Treatment of cytomegalovirus anterior segment infection with intravitreal injection of ganciclovir in adjunction with or without oral valganciclovir: a long-term results.

We evaluated the therapeutic outcome of intravitreal injection (IVI) of ganciclovir with/without oral valganciclovir for cytomegalovirus (CMV) anterior segment infection. We enrolled 61 patients (61 eyes) with PCR-proven CMV anterior segment infection. IVI of ganciclovir (2 mg/0.05 mL) was given as a loading dose; subsequent use of oral valganciclovir (900 mg twice daily) was determined according to the severity of anterior chamber inflammation after injection. All eyes had IVI of ganciclovir, and 53 patients received oral valganciclovir as adjunctive therapy with a mean duration of 1.9 months to achieve disease remission. Repeated diagnostic aqueous taps were performed in 37 eyes with suspected recurrence, and CMV DNA was positive in 24 eyes. This therapeutic strategy afforded a median 50% recurrence-free survival time of 47.0 ± 8.12 months. The patients' mean best corrected visual acuity, intraocular pressure and corneal endothelial cell counts stabilized or improved. Corneal transplantation before CMV infection diagnosis was identified as an independent risk factor for recurrence (hazard ratio 6.81, 95% confidence interval 1.21-38.23, P = 0.029). In patients with CMV anterior segment infection, the relative short-term therapeutic strategy, IVI of ganciclovir in adjunction with/without oral valganciclovir, effectively achieved a median recurrence-free survival time of nearly 4 years.

Clinical Findings of Anterior Segment Spectral Domain Optical Coherence Tomography Images in Cytomegalovirus Corneal Endotheliitis.

PURPOSE: To evaluate the morphological characteristics of posterior corneal regions including keratic precipitates in eyes with cytomegalovirus (CMV) corneal endotheliitis using anterior segment spectral domain optical coherence tomography (SD-OCT). METHODS: Thirteen eyes of 13 patients with polymerase chain reaction-proven CMV corneal endotheliitis were included in this study. Slit-lamp images and anterior segment SD-OCT images of the posterior cornea were obtained to analyze the clinical characteristics of corneal structures and keratic precipitates. Morphological changes in the posterior cornea throughout the course of an antiviral treatment were also investigated. RESULTS: Anterior SD-OCT images showed protruding structures at the posterior cornea. These protruding structures exhibited dendritic, dome-shaped, quadrangular, or saw-tooth appearance, and reflectivity of these structures was high. Reflectivity of posterior corneal images including the endothelium and deep stromal corneal regions were also high (76.9%). Because corneal inflammation and corneal edema improved, the protruding structures and high-intensity regions of posterior corneal images were resolved after a course of antiviral treatment. CONCLUSIONS: The anterior segment SD-OCT examination represents a useful noninvasive alternative to diagnose and monitor CMV corneal endotheliitis.

Long-Term Topical Ganciclovir and Corticosteroids Preserve Corneal Endothelial Function in Cytomegalovirus Corneal Endotheliitis.

PURPOSE: To report the long-term outcomes of topical ganciclovir (GCV) and corticosteroids as a maintenance therapy for cytomegalovirus (CMV) corneal endotheliitis. METHODS: This retrospective study included 10 eyes of 9 patients diagnosed with CMV corneal endotheliitis with a minimum 1-year follow-up at a tertiary referral hospital between 2008 and 2014. CMV corneal endotheliitis was defined by corneal edema associated with typical keratic precipitates (KPs) and a positive CMV polymerase chain reaction from aqueous humor taps. Patients receiving long-term topical 0.5% GCV and topical corticosteroids without discontinuation were included. The final corneal condition and endothelial cell density (ECD) were reported. RESULTS: The mean age was 45.6 ± 11.7 years. The mean follow-up duration was 48 ± 25 months. All patients exhibited typical coin-shaped and/or linear KPs. A significant resolution of corneal edema and decreased KPs were achieved within 1 month in all patients after initiating topical 0.5% GCV every 2 hours and topical corticosteroids twice a day. The dose frequency was gradually tapered to GCV 4 times and corticosteroids once or twice a day as a maintenance therapy. All 10 eyes had a clear graft or corneas at the end of this study. The mean ECD was 1630 ± 699 cells per millimeter square before treatment and 1776 ± 834 cells per millimeter square at the end of the study period. CONCLUSIONS: Topical 0.5% GCV and corticosteroids as a maintenance regimen without interruption effectively preserved long-term corneal endothelial function.

