CLINICAL PRACTICE GUIDELINES
Year : 2019 | Volume
: 57 | Issue : 4 | Page : 308--310
Nummular keratitis – A modern-day conundrum
Srinivas K Rao1, Sanjeev P Srinivas1, Anil K Nair2,
1 Darshan Eye Care and Surgical Centre, Chennai, Tamil Nadu, India
2 Darshan Eye Care and Surgical Centre, Chaithanya Eye Hospital and Research Institute, Trivandrum, Kerala, India
Dr. Srinivas K Rao
T 80 (New No. 24), 5th Main Road, Anna Nagar, Chennai - 600 040, ,Tamil Nadu
|How to cite this article:|
Rao SK, Srinivas SP, Nair AK. Nummular keratitis – A modern-day conundrum.TNOA J Ophthalmic Sci Res 2019;57:308-310
|How to cite this URL:|
Rao SK, Srinivas SP, Nair AK. Nummular keratitis – A modern-day conundrum. TNOA J Ophthalmic Sci Res [serial online] 2019 [cited 2022 Nov 29 ];57:308-310
Available from: https://www.tnoajosr.com/text.asp?2019/57/4/308/273990
Normal corneal structure and function is essential for excellent vision and comfort. Sometimes, however, the presence of fine granular opacities in the shape of a coin can cause extreme patient discomfort and vision loss, and this condition is termed nummular keratitis. This is not a new entity, although it has acquired greater significance in recent times. With the recent endemic presence of severe adenovirus keratoconjunctivitis, this is probably the most important cause of nummular keratitis today. This article attempts to answer these questions and provide a rationale for the clinical approach to the management of adenoviral keratoconjunctivitis.
Normal corneal structure and function is essential for excellent vision and comfort. Sometimes, however, the presence of fine granular opacities in the shape of a coin can cause extreme patient discomfort and vision loss, and this condition is termed nummular keratitis. This is not a new entity, although it has acquired greater significance in recent times. It was first described by Dimmer in 1905, and in an elaborate article in 1957, Pillat tried to distinguish Dimmer's keratitis from the changes that occur after adenovirus keratoconjunctivitis, as he believed that the two were distinct entities. However, despite his elaborate discussion, no clear distinction could be found, and in 1983, von Bijsterveld and Obster confirmed that Dimmer's keratitis falls under a heterogeneous group of diseases, characterized by distinct corneal changes, and it is difficult to distinguish the various entities causing these changes on corneal appearance alone. With the recent endemic presence of severe adenovirus keratoconjunctivitis, this is probably the most important cause of nummular keratitis today.
Adenovirus is a double-stranded DNA virus comprising of seven species (HAdV A–G), with fifty serotypes and seventy genotypes. It is responsible for respiratory, enteric, and ocular infections, and strains 8, 19, and 37 cause epidemic keratoconjunctivitis (EKC). It is an unusually stable virus, resistant to a wide variety of physical, chemical, and pH changes, and this is responsible for its endemic presence over the centuries, and from clinical experience, it appears that its virulence has increased in recent times. Adenoviral infections, like all viral infections, are designed to be self-limited. The virus takes over the cellular machinery to multiply and propagate itself to other hosts. In immunocompromised hosts, it can destroy the tissue of residence as in Cytomegalovirus retinitis, but is usually eliminated by the host immune response, as in rhinovirus infections. In order to exist and multiply in the host, viral infections reduce host inflammatory responses and inhibit cellular apoptotic mechanisms to allow viral replication. However, a knockout of some genes in the adenovirus, which decreases the expression of the E1a and E3 proteins, reduces the ability of the virus to mute the host immune response, resulting in more severe clinical features.
The usual course of adenovirus infections is to produce an infection of corneal epithelial cells, causing a fine superficial punctate keratitis in the 1st week, followed by the appearance of nummular subepithelial infiltrates (SEIs) at the level of the basement membrane and Bowman's layer by 2–3 weeks. It is believed that these changes represent a host immune response using polymorphonuclear leukocytes and lymphocytes. However, when managing adenovirus keratoconjunctivitis, several questions remain. Why do these subepithelial “nummular” lesions not occur in all adenovirus infections, what is the pathogenesis of these lesions, do they occur only in the more severe infections, is routine steroid use at the start of the infection deleterious to the cornea, is scarring inevitable in the natural history of SEI, and what is the best approach to managing and also preventing the occurrence of these lesions. This article attempts to answer these questions and provide a rationale for the clinical approach to the management of adenoviral keratoconjunctivitis.
