Search PubMed⌕ Search

Biomedical subjects

J S Pepose

Publications and source records attributed to J S Pepose.

At least 37 records · Page 2Linked to original sources

Neural network computer program to determine photorefractive keratectomy nomograms.

PURPOSE: To evaluate a commercially available neural network program for calculation of photorefractive keratectomy treatment nomograms. SETTING: University referral refractive surgery clinic. METHODS: PRK/LASIK Brain, a commercial neural network computer program, was trained using the demographics, preoperative clinical data, surgical parameters, and 1 year postoperative clinical data of 44 patients treated with a Summit Technology excimer laser using a 5.0 mm optical zone. The neural-network derived nomogram was compared with the standard treatment nomogram for each patient. The relative contribution of age, sex, keratometry, and intraocular pressure (IOP) to the predicted nomograms was also assessed. RESULTS: Nomograms produced by the neural network were qualitatively similar to the standard nomogram. The sequence of data entry during training affected the network's predictions. Entry ordered by outcome (as opposed to entry by chronological order) yielded a nomogram that was more consistent with the standard nomogram. However, both outcome- and chronologically ordered network-derived nomograms diverged from the standard nomogram in individual patients, including a subset for whom use of the standard nomogram yielded desired refractive results (within 0.25 diopter of emmetropia). Further analysis of the neural-network-derived nomograms revealed marked sensitivity to sex, age, keratometry readings, and IOP. CONCLUSIONS: Neural networks offer a potential means of individualizing treatment nomograms, to account for patient demographics, preoperative examination, surgeon style, and equipment bias. However, a data set of 44 patients was not sufficient to train the PRK/LASIK Brain network to accurately predict treatment parameters in individual cases in the training set. A larger training set or a different learning algorithm may be required to improve the neural network's performance.

Adult↗

Lack of diurnal variation in vision, refraction, or keratometry after excimer laser photorefractive keratectomy.

PURPOSE: To examine whether diurnal variation in visual acuity, spherical equivalent, keratometry, or intraocular pressure occurs in patients who have undergone photorefractive keratectomy. METHODS: Twenty-nine post-photorefractive keratectomy patients underwent morning and evening measurements of visual acuity, spherical equivalent, keratometry, and intraocular pressure at intervals between 5 and 13 months after photorefractive keratectomy. RESULTS: There was no statistically significant post-photorefractive keratectomy diurnal variation in visual acuity, spherical equivalent, or keratometry in the group studied. Diurnal variation in post-photorefractive keratectomy intraocular pressure was not significantly different between patients' treated and untreated eyes. CONCLUSION: Photorefractive keratectomy does not appear to result in diurnal variation in visual acuity, spherical equivalent, or keratometry post-operatively, nor does it seem to effect normal diurnal variation in intraocular pressure.

Adult↗

An in vivo model of human cytomegalovirus retinal infection.

PURPOSE: To develop an animal model system in which human retina implanted in the anterior chamber of the eyes of rats would support human cytomegalovirus replication. Cytomegalovirus retinitis currently represents the most common cause of posterior uveitis in many urban areas in North America. Despite the tremendous interest in cytomegalovirus retinitis as a result of the acquired immunodeficiency syndrome (AIDS) epidemic, human cytomegalovirus infection has been difficult to model in vivo because of its extreme species-specificity. METHODS: Human retina was introduced into the anterior chamber of athymic rats and allowed to attach to the rat iris. A human cytomegalovirus mutant carrying a beta-galactosidase indicator gene was then injected into the anterior chamber to infect the implanted tissue. After 4 weeks, the eyes were removed, sectioned, and developed with a chromogenic substrate to demonstrate the presence and location of beta-galactosidase expression. RESULTS: Multiple spreading foci of beta-galactosidase expression were found in the retinal implants, indicating that human cytomegalovirus replication had occurred within the human tissue. There was no infection of rat tissue. CONCLUSIONS: This model allows human cytomegalovirus infection of human retina to be established in vivo and sustained long enough to permit multiple cycles of viral replication to occur. The model thus has potential for evaluating antiviral therapies directed against human cytomegalovirus retinal disease.

