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Biomedical subjects

Todd P Margolis

Publications and source records attributed to Todd P Margolis.

15 recordsLinked to original sources
PubMed2015

Dry eye symptoms align more closely to non-ocular conditions than to tear film parameters.

OBJECTIVE: To evaluate the relationship between dry eye symptoms, non-ocular conditions and tear film parameters. DESIGN: Cross-sectional study. PARTICIPANTS/SETTING: The study population consisted of patients who were seen in the Miami Veterans Affairs eye clinic. Patients filled out standardised questionnaires assessing dry eye symptoms (dry eye questionnaire 5 (DEQ5) and ocular surface disease index (OSDI)), non-ocular pain, depression and post-traumatic stress disorder (PTSD), and also underwent measurement of tear film parameters. MAIN OUTCOME MEASURES: Correlations between dry eye symptoms and non-ocular conditions as compared with tear film parameters. RESULTS: 136 patients with a mean age of 65 (SD 11) years participated in the study. All correlations between the dry eye questionnaire scores (DEQ5 and OSDI) and (A) self-reported non-ocular pain measures (numerical rating scale and pain history), (B) depression and (C) PTSD were significant and moderate in strength (Pearson's coefficient 0.24 to 0.60, p<0.01 for all). All correlations between the dry eye questionnaires and tear film measures were weak (Pearson's coefficient -0.10 to 0.18) and most were not significant. Multivariable linear regression analyses revealed that PTSD and non-ocular pain more closely associated with dry eye symptoms than did tear film parameters. Specifically, non-ocular pain and PTSD accounted for approximately 36% of the variability in DEQ5 scores (R=0.60) and approximately 40% of variability in OSDI scores (R=0.64). Of note, none of the tear parameters remained significantly associated with dry eye symptoms in either model. CONCLUSIONS: Dry eye symptoms more closely align to non-ocular pain, depression and PTSD than to tear film parameters.

Aged↗
PubMed2004

Emergence of drug-resistant cytomegalovirus retinitis in the contralateral eyes of patients with AIDS treated with ganciclovir.

The purpose of the present study was to examine the emergence of ganciclovir-resistant virus in the contralateral eyes of patients who received treatment for cytomegalovirus retinitis with either a ganciclovir implant plus oral placebo, a ganciclovir implant plus oral ganciclovir, or intravenous (iv) ganciclovir. Viral DNA was amplified from vitreous specimens and was assayed for UL97 and UL54 resistance mutations. Resistant viral genotypes were found in the contralateral eyes of 0 of 28 patients treated with a ganciclovir implant plus oral placebo, in 5 of 23 patients treated with a ganciclovir implant plus oral ganciclovir, and in 1 of 6 patients treated with iv ganciclovir. All resistance mutations were in codons 591, 592, or 594 of the UL97 gene. Treatment of unilateral cytomegalovirus retinitis with systemic ganciclovir decreases the risk of development of secondary sites of infection, but, in contralateral eyes that develop retinitis, this approach to treatment is associated with a higher prevalence of drug resistance, compared with treatment with the ganciclovir implant alone (P=.023; Fisher's exact test).

AIDS-Related Opportunistic Infections↗
PubMed2004

Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy.

PURPOSE: To further characterize the mutations within the CHST6 gene responsible for causing macular corneal dystrophy in a cohort of affected patients from the United States. DESIGN: Experimental study. METHODS: Genomic DNA was extracted from buccal epithelium of 16 affected patients (14 families), 17 unaffected relatives, and 127 controls, followed by polymerase chain reaction amplification and direct sequencing of the CHST6 coding region. Subtyping of affected patients into type I and II macular corneal dystrophy was performed by measuring antigenic keratan sulfate (AgKS) serum levels. Haplotype analysis was performed in families that demonstrated common mutations. RESULTS: CHST6 coding region analysis in 10 patients identified as having type I macular corneal dystrophy revealed 10 sequence changes: eight missense mutations, four of which are novel (Met104Val, Tyr110Cys, Gln122Pro, and Leu276Pro) and four of which have been reported previously (Ser51Leu, Pro72Ser, Cys102Gly, and Leu200Arg); one novel homozygous nonsense mutation in two patients from a single family (c. 1683C>T, Gln331X); and one frameshift mutation in a heterozygous state in a single patient (c.1744_1751dupGTGCGCTG). Mutation analysis in the four patients identified as having type II macular corneal dystrophy (serum samples were not obtained from two affected patients) revealed three patients heterozygous for either the c.923G>C, c.969C>A, or c.1519T>C sequence changes. The fourth patient was compound heterozygous for c.969C>A and c.1291T>G. None of these changes was observed in 127 control individuals. Haplotype analysis using microsatellite markers flanking the CHST6 gene did not reveal a common founder for the Leu200Arg (1291T>G) missense mutation, present in five families, identifying this position as a mutation hot-spot. CONCLUSIONS: A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I macular corneal dystrophy in a cohort of patients from the United States.