Oral steroid therapy as an adjuvant treatment for severe epidemic keratoconjunctivitis in patients younger than 3 years.

PURPOSE: To evaluate the therapeutic effect of oral steroids given to patients younger than 3 years with epidemic keratoconjunctivitis (EKC) accompanied by severe eyelid edema and inflammatory ptosis, in whom eye drops were not feasible. METHODS: This study included 9 patients treated for EKC in local clinics whose condition failed to improve due to severe eyelid swelling together with difficulties in application of eye drops and pseudomembrane removal. We analyzed the extent of eyelid swelling, corneal damage, follicles, chemosis, and pseudomembrane formation in these patients before and after oral corticosteroid therapy in collaboration with the pediatrics department. RESULTS: After a mean of 1.8 ± 0.7 days of oral steroid treatment, eyelid edema, corneal damage, conjunctival injection, follicles, and chemosis improved in all patients. CONCLUSIONS: Oral steroids are an effective adjuvant treatment for EKC in patients younger than 3 years in whom eye drops could not be administered frequently due to severe eyelid edema.

Concomitant herpes simplex virus and cytomegalovirus endotheliitis in immunocompetent patient.

A case of an immunocompetent 51-year-old healthy man with chronic recurrent disciform corneal oedema and hypertensive anterior uveitis in the right eye for 2 years was unresponsive to topical corticosteroid and systemic acyclovir. Diagnostic anterior chamber tapping was performed and viral DNA PCR was positive for both cytomegalovirus and herpes simplex virus. The patient was treated with both oral valganciclovir for 3 months and long-term oral acyclovir. His condition improved significantly after the treatment; intraocular pressure and anterior chamber inflammation were controlled and the remaining keratic precipitates in the cornea started to clear up.

Outcomes of corneal transplantation for irreversible corneal decompensation secondary to corneal endotheliitis in Asian eyes.

PURPOSE: To describe outcomes of corneal transplantation for irreversible corneal decompensation from corneal endotheliitis in Asian eyes. DESIGN: Retrospective, observational case series. METHODS: We reviewed consecutive patients with corneal endotheliitis (32 eyes of 31 subjects) who underwent keratoplasty (January 1, 2008-December 1, 2009). All eyes had preoperative aqueous polymerase chain reaction (PCR) analysis for viruses, including cytomegalovirus (CMV). CMV-positive patients were treated preoperatively with topical corticosteroids and anti-CMV treatment (oral valganciclovir 900 mg twice daily, topical ganciclovir 0.15% 5 applications per day, for 6 weeks) with complete resolution of ocular inflammation, and quiescence for at least 6 months before corneal transplantation. Our main outcome measure was recurrence of endotheliitis within 1 year after corneal transplantation. RESULTS: Five eyes were CMV positive; the remaining 27 eyes were negative for all viruses on PCR analysis. CMV-positive patients had a higher rate of recurrence of endotheliitis within 1 year after corneal transplantation, compared with CMV-negative eyes (60% vs 7.4%, P = .01). The CMV-positive eyes had recurrent endotheliitis at a median of 10 months (range 3-11 months) after corneal transplantation. After successful anti-CMV treatment, all 5 CMV-positive eyes then continued to have clear grafts for a median duration of 21 months (range 13-44 months). CONCLUSION: Our study suggests that Asian patients with corneal endotheliitis may benefit from preoperative aqueous PCR analysis before corneal transplantation. Such patients were more likely to have a recurrence of endothelial inflammation if they were CMV positive preoperatively, despite successful anti-CMV treatment before surgery.

Cytomegalovirus-positive corneal stromal edema with keratic precipitates after penetrating keratoplasty: a case-control study.

