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Ophthalmology in Russia

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Vol 11, No 3 (2014)
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https://doi.org/10.18008/1816-5095-2014-3

REVIEWS

4-12 5482
Abstract

Glaucoma and diabetic retinopathy (DR) are the most frequent reasons of visual loss and disability. Combination of glaucoma and DR causes worse prognosis. Similarity of pathogenetic mechanisms of DR and glaucoma allows consideration of more frequent development of primary open-angle glaucoma among patients suffering diabetes mellitus. To reveal these diseases at the earliest stages is one of the most difficult ophthalmological problems. The contemporary methods of DR and glaucoma diagnostics are optical coherence tomography and Heidelberg retina tomography. They give an opportunity to estimate the dynamics of pathological process and the efficiency of surgical and pharmacological treatment. Optical scanning of an optic disk and peripapillary retina gives a chance to estimate up to 20 morphometric parameters. Determination of retinal nerve fiber layer (RNFL) thickness in peripapillary zone reflects a condition of nerve fibers and extent of their defeat. It is shown that in glaucoma there is a thinning of RNFL and a neuroretinal rim. In early diagnostics of glaucoma the parameters of optic disk characterizing neuroretinal rim are considered the most informative. OCT considerably expands diagnostic research possibilities of structural and morphological retinal changes in a 
macular zone in patients with DR and DME. Measurement of retinal thickness in macular area is a key point in diagnostics and tactics of treatment. The standard method of DR therapy is retinal laser coagulation. However, laser photocoagulation as monotherapy is not effective enough in patients with diffuse and cystoid macular edema. It is more reasonable to use retinal laser photocoagulation in combination with antiangiogenic therapy for treatment of the diabetic macular edema (DME) and DR. The special emphasis is put on development of treatment algorithm of combination of glaucoma and diabetic retinopathy. Therapy of neovascular glaucoma in patients with diabetes mellitus type 2 is a complex problem. Such patients traditionally get panretinal laser photocoagulation. Recently anti-VEGF-agents are used as additional therapy of neovascular glaucoma. However, nowadays the influence of antiangiogenic treatment on dynamics of clinical and morphological parameters in patients with the combined pathology is insufficiently investigated.

13-19 1824
Abstract

Photochemical crosslinking is widely applied in ophthalmology. Its biochemical effect is due to the release of singlet oxygen that promotes anaerobic photochemical reaction. Keratoconus is one of the most common corneal ectasia affecting 1 in 250 to 250 000 persons. Currently, the rate of iatrogenic ectasia following eximer laser refractive surgery increases due to biomechanical weakening of the cornea. Morphologically and biochemically, ectasia is characterized by corneal layers thinning, contact between the stroma and epithelium resulting from Bowman’s membrane rupture, chromatin fragmentation in keratocyte nuclei, phagocytosis, abnormal staining and arrangement of collagen fibers, enzyme system disorders, and keratocyte apoptosis. In corneal ectasia, altered enzymatic processes result in the synthesis of abnormal collagen. Collagen packing is determined by the activity of various extracellular matrix enzymes which bind amines and aldehydes of collagen fiber amino acids. In the late stage, morphological changes of Descemet’s membrane (i.e., rupture and detachment) develop. Abnormal hexagonal-shaped keratocytes and their apoptosis are the signs of endothelial dystrophy. The lack of analogs in domestic ophthalmology encouraged the scientists of Ufa Eye Research Institute to develop a device for corneal collagen crosslinking. The parameters of ultraviolet (i.e., wavelength, exposure time, power) to achieve the desired effect were identified. The specifics of some photosensitizers in the course of the procedure were studied. UFalink, a device for UV irradiation of cornea, and photosensitizer Dextralink were developed and adopted. Due to the high risk of endothelial damage, this treatment is contraindicated in severe keratoconus (CCT less than 400 microns). Major effects of corneal collagen crosslinking are the following: Young’s modulus (modulus of elasticity) increase by 328.9 % (on average), temperature tolerance increase by 5°C, and collagen fiber diameter increase by 12.2 % (anterior stroma) and 4.6 % (posterior stroma). In mild bullous keratopathy, corneal crosslinking provides antimicrobial effect. In moderate and severe keratopathy, crosslinking reduces pain and corneal edema and improves visual acuity immediately after the procedure. A case of HSV keratitis exacerbation was described. Amongst the complications, infection, halos, and posterior segment damage should be mentioned. Poor refractive results can be improved by the implantation of intrastromal corneal ring segments.