Animals↗

Retreatment of decentered excimer photorefractive keratectomy ablations.

PURPOSE: To present two cases of excimer photorefractive keratectomy decentration associated with visual distortion secondary to irregular astigmatism. METHOD: Patients were retreated with a repeat photorefractive keratectomy using a technique whereby the circle of adherent epithelium overlying the decentered ablation served as a mask. RESULTS: After retreatment, there was significant improvement in the patients' visual symptoms, decreased astigmatism on refraction, and better centration on corneal topography. CONCLUSION: This method appears to offer an effective means to treat photorefractive keratectomy ablation zone decentration by improving the abnormalities introduced by the initial decentration.

Adult↗

Differential effects of HSV-1 and HCMV infection on adhesion molecule expression on human corneal keratocytes.

PURPOSE: Previous studies have shown that keratoplasty buttons obtained at surgery from patients with herpes simplex virus-1 (HSV-1) keratitis have elevated localized expression of the adhesion molecule ICAM-1, which plays a critical role in the initiation and amplification of an immune response. We performed studies to determine whether changes in expression of ICAM-1 and HLA class I are direct effects of productive infection of human corneal fibroblasts with HSV-1. METHODS: Immunocytologic and flow cytometric analyses were performed to analyze the ability of HSV-1 to induce ICAM-1 and HLA class I expression in a primary cornea-derived keratocyte cell line, E-2. Positive controls for these experiments were E-2 cells infected with human cytomegalovirus (HCMV), which has been shown to increase ICAM-1 expression in selected cells, and E-2 cells treated with IFN-gamma, which upregulates both ICAM-1 and HLA class I expression in most cell types. RESULTS: Kinetic cytometric analysis indicated decreased ICAM-1 expression 3 hours following HSV-1 infection of E-2 cells. In contrast, HCMV led to detectable increases in ICAM-1 expression starting 6 hours after infection. Infections with either HSV-1 or HCMV resulted in reduced HLA class I expression on E-2 and SF cells. CONCLUSIONS: These studies suggest that increased ICAM-1 expression seen on corneal stromal cells during clinical HSV-1 infection is not a direct result of productive viral infection, but of other mechanisms such as cytokine release by infiltrating mononuclear cells.

Adolescent↗

Efficacy of a recombinant glycoprotein D subunit vaccine on the development of primary and recurrent ocular infection with herpes simplex virus type 1 in mice.

The protective efficacy of a glycoprotein D subunit vaccine (gD2 SB AS4) was evaluated in a mouse model of human recurrent herpetic stromal keratitis (HSK). When administered before primary infection, gD2 SB AS4 protected mice against corneal pathology, mortality, and latency resulting from ocular viral challenge with herpes simplex virus type 1 (HSV-1) McKrae strain. In addition, gD2 SB AS4 significantly decreased postreactivation corneal disease. A control vaccine, gD2 alum, protected against acute ocular infection only. When administered after primary infection, gD2 SB AS4 vaccination decreased postreactivation ocular shedding but had no other significant effects. Vaccination with gD2 SB AS4 was associated with high anti-gD antibody responses and low delayed-type hypersensitivity responses. These results have identified a prophylactic vaccine, gD2 SB AS4, with activity against acute and recurrent HSK in mice and emphasize the need for vaccine evaluation in both primary and recurrent ocular herpetic disease models.

Animals↗

A critical evaluation of hepatitis C testing of cadaveric corneal donors.

