In Vivo Analysis of Prostaglandins-induced Ocular Surface and Periocular Adnexa Modifications in Patients with Glaucoma

Staso, Silvio Di; Agnifili, Luca; Cecannecchia, Sara; Gregorio, Angela Di; Ciancaglini, Marco

doi:10.21873/invivo.11227

Cited by 22 publications

(17 citation statements)

References 73 publications

(64 reference statements)

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“…При этом некоторые молекулы даже в определенной степени способны «смягчать» действие консерванта! Так, уже известно, что бесконсервантные АПг стимулируют активность бокаловидных клеток [20], тем самым увеличивая синтез муцинов слезной пленки и, по-видимому, количество микроцист в стенке фильтрационной подушки, свидетельствующих об эффективности гипотензивной операции [21].…”

Section: комбинированное воздействие бх и лекарственного вещества преunclassified

“…К прочим проблемам относятся опосредованная АПг периорбитопатия, пигментация кожи век, гипертрихоз, активация вирусной инфекции [21], эндотелиальная декомпенсация при использовании ингибиторов карбоангидразы [39], хотя обусловлено ли на фоне гипотензивной терапии повышение толщины роговицы именно угнетением ее эндотелия карбоангидразой, пока не доказано.…”

Section: комбинированное воздействие бх и лекарственного вещества преunclassified

“…В целом БХ вызывает разнообразные изменения глазной поверхности, включая ксеротические, аллергические и иммуновоспалительные реакции с экспрессией и/или синтезом антигенов II класса, молекул адгезии, хемокинов и их рецепторов, ИЛ, маркеров и медиаторов клеточной смерти, деструкцию бокаловидных клеток, а также фибробластическую гиперактивность и воспалительную клеточную инфильтрацию, вовлекающую не только глазную поверхность, но и собственное вещество конъюнктивы [21,22]. В результате БХ-содержащие препараты как минимум вдвое повышают частоту симптомов и клинических признаков ССГ по сравнению с бесконсервантными аналогами, что существенно снижает качество жизни таких больных.…”

Section: комбинированное воздействие бх и лекарственного вещества преunclassified

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IOP-lowering therapy and ocular surface in glaucoma. Part 2. The effect of preservatives on ocular surface

Аntonova¹,

Nikolaenko²,

Brzheskiy³

2020

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Обзоры консерВанты гиПотензиВных ПреПаратоВ и слезная Пленка Как известно, наиболее распространенным консервантом является бензалкония хлорид (БХ), на долю которого приходится три четверти всех выпускаемых в мире «консервантных» глазных капель (табл. 1). БХ закономерно привлекает самое пристальное внимание на протяжении последних 20 лет [1, 2].

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Section: комбинированное воздействие бх и лекарственного вещества преunclassified

See 1 more Smart Citation

IOP-lowering therapy and ocular surface in glaucoma. Part 2. The effect of preservatives on ocular surface

Аntonova¹,

Nikolaenko²,

Brzheskiy³

2020

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“…While lowering the intraocular pressure (IOP) is the most important measure to prevent further damage to the optic disc, long-term topical treatment represents a continuous hazard to the ocular surface homeostasis. Longterm topical glaucoma therapy has been associated with reduced density of goblet cells and squamous metaplasia of the conjunctival epithelium, 1 dysfunction of meibomian glands, conjunctival and corneal desquamation, 2 and overexpression of proinflammatory cytokines. 3 Significative loss of goblet cells, which can cause dry eye, inflammation, and fibrosis, was observed in animal and human models.…”

Section: Introductionmentioning

confidence: 99%

<p>Impact of Ocular Surface Disease Treatment in Patients with Glaucoma</p>

Boso¹,

Gasperi²,

Fernandes³

et al. 2020

OPTH

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Purpose: Chronic topical treatment for glaucoma may lead to Ocular Surface Disease (OSD). This study aimed to evaluate: (1) the prevalence of OSD in glaucoma patients under topical treatment, quantifying symptoms and objective ocular surface parameters and (2) the impact of ocular surface treatment on OSD and IOP control. Methods: Patients with primary open angle or primary angle closure glaucoma under topical treatment for at least 6 months were enrolled in the study. Patients underwent symptom screening with the ocular surface disease index (OSDI) questionnaire, assessment of objective ocular surface parameters, ocular surface staining and Schirmer test. A treatment for OSD with eyelid hygiene, fluorometholone acetate 0.1%, preservative-free lubricants, free-acid supplementation and oral tetracyclin derivate was started, and the same evaluation was performed. Results: In our sample (n=19), 73.68% of the patients reported severe symptoms of dry eye disease, with OSDI scores higher than 33 at baseline. Tear film instability was found in 50% of patients, while 23.53% had severe meibomian gland abnormalities. Fluorescein and lissamine green stainings were abnormal in 88.24% and 82.35% of patients, respectively. After ocular surface treatment, statistically significant improvement was found in bestcorrected visual acuity (p=0.0003), OSDI score (p<0.0001), bulbar redness (p=0.0196) and fluorescein staining (p<0.0001.) Mean IOP following OSD treatment reduced −1.59 mmHg from baseline in the left eye (p=0.0510). Conclusion: The prevalence of OSD signs and symptoms was high in glaucoma patients under medical treatment. Short-term OSD treatment may improve ocular surface disease and IOP control, with no need to discontinue glaucoma medications.