CLINICAL & EXPERIMENTAL RESEARCH

20-27 1311
Abstract

Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR) and agerelated macular degeneration (AMD).

Patients and Methods. In the main study group included 22 patients (22 eyes) with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis) was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA). The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR).

Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05) was significantly lower than in the control group (0,8±0,01, p <0.05); retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment), a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB) to 14,58±1,68 (dB), (p <0.05). The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively.

Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of type 2 diabetes pathogenesis is justified and leads to a significant improvement in clinical and functional and morphological parameters of the retina.

28-32 1610
Abstract

Purpose: To evaluate the sensitivity and specificity of ganglion cell complex (GCC) parameters, obtained with optical coherence tomography (OCT) and to determine their accuracy and ability to differentiate healthy from primary open-angle glaucoma patients.

Patients and methods. 84 eyes of primary open-angle glaucoma patients and 40 eyes of healthy individuals were enrolled in the study. All of them underwent complete eye examination, including standard automated perimetry (HFA II) and OCT (RTVue-100). Avg. GCC (average GCC), Sup. GCC (superior GCC), Inf. GCC (inferior GCC), GLV (globаl loss volume), FLV (focal loss volume) and RNFL (retinal nerve fiber layer — ONH map) were measured. ROC curves
were created and sensitivity and specificity were calculated for each of these parameters.

Results.The highest sensitivity and specificity was found for GLV and the lowest for Sup. GCC. Area under the ROC curves (AUC) for GLV was found to be the largest and the smallest for Sup. GCC.

Conclusion. Parameters from GCC map have high sensitivity and specificity. Their diagnostic capability is similar, even slightly better than the one of RNFL. GLV has the highest diagnostic accuracy for primary open-angle glaucoma detection in this study.

33-37 1178
Abstract

Purpose: To conduct a comparative analysis of YAG laser vitreolysis and posterior vitrectomy in diabetic hemophthalmus.

Materials and Methods. The study included 96 patients (106 eyes) aged 43‑72, 57 women and 39 men, with PDR complicated by hemophthalmus. Of them, there were 57 women and 39 men. All the patients have been divided into 2 groups. Group I consisted of 61 patients (67 eyes) with YAG laser vitreolysis. 35 patients (39 eyes) in group II had a retrospective analysis of the results of surgical vitrectomy for PDR complicated by hemophthalmus. There were 10 men and 25 women with the average age of 59,4±9,2. All the patients were examined prior to the treatment and in the dynamics on the 10th day; 1, 3, 6, 9 and 12 months. Examination methods: visometry, tonometry, biomicroscopy, ophthalmoscopy and ultrasound methods (B-scan and quantitative sonography). Quantitative sonography was performed to determine the density of the hemophthalmus.

Results. Visual acuity 1st group patients before treatment in 1st subgroup was 0,169±0,05, in 2nd subgroup — 0,05±0,007, in 3rd subgroup — 0,012±0,003, the subgroups have to be reflected in the previous section, in group II — 0,039±0,012 (Fig. 6). Visual acuity was significantly higher in subgroup 1 compared to 2 — (р<0,005), compared to 3 (р<0,001) and to a comparison group (р<0,005). In subgroup 2 it was significantly higher compared to 3 (p <0.001), there was no significant difference  ith the group II (p> 0.05). Compared with the group II visual acuity in subgroup 3 was significantly lower (р<0,05). Period of hemophthalmia in 1st subgroup was 1,71±0,62 months, in 2nd subgroup — 2,77±1,48, in the 3rd subgroup — 2,64±1,32 months, in group II — 2,32±1,05 months.Vitreous surgery remains the treatment of choice, but the complications after it are observed in 15‑46 % of cases, the recovery of visual function is only in 45 % of cases.

