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UDC 617.713-002-053.2-08:615.03

G.Z. GALEEVA1,2, A.Yu. RASCHESKOV2

1Kazan State Medical University, 420012, Kazan, st. Butlerova, 49

2Children's Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, 420138, Kazan, st. Orenburgsky tract, 140

Galeeva Guzel Zakirovna - candidate of medical sciences, assistant at the department of ophthalmology, ophthalmologist, tel. +7-937-288-06-18, e-mail:

Rascheskov Alexey Yurievich - Candidate of Medical Sciences, Head of the Ophthalmology Department, tel. +7-987-296-97-44, e-mail:

The article provides a detailed description of the etiological structure and variability of clinical forms of keratitis in young children at the present stage. In 35% of cases, it is not possible to determine the etiology of keratitis, which requires combination therapy and a more careful approach to the selection of antibacterial drugs. In this regard, the influence of preservatives in eye drop forms of modern antibacterial drugs on the corneal epithelium was studied and the advantages of using a modern ointment form based on lanolin and the preservative nipagin (methyl parahydroxybenzoate) for the treatment of keratitis were substantiated.

Key words: keratitis, etiological structure, young children, corneal epitheliopathy, preservatives for ophthalmic dosage forms.

GZ GALEEVA1,2, A.Yu. RASCHESKOV2

1Kazan State Medical University, 49 Butlerov St., Kazan, Russian Federation, 420012

2Children Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, 140 Orenburgskiy Trakt, Kazan, Russian Federation, 420138

Eye ointment Oftocipro for combination treatment of keratitis in children

Galeeva GZ - Cand. Med. Sc., Assistant of Ophthalmology Department, ophthalmologist, tel. +7-937-288-06-18, e-mail:

Rascheskov A. Yu. - Cand. Med. Sc., Head of Ophthalmology Department, tel. +7-987-296-97-44, e-mail:

The article gives a detailed description of the etiological structure and variability of the clinical forms of keratitis in infants at the present stage. In 35% of cases it is not possible to determine the etiology of keratitis, which requires combination therapy and a more careful approach to the selection of antibacterial drugs. In this regard, there has been studied the effect of preservatives of ophthalmic dosage forms of modern antibacterial drugs on the corneal epithelium and proven the advantages of using modern ointment form based on Lanolin and preservative Nipagin (Methyl parahydroxybenzoate) for treatment of keratitis.

Key words: keratitis, etiological structure, infants, corneal epitheliopathy, preservatives of ophthalmic dosage forms.

Keratitis occupy a significant place in the structure of eye morbidity in young children. It should be noted that most children with this nosology are patients in ophthalmological hospitals. According to the ophthalmology department of the Children's Clinical Hospital, there has been an increase in the number of patients treated with keratitis over the past 3 years. The proportion of hospitalized patients with keratitis in 2012 was 5.6%, in 2014 - 6.6%. Noteworthy is not only the increase in the number of patients, but also the increase in the number of relapses of keratitis, reaching, in some children, up to 7-8 per year.

In this regard, it should be noted that in modern conditions the child’s body is exposed to many adverse environmental factors. Their implementation occurs through a decrease in the immunological reactivity of the body and local mechanisms of nonspecific resistance [1]. There is extreme tension in the immune response processes and insufficient reserve capabilities [2].

The mechanism described above affects all organs and systems, including the organ of vision. He, in our opinion, is leading in changing the nature of the course and clinical manifestations of keratitis in young children, the appearance of protracted, repeatedly recurrent cases of the disease that are difficult to treat, especially in an outpatient setting.

In connection with all of the above, the purpose of our study was to determine the etiological structure and clinical picture of keratitis in young children according to the ophthalmology department of the Children's Clinical Hospital and to determine the role of Oftocipro eye ointment in their complex treatment.

The study was conducted from 2012 to 2014. on the basis of the ophthalmology department of the Children's Clinical Hospital. We observed 56 children (88 eyes) aged 2 to 7 years with a diagnosis of keratitis. Of these, 24 children had a unilateral process, 32 children had a bilateral process. All children underwent a standard ophthalmological examination, including testing of visual acuity and refraction under conditions of cycloplegia, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, determination of corneal sensitivity, staining of the cornea with a 1% fluorescein solution (to determine the degree of epithelization of the infiltrate and the severity of corneal epitheliopathy). Additional research methods included a general blood and urine test, a blood test using PCR and ELISA for antibodies (Ig G, Ig M) to HSV, CMV, a quantitative test for antibodies to Giardia, roundworm, a blood test for total Ig E, a conjunctival smear culture for microflora, determination of eosinophils in scrapings from the conjunctiva, examination by a pediatrician, otolaryngologist, infectious disease specialist.