PURPOSE: Enzyme immunoassays (EIAs) for hepatitis C virus (HCV) antibodies used to screen corneal donors are optimized for testing premortem sera. This study evaluated their efficiency when screening cadaveric sera. METHODS: Abbott HCV EIA 2.0 was used to rescreen 101 cadaveric sera, 70 of which had tested positive and 31 negative by EIA 1.0. Matrix-HCV recombinant immunoblot assay was used as a reference standard. Antibody titers and reactivities were compared in premortem and cadaveric sera. Selected sera from confirmed seropositive donors were screened for virus by polymerase chain reaction (PCR). RESULTS: HCV EIA 2.0 was 100% sensitive and 92.7% specific. EIA and Matrix-HCV gave similar end-point titers with pre- and postmortem sera. Viral RNA was detected in only three of 15 sera from seropositive donors. CONCLUSIONS: EIA 2.0 and Matrix-HCV efficiently screen cadaveric sera. However, HCV seropositivity does not necessarily indicate the presence of viral genomes in sera and tissues.

Adolescent↗

In vitro and in vivo effects of polyhexamethylene biguanide against herpes simplex virus infection.

PURPOSE: The differential diagnosis of Acanthamoeba keratitis frequently includes herpes simplex viral keratitis. Previous in vitro studies with chlorhexidine, a drug with antiacanthamoebic action, have suggested concomitant antiviral activity against herpes simplex virus. We tested another related antiacanthamoebic compound, polyhexamethylene biguanide (PHMB), to determine its activity against herpes simplex virus (HSV) in vitro and herpes simplex viral keratitis in vivo. METHODS: Equal aliquots of HSV-1 (McKrae) strain were incubated in a medium with no PHMB or with PHMB at 0.01, 0.02, or 0.05 for 5 min at 35 degrees C and the inoculum was then titered on a monolayer of E-2 cells (human corneal fibroblasts). Monolayers were examined on consecutive days and the percentage of plaque reduction was calculated. Eighteen rabbits (36 eyes) were inoculated with HSV-1 McKrae strain (10(5) pfu [plaque-forming units]/per eye). Rabbits were divided into three groups and treatment was initiated on day 3 postinfection. Group I received trifluorothymidine, group II received PHMB, and group III received artificial tears, each given five times daily in both eyes until day 10. Daily corneal swabbing to detect viral shedding and slit-lamp examination every 3 days were performed during this period. RESULTS: In vitro studies showed 62.5, 100, and 100% plaque reduction with 0.01, 0.02, and 0.05% PHMB, respectively. Slit-lamp examination of the rabbit corneas revealed faster resolution of dendrites in animals in group I treated with trifluorothymidine. Virus was not recoverable from corneal swabs in nine of 10 rabbits in group I by day 5, but all animals in groups II and III were still shedding HSV through day 8. CONCLUSION: Although PHMB has potent in vitro activity against HSV, it was not an effective treatment in the in vivo rabbit model of primary HSV keratitis at the concentration commonly used for treatment of Acanthamoeba infection. This suggests that 0.02% PHMB will not provide adequate antiherpetic coverage with treatment of keratitis of undetermined etiology in which the clinical differential diagnosis includes both herpes simplex and Acanthamoeba.

Administration, Topical↗

Cystic hydrops and spontaneous perforation in Fuchs' superficial marginal keratitis.

PURPOSE: We studied a case of Fuchs' superficial marginal keratitis in which cystic corneal hydrops developed in one eye, and spontaneous corneal perforation occurred in the fellow eye. METHODS: The patient underwent bilateral annular corneoscleral lamellar patch grafts for tectonic support. RESULTS: The patient had an uncomplicated postoperative course and visual acuity of 20/25 bilaterally. CONCLUSION: Stromal loss in Fuchs' superficial marginal keratitis may be severe enough to result in cystic corneal hydrops. Patients with this disorder should be counseled regarding the possibility of corneal perforation.

Adult↗

Screening potential corneal donors for HIV-1 by polymerase chain reaction and a colorimetric microwell hybridization assay.