Conclusions. 1. Vitrectomy being the gold standard and cardinal solution in the treatment of diabetic hemophthalmus has a number of complications and requires expectant tactics and satisfactory somatic status of the patients. 2. Use of YAG laser vitreolysis at early stages, the possibility of repeated surgeries, a favorable safety profile and a narrow range of complications make it possible to recommend this method to treat patients with DR complicated by hemophthalmus. 3. Given that vitrectomy is performed at later stages of the hemophthalmus the YAG laser vitreolysis can be used at early stages as an alternative method to treat diabetic retinopathy complicated by recidivous hemophthalmus.

38-44 1074
Abstract

Aim. To perform immune mapping of the peripheral part of visual analyzer and optic nerve in order to identify potential antigenic targets of autoimmune attack.

Methods. Eyes enucleated for terminal painful glaucoma (n = 30) were studied. Immunohistochemistry (IHC) was performed on paraffin-embedded sections of isolated retina and optic nerve using a broad panel of antibodies, i.e., monoclonal murine anti-MBP (myelin basic protein) antibodies, polyclonal rabbit anti-alpha fodrin antibodies, monoclonal murine anti-NSE2 (neuron-specific enolase) antibodies, monoclonal murine anti-GFAP (glial fibrillary acidic protein), and polyclonal rabbit anti-S100 antibodies. IHC reaction was visualized using Mouse and Rabbit Specific HRP / AEC Detection IHC Kit. IHC reaction without primary antibodies included was a negative control. IHC reaction was considered as follows: negative — no specific cellular staining or less than 10 % of cells are stained; mild — 10‑30 % of cells are stained (+); moderate — 30‑75 % of cells are stained (++); marked — more than 75 % of cells are stained (+++); overexpression — 100 % of cells intensively express markers. Additionally, staining intensity was considered as mild (+1), moderate (+2), strong (+3) and intense (+4).

Results. Immune mapping with a broad panel of monoclonal antibodies identified ocular structures which were stained with IHC markers. Retina was stained with almost all markers of neural differentiation (i.e., antibodies against NSE, GFAP, S100, and α-fodrin) excepting anti-MBP autoantibodies. IHC reaction intensity in retinal layers and structures varied and depended on markers. Moderate (2+) staining with antibodies against MBP, NSE, GFAP, and S100 and marked (3+) staining with antibodies against alpha-fodrin was detected in the cytoplasm of optic nerve glia.

Conclusion. Complete labelling of retina structures was performed. As a result, IHC profiles of retinal neurons, optic nerve axons, interneurons, and microglial cells were described. IHC profiles of retinal layers and optic nerve are useful markers which can be applied in serological diagnostics of various ocular disorders.

45-51 1041
Abstract

Purpose: is to develop a technique for local subretinal injection of xenogeneic stem cells labeled with magnetic particles and to prove experimentally its effectiveness.

Material and methods: We used a line of stem cells HEK-293 GFP,
labeled with magnetic particles. The study was made on 84 eyes of 42 chinchilla rabbits 6 months of age, the weight were from 2.5 to 3.5 kg. All right eyes were experimental (42 eyes) and all left eyes (42 eyes) were the control group. In the experimental group we used original complex of polymer elastic magnetic implant (PEMI) with laser probe and fixed it to the sclera, then we made a median vitrectomy and injected HEK-293 GFP under the retina using a specially designed dispenser. In the control group PEMI was not fixed. We examined animals using biomicroscopy, ophthalmoscopy, ultrasound scanning, optical coherence tomography  OCT), computer tomography (CT), morphological study (cryohistological sections) in 1, 3, 5, 7, 14 day and 1 month after surgery.

Results: According the results of biomicroscopy in observation periods up to 3 days the vascular injection was visualized in the area operation. According the results of ophthalmoscopy and ultrasound scanning in 1 day the local retinal detachment was visualized in the area of local injection of the stem cells, which was not visualized in terms of further observations. CT helped us to confirm the local place of PEMI fixation. The morphological study results showed that cells were located in the subretinal space up to 14 days in the experimental group, and only up 3 days in the control group.