PURPOSE: To identify differences between cytomegalovirus (CMV)-positive and CMV-negative eyes presenting as suspected endothelial graft rejection after penetrating keratoplasty (PK). METHODS: A retrospective consecutive case-control series. Aqueous humor samples of all eyes with corneal stromal edema and keratic precipitates (KPs) after PK, seen at the Singapore National Eye Centre from 2007 to 2010, were analyzed for CMV DNA by polymerase chain reaction. Their charts were reviewed for demographic data, medical and ocular history, best-corrected visual acuity, intraocular pressure, anterior segment clinical findings, and therapy. RESULTS: Of 11 eligible eyes (11 patients), 7 were CMV positive. All eyes were negative for herpes simplex virus and varicella zoster virus. The 2 groups were similar in age, gender, and previous ocular surgery. The main differences were the presence of extensive heavily pigmented KPs, Descemet membrane folds, and the absence of vascularization of the donor in CMV-positive eyes (100% vs. 0%, P = 0.003, Fisher exact test). All the CMV-positive eyes were treated with ganciclovir (5 systemic, 2 topical), and the control eyes received immunosuppression. However, all the grafts failed. Best-corrected visual acuity at the last visit was worse than 20/400 in all except 1 control eye, which had a follow-up of 30 months. CONCLUSIONS: There is a high prevalence of CMV infection in eyes that develop corneal stromal edema with KPs after PK. Heavy endothelial pigmentation, Descemet membrane folds, and the absence of donor vascularization may aid in the diagnosis of CMV in the event that aqueous analysis is not possible.

Cytomegalovirus endotheliitis after fluocinolone acetonide (Retisert) implant in a patient with Behçet uveitis.

PURPOSE: To report a case of cytomegalovirus (CMV) endotheliitis after insertion of an intravitreal fluocinolone acetonide (Retisert) implant. DESIGN: Interventional case report. METHODS: Retrospective chart review. RESULTS: A 40-year-old man received a Retisert implant in the left eye for recurrent Behçet uveitis. Although inflammation became quiescent within a month, corneal edema developed 4 months after insertion. Polymerase chain reaction analysis for aqueous humor detected 3.9 × 10(4) copies/mL of CMV DNA. After treatment with oral valganciclovir, CMV DNA nearly disappeared but visual outcome was poor due to corneal decompensation resulting from severe endothelial cell loss. CONCLUSIONS: After Retisert implant, clinicians should be attentive to the potential risk of CMV endotheliitis.

Atypical presentation of cytomegalovirus endotheliitis: a case report.

PURPOSE: To describe an atypical case of cytomegalovirus (CMV) endotheliitis in a 74-year-old man who presented with chronic corneal edema without keratic precipitates (KPs) and intraocular pressure (IOP) elevation. DESIGN: Case report. METHODS: A complete ophthalmologic examination was performed. Polymerase chain reaction was used to test for herpes simplex virus, varicella zoster virus, and CMV DNA in aqueous humor samples to rule out viral endotheliitis. RESULTS: Severe bullous keratopathy was found in the temporal part of the cornea without KPs or elevated IOP. CMV DNA was detected. Corneal edema subsided with oral valganciclovior. CONCLUSIONS: CMV endotheliitis may present as corneal edema that lacks typical features, such as KPs or elevated IOP.

Cytomegalovirus endotheliitis in Descemet's stripping endothelial keratoplasty.

