Progression Of Glaucomatous Optic Neuropathy Research Articles

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation. These include: (1) perfused whole globes, (2) stationary anterior segment organ culture, (3) perfused human anterior segment organ culture, (4) perfused animal anterior segment organ culture, (5) perfused human corneal rims, and (6) perfused human anterior segment wedges. These methods, with due consideration paid to their strengths and limitations, comprise a set of very strong tools for extending our understanding of IOP regulation.

Main morphofunctional correlations between indicators of intraocular pressure fluctuations and glaucomatous optic neuropathy progression

Main morphofunctional correlations between indicators of intraocular pressure fluctuations and glaucomatous optic neuropathy progression

Efficacy of new two-stage methods of surgical and laser treatment for primary open-angle glaucoma combined with cataract

Background. Lowering the intraocular pressure (IOP) is the only proven method to slow the progression of glaucomatous optic neuropathy. Successful conservative treatment or surgery do not guarantee the preservation of visual fields throughout life. Despite the current advances in conservative treatment of primary open-angle glaucoma, about 5.3 % of patients still require surgical or combined treatment. There is no consensus yet on approaches to the treatment of patients with glaucoma and cataract. The objective was to evaluate the effectiveness of new two-stage methods for surgical and laser treatment of patients with primary open-angle glaucoma associated with cataract. Materials and methods. Seventy patients (70 eyes) with primary open-angle glaucoma stages I–IV complicated by cataract were included in this study. There were two observation groups. All patients received a two-stage treatment — micropulse transscleral cyclophotocoagulation (MP-TSCPC) and phacoemulsification with a monofocal intraocular lens (IOL) implantation. The first group (n = 34) included participants who underwent phacoemulsification with IOL implantation (stage 1) one month prior to MP-TSCPC (stage 2). The second group (n = 36) consisted of patients who underwent MP-TSCPC (stage 1) and phacoemulsification with IOL implantation a month after (stage 2). These groups did not statistically differ in terms of age, gender, baseline IOP, and stage of primary open-angle glaucoma. The primary outcome measure was the normalization of IOP with or without the use of antiglaucoma medications and without a need for further laser and incisional procedures in 1, 3 and 6 months. The secondary outcome was stabilization or expansion of visual fields when evalua­ting 1, 3, and 6 months after stage 2. Results. The average IOP level with antihypertensive medications before the treatment in group 1 was 27.5 ± 1.3 mmHg, in group 2 — 27.0 ± 1.1 mmHg. One month after the treatment, patients of group 1 had normal IOP in 94.2 % of eyes and in 5.8 % of eyes with local antihypertensive medications; in group 2, IOP was normal in 100 % of eyes without antiglaucoma medications (p < 0.05). In 3 and 6 months, better hypotensive results were in group 2, but outcomes were not statistically significant. The visual fields were preserved at the preoperative level or expan­ded in patients from groups 1 and 2 one month after the treatment in 91.2 and 97.2 % of the eyes, respectively, 3 months after — in 91.2 and 97.2 %, 6 months after — in 88.2 and 94.4 % of the eyes, respectively. In group 2, better functional results were obtained at all time points, but it was not statistically significant. Conclusions. The studies have established a high efficacy and safety of new two-stage methods for surgical and laser treatment of patients with primary open-angle glaucoma and cataract with a follow-up period of 6 months. There was a tendency to greater efficacy of the method, where MP-TSCPC as stage 1 was followed by phacoemulsification with IOL implantation as stage 2. The nature and frequency of surgical and postoperative complications in both groups did not differ.

Clinical Perspectives on the Use of Computer Vision in Glaucoma Screening.

