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1.
Prog Retin Eye Res ; 32: 88-101, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22944008

ABSTRACT

Herpes simplex virus-1 (HSV-1) infects the majority of the world's population. These infections are often asymptomatic, but ocular HSV-1 infections cause multiple pathologies with perhaps the most destructive being herpes stromal keratitis (HSK). HSK lesions, which are immunoinflammatory in nature, can recur throughout life and often cause progressive corneal scaring resulting in visual impairment. Current treatment involves broad local immunosuppression with topical steroids along with antiviral coverage. Unfortunately, the immunopathologic mechanisms defined in animal models of HSK have not yet translated into improved therapy. Herein, we review the clinical epidemiology and pathology of the disease and summarize the large amount of basic research regarding the immunopathology of HSK. We examine the role of the innate and adaptive immune system in the clearance of virus and the destruction of the normal corneal architecture that is typical of HSK. Our goal is to define current knowledge of the pathogenic mechanisms and recurrent nature of HSK and identify areas that require further study.


Subject(s)
Antiviral Agents/therapeutic use , DNA, Viral/analysis , Herpesvirus 1, Human/genetics , Keratitis, Herpetic/virology , Cornea/virology , Humans , Keratitis, Herpetic/diagnosis , Keratitis, Herpetic/drug therapy
2.
J Cataract Refract Surg ; 27(8): 1288-93, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11524202

ABSTRACT

PURPOSE: To determine whether the systemic administration of valacyclovir (Valtrex) reduces ocular shedding of herpes simplex virus type 1 (HSV-1) after laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit latency model. SETTING: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. METHODS: New Zealand White rabbits latently infected with HSV-1 W strain were divided into 3 groups. The first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of valacyclovir; and the third (control), saline. One half the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with 1 dose before LASIK. The HSV-1 ocular shedding was determined from eye cultures for 7 days after LASIK. RESULTS: The administration of both 100 mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of eyes (1/16 in both groups) and the total number of HSV-1 shedding days (1/122 and 2/122, respectively) from which HSV-1 was recovered compared to the control group (7/16 [P =.0396] and 14/129 [P <.007], respectively). CONCLUSIONS: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding after LASIK in the NZW rabbit latency model. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode while on valacyclovir antiviral prophylaxis.


Subject(s)
Acyclovir/analogs & derivatives , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Cornea/virology , Herpesvirus 1, Human/growth & development , Keratitis, Herpetic/drug therapy , Keratomileusis, Laser In Situ , Valine/analogs & derivatives , Valine/therapeutic use , Virus Activation/drug effects , Virus Shedding/drug effects , Animals , Cornea/surgery , Female , Herpesvirus 1, Human/drug effects , Injections, Intraperitoneal , Keratitis, Herpetic/virology , Rabbits , Valacyclovir
4.
Am J Ophthalmol ; 131(4): 506-7, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11292417

ABSTRACT

PURPOSE: We determined whether laser-assisted in situ keratomileusis acts as a trigger for the reactivation and ocular shedding of herpes simplex virus type-1 in a rabbit latency model. METHODS: Herpes simplex virus type-1 latently infected rabbits were divided into three treatment groups: Group I received surface excimer laser ablation in both eyes (positive control), Group II received laser-assisted in situ keratomileusis in both eyes, and Group III received no treatment (negative control). Eyes were cultured daily for 10 days to determine herpes simplex virus type-1 reactivation. RESULTS: The number of herpes simplex virus type-1 positive eye cultures and total herpes simplex virus type-1 shedding days were significantly greater after surface excimer laser ablation and laser-assisted in situ keratomileusis compared with the untreated control group (P < 0.002 and P < 0.000001, respectively). CONCLUSION: Laser-assisted in situ keratomileusis as well as surface excimer laser ablation act as a trigger for the reactivation of herpes simplex virus type-1 in the rabbit latency model.


Subject(s)
Cornea/virology , Herpesvirus 1, Human/growth & development , Keratitis, Herpetic/etiology , Keratomileusis, Laser In Situ/adverse effects , Virus Activation , Animals , Cornea/surgery , Keratitis, Herpetic/virology , Rabbits , Virus Cultivation , Virus Latency
5.
Cornea ; 18(6): 693-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10571301

ABSTRACT

PURPOSE: The goal of this was to determine whether the systemic administration of valacyclovir (Valtrex) would reduce ocular shedding of herpes simplex virus 1 (HSV-1) after excimer laser ablation in the New Zealand rabbit latency model. METHODS: The in vitro 50% inhibitory concentration (IC50) of HSV-1 W strain was determined by using a plaque-reduction assay to verify its sensitivity to acyclovir. Forty-seven NZW rabbits latently infected with HSV-1 W strain were divided into four groups: I, 50 mg/kg/day valacyclovir; II, 100 mg/kg/day valacyclovir; III, 150 mg/kg/day valacyclovir; and IV, saline control. One half of the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with one dose before excimer laser keratectomy. HSV-1 ocular shedding was determined from eye cultures for 7 days after treatment. RESULTS: The IC50 for HSV-1 W was determined to be 2.9 microg/ml. The administration of both 100 mg/kg/day (group II) and 150 mg/kg/day (group III) of valacyclovir significantly reduced the number of eyes from which latent HSV-1 was recovered compared with the control group. There was no difference between the control group and group I (50 mg/kg/day valacyclovir). However, all three valacyclovir dosages significantly reduced the total number of HSV-1 shedding days compared with the control group, and 100% HSV-1 TG latency was demonstrated for all four groups. CONCLUSION: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding in a dose-dependent manner after excimer laser keratectomy in the NZW rabbit latency model.


