий и о возможности расширения показаний для использования технологии ЛАГС в лечении глаукомы, в том числе на более ранних ее стадиях.

Laser cyclodestructive interventions are considered the method of choice in the treatment of refractory glaucoma. However, the traumatic nature of cyclocoagulation makes it necessary to search for more gentle methods of laser treatment. One of the possible directions is the development of laser transscleral technologies that mainly affect the uveoscleral outflow. This article presents a new technique for laser activation of scleral hydropermeability (LASH) using pulse-periodic erbium glass (Er-glass) fiber-optics laser with wave length of 1.56 μm. The article describes the parameters of laser emission and the technique of LASH, and presents the mechanism of reducing intraocular pressure associated with increased transcleral drainage of intraocular fluid by forming new pores in the sclera. The effectiveness and safety of LASH is supported by a detailed example from clinical practice. This technology has proven itself as a possible alternative to the conventional contact transcleral cyclocoagulation.
Лазерные циклодеструктивные вмешательства считаются методом выбора в лечении рефрактерной глаукомы. Однако достаточно травмирующий характер таких вмешательств ставит задачи по поиску более щадящих способов лазерного лечения. Одним из возможных направлений является разработка лазерных транссклеральных технологий, воздействующих главным образом на увеосклеральный отток. В статье представлена новая технология лазерной активации гидропроницаемости склеры (ЛАГС) с использованием импульсно-периодического излучения эрбиевого (Er-glass) волоконного лазера (λ=1,56 мкм). Показаны параметры лазерного излучения и методика проведения ЛАГС. Изложен механизм снижения внутриглазного давления, связанный с усилением транссклерального дренирования внутриглазной жидкости за счет формирования в склере новых пористых структур. Эффективность и безопасность ЛАГС подкреплены подробно описанным примером из клинической практики. Данная технология зарекомендовала себя в качестве возможной альтернативы классической контактной транссклеральной циклокоагуляции.

UNASSIGNED: Bimatoprost 0.03% is an intraocular pressure (IOP) lowering prostaglandin analog with different adverse side effects such as potential ocular inflammatory effect and ocular hyperemia.
UNASSIGNED: We report a case of 80-year-old woman diagnosed with bilateral glaucomatous uveitis, and choroidal detachment in the left eye after topical bimatoprost administration. During the patient\'s hospitalization, Bimatoprost treatment was discontinued and local steroid therapy was administrated. After 1 week we reported a marked improvement of visual acuity, IOP measurement was 12 mmHg in both eyes. Anterior segment examination showed complete resolution of conjunctival and pericheratic hyperemia with significant reduction of endothelial precipitates in both eyes.
UNASSIGNED: In our case, the anterior granulomatous uveitis occurred in both pseudophakic eyes and the choroidal detachment (CD) in the eye that previously had trabeculectomy. Probably the scar tissue of the trabeculectomy allowed a better penetration of the Bimatoprost or a greater sensitivity due to an altered trabecular tissue. This work confirms that the onset physiopathology mechanism of granulomatous uveitis and CD following instillation of Bimatoprost remains uncertain.

OBJECTIVE: The aim of this study was to report the use of micropulse trans-scleral cyclophotocoagulation as an adjunct therapy for two cases of medically uncontrolled intraocular pressure spikes due to anterior segment inflammation.Case description: Case 1 had previous cataract surgery and exhibited an intraocular pressure spike due to phacoantigenic uveitis (right eye intraocular pressure = 52 mmHg). Despite medical treatment, the right eye intraocular pressure remained high (43 mmHg), thus micropulse trans-scleral cyclophotocoagulation was carried out as a rescue therapy. After micropulse trans-scleral cyclophotocoagulation, the intraocular pressure at 1 day and 3 weeks was 9 and 16 mmHg, respectively. Case 2 had a history of previous blunt ocular trauma and 180° of angle recession. Both eyes were pseudophakia and underwent right eye Nd:YAG laser capsulotomy for posterior capsular opacification. Immediately after the procedure, the right eye intraocular pressure increased to 64 mmHg. Due to poor response to medical therapy, rescue micropulse trans-scleral cyclophotocoagulation was performed. After micropulse trans-scleral cyclophotocoagulation, the intraocular pressure at 1 day and 2 months was 12 and 21 mmHg, respectively.
CONCLUSIONS: Micropulse trans-scleral cyclophotocoagulation successfully decreased intraocular pressure in both cases of acute rise in intraocular pressure. Micropulse trans-scleral cyclophotocoagulation can potentially be useful as a rescue procedure to safely reduce medically uncontrollable intraocular pressure spike due to anterior segment inflammation.

BACKGROUND: Brimonidine tartrate is a commonly used eyedrop for short- and long-term lowering of intraocular pressure. Its use has been popularized due to its effects on aqueous suppression and uveoscleral outflow, as well as the suggestion of neuroprotection. Although available with alternative preservative vehicles, brimonidine is associated with high rates of local allergy and is contraindicated in breastfeeding women, neonates, young children, and the elderly due to risk of central nervous system depression. Other topical agents with differing advantages have challenged brimonidine\'s role in the treatment algorithm of ocular hypertension and glaucoma. Areas covered: The authors review the development of topical alpha-adrenergic agonists, with particular attention to the currently available formulations of brimonidine tartrate. Its mechanism of action, pharmacodynamics and safety, and clinical efficacy are analyzed. Expert opinion: Despite clinical familiarity with brimonidine after two decades of use, agents that offer daily dosing, nocturnal effect, and more favorable ocular and systemic side effect profiles have ultimately led to brimonidine\'s adjunctive use in patients with elevated intraocular pressure or high- or low-tension glaucomas. Still, brimonidine may be advantageous in patients undergoing laser trabeculoplasty or iridotomy, in certain forms of glaucoma, or in pregnant individuals prior to the last trimester, underscoring its clinical importance.

