Assessment of the effectiveness and safety of fixed combination eye drops in the treatment of primary glaucoma

Introduction. Glaucoma is a progressive disease of the vision organ that leads to irreversible blindness. Due to increased intraocular pressure in this disease, retinal cells are destroyed, the optic nerve of the eye atrophies, and visual signals stop entering the brain. A person begins to see worse, peripheral vision is impaired, as a result of which the visibility area is limited. Mentions of glaucoma (translated from Greek this word means “green color of the sea”) are found in the works of Hippocrates dating back to 400 BC. However, modern ideas about this disease began to take shape only in the middle of the 9th century. Currently, glaucoma is understood as a fairly large group of diseases, often of different origins and with different courses. There is still no consensus on what causes the development of these ailments, but if left untreated, their outcome is the same — optic nerve atrophy and blindness. Target pressure is the level of intraocular pressure at which further death of optic nerve fibers is stopped; this is the pressure to aim for when treating a patient with glaucoma. It is also possible to conduct an examination — electrotonography, with which it is possible to determine the ratio of inflow and outflow of intraocular fluid. Electrotonography indicators influence the choice of further treatment. Additional comfort of use is provided by the keratoprotector carbomer with a pronounced moisturizing effect. The term «glaucoma» includes diseases that combine effective signs. These include: optic neuropathy, typical changes in visual function (central visual fields of the uterus and peripheral), atrophy (excavation) of the optic nerve, increased intraocular pressure. In the case of primary closed-angle glaucoma, which affects the increase in IOP, there is a blockage (complete or partial) of the outflow of intraocular fluid due to the overlap of the angle of the anterior chamber by the root of the iris or due to pupillary block.The disease occurs in people over 40 years old, and over the years its frequency only increases, which is approximately 20–30 % of all detected cases of primary glaucoma. In women, it is diagnosed 4 times more often than in men.

Primary closed-angle glaucoma is especially common among residents of Southeast Asia, Eskimos, and Chinese. The pathology has a genetically determined natural heritage, so first-line relatives have a very high risk of developing the disease due to predisposing anatomical causes of development. Closed-angle glaucoma develops extremely rarely in people with myopia; its successes are greater in people with hypermetropic refraction. An important role in the development of glaucoma belongs to the increase in pressure in the posterior chamber, the norm of which is determined by the mobility of the pupil. If the pupil is dilated, this causes the fold of the root of the iris. Thus, an increase in intraocular pressure in the posterior chamber occurs due to pupillary block; when the root of the iris moves forward, its bombage occurs. When the iris and the posterior surface of the cornea come into contact with the trabecula and Schwalbe's ring, the anterior chamber angle (ACA) is blocked, which increases intraocular pressure. When the entire perimeter of the ACA is blocked, an acute attack of glaucoma occurs.In flat iris glaucoma, the anterior chamber angle is gradually blocked, with impaired fluid drainage, which causes an increase in IOP and makes the iris flatter.Contributing factors may include: anterior attachment of the iris, location of the ciliary body processes in front, «beak-shaped» profile of the anterior chamber angle, which reduces its volume».Creeping» glaucoma occurs due to pressure of the iris on the trabecular tissue and the occurrence of anterior synechiae, causing an increase in IOP. The mechanism of occurrence of glaucoma with vitreous lens block has not been studied to date. Presumably, in eyes with hyperopia with a large lens size, there is an anatomical connection between it, the ciliary processes and the anterior surface of the vitreous body. Natural outflow of fluid into the vitreous body and into the retrovitreal space causes the formation of additional cavities that press the vitreocrystalline diaphragm forward. This leads to closure of the anterior chamber angle, development of goniosynechia, angle block. The situation takes the form of a constant acute attack. Most often, malignant glaucoma begins after antiglaucoma operations, although it can also develop spontaneously.

Diagnosis of primary glaucoma. To perform the diagnosis, the doctor measures the pressure of the eyeballs, measures the intraocular fundus and the optic nerve. Thanks to computerized high-precision equipment, the ophthalmologist can make a comprehensive conclusion, during which an accurate picture of the disease and its severity will be built.

During the adhesion test: IOP; field of vision; the ability of the eyes to refract light rays (refraction); angle and depth of the anterior chamber;strength of the lens.Periodic follow-up examinations will help to detect the insidious disease in time and stop its progression.