It is known that ocular adenovirus infections can occur in three forms – simple follicular conjunctivitis, pharnygoconjunctival fever, and EKC. Keratitis is seen only in EKC. The Adenoplus rapid detection kit (Visufarma, Amsterdam, Netherlands) cannot distinguish between adenovirus strains; it can confirm the presence of adenovirus infection, but not the type. Hence, infections by strains 8, 19, and 37 are more likely to cause SEIs. Jones reported that SEIs represent the host immune response to the presence of viral antigens in the superficial stroma, thereby reaching diffusion during the epithelial infection stage. Recently, Chodosh et al. have suggested that SEI may represent stromal infection by the virus, with a resultant host immune response. That these lesions are immunological in origin is further confirmed by the similarity in clinical appearance with Krachmer spots seen in corneal graft rejection, a host immune response against the graft antigens. More severe infections occur when the viral pathogenicity is increased in some strains, resulting in increased antigenic load, or when host immune tolerance is abrogated, resulting in increased immune response. As SEIs represent an immune reaction, in both of these instances with more severe infections, the occurrence of SEIs increases.
Rabbit studies have shown that steroid use increases adenoviral replication, and as increased epithelial infection promotes viral diffusion into the anterior stroma, steroids are best avoided in the routine initial management of EKC to decrease the occurrence of SEI. Untreated SEIs, with increased accumulation of immune cells and mediators in the anterior stroma, can result in the destruction of corneal collagen and stromal scarring. Hence, steroid use should be considered when appropriate to protect corneal clarity. These situations for steroid use include central SEI causing visual degradation; occupational requirements for clear vision, namely, ophthalmic surgeons; and when there is a confluence of SEI with overlap of adjacent spots as this can result in accelerated corneal damage and scarring. Thus, peripheral SEI or those causing only irritative symptomatology are best observed. Such lesions usually clear with time, as the immune defense removes the viral antigen – usually three episodes occur at 6–8 weeks, 3–4 months, and 9–12 months, with successive episodes being shorter in duration and lesser in severity.
Usually, surface-acting steroids such as loteprednol and fluorometholone suffice, although in the most severe cases, initiation of therapy with prednisolone or dexamethasone may be necessary. Once started, however, a very gradual taper of steroid therapy is required to reduce the chance of recurrence. The addition of 0.05% or 1% topical cyclosporine A and 0.03% tacrolimus ointment has been reported to reduce the recurrence rate. A recent article describes the use of intracorneal injection of 0.2-ml betamethasone and 0.2-ml ganciclovir adjacent to the SEI, with good success. Although the adenovirus does not respond to antivirals except cidofovir, there are reports that topical ganciclovir therapy or treatment with 5% povidone-iodine, or the combination of 1% povidone-iodine with 0.1% dexamethasone, may limit the initial viral proliferation and antigenic load. Once SEIs are established, excimer surface ablation has been reported in the removal of these lesions, although the results are variable, with some articles reporting increased scarring after treatment., Once scars are formed, however, the treatment is either a rigid contact lens or superficial anterior lamellar keratectomy.
While adenovirus infections are currently the predominant cause of corneal SEIs, other conditions have been described. These include brucellosis, acanthameba, lyme disease, adult inclusion conjunctivitis, Epstein–Barr virus, herpes simplex virus and herpes zoster corneal infections, and hyperimmunoglobulin D disease. Recognizing these entities from adenovirus SEIs is usually based on the absence of a preceding attack of conjunctivitis, unusual persistence of lesions, a strictly unilateral occurrence, altered morphology and deeper location of the SEI, the presence of corneal findings such as peripheral vascularization and opacification, ocular findings such as keratic precipitates and anterior chamber reaction, and the occurrence of features of the accompanying systemic disease. However, adenovirus EKC still remains the most important cause of SEI, and it is important when such patients present in the acute stage to try and avoid steroid therapy unless imperative to reduce the occurrence of SEIs. If SEIs occur, however, appropriate initiation and taper of steroid therapy along with other immunomodulators can help protect corneal clarity and visual function, although this may be a protracted process requiring patience on the part of the surgeon and the patient. Hence, although common, nummular keratitis remains a corneal sign and not a specific disease.
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