Biomedical subjects
Publications and source records attributed to H E Kaufman.
Ocular trauma from nylon line lawn trimmers is becoming more prevalent. Previous case reports have described penetrating trauma caused by these tools. We managed three cases of fungal keratitis caused by injuries from nylon line trimmers. Fungal keratitis should be strongly considered as the cause of any corneal ulcer related to trauma from a nylon line lawn trimmer.
We compared the safety and efficacy of Optisol (Chiron Ophthalmics, Irvine, California), a new corneal storage medium, with McCarey-Kaufman and Dexsol corneal storage media (Chiron Ophthalmics, Irvine, California) and K-Sol corneal storage medium (Cilco, Huntington, West Virginia). Optisol contains dextran, 2.5% chondroitin sulfate, vitamins, and precursors of adenosine triphosphate (adenosine, inosine, and adenine). In in vitro studies, rabbit and human corneas stored in Optisol were thinner after 12 to 14 days at 4 C than tissue stored in other media. Thymidine uptake showed increased mitotic activity in human corneal endothelial cells cultured in Optisol, compared to Dexsol. Specular microscopic fields showed larger are-as of visibly intact endothelial cells and ultrastructural examination disclosed fewer structural changes in endothelial cells stored in Optisol, compared to tissue stored in Dexsol. In vivo, no clinical signs of epithelial toxicity or histologic evidence of intraocular inflammation were observed in rabbit eyes in which Optisol drops were instilled four times a day for 14 days. Finally, 51 patients undergoing penetrating keratoplasty with tissue stored in Optisol for one to six days (mean, 3.6 days) were enrolled in an uncontrolled, open-label clinical study. The percentage of clear grafts (93%, 41 of 44 patients examined at three months; and 98%, 42 of 43 patients examined at six months) and endothelial cell loss (5.0% and 11.5% at three and six months, respectively) were comparable to data from previous studies that used tissue stored in other short-term and intermediate-term media. The results suggest that Optisol storage preserves corneal endothelial cells for up to two weeks at 4 C, thereby permitting flexibility in the use of donor tissue for corneal transplantation, and that Optisol storage yields thinner tissue, which may allow for more accurate evaluation and more effective surgical manipulation.
Antibiotics in a corneal preservation solution probably have little effect during storage at 4 C, but are effective as the tissue is warmed. The tissue acts as a sponge, soaking up the antibiotic from the solution and releasing it into the eye, where the bactericidal effect is achieved. Currently, high concentrations of gentamicin (relative to the minimal inhibitory concentration) are used in the preserving solution for this purpose. Presumably, proportionately high concentrations of any proposed new antibiotic added to supplement the bactericidal effect of gentamicin, such as the vancomycin used in this study, would be required. However, neither the ability of donor tissue to tolerate high concentrations of vancomycin nor the stability of vancomycin at neutral pH in appropriate storage media has been documented. We evaluated the addition of vancomycin (100 micrograms/ml) to two corneal storage media that contained gentamicin in terms of stability of the antibiotic in solution and the effect on the endothelial cells of donor tissue stored for two weeks at 4 C. Vancomycin was stable in solution at neutral pH (7.2) during the five-month period of the study; the concentration exceeded 90 micrograms/ml for the first five weeks. The endothelial cells from donor tissue stored in the vancomycin-enriched media showed no notable differences from those stored in the same media without vancomycin in terms of cell shape, cell borders, cell swelling, and apical holes. The stability of vancomycin in storage and the absence of endothelial toxicity in vitro support the potential use of this antibiotic as a supplement to gentamicin for the prevention of endophthalmitis in patients receiving corneal transplants.
We describe a new technique to correct inadvertent conjunctival filtering blebs. This method creates a partial-thickness scleral flap to seal the region of the excised fistula. Closure of this flap with sutures permanently covers the fistula and eliminates any route for recurrence of the bleb or downgrowth of epithelium. No complications have been associated with this procedure, which has been used in more than 10 cases during the last 3 years.
New approaches to improving corneal epithelial wound healing include stromal puncture and removal of abnormal basement membrane material by excimer laser ablation (phototherapeutic keratectomy). Non-healing corneal erosions and chemical burns may also benefit from laser excision of the damaged surface to permit more normal epithelial attachments. Reduction of postsurgical astigmatism may be facilitated by adjustable sutures after penetrating keratoplasty or by molding the cornea with the use of a rigid contact lens in the immediate postoperative period.
