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Forty four patients with virus conjunctivitis, keratitis, uveitis and retinitis were treated by acyclovir in tablets--5 times a day 400 mg.; the results were satisfactory. The drug was well tolerated and it could be used also in patients who showed hypersensitivity for acyclovir after ++intra-conjunctival application in the form of ointment.
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Trifluridine (trifluorothymidine) is an antiviral agent for topical use in the eye, and is structurally related to idoxuridine. In vitro studies have shown that it effectively inhibits the replication of herpes simplex virus type 1, which causes primary keratoconjunctivitis and recurrent epithelial keratitis in man. In masked comparative studies, predominantly in patients with dendritic ulcers, trifluridine 1% solution was effective in over 90% of patients; in such studies it was comparable with vidarabine in treating dendritic ulcers, and was at least as effective as, and in some studies more effective than, idoxuridine. The drug was also effective in treating a small number of patients with geographic ulcers (sometimes associated with the usage of topical corticosteroids), and this could be an important advantage if confirmed in further well-designed studies. However, experience at present is too limited to reliably determine the usual response rate in this difficult therapeutic area. In open studies the drug proved to be particularly useful in treating ulcers previously unresponsive to idoxuridine or vidarabine, and in treating patients intolerant of idoxuridine, with a high success rate and minimal side effects being reported. The role of trifluridine in treating deep stromal disease, uveitis, or adenovirus kerato-conjunctivitis has not been established. The drug is well tolerated and cross-hypersensitivity and cross-toxicity between trifluridine, idoxuridine and vidarabine are rare. Thus, trifluridine is an effective alternative to the drugs available for treating herpetic keratitis, and seems especially useful in 'difficult' cases.
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Acute retinal necrosis is a severe form of necrotizing retinitis. Acute retinal necrosis has been demonstrated to be caused by varicella-zoster virus and herpes simplex virus type 1. We treated three patients with acute retinal necrosis apparently caused by recrudescence of latent herpes simplex virus type 2. Primary viral infection was probably congenital, with documented perinatal herpes simplex virus type 2 infection in two patients. Bilateral chorioretinal scars were present in two patients, neither of whom had a history of ocular herpetic infection, suggesting that earlier subclinical chorioretinitis had occurred. In each case, periocular trauma preceded the development of retinitis by two to three weeks. These cases are evidently caused by trauma-induced reactivation of latent virus rather than the onset of a primary infection.
PURPOSE: To investigate the role of human papillomavirus (HPV) types, 6, 11, 16 and 18 in corneal and conjunctival carcinoma, we examined 88 dysplastic corneal and conjunctival specimens and 66 controls that had been formalin-fixed and paraffin-embedded. METHODS: Sections were graded for histological abnormality by light microscopy and the presence of HPV DNA was determined by polymerase chain reaction using LI consensus primers. RESULTS: Human papillomavirus DNA was detected in 34 (39%) dysplasias and in five (7.5%) controls. Of dysplasias that were HPV-positive, 20 (59%) contained either types 16 or 18, 13 (38%) contained only types 6/11, while combinations of HPV types were present in 11 (32%). A histological correlation was found with HPV positivity (all genotypes) and unusually large ('epithelioid') dysplastic cells. CONCLUSION: The present study demonstrates a lower incidence of HPV in corneal and conjunctival carcinoma than previously reported, but shows an unexpectedly high incidence of HPV 6/11 in conjunctival carcinomas.
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Rapid and sensitive techniques with a high degree of accuracy are necessary for the diagnosis and management of cytomegalovirus (CMV) retinitis presenting with atypical clinical manifestations. Light microscopy and immunohistochemical studies have limitations in the identification of this virus, but in situ DNA hybridization offers a rapid, highly specific, and easily interpretable means of identifying CMV. A new procedure of enzymatic amplification of DNA in vitro, called the polymerase chain reaction (PCR), has yielded excellent results in the identification of various viruses. In the study described herein, we evaluated the diagnostic usefulness of PCR and compared its reliability with that of in situ DNA hybridization for the detection of CMV in ocular tissues. We found that the reliability of the PCR method is similar to in situ DNA hybridization for the detection of CMV, although morphologic correlation is provided only by the latter technique. False-negative results can occur in PCR if the correct primer is not used.
BACKGROUND: Ganciclovir, administered systemically or intraocularly, is effective in controlling cytomegalovirus (CMV) retinitis in immunocompromised patients. The efficacy of therapy with this antiviral substance was investigated in an immunocompetent patient with CMV uveitis causing secondary glaucoma. METHODS: To identify the presence of an intraocular viral infection, anterior chamber taps to detect the intraocular synthesis of IgG antibodies and PCR testing were carried out. Clinically, the degree of intraocular inflammation and the intraocular pressure (IOP) values were monitored. During this time, the patient was treated systemically with ganciclovir administered orally and intravenously. RESULTS: The intraocular synthesis of IgG antibodies specific for CMV was found in two samples of aqueous humor, but negative for other viruses. PCR testing was negative for HSV, VZV and CMV at each time. During this time, the patient was treated systemically with ganciclovir administered either intravenously or orally. As a response to therapy with ganciclovir, the elevated IOP values decreased to normal and the intraocular inflammation declined. After cessation of ganciclovir administration, the inflammation and secondary glaucoma recurred. CONCLUSION: In this case of anterior uveitis presumably caused by CMV inducing secondary glaucoma, treatment with ganciclovir led to a decrease of the inflammation and normalization of IOP. It appears that continuous administration may be required to control the infection in an immunocompetent patient.