Glaucoma is one of the leading causes of irreversible blindness in the world. Early diagnosis and treatment increase the chances of preserving vision. However, despite advances in techniques for the functional and structural assessment of the retina, specialists still encounter many challenges, in part due to the different presentations of the standard optic nerve head (ONH) in the population, the lack of explicit references that define the limits of glaucomatous optic neuropathy (GON), specialist experience, and the quality of patients' responses to some ancillary exams. Computer vision uses deep learning (DL) methodologies, successfully applied to assist in the diagnosis and progression of GON, with the potential to provide objective references for classification, avoiding possible biases in experts' decisions. To this end, studies have used color fundus photographs (CFPs), functional exams such as visual field (VF), and structural exams such as optical coherence tomography (OCT). However, it is still necessary to know the minimum limits of detection of GON characteristics performed through these methodologies. This study analyzes the use of deep learning (DL) methodologies in the various stages of glaucoma screening compared to the clinic to reduce the costs of GON assessment and the work carried out by specialists, to improve the speed of diagnosis, and to homogenize opinions. It concludes that the DL methodologies used in automated glaucoma screening can bring more robust results closer to reality.

Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients.

Serious vision loss occurs in patients affected by chronically raised intraocular pressure (IOP), a characteristic of many forms of glaucoma where damage to the optic nerve components causes progressive degeneration of retinal and brain neurons involved in visual perception. While many risk factors abound and have been validated for this glaucomatous optic neuropathy (GON), the major one is ocular hypertension (OHT), which results from the accumulation of excess aqueous humor (AQH) fluid in the anterior chamber of the eye. Millions around the world suffer from this asymptomatic and progressive degenerative eye disease. Since clinical evidence has revealed a strong correlation between the reduction in elevated IOP/OHT and GON progression, many drugs, devices, and surgical techniques have been developed to lower and control IOP. The constant quest for new pharmaceuticals and other modalities with superior therapeutic indices has recently yielded health authority-approved novel drugs with unique pharmacological signatures and mechanism(s) of action and AQH drainage microdevices for effectively and durably treating OHT. A unique nitric oxide-donating conjugate of latanoprost, an FP-receptor prostaglandin (PG; latanoprostene bunod), new rho kinase inhibitors (ripasudil; netarsudil), a novel non-PG EP2-receptor-selective agonist (omidenepag isopropyl), and a form of FP-receptor PG in a slow-release intracameral implant (Durysta) represent the additions to the pharmaceutical toolchest to mitigate the ravages of OHT. Despite these advances, early diagnosis of OHT and glaucoma still lags behind and would benefit from further concerted effort and attention.

Overview and update on cytomegalovirus-associated anterior uveitis and glaucoma.

Cytomegalovirus anterior uveitis is the most common ocular inflammatory disease caused by cytomegalovirus infection. It mainly occurs in middle-aged males with competent immunologic function, and the incidence is higher in Asia. The clinical manifestations vary from Posner-Schlossman syndrome and corneal endotheliitis to Fuchs uveitis syndrome, and are often accompanied by intraocular hypertension. Secondary glaucoma is a potentially blinding ocular complication with a pathogenesis that includes complicated immunological factors, intraocular inflammation, different types of angle abnormalities, and the administration of steroids, which may result in physical discomfort and visual impairment. Diagnostic tests, such as the polymerase chain reaction, optical coherence tomography, ocular microscopy, and confocal microscopy, might help in identifying anterior uveitis caused by other viruses. Combinations of antiviral medications and anti-inflammatory agents are effective treatments. If pharmacological therapy cannot reduce intraocular pressure or slow the progression of glaucomatous optic neuropathy, surgical intervention is required as a last resort.

Optic Nerve Injury Enhanced Mitochondrial Fission and Increased Mitochondrial Density without Altering the Uniform Mitochondrial Distribution in the Unmyelinated Axons of Retinal Ganglion Cells in a Mouse Model.

Glaucomatous optic neuropathy (GON), a major cause of blindness, is characterized by the loss of retinal ganglion cells (RGCs) and the degeneration of their axons. Mitochondria are deeply involved in maintaining the health of RGCs and their axons. Therefore, lots of attempts have been made to develop diagnostic tools and therapies targeting mitochondria. Recently, we reported that mitochondria are uniformly distributed in the unmyelinated axons of RGCs, possibly owing to the ATP gradient. Thus, using transgenic mice expressing yellow fluorescent protein targeting mitochondria exclusively in RGCs within the retina, we assessed the alteration of mitochondrial distributions induced by optic nerve crush (ONC) via in vitro flat-mount retinal sections and in vivo fundus images captured with a confocal scanning ophthalmoscope. We observed that the mitochondrial distribution in the unmyelinated axons of survived RGCs after ONC remained uniform, although their density increased. Furthermore, via in vitro analysis, we discovered that the mitochondrial size is attenuated following ONC. These results suggest that ONC induces mitochondrial fission without disrupting the uniform mitochondrial distribution, possibly preventing axonal degeneration and apoptosis. The in vivo visualization system of axonal mitochondria in RGCs may be applicable in the detection of the progression of GON in animal studies and potentially in humans.