Conclusion: The suggested surgical technique enables to control the injection of cells into the subretinal space, reduces the risk of tissue damage and exit cells in the vitreous space. The suggested methodology allows the fixing of the cellular material in the local place of the injection and enables to predict cells`s movement.

52-55 1211
Abstract

The impossibility of lacrimal apparatus direct examination impedes the diagnostics of its disorders, particularly in younger children. Modern diagnostic technology, multi-spiral computed tomography (CT), can help to resolve this problem. However, this method is rarely used in pediatrics. Contrast-enhanced CT of lacrimal ducts was performed in 37 children (41 eyes) with lacrimal drainage disorders (local obstruction on various levels, n = 20; posttraumatic changes, n = 8; tumors, n = 4). Ultravist was used as a contrast since its viscosity and pH are similar to tear. Additionally, this agent has low toxicity and good tolerability (these characteristics are of great value for this age group). The indications were nasolacrimal duct obstruction; associated lacrimal ducts and surrounding tissues trauma; concomitant ear, nose, and throat problems; lacrimal sac tumors. Multi-spiral CT identified the cause and the level of lacrimal ducts obstruction as well as the relationship between the ducts and surrounding tissues. Detailed lacrimal ducts examination by multi-spiral CT provided pathogenically relevant treatment thus increasing its efficacy. The treatment restored tear drainage in 100 % of children. Ear, nose, and throat problems that accompany lacrimal drainage disorders affects the outcome of forthcoming surgery. Their pre- or intraoperative treatment increases the efficacy of the procedure. Water-soluble contrast, Ultravist, is safe and decreases exam

time. Multi-spiral CT provides 3 D image reconstruction which is of great importance for data interpretation.

56-62 1226
Abstract

Currently, most surgeons use 27G needles to perform intravitreal and endolymphatic administration and reflexogenic zone blockade. However, their use is associated with certain disadvantages and complications.

Aim. To develop a device for intravitreal and endolymphatic drug administration and sinocarotid zone blockade.

Methods. A device for intravitreal and endolymphatic drug administration and sinocarotid zone blockade was developed. It consists of an original adapter, 30G carpule needle, and a syringe. Pre-clinical trials included comparative evaluation of this device and a rather well-known instrument for intravitreal and endolymphatic drug administration and sinocarotid zone blockade (a syringe with 27G needle). Clinical trials involved 150 patients aged 36 years and older.

Results. The device consists of a syringe, 30G carpule needle, and an original three-stage hollow adapter that attaches the needle to the syringe. The needle has a cannula to be attached to the adapter. The cannula and the second stage of the adapter have the thread with an aligning arrangement The third stage of the adapter is made in a form of a truncated cone that tightly goes into the cannula thus providing reliable fixation of the needle. The device: (1) minimizes the leakage of a drug in the course of the procedure thus providing more accurate drug administration and preventing its overuse; (2) reduces complication risk and improves the safety of intravitreal and endolymphatic drug administration and sinocarotid zone blockade; (3) improves the tolerability of intravitreal and endolymphatic drug administration and sinocarotid zone blockade; (4) improves personal readiness to undergo maintenance retreatment. The utility model application was filed, and the filing receipt No. 2014109466 was acquired on March 12, 2014.

Conclusion. The device provides optimal intravitreal and endolymphatic drug administration and sinocarotid zone blockade.

63-67 1007
Abstract

Possible association between corneal infections and contact lenses (CLs) wearing of various design to correct ametropia in children was analyzed. Between 2011 and April 2014, 20 children (7 boys, 13 girls) aged 9‑17 years which were diagnosed with traumatic keratitis were admitted to Morozov Children’s Hospital. All patients used CLs (rigid, n = 1; soft, n = 9; orthokeratology, n = 10) to correct ametropia for 6‑48 months. There are pretty strong evidences that CLs (including orthokeratology ones) provide better quality of vision and life as compared with spectacles, reduce myopia progression, and promote better accommodation. However, in spite of these advantages, CLs have disadvantages as well. People who wear CLs may require frequent eye care specialist follow-up due to the higher risk of corneal disorders. Even nearly perfect CL represents a foreign body (especially for a children eye) that may provoke numerous complications including severe ones. With accurate fitting, proper care, and careful monitoring of the cornea, CLs should be safe and effective.

