Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma‐associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long‐term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open‐angle glaucoma. In a laboratory study in 15 of them, 24‐hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time‐dependently decreased IOP and IOP standard deviation (SD). IOP 24‐hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24‐hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G‐allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.
Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of “marker” circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.
Purpose: to study the antioxidant system and lipid status of serum and evaluate the effect of Cytoflavin on these characteristics in patients with progressive and stable primary open angle glaucoma (POAG).Patients and methods. 67 patients with advanced stage POAG were observed. The average age was 66.3 ± 1.5 years. According to the course of the glaucoma process all patients were randomized into 2 groups: the 1st group with the stable glaucoma (31 patients) and the 2nd group with rapidly progressive glaucoma (36 patients). The progression criteria of POAG were global ganglion cell loss volume (GLV) and perimetric index (mean deviation-MD). For assessment of the reactivity of the vascular endothelium, a test with reactive hyperemia was performed using ultrasound method. The assessment of oxidative stress (OS) including peroxides, malonyldialdehyde (MDA) and the total antioxidant capacity of serum (AOS) were evaluated. The investigations of lipid metabolism included the level of cholesterol total (CT), cholesterol of low-density lipoproteins cholesterol (LDL-C), high-density lipoproteins cholesterol (HDL-C), triglycerides (TG) and atherogenic index (AI).Results. In the 2nd group there was the significant decrease of the mean GLV indices compared to those in the 1st group (7.16 ± 2.5 и 1.06 ± 0.2, respectively, р < 0.001). The mild degree of endothelial dysfunction (ED) predominantly was detected in patients of the 1st group (69 % of cases). The moderate and marked ED were found in patients with progressive POAG (68 and 25 %, respectively). The high level of OS in serum was determined in 43 % of patients of the 1st group and in 69 % of patients of the 2nd group (significant increase of peroxides and MDA). In patients with progressive POAG the mean indices of lipid metabolism (CT, LDL-C, HDL-C, TG, AI) were significantly higher than in healthy subjects (р < 0.001). Cytoflavin had a positive effect on the vascular endothelium function, normalization of lipid metabolism and decrease of OS in serum with increasing AOS in patients with progressive POAG.Conclusion. The assessment of the indices of OS, AOS and lipid metabolism enable us to determine the risk of progression of POAG and evaluate of the effectiveness of treatment.
Одним из основных факторов развития и прогрессирования первичной открытоугольной глаукомы (ПОУГ) принято считать повышенный уровень внутриглазного давления (ВГД). Большинство схем медикаментозного лечения и защиты клеток от глаукоматозного повреждения направлены именно на снижение значений ВГД. Однако заболевание может прогрессировать и при нормализованном офтальмотонусе. Это определяет необходимость поиска лекарственных средств, действующих на другие патогенетические звенья прогрессирования ПОУГ. Цель. Изучить влияние препарата «Цитофлавин» на стабилизацию глаукомной оптической нейропатии у пациентов с ПОУГ. Материал и методы. В исследование включено 103 пациента с начальной и развитой стадиями ПОУГ, которые с помощью метода случайных чисел Сепетлиева были рандомизированы на две группы: группу контроля (n=50) (пациенты, получавшие стандартное консервативное лечение) и основную (n=53) (пациенты, получавшие комбинированный препарат метаболического действия «Цитофлавин»). Всем больным до и после лечения, помимо стандартного офтальмологического обследования, проводили биологические, электрофизиологические, периметрические, структурно-топографические, лабораторные и социологические исследования. Результаты. К концу 3-го месяца лечения у пациентов основной группы отмечали положительную динамику амплитудных и фазовых характеристик биоэлектрической активности сетчатки, улучшение суммарной светочувствительности сетчатки центрального поля зрения. Применение Цитофлавина способствовало снижению темпов прогрессирования глаукомы по данным оптической когерентной томографии: стабилизации толщины слоя нервных волокон, снижению скорости глобальных и фокальных потерь ганглиозных клеток сетчатки. У пациентов основной группы к концу 3-го месяца лечения достоверно уменьшилась выраженность окислительного стресса и улучшились показатели антиоксидантной защиты. На фоне стабилизации глаукомного процесса у коморбидных пациентов основной группы наблюдались субъективное улучшение общего и психоэмоционального здоровья, повышение уверенности в успехе проводимой терапии и тем самым улучшение качества жизни. Заключение. Цитофлавин, действуя на механизмы, усиливающие защиту сетчатки от последствий реперфузионного повреждения и оксидативного стресса, способствует метаболической адаптации нейронов и развитию более благоприятного варианта течения ПОУГ.
Drug treatment optimization in primary open-angle glaucoma (POAG) is a topical issue of ophthalmology in recent decades. The review focuses on the choice of local hypotensive therapy and the effectiveness of a fixed combination (FC) of dorzolamide / timolol in glaucoma treatment. Since decreased perfusion eye pressure and disturbed regulation of local hemodynamics affect the development and progression of glaucomatous optical neuropathy, the use of anti-glaucomatous drugs or other hypotensive agents requires taking account of their effect on intraocular pressure (IOP), visual functions, and ocular blood flow. Most studies show that the hypotensive and hemodynamic effects of dorzolamide/timolol FC contribute to the preservation of visual fields in POAG patients by reducing significant risk factors for POAG progression, such as increased IOP and blood flow deficiency in the retinal and choroidal vessels. Improved hemodynamic parametersdue to local hypotensive treatment can be considered as basis for visual function stabilization, especially in long-term chronic courses of the disease.
Purpose. To analyze the daily dynamics and the parameters of intraocular pressure circadian rhythm (IOP CR) in patients with primary open-angle glaucoma (POAG) (stable and progressive forms) and determine chronobiological regularities of glaucoma progression depending on the patterns of restructuring the daily dynamics of IOP CR and body temperature.Material and methods. The study included 75 POAG patients, of which 35 had a stable form (S-POAG) and 40 had a rapidly progressing form (P-POAG). The control group was composed of 80 subjects without POAG. The index of retinal ganglion cell loss measured by optical coherence tomography (OCT) was used as a criterion of POAG progression. IOP was measured by the patients themselves for 72 hours at 7 time points (3 am, 8 am, 11 am, 2 pm, 5 pm, 8 pm, and 11 pm, who used an Icare ONE portable intraocular pressure tonometer for individual use.Results. IOP daily dynamics was distributed differently in the different groups. In S-POAG, the peak values were mainly reached in the morning hours, while the minimum values were observed at night. In P-POAG, the peak values of IOP were contrariwise recorded at night. In both POAG groups, an increase of irregular fluctuation share was noted, which indicated a decrease of the CR contribution to the IOP CR. Moreover, in POAG, a change in the phase ratio between the IOP CR and CR of body temperature was observed. For IOP CR phase violation manifestations, the threshold value of GCS global loss index was determined at 10–15 % according to OCT data.Conclusion. IOP daily dynamics were shown to differ in S-POAG and P-POAG patients. In both groups. Signs of desynchronization were detected. The ganglion retinal cell global loss index can be used to determine phase disturbances of IOP CR.
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