Demonstration of "owl's eye" morphology by confocal microscopy in a patient with presumed cytomegalovirus corneal endotheliitis

PURPOSE: To report confocal microscopic observations of characteristic corneal endothelial lesions in a patient with presumed cytomegalovirus (CMV) corneal endotheliitis. DESIGN: Case report. METHODS: A 77-year-old, immunocompetent man was admitted with corneal edema, keratic precipitates, and coin-shaped lesions in the right eye. Confocal microscopy was performed to examine the corneal endothelium. Polymerase chain reaction (PCR) was used to identify viral DNA in an aqueous humor sample. RESULTS: CMV DNA was detected by PCR. Confocal microscopy showed large corneal endothelial cells with an area of high reflection in the nucleus surrounded by a halo of low reflection. This "owl's eye" morphology is characteristic of CMV infection. Topical and intravenous ganciclovir treatment resulted in rapid resolution of the corneal precipitates and edema, followed by disappearance of the owl's eye morphology. CONCLUSIONS: Confocal microscopy can detect the owl's eye morphology in the corneal endothelium of patients with presumed CMV corneal endotheliitis.     

Cytomegalovirus in aqueous humor from an eye with corneal endotheliitis

PURPOSE: To report cytomegalovirus (CMV) DNA in aqueous humor from a patient with unilateral corneal endotheliitis. DESIGN: Case report. METHODS: A 51-year-old man presented with unilateral corneal endotheliitis with linear keratic precipitates and coin-shaped lesions. Tear and aqueous humor samples were subjected to polymerase chain reaction to look for DNA from herpes simplex virus (HSV), varicella zoster virus (VZV), and CMV. RESULTS: Aqueous humor from the diseased eye contained DNA from CMV but not HSV or VZV. Its specificity was confirmed by Southern blot tests. Intravenous ganciclovir treatment resulted in the localization of his corneal edema and the reduction in keratic precipitates. There was severe destruction of corneal endothelial cells. CMV DNA was not detected in tears or control samples. CONCLUSIONS: In this healthy man with corneal endotheliitis, we detected CMV DNA in aqueous humor from the affected eye, but not HSV or VZV. This suggests that CMV may cause corneal endotheliitis in patients without immunodeficiency.     

更昔洛韦眼用凝胶和阿昔洛韦滴眼液治疗病毒性角膜炎疗效对比

目的：探讨病毒性角膜炎应用更昔洛韦眼用凝胶的疗效。

方法：随机选择2013-05/2014-10我院收治的84例101眼病毒性角膜炎患者作为研究对象,随机分为更昔洛韦组和对照组,分别给予更昔洛韦眼用凝胶和阿昔洛韦滴眼液治疗,2wk后观察疗效。

结果：两组患者治疗后较治疗前病毒性角膜炎各症状(畏光、流泪、疼痛、异物感)及各体征(睫状充血、角膜上皮缺损、角膜基质水肿、角膜荧光素染色)评分均有显著改善,更昔洛韦组改善更为明显(P<0.05); 更昔洛韦组有效率(92.9%)明显高于对照组(59.5%),差异有统计学意义(P<0.05); 两组患者不良反应无统计学差异(P>0.05),更昔洛韦组复发率明显低于对照组(P<0.05)。

结论：更昔洛韦眼用凝胶是一种安全有效的抗病毒滴眼液,治疗病毒性角膜炎疗效确切,值得临床中推广应用。     

Cytomegalovirus-related corneal endotheliitis: A review article

Cytomegalovirus (CMV)-related corneal endotheliitis is an inflammation of the corneal endothelium caused by CMV. It typically presents as coin-shaped keratic precipitates (KPs), with or without corneal edema, in otherwise healthy individuals. It may be associated with anterior uveitis and raised intraocular pressure (IOP). Patients with CMV-related corneal endotheliitis respond to systemic and topical ganciclovir with the use of topical steroid. Making an accurate early diagnosis is crucial in preventing loss of corneal endothelial cells and unnecessary treatment resulting from misdiagnosis in these patients.     

DNA of cytomegalovirus detected by PCR in aqueous of patient with corneal endotheliitis after penetrating keratoplasty

PURPOSE: Corneal endotheliitis often leads to severe endothelial dysfunction and can be caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and other viruses (eg, the mumps virus). We report a case of corneal endotheliitis caused by cytomegalovirus (CMV) that developed after a penetrating keratoplasty. METHODS: A complete ophthalmologic examination was performed on a patient with corneal endotheliitis that developed after a penetrating keratoplasty. To determine the cause of the endotheliitis, polymerase chain reaction (PCR) was used to amplify the DNA of HSV, VZV, and CMV in samples of the aqueous humor. RESULTS: Slit-lamp biomicroscopy showed a moderate stromal edema in the upper temporal part of the transplanted cornea along with keratic precipitates (KPs) arranged in a coin-shaped pattern. Repeated treatments with steroids and acyclovir were only temporarily successful. PCR detected the DNA of CMV in an aqueous sample, and the treatment was switched to topical and systemic application of ganciclovir. This resulted in the disappearance of the KPs and resolution of the stromal edema within 2 weeks. CONCLUSIONS: From the PCR results and the favorable response to ganciclovir, the corneal endotheliitis was most likely caused by cytomegalovirus in this case.     

