Bilateral Necrotizing Scleritis with Scleral Melt associated with Herpes Simplex Infection: A Case Report

Objective (Aim): The article is a case report of a very rare case of bilateral herpes simplex virus infection associated with bilateral necrotizing scleritis with scleral melt in an elderly north Indian female of lower middle socioeconomic status. Methods: A 65-year-old female presented to our clinic with a wide variety of presentations ranging initially from neurotropic corneal ulcer to necrotizing scleritis with scleral melt for 2 years. The patient records were evaluated and computed. A PubMed literature search on herpes scleritis was conducted and reviewed. Results: A keen sense of judgment, timely management, and patient counseling are crucial for a rapid and favorable outcome. Conclusions: Bilateral necrotizing scleritis with scleral melt can be a rare atypical presentation of herpes simplex keratitis. In such atypical cases, diagnosis may be challenging. Associated clinical findings, history of herpes keratitis, which may be recurrent, and response to antiviral drugs, may give clues towards the diagnosis in such atypical cases. In addition to this, surgical intervention should not be delayed if it seems inevitable. Abbreviations: RE = right eye, LE = left eye, BCL = bandage contact lens, KP = keratic precipitate, mm = millimeter, mg = milligram


Introduction
Inflammation of the sclera is termed Scleritis, which is a rare ocular inflammatory disease caused by occlusive vasculitis of the deep episcleral plexus with a risk of ischemia and necrosis [1].It can be classified anatomically as anterior or posterior, depending on the site of the lesion.Anterior scleritis is further classified into diffuse, nodular, and necrotizing, depending on the type of lesion [2,3].Immunological etiologies have been implicated in most of cases (90%-95%) of scleritis while 5%-10% of cases of scleritis develop from infections [4][5][6][7][8].Although rare, an infectious etiology may be considered in cases of scleritis, especially those that are long-standing, fail to respond to standard therapies, or are of necrotizing type.
Herpes keratitis has a global incidence of 1.5 million yearly with nearly 40,000 cases contributing to severe visual impairment, although its prevalence depends upon age, socioeconomic status, and geographic location [9,10].
This case report presents an unusual case of herpes infection associated with bilateral necrotizing scleritis with scleral melt in one eye in an elderly north Indian female of lower middle socioeconomic status.rural community in Prayagraj, Uttar Pradesh, India, who presented in our clinic around 2 years back with a history of pain, redness, photophobia, and diminution of vision in the right eye (RE).She had a history of uneventful cataract surgery in both eyes 5-6 years back.She also had similar complaints in her left eye (LE) a few years back of which no documents were available.According to the patient, no systemic co-morbidity existed.Her vision was finger counting in RE and 6/36 in LE.On slit-lamp examination, a large corneal defect, having a smooth base and margins with no infiltrate, was observed, extending from 10 to 5 o'clock and was associated with peripheral corneal melting in RE (Fig. 1).Her Schirmer's value was 10 mm in RE and 12 mm in LE.Corneal sensations were diminished in RE.Based on clinical presentation, she was diagnosed with neurotrophic corneal ulcer stage 3 with peripheral corneal melting (RE).She was started on topical lubricating eye drops in RE and a bandage contact lens (BCL) was also applied.The defect healed in 6 weeks with peripheral corneal thinning when BCL was removed and lubricating drop was continued.

A B
The patient remained asymptomatic for 2 months when she presented again with pain, redness, and watering in the same eye (RE).Slit-lamp examination showed epithelial keratitis with a greyish elevated margin with subepithelial infiltrate in the central cornea along with a few medium-sized greyish keratic precipitates (KPs) with 2+ cells and mild flare (Fig. 2).Typical corneal lesion and anterior chamber reaction along with the previous clinical history of the patient, suggested the diagnosis of herpetic kerato-uveitis.Oral Acyclovir 400 mg 5 times a day for 14 days was administered, thereafter the dosage was reduced to twice a day.Along with systemic medications, topical corticosteroids, and lubricating eye drops were administered in RE.She showed improvement within 2 weeks and thus topical corticosteroids were tapered and she was kept on follow-up with lubricating eye drops and oral Acyclovir 400 mg twice a day.A detailed dilated fundus evaluation and refraction were also performed.Her fundus examination was within normal limits and visual acuity improved to 6/24 in RE and 6/12 in LE with spectacles.3).Conjunctival scrapping was sent for gram staining and culture sensitivity, which came out to be negative for any microbial growth.Clinical findings and typical epithelial keratitis lesion suggested the recurrence of herpetic infection with necrotizing scleritis, which progressed to scleral melt in LE.A conjunctival advancement flap was performed to cover the scleral melt at 12 o'clock in LE under sterile aseptic conditions.Oral Acyclovir 400 mg was started 5 times a day along with topical antibiotic and lubricating eye drops in both eyes and in addition, topical corticosteroid eye drops were started in RE.She showed gradual improvement in signs and symptoms and scleral necrosis and corneal epithelial keratitis lesions gradually disappeared and only a few superficial punctate keratitis lesions were seen at the end of 3 weeks post-surgery.

