Melvin D. Trousdale

Prevalence, Pathophysiology, and Treatment of Rhegmatogenous Retinal Detachment in Treated Cytomegalovirus Retinitis

Seventeen patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis were treated with the antiviral drug ganciclovir (9-[1,3-dihydroxy-2-propoxy-methyl]-guanine, DHPG). Eight eyes of five patients developed rhegmatogenous retinal detachment after initiation of treatment. Multiple breaks in areas of peripheral, healed, atrophic retina accounted for the detachments. All seven eyes that underwent surgery had extensive retinal detachments that were reattached with vitrectomy and silicone oil. Retinotomy and retinal tacks were necessary in two cases that were complicated by severe proliferative vitreoretinopathy. In the fellow eye of one patient, laser treatment was used prophylactically to wall off a peripheral patch of healed retinitis. Endoretinal biopsies and culture were taken in five eyes; evidence of persistent cytomegalovirus was seen in two cases despite concurrent and clinically effective antiviral therapy.

Optisol Corneal Storage Medium

Optisol is an investigational, intermediate-term corneal storage medium containing chondroitin sulfate and dextran to enhance corneal dehydration during storage. We used scanning electron microscopy to grade endothelial cell morphologic characteristics in terms of cell shape, cell borders, cell swelling, and apical holes in pairs of corneas stored in Optisol and Dexsol. Optisolstored corneas showed significantly fewer morphologic changes after 14 days at 4 degrees C than did Dexsol-stored corneas. No significant differences were seen after 1 to 4 days at 26 degrees C. Temperature-reversal analysis showed no significant change in corneal thickness with warming after 2-week storage at 4 degrees C in either medium, although Optisol-stored corneas were significantly thinner than those stored in Dexsol at all times. The results of scanning electron microscopy suggest that preservation at refrigerator temperature for 2 weeks in Optisol is superior to preservation in Dexsol. Both media may be useful in preserving endothelial structure for limited periods at room temperature, which could provide a measure of safety in shipping or storage where refrigeration is unreliable.

Demonstration of Herpes Group Virus in Acute Retinal Necrosis Syndrome

Tissue for pathologic examination was obtained from three cases of acute retinal necrosis syndrome. Virus particles belonging to the herpesvirus family were demonstrated in retinal biopsies from two patients, one of whom was immunosuppressed. Despite removal of large biopsy specimens, the retina has remained attached for 20 months postoperatively in one case and for three months in the other. In a third patient with acquired immune deficiency syndrome, the clinical course and postmortem immunopathology were suggestive of a herpes simplex virus infection, initially affecting the retina and subsequently the optic nerves, chiasm, tracts, and central nervous system. These cases illustrate that the virus associated with the acute retinal necrosis syndrome is easily demonstrable using vitrectomy and endoretinal biopsy in the acute phase of the disease, but may be difficult to demonstrate in chronically detached atrophic retinas.

The Comparative In Vitro Activity of Ofloxacin and Selected Ophthalmic Antimicrobial Agents Against Ocular Bacterial Isolates

The in vitro activity of ofloxacin, a new fluoroquinolone anti-infective agent, was evaluated against 419 ocular bacterial isolates of 55 species to determine its potential as a topical agent for the treatment of ocular infections. Other agents tested in this study, in which a modified tube-dilution procedure was used, include norfloxacin, gentamicin, tobramycin, chloramphenicol, and polymyxin B. Ofloxacin demonstrated good to excellent activity against a variety of gram-positive and gram-negative pathogens. The minimum inhibitory concentration against 90% of all bacterial strains tested (MIC90) of ofloxacin was 0.5 microgram/ml for Staphylococcus aureus and S. epidermidis, 2 micrograms/ml for Streptococcus pneumoniae, and 4 micrograms/ml for Pseudomonas aeruginosa. These species were more susceptible to ofloxacin than to any of the nonquinolones tested. The MIC90 of ofloxacin was lower than that of norfloxacin, another quinolone, against S. aureus, S. epidermidis, and St. pneumoniae and equal to that of norfloxacin against P. aeruginosa. Because of its broad spectrum of activity and excellent in vitro activity, we concluded that ofloxacin has the potential for development into a superior topical treatment for ocular infection.

Evaluation of Cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zealand rabbit ocular model

The antiviral inhibitory activity of Cidofovir [1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate, HPMPC, GS-504] against adenovirus type 5 (Ad5) in the New Zealand rabbit ocular replication model was evaluated. The 50% inhibitory dose (ID50) of Cidofovir was determined to be 4.7-9.5 micrograms/ml against four adenoviruses (two Ad5, Ad8 and Ad14) by plaque reduction assay in A549 cells. Twenty-four New Zealand rabbits received intrastromal inoculation and topical application of 2 x 10(6) plaque-forming units (PFU) per eye of Ad5 McEwen, a clinical isolate. Cidofovir was administered topically at three different concentrations twice per day, beginning 16 h postinoculation and continuing for 20 consecutive days. The inhibitory effects were determined by measuring suppression of virus replication and by observation of the clinical effects. Compared to the placebo group, the 1% and 0.5% Cidofovir-treated groups showed significantly reduced Ad5 ocular titers, fewer days of viral shedding and less severe subepithelial opacities (P = 0.0001). The 1% Cidofovir group had the lowest humoral antibody titer against adenovirus antigens, but the difference was not significant (P = 0.24). Cidofovir proved to have potent antiviral activity against adenovirus replication and may have great promise for the treatment of adenovirus infection. Further investigation is recommended.