Corneal Epithelial Lesions in Keratosis Follicularis (Darier's Disease)

The prevalence of eyelid keratotic plaques and unique corneal changes associated with Darier's disease, peripheral epithelial nebular opacities associated with irregular surface of the central corneal epithelium, are described. These corneal lesions occurred in 16 of 21 patients. The corneal lesions were asymptomatic, stable, and did not respond to oral retinoid therapy. Histopathology of the peripheral corneal opacities showed epithelial cell edema especially in the basal layer, and decreased desmosomes.     

The Effect of Topical Ganciclovir and Corticosteroid on Cytomegalovirus Corneal Endotheliitis in Korean Patients

Purpose: To report long-term outcomes of topical ganciclovir (GCV) and corticosteroids in Korean patients with cytomegalovirus (CMV) corneal endotheliitis.

Methods: This retrospective study included 13 eyes from 13 patients with CMV corneal endotheliitis, with a follow-up period of 24.5 ± 8.2 months. The patients were consistently maintained with topical 2% GCV and 1% prednisolone acetate eyedrop.

Results: All patients demonstrated unilateral typical coin-shaped keratic precipitates (KPs) or linear KP, and positive CMV polymerase chain reaction of aqueous humor. After 2 weeks of treatment, all patients showed decrease of clinical signs. During the follow-up, four patients developed mild anterior chamber inflammation with increased intraocular pressure without typical coin-shaped KPs or edema, started to use the initial dose, and resolved the clinical signs. One patient showed recurrence of corneal edema twice, and was administered systemic valgancyclovir for 2 weeks upon second recurrence with resolution of clinical signs.

Conclusion: Long-term maintenance therapy with topical GCV and corticosteroids are effective and maintain corneal endothelial function in Korean patients with CMV endotheliitis.     

Production of corneal lesions using high-intensity focused ultrasound

In order to study the potential use of ultrasound as a noninvasive system for altering corneal curvature, we used high-density focused ultrasound at a frequency of 4.8 MHz and 7.9 MHz to produce corneal lesions in the rabbit eye. Intensity and duration threshold exposure conditions were determined for the production of minimally visible lesions. Threshold lesions were initially apparent as discrete white opacities resulting from stromal edema and disruption. Light and scanning electron microscopy of higher-energy, suprathreshold lesions revealed more extensive disruption, including the formation of a superficial stromal depression and a larger zone of edema and disorganization surrounding each lesion. Posterior stromal lamellae, endothelium, and Descemet's membrane were intact. Healing and reepithelialization resulted in a smooth corneal surface with no residual opacification. Threshold determinations predict safe exposure levels to the cornea during insonification of other ocular structures. Selective heating of the peripheral cornea using focused ultrasound may be a useful technique for correcting astigmatism.     

IFN-α-2b联合更昔洛韦治疗角膜内皮炎

目的：探讨人重组α-2b干扰素(Interferon alpha-2b,INF-α-2b)联合更昔洛韦对角膜内皮炎的疗效。

方法：对确诊的15例患者均予以150万U INF-α-2b球周注射,静脉滴注更昔洛韦针剂0.25g 1次/ d,局部给予阿昔洛韦滴眼液每2h 1次,妥布霉素地塞米松滴眼液4次/ d,连续用药1wk,对于高眼压患者局部或全身予以降眼压治疗。

结果：经上述方法治疗1wk后,所有患者均治愈,视力提高,治愈率100%; 随访4～12mo,无复发病例。

结论：局部球周注射INF-α-2b联合静脉滴注更昔洛韦治疗角膜内皮炎具有疗程短、疗效好、治愈率高、复发率低的优点。     

Experimental tyrosine keratopathy in rabbits

Tyrosine was given to White New Zealand and Chinchilla bastard rabbits. The corneal epithelium showed pinpoint lesions and a pseudokeratitis dendritica from the fourth day on. In spite of continued tyrosine dosage these lesions disappeared clinically within 6 days. Scanning electron microscopy revealed necrosis of isolated epithelial cells even after the twentieth day of tyrosine dosage. Specular microscopy sporadically revealed glittering pre-endothelial structures. It was found by light microscopy that there was a tendency to focal proliferation of corneal epithelial cells and a vacuolization in the basal epithelial cell layers. Endothelial defects may be responsible for circumscribed edema of the corneal stroma.     

