Ophthalmoherpes

Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VO-OG) remain the most relevant viral pathogens causing various damage to the visual organ. Traditionally, it is considered that ophthalmoherpes causes HSV-1.

Nevertheless, a number of researchers cite data on a significant percentage of cases of detection of HSV-2 in the eye , which often causes genital herpes. Discussion remains the question of the possible role of HSV type 6 in the pathogenesis of severe herpetic keratitis.

[1], [2], [3], [4], [5], [6]

Epidemiology of ophthalmoherpes

Unfortunately, ophthalmoherpes is not subject to compulsory registration on the territory of Ukraine, therefore, the distribution of this eye infection can be estimated only tentatively, relying on similar statistical data of foreign authors.

In the structure of ophthalmoherpes lesions of the cornea (keratitis) predominate. Herpetic keratitis (HA) is 20-57% among adults, and among children - 70-80% of all inflammatory diseases of the cornea. Studies conducted during the period 1985-1987. In the eye clinic in Bristol, England, showed that there were 120 cases of primary herpetic keratitis recorded annually on 863,000 people, which corresponds to a frequency of primary herpetic keratitis of approximately 1: 8,000. These calculations are consistent with the data given earlier by various authors.

Recurrences of HA occur in 25% of cases after the first eye attack and in 75% after repeated attacks. Factors of the disease development are reactivation of persistent virus or reinfection with exogenous herpes virus. Recurrent corneal herpes is a disease that has become one of the leading causes of invalidating corneal opacities and corneal blindness in the temperate countries.

[7], [8], [9], [10], [11]

Pathogenesis of ophthalmoherpes

The pathogenesis of ophthalmoherpes is determined by the properties of the virus and the specific immune responses of the macroorganism arising in response to the introduction of HSV. The virus affects the tissues of the eye when it overcomes local defense mechanisms, which include the production of secretory antibodies (S-IgA) by cells of subepithelial lymphoid tissue, local interferon production, sensitized lymphocytes.

Getting into the eye tissue exogenously (through the epithelium), neurogenic or hematogenous way, HSV begins to actively multiply in the corneal epithelium cells, which, due to cytopathic and dystrophic processes, are subjected to necrosis and sloughing. With superficial keratitis (mainly corneal epithelium is affected), at this stage further reproduction of the virus stops in the cornea, the defect of the corneal tissue is epithelialized, the virus becomes persistent. In a persistent state, the virus can be located not only in the trigeminal node, but also in the cornea itself.

The persistent virus can become active under any adverse conditions. The most common causes are stress, pregnancy, trauma, insolation, infection, hypothermia. In individual publications of foreign authors, there was no dependence of the frequency of recurrences of HA on age, sex, seasonality, cutaneous manifestations of herpetic infection. In recent years, the literature began to appear data on the occurrence of relapses of ophthalmoherpes after laser exposure and against treatment with prostaglandins (latanoprost). Data on the recurrence of ophthalmoherpes in the treatment of immunodepressants - cyclophosphamide and dexamethasone are given. The role of latanoprost as a factor provoking the development of exacerbations of GI is confirmed by experimental work on rabbits.

The pathogenesis of deep (with deep involvement of the stroma of the cornea) forms of HA is ambiguous. On the one hand, HSV has a direct damaging effect on cells, causing their death with the subsequent development of inflammatory reactions. On the other hand, a number of authors point to the ability of HSV to antigenic mimicry with the emergence of cross-reacting antigens responsible for triggering autoimmune reactions in the cornea.

Clinical forms and symptoms of ophthalmoherpes

The most complete classification, encompassing both pathogenetic and clinical variants of ophthalmoherpes, is the classification of prof. A.A. Kasparov (1989). It takes into account the pathogenetic (primary and recurrent) and clinico-anatomical (lesions of the anterior and posterior parts of the eye) of the shape of the ophthalmoherpes.

Primary ophthalmoherpes as an independent form is rare enough (according to the data of different authors - not more than 10% of cases of all herpetic lesions of the eyes). Most (over 90%) is recurrent (secondary) ophthalmoherpes, with one eye being more often affected.