Therapeutic possibilities of stimulating reparative neurogenesis in patients with glaucoma who have recovered from a coronavirus infection

This study aimed to conduct a comprehensive diagnosis of the severity of oxidative stress, identify changes in the neuroplasticity and reparative ability of the retina in patients with primary open-angle glaucoma (POAG) who have recovered after a coronavirus infection, and are undergoing therapy with the complex drug Cytoflavin. The study included 40 patients (mean age 57.2±3.6 years) with advanced POAG compensated by hypotensive agents; all of them recovered from moderate Covid-19 30 to 90 days prior to inclusion in the study. Twenty patients of the main group received therapy with the complex drug Cytoflavin, 20 other patients comprised the control group. In the comparison groups, the concentration of BDNF and CNTF in blood serum (SC) was determined by enzyme-linked immunosorbent assay (ELISA). Overall assessment of oxidative stress was done by high performance liquid chromatography. Studies of the functional activity of the retina were performed using the Tomey EP 1000 electroretinograph according to the standard method. Retinal photosensitivity significantly improved in patients of the main group taking the complex drug Cytoflavin (mD mean after treatment increased from -7.34±0.62 dB to -4.52±0.12 dB (p>0.001), PSD mean decreased from 6.23±0.21dB to 4.27±0.13 dB (p>0.001)); the neural activity of the retina improved according to PERG (the amplitudes of the P50 and N95 components increased from 0.92±0.04 µv to 1.65±0.01 µv and from 1.83±0.06 µv to 2.68±0.01 µv, respectively (p>0.001), the latency of the P50 and N95 components decreased from 53.40±2.51 ms to 49.37±2.22 ms and from 112.40±5.23 ms to 107.4±8.11ms, respectively (p>0.001); the concentration of BDNF increased (from 18.65±5.32 ng/ml to 20.23±4.05 ng/ml (p>0.001)) and the concentration of CNTF in the blood serum decreased (from 3.99±0.37 pg/ml to 1.85±0.02pg/ml (p>0.001)), the severity of oxidative stress decreased (the indicator of oxidative stress decreased by 1.4 times after treatment p>0.001) and the content of antioxidant protection indicators increased: the indicator of antioxidant protection of blood serum increased by 1.4 times, the concentration of superoxide dismutase - by 1.9 times (p>0.001), glutathione peroxidase - by 1.4 times (p>0.001), coenzyme Q10 - by 4.5 times (p>0.001). The obtained data can be used to determine the risk of progression of glaucomatous optic neuropathy in patients with glaucoma who have had a coronavirus infection.

Системная гипотония и низкое перфузионное давление как факторы прогрессирования первичной открытоугольной глаукомы

Glaucoma progression is still a relevant issue in up-to-date ophthalmology. An important prerequisite for stabilizing glaucoma is the achievement of the target intraocular pressure (IOP). However, many patients with primary open-angle glaucoma (POAG) continue to suffer vision loss despite IOP reduction. Additional factors are also important for glaucoma progression, e.g., blood pressure (BP) and ocular perfusion pressure (OPP). Multiple published data have shown a decrease in blood flow velocity in the retrobulbar vessels, choroid, retina, and optic nerve in patients with glaucoma. A decrease in OPP is a predictor of insufficient intraocular blood supply. Systemic BP has a strong effect on OPP. Intensive treatment for hypertension significantly reduces BP, decreases OPP, and prevents the progression of glaucomatous optic neuropathy. A new paradigm shift that implies a personalized approach to the choice of diagnostic and treatment strategy for glaucoma is emerging. This paper reviews current published data on the effect of systemic hypotension and low OPP on POAG progression. KEYWORDS: glaucoma, intraocular pressure, blood pressure, hypertension, hypotension, perfusion pressure. FOR CITATION: Мyakonkaya O.S., Sarkisyan A.S., Seleznev A.V., Kuroyedov A.V., Brezhnev A.Yu. Systemic hypotension and low perfusion pressure as risk factors for primary open-angle glaucoma progression. Russian Journal of Clinical Ophthalmology. 2023;23(4):202–206 (in Russ.). DOI: 10.32364/2311-7729-2023-23-4-5.