Participation of T lymphocyte in corneal edema in the early stage of herpetic stromal keratitis

The participation of T lymphocytes in the immunopathogenesis of corneal opacity in herpetic stromal keratitis was investigated. In BALB/c mice infected intracorneally with herpes simplex virus type 1, corneal opacity was manifested 10 days after infection, while in athymic mice corneas remained almost clear. Histologically, all opaque corneas revealed stromal edema accompanied by the diffuse presence of polymorphonuclear cells and lymphocytes. When complement (C')-treated immune spleen cells were adoptively transferred into athymic mice 6 or 72 h after corneal infection, stromal keratitis with mild opacity was observed 10 days after transfer. The athymic mice given anti-Thy 1.2+C'-treated immune spleen cells failed to develop corneal opacity. The difference, as revealed by light and electron microscopy, was the presence or absence of lymphocytic infiltration and edema in the posterior third layers of the stroma and endothelial lesions. The endothelium was infiltrated by lymphocytes or macrophages and showed various stages of destruction. The main cause of corneal opacity in the early stage of herpetic stromal keratitis is thought to be stromal edema due to an adverse effect on the endothelium by immune T lymphocytes.     

Rapid diagnosis of herpetic infections by immunoperoxidase method

The PAP-(peroxidase-antiperoxidase)-immunohistochemical method was tested for rapid diagnosis on corneal specimens in clinically suspected herpetic disease. The method proved accurate, easy and useful in rapid diagnosis of corneal specimens from epithelial keratitis. Corneal buttons after keratoplasties for herpetic lesions were similarly tested for the presence of herpetic antigen. In a total of five corneal buttons, antigen was found in two corneas with necrotizing keratitis, whereas it was not noted in the three corneas opacified by disciform edema.     

The relation of conjunctival and corneal findings in severe ocular allergies

OBJECTIVE: Corneal lesions such as ulcers and erosions are major complications observed in patients with severe ocular allergic diseases. We aimed to look into the relationship between specific clinical conjunctival findings and the severity of corneal complications. METHODS: Thirty eyes of 6 patients with vernal keratoconjunctivitis (VKC) and 13 patients with atopic keratoconjunctivitis (AKC) were evaluated in this study. Slit-lamp photographs of upper tarsal conjunctiva and cornea were used to evaluate the clinical findings objectively. The corneal findings and clinical findings of upper tarsal conjunctiva such as conjunctival injection, edema, the height of papillae, and mucous discharge were evaluated and graded. Statistical correlations between conjunctival findings and the severity of corneal damage were analyzed. RESULTS: Conjunctival injection and edema significantly correlated with the severity of corneal complications. The height of the papillae and the amount of mucous discharge did not correlate with the severity of corneal complications. CONCLUSION: Direct signs of inflammation such as injection and edema correlated with corneal damage. The height of papillae did not show a significant correlation with the corneal findings. Our results suggest that inflammation of the conjunctiva rather than mechanical factors may play a greater role in the formation of corneal damage in severe ocular allergies.     

Identification of cytomegalovirus and human herpesvirus-6 DNA in a patient with corneal endotheliitis

Purpose

To report the case of a patient with unilateral corneal endotheliitis in which both cytomegalovirus (CMV) and human herpesvirus-6 (HHV6) DNA was identified in the aqueous humor.

Case

A 67-year-old man with corneal endotheliitis OD was referred to us for decreased visual acuity. Local corneal stromal edema, pigmented keratic precipitates, a coin-shaped lesion and minimal anterior chamber reaction were observed by slit-lamp biomicroscopy. Cells with owl’s eye appearance in the endothelial cell layer were observed by in vivo laser confocal microscopy. The patient had rheumatoid arthritis, which was treated by oral prednisolone and intravenous abatacept. Polymerase chain reaction analysis of aqueous humor samples detected both CMV and HHV6 DNA, but not other HHVs. Treatment with topical ganciclovir and systemic valganciclovir resulted in a clear cornea.

Conclusions

A patient with corneal endotheliitis had both CMV and HHV6 DNA identified in the aqueous humor. Although both viruses were identified in this case, clinical manifestations resembled CMV corneal endotheliitis, and it was unclear whether HHV6 could affect the clinical course. Systemic abatacept and corticosteroid therapy might play a positive role in cases with both CMV and HHV6 DNA in this corneal endotheliitis.     