Objective: To assess the capability and security of the fixed combination drug brinzolamide 1 % + timoloili 0,5 % in the cure of patients with primary open angle glaucoma.

Material and methods of research : Atotal of 32 patients (48 eyes) were under observation, among them there were 19 men (59.4 %), 13 women (40.6 %) aged from 48 to 76 years, the average age was 66 + 7.8 years. The study included patients with POAG at an advanced stage in 27 (56.2 %) eyes and at an advanced stage in 21 (43.8 %) eyes with elevated IOP on local therapy with the drug brinarga 2 times a day for 2 months. The examination of patients included: medical history, standard examination methods and optical coherence tomography. The standard deviation of photosensitivity and the standard deviation pattern were determined using computer static perimetry using the threshold testing method.

Results of the study and their discussion: Among patients with an advanced stage of POAG (27 eyes), during treatment with brinarga, there was a significant decrease in elevated IOP by 7.8 ± 1.2 mm Hg, which amounted to 31.4 % of its initial level (p<0.001). In this group of patients with advanced POAG, the average individually tolerated pressure was 16.8±1.2 mmHg . With the use of brinarga 1 drop 2 times a day, individual IOP was achieved in these patients. After 1-month IOP was compensated and amounted to 16.4±2.1 mmHg. The values of visual acuity and computer perimetry corresponded to the values before the use of a fixed combination of antihypertensive drops. IOP values remained within 16.0±1.8 mm Hg. The initial IOP before treatment in patients of group 2 (21 eyes) with advanced stage glaucoma was on average 25.4±2.1, there was a significant decrease in increased intraocular pressure by an average of 7.6±1.6 mmHg. After 1-month IOP was compensated and amounted to 17.2±1.8 mmHg. The hypotensive effect during the use of brinarga in patients of group 2 (21 eyes) was on average and persisted for 2 months. observations. By the end of 2 months. observation, the decrease in IOP from the initial level was 30.3 %. In the second month of the study, both groups underwent visual acuity testing, computer perimetry and OCT, the data of which showed the absence of negative dynamics of the glaucomatous process and corresponded to the indicators before the drug change. The safety of using the study drug was assessed by the following subjective data: burning sensation, tingling during instillation, blurred vision. Two patients (3.8 %) had a feeling of burning and tingling with hyperemia of the conjunctiva in the eye after instillation of the drug, a feeling of temporary blurred vision was recorded in 3 (5.7 %) cases, a feeling of mild weakness and insomnia was observed in 1 (1.9 %). %) of the patient. According to the survey, in 87.6 % of cases, patients rated the drug tolerability as good. In addition, patients found the bottle of the drug to be soft and easy to use.

Conclusions: Brynarga is a well-tolerated and easy-to-use drug, which allows it to be recommended for the treatment of patients with POAG.

References:

1. Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology/2014;21(11):2081–. doi: 10.1016/j.optha.2014.05.13

3. Le A, Mukesh BN, McCarty CA. Risk factors associated with the incidence of open-angle glaucoma: the visual impairment project. Investigative Ophtalmology &Visual Science 2003;44(9): 3783–3789.doi.org/10.1167/iovs.03–0077

4. Barnebey H., Kwok S. Y. Patients' acceptance of a switch from dorzolamide to brinzolamide for the treatment of glaucoma in a clinical practice setting. Clinical therapeutics. 2000; 22(10):1204–1212.

5. Lanzl I, Raber T. Efficacy and tolerability of the fixed combination of brinzolamide 1 % and timolol 0.5 % in daily practice. Clin Ophthalmol. 2011; 5:291–298. https: doi.org/10.2147/OPTH.S16355

6. Lorenz K, Rosbach K, Matt A, Pfeiffer N. Addition of a fixed combination of brinzolamide 1 % / timolol 0.5 % to prostaglandin monotherapy in patients with glaucoma or ocular hypertension. Clin Ophthalmol. 2011; 5: 1745–50. doi:10.2147/OPTH.S25987

7. Shimizu Y, Nakakura S, Nishiyama M, Tabuchi H, Kiuchi Y. Efficiency, safety, and patient preference of switching from dorzolamide 1 % / timolol 0.5 % to brinzolamide 1 % / timolol 0.5 % while maintaining the prostaglandin F2-alpha analog. Clin Ophthalmol. 2015; 9: 475–82. doi:10.2147/OPTH.S79680