The place of endoscopic laser cyclodestruction in the system of microinvasive glaucoma surgery

Glaucoma is one of the leading causes of irreversible blindness in the world. Reducing intraocular pressure is the only way to slow down the progression of glaucomatous optic neuropathy. Minimally invasive glaucoma surgery aims to provide a safer way of reduction of intraocular pressure than traditional methods, and at the same time it is capable to reduce dependence on antihypertensive therapy. Cyclodestructive high-precision method of reducing the production of aquоeus humor occupies a confident position among modern minimally invasive glaucoma surgery methods. The data obtained as a result of studying the literature confirm our idea on the endoscopic laser cyclodestruction method as a minimally invasive, safe, reliable antiglaucomatous component of the combined surgical treatment of cataract and glaucoma.

Значимость нарушений ретинальной микроциркуляции как предикторов прогрессирования глаукомной оптической нейропатии

Purpose – to assess the significance of retinal microcirculation disorders in progression of glaucomatous optic neuropathy (GON). Material and methods. In this 2-year prospective study 85 patients (124 eyes) the vessel density of the superficial parafoveal plexus (VD parafovea) and peripapillary retina (VD ppr) were measured with optical coherence tomography angiography, peripheral resistance index (RI) and blood flow velocity of the posterior short ciliary arteries (PSCA) and the central retinal artery (CRA) were studied by color Doppler flow mapping method. The predictor properties of each indicator were calculated from the area under the ROC curve (AUC). Results. The results of the study revealed a high significance of the values of relative density of the superficial plexus vessels in the parafoveolar region (VD parafovea AUC 0.70 ± 0.07), and the relative density of the microvasculature of the optic nerve head (ONH) and peripapillary retina (VD ppr 0.715 ± 0.07) as predictors of the progression of GON. Keywords: primary open-angle glaucoma, glaucomatous optic neuropathy, ocular blood flow, optical coherence tomography angiography

Significance of dyslipidemia for primary open-angle glaucoma

Reduction of intraocular pressure is currently considered as the main strategy to stop or slow down the progression of glaucomatous optic neuropathy. However, this goal is achieved in only 1 in 7 patients with primary open-angle glaucoma (POAG). Therefore, it is important to determine further risk factors that can be therapeutically influenced. One example of such risk factors is lipid metabolism disorders. Material and methods. Literature search in PubMed using the queries “primary open-angle glaucoma” and “dyslipidemia” limiting oneself to the period from 2000 to 2021. Results. POAG is currently considered to be a systemic neurodegeneration with neuroinflammation at the forefront. Oxidized low density lipoprotein (oxLDL) acts as a free radical (so-called bioactive lipid) with pro-inflammatory properties and promotes glaucomatous neuroinflammation. Conclusion. In addition to a personalized targeted pressure-oriented intraocular pressure reduction, LDL-associated lipid metabolic disorders should be corrected in every POAG patient. LDL cholesterol below 100 mg/dl (2.6 mmol/l) in the blood is the critical threshold level.

Analysis on the effect of eye globe diameters on the biomechanics of posterior ocular tissues during horizontal adduction

Abstract In this work, an attempt has been made to analyze the influence of pathological changes in eye globe dimensions towards the mechanical responses of optic nerve head tissues during eye adductions. For this study, a 3D baseline model geometry of posterior ocular tissues has been constructed. The eye globe diameters of the model are modified to mimic the changes in ocular globe morphology in control, glaucoma, myopia and glaucoma with myopia conditions. Adductions are simulated for each modified model as the rotation of the globe from 1o to 10o in steps of 1o. von Mises strain in lamina cribrosa (LC) and posterior displacement of LC are estimated. Results show that strains developed in LC and its posterior displacement are higher in diseased eyes compared to healthy eyes. It appears that eyes with higher axial length and globe anisotropy are more susceptible to optic nerve head damage. This study might be extended to assess the progression of glaucomatous optic neuropathy.