PHARMACOLOGY

68-73 1150
Abstract

Aim. To measure minimal inhibitory concentration (MIC) values for modern topical antimicrobials against common ocular pathogens.

Methods.Antimicrobials most commonly used in ophthalmology (fluoroquinolones and aminoglycosides) are dose-dependent drugs, i.e., the rate of microbial death increases in direct proportion to their concentrations. To determine MICs, we applied Hi Comb MIC Test (E-test). 105 patients aged 2 months through 7 years which were diagnosed with various inflammatory disorders of anterior segment were  xamined. MIC values for most commonly used antimicrobials, i.e., ciprofloxacin / Cipromed (Sentiss Pharma, Gurgaon, India), ofloxacin / Floxal (Baush & Lomb, Rochester, New-York), levofloxacin / Signicef (Sentiss Pharma, Gurgaon, India), moxifloxacin / Vigamox (Alcon, Fort Worth, Texas), gatifloxacin / Zymar (Allergan, Irvine, California), and tobramycin / Tobrex (Alcon, Fort Worth, Texas), were measured.

Results. The analysis revealed that the most effective antibacterial drug against microbial isolates in children (i.e., Staphylococci spp.) was levofloxacin. MIC for this agent against Streptococci spp. and Gram-negative microbes was low as well. Moxifloxacin is preferred for the treatment of ocular inflammation provoked by Streptococci spp. as MIC of this antimicrobial against Streptococci spp. was the lowest. MIC of ciprofloxacin against Gram-negative flora was the lowest. These data demonstrate generally recognized high efficacy of this drug. MIC value for tobramycin against all bacterial isolates was the highest.

74-79 893
Abstract

Aim. To assess the effectivity of autumnal allergic blepharoconjuctivitis complex therapy.

Methods. 25 autumnal allergic blepharoconjuctivitis patients (50 eyes) were examined before and after complex treatment that included olopatadine hydrochloride 1 mg / ml (instillations 2 times a day), cetirizine 10 mg (1 tablet a day), and steroid drug (insufflations 2 times a day). Dry eye patients additionally received hyaluronic acid 1 mg / ml (instillations 2 times a day). 10 controls (20 eyes) were prescribed only the above-mentioned treatment. In 15 study group patients (30 eyes), Blepharogel 1 was applied on lid margins. Routine eye examination, clinical symptom assessment, Schirmer’s and Norn’s tests, xerosis meter and lissamine green staining evaluation, and anterior segment photography with computed morphometry were performed.

Results. Compositae allergy was diagnosed in all patients. Dry eye due to tear film instability, lipid deficiency, and mucin deficiency and epitheliopathy were diagnosed in 55 %, 35.5 % and 28.3 %, respectively. In study group, the treatment significantly and rapidly reduced patient-reported symptoms and blepharoconjunctivitis signs as well as significantly improved tear stability, lipid deficiency, mucin deficiency, and epitheliopathy as compared with controls.

Conclusion. Blepharogel 1 as a component of complex therapy increases the efficacy of autumnal allergic blepharoconjuctivitis treatment.

CASE REPORT

80-88 2705
Abstract

The article presents a case report of a patient with a cystic bleb in the early postoperative period after trabeculectomy. Patient complained of discomfort in a recently (4 weeks) operated eye. Medical regimen administered previously had been taken irregularly. Biomicroscopy revealed a high, encapsulated cystic bleb with thin walls and hyperemia. Intraocular pressure at the moment of examination was 27 mmHg. Local hypotensive therapy had been neglected by the patient. A local anti-inflammatory (tobramycin / dexamethasone fixed combination) and hypotensive (brimonidine / timolol fixed combination) therapy was administered. 24 hours later, when intraocular pressure decreased to 20 mmHg, a needle revision procedure was conducted for partial bleb wall destruction and subconjunctival injection of dexamethasone, fluorouracil and ranibizumab. During the next day examination the bleb was diffuse, with less hyperemia and an abundance of conjunctival microcysts in the central bleb’s zone. Intraocular pressure was 10.2 mmHg. No choroidal detachment was noted during ophthalmoscopy and OCT examination. The patient continued anti-inflammatory therapy. Another needling procedure with the same drug combination was repeated two weeks after due to an increased hyperemia. At the end of the four-week follow-up period the filtering bleb remained diffuse and the intraocular pressure was 13.2 mmHg. Dexamethasone drops were prescribed to be instilled 1‑2 times a day for a month. This case report demonstrates the method of restoring a functioning filtering bleb by the needle revision with antiinflammatory, cytostatic and anti-VEGF therapy for prolonging the hypotensive effect of a trabeculectomy in the presence of wound healing.