Adult↗
PubMed2004

Trends in the etiology of infectious corneal ulcers at the F. I. Proctor Foundation.

OBJECTIVE: We analyzed laboratory results from corneal ulcers seen from 1976 to 1999 at the Francis I. Proctor Foundation, a referral center in San Francisco, to determine the relative frequencies of pathogens and to analyze for trends in frequencies of the most common pathogens. The results were compared with a previous study of corneal ulcers seen from 1948 to 1976 at the same institution. METHODS: Ulcers presenting to the Proctor Foundation were Gram stained and cultured using standard techniques. Herpetic corneal ulcers were excluded from the study. RESULTS: Organisms were isolated from 427 ulcers, 38% of all cases. Two hundred seventy-eight (59%) isolates were gram-positive bacteria, 145 (31%) gram-negative bacteria, 16 (3%) Acanthamoeba spp., and 36 (8%) fungi. Staphylococcus aureus was the most common organism, composing 20% of all isolates, followed by viridans group streptococci (12%), Streptococcus pneumoniae (11%), Pseudomonas aeruginosa (6%), Moraxella spp. (5%), and Serratia marcescens (4%). Over the 24-year study period the proportion of positive cultures decreased and the incidence of S. marcescens increased significantly. Comparing the period of 1948-1976 to 1976-1999, the frequency of S. pneumoniae and P. aeruginosa decreased, and that of S. marcescens increased significantly. CONCLUSION: The common pathogens associated with corneal ulcers have changed over the past 50 years in Northern California, with S. pneumoniae and P. aeruginosa being isolated relatively less often and S. marcescens being isolated with increasing frequency. The decrease in isolation of organisms over the 1976-1999 period may have resulted from increasing empiric antibiotic treatment by referring ophthalmologists.

Acanthamoeba↗
PubMed2004

Pseudogerontoxon.

Pseudogerontoxon is a lesion that resembles a small segment of arcus senilis or gerontoxon and is seen in many individuals with limbal vernal or atopic keratoconjunctivitis. It is an important clinical finding because pseudogerontoxon is often times the only clinical evidence of previous allergic eye disease. To the authors' knowledge, pseudogerontoxon has only rarely been mentioned, and has never been pictured, in the peer-reviewed literature. Three examples are presented of this important clinical entity.

Adult↗
PubMed2003

Analysis of the herpes simplex virus type 1 UL6 gene in patients with stromal keratitis.

Recent work suggests that herpes simplex virus (HSV) stromal keratitis in the mouse is caused by autoreactive T lymphocytes triggered by a 16 amino acid region of the HSV UL6 protein (aa299-314), Science 279, 1344-1347). In the present study we sought to determine whether genetic variation of this presumed autoreactive UL6 epitope is responsible for different pathogenic patterns of human HSV keratitis. To accomplish this, we sequenced the HSV UL6 gene from ocular isolates of 10 patients with necrotizing stromal keratitis, 7 patients with recurrent epithelial keratitis, and 8 patients with other forms of HSV keratitis. The sequences obtained predicted identical UL6(299-314) epitopes for all 25 viral isolates. Furthermore, the upstream sequence of all isolates was free of insertions, deletions, and stop codons. We conclude that different pathogenic patterns of human HSV keratitis occur independent of genetic variation of the HSV UL6 (299-314) epitope.

