Rubella virus is associated with fuchs heterochromic iridocyclitis

PURPOSE: To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). DESIGN: Retrospective patient-controlled study. METHODS: Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC). RESULTS: All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test). CONCLUSION: Rubella virus, but not HSV, VZV, or T gondii, is associated with FHI.     

Polymerase chain reaction for diagnosis of herpetic intraocular inflammation

The authors present a polymerase chain reaction method for rapid and direct diagnosis of herpetic intraocular infections using small volume samples of intraocular fluid from 29 patients with various intraocular inflammatory diseases and 24 controls with senile cataract. Of six patients with early acute retinal necrosis from whom aqueous humor was tested, four were found to be positive for the presence of varicella-zoster (VZV) DNA while the other two were positive for the presence of herpes simplex virus (HSV) DNA. One of the patients with HSV DNA had been tested at an extremely early stage, at which time the aqueous humor viral antibody ratio did not predict a specific viral infection. Among four patients with acute retinal necrosis in relatively late stages following treatment with acyclovir from whom vitreous was obtained and tested, only one was found to have the presence of any viral DNA (VZV). On the other hand, the vitreous viral antibody ratio was found to be predictive of VZV infection in all four cases. VZV DNA was also detected in aqueous humor samples from four patients with suspected herpes zoster anterior uveitis, while HSV DNA was found in the aqueous humor of one patient with nonspecific keratouveitis. Neither human cytomegalovirus DNA nor human herpesvirus-6 DNA was detected in any sample included in this study. Finally, Epstein-Barr virus DNA was detected in the aqueous humor of the majority of patients studied and identified in cataract patients as well, suggesting either low specificity of the authors' assay for this virus or ubiquity of this virus in human eyes. In summary, the PCR method proved to be a very useful tool in establishing an etiological diagnosis in patients in the early stages of acute retinal necrosis, and in patients with anterior uveitis due to suspected HSV or VZV infection.     

Polymerase chain reaction for diagnosis of herpetic intraocular inflammation

The authors present a polymerase chain reaction method for rapid and direct diagnosis of herpetic intraocular infections using small volume samples of intraocular fluid from 29 patients with various intraocular inflammatory diseases and 24 controls with senile cataract. Of six patients with early acute retinal necrosis from whom aqueous humor was tested, four were found to be positive for the presence of varicella-zoster (VZV) DNA while the other two were positive for the presence of herpes simplex virus (HSV) DNA. One of the patients with HSV DNA had been tested at an extremely early stage, at which time the aqueous humor viral antibody ratio did not predict a specific viral infection. Among four patients with acute retinal necrosis in relatively late stages following treatment with acyclovir from whom vitreous was obtained and tested, only one was found to have the presence of any viral DNA (VZV). On the other hand, the vitreous viral antibody ratio was found to be predictive of VZV infection in all four cases. VZV DNA was also detected in aqueous humor samples from four patients with suspected herpes zoster anterior uveitis, while HSV DNA was found in the aqueous humor of one patient with nonspecific keratouveitis. Neither human cytomegalovirus DNA nor human herpesvirus-6 DNA was detected in any sample included in this study. Finally, Epstein-Barr virus DNA was detected in the aqueous humor of the majority of patients studied and identified in cataract patients as well, suggesting either low specificity of the authors' assay for this virus or ubiquity of this virus in human eyes. In summary, the PCR method proved to be a very useful tool in establishing an etiological diagnosis in patients in the early stages of acute retinal necrosis, and in patients with anterior uveitis due to suspected HSV or VZV infection.     