On the optimal values of «target» intraocular pressure

Current statistics show that glaucoma is the main cause of irreversible blindness worldwide. This fact generates continued interest in the search for new methods of rapid and accurate diagnosis of the disease. Presently, reducing the level of intra-ocular pressure (IOP) is the only proven strategy for slowing the progression of glaucomatous optic neuropathy. As such, achieving the so-called «target» pressure is the aim of any effective anti-glaucoma therapy. However, as practice shows, compensation of IOP does not always lead to stabilization of glaucoma progression. The concept of determining the «target» level of IOP implies a percentage decrease calculated by formulas, or a predetermined value, or a range of values. However, none of these strategies are considered as the leading one. The definition of «target pressure» is multifaceted and requires attention to many different factors. In addition, the understanding of how the level of IOP affects the progression of glaucoma is constantly evolving. In this review we summarize the data on the concept of «target» IOP, as well as on various concepts of achieving it.

Secondary Glaucoma After Blunt Ocular Trauma

Introduction: Ocular trauma is an important cause of unilateral visual impairment and blindness. Among several agents of ocular trauma, blunt trauma is the most common and can lead to secondary glaucoma. Secondary glaucoma due to blunt ocular trauma can be unnoticed and undetected until the formation of glaucomatous optic neuropathy (GON) occurs. This case might not be neglected. Delay in treatment can lead to the progression of GON. Case Presentation: A 68-year-old woman presented to the outpatient clinic in Undaan Eye Hospital complaining of decreased vision and pain in the left eye after blunt trauma to the eye. Her left eye vision was limited to detecting hand motions (1/300) and the intraocular pressure (IOP) was 37.8 mmHg. On the slit lamp biomicroscopic examination, the left pupil was mid-dilated, lens opacification and phacodenesis were detected. The cup-to-disc ratio (CDR) of the left eye increased (0.8-0.9) through the funduscopic examination. Secondary glaucoma due to subluxated lens was diagnosed for the left eye. The patient was given topical and oral antiglaucoma medications and was evaluated after one week of drug use. Since the IOP remained elevated after medical therapy, left eye trabeculectomy was conducted. Bleb was formed postoperatively and the IOP was getting normal without oral glaucoma medications. Conclusion: Blunt ocular trauma can lead to secondary glaucoma. Thorough examinations and immediate treatments should be conducted to preserve patient’s vision and prevent further optic nerve damage.

Rationale for early lens extraction in the treatment of primary angle closure disease

PURPOSE. To demonstrate the advisability of early lens extraction in the treatment of primary angle closure disease in clinical practice.METHODS. The study presents three clinical cases with patients at different stages of primary angle closure disease (PACD). The first one is related to the development of a bilateral acute attack of primary angle closure (PAC) that happened in the intensive care unit during treatment for acute respiratory distress syndrome (ARDS) associated with COVID-19 pneumonia in a patient with a previously undiagnosed PACD. The second case demonstrates the progression of glaucomatous optic neuropathy (GON) in early primary angle-closure glaucoma (PACG) after laser peripheral iridotomy (LPI) and delayed selective laser trabeculoplasty (SLT) in a patient with increased lens thickness. The third example illustrates the progression of advanced PACG in the right eye (OD) and moderate PACG in the left eye (OS) due to formation of goniosynechiae after bilateral LPI, which required transscleral diode cyclophotocoagulation (TSCP) in OD and trabeculectomy in OS. Subsequently, bilateral cataract phacoemulsification with intraocular lens implantation (CPE+IOL) and SLT were performed.RESULTS. In the first clinical case, advanced PACG developed in both eyes within 2 months. After bilateral LPI, trabeculectomy, compensation of intraocular pressure (IOP) was achieved, visual functions stabilized. In the second clinical case, 5.5 years after LPI and SLT, an increase in the thickness of the lens was revealed (in OD by 0.2 mm, in OS by 0.48 mm). GON did not progress in OD (thinning rate of the retinal nerve fiber layer was 0.94 µm/year, p=0.32) and the progression rate in OS was -1.04 µm/year (p=0.018). Taking into account the lens-involved mechanism of PACD progression, bilateral CPE+IOL was recommended. In the third clinical example, IOP remained elevated after bilateral LPI, TSCP in OD and trabeculectomy in OS as a result of goniosinechiogenesis, and therefore CPE+IOL also did not lead to its decrease. After bilateral SLT, compensation of IOP was achieved without local hypotensive therapy (IOP measured by Icare: OD 18.0 mm Hg, OS 15 mm Hg).CONCLUSION. In order to preserve visual functions, CPE+IOL is highly recommended at the very beginning of PACD, before the formation of GON and goniosynechiae. This is dictated by the dominant role of the lens-involved mechanism in PACD formation, as demonstrated in the described clinical examples.