Subject(s)
Acyclovir/analogs & derivatives , Antiviral Agents/pharmacology , Cornea/surgery , Eye/virology , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/growth & development , Laser Therapy , Valine/analogs & derivatives , Virus Activation , Acyclovir/blood , Acyclovir/pharmacology , Animals , Antiviral Agents/blood , Female , Inhibitory Concentration 50 , Rabbits , Trigeminal Ganglion/virology , Valacyclovir , Valine/blood , Valine/pharmacology , Virus Latency , Virus Shedding/drug effects
6.
Am J Ophthalmol ; 125(4): 488-92, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9559734

ABSTRACT

PURPOSE: To investigate the role of excimer laser keratectomy as a trigger for the reactivation of latent HSV type 1 (HSV-1) in the New Zealand rabbit ocular model. There are conflicting reports in the current literature about reactivation of HSV-1 after excimer laser photoablation. METHODS: New Zealand rabbits were inoculated topically with HSV-1 McKrae or W strain in each eye, and culture-positive dendritic keratitis was documented on day 7. After the establishment of latency (21+ days), animals were divided into three groups: group I animals underwent excimer laser photoablation in each eye; group II animals received intrastromal injections of sterile water to act as positive controls (a standard method); and group III animals received no treatment and represented spontaneous shedders. All eyes were swabbed daily from days 1 through 10 and plated on A549 cells. Recovery of HSV-1 on days 1 through 10 postinduction was analyzed to compare the efficiency of the different methods of viral reactivation. RESULTS: Reactivation of latent HSV-1 after excimer treatment was observed in nine (45%) of 20 eyes and was equivalent to the rate of reactivation seen in the positive control animals (eight [44.4%] of 18 eyes) (P=.99). Both of these rates were significantly greater than those of the untreated animals (one [5.6%] of 18 eyes) (P=.018). CONCLUSION: Excimer laser keratectomy appears to be an efficient trigger for the reactivation of latent HSV-1 in the New Zealand rabbit ocular model.


Subject(s)
Cornea/virology , Herpesvirus 1, Human/physiology , Keratitis, Dendritic/virology , Photorefractive Keratectomy , Virus Activation , Virus Latency/physiology , Animals , Chlorocebus aethiops , Cornea/surgery , Disease Models, Animal , Female , Herpesvirus 1, Human/isolation & purification , Keratitis, Dendritic/surgery , Lasers, Excimer , Rabbits , Vero Cells/virology , Virus Cultivation/methods
7.
Cornea ; 16(4): 483-5, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9220249

ABSTRACT

PURPOSE: Pellucid marginal degeneration is a noninflammatory thinning disorder typically involving the inferior cornea. We describe a patient with superior corneal thinning similar to classic pellucid marginal degeneration. METHODS: An 80-year-old man was evaluated for high astigmatism. RESULTS: The right superior cornea had a prominent band of thinning with ectasia. Both inferior corneas had characteristic zones of thinning without inflammation. CONCLUSIONS: Superior pellucid marginal corneal degeneration should be considered in the differential diagnosis of superior corneal ectatic disorders.


Subject(s)
Cornea/pathology , Corneal Dystrophies, Hereditary/diagnosis , Aged , Aged, 80 and over , Astigmatism/diagnosis , Astigmatism/therapy , Diagnosis, Differential , Eyeglasses , Follow-Up Studies , Humans , Image Processing, Computer-Assisted , Male , Visual Acuity
8.
Am J Ophthalmol ; 121(6): 711-2, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8644817

ABSTRACT

PURPOSE: We evaluated patients' hands as a possible vector for the spread of epidemic kerato-conjunctivitis. METHODS: The hands and conjunctivitis of 26 patients with epidemic keratoconjunctivitis and the hands of 26 uninfected control patients were cultured for infectious adenovirus. RESULTS: In 12 (46%) of 26 patients with epidemic keratoconjunctivitis, cultures from the hands were positive for adenovirus, whereas cultures from the hands of all uninfected control patients were negative. CONCLUSIONS: Simultaneous coinfection of patients' hands and eyes with adenovirus may contribute to office epidemics. Ophthalmologists and coworkers should not shake the hands of patients suspected of having epidemic keratoconjunctivitis unless properly gloved.