Mice and rats are being increasingly used in glaucoma research and much useful data have been generated from them. One aspect of using these animals for this purpose involves assessment of aqueous humor dynamics. Several techniques have been described in the literature for the determination of one or more of these parameters in rodents, in both living animals and eyes perfused ex vivo. Here, we describe the practical details for a technique for the determination of all principal parameters of aqueous humor dynamics (intraocular pressure (IOP), aqueous humor formation rate (Fin), uveoscleral outflow rate (Fu), aqueous outflow facility (C), and episcleral venous pressure (Pe)) in the living rat and mouse eye, in a single experimental session.

The uveoscleral outflow route is via the ciliary muscles into the suprachoroidal spaces and then to the orbital blood and lymph systems. The main driving force behind this uveoscleral outflow is the high oncotic pressure in the choroidal vessels. Currently, the CyPass microstent is the only available suprachoroidal device for ab interno minimally invasive glaucoma surgery. The CyPass achieves a maximum reduction of intraocular pressure (IOP) to 16-17 mm Hg over 12-24 months and is approved for mild to moderate primary open-angle glaucoma. The CyPass is an easy to use minimally invasive glaucoma surgery stent operation and has few intraoperative as well as short and long-term complications. Postoperative management is unproblematic and the postoperative burden for patients is low, which leads to rapid recovery of patients; however, the correct selection of glaucoma patients is crucial for maintaining a sustainable success rate. Long-term studies are necessary to demonstrate the persistence of the IOP lowering effect.

Reduction of intraocular pressure is the sole therapeutic target for glaucoma. Intraocular pressure is determined by the dynamics of aqueous humour secretion and outflow, which comprise several pressure-dependent and pressure-independent mechanisms. Accurately quantifying the components of aqueous humour dynamics is essential in understanding the pathology of glaucoma and the development of new treatments. To better characterise aqueous humour dynamics, we propose a method to directly measure pressure-independent aqueous humour flow. Using the iPerfusion system, we directly measure the flow into the eye when the pressure drop across the pressure-dependent pathways is eliminated. Using this approach we address i) the magnitude of pressure-independent flow in ex vivo eyes, ii) whether we can accurately measure an artificially imposed pressure-independent flow, and iii) whether the presence of a pressure-independent flow affects our ability to measure outflow facility. These studies are conducted in mice, which are a common animal model for aqueous humour dynamics. In eyes perfused with a single cannula, the average pressure-independent flow was 1 [-3, 5] nl/min (mean [95% confidence interval]) (N = 6). Paired ex vivo eyes were then cannulated with two needles, connecting the eye to both iPerfusion and a syringe pump, which was used to impose a known pressure-independent flow of 120 nl/min into the experimental eye only. The measured pressure-independent flow was then 121 [117, 125] nl/min (N = 7), indicating that the method could measure pressure-independent flow with high accuracy. Finally, we showed that the artificially imposed pressure-independent flow did not affect our ability to measure facility, provided that the pressure-dependence of facility and the true pressure-independent flow were accounted for. The present study provides a robust method for measurement of pressure-independent flow, and demonstrates the importance of accurately quantifying this parameter when investigating pressure-dependent flow or outflow facility.

BACKGROUND: Glaucoma is a collection of optic neuropathies consisting of retinal ganglion cell death and corresponding visual field loss. Glaucoma is the leading cause of irreversible vision loss worldwide and is forecasted to precipitously increase in prevalence in the coming decades. Current treatment options aim to lower intraocular pressure (IOP) via topical or oral therapy, laser treatment to the trabecular meshwork or ciliary body, and incisional surgery. Despite increasing use of trabecular laser therapy, topical therapy remains first-line in the treatment of most forms of glaucoma. Areas covered: Novel glaucoma therapies are a long-standing focus of investigational study. More than two decades have passed since the last United States Food and Drug Administration (FDA) approval of a topical glaucoma drug. Here, the authors review established topical glaucoma drops as well as those currently in FDA phase 2 and 3 clinical trial, nearing clinical use. Expert opinion: Current investigational glaucoma drugs lower IOP, mainly through enhanced trabecular meshwork outflow. Although few emerging therapies show evidence of retinal ganglion cell and optic nerve neuroprotection in animal models, emerging drugs are focused on lowering IOP, similar to established medicines.

Latanoprostene bunod (LBN) is a novel nitric oxide-donating prostaglandin F2α receptor agonist in clinical development for intraocular pressure lowering in open-angle glaucoma and ocular hypertension. Currently in Phase III clinical trials in the USA, European Union, and Japan, LBN has demonstrated promising efficacy while maintaining safety and tolerability. We review preclinical and clinical developmental efforts and evaluate the potential role of LBN monotherapy in the management of open-angle glaucoma and ocular hypertension. The current LBN clinical development program comprises eight trials, four of which have resulted in publication of complete methodology and outcomes. We additionally pool adverse events data to determine incidences across three pivotal studies. Evidence thus far indicates that LBN may be a safe and effective ocular hypotensive agent, although the potential neuroprotective effects and the impact on visual field loss remain to be evaluated.