Fuchs heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor

PURPOSE: To characterize the polyspecific intraocular antibody synthesis in aqueous humor of patients with chronic inflammatory diseases of the eye and to detect the causative antigen in Fuchs heterochromic cyclitis (FHC). DESIGN: Retrospective case-control study. METHODS: Intraocular antibody synthesis is detected in aqueous humor with the Antibody Index [AI] (improved Goldmann-Witmer Index) and quantified as specific antibody fraction, F(s) (intraocular specific antibody concentration in percent of intraocular total immunoglobulin G in aqueous humor). Virus detection is by nested polymerase chain reaction. RESULTS: Fifty-two eyes of 52 patients with clinically defined FHC (aged 16-73 years) had an intraocular synthesis of rubella antibodies (AI > or =1.5). The rubella genome was detected in 5 (18%) of 28 aqueous humor samples investigated, or in 5 (56%) of 9 patients aged <40 years. Oligoclonal IgG was synthesized in 34 (87%) of 39 eyes. Unaffected fellow eyes (n = 3) or cerebrospinal fluid (n = 2) were normal. In FHC the median rubella AI = 20.6 (total range 1.5-309) was seven times higher than in multiple sclerosis (MS) patients (n = 15) with uveitis intermedia or periphlebitis retinae. In MS the intraocular rubella antibody synthesis (frequency 73%) is part of a polyspecific immune response (increased measles AI in 80%, varicella zoster virus AI in 47%, herpes simplex virus AI in 23%). The median rubella-F(s) = 2.6% in FHC (range = 0.14%-45.9%) was approximately 40 times higher than in MS, consistent with a virus-driven antibody response in FHC. Noninflammatory controls (50 senile cataracts) had neither an intraocular rubella antibody synthesis (normal AI < or =1.4) nor rubella antigen in aqueous humor. The rubella AI was normal in all patients with an intraocular toxoplasmosis (n = 24), anterior uveitis (n = 27), herpes simplex virus iritis (n = 25), and varicella zoster virus iritis (n = 14). CONCLUSIONS: Fuchs heterochromic cyclitis is a rubella virus-driven disease with persistence of the virus preferentially detected in the younger patients. The proposed laboratory supported diagnosis of FHC is based on the increased rubella Antibody Index. The virus etiology gives a rationale for omitting the ineffective corticosteroid therapy of FHC.     

A comparative study of the polymerase chain reaction and local antibody production in acute retinal necrosis syndrome and cytomegalovirus retinitis

• Background: It has been thought that herpes viruses may play an important role in acute retinal necrosis syndrome (herpes simplex and varicella-zoster viruses) as well as in cytomegalovirus retinitis and it would be useful to know the specificity of the methods for detecting the viruses. • Methods: Amplification of the herpetic viral genome DNA by polymerase chain reaction (PCR) in aqueous and vitreous humor was compared with Goldmann-Witmer coefficients against herpetic antigens in five patients with acute retinal necrosis syndrome and in two patients with cytomegalovirus retinitis, using vitreous samples to determine the specificity of these diagnostic methods. • Results: The varicella-zoster virus genome DNA was amplified by PCR in four of the five patients with acute retinal necrosis syndrome, and cytomegalovirus genome DNA was enhanced in both patients with cytomegalovirus retinitis. Four patients who exhibited the varicella-zoster viral genome showed marked increase of the Goldmann-Witmer coefficient against varicella-zoster virus. Conversely, the two patients with cytomegalovirus retinitis showed no remarkable changes among the antigens. • Conclusion: Our results showed that the amplification of the viral genome DNA in the samples by PCR is specific in both diseases, and that the increased level of local antibody production also is specific in varicella-zoster retinitis. In cytomegalovirus retinitis, however, antibody production against cytomegalovirus does not show increase of the Goldmann-Witmer coefficient.     

Corneal endotheliitis and idiopathic sudden sensorineural hearing loss

PURPOSE: To report a case with corneal endotheliitis and idiopathic sudden sensorineural hearing loss, in which herpes simplex virus type 1 DNA was demonstrated in the trabeculum and the aqueous humor by polymerase chain reaction. DESIGN: Interventional case report. METHODS: A 60-year-old man presented with corneal stromal edema in the right eye and sudden bilateral sensorineural hearing loss. The trabeculum excised during trabeculectomy and the aqueous humor were examined for the presence of herpes simplex virus type 1 DNA by polymerase chain reaction. RESULTS: Polymerase chain reaction demonstrated herpes simplex virus type 1 DNA in the aqueous humor and the trabeculum. CONCLUSION: Herpes simplex virus type 1 may cause corneal endotheliitis and idiopathic sudden sensorineural hearing loss simultaneously.     

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.     

Polymerase chain reaction for the detection of the varicella-zoster genome in ocular samples from patients with acute retinal necrosis.

We used the polymerase chain reaction to detect the virus genome in ocular samples from patients with clinically diagnosed acute retinal necrosis. Four samples from four patients with acute retinal necrosis, and five samples from three patients with other ocular diseases (sarcoidosis, rhegmatogenous retinal detachment, and epiretinal membrane of unknown origin) were evaluated. The samples consisted of aqueous humor, vitreous, or subretinal fluid. Primers were specific for varicella-zoster virus, herpes simplex virus, or cytomegalovirus. The varicella-zoster virus genome was detected in three of the four samples from patients with acute retinal necrosis. Among these three positive samples, two had PstI-site-less point mutation, strains that have been described only in Japan and of low prevalence. Samples from patients with diagnoses other than acute retinal necrosis yielded negative results when varicella-zoster virus primer was used. No sample was positive for herpes simplex virus or cytomegalovirus primers.     