89-93 1463
Abstract

Purpose: Evaluation of the results of various treatment tactics of patients with post-traumatic retinal detachment pathology combined with aniridia and aphakia.

Patients and methods.The analysis of four clinical cases of surgical treatment of post-traumatic retinal detachment in conjunction with aniridia and aphakia was carried out. There was used a gradual approach of optic-reconstructive surgery: vitreoretinal stage by the standard method 23‑25 Ga with tamponade of vitreous cavity with silicone oil in two different ways. In one case, full eyeball tamponade was made, and in the other one it was made up to the diaphragm formed of polypropylene sutures. At the final stage — iridolenticular diaphragm was implanted (Reper-NN, Russia).

Results. In all cases, early postoperative reaction proceeded with the phenomena of fibrino-plastic iridocyclitis, which corresponded to the severity of the initial state and the volume of surgical intervention. Periods of observation of patients in the postoperative period ranged from 3 to 12 months. In three cases where the diaphragm was formed from polypropylene sutures there was noticed full retina adaptation, wherein silicone oil, introduced in the vitreous cavity, did not penetrate into the anterior chamber during the entire period of observation. In one case, where there was a complete eyeball tamponade with silicone oil epithelial and endothelial corneal dystrophy developed. Such an outcome of a clinical case, despite high functional results, is apparently related to the severity of the initial state, the need to re-intervention for recurrent retinal detachment and relatively early stages of iridolenticular diaphragm implantation.

Conclusion. Reconstructive surgery of posttraumatic aniridia and aphakia combined with retinal detachment requires a multistage approach. Reconstruction of anterior segment of the eye is preferably to carry out in long-term periods as after the trauma so after surgical treatment of retinal detachment. Choice of the method of eye cavity tamponade by silicone oil depends on the severity of the initial state, at that the formation of the diaphragm from polypropylene sutures provides longer tamponing by silicone, reduces the risk of postoperative complications.

GUIDELINES FOR THE PRACTITIONER

94-103 3168
Abstract

Allergic rhinoconjunctivitis is a chronic inflammatory IgE-mediated reaction to relevant allergens encountering nasal mucosa and conjunctiva. Allergen-specific IgE binds to high-affinity Fcε receptors (Fcε RI) expressed by ocular and nasal mast cells. Therefore, nasal mucosa and conjunctiva have common mechanisms of antigen recognition. Detailed clinical history and examination provide correct diagnosis, relevant allergen identification, symptom severity assessment, and therapeutic algorithm. Recently, an assay for the measurement of specific IgE antibodies against numerous (120) allergens in human blood, ImmunoCAP, was developed. Conventional allergic rhinoconjunctivitis treatment includes allergen avoidance, pharmacotherapy, and allergen-specific immune therapy. Four major classes of drugs are used for the treatment, i.e., antihistamines, corticosteroids, mast cell stabilizers, and vasoconstrictor agents (or decongestants). Occasionally, muscarinic receptor antagonists, antileukotrienes, and immunemodulators are used. Therapeutic strategy is determined by the effect of a drug on certain symptoms and allergy clinical course, adverse reaction and complication risks, age limitations, and costs. Stepwise approach to the treatment of allergic rhinoconjunctivitis should be based on
symptom severity. Full-text clinical guidelines are available on the official website of Russian Rhinologic Society (http://www.rhinology.ru / index1. php?id_page = 3&id_text2 = 43&num_text2 = 1).



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ISSN 1816-5095 (Print)
ISSN 2500-0845 (Online)