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Herpes Simplex Keratitis: Case Study

Abstract

Herpetic keratitis is an inflammation of the cornea caused by the herpes simplex virus, which is a neurodermotropic virus that has been present in the human body since childhood. Herpes simplex virus is the most common infectious cause of blindness in developing countries, and a high titer of specific antibodies is a sign of herpes virus infection. Most babies are born with antibodies to the herpes simplex virus due to their presence in mothers, and during the first six months of their life, antibodies to herpes disappear. The overall purpose of the paper is to assess the herpes simplex keratitis of the PAM case. Most adults are healthy carriers of the virus, and with certain indicators of immunity, the herpes virus does not cause disease until its virulence intensifies.

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Keywords used: microbial keratitis, neurotrophic keratopathy, viral keratitis, herpes simplex virus.

Introduction

Herpes simplex keratitis or, as it is also called, keratitis of the herpes simplex virus is one of the common ophthalmic diseases. The herpes simplex virus, getting into the eye tissue, actively multiplies in the cells of the corneal epithelium. An active inflammatory reaction ultimately leads to the appearance of the clouding of the cornea, superficial or deep, and decreased vision. In some cases, episcleritis, secondary glaucoma, herpetic keratoiritis, complicated cataracts, retinitis, neuritis, leading to a significant decrease in vision, can develop. Factors such as hypothermia, stress, ultraviolet radiation, and neuroendocrine shifts usually contribute to the activation of the virus. The disease is often a systemic lesion of the eyes, mucous membranes, central and peripheral nervous systems. Herpetic pathology manifests itself in the form of primary herpes, and in this case, there are no antibodies to this virus in the body. In addition, the disease manifests itself in the form of post-primary herpes, that is, the infection has already occurred, and the patient has cellular and humoral immunities.

Most cases occur subclinically or are manifested only by an increase in body temperature, malaise, and symptoms of upper respiratory tract damage. Blepharoconjunctivitis may develop, often proceeding favorably and spontaneously resolving. In rare cases, micro-tree-like infiltrates on the cornea develop. Post-primary herpes is most commonly detected in children from 3 years. In adults, the development of post-primary herpes occurs against a background of weak antiherpetic immunity. The greater the number of previous herpes attacks, the higher the risk of relapse. Post-primary herpetic keratitis is manifested by a feeling of moderate discomfort in the eye, lacrimation, decreased vision, and the sensitivity of the cornea decreases1. With a superficial process, infiltrates of a characteristic tree-like form appear in the cornea, either in the formation of single or multiple vesicles. In more severe cases, the pathological process may cover deeper and larger areas of the cornea. The process may be accompanied by the occurrence of non-healing defects due to toxic damage, the insufficient regenerative ability of corneal tissue. The epithelial form is the most common form of the disease, usually its initial stage. At first, point opacities or vesicles appear – small vesicles in the corneal epithelium. Further, the bubbles, merging, form on the surface of the eye a pattern resembling branches of a tree, therefore this keratitis is also called tree-like.

As the disease progresses, the number of vesicles increases and superficial ulceration develops, which, as a rule, affects the optical zone and begins to capture the superficial stroma of the cornea. At this stage, iridocyclitis may occur. Treelike keratitis is accompanied by photophobia, lacrimation, blepharospasm, neuralgic pain2. Corneal ulceration leads to a significant decrease in vision. Herpetic keratitis is a severe disease, faced with which it is essential to make an appointment with an ophthalmologist on time and begin treatment.

In some cases, delaying even a couple of days can result in complete blindness. During the initial appointment, an ophthalmological center specialist collects an anamnesis and examines the patient, after which he concludes what other laboratories or instrumental studies need to be done to confirm the diagnosis. Depending on the diagnostic results, conservative or surgical treatment can be prescribed. In the first case, ophthalmologists successfully use antiviral and immunotherapy. Some patients have to resort to surgical treatment – removal of a pathologically altered zone, that is, therapeutic keratoplasty.

Differential Diagnoses

The differential diagnoses include:

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  • microbial keratitis
  • neurotrophic keratopathy
  • viral keratitis