Lesions of the anterior part of the eye are subdivided into superficial forms - blepharoconjunctivitis, conjunctivitis, vesicular, dendritic, geographical and marginal keratitis, recurrent corneal erosion, episcleritis, and deep forms:

Lesions of the posterior eye include retinchoroiditis of newborns, chorioretinitis, uveitis, optic neuritis, perivascular, acute retinal necrosis syndrome, central serous retinopathy, anterior ischemic retinopathy.

Among the superficial forms of damage to the anterior part of the eye (superficial keratitis), tree keratitis is most common. In the epithelium of the cornea, groups of small vesicular-like defects are formed, which tend to open and form an eroded region after themselves. As the disease progresses, they merge, forming a so-called tree-like defect with raised and swollen edges, well defined when viewed with a slit lamp. In half the cases, tree ulceration is localized in the optic center of the cornea. Clinically, dendritic keratitis is accompanied by lacrimation, blepharospasm, photophobia, pericorneal injection and neuralgic pain. Often there is a decrease in the sensitivity of the cornea. Tree-like keratitis is generally considered a pathognomonic form of GI of the eye, and such a characteristic form of an ulcer is caused by the spread of the virus along the dichotomously branched superficial nerves of the cornea.

Geographic keratitis develops, as a rule, from the tree, due to progression or improper treatment with corticosteroids. Marginal keratitis is characterized by perilimbal infiltrates, capable of merging.

The etiological role of HSV in the development of recurrent corneal erosion is ambiguous, since the causes of its existence may be, along with a viral infection, a previous eye trauma, corneal dystrophy, endocrine disorders.

Deep (with deep involvement of the corneal stroma) forms in most cases are combined with inflammation of the anterior vascular tract, i.e. In fact are keratoiridocyclites. Herpetic keratoiridocyclites are divided into two variants, depending on the nature of the cornea lesion - with the presence of ulceration (metaherpetic) and without it (varieties - focal, discoid, bullous, interstitial). Herpetic keratoiridocyclitis is characterized by general clinical characteristics: chronic course, the presence of iridocyclitis with serous or serous-fibrinous effusion and large precipitates on the posterior surface of the cornea, edema of the iris, ophthalmic hypertension.

The establishment of herpesviral etiology of the lesion of the posterior eye is rather ambiguous, since in some cases (anterior ischemic neuropathy, central serous retinopathy), the clinical picture differs little from the pattern of this disease of another genesis. To bring a doctor to the idea of the herpes simplex virus as the reason for the ophthalmopathology of the posterior eye can be: a young patient's age, the presence of a previous ARVI in the anamnesis, a recurrent herpes of the facial skin.

[12], [13], [14], [15]

Diagnosis of ophthalmoherpes

The characteristic clinical picture of ophthalmoherpes (in 70% of cases it is manifested by keratitis), the recurring nature of the course, herpetic infection in the anamnesis, the positive dynamics against the background of the use of specific antiviral agents - all this allows to establish the correct diagnosis in most cases. In doubtful cases, with atypical manifestation of ophthalmoherpes, especially in severe cases, it is necessary to verify herpesvirus etiology for the purpose of timely etiotropic treatment. Despite the many methods proposed over the last fifty years to detect both the virus itself and specific antibodies, the fluorescent antibody method (MFA) in the AA modification has proven itself in a wide clinical practice. Kasparov. The essence of the method is based on the detection of viral particles in conjunctival cells of the diseased eye with the help of serum containing labeled antibodies. To exclude normal virus carrying, the reaction is carried out at once in several dilutions of serum (standard, 10-fold, 100-fold and 1000-fold). The increase in luminescence by a factor of 10-100 compared to the luminescence in standard dilution is associated with a truly herpetic lesion of the eye. In this case, like any method of laboratory diagnosis, the result of MFA depends on the form of keratitis, the period of the disease, the previous treatment, etc.