Subject(s)
Adenovirus Infections, Human/prevention & control , Conjunctiva/virology , Eye Infections, Viral/prevention & control , Hand/virology , Infectious Disease Transmission, Patient-to-Professional , Keratoconjunctivitis/prevention & control , Adenovirus Infections, Human/transmission , Adenovirus Infections, Human/virology , Adenoviruses, Human/isolation & purification , Carrier State , Disease Outbreaks/prevention & control , Eye Infections, Viral/transmission , Eye Infections, Viral/virology , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Keratoconjunctivitis/epidemiology , Keratoconjunctivitis/virology , Risk Factors , Virus Cultivation
9.
J Cataract Refract Surg ; 22(4): 452-7, 1996 May.
Article in English | MEDLINE | ID: mdl-8733849

ABSTRACT

PURPOSE: To investigate the visual significance of "glistenings" in acrylic intraocular lenses (IOLS). SETTING: John Moran Eye Center, University of Utah, Salt Lake City. METHODS: Seventeen patients who had phacoemulsification with implantation of the AcrySof acrylic IOL were evaluated by slitlamp examination and visual acuity, contrast sensitivity, and glare testing. Ten patients had a silicone posterior chamber IOL in the opposite eye and had testing with similar visual parameters for comparison. Glistenings noted in the acrylic IOLs were graded at the slitlamp. Laboratory analysis of five acrylic IOLs was also done to reproduce the glistenings noted clinically. RESULTS: All 17 patients with the acrylic IOLs had some lenticular glistenings, ranging from trace to 2+. Statistical analysis of visual acuity, contrast sensitivity, and glare testing revealed a statistically significant difference between the acrylic and the silicone IOLs only in contrast sensitivity. Laboratory analysis of the acrylic IOLs showed similar glistenings from 48 to 72 hours after they were placed in balanced salt solution. CONCLUSIONS: A patients who received AcrySof IOLs that came in the AcryPak had some degree of glistenings. There was also a significant decrease in contrast sensitivity compared with that of fellow eyes with silicone IOLs. The glistenings are likely caused by water vacuoles that form within the lens after hydration within the eyes. Further studies are necessary to assess the exact cause of these glistenings.


Subject(s)
Acrylates/adverse effects , Contrast Sensitivity , Lenses, Intraocular/adverse effects , Phacoemulsification , Vision Disorders/etiology , Humans , Silicone Elastomers , Visual Acuity/physiology
10.
Am J Ophthalmol ; 119(1): 62-4, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7825691

ABSTRACT

PURPOSE: We sought to determine whether a venturi-aspiration vitrectomy machine could contaminate a vitrectomy culture. METHODS: Ninety vitrectomies were simulated in a hospital operating room and were cultured with standard techniques. An additional 90 control specimens were cultured in the exact same manner, but the vitrectomy machine was not used. Instead, the control specimens were placed directly into a sterile vitrectomy cassette. Contamination rates in the two groups were compared. RESULTS: Contamination occurred in four of 90 vitrectomy-simulation cultures and in three of 90 control cultures. This difference in contamination rate was not statistically significant. CONCLUSIONS: Although the result of a culture of the vitrectomy effluent can be false-positive, the source of contamination is not likely to be the vitrectomy machine.


Subject(s)
Endophthalmitis/etiology , Equipment Contamination , Eye Infections, Bacterial/etiology , Vitrectomy/instrumentation , Bacteria/isolation & purification , Endophthalmitis/microbiology , Evaluation Studies as Topic , False Positive Reactions , Humans , Isotonic Solutions , Microbiological Techniques , Vitreous Body/microbiology
11.
J Neurochem ; 40(2): 514-21, 1983 Feb.
Article in English | MEDLINE | ID: mdl-6130128

ABSTRACT

Verapamil at 200 microM, prevented the respiratory stimulation, K+ loss, transmitter release, and 45Ca2+ entry into incubated synaptosomes evoked by veratrine (25 to 75 microM) or by high K+ (56 mM). Verapamil (100 microM) also blocked gamma-aminobutyric acid homoexchange, whilst tetrodotoxin was ineffective. Much lower concentrations of verapamil (less than 1 microM) blocked the 45Ca2+ entry caused by veratrine, but not its action in releasing neurotransmitter or K+. It is concluded that verapamil, at 30 to 200 microM, blocks active Na+ channels, thereby preventing depolarization. At greater than 1 microM, verapamil blocks Ca+ channels selectively.


Subject(s)
Amino Acids/metabolism , Cerebral Cortex/metabolism , Neurotransmitter Agents/metabolism , Synaptosomes/metabolism , Verapamil/pharmacology , Animals , Aspartic Acid/metabolism , Biological Transport, Active , Calcium/metabolism , Cerebral Cortex/drug effects , Female , Glutamates/metabolism , Glutamic Acid , Rats , Rats, Inbred Strains , Synaptosomes/drug effects , Tetrodotoxin/pharmacology , Threonine/metabolism , Veratridine/pharmacology , gamma-Aminobutyric Acid/metabolism
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