PURPOSE: Current screening of potential corneal donors for human immunodeficiency virus type 1 (HIV-1) involves serologic detection of antibodies to the virus. However, this approach cannot detect infection during the seronegative window period of the disease. We therefore evaluated the polymerase chain reaction (PCR) assay for viral nucleic acid as a possible alternative to screening cadaveric blood for HIV-1. METHODS: Blood specimens from cadavers diagnosed at autopsy with acquired immunodeficiency syndrome (AIDS) (n = 21), at high risk for HIV-1 infection (n = 47), and at no known risk (n = 350) were screened by PCR for HIV-1 proviral DNA and human leukocyte antigen (HLA)-DQ alpha sequences, and for HIV antibodies. RESULTS: All AIDS group samples were seropositive; of these, 18 (86%) and 20 (95%) of 21 were positive for HIV by PCR of proteinase K- and Chelex-extracted pellets, respectively. The seropositive samples negative by PCR testing were shown to inhibit PCR amplification. Nine (19%) of 47 high-risk specimens were HIV-positive. The no-known-risk group yielded negative results. The overall sensitivities for PCR in the proteinase K- and Chelex-treated groups were 90% and 97%, respectively, compared with Western blot reactivity. If PCR-inhibitory samples and HLA-DQ alpha-negative samples had been eliminated, sensitivity would have been 100%. Specificity was 100% for each group. CONCLUSIONS: Screening cadaveric blood by PCR may be feasible, but further refinement of the assay and blood specimen collection practices will be necessary for it to become routine. Future studies should focus on optimizing specimen procurement and preparation to reduce or eliminate specimens that inhibit PCR.

AIDS Serodiagnosis↗

A comparison of recurrent and primary herpes simplex keratitis in NIH inbred mice.

Herpes simplex virus (HSV) infection is one of the leading causes of corneal blindness. This study compared the clinical, virologic, and immunopathologic features of primary and recurrent murine models of herpes simplex keratitis (HSK) in the National Institutes of Health (NIH) inbred mouse strain. Primary infection resulted in multiple epithelial dendrites, followed by diffuse stromal opacification, symptoms that do not mimic what is seen in human HSK. In contrast, recurrent infection presented clinical features that included microdendrites, focal stromal opacities, disciform endotheliitis, and corneal neovascularization, which were similar to those observed in human disease. Immunohistochemical characterizations indicated that the number and duration of T cells and macrophages in recurrent HSK resemble those observed in primary disease. Results also indicated that the amount of infectious virus detected in the cornea during primary and recurrent disease was similar. However, when corneas were stained for HSV-1 antigens, mice with primary HSK displayed diffuse HSV antigen expression throughout the cornea, whereas HSV antigens were more focally distributed in recurrent disease. These data suggest that the clinical differences between the recurrent and primary herpetic keratitis may, in part, reflect the different distribution of HSV-1 antigens within the cornea.

Animals↗

AIDS-related optic neuropathy: a histological, virological and ultrastructural study.

BACKGROUND: Clinical and histopathological evidence of optic nerve axonal loss has been reported in AIDS patients without retinitis. The study was carried out to investigate the possible involvement of HIV-infected cells in the development of optic nerve degeneration. METHODS: Optic nerves were obtained from eight AIDS patients and four normal controls. These nerves were morphologically and immunohistochemically analyzed. Additionally, using PCR amplification techniques, the retina and optic nerve samples obtained from three HIV-seropositive patients and one control were examined for the presence of HIV and cytomegalovirus antigens. RESULTS: We noted various stages of axonal degeneration in the optic nerves obtained from AIDS patients in whom there was an absence of retinal findings. Characteristic glial changes involving hypertrophic astrocytes, vacuolated oligodendrocytes, and mononuclear phagocyte series cells were also seen in the AIDS optic nerves. HIV DNA was present in at least four of five optic nerves but in only one of five retinas. Control specimens were each negative for all cytomegalovirus and HIV antigens. CONCLUSIONS: Degeneration in the optic nerve may be mediated by HIV-infected macrophages rather than by direct viral infection of neurons. Axonal degeneration due to AIDS at the level of the optic nerve can occur independently of retinal infection.