[16], [17], [18], [19]

Treatment of ophthalmoherpes

To date, the main areas of treatment and prevention of ophthalmoherpes are chemotherapy, immunotherapy or a combination of these methods, as well as methods of microsurgical treatment (microdiathermocoagulation, various variants of keratoplasty, local auto-express cytokine therapy). The beginning of the era of chemotherapy for viral eye diseases was laid in 1962 by N.E. Kaiipapp, who scientifically substantiated and successfully applied 5-iodine-2-deoxyuridine (IMU) in the clinic for the treatment of patients with herpetic keratitis.

IMU-5-iodo-2-deoxyuridine (kerecid, goocollal, stoxyl, dendril, herplex, otan-IMU) is highly effective in the treatment of superficial HC, but it is ineffective in the deep forms of herpetic keratitis and isolated iridocyclitis. Following the discovery of IMU, the screening of compounds of this group allowed the creation of a number of widely known drugs such as acyclovir, TFT (triflurotimidine), vidarabine, ganciclovir, valaciclovir (valtrex), famciclovir, foscarnet, brivudine and sorivudine.

Trifluorothymidine (TFT, viropiticum, triherpin) - similar in structure and mechanism of action (thymidine analogue) is similar to IMU, but unlike it is less toxic and more soluble. TFT is used in the form of instillations of 1% solution in the conjunctival sac every 2 hours (up to 8-10 times a day), and 2% ointment - in applications (5-6 times a day). TFT is more effective than IMU in superficial forms, as well as in preventing complications caused by the use of corticosteroids.

Adenine-arabinoside-9-ß-D-arabinofuranosal-adenine (vidarabine, Ara-A) is used in herpetic keratitis as a 3% ointment 5 times a day, the therapeutic efficacy is equal to or slightly higher, and the toxicity is lower than that of the IMU. Vydarabin is effective in IMU resistant strains of HSV.

Synthesized in the early 70's. Preparations with antiviral activity tebrofen, florenal, rhyodoxol are used mainly with superficial forms of HA in the form of ointments and drops.

The most significant progress in the treatment of ophthalmoherpes was observed after the appearance in the arsenal of antiviral agents acyclovir - a highly active drug with a unique mechanism of selective action on HSV. Over the past ten years, acyclovir is considered as a standard anti-herpetic drug. There are three dosage forms of acyclovir: 3% paraffin-based ointment (Zovirax, Virolex); tablets of 200 mg; lyophilized sodium salt of acyclovir for intravenous administration in vials of 250 mg. Ointment is usually prescribed 5 times a day at intervals of 4 hours. The usual dose for oral administration is 5 tablets per day for 5-10 days. Acyclovir of the second generation - valtrex and famciclovir are highly bioavailable (70-80%) when taken orally, which makes it possible to reduce the frequency of reception from 5 to 1 2 times a day.

The drugs of the new treatment are interferons (human leukocyte and recombinant) and their inducers. In ophthalmology, leukocyte interferon (a) with activity of 200 U / ml and interlock, one ampule of which contains 10 000 IU of interferon in 0.1 ml of phosphate buffer is used. Both preparations are allowed for use only in the form of instillations. Reaferon (recombinant a2-interferon) is applied topically in the form of eye drops and periocular injections with superficial and deep keratites.

Poludan (high-molecular inducer of interferonogenesis) is used in the form of instillations, periocular injections; it is also possible to administer it by the method of local electrophoresis and phonophoresis, and also directly into the anterior chamber of the eye. Poludan stimulates the formation of a-IFN, to a lesser extent a- and y-interferons. The wide antiviral spectrum of the action of the half-day (herpesviruses, adenoviruses, etc.) is also due to its immunomodulating activity. In addition to interferon formation, the administration of half-decay leads to a significant increase in the activity of natural killers, whose level is initially lower in patients with ophthalmoherpes. With frequent repeated administration of the drug, the level of interferon formation in the blood serum reaches 110 U / ml. There were reports of the creation of a suppository with a half-day for the treatment of patients with genital and ophthalmoherpes. The interferonogenic effect of the half-moon is enhanced in suppositories by the addition of hyaluronic acid and antioxidants.