Predictors of glaucoma in patients with uveitis and scleritis.

To examine risk factors for development of glaucoma in a large cohort of subjects with uveitis and scleritis. Retrospective review of subjects diagnosed with uveitis or scleritis between 2006 and 2019 at Auckland District Health Board. Subjects were excluded if they had glaucoma due to another cause. Main outcome measure was development of glaucoma. Data for local steroid use was not available. 3462 eyes of 2414 subjects were included in the study. Mean follow-up was 5.7 years (total follow-up time 19,897 eye years). Median age was 44.3 years and 1189 (49.3%) were female. Glaucoma developed in 222 eyes (6.3%) during the follow-up. Five-year cumulative risk of glaucoma was 6.2% (CI 5.0-7.5%) for anterior uveitis, 5.4% (CI 3.2-9.0%) for intermediate uveitis, 1.6% (CI 0.4-6.7%) for posterior uveitis, 8.7% (CI 6.5-11.7%) for panuveitis, and 3.2% (CI 1.0-9.5%) for scleritis. Five-year cumulative risk of glaucoma was lowest in HLA-B27 uveitis at 0.9% (CI 0.4-2.1%) and highest in viral uveitis 15.1% (CI 10.1-22.3%), sarcoidosis 9.9% (CI 6.1-15.9%) and tuberculosis 9.7% (CI 5.4-17.0%). On multivariate analysis, risk factors for development of glaucoma were older age at presentation, higher presenting intraocular pressure, chronic inflammation, and cystoid macular oedema. Glaucoma is a common complication of uveitis and scleritis and was more frequent in older subjects, high presenting IOP, chronic inflammation and those with cystoid macular oedema. Local steroid therapy contributes to this, but is not quantifiable in this study. Targeted screening is required to avoid irreversible progression of glaucomatous optic neuropathy.

Efficacy of Laser Iridotomy in Primary Angle Closure Suspects and Primary Angle Closure Glaucoma

Addressing the issue of a closed angle of the anterior chamber plays a key role in preventing the development of angleclosure glaucoma.The purpose: to compare the efficacy of Laser Peripheral Iridotomy (LPI) at the stage of primary angle closure suspects (PACs) with LPI carried out at the initial stage of primary angle-closure glaucoma (PACG).Materials and methods. A clinical case of a primary angle closed disease (PACD) in a patient with PACs after LPI in the right eye and with PACG after LPI, selective laser trabeculoplasty (SLT) and phacoemulsification with intraocular lens implantation in the left eye is presented. A detailed examination was performed in dynamics, including methods of visualization of the anterior and posterior segments of the eye.Results. After 2.5 years, the anterior chamber angle in the right eye retained an expanded profile after LPI (up to 30°), no signs of PACG development were recorded. On the left eye, the anterior chamber angle remained closed (9°) with an IOP of 24 mm Hg at the maximum hypotensive therapy with eye drops. Despite the absence of progression of glaucomatous optic neuropathy in both eyes, the risk of the transition from the initial stage to the moderate and advanced stage of PACG in the left eye still remains due to the presence of goniosynechia and possible fluctuations of intraocular pressure.Conclusion. LPI is more effective at the stage of PACs and its implementation is advisable in order to prevent the development of PACG.