INTRODUCTION: Eye anomalies, including anophthalmos and microphthalmos (absent eye and small eye), are common features in congenital infection syndromes such as rubella. Influenza, Coxsackie virus, and Parvovirus are less well-established teratogens. We report an ecologic analysis of anophthalmia/microphthalmia prevalence in England in relation to temporal variation in these infections using routine infection data. METHODS: The national (England) anophthalmos/microphthalmos register holds details of 406 babies (excluding chromosomal anomalies) born 1988-1994. Weekly infection data were obtained from the U.K. Public Health Laboratory Service and Royal College of General Practitioners Weekly Returns Service. We assigned cases and births an estimated exposure based on the population infection counts in the gestational weeks known to be critical for ocular development. We calculated the rate ratio of anophthalmos/microphthalmos prevalence for infection in the 90th percentile compared with the 10th percentile by Poisson regression. RESULTS: There was a positive association between severe anophthalmos/microphthalmos prevalence and Parvovirus B19 (rate ratio = 1.26; 95% confidence interval = 1.00-1.58) and for influenza (1.41; 1.08-1.84). Coxsackie virus showed a negative association with any anophthalmos/microphthalmos (0.75; 0.58-0.98) and with severe cases (0.66; 0.46-0.95). CONCLUSIONS: This analysis provides suggestive evidence for a teratogenic role of influenza and Parvovirus in anophthalmos/microphthalmos. The role of maternal infections in congenital anomaly etiology is worthy of further investigation.
AIM: To describe the diagnostic and therapeutic management of cytomegalovirus (CMV) anterior uveitis unassociated with retinal necrosis in immunocompetent patients. METHODS: Patients referred between 2001 and 2003 for management of unilateral, chronic, recurrent uveitis associated with secondary glaucoma underwent extensive investigation including laboratory tests for herpes virus infections. Specific antiviral treatment was initiated in all cases and the level of ocular inflammation was evaluated during the follow up. RESULTS: Five patients, three men and two women, were included. Median age was 50 years old (range 30-80 years). Anterior unilateral uveitis without iris atrophy was observed in all cases. Uveitis was chronic in three cases and recurrent in two cases. Glaucoma was observed in all patients with a median intraocular pressure of 30 mm Hg (range 22-43 mm Hg). Five patients responded initially to specific anti-CMV therapy. Even though glaucoma surgery was necessary in two cases, both ocular inflammation and glaucoma were controlled in all cases. Relapses occurred in three cases after cessation of therapy, requiring prolonged maintenance therapy with valganciclovir. CONCLUSIONS: CMV infection and specific antiviral therapy should be considered in all cases of relapsing or chronic iridocyclitis and secondary glaucoma. Maintenance regimens of valganciclovir may be necessary to prevent further relapses.
Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravitreal inoculation) was examined on interphotoreceptor retinoid-binding protein (IRBP), the glycolipoprotein in the interphotoreceptor matrix (IPM) thought to transport retinoids between the photoreceptors and the RPE. Changes in IRBP distribution accompanied virus-associated retinal pathology, including photoreceptor loss and RPE abnormalities. Immunohistochemistry on days 3 and 6 showed that IRBP had diffused into the neural retina away from the IPM. The IRBP became localized abnormally in the same areas as virus-induced lesions, shown by staining adjacent sections with a monoclonal antibody specific for the viral nucleocapsid protein. Moreover, the level of IRBP in isolated retinas, measured in an immunoslot-blot assay, decreased significantly by day 3 and remained low through day 23. This decrease was confirmed in eyecups isolated on day 6. It may be caused in part by loss of photoreceptors and diffusion of IRBP through the retina into the vitreous. These studies show that a virus may induce an acute, limited infection in the retina that can be cleared by the host. However, the infection initiated a series of events resulting in long-term reduction and redistribution of a critical photoreceptor protein.
This study determined the frequency of multiple viral (HIV-1, HHV-6, and CMV) infections in 26 retinas from 16 AIDS patients. Of the 12 retinas of 26 that tested positive for HIV-1 DNA sequences, seven also were positive for HHV-6 DNA sequences. Four of these seven retinas were culture positive for HIV-1 and two of the four contained CMV DNA sequences and antigens. Using RNA probes, HIV-1 and HHV-6 transcriptional activity was demonstrated in two of the four HIV-1 culture positive retinas. These retinas also contained CMV DNA sequences and antigens. The results demonstrate that more than 35% of AIDS patients suffer from at least two simultaneous viral infections and 15% suffer from three viral infections. The presence of transcriptional activity of HIV-1 and HHV-6 suggests an active infection.
