Deborah Pavan-Langston

• MD, FACS
• Professor (Full) at Massachusetts Eye and Ear Infirmary/Harvard Medical School

Purpose The purpose of this study was to assess potential corneal reinnervation and recovery of corneal sensation in patients with severe neurotrophic keratopathy (NK) secondary to herpes zoster ophthalmicus (HZO) after treatment with topical autologous serum tears (AST). Method Four cases of HZO with severe NK were followed clinically and by seri...

Purpose: To assess the effect of corneal scarring location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. Methods:...

Viral infections of the external eye range from benign to malignant, from a transient keratitis of mononucleosis to the progressive sarcoma associated with AIDS. Transient acute follicular conjunctivitis, with or without keratitis, may be seen with any of the DNA or RNA agents. The former include the herpes viruses, adenoviruses, poxviruses, and pa...

Aims To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM). Methods Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 per...

Herpes simplex virus (HSV) can present as a variety of ocular diseases. Keratitis, including epithelial and stromal, is a leading cause of infectious corneal blindness, particularly in developed countries. Most humans are infected with HSV-1 in early childhood and maintain latent infection throughout their lifetime. While majority remain asymptomat...

Purpose: To evaluate the long-term alterations in corneal nerves in patients with herpes simplex virus (HSV) keratitis using in vivo confocal microscopy (IVCM). Design: Prospective longitudinal, cross sectional. Methods: This study included 16 patients with history of HSV keratitis and 15 age-matched normal controls. Slit-scanning IVCM was per...

Purpose: To analyze bilateral corneal immune cell and nerve alterations in patients with unilateral herpes zoster ophthalmicus (HZO) by laser in vivo confocal microscopy (IVCM) and their correlation with corneal sensation and clinical findings. Materials and methods: This is a prospective, cross-sectional, controlled single-center study. Twenty-...

Herpes zoster ophthalmicus (HZO) is the reactivation of latent varicella zoster virus (VZV) in the first and/or second division of the trigeminal nerve. The dermatome served by the trigeminal nerve is a common site for reactivation, second only to the thoracic dermatomes, with approximately 250,000 cases of HZO annually in the United States [1, 2]....

Purpose: To investigate the morphological changes of the corneal epithelium and sub-basal nerves in patients with corneal allodynia using in vivo confocal microscopy (IVCM). Design: Case-control study of patients with corneal allodynia and healthy controls. Methods: Ten eyes of six patients were diagnosed with corneal allodynia at a single cen...

Purpose: To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). Methods: Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluoresc...

Purpose: To analyze the contralateral unaffected eyes of patients with microbial keratitis (MK) for any immune cell or nerve changes by laser in vivo confocal microscopy (IVCM). Methods: A prospective study was performed on 28 patients with MK, including acute bacterial, fungal, and Acanthamoeba keratitis, as well as on their contralateral clini...

To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in vivo confocal microscopy (IVCM). Prospective, longitudinal, case-control, single-center study. Fifty-six eyes of 56 patients with the diagnosis of bacterial (n...

To report bilateral corneal endothelial cell density (ECD), as well as its correlation with subbasal nerve changes, in patients with unilateral herpes simplex keratitis (HSK). Thirty-six eyes of 36 patients with corneal scarring caused by HSK, as well as their respective contralateral clinically unaffected eyes, were prospectively studied and compa...

To analyze the density and morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes zoster ophthalmicus (HZO) as associated with corneal innervation. Prospective, controlled and masked cross-sectional study. Setting: Single center study. Patients: Thirty eyes with the diagnosis HZO and the...

There is no standard of treatment for epithelial pseudodendrites in herpes zoster ophthalmicus (HZO). The purpose of this study is to report the topical antiviral drug, 0.15% ganciclovir for treatment of these lesions. This is a retrospective, interventional case series of 4 patients who were diagnosed with HZO epithelial pseudodendrites despite be...

PURPOSE: Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease, results in loss of corneal sensation, leading to neurotrophic keratopathy. This study aimed to analyze bilateral corneal nerve changes in patients with HZO by in vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a measure of nerve function....

To describe the clinical characteristics, treatment, and outcomes of herpes simplex virus (HSV) infections of the cornea and adnexae to raise awareness and to improve management of this important eye disease in children. Retrospective case series. Fifty-three patients (57 eyes) 16 years of age or younger with HSV keratitis (HSK), HSV blepharoconjun...

To analyze the morphologic features of corneal epithelial cells and keratocytes by in vivo confocal microscopy in patients with herpes simplex keratitis (HSK) as associated with corneal innervation. Prospective, cross-sectional, controlled, single-center study. Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eye...

To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17)...