The detection of herpesviral DNA in aqueous fluid samples from patients with Fuchs' heterochromic cyclitis

Members of the herpesvirus family have been found in association with a variety of intraocular inflammatory conditions. The aetiology and pathogenic mechanisms underlying the specific uveitis entity Fuchs' heterochromic cyclitis (FHC) have yet to be determined. This study investigates the presence of specific herpesviral DNA in samples of aqueous fluid from patients with FHC. Aqueous humour was obtained from 40 patients undergoing cataract surgery, 20 patients with a clinical diagnosis of FHC and 20 patients with senile cataract who acted as controls. Each sample was tested for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA after initial amplification with virus specific primers using the polymerase chain reaction (PCR). Herpesviral DNA could not be detected in any of the aqueous samples from the FHC patients. Although a viral aetiology is unlikely, this study cannot exclude the possibility that a virus may be the initiating factor in the development of FHC or that virus may be sequestered in different ocular tissues. Control patients also showed no significant carriage of herpesvirus in their aqueous humour implying that detection of any herpesviral DNA in aqueous samples may be clinically relevant.     

Detecting herpesvirus DNA in uveitis using the polymerase chain reaction.

BACKGROUND: Herpesviruses are involved in the pathogenesis of many ocular diseases including keratitis, iridocyclitis, and acute retinal necrosis syndrome. The rapid and accurate diagnosis of herpetic infections has become increasingly important with the rising incidence of immunosuppressive diseases. The purpose of this study was to evaluate the use of the polymerase chain reaction (PCR) to detect herpesvirus DNA in uveitis patients. METHODS: Aqueous samples were aspirated from 11 patients with active uveitis of suspected viral origin. Using PCR, masked samples were assayed for herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) to assist in supporting the clinical diagnosis of viral aetiology. Masked controls included 10 aqueous humour specimens from normal patients undergoing cataract surgery and specimens from seven patients diagnosed with active non-viral uveitis--Behçet's disease, sarcoidosis, Fuchs' heterochromic iridocyclitis, or Harada's disease. RESULTS: Ten of 11 cases clinically diagnosed as being of possible viral aetiology yielded aqueous PCR positive for a herpesvirus. Eight patients were PCR positive for amplified HSV DNA, of whom two had acute retinal necrosis, one had corneal endotheliitis, and five had recurrent iridocyclitis. VZV DNA was detected in one case of iridocyclitis, and CMV DNA in one case of chorioretinitis. Successful therapy was based on the PCR results. Ten normal aqueous specimens and the seven uveitis samples from cases not suspected of a viral aetiology were PCR negative for HSV, VZV, and CMV. CONCLUSION: These results demonstrate that detecting herpesvirus DNA in the aqueous humour is useful to support a clinical diagnosis of viral uveitis.     

A case of hypertensive keratouveitis with endotheliitis associated with cytomegalovirus

AIM: While cytomegalovirus is well known as a pathogenic organism of retinitis, especially associated with human immunodeficiency virus infection, there are few reports of anterior uveitis associated with cytomegalovirus. METHODS: The authors present a case of keratouveitis associated with cytomegalovirus. RESULTS: A 70-year-old Japanese man was referred to the authors because of poorly controlled hypertensive keratouveitis in the left eye. The patient had a history of recurrent hypertensive anterior uveitis. At presentation, the corneal stroma was edematous, with Descemet's folds and pigmented keratic precipitates. The anterior chamber angle was depigmented compared to the fellow eye. Even though pupil dilation and posterior synechiae were absent, iris atrophy was not evident. His right eye appeared normal except for moderate cataract. Funduscopy of the left eye was hazy, with the optic disc showing a normal color but poorly defined details, and no apparent exdative retinitis. The best-corrected decimal visual acuity of the right and left eyes was 0.4 and 0.02, respectively. Intraocular pressure was 11 mmHg in the right eye and 35 mmHg in the left, despite maximum medical therapy. Systemic acyclovir and prednisolone for a month did not improve the hypertensive keratouveitis. The aqueous humor was investigated for herpes simplex virus, varicella-zoster virus and cytomegalovirus. Cytomegalovius genome was detected by polymerase chain reaction analysis. Oral valganciclovir rapidly reduced ocular hypertension within a week. CMV DNA disappeared 3 months after the initiation of valganciclovir. CONCLUSION: The authors reported a case of hypertensive keratouveitis with endotheliitis associated with cytomegalovirus.     