Capsid↗
PubMed2003

Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India.

OBJECTIVE: To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. METHODS: Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. RESULTS: Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations. CONCLUSION: A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India. CLINICAL RELEVANCE: An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.

Corneal Dystrophies, Hereditary↗
PubMed2003

Genotypic analysis of cytomegalovirus retinitis poorly responsive to intravenous ganciclovir but responsive to the ganciclovir implant.

PURPOSE: To determine whether cytomegalovirus (CMV) retinitis that responded poorly to intravenous ganciclovir therapy but responded to the ganciclovir implant was caused by virus with resistance mutations in the viral UL97 and UL54 genes. DESIGN: Retrospective chart review and laboratory-based experimental study. METHODS: Regions of the CMV UL97 and UL54 were amplified from the vitreous and analyzed for resistant mutations by a combination of DNA sequencing and restriction digestion. Vitreous from patients with AIDS and retinal infections other than CMV retinitis served as negative controls. RESULTS: We amplified all target regions of UL97 DNA and most target regions of UL54 DNA from eight eyes with CMV retinitis. In one eye we found a ganciclovir resistance mutation at base 1781 of the UL97 gene, predicting an alanine to valine mutation at codon 594. In a second eye we found a ganciclovir resistance mutation at base 2960 of the UL54 gene, predicting an alanine to glycine mutation at codon 987. In two additional eyes, both from patients with bilateral retinitis, we found UL54 mutations that are likely to confer resistance to ganciclovir but have not been previously described. In both of these patients the UL54 genotype differed between the two diseased eyes. CONCLUSIONS: Failure to control CMV retinitis with intravenous ganciclovir does not necessarily imply infection with a virus having a known mutation that confers drug resistance. The ganciclovir implant can be an effective therapy for CMV retinitis caused by virus with certain UL97 and UL54 resistance mutations. Cytomegalovirus UL54 genotypes can differ between eyes in patients with bilateral retinitis.

AIDS-Related Opportunistic Infections↗
PubMed2003

Diagnosis of conjunctival B-cell lymphoma by polymerase chain reaction heteroduplex analysis.

PURPOSE: To report a case initially assessed as giant papillary conjunctivitis and subsequently as B-cell lymphoma by the molecular technique of polymerase chain reaction heteroduplex analysis. DESIGN: Observational case report. METHODS: Clinical, histologic, immunohistochemical, and polymerase chain reaction heteroduplex analysis findings are presented. RESULTS: A 32-year-old man developed unilateral blepharoptosis secondary to an extensive palpebral conjunctival follicular-like process. Excisional biopsy showed a dense small lymphocyte infiltrate consistent with benign lymphoid hyperplasia by histology and immunohistologic marker studies. Polymerase chain reaction heteroduplex analysis revealed low-grade B-cell lymphoma, however. Systemic examination was negative. Focal radiation therapy was performed, and preliminary results show no signs of lymphoma. CONCLUSIONS: Polymerase chain reaction heteroduplex analysis established a diagnosis of conjunctival B-cell lymphoma in the absence of supporting histology and immunohistochemistry studies. This technique may provide independent, diagnostic distinction between benign lymphoid hyperplasia and low-grade B-cell lymphoma of the ocular adnexa.

Adult↗
PubMed2003

Ocular complications of smallpox vaccination.

PURPOSE: To describe the ocular complications of smallpox vaccination and to discuss potential therapeutic options. DESIGN: Review of pertinent medical literature and recent treatment recommendations of the Centers for Disease Control and Prevention. RESULTS: After immunization against smallpox, vaccinia infection of the eyelid, conjunctiva, or ocular surface can result from accidental autoinoculation from a vaccination site before scab formation or from contact with a recently vaccinated individual. While uncommon, corneal involvement can lead to stromal opacification and scarring. Clinical findings of ocular and periocular vaccinia must be differentiated from those produced by other pathogens such as molluscum contagiosum, herpes simplex, varicella zoster, and acanthamoeba infections. Clinical diagnosis can be confirmed by electron microscopy to identify the presence of orthopoxvirus, as well as by virologic culture, polymerase chain reaction, and/or restriction endonuclease analysis of viral isolates. CONCLUSIONS: While the majority of ocular complications of smallpox vaccination in immunocompetent patients are self-limiting, selective cases may require treatment with trifluridine drops, topical corticosteroids and vaccinia immune globulin (VIG). Vaccinia virus does not appear to be sensitive to acyclovir. Specific treatment recommendations are outlined for the spectrum of ocular manifestations.