The etiology of keratitis was determined by the following parameters. The diagnosis of herpetic keratitis was established on the basis of anamnesis, clinical data (characteristic form of infiltrate, decreased sensitivity of the cornea), laboratory research methods (increased titer of Ig M antibodies to HSV, detection of viral DNA in the blood by PCR, increase in Ig G using the method of paired sera), the conclusion of an infectious disease specialist .

The etiology of CMV keratitis was established on the basis of anamnesis, laboratory research methods (increased titer of Ig M antibodies to CMV, detection of viral DNA in the blood by PCR, increase in Ig G by the method of paired sera), the conclusion of an infectious disease specialist, the characteristic clinical picture of this type of keratitis has not been described in the literature.

Allergic keratitis was diagnosed on the basis of a characteristic history, complaints, clinical picture (peripheral location of the infiltrate), detection of eosinophils in scrapings from the conjunctiva, elevated levels of total Ig E, and the conclusion of a pediatrician or otolaryngologist.

Post-traumatic keratitis was established on the basis of medical history, clinical presentation, and negative laboratory results.

Bacterial etiology was determined on the basis of anamnesis, complaints, clinic (yellowish infiltrate in the central and paracentral parts of the cornea), a positive culture result of a smear from the conjunctiva with the detection of pathogenic microflora.

We diagnosed keratitis of unknown etiology in the absence of characteristic complaints, anamnesis, clinical picture (for any type of keratitis) and negative results of laboratory research methods.

Children with all types of keratitis, except allergic (52 children, 80 eyes) were divided into 2 groups. Group 1 - 24 children (38 eyes), group 2 - 28 children (42 eyes). The groups were identical in age and etiology of keratitis. The difference between the groups was in the approaches to treatment. Children from groups 1 and 2 received, depending on the etiology of keratitis, instillation of NSAIDs, antiviral drugs (natural and recombinant interferons, interferon inducers, acyclovir drugs), and keratoprotectors. Children from group 1 received antibacterial drugs in the form of drops (2nd and 3rd generation fluoroquinolones, aminoglycosides) containing the preservative benzalkonium chloride. Children from group 2 received this form of antibacterial drugs only at the initial stage of treatment; at the first signs of epithelization of the infiltrate, we switched to Oftocipro eye ointment containing ciprofloxacin as an antibacterial agent and the preservative methyl parahydroxybenzoate. The presence of epitheliopathy of the cornea and conjunctiva in groups 1 and 2 was determined.

Our analysis showed the following results. Keratitis was localized in the central and paracentral regions in 37 children (58 eyes, 65.9%)1, and in the periphery in 19 children (30 eyes, 34.1%)1. A superficial process was observed in 39 children in 64 eyes (72.7%)1, localization in the middle layers of the stroma was determined in 17 children in 24 eyes (27.3%)1.

1Percentage is based on the number of eyes

2Percentage is based on the number of children

This is a footnote under all the columns below the line do

The results of laboratory tests in children with keratitis are presented in Table 1.

Table 1.

Results of laboratory tests in children with keratitis

Laboratory indicator	Ig G to HSV	Ig M to HSV	Ig G to CMV	Ig M to CMV	General IgE	Antibodies to Giardia	Antibodies to roundworms
Number of children, %2	32 (57,1%)	5 (8,9%)	18 (32,1%)	4 (7,1%)	4 (7,1%)	5 (8,9%)	—

Analyzing Table 1, it should be noted that there are a large number of children with the presence of Ig G antibodies to HSV and CMV (57.1 and 32.1%, respectively) with a relatively low detection of positive Ig M to the same infections (8.9 and 7.1% , respectively). The number of children who showed an increase in total Ig E and antibodies to Giardia is small. Antibodies to roundworms were not detected in the patients we examined.

The diagram in Figure 1 shows the etiological structure of keratitis in children according to our study. First of all, attention is drawn to the unclear etiology of keratitis in 35.8% (20)2 of children, despite a large-scale study aimed at elucidating the causes of keratitis. Among the established causes of keratitis, 10.7% (6 people) have CMV etiology, 25% (14)2 - herpetic, 7.1% (4)2 - allergic, 12.5% (7)2 - bacterial, 8.9% (5)2 - the cause was an eye injury.

Picture 1.

Etiological structure of keratitis in children according to the Children's Clinical Hospital of the Republic of Tatarstan, Kazan

It should be noted that keratitis of herpetic, CMV etiology in children has a long, torpid course, frequent relapses, the number of which reaches 7-8 per year. The persistence of the above viruses in the child’s body leads to secondary immunodeficiency, which requires additional examination and correction of the immune status for successful treatment of keratitis.

