The endothelium is the deepest layer of the cornea; it maintains corneal transparency and has a barrier function.1 Viral endotheliitis is an infection of this layer and can be caused by herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), varicella zoster virus, and Epstein Barr virus (EBV).1–3 Endotheliitis is characterized by corneal edema, keratic precipitates, and mild anterior chamber reaction.1–4
Depending on the alignment of the stromal edema and the placement of the keratic precipitate, herpetic endotheliitis can be classified as disciform (most common), diffuse, or linear.1–5 Although the exact pathogenesis of endotheliitis in HSV is unknown, the response to steroid treatment supports an immunologic hypothesis.5 The complications depend on the severity of the immune reaction to the viral antigens within the endothelial cells.2 The edema caused by direct infection of the endothelium can lead to endothelial decompensation and overlying stroma and epithelial edema.1–3,6
Different measures can be used to treat the herpes endotheliitis depending on the severity of the infection and the patient’s immune status. The standard care for treatment of herpes simplex keratitis involves antiviral therapy, often in form of oral acyclovir, valacyclovir, or famciclovir, as well as topical and systemic steroids.5,7 We report a case of corneal decompensation caused by recurrent herpetic endotheliitis which was treated successfully with Descemet membrane endothelial keratoplasty (DMEK).
A 62-year-old woman presented to our department in October 2015 with persistent foreign-body sensation and a corrected distance visual acuity (CDVA) of 0.1 (20/200) in the right eye. She had a history of recurrent herpetic infections of the right cornea for 5 years, which were treated conservatively with antiviral and antiinflammatory topical and systemic medications.
At presentation, the patient was on oral acyclovir (800 mg, 5 times a day), dexamethasone eyedrops (Dexa-sine) (4 times a day), and ganciclovir ophthalmic gel (Virgan) (4 times a day). Light biomicroscopy showed corneal edema caused by central and paracentral endothelial–epithelial decompensation, remarkable corticonuclear cataract, and no signs of active infection or scarring of the corneal stroma (Figure 1). The intraocular pressure (IOP) was 12 mm Hg, and there was a reduction in corneal sensitivity. The central corneal thickness (CCT) at the time was 608 μm.
After a systemic treatment with acyclovir 800 mg 5 times a day, dexamethasone eyedrops 4 times a day, ganciclovir ophthalmic gel 4 times a day, and sodium chloride eyedrops (Omnisorb) 5 times a day for 5 months, there was some response to the recommended therapy in terms of the CCT, which was 521 μm. However, light biomicroscopy showed further signs of endothelial decompensation with epithelial edema combined with a more distinct corticonuclear cataract. The CDVA was 0.16 (20/125), and the IOP was 17 mm Hg. Thus, DMEK (8.0 mm) combined with phacoemulsification and posterior chamber intraocular lens (PC IOL) implantation was performed. Two weeks postoperatively, the CDVA in the right eye was 0.3 (20/60), and the IOP was 17 mm Hg. The patient was discharged on systemic acyclovir 400 mg, prednisolone 21-acetate eyedrops (Inflanefran forte), ganciclovir ophthalmic gel, and sodium chloride eyedrops, all 5 times a day.
The patient’s CDVA was 0.8 (20/25) 6 months postoperatively and 1.0 (20/20) at 1 year. The CCT was 423 μm and 425 μm, respectively, and light biomicroscopy showed no signs of graft rejection or herpetic recurrence (Figure 2). Systemic acyclovir therapy (400 mg 2 times a day) was continued for 1 year postoperatively. Lifelong treatment with prednisolone acetate eyedrops (Predforte) (once a day) and ganciclovir eye gel (once a day) was prescribed.
Corneal endotheliitis is identified by corneal edema, keratic precipitates, and mild anterior chamber reaction.1–3 Viral endotheliitis can be caused by many viruses (HSV-1, CMV, EBV, varicella zoster).1–3 Herpes simplex-1 causes more than 95% of ocular herpes infections. It can cause blepharoconjunctivitis, epithelial keratitis, stromal keratitis, iridocyclitis, or retinal infection and is a main cause of unilateral corneal blindness resulring from infection.2,8,9 Bilateral disease is found in 4% to 6% of the patients with a higher incidence in children and in conjunction with atopy and immune abnormalities.10,11 Recurrent attacks of herpes simplex keratitis are triggered by fever, trauma, overexposure to ultraviolet light, the onset of menstruation, and immunosuppressive status.2
The sex of the patient has an impact on the severity of the disease; it is more frequent and more severe in women.6 Visual loss results from scarring associated with recurrent corneal keratitis.10
The pathogenesis of scarring and neovascularization is unclear but thought to be a complex interaction of various cytokines, chemokines, and growth factors.9,10 This interaction causes endothelial dysfunction, and damaged endothelium can result in corneal edema secondary to endothelial decompensation.12 Complicated cases of viral keratitis are still treated by penetrating keratoplasty (PKP).6 One of the major complications after PKP for herpes simplex keratitis is recurrence of the HSV and rejection of corneal transplants after recurrent herpetic disease.10
Our patient had a history of recurrent herpetic keratitis for 5 years. At presentation, she reported a significant decrease in visual acuity and persistent foreign-body sensation. Endothelial decompensation was diagnosed. The clinical examination showed an affected endothelium; however, the stroma was without scars. We treated our patient with DMEK combined with cataract surgery. The patient had remarkable improvement in her symptoms and in visual acuity, which increased from 0.2 (20/100) before surgery to 1.0 (20/20) 1 year after surgery.
Descemet membrane endothelial keratoplasty provides an exact anatomic replacement of dysfunctional host corneal endothelium with healthy donor endothelium. Therefore, it can be applied in the treatment of endothelial dysfunctions, such as endothelial failure from trauma or infection, Fuchs endothelial dystrophies, and pseudophakic bullous keratopathy.13–16
The donor preparation and the maneuvers of the graft roll in the anterior chamber are the most challenging aspects of performing DMEK.13,17 However, DMEK provides fast visual recovery and a lower risk for rejection by considerably reducing the donor tissue volume.17
Descemet membrane endothelial keratoplasty can be combined with phacoemulsification and PC IOL implantation, which can avoid the risk for endothelial damage associated with subsequent cataract surgery.13 Antiviral medication after surgery might help reduce the risk for recurrence.18
In conclusion, corneal decompensation caused by herpetic endotheliitis used to be treated exclusively with PKP. Descemet membrane endothelial keratoplasty combined with cataract surgery seems to be a favorable surgical option in the treatment of corneal endothelial decompensation after recurrent herpetic endotheliitis.
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None of the authors has a financial or proprietary interest in any material or method mentioned.