Epithelial wound closure following superficial corneal abrasions precipitates a complex series of cellular changes in the stroma. Transmission electron microscopy and light microscopy have demonstrated that keratocytes in the anterior stroma show prominent cytoplasmic process and granularity within an hour after this injury. Cell degeneration follows rapidly, with almost complete depletion of these keratocytes by 6-12 hours. Regeneration then occurs by 24-48 hours. These findings were confirmed in-vivo by tandem-scanning confocal light microscopy in rabbits. The optical sectioning capability of this instrument allowed us to demonstrate the three-dimensional array of fibroblast process, their subsequent condensation, and loss by sequential examinations on the same animals. Cell shrinkage and other fixation artifacts common in corneal histological sections were avoided by this technique. Using this method, we investigated the corneal cytotoxicity of an antimitotic agent, mitomycin-C and a muscarinic antagonist, atropine sulphate. Mitomycin-C, an antimetabolite used in pterygium treatment, led to irreversible keratocyte depletion even after four days of observation. However, cellular reaction to the wound were attenuated by atropine sulphate suggesting that it may be useful as a novel inhibitor of fibroblast proliferation.
The tandem scanning confocal microscope (TSM) was adapted for in vivo examination of the cornea in rabbits with experimental bacterial and fungal keratitis. Compared to slit lamp biomicroscopy, the TSM provides superior lateral and axial resolution and serial optical sectioning capability, which may be useful for identification of corneal pathogens in the early stages of infection. We used the TSM to examine normal rabbit eyes infected with bacteria (Bacillus cereus) and a filamentous fungus (Aspergillus). We also examined a human cornea removed by penetrating keratoplasty after a clinical diagnosis of amoebic keratitis. In the early stages of bacterial infection, slit lamp examination revealed a nonspecific minimal stromal haze and limbal injection indistinguishable from sterile ulcers and epithelial defects. With the TSM, bacteria were visible as highly refractile bodies in the epithelium and superficial stroma. Branching fungal hyphae were also easily identified by the TSM, as were Acanthamoeba cysts and parasites in the subepithelial stroma. Our results indicate that this technique may provide a new modality for quickly and accurately identifying the agent of corneal infection, thereby facilitating prompt and appropriate treatment.
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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.
5'-Ethynylthymidine, an inhibitor of viral thymidine kinase (TK), was given intraperitoneally to squirrel monkeys previously infected by the ocular route with Rodanus strain herpes simplex virus. Spontaneous ocular recurrences were reduced during therapy, compared to saline-treated controls. This is the first in vivo demonstration that a viral TK inhibitor can reduce recurrences of HSV-1. Similar benefit would be expected for HSV-2 and perhaps VZV (varicella zoster virus).
HSV-1 multiplication rates have been shown to vary in different tissues and the rate of multiplication may correlate with susceptibility to antiviral chemotherapy. Herpetic stromal keratitis is a necrotizing condition refractive to antiviral therapy and this lack of antiviral efficacy in stromal disease may be the result of very low rates of viral replication in the corneal stromal keratocytes. In this study, we investigated the efficacy of antiviral drugs in an in vitro system in which the virus multiplication rate is slow. In this system, the reduced rate of virus multiplication is achieved by a reduction in the incubation temperature. Vero cells were infected at one of several multiplicities of infection with McKrae strain HSV-1 and incubated for 24, 48, or 72 h at 26 or 36.5 degrees C in the presence or absence of trifluridine (50 micrograms/ml) or acyclovir (20 micrograms/ml). Both drugs suppressed viral replication at 36.5 degrees C. However, under some specific sets of conditions, trifluridine was not effective in suppressing viral replication in cells incubated at 26 degrees C. At this temperature, viral replication and cell metabolism are slowed to a pace which may be similar to that which occurs in corneal stromal keratocytes in vivo. Acyclovir significantly reduced HSV-1 replication under all conditions at 26 degrees C, indicating that the antiviral activity of this compound is effective in cells whose metabolic rate is slow and in which viral replication is taking place slowly.
Computer-assisted analysis of corneal topography was performed in 17 normally sighted human eyes during the first year after excimer laser photorefractive keratectomy (PRK) for myopia. Laser ablation of the central cornea produced an optical zone with a smooth power transition to the peripheral cornea. Decentration of the ablation was noted in some eyes (less than 0.5 mm in 3 eyes, 0.5 to 1.0 mm in 10 eyes, 1 to 1.5 mm in 3 eyes, and 2.1 mm in 1 eye), suggesting that careful alignment of the laser beam is critical. Improved methods to align the ablation within the center of the entrance pupil are needed. In 12 of 17 eyes, the topographic pattern appeared to stabilize between 3 and 7 months after PRK. In the remaining five eyes, central ablation power changed by more than 0.5 diopters (D) between the 6- and 12-month examinations. Regression was more common and more pronounced in eyes with intended corrections more than 5 D, whereas the majority of eyes with intended corrections of 5 D or less showed good correspondence between the final change in central ablation power and the attempted correction. Two eyes had a loss of at least two lines of best spectacle-corrected visual acuity that was attributable to irregular astigmatism, decentration of the ablation, and/or corneal opacification.