Corneal confocal microscopy is a growing technique for the study of the cornea at the cellular level, providing images comparable to ex vivo histochemical methods. In vivo confocal microscopy (IVCM) has an enormous potential, being a noninvasive procedure that images the living cornea, to study both its physiological and pathological states. Cornea...

To study and correlate corneal sensation in patients with herpes simplex keratitis (HSK) with density and morphologic features of subbasal corneal nerves by in vivo confocal microscopy (IVCM). Prospective, cross-sectional, controlled, single-center study. Thirty-one eyes with the diagnosis of acute (n = 7) or chronic (n = 24) HSK and their contrala...

To study the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization (NV). In a prospective, open-label, noncomparative study, 10 eyes from 10 patients with stable corneal NV were treated with topical bevacizumab, 1.0%, for 3 weeks and followed up for up to 24 weeks. The primary safety variables were the occurrence...

Herpes simplex keratitis (HSK) is the leading infectious cause of corneal blindness in the Western Hemisphere. The term “herpes” is derived from the Greek word herpein, which means “to creep,” and stands for the characteristic creeping of the eruptions caused by the virus. HSK is a multifaceted disease, able to induce some of the most difficult man...

Evaluation of evidence-based strategies for managing herpes zoster (HZ) and the pain of postherpetic neuralgia (PHN). Approximately 20% of the world's population suffers from herpes zoster at least once in a lifetime, with 10% to 20% having ophthalmic involvement. Treatment of the acute disease with oral antivirals may reduce the incidence and seve...

The successful use of the Boston keratoprosthesis in a severely inflamed ulcer in herpes zoster neurotrophic keratopathy. Approximately 10% to 20% of patients with herpes zoster will develop herpes zoster ophthalmicus (HZO). Antiviral medication forms the foundation of pharmacologic treatment for acute herpes zoster, but management of HZO is supple...

To evaluate the role of an artificial cornea (Boston Keratoprosthesis [KPro]) in herpetic corneal graft failures. A series of 17 herpetic eyes of 14 patients with failed transplantations, treated with implantation of a corneal graft with a KPro, was reviewed. Outcomes measured were retention of the device, visual acuity at 1 week, best visual acuit...

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' cli...

To evaluate the complications of herpes zoster ophthalmicus (HZO) in children. Prospective-observational case series. Ten healthy patients (five boys, five girls) with HZO were prospectively followed. Data regarding best-corrected visual acuity, biomicroscopy, intraocular pressure, corneal sensitivity, and funduscopy were collected. The median dura...

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HSV is a ubiquitous virus, whose involvement in chronic and repetitive infection is well known. Ocular involvement may be either through direct infection of the cornea, conjunctiva, or retina, or through HSV-induced immune reactions, which can target practically any ocular structure. HSV-related uveitis can cause a wide range of disease severity, f...

To describe the ocular complications of smallpox vaccination and to discuss potential therapeutic options. Review of pertinent medical literature and recent treatment recommendations of the Centers for Disease Control and Prevention. After immunization against smallpox, vaccinia infection of the eyelid, conjunctiva, or ocular surface can result fro...

As ophthalmologists, many of our patients suffer from the ravages, both ocular and non-ocular, of the varicella-zoster virus. This article is a comprehensive review of the pathogenetic mechanisms of this ubiquitous virus. We review the basic virology, mechanisms of varicella, zoster, latency, reactivation, and the host immune response to the virus....

THE NEW ENGLAND JOURNAL OF MEDICINEAcyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye DiseaseThe Herpetic Eye Disease Study Group. Background: Long-term treatment with antiviral agents has been shown to prevent recurrences of genital and orofacial herpes simplex virus (HSV) disease, but it is uncertain whether prophylactic treatmen...

To evaluate the efficacy of long-term oral acyclovir therapy in reducing recurrences of dendritic or geographic herpes simplex keratitis (HSK). Thirteen patients with a history of frequently recurring HSK were followed before (mean, 27 months) and during long-term systemic acyclovir, and eight were followed after the acyclovir was discontinued. Tre...

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 po...

The destructive effects of herpetic ocular involvement involve both the cytotoxic effects of the viral particles directly and a variety of immunological mechanisms that are activated even after the acute stage of infectious disease has passed. These so-called noninfectious immune reactions represent a host response to rid the body of an antigen tha...

The late-onset pseudodendrites, delayed corneal mucous plaques, of herpes zoster ophthalmicus are reported to be of mechanical or immune origin and to be worsened by antiviral therapy. To study pseudodendrites to ascertain a viral presence in the lesions and their response to antiviral therapy. Prospective clinical study. Outpatient and inpatient h...

Background: The late-onset pseudodendrites, delayed corneal mucous plaques, of herpes zoster ophthalmicus are reported to be of mechanical or immune origin and to be worsened by antiviral therapy.Objective: To study pseudodendrites to ascertain a viral presence in the lesions and their response to antiviral therapy.Design: Prospective clinical s...