Rubella Virus-associated Anterior Uveitis in a Vaccinated Patient: A Case Report

Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and almost all cases in Europe show an active antibody production in the aqueous humor against rubella virus. Herein we report a case of a fully vaccinated patient with common variable immunodeficiency who developed unilateral Fuchs heterochromic uveitis secondary to rubella virus which was proven by intraocular fluid examination. Awareness of rubella associated anterior uveitis should remain also in vaccinated patients, especially those without a fully competent immune system.     

Kinetics of aqueous flare,intraocular pressure and virus-DNA copies in a patient with cytomegalovirus iridocyclitis without retinitis

Background A case report of recurrent unilateral granulomatous iridocyclitis with ocular hypertension without retinitis caused by cytomegalovirus (CMV) in an immunocompetent patient. Methods Aqueous humor was analysed by multiplex PCR to detect viral DNA, and real-time PCR was used to evaluate virus copies before and after anti-virus treatments. Inflammation of the anterior chamber was evaluated by a laser flare photometry. Results Genomic DNA of CMV – but not of other herpes viruses – was detected in the aqueous humor. Quantitative real-time PCR revealed 2.3 × 10⁵ copies/ml of CMV DNA from the specimen. Oral valganciclovir was added to the ongoing treatment, which consisted of topical corticosteroid, timolol and latanoprost as well as systemic acetazolamide, resulting in the reduction of aqueous flare correlated with the reduction of virus copies in aqueous humor. Conclusions In this case of CMV-related iridocyclitis in an immunocompetent patient, specific additional anti-viral therapy was effective in controlling inflammation of anterior chamber but, as is so often the case, it was unable to control intraocular pressure. We show that inflammatory activity correlated well with the number of virus copies in the aqueous humor.     

Chikungunya virus iridocyclitis in Fuchs' heterochromic iridocyclitis

We are reporting a case of bilateral Fuchs' heterochromic iridocyclitis with chikungunya virus infection in the left eye. A 20-year-old female was presented with a past history of fever suggestive of chikungunya with bilateral Fuchs' heterochromic iridocyclitis and complicated cataract. She had a tripod dendritic pattern of keratic precipitates by confocal microscopy in the left eye with a stippled pattern of keratic precipitates in both eyes. The real-time polymerase chain reaction (RT-PCR) assay in the aqueous humor detected 98 copies/ml of chikungunya virus RNA. The patient underwent clear corneal phacoemulsification with in-the-bag intraocular lens implantation in the left eye with a good visual outcome. This is the first report where the presence of chikungunya virus RNA has been associated with a case of bilateral Fuchs' heterochromic iridocyclitis.     

Acute retinal necrosis following contralateral herpes zoster ophthalmicus

BACKGROUND: A case report of contralateral acute retinal necrosis (ARN) following herpes zoster ophthalmicus. CASE: A 61-year-old male patient developed iridocyclitis and well-demarcated creamy-white retinal lesions at the nasal periphery in the right eye 1 month after herpes zoster ophthalmicus in the left eye. The patient had undergone surgery for primary lung cancer, and had subsequent intracranial metastasis of the tumor. OBSERVATIONS: The clinical diagnosis of ARN was supported by polymerase chain reaction investigation of the aqueous humor resulting in positive for varicella-zoster virus. Retinal lesions disappeared after systemic treatment with acyclovir, corticosteroids, and acetylsalicylate. No retinal detachment developed. CONCLUSIONS: We propose a careful ophthalmic follow-up for herpes zoster ophthalmicus patients because of the possibility of acute retinal necrosis developing in the contralateral eye.     

Varicella-zoster viral antigen identified in iridocyclitis patient

BACKGROUND: The varicella-zoster virus (VZV) antigen has not been identified immunohistologically in iridocyclitis due to VZV. CASE: A 65-year-old woman diagnosed with iridocyclitis and secondary glaucoma underwent trabeculectomy. Samples of aqueous humor and juxtacanalicular and iris tissue were obtained for immunohistological and polymerase chain reaction (PCR) study. OBSERVATIONS: Slit-lamp microscopy revealed ciliary injection, corneal epithelial edema, mutton fat precipitates, flare, cells, and progressive iris atrophy in the right eye. Subsequently, scant eruptions on her right upper eyelid appeared and disappeared within a week. Although a diagnostic increase in the complement fixation antibody titer to VZV was not observed, we started medical treatment for VZV, on suspicion of iridocyclitis due to VZV. Despite medical treatment, the ratio of peripheral anterior synechia was greater than 60% and iris atrophy progressed in parallel. The intraocular pressure in the right eye remained above 30 mm Hg at 6 months after the first visit, so trabeculectomy was performed. VZV-specific DNA was detected in the aqueous humor by the PCR study. Immunohistological examination demonstrated numerous VZV antigen-positive cells in the iris stroma, in particular, vascular endothelial cells. CONCLUSION: To our knowledge, this is the first report of the detection of VZV antigen in the iris of an iridocyclitis patient.     