Centers for Disease Control and Prevention, U.S.↗
PubMed2003

A new mutation (Leu569Arg) within exon 13 of the TGFBI (BIGH3) gene causes lattice corneal dystrophy type I.

PURPOSE: To describe an American family with lattice corneal dystrophy type I, which associates with a novel mutation, Leu569Arg, of the TGFBI (BIGH3) gene. DESIGN: Experimental study. METHODS: Genomic DNA was extracted from buccal epithelial cells of four affected members of an American family with lattice corneal dystrophy type I. All 17 exons of the TGFBI gene were evaluated by PCR amplification and direct sequencing. Clinical and histologic data were also collected. RESULTS: Three generations of this family have been positively diagnosed with lattice corneal dystrophy, indicating autosomal dominant inheritance. We identified a heterozygous point mutation that associates with the disease phenotype. The single base-pair substitution (T1753G) results in an amino acid substitution (Leu569Arg) in exon 13 of the TGFBI gene. CONCLUSIONS: Substitution of arginine for leucine at position 569 of the TGFBI gene results in a form of lattice corneal dystrophy that is phenotypically similar to other genetically distinct forms of type I disease. This is the first report of disease correlated with changes in exon 13 of the TGFBI gene.

Adult↗
PubMed2002

Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice.

Infection of the mouse trigeminal ganglia (TG) is the most commonly used model for the study of herpes simplex virus type 1 (HSV-1) latency. Its popularity is caused, at least in part, by the perception that latent infection can be studied in this system in the absence of spontaneous viral reactivation. However, this perception has never been rigorously tested. To carefully study this issue, the eyes of Swiss-Webster mice were inoculated with HSV-1 (KOS), and 37-47 days later the TG were dissected, serial-sectioned, and probed for HSV-1 ICP4, thymidine kinase, glycoprotein C, and latency-associated transcript RNA by in situ hybridization. Serial sections of additional latently infected TG were probed with HSV-1-specific polyclonal antisera. Analysis of thousands of probed sections revealed abundant expression of viral transcripts, viral protein, and viral DNA replication in about 1 neuron per 10 TG tested. These same neurons were surrounded by a focal white cell infiltrate, indicating the presence of an antigenic stimulus. We conclude that productive cycle viral genes are abundantly expressed in rare neurons of latently infected murine TG and that these events are promptly recognized by an active local immune response. In the absence of detectable infectious virus in these ganglia, we propose the term "spontaneous molecular reactivation" to describe this ongoing process.

Animals↗
PubMed2002

Treatment of conjunctival squamous cell carcinoma with topical cidofovir.

PURPOSE: To describe a case of conjunctival squamous cell carcinoma in situ that was successfully treated with adjunctive topical cidofovir. DESIGN: Interventional case report. METHODS: A 52-year-old woman presented with a diagnosis of diffuse conjunctival papillomatosis in the right eye. She underwent conjunctival biopsy followed by a 6-week course of cidofovir eyedrops (2.5 mg/ml). RESULTS: The biopsy specimen demonstrated squamous cell carcinoma in situ. After this biopsy and treatment with cidofovir, the mass regressed into a small vascular tuft, which was excised and treated with cryotherapy. Six months after cidofovir treatment, the patient developed cicatricial changes of the inferior punctum. No recurrence of the squamous cell carcinoma has occurred in 24 months of follow-up. CONCLUSION: Cidofovir has shown effectiveness in the treatment of neoplastic lesions involving various mucus membrane sites. This antiviral drug may be a valuable addition to our treatment armamentarium for patients with squamous cell carcinoma in situ of the conjunctiva. The possible relationship between topical cidofovir and cicatricial changes of the lacrimal system cannot be determined from this isolated report, but further investigation is indicated.

Antineoplastic Agents↗