Discussion
Herpes keratitis is one of the leading causes of infectious keratitis worldwide and can involve any part of the eye.The manifestations range from dendritic ulcer, and necrotizing stromal keratitis, to scleritis, retinitis, and peripheral ulcerative keratitis.
While in some cases the patient has a typical clinical appearance of dendritic ulcer and the pathological process is straightforward, there are many cases in which this demarcation seems blurry and diagnosis may be challenging.Scleritis is one such atypical presentation of herpes infection.Although herpetic scleritis is not uncommon, necrotizing scleritis type associated with herpes infection has been rarely seen and only a handful of cases have been reported.On thorough literature search, we obtained a total of 4 cases of necrotizing scleritis, most of them being unilateral and without any scleral melt [11,12,14].Although, the diagnosis can be confirmed on conjunctival scleral biopsy, polymerase chain reaction analysis of the aqueous sample, and positive serum anti-herpes virus titers, in most cases the decision has to be made on clinical grounds [11][12][13][14][15][16].The literature search performed on herpetic scleritis was tabulated (Table 1).

Nodular scleritis Clinical features of skin lesions
Oral Acyclovir and corticosteroids [16] This case report presented a case of bilateral necrotizing scleritis with scleral melt, though not previously reported in the literature, the diagnosis was made based on typical associated clinical findings of keratouveitis, based on previous clinical episodes and rapid response to antiviral therapy.Because of the straightforward diagnosis, scleral biopsy was not performed.
While the treatment for direct viral invasion is antiviral medication, the treatment for the immune reaction is corticosteroid therapy to suppress the immune reaction.For necrotizing scleritis, surgical options may be included to tackle problems of associated scleral melt.Antiviral drugs with judicial use of corticosteroids may act as a boon for the patient if used timely and in the right dosage.Hence, the significance of determining the pathological process through keen observation of signs and symptoms, cannot be underestimated.

Conclusion
This case report aimed to demonstrate a rare atypical presentation of bilateral herpetic necrotizing scleritis with scleral melt.While the diagnosis is straightforward in cases with typical findings, in atypical cases the diagnosis may be challenging.Associated clinical findings, history of herpes keratitis that may be recurrent, and response to antiviral drugs may give clues toward diagnosis in such atypical cases.In addition, surgical intervention should not be delayed if it seems inevitable.

ABFig. 1 A
Fig. 1 A. Initial presentation with large ulcer having a smooth base and margins extending from 10 to 5 o'clock mid-peripheral to peripheral cornea associated with peripheral corneal thinning.B. Healed corneal ulcer with thinning of the peripheral cornea

Fig. 2 A
Fig. 2 A. 2 nd episode showing epithelial keratitis with a greyish elevated margin with subepithelial infiltrate in the central cornea along with a few medium-sized grey keratic precipitate (KP) with 2+ cells and mild flare.B. Presentation after 2 weeks showing healed corneal lesions and no KPs

Fig. 3 A
Fig. 3 A. 3 rd episode showing an inferotemporal scleral necrotic lesion (arrowheads) at 3-5 o'clock near limbus in RE.B. At the same visit, the patient also had scleral necrosis with scleral melt at 12 o'clock (arrow) and at 9-10 o'clock near limbus along with epithelial keratitis lesion at 1 o'clock in LE. C. Presentation after 3 weeks showing healed scleral lesion in RE.D. Presentation after 3 weeks showing healed scleral and corneal lesions in LE

Table 1 .
Summary of the literature search on herpetic scleritis