To identify potential differences in time to diagnosis and final visual outcome between contact lens and noncontact lens users with Acanthamoeba keratitis. Prior studies have shown early diagnosis and therapy to be related to outcome but have not analyzed differences among patients with and without contact lenses. A retrospective analysis of 11 con...

Purpose/methods: We conducted this study to determine if the herpesviruses are possible etiologic agents in Posner-Schlossman syndrome. We aspirated aqueous humor samples from patients during acute attacks of the syndrome. Ten normal aqueous humor specimens from patients undergoing cataract surgery were used as controls. DNA was extracted and subj...

Viruses are the second most common cause of ocular infections. Necrosis and proliferation are salient features of viral pathology. Herpes simplex virus is one of the most common infectious causes of blindness in the U.S. The eye is involved in more than 50% of AIDS cases.

AD169, a well-characterized laboratory strain of human cytomegalovirus (HCMV), was used to establish an animal model of progressive HCMV chorioretinal disease by injection of 105 pfu into the rabbit vitreous. Chorioretinal, vitreous, and pulmonary disease were monitored by HCMV recovery, clinical observation, antigen localization, and histopatholog...

First, to characterize the histologic features of corneal buttons taken from two patients with chronic active herpetic stromal keratitis. Both eyes had suffered frequent and prolonged viral epithelial recurrences despite topical and systemic antiviral therapy and developed uniquely rapid deposition of chalklike stromal deposits. Second, to determin...

Ophthalmic involvement may be noted in < or = 58% of Wegener's granulomatosis cases, scleritis being one of the most frequent and potentially devastating manifestations. Cytotoxic immunosuppressive drug therapy is effective treatment for this disorder but potentially highly toxic. Recent uncontrolled and anecdotal reports have suggested a possible...

Although varicella is one of the most common infectious diseases in the United States, systemic and ocular complications are rare. We report a patient who developed disciform edema followed by microdendritic keratitis 1 and 2 months, respectively, after resolution of the acute phase of varicella. Cultures were negative, but serologic analysis found...

Several putative NF-kappa B-binding sites in the ICP0 and Vmw65 herpes simplex virus type-1 (HSV-1) genes have been identified. Oligonucleotides encoding some of these sites bind specifically to purified NF-kappa B protein and an NF-kappa B-like protein in nuclear extracts of phorbol ester- or cycloheximide-induced human embryonic lung (HEL) cells....

Herpes simplex virus (HSV) latency in sensory ganglion neurons is well documented, but the existence of extraneuronal corneal latency is less well defined. To investigate the possibility of extraneuronal latency during ocular HSV infection, corneal specimens from 18 patients with quiescent herpes simplex keratitis (HSK) were obtained at the time of...

A new 4h rapid enzyme-immunoassay for direct detection of herpes simplex virus (HSV) antigen (Du Pont Herpchek) was evaluated with 743 clinical samples collected at obstetrics and gynecology (OB/GYN), sexually transmitted diseases (STD), and ophthalmology clinics. The sensitivity and specificity of Herpchek was 98.0% and 98.4% respectively compared...

Corneal intrastromal inoculation of guinea pigs with approximately 10(4) plaque-forming units of live, adapted varicella-zoster virus (VZV) resulted in reproducible, acute, superficial corneal disease in all animals. The culture-positive VZV ocular infection progressed to involve 30% to 40% of the corneal surface in a diffuse punctate keratitis and...

HSV DNA has been previously detected by both in situ and dot blot hybridization in neuronal tissues latently infected with herpes simplex virus (HSV), but not in extraneuronal tissues. The present study, using dot blot hybridization with a cloned full-length HSV DNA probe and subtractive hybridization assays for detecting HSV RNA, reveals both the...

This study evaluated the continued presence of herpes simplex virus (HSV) nucleic acid sequences after resolution of acute herpetic stromal keratitis in the rabbit ocular model. Forty-four rabbits were inoculated bilaterally with 10(5) plaque-forming units of RE strain HSV-1 by intrastromal injection. All eyes were cultured for the presence of HSV...

Using an in vitro system we measured the corneal epithelial cytotoxicity and the antiviral activity of the antiviral agents idoxuridine (IDU), trifluridine (TFT), ethyldeoxyuridine (EDU), and (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU). Confluent rabbit corneal epithelial cell cultures were established, and the antiviral agents were added for 5, 30...

The new HERPCHEK (Dupont, No. Billerica, MA) enzyme immunosorbent assay (EIA) was used in a double-blind clinical study for rapid and specific detection of ocular herpes simplex virus (HSV) infection. This 4-hour assay can be used to demonstrate conclusively the presence of HSV antigen without culture and thereby rapidly differentiate between HSV a...