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“…The most commonly reported effects with prostaglandin analogs are periorbitopathy, skin pigmentation and hypertrichosis, eyelash growth, and meibomian gland dysfunction, while inflammatory changes of the cornea, corneo-scleral limbus, conjunctival stroma, and conjunctiva-associated lymphoid tissue are also frequently observed. 10,11 Further, inflammation of the conjunctiva can adversely impact the success rate of filtration surgery. 12 In some patients, the disease can become refractory to specific topical ocular hypotensive drugs, 13 with a proportion of patients failing to respond adequately to available medical or surgical therapies, 14 necessitating the combination of different drug classes to achieve adequate IOP lowering.…”

Section: Introductionmentioning

confidence: 99%

<p>Randomized, Double-Masked, Placebo-Controlled Dose Escalation Study of TAK-639 Topical Ophthalmic Solution in Subjects with Ocular Hypertension or Primary Open-Angle Glaucoma</p>

Martin

Cohen

Uddin

et al. 2020

OPTH

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Purpose: TAK-639 is a topical, nine-amino acid, synthetic, C-type natriuretic peptide analog in Phase 1 development for the treatment of ocular hypertension (OHT) and primary open-angle glaucoma (POAG). TAK-639 is postulated to lower intraocular pressure (IOP) through a novel mechanism of action (MOA) that increases trabecular meshwork outflow. We investigated the safety and tolerability of TAK-639 in subjects with OHT or POAG. Methods: This was a phase 1, multicenter, randomized, double-masked, placebo-controlled, single-and multiple-dose escalation study. Subjects (aged 18-90 years) with OHT or POAG were randomized 5:2 to TAK-639 or placebo. Three dose levels were planned (0.1%, 0.3%, 0.6% TAK-639), each with four dosing regimens (QD, BID, TID, QID). Safety measures included treatment-emergent adverse events (TEAEs) and ophthalmologic examinations. Pharmacokinetics and pharmacodynamics (reduction of IOP) were also evaluated. Results: In total, 63 subjects were randomized and received 0.1%, 0.3% and 0.6% TAK-639, as single dose, QD, or BID, and 0.1% and 0.3% TID. The study was terminated before 0.6% TID or QID dosing cohorts were studied; instead, 0.6% BID was repeated in a new cohort. TEAEs were instillation related and of mild-to-moderate intensity. There were no TEAEs leading to premature discontinuation, and no serious TEAEs. The most common treatmentrelated TEAEs were instillation site pain and transient corneal staining with fluorescein. There were no clinically significant concerns across dose groups for all other safety measures, including drop comfort, best corrected visual acuity, slit-lamp biomicroscopy, and corneal epithelial integrity. Little or no systemic exposure was observed. There was a marginal reduction in IOP in one cohort at the highest dose (0.6%) and regimen (BID) tested, suggesting biological plausibility of targeting the trabecular meshwork through this mechanism. Conclusion: TAK-639 was generally well tolerated up to 0.6% BID. Further non-clinical studies will improve understanding of the MOA and the penetration of TAK-639 to the anterior chamber.

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In Vivo Analysis of Prostaglandins-induced Ocular Surface and Periocular Adnexa Modifications in Patients with Glaucoma

Cited by 22 publications

References 73 publications

IOP-lowering therapy and ocular surface in glaucoma. Part 2. The effect of preservatives on ocular surface

IOP-lowering therapy and ocular surface in glaucoma. Part 2. The effect of preservatives on ocular surface

<p>Impact of Ocular Surface Disease Treatment in Patients with Glaucoma</p>

<p>Randomized, Double-Masked, Placebo-Controlled Dose Escalation Study of TAK-639 Topical Ophthalmic Solution in Subjects with Ocular Hypertension or Primary Open-Angle Glaucoma</p>

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