Intravitreal Penetration of Oral Ciprofloxacin in Humans

Nineteen patients about to undergo elective vitreous surgery received 1 oral dose of 750 mg of ciprofloxacin before surgery. Specimens of serum and vitreous were collected 90 minutes to 18 hours after drug administration and were assayed for antibiotic content with a microbiologic disk agar technique. From 4 hours and 50 minutes to 16 hours and 50 minutes after a single oral dose, ciprofloxacin reached intravitreal levels above its minimal inhibitory concentration for 90% of Staphylococcus epidermidis, Bacillus species, and Enterobacteriaceae. However, intravitreal levels never exceeded the MIC90 for Staphylococcus aureus and Pseudomonas.

Immunostimulating polysaccharides from Panax notoginseng.

AbstractPurpose. The main purpose of this study is to prepare and characterize polysaccharides from Panax notoginseng, investigate their effects on immune system in vitro in order to find new immunostimulants for the prevention and supporting treatment of infection and immunodeficiency related diseases. Methods. Polysaccharides were extracted with aqueous solution, separated with column chromatography. Their anticomplementary activities were investigated by using human serum and antibody-sensitized sheep red blood cells. Interferon-γ and tumor necrosis factor inductive activities were studied by using isolated mouse spleen lymphocytes and peritoneal macrophages, respectively. Results. Four polysaccharides, homogeneous in gel-filtration chromatography, were prepared and designated PF3111, PF3112, PBGA11, and PBGA12. Component sugar analysis revealed that they are heteroglycans with MWs ranging from 37 kD to 760 kD, composed of glucose, galactose, arabinose, mannose, and xylose in different molar ratios. Fraction PBGA12 has the most anticomplementary activity which is mediated through both alternative and classical pathways. All the polysaccharides except PBGA11 induced the production of interferon-γ in the presence of concanavalin A. They induced the production of significant amount of TNF-α in cell cultures. Conclusions. The polysaccharides from P. notoginseng have immunostimulating activities invitro.

Experimental demyelination induced by coronavirus JHM (MHV-4): molecular identification of a viral determinant of paralytic disease

Abstract The molecular basis for demyelination induced by the neurotropic murine coronavirus JHM (JHMV or MHV4) is unknown. We have attempted to explore this issue by using neutralizing monoclonal antibodies specific for the major JHMV glycoprotein (E2) to select sets of neutralization resistant (NR) antigenic variant viruses. Monoclonal antibodies J.7.2 and J.2.2 bind to topographically distinct sites on E2. NR variants selected with J.7.2, like parental JHMV, predominantly cause a fatal encephalitis when given intracerebrally to mice, while J.2.2-selected NR variants cause a subacute disease characterized by paralysis and severe demyelination. We report here that consecutive selection with both J.2.2 and J.7.2 monoclonal antibodies results in NR variants which are markedly attenuated in both encephalitic potential and ability to induce demyelination. Analysis of the different variants suggests that the subregion of E2 bound by monoclonal antibody J.7.2 may be a critical viral determinant of paralysis and demyelination in this model system.

Mycobacterium chelonei Keratitis After Radial Keratotomy

Two patients who had undergone radial keratotomy developed delayed postoperative infectious keratitis. Both patients had surgery at the same outpatient facility, and their procedures had been performed by the same surgeon. The corneal lesions appeared similar in both cases, consisting of white irregular infiltrates with radiating projections and fluffy, indistinct margins. Although they were found at all levels, the lesions were most concentrated in the mid-to-deep stroma and were associated with overlying epithelial defects. In both cases, Mycobacterium chelonei was isolated from corneal biopsy specimens. Both patients were treated with topical fortified amikacin; in one there was complete resolution of the corneal infiltrates with medical therapy alone. Although the other patients lesions initially appeared to resolve with medical therapy, she eventually required corneal transplantation because of recurrence of the infiltrates. Histopathologically, the infiltrates consisted of myriads of acid-fast bacteria with rare inflammatory cell infiltrations.

Donor cornea bacterial contamination.

The incidence of culture-positive cornea rims from 446 consecutive donor corneas cultured at the Doheny Eye Institute between 1986 and 1988 was determined. Both the identity and antibiotic sensitivities of the contaminating organisms were reviewed. Sixty-three (14.1%) of 446 cornea rims were culture-positive, but none of the 63 patients who received these contaminated donor corneas developed endophthalmitis. Streptococcus (26 of 63), Propionibacterium (15 of 63), Staphylococcus (14 of 63) species and diptheroids (8 of 63) were the most common cornea rim contaminants, and in most cases were resistant to gentamicin (i.e., 21 of 26 or 81%, 9 of 15 or 60%, 10 of 14 or 71%, 4 of 8 or 50%, respectively). Virtually all of the gentamicin-resistant bacteria isolated from cornea rims were found to be sensitive to vancomycin. Eye banks should consider the addition of other antibiotics to storage media to reduce donor cornea contamination. Surgeons performing corneal transplantation should also consider these results when selecting antibiotics for use at the time of surgery and in the postoperative period.