External ocular disease associated with human immunodeficiency virus (HIV) infection can often be overlooked by the eye care practitioner. Different types of external ocular disease can be an indication of the patient's overall immune status as well as the stage of HIV infection. The external ocular sequelae of HIV infection can be of visual consequence for the patient. Eye care practitioners need to become familiar with these conditions. The diagnosis and management of the following ocular conditions associated with HIV infection are reviewed: conjunctival microvascular disease, dry eye, allergic conjunctivitis, microsporidial keratoconjunctivitis, herpes zoster ophthalmicus, herpes simplex keratitis, molluscum contagiosum, fungal keratitis, bacterial keratoconjunctivitis, and Kaposi's sarcoma (KS).
Twenty nine strains of adenovirus 8 have been isolated over nine years in Strasbourg, France, 22 of which were from one private ophthalmologist. To assess a possible relation between these strains, the DNA of adenovirus was analysed by restriction fragment length polymorphism using eight different enzymes. Among these, three proved discriminant (Xba I, Bgl II, Eco RI) and made it possible to define 13 genotypes differing from each other by one to three DNA bands. Seven genotypes were unique isolates, while three, representing 16 strains, were isolated over five to eight years. All the genotypes but one were closely related, with 87% homology. All 13 differed from an adenovirus 8 strain from Lyon (homology 68-76%). This study confirmed the stability of adenovirus 8 in a given population.
In AIDS the onset of the ocular dry syndrome, characterized by lacrimal hyposecretion and deterioration of the corneal and conjunctival epithelium, generally accompanies the clinical aggravation of immunodepression. The study of serum and lacrimal proteins contributes to our knowledge of the pathophysiology of this syndrome. The lacrimal clearance of albumin indicates changes in the permeability of the haemato-lacrimal and conjunctival barrier. Lacrimal monomeric IgA and IgG are mainly of plasmatic origin, while polymeric IgA and IgM are synthesized in situ. The concentrations of these analytes thus reflect ocular humoral immune status. They show a strong humoral protein response in patients with cytomegalovirus retinitis. Lacrimal concentrations of lactoferrin and lysozyme were found to be significantly decreased in AIDS patients with ocular dryness, reflecting a decrease in the secretory activity of the lacrimal gland. Moreover, ocular lympho-plasmocyte infiltration was observed in several patients, with an increase in lacrimal beta 2-microglobulin concentrations. These various lacrimal proteins could be good markers of the ocular dry syndrome in AIDS.
BACKGROUND: The tumor suppressor gene p53 is expressed without apoptosis in the limbal basal stem cells of all pterygia and limbal tumors and most pingueculae from which these growths seem to originate. Oncogenic human papillomaviruses (HPVs) have been found in pterygia and limbal tumors, and HPV and p53 overexpression commonly coexist in oropharyngeal and penile carcinomas. OBJECTIVE: To search for HPV DNA as a cofactor in the development of pingueculae, pterygia, and limbal tumors. METHODS: We examined specimens--1 of pinguecula, 13 of pterygia (7 primary, 1 recurrent, 1 with dysplasia, and 4 primary not tested for p53), and 10 of limbal tumors (2 with actinic keratosis dysplasia, 1 with conjunctival intraepithelial neoplasia, 3 with carcinoma in situ, and 4 with squamous cell carcinoma)-expressing p53. Specimens were tested for the presence of HPV DNA by the polymerase chain reaction using degenerate consensus primers for the highly conserved portion of the L1 region that encodes a capsid protein of the virus. This assay has a wide spectrum with capability of detecting essentially all known HPV types. Nested polymerase chain reaction was performed on all specimens. Primers of the cystic fibrosis gene were used to confirm the presence of genomic DNA and to rule out inhibitors. Purified HPV DNA type 11 was the positive control, and HPV-negative genomic DNA was the negative control. RESULTS: Using consensus primers for the highly conserved portion of the L1 region, all specimens of pingueculae, pterygia, and limbal tumors studied were negative for HPV DNA by nested polymerase chain reaction. CONCLUSIONS: Human papillomavirus DNA is not required as a cofactor in the development of pterygia and limbal tumors. These data support the theory that increased p53 expression in the limbal epithelia of pingueculae, pterygia, and limbal tumors indicates the probable existence of p53 mutations in these cells as an early event in their development, which is consistent with UV irradiation causation. Thus, due to a damaged p53-dependent programmed cell death mechanism, mutations in other genes may be progressively acquired. This would allow for the multistep development of pterygia and limbal tumor cells from p53-mutated limbal epithelial basal stem cells overlying pingueculae.