The role of Brinzolamide 1% ophtalmic suspension in corneal edema

PURPOSE: The study is aimed at assessing the efficacy and safety of topical carbonic anhydrase inhibitor (IAC--i.e. ophthalmic suspension of brinzolamide 1%--Azopt) in the treatment of corneal edema. METHOD: For this purpose, we carried out an experimental, epidemiological-operational, randomised, placebo-controlled and double blind study, on three groups of laboratory animals (rabbits): group 1 (5 rabbits) included endothelial corneal injuries inflicted by ultrasound exposure by means of a phacoemulsification sound in both eyes group 2 (5 rabbits) included endothelial corneal injuries inflicted by direct trauma in both eyes group 3 (3 rabbits)--no endothelial corneal lesions (control group) In each group we instilled, all the animals, with ophthalmic suspension of brinzolamide 1% (Azopt), 1 drop t.i.d., in one eye for 14 days (starting the following day after infliction of endothelial injuries, when the corneal edema was evidenced by biomicroscopic examination) and placebo (saline solution 0.9% with the same osmolar and pH values as the Azopt) in the other eye. The assessment was performed throughout the following stages: To: preceding the infliction of corneal endothelial injuries, resorting to: biomicroscopic examination ultrasound pahimetry direct specular microscopy T1: the following day after infliction of corneal endothelial injuries, resorting to: biomicroscopic examination (the assessment of corneal edema) ultrasound pahimetry (measurement of corneal thickness and, hence edema) direct specular microscopy (cell density and endothelial ultrastructure evaluation: cellular polimegetism, pleiomorphism) T2: in the wake of 14 days therapy (after eye removal), adding to the previous examinations: indirect specular microscopy (with the same aim as the direct examination, yet examination carried out from the endothelial side) pathologic examination (using hematoxilin-eosin dye and Van-Gieson dye).     

An obstetrical injury as the etiology of chronic corneal edema. Clinical study with scanning microscopy

The case of a young woman with an unilateral corneal edema with regular folds of the descemet's membrane is reported. These lesions originate from an obstetrical traumatism by forceps and are associated with cutaneous scars of the temples. Scanning electron microscopy of the cornea shows multiple endothelial fissures; they are responsible for the late corneal decompensation.     

Corneal edema with several hard corneal contact lenses.

Five patients were each fitted with polymethylacrylate (PMMA), BP Flex, and Polycon corneal contact lenses of the same dimensions. Corneal edema was monitored with a slit-lamp biomicroscope and pachometer. Lenses were worn in a double-masked and random sequence for periods of 6 hr. Patients developed less corneal edema with Polycon lenses than with PMMA lenses. There was no significant difference in corneal edema with PMMA and BP Flex lenses. Those patients who developed little corneal edema with optimum-fitting PMMA lenses also developed little edema with the BP Flex and Polycon lenses. Steeper-fitting PMMA and BP Flex lenses produced more corneal edema than optimum-fitting lenses made of the same materials, while steeper-fitting Polycon lenses produced only slightly more edema than the optimum-fitting Polycon lenses.     

Impression cytology of herpetic simplex keratitis in rabbits

PURPOSE: To use impression cytology to examine the structural changes in corneal epithelial cells infected with the herpes simplex virus in rabbit eyes. METHODS: Corneal surfaces of 7 rabbits were scratched using a 25-gauge needle. Herpes simplex virus (type 1, Kos strain) was inoculated to the injured cornea. As the corneal diseases were observed using slit lamp biomicroscopy, impression cytology was performed for 18 days after inoculation. Specimens were stained with hematoxylin-eosin and examined using optical microscopy. RESULTS: Corneal lesions consisted mainly of round epithelial cells, inflammatory cells, ballooning cells, multinucleated giant cells, and various inclusion bodies. Over time, the comeal epithelial cells peeled away as a result of corneal edema in the comeal lesions. Dendritic lesions were also observed. In the recovery phase, the number of detached cells and infiltrated inflammatory cells decreased. CONCLUSIONS: It was presumed that dendritic lesions might have been formed at the scratched cornea region, thereby aggravating the epithelial cells falling off as a result of the infiltration of inflammatory cells. These cytopathologic effects occur in experimental herpes simplex keratitis.     

Reversible amantadine-induced corneal edema in an adolescent

PURPOSE: To document reversible corneal edema caused by amantadine in a pediatric patient. METHODS: A 14-year-old boy with a neurologic tremor was referred for bilateral visual loss. Our examination disclosed bilateral corneal edema without ocular inflammation. Pachymetry confirmed significantly increased corneal thickness above 900 microm. RESULTS: Review of the patient's medical information revealed recent institution of amantadine as a means to control the patient's tremor. On cessation of this agent, rapid resolution of corneal edema and recovery of visual acuity occurred. Repeat pachymetry measurement revealed normal corneal thickness. CONCLUSION: In cases of corneal edema and in the absence of any identifiable ocular causes, a review of toxic effects of systemic medication should be undertaken. Amantadine can cause corneal decompensation and needs to be considered as part of the differential diagnosis of corneal edema.