Microbial keratitis is an infectious disease of the cornea caused by bacteria, fungi, amoeba, or viruses. Keratitis is manifested by pain and inflammation and, in severe cases, can lead to loss of vision or blindness. The key risk factors for developing this type of serious infection are improper storage or routine use of contact lenses. This is an acute inflammation of the cornea of ​​the eye of bacterial origin. It is clinically manifested by acute pain in the eye, edema, corneal syndrome, severe inflammatory injection of the eyeball, the presence of mucopurulent discharge, corneal opacity, superficial or deep ulceration3. Diagnosis of bacterial keratitis includes biometrics of the eye, microbiological examination of a smear from the cornea, confocal and endothelial microscopy, pachymetry, keratometry, corneal topography, determination of the sensitivity of the cornea. Priority in the treatment of bacterial keratitis is local and systemic antibiotic therapy, supplemented by the use of specialized instruments, epithelizing agents, mydriatics, and in case of complications – surgical intervention. Bacterial keratitis is the most common corneal disease. There is primary and secondary, endogenous and exogenous, superficial and deep bacterial keratitis. With microbial damage to the cornea, in addition to edema and purulent infiltration, increased vascularization, the formation of a stromal abscess, erosion, and ulceration with possible tissue necrosis are noted in it. Bacterial keratitis is a serious problem of practical ophthalmology, as in most cases, it causes temporary disability, and in the future, it can lead to a decrease in visual acuity and blindness.

Neurotrophic keratopathy is a degenerative disease of the epithelium and stroma of the cornea, causing a violation of the sensitivity of the cornea. In turn, a decrease in sensitivity leads to the occurrence of chronic or recurrent erosion of the epithelium, and then ulcers and perforation of the cornea4. The reasons for the development of neurotrophic keratopathy may be the use of local medications, the presence of a prolonged course of diabetes mellitus, lesions of herpes zoster or herpes simplex, neurological diseases, or localized trauma. As a treatment, patients with Neurotrophic keratopathy are prescribed instillations of an antibiotic solution, an artificial tear preparation that does not contain preservatives, with a bandage or bandage contact lens. In cases where a topical treatment is ineffective, systemic administration of doxycycline, treatment with autologous blood plasma, application of the amniotic membrane, as well as the use of a conjunctival flap is recommended. Herpetic keratitis, the state after some eye operations, and wearing contact lenses can be listed among the ocular causes of the development of the condition. Among the reasons for the development of the disease, the leading place is occupied by neurosurgical operations, prolonged anesthesia, and conditions after an acute cerebrovascular accident. The clinical picture of neurotrophic keratopathy is characterized by the presence of epithelial defects – from a single superficial punctate keratopathy in the initial stage, confluent erosion, and corneal ulcers to the development of its thinning and perforation. Diagnosis of neurotrophic keratopathy is quite painstaking work and begins with a thorough history taking, with an emphasis on questioning the presence of processes that alter neurotrophy. Since the causes of neurotrophic keratopathy are very diverse, the patient’s medical history should be thoroughly studied.

Viral keratitis arises as a result of infection with the herpes simplex virus or herpes zoster. The pathological process of the cornea of ​​an inflammatory nature that causes a viral infection is expressed by a rash of a bubbling nature, swelling, ulcers, and clouding of the cornea, redness of the eyes, pain, and also visual impairment. It is mainly found in children and young patients. In severe cases of the disease, complications such as corneal dying, abscess, ulcerations develop. The most severe illness is caused by the viruses of simple and herpes zoster. The causative agents of the disease can be adenovirus and herpetic infections, chickenpox viruses, and measles. If untreated on time, viral keratitis is also able to cause adenoviral conjunctivitis. If the integrity of the cornea is broken or the immune system is weakened, the body is often affected by stress, or there was hypothermia – the risk of developing the disease increases5. Herpetic keratitis can even cause an acute respiratory viral infection or influenza, which reduces immunity and activate the causative agent of latent infection. The disease has a long course and can often recur. The characteristic signs of the disease are a blistering rash, infiltrates of irregular and treelike forms, as well as a decreased sensitivity of the cornea.

Discussion

To properly treat and manage herpes simplex keratitis, it is important to understand its key epidemiological, clinical, symptomatic, and diagnostic features. It is stated that approximately 500000 American citizens suffer from herpes simplex keratitis each year6. However, primary forms of the disease are mostly mild and even asymptomatic7. Therefore, complications are not common, but the instances can be overwhelming. It is especially true in the case of individuals with AIDS, who lack a strong immune system, and thus, they are more likely to suffer from herpes simplex keratitis8. Its pathophysiology and clinical features include a sensitivity decrease in the cornea, irritation, and viral presence of the herpes simplex virus. Signs and symptoms can vary depending on their prominence, but it is important to note that conducting diagnosis solely based on symptomatic characteristics can be highly challenging. Characteristic symptoms include eye irritation symptoms such as lacrimation, photophobia, and blepharospasm. In addition, there is the presence of precorneal hyperemia or mixed, combined with conjunctival redness, and possibly clouding of the cornea, accompanied by a violation of specularity, gloss of the cornea. In old age, a herpetic ulcer may occur asymptomatically, redness of the eye is small or maybe absent, the pain is minor. In childhood, on the contrary, herpetic lesion of the cornea is accompanied by sharp pain, severe eye irritation, photophobia.