In the group of keratitis of unknown etiology, repeatedly recurrent keratitis with a protracted course also occurs.

The results of culture of a smear from the conjunctiva for microflora are presented as follows: in 58 eyes (65.7%) no microflora was isolated, in 17 (19.3%) - H. Influenza, in 8 (9.1%) - S. pneumonia, by 5 (5.7%) - S. aureus.

Noteworthy is the discrepancy between some of the keratitis we observed and the generally accepted clinical picture. In particular, in children with a seemingly typical clinical picture of herpetic keratitis (the presence of a twig-shaped infiltrate in the superficial layers of the cornea, photophobia classic for this keratitis, pain in the eyes) there is no such pathognomonic sign as decreased corneal sensitivity. And laboratory tests in this situation show a moderate increase in class G antibodies with high avidity. In this situation, an infectious disease specialist does not make a diagnosis of herpes virus infection.

Thus, taking into account the polymorphism of manifestations, the absence of a classical clinical picture, the presence of immunosuppression and the ambiguity of laboratory parameters, it is necessary to carry out treatment that affects various stages of the development of keratitis in most children.

These children receive instillations of NSAIDs, antibiotics or antiseptics, antiviral drugs, inducers of interferon production, and keratoprotectors in various combinations.

Undoubtedly, this therapy is justified, as it allows one to achieve recovery or long-term remission in recurrent keratitis. However, she also has another side. The fragile body of a child, especially of an early age, and the immaturity of local protective barriers, combined with frequent and prolonged instillation of drops that contain preservatives, lead to the development of epitheliopathy of the cornea and conjunctiva at the final stage of treatment after epithelization of the cornea and resorption of the infiltrate in some of the children we observed.

The number of children with epitheliopathy of the cornea and conjunctiva in groups 1 and 2 is presented in the diagram in Figure 2.

Figure 2.

Number of children with epitheliopathy of the cornea and conjunctiva in groups 1 and 2

It should be noted that in group 2 the number of eyes with epitheliopathy of the cornea and conjunctiva is much lower (in 2 children in 2 eyes (4.8%1)) than in group 1 (in 10 children in 18 eyes (41.7%1) ).

To prevent and combat epitheliopathy in the complex treatment of keratitis in children, we used Oftocipro eye ointment as an antimicrobial agent. Our choice is justified as follows. This ointment contains the active ingredient ciprofloxacin, a second generation fluoroquinolone. Fluoroquinolones are the most promising antibacterial drugs in modern ophthalmology, as they have a wide spectrum of antimicrobial action and a complex mechanism (compared to other groups of antibiotics) for the development of drug resistance to them. The addition of lanolin to the ointment base ensures good wetting of the ointment with tear fluid and fixation of the ointment on the conjunctiva and cornea of the eye. The preservative included in the ointment, methyl parahydroxybenzoate, is less toxic to epithelial cells of the cornea and conjunctiva compared to benzalkonium hydrochloride, which is part of eye drops [3]. Also, the ointment stays in the conjunctival cavity longer and requires a smaller frequency of instillations compared to drops.

conclusions

1. In the majority of children (35.8%) the etiology of keratitis could not be established. Among the established etiologies, 25% are herpetic keratitis, 12.5% are bacterial, 10.7% are CMV etiologies, 8.9% are post-traumatic, 7.1% are allergic.

2. Clinically, inflammation of the cornea in children is presented mainly in the form of superficial (69.9%) central (72.7%) keratitis.

3. Epitheliopathy of the cornea and conjunctiva in response to instillation of eye drops containing the preservative benzalkonium chloride occurs in 41.7% of cases at the final stage of treatment of keratitis.

4. The use of Oftocipro ophthalmic ointment in the complex treatment of keratitis in children can significantly reduce the number of cases of epitheliopathy - up to 4.5%, due to the long-term fixation of the ointment on the cornea, which reduces the number of instillations, good wetting of the ointment with tear fluid and the presence of methyl parahydroxybenzoate as a preservative, which is less toxic to the epithelial structures of the eye.

LITERATURE

Yartsev M.N., Yakovleva K.P., Plakhtienko M.V. Immune deficiency and frequently ill children // Conslium medicum. Pediatrics application. ― ― T. 8, No. 1. - pp. 13-18.
Romantsov M.G., Ershov F.I. Frequently ill children: modern pharmacotherapy. Guide for doctors. - M.: GEOTAR-Media, 2009. - 192 p.
RF Patent No. 2317810 “Composition and method of producing ciprofloxacin ophthalmic ointment” CJSC “Tathimfarmpreparaty” dated July 27, 2006.

Russian ophthalmological journal, 2015, No. 4, pp. 1-4