In the treatment of patients with dendritic keratitis, poludan and aciclovir (3% ointment) have equal opportunities. The early administration of the drug in the form of subconjunctival injections in combination with instillations (4 times a day) leads to the cure of 60% of patients with the most severe deep forms of herpetic corneal damage. Among other interferonogens, lipopolysaccharide of bacterial origin, pyrogenal, was most widely used. The literature presents data on the high efficacy of para-aminobenzoic acid (PABA) -actipol in patients with various forms of ophthalmoherpes with periocular administration and instillations.

Widely prescribed in the therapy of herpetic infection as a whole, no less effective than poludan, low-molecular inducer of interferonogenesis, cycloferon is successfully used in ophthalmoherpes according to the following scheme: 250 mg once a day every other day for 7-10 days. Cycloferon normalizes serum interferon levels in tear fluid and serum. In another study, under supervision of an ophthalmologist, there were 18 patients with ophthalmoherpes who received complex therapy of the central nervous system, 25 patients received traditional (BT) therapy. As a comparison, the results of treatment of patients with orgalmoherpesom half-way are given. CF was used according to the author's scheme: the drug was administered 250 mg once a day, every other day, intravenously, for 7-10 days, depending on the severity of the inflammatory process. The course dose was from 1250 to 2500 mg. Also, the administration of CF was performed by electrophoresis endonasal from the positive pole, every other day for 10 days.

The treatment with Ophalmoherpes with the use of CF with a positive effect was in 94.4% of patients. Visual acuity increased in the group of patients receiving CF, in 91.6% of cases, and in patients with CG in 3 patients (12%). Thus, CF is quite effective in herpetic lesions of the eyes (67.0-94.4% - superficial forms and stromal lesions of the cornea).

Well established in the treatment of slow forms of ophthalmoherpes timalin - a complex polypeptide isolated from thymus calves. Has interferonogenic properties, increases the interferon titer in the lacrimal fluid to 20-40 U / ml, introduced periocularly.

To date, the total number of immunocorrectors used in the complex therapy of ophthalmoherpes has exceeded two dozen. Levamisol was replaced by a powerful tactivin in injections, later affinity leukemia in injections and tableted amixin and lycopid. Amiksin (a low-molecular inducer of interferonogenesis) shortens the treatment time, accelerates the healing of the cornea, and has an antiviral effect. Amiksin is prescribed according to the following scheme: the first two days of 250 mg (2 tablets), then 1 tablet every other day.

One of the most promising areas is the method of local auto-express cytokine therapy (LAETCT), proposed by A.A. Kasparov

In the literature, the question of the significance of end-to-end keratoplasty in the treatment of recurrent ophthalmoherpes is still being addressed. On the one hand, keratoplasty gives a certain anti-relapse effect, caused by the elimination of the focus of active viral inflammation in the cornea, but does not guarantee the patient completely from subsequent relapses. On the other hand, in the postoperative period, for the prevention of transplant rejection, long-term use of cyclodefosamide and dexamethasone immunosuppressants, which can provoke the recurrence of HA, is necessary.

Prevention of ophthalmoherpes

An important aspect of managing patients with ophthalmoherpes is the prevention of relapses. According to different authors, none of the existing methods for treating the acute period of ophthalmoherpes (medicamentous and microsurgical) has a significant effect on the frequency of relapses. A.K. Shubladze, TM. In May 1966, an antiherpetic vaccine (PGV) was developed on the basis of the most common immunogenic strains of HSV isolated in the territory of our country. For the first time for the prevention of recurrence of ophthalmic herpes, the antiherpetic vaccine was successfully applied in 1972 by A.A. Kasparov, TM. Mayevskaya in patients with frequently recurring ophthalmoherpes in the "cold period".

In order to increase the effectiveness of antiherpetic vaccination, it is possible to combine PGV with interferonogens (poludan, tsikloferon, pyrogenal, actipol, amixin). Poludan and actipol are used in this case in instillations for 4-7 days 2-3 times a day. It is recommended to start taking amixin concomitantly with PGV (1 tablet once a week) and continue at the end of the vaccination course as a monotherapy.