Due to the high sensitivity of PCR diagnostics and serological studies, false-positive results are possible. The determination of the herpes simplex virus nucleic acid in biological material is the current gold standard for clinical diagnosis. PCR diagnostics is the most expensive method, but the fastest, most accurate, and reliable method for determining viral DNA with herpetic keratitis due to its high specificity and sensitivity. With superficial herpetic keratitis, it allows for very accurate monitoring of the effectiveness of treatment. The typical clinical picture of keratitis correlates well with a positive PCR result, especially with epithelial defects or tree keratitis. In half the cases of atypical keratitis, a positive PCR result is determined. With DNA epithelial keratitis, the herpes simplex virus is detected in all cases, with active stromal keratitis in half the cases. It is not detected in the case of stromal keratitis or endothelium.

When infected with the herpes virus, sequential synthesis is observed, and their main effect is aimed at blocking the pathogen due to the formation of antigen-antibody immune complexes and thereby reducing its pathogenetic effect on epithelial cells and the body as a whole. The mechanism of action of antibodies is aimed at HSV and cells infected by it, inhibition of pathogen reproduction in the focus of its penetration, prevention of the spread of infection through intercellular spaces, reduction of viremia in the body, but humoral mechanisms cannot completely prevent the activation of latent herpes simplex virus. In relapses, the same sequence of immunoglobulin formation is observed as in the initial infection, the synthesis of which occurs against the background of existing antibodies to the virus, which leads to an increase in their level during exacerbations9. In cases of subclinical or unrecognized herpetic infection, a serological determination of class G immunoglobulins may be useful. Isolation and cultivation of the pathogen in cell cultures provide the possibility of direct observation and analysis of the spread of the herpes simplex virus in laboratory animals and human embryonic tissues. A biological test is the rarest type of diagnosis and, as a rule, is used to reproduce herpetic keratitis in experimental animals.

DNA diagnostics is a commercially available, quick, and reliable method for determining the etiological cause of the disease in patients with superficial forms of keratitis and some types of stromal keratitis. PCR diagnostics is necessary not only to determine treatment tactics but also for accurate monitoring and correction of therapy, taking into account laboratory results. With deep pathological changes in the cornea and the absence of damage to the surface epithelium, it is less likely to detect virus DNA in a tear10. Therefore, despite the highest sensitivity and specificity of PCR, it is not possible in all cases of herpetic keratitis to determine the DNA of the virus in a tear. For this reason, it is advisable to also determine immunoglobulins to the virus in the blood of patients with suspected herpetic keratitis.

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Conclusion

In conclusion, the herpes simplex virus infected most of the world population, and this infection is often asymptomatic, but the ocular form of the disease with the virus leads to a complex pathology with significant damage to the cornea. The herpes simplex virus is considered the leading cause of blindness in developed countries. Herpetic eye diseases manifest a diverse clinical picture: treelike keratitis, persistent epithelial erosion, disciform keratitis, endothelins, which creates difficulties in making a diagnosis. Confirmation of the herpetic nature of the infection is based on the clinical picture, supported by laboratory tests. There are several methods of laboratory diagnosis of herpes such as PCR diagnostics, serological studies, isolation and cultivation of the pathogen in cell cultures, and biological samples.

References

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Valls-Sole, J., Defazio, G. Blepharospasm: update on epidemiology, clinical aspects, and pathophysiology. Front Neurol. 2016; 7(45):1-8.

Lakhundi, S., Siddiqui, R., Khan, NA. Pathogenesis of microbial keratitis. Microbial Pathogenesis. 2017; 104: 97-109.

Versura, P., Giannaccare, G., Pellegrini, M., Sebastiani, S., Campos, EC. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018; 10:37-45.

Austin, A., Lietman, T., Rose-Nussbaumer, J. Update on the management of infectious keratitis. Ophthalmology. 2017; 124(11): 1678-1689.

Azher, TN., Yin, XT., Tajfirouz, D., Huang, AJ., Stuart, PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017; 11:185-191.

Jester, JV., Morishige, N., BenMohamed, L., Brown, DJ., Osorio, N., Hsiang, C., Perng, GC., Jones, C., Wechsler, SL. Confocal microscopic analysis of a rabbit eye model of high incidence recurrent herpes stromal keratitis (HSK). Cornea. 2016; 35(1):81-88.

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Burcea, M., Gheorghe, A., Pop, M. Incidence of herpes simplex virus keratitis in HIV/AIDS patients compared with the general population. J Med Life. 2015; 8(1):62-63.

Lobo, AM., Agelidis, AM., Shukla, D. Pathogenesis of herpes simplex keratitis: the host cell response and ocular surface sequelae to infection and inflammation. The Ocular Surface. 2019; 17(1): 40-49.

Carroll, KC., Jorgensen, JH., Pfaller, MA. Manual of clinical microbiology. ASM Press. 2015.

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