An in vitro HSV drug-suppression model has been established in rabbit corneal cell (SIRC) monolayers. Confluent SIRC monolayers were inoculated with McKrae strain HSV-1 (0.014 PFU/cell) and subsequently suppressed with acyclovir (ACV) (40 micrograms/ml) after adsorption for 1 hr at 37 degrees C. On days 0-5 postinoculation (PI), infectious HSV-1 wa...

Immunization and immunosuppression were evaluated during latent ocular herpes simplex virus, type 1 (HSV-1) infection in the rabbit, using the following parameters: (1) ability to recover virus from preocular tearfilm cultures; (2) reactivation of latent infection by direct electrical stimulation; and (3) recovery of virus from latently infected ga...

A modified, bilateral iontophoresis technique was used to evaluate herpes simplex virus (HSV) reactivation and epinephrine distribution and concentration in full-thickness corneas and in trigeminal ganglia of rabbits. Infectious virus was recovered from 58% of epinephrine-induced eyes 24-96 hours after iontophoresis. A histochemical adrenochrome ox...

This book is the third in a series of monographs on major problems in ophthalmology. The authors address recent advances in the understanding of virus-induced ocular diseases, including origins, clinical presentation, viral latency, and current concepts for the management of these debilitating diseases. The major goal of this book is to present the...

We determined the anti-inflammatory prophylactic effect of topical cyclosporine in a rabbit model of herpetic stromal keratitis. In a first study, we established that presensitization of rabbits prior to corneal intrastromal injection of herpes simplex virus produced a severe stromal keratitis beginning on day 7 after the intrastromal challenge. Tw...

The present epidemic of genital herpes has led to broad concern among both physicians and lay persons. For those who specialize in cornea and external disease, this new awareness provides a much needed opportunity to discuss ocular herpetic disease. Through ongoing medical education, great strides are being made toward early diagnosis and appropria...

Masked controlled rabbit studies were done to determine the toxic effects on corneal wound healing of the antiviral ointments 0.5% idoxuridine, 3% Ara A, and 3% acyclovir, and the antiviral drops 0.1% idoxuridine, 3% Ara AMP, and 1% trifluridine. Ara A, acyclovir, trifluridine and idoxuridine drops had no significant effects on the rate of closure...

Acyclovir and vidarabine exerted a less-than-additive effect on the replication of herpes simplex virus type 1 (HSV-l) in green monkey kidney cells. The synthesis of viral DNA was reduced much more (97%) than that of cellular DNA (45%) by combined acyclovir and vidarabine in cell culture. Furthermore, the combined drugs, given topically or systemic...

(E)-5-(2-Bromovinyl)-2′-deoxyuridine (BVDU) and 5′-amino-5-iodo-2′,5′-dideoxyuridine AIdUrd) blocked the reactivation of latent ganglionic herpes simplex virus in vitro. Furthermore, BVDU, but not AIdUrd, blocked the multiplication of reactivated latent virus and transiently suppressed emergence of reactivated virus from the sensory ganglia after r...

Acyclovir is a potent and selective antiviral agent. Unfortunately, drug-resistant (acyclovir-resistant) mutants have already been reported in herpes simplex virus type 1 (HSV-1) orofacial infections. We have developed a laboratory acyclovir-resistant HSV-1 mutant. The natural course of acyclovir-resistant HSV-1 keratitis was found to be less virul...

We reviewed 15 cases of culture-proven corneal superinfections in 15 patients (eight men and seven women ranging in age from 41 to 86 years) with recurrent herpes simplex keratitis. The factors that appeared to increase the risk of superinfection were the presence of an epithelial defect (found in all 15 cases), a history of recurrent herpetic kera...

The most important viral organisms involving the eye are the DNA viruses herpes simplex, varicella-zoster, cytomegalovirus, adenovirus, and vaccinia virus. All of these agents except CMV may cause acute epithelial infection, sterile trophic ulceration due to basement membrane damage, deep corneal stromal immune reaction, and iritis. Although there...

Systemic treatment of mice with (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) showed a significant therapeutic efficacy against herpes simplex type 1 virus (HSV-1) encephalitis. With treatment initiated 12 h after viral inoculation and continued for 10 consecutive days, BVDU administered intraperitoneally in daily doses of 100–500 mg/kg increased the...

Seventy-three patients were studied in a prospective, randomized double-controlled trial to determine the efficacy and side effects of 3 percent acyclovir or 3 percent vidarabine ointment in treating epithelial herpetic keratitis. Thirty-eight patients were treated with vidarabine and 35 patients with acyclovir. Sixty-eight patients ahd dendritic k...