Acquired Immunodeficiency Syndrome↗

Air bag-related corneal rupture after radial keratotomy.

PURPOSE: We studied a case of air bag-associated corneal rupture in a patient who had previously undergone radial keratotomy surgery. METHODS: The patient was struck in the right eye when his driver's side air bag inflated during a low-speed collision. RESULTS: Inflation of the air bag resulted in rupture of the patient's right cornea. The rupture involved all but one of his old radial keratotomy wounds. CONCLUSIONS: Patients who have undergone radial keratotomy may be at increased risk for corneal rupture caused by air bag trauma. These patients may benefit by wearing protective eyewear while driving cars equipped with air bags.

Adult↗

Poor correlation between reactive syphilis serology and human immunodeficiency virus testing among potential cornea donors.

PURPOSE: The current practice in which eye banks screen cornea donors for syphilis is based mainly on the potential utility of positive syphilis serology as a surrogate marker for human immunodeficiency virus-1 (HIV-1) infection. We examined the correlation between positive syphilis and HIV-1 serologies within the potential cornea donor population. METHODS: We distributed a questionnaire to 94 eye banks in the United States regarding their rates of positive serology for syphilis and HIV-1 between Feb. 1 and July 30, 1992. We subsequently used the polymerase chain reaction for HIV-1 to further evaluate the whole blood of 21 rapid plasma reagin and fluorescent treponemal antibody-positive, HIV-1 enzyme-linked immunosorbent assay (ELISA)-negative cornea donors to determine whether these donors were infected with HIV-1 but were within a seronegative window for HIV-1 antibodies at their time of death. RESULTS: Of 8,932 donors screened, 103 (1.15%) had reactive screening for syphilis serology and 35 (0.39%) were HIV-1 seropositive. No donor with positive syphilis serology was also HIV-1 seropositive. Twelve of 31 donors who originally tested seropositive for syphilis by nontreponemal screening tests (Venereal Disease Research Laboratory or rapid plasma reagin tests) proved seronegative for syphilis when further tested with a treponemal test (FTA-ABS or microhemagglutination-Treponema pallidum), suggesting a high (38.7%) false-positive rate for the syphilis screening tests. Additionally, all 21 rapid plasma reagin and fluorescent-treponemal antibody-positive, HIV-1 ELISA-negative donors further tested were also negative for HIV-1 by the polymerase chain reaction. CONCLUSIONS: Among potential cornea donors, a population prescreened for identifiable HIV-1 risk factors, positive syphilis serology appears to be a poor marker for HIV-1 infection. The role of syphilis screening of potential cornea donors may need to be reevaluated.

AIDS Serodiagnosis↗

Screening corneas for human immunodeficiency virus type 1 proviral DNA by polymerase chain reaction.

PURPOSE: We evaluated the sensitivity of the polymerase chain reaction as a technique to directly screen potential donor corneas for human immunodeficiency virus type 1 (HIV-1) proviral DNA. METHODS: DNA from the central 8.0-mm cornea, limbal cornea, aqueous humor, and retina from 22 eyes of 11 cadavers seropositive for HIV was extracted and amplified by polymerase chain reaction using primers specific for the gag and env regions of the HIV-1 genome. The identity of amplification products was confirmed by Southern blot hybridization. RESULTS: Viral DNA was detected in four (18.2%) of 22 central corneas, one (4.5%) of 22 limbal corneas, one (6.3%) of 16 aqueous humor samples, and seven (31.8%) of 22 retinas. No correlation was noted between the presence of HIV-1 proviral DNA in samples from the central cornea and from the other tissues tested from the same eye. CONCLUSIONS: Within the limits of our assay, processing and analysis of limbal cornea, aqueous humor, and retina by polymerase chain reaction may not reliably ascertain the presence of HIV-1 in the central, transplantable cornea.

Base Sequence↗