OBJECTIVE: To report 4 cases of undiagnosed cytomegalovirus (CMV) endotheliitis in patients who underwent Descemet's stripping automated endothelial keratoplasty (DSAEK). DESIGN: Retrospective interventional case series. PARTICIPANTS: Four eyes of 4 patients diagnosed with active CMV endotheliitis after DSAEK. METHODS: Retrospective review of the medical records of 4 patients with DSAEK who had an aqueous tap that was positive for CMV DNA but negative for herpes simplex virus (HSV) and varicella zoster virus. MAIN OUTCOME MEASURE: Clinical features and management. RESULTS: Four immunocompetent Chinese male patients with a mean age of 67 years underwent DSAEK for posterior polymorphous dystrophy (1), Fuchs' heterochromic cyclitis (1), pseudophakic bullous keratopathy (1), and herpetic keratouveitis (1). Clinical findings seen in all patients were localized corneal edema, increased intraocular pressure, pigmented keratic precipitates (KPs), and no/minimal anterior chamber (AC) activity. An unexplained sudden decrease in endothelial cell count (ECC) in the absence of rejection or significant inflammation was seen in 3 patients, whereas 1 patient also developed concomitant retinitis. CMV DNA was positive in all aqueous specimens and from the vitreous of the patient with retinitis. All patients were treated with oral valganciclovir with resolution of inflammation; 2 patients had recurrences; 1 patient developed recurrent retinitis; and 1 patient developed recurrent CMV endotheliitis and is currently receiving maintenance therapy with oral valganciclovir. CONCLUSIONS: CMV endotheliitis with corneal edema masqueraded as a variety of other endothelial conditions, which resulted in DSAEK surgery being performed in these patients who may have responded to antiviral treatment without the need for endothelial transplantation. A heightened awareness is required to exclude CMV endotheliitis as the cause for endothelial decompensation or unexplained, sudden reduction in ECCs post-DSAEK in the absence of other complications, and it should be differentiated from allograft rejection in view of the critical difference in treatment.

Case of bilateral multiple herpetic epithelial keratitis manifested as dendriform epithelial edema during primary Kaposi's varicelliform eruption.

BACKGROUND: Bilateral herpetic keratitis has been reported in patients with atopy, measles, graft-versus-host disease, and altered immune status. We report a serologically verified case of primary, simultaneous onset, bilateral, atypical epithelial herpetic keratitis that manifested as dendriform epithelial edema during a generalized dermatitis incident. CASE: A 37-year-old man with chronic atopic dermatitis developed Kaposi's varicelliform eruption and bilateral dendritic epithelial keratitis with corneal epithelial edema. OBSERVATIONS: The pathogens isolated from both eyes were identified as herpes simplex virus type 1 (HSV-1) by a direct immunofluorescence method. Serological tests obtained on three different occasions over a 5-week period verified a primary HSV infection. CONCLUSIONS: With serological verification, we report a rare case of primary, simultaneous onset, bilateral, dendritic epithelial keratitis at a very early stage with complications of generalized herpetic disease in a patient with atopic dermatitis.

Corneal endotheliitis.

Corneal endotheliitis is an intriguing clinical entity manifested by corneal edema, keratic precipitates, and mild anterior chamber reaction, and can be defined as a spectrum of the disorder in which the corneal endothelium is the primary site of the inflammation. The disease etiology consists of accumulating evidence of various viral infections including herpes simplex virus, varicella zoster virus, and cytomegalovirus. Corneal endotheliitis can be classified clinically into four forms: linear, sectorial, disciform, and diffuse. Antiviral treatment in combination with topical corticosteroids is generally effective to suppress the inflammation; however, irreversible corneal endothelial dysfunction may develop in some cases.

Herpes zoster sine herpete presenting with hyphema.

PURPOSE: To report a case of herpes zoster sine herpete presenting with hyphema. METHODS: A 69-year-old man was referred for traumatic hyphema and corneal edema in his left eye after a sandblast exposure three weeks previously. Slit-lamp examination demonstrated hyphema, anterior chamber inflammation, mid-dilated pupil, impaired corneal sensation, and high intraocular pressure, without any facial skin lesions. Iris fluorescein angiography revealed tortuosity and extensive occlusion of iris vessels. The patient was treated with oral acyclovir and intensive topical steroids with a presumed diagnosis of severe herpes zoster uveitis. RESULTS: Clinical findings improved dramatically within several days. Typical sectorial iris atrophy with pupillary sphincter dysfunction and complete loss of corneal sensation developed after the resolution of intraocular inflammation. CONCLUSION: Herpes zoster should be considered in patients with uveitis and hyphema even in the absence of typical skin rash.

Herpes simplex virus in the trabeculum of an eye with corneal endotheliitis.