New approaches to the detection of locally produced antiviral antibodies in the aqueous of patients with endogenous uveitis

A local synthesis of IgG antibodies against herpes simplex virus, cytomegalovirus, varicella-zoster virus and Chlamydia trachomatis was assayed for in aqueous humor and sera from 226 patients with various clinical types of uveitis. Comparison of the ratios of specific antibodies tested for in aqueous humor and serum (C') and the evaluation of the Goldmann-Witmer coefficient (C) to each specific antibody were simultaneously studied in each case. The combination of these two methods allowed for the diagnosis of viral uveitis in 37.7% of selected uveitis patients and in 13.27% of randomized uveitis patients.     

Zoster sine herpete with bilateral ocular involvement

PURPOSE: To report a case of zoster sine herpete with bilateral ocular involvement. METHOD: Case report. RESULTS: A 65-year-old man showed bilateral iridocyclitis with sectoral iris atrophy and elevated intraocular pressure unresponsive to steroid treatment. No cutaneous eruption was manifest on the forehead. A target region of varicella-zoster virus DNA sequence was amplified from the aqueous sample from the left eye by polymerase chain reaction. Bilateral iridocyclitis resolved promptly after initiation of systemic and topical acyclovir treatment. Secondary glaucoma was well controlled by bilateral trabeculectomy. CONCLUSIONS: Zoster sine herpete should be considered and polymerase chain reaction performed on an aqueous sample to detect varicella-zoster virus DNA for rapid diagnosis whenever anterior uveitis accompanies the characteristic iris atrophy, even in the case of bilateral involvement.     

Demystifying viral anterior uveitis: A review

A viral aetiology should be suspected when anterior uveitis is accompanied by ocular hypertension, diffuse stellate keratic precipitates or the presence of iris atrophy. The most common viruses associated with anterior uveitis include herpes simplex virus, varicella‐zoster virus, cytomegalovirus and rubella virus. They may present as the following: Firstly, granulomatous cluster of small and medium‐sized keratic precipitates in Arlt's triangle, with or without corneal scars, suggestive of herpes simplex or varicella‐zoster virus infection. Secondly, Posner‐Schlossman syndrome with few medium‐sized keratic precipitates, minimal anterior chamber cells and extremely high intraocular pressure; this is mainly associated with cytomegalovirus. Thirdly, Fuchs uveitis syndrome, with fine stellate keratic precipitates diffusely distributed over the corneal endothelium, with diffuse iris stromal atrophy but without posterior synechiae, is associated mainly with rubella or cytomegalovirus infection. In rubella, the onset is in the second to third decade. It presents with posterior subcapsular cataract, may have iris heterochromia and often develops vitritis without macular oedema. Cytomegalovirus affects predominantly Asian males in the fifth to seventh decade, the keratic precipitates may be pigmented or appear in coin‐like pattern or develop nodular endothelial lesions, but rarely vitritis. Eyes with cytomegalovirus tend to have lower endothelial cell counts than the fellow eye. As their ocular manifestations are variable and may overlap considerably, viral AU can pose a diagnostic dilemma. Thus, quantitative polymerase chain reaction or Goldmann‐Witmer coefficient assay from aqueous humour samples are preferred to confirm the aetiology and determine the disease severity as this impacts the treatment.     

American Uveitis Society Meeting 4 May 2002

Purpose: To describe the development of Fuchs’ heterochromic iridocyclitis (FHI) following bilateral ocular toxoplasmosis in an Asian Indian female. Methods: Case report of a patient with bilateral ocular toxoplasmosis who developed bilateral Fuchs’ heterochromic iridocyclitis. Results: Features characteristic of bilateral Fuchs’ heterochromic iridocyclitis developed following several attacks of bilateral toxoplasmic retinochoroiditis in a 26-year-old Indian female patient. Conclusion: Fuchs’ heterochromic iridocyclitis can develop over a period of time in patients with ocular toxoplasmosis.