Ретинопротективная терапия глаукомы

Background: a fluctuating blood pressure (BP) and particularly an overnight hypotension is the key adverse factor leading to the progression of glaucomatous optic neuropathy. Aim: to study the effectiveness of a neuroprotective drug (a complex of water-soluble polypeptide fractions) in patients with unstable primary open-angle glaucoma and normalized ophthalmotonus by monitoring the morphological and functional parameters of the retina and optic nerve. Patients and Methods: this six-month study included 30 patients (60 eyes) with primary open-angle stage 2 or 3 compensated glaucoma and unstable course. At the first stage of the study, a daily blood pressure monitoring (DBPM) was used for all patients to assess changes in systemic hemodynamics. The patients were split into 2 groups, each group consisting of 15 individuals, who received a different number of intramuscular (IM) injections of a neuroprotective drug, 5.0 mg: 10 injections in group 1 and 20 injections group 2. A comprehensive examination of patients was carried out at the beginning of the follow-up period, and at 3 and 6 months after the completion of the course of treatment with the drug. It included visometry, tonometry, static perimetry and optical coherence tomography of the retina and optic nerve. Results: based on the DBPM, the normal circadian BP pattern was disturbed in 27 (90%) patients. During the entire follow-up period, both groups demonstrated an improvement in visual acuity. The results of static perimetry indicated the stabilization of the glaucoma process in group 1 patients, while in group 2 where the treatment course with the neuroprotective drug lasted twice longer, it was possible to achieve an improvement in photosensitivity of the retina, as proven by the positive trends in MD and PSD indices. The results of the functional studies fully correlated with the morphological findings as demonstrated by a reliable stabilization of the status of the retinal nerve fiber layer and ganglion complex, as well as the volume of the optic nerve head. At the same time, a longer course of therapy with the drug was accompanied not only by a significant increase in the above parameters, but also by a decline in the volume of excavation of the optic nerve disc. Conclusions: the use of the neuroprotective drug in patients with the progression of primary open-angle glaucoma co-occurring with the changes in systemic hemodynamics enabled to achieve stabilization and improvement of the visual functions. Keywords: glaucoma, systemic blood pressure, peptide preparation, retinal ganglion cells, neuroprotection, retinoprotection. For citation: Makarova A.S. Retinoprotective therapy of glaucoma. Russian Journal of Clinical Ophthalmology. 2022;22(4):210–215 (in Russ.). DOI: 10.32364/2311-7729-2022-22-4-210-215.

The connection of polymorphism and diurnal changes of the biological clock gene expression with the risk of progression of primary open-angle glaucoma

The purpose of this work is to study the connection betweengenetic factors (polymorphism and expression of key genes of the biological clock (KGBC), key genes controlled by KGBC, melatonin receptors) and the diurnal oscillation of melatonin in patients with stable and progressing primary open-angle glaucoma. Materials and methods. The study involved 115 patients aged 53–86 (averagely, 68.8 ± 7.9 years) with stable and progressive glaucoma. All patients underwent primary ophthalmological examination, tested for diurnal body temperature profile, intraocular pressure (IOP), melatonin (by the DLMO protocol) and were typed for key genes of the biological clock using the real-time polymerase chain reaction. We studied the sleep phase shift to later hours in carriers of the G-allele of the melatonin receptor gene during the progression of glaucoma. Results. The study of the clinical and genotypic features of the POAG course revealed phasal shifts of the circadian rhythms of body temperature, IOP, salivary melatonin levels and sleep phases which contributed to the progression of glaucomatous optic neuropathy. Certain polymorphic variants of genes contribute to individual frequent manifestations of desynchronosis. The clock rs1801260 and MTNR1B rs10830963 gene polymorphism was found to be related to disturbances in melatonin production and sleep phase. Conclusion. Complex manifestations of circadian desynchronization accompanying the progressive course of glaucoma are the late phase of rhythms and a decrease in sleep duration, body temperature, salivary melatonin and IOP, internal desynchronization between IOP and body temperature, IOP and sleep, evening dyslipidemia. The revealed patterns open up prospects for future studies of the relationship between polymorphism and daily changes of the expression of key genes in the biological clock with the risk of progression of primary open angle glaucoma.