PURPOSE: To report an eye with corneal endotheliitis and increased intraocular pressure in which the trabeculum demonstrated immunoreactivity for herpes simplex virus. METHOD: Case report. A 62-year-old man presented with increased intraocular pressure, keratic precipitates, and corneal stromal edema in his left eye. The tissue excised during trabeculectomy was immunohistochemically examined for herpetic viruses. RESULT: Immunoreactivity for herpes simplex virus was identified in the trabeculum. CONCLUSION: Herpes simplex virus may cause trabeculitis and increased intraocular pressure in patients with corneal endotheliitis.

Disciform keratitis: a case of herpes zoster sine herpete.

PURPOSE: To describe a case of disciform keratitis in a patient with acquired immunodeficiency syndrome (AIDS) in which varicella-zoster virus was the causative agent. METHOD: Case report, Polymerase chain reaction-based assays for varicella-zoster virus, cytomegalovirus, and herpes simplex virus were used to analyze an aqueous aspirate. RESULTS: We examined a 41-year-old man with AIDS but without a history of varicella-zoster virus dermatitis who had disciform corneal edema in his left eye. Varicella-zoster virus was detected by a polymerase chain reaction-based assay in the aqueous of the left eye; however, neither cytomegalovirus nor herpes simplex virus DNA were detected by polymerase chain reaction-based assays. The corneal edema slowly resolved while the patient was treated with famciclovir. CONCLUSION: Varicella-zoster virus may cause disciform keratitis without a preceding skin eruption.

Endothelial barrier function and Na+/K(+)-ATPase pump density in herpetic stromal disease.

PURPOSE: Corneal edema is a significant component of the various forms of herpes simplex virus type 1 (HSV-1)-induced stromal disease. Maintenance of corneal thickness, a reflection of corneal hydration, depends on a physical barrier formed by endothelial cell-cell junctions and by the activity of Na+/K(+)-ATPase pumps that regulate ion flux and thus influence water movement through this cell layer. These functions were measured in corneas with increased corneal thickness caused by HSV-1-induced stromal disease to determine their contribution to the pathogenesis of the edema. METHODS: Stromal disease with corneal edema was induced in rabbits by intrastromal injection of the RE strain of HSV-1. At various times after infection, during the development of and recovery from stromal disease, endothelial barrier function and Na+/K(+)-ATPase pump sites were measured in excised rabbit corneas. RESULTS: The endothelial permeability coefficient, Ktrans, for 14C-dextran, 3H-inulin, and 14C-mannitol, were not altered significantly during periods of maximal corneal edema and stromal disease. Endothelial Na+/K(+)-ATPase pump density, as measured by ouabain binding, showed a statistically significant (P < 0.05) decrease in HSV-1-infected corneas during peak edema compared to mock antigen-injected or uninjected control corneas. Pump density returned to baseline values by 24 days after infection, concurrent with the resolution of corneal edema. CONCLUSIONS: These results indicate that corneal endothelial barrier function was not altered in this form of HSV-1-induced stromal edema; however, pump density was reduced significantly.

Atypical herpetic endotheliitis.

BACKGROUND: Three patients ranging in age from 26 to 40 years presented with unilateral posterior stromal lesions with diffuse stromal edema. There was no history of prior surgery, trauma, infectious disease, dystrophy or exposure to noxious agents. Only one patient had signs of anterior chamber reaction and none of the patients showed any sign of epithelial involvement or of associated blood vessels or scarring. All three patients presented with features atypical of herpetic disease, such as lack of epithelial involvement and posterior stromal opacification. They also demonstrated many of the typical characteristics of herpetic disease, however, and thus were diagnosed as having herpetic endotheliitis. RESULTS: All three patients were treated with a regimen of antiviral agents and corticosteroids. Two patients improved, although the time frame differed in each. One patient subjectively improved, then worsened 1 month later after discontinuing treatment on her own. She was lost to subsequent follow-up. CONCLUSIONS: Young patients presenting with unilateral posterior stromal opacification and stromal edema in the absence of epithelial involvement are likely to have endotheliitis of herpetic origin.