Ten partially sighted and 19 normally sighted eyes underwent excimer laser photorefractive keratectomy for the correction of myopia. Nine of the partially sighted and 17 of the normally sighted eyes had 12 months of follow-up. Epithelial healing was complete in all eyes by day 6. None of the eyes had recurrent erosions, infections, or other medical complications. An increase in corneal haze after surgery was followed by a slow trend toward clearing. Average uncorrected visual acuity in the 7 normally sighted eyes with attempted corrections of 5 diopters (D) or less was 20/40 from month 2 on; the eyes with greater than 5 D attempted corrections had an average of 20/80--at month 2, which declined to 20/200--by month 6. Best spectacle-corrected visual acuity was within +/- 1 Snellen line of preoperative values in 14 of the normally sighted eyes, improved 2 or more lines in 2 eyes, and worsened two or more lines in two eyes. Hard contact lens overcorrection restored all of the two-line loss in 1 eye and 1 line of the 3-line loss in the other. Refraction and keratometry indicated corneal flattening without induced astigmatism.
Absorbable intracanalicular collagen implants were placed in both canaliculi of one eye of nine human volunteers. The other eye served as a control. Twenty-four hours later 2% sodium fluorescein was placed into both conjunctival sacs. Serial corneal fluorescein concentrations were measured with a scanning ocular fluorophotometer from 2 to 90 min after fluorescein administration. The mean corneal fluorescein concentration averaged over all time points was greater in 7 of 9 eyes with collagen implants compared to unimplanted controls. When the data from each subject were analyzed collectively, the mean corneal fluorescein concentration in the implanted eyes (1,218 micrograms/ml +/- SEM 83) was significantly greater (p less than 0.001) than the mean concentration in the control eyes (823 micrograms/ml +/- SEM 83). The use of absorbable intracanalicular collagen implants may increase the bioavailability of topically applied ocular solutions.
The Herpetic Eye Disease Study (HEDS) includes three double-masked, placebo-controlled clinical trials for potentially blinding herpes simplex virus (HSV) eye infections. One study compares a tapering dosage of topical prednisolone or placebo eye drops for HSV stromal keratitis (HEDS-SKN). Two other trials compare oral acyclovir to placebo capsules for HSV stromal keratitis (HEDS-SKS) or iridocyclitis (HEDS-IRT) in patients on a tapering dosage of topical prednisolone drops. All medications are administered for 10 weeks. Outcome is judged by time to recurrent disease or treatment failure. This paper presents the design, estimated sample size and recruitment as of July 25, 1990.
The authors first report in China the detection of HSV-1 antigen in 36 human corneas with recurrent HSK, using the horse radish peroxidase staining technique. The results were that in 16 eyes of quiescent HSK, the HSV antigen was negative, and in 11 of 20 corneas with active HSK, the HSV antigen was positive. When 5 corneas with quiescent HSK were cultured in vitro, 3 again became HSV antigen positive. The findings may be useful in the treatment of HSK.
Penetrating keratoplasty (PKP) in conjunction with postoperative corticosteroids may reactivate latent herpes simplex virus type 1 (HSV-1) to cause persistent postoperative epithelial defects. The clinical diagnosis of HSV keratitis after penetrating keratoplasty is difficult because the postoperative appearance may be nondendritic and, therefore, not characteristic of HSV-1 infection. Presently, the most reliable method to diagnose HSV-1 under these conditions is to culture eyes for the presence of HSV-1. To determine the coincidence of positive HSV-1 ocular cultures with HSV-1 epithelial defects, 15 rabbits (20 eyes) latently infected with HSV-1 underwent autograft PKP with postoperative corticosteroids. Daily ocular cultures and slit-lamp examinations were performed on postoperative days 1-8 and 10. Viral shedding occurred in 15 of 19 (79.0%) of the eyes postoperatively. Superficial punctate keratopathy (SPK) was observed in 19 of 19 (100%) of the eyes and coincided with positive HSV-1 cultures 24% of the time. Dendritic lesions were observed in three of 19 (15.8%) of the eyes; the dendrites coincided with positive HSV-1 cultures 60% of the time. Finally, epithelial ulcers were seen in eleven of 19 (57.9%) of the eyes, thus coinciding with HSV-1 positive cultures 29% of the time. The greatest coincidence of positive HSV-1 cultures with nondendritic epithelial lesions occurred on postoperative day number 4. The results suggest that an epithelial lesion following PKP and postoperative corticosteroids could represent HSV infection, even if a single HSV ocular culture is negative.
A herpes simplex stromal keratitis rabbit model, which was produced by intrastromal injection of live virus, was used to evaluate the effects of local antivirals on the natural course of the disease. Topical trifluridine (trifluorothymidine) and vidarabine monophosphate (adenine arabinoside monophosphate), when given early and frequently, suppressed the disease, indicating that viral replication was important in initiating the disease. However, seven days after the stromal disease had begun to develop, neither drug had an appreciable effect. Since the early drug effect had suggested adequate drug penetration, the abscence of drug effect later in the disease indicates that viral multiplication may not be important in maintaining the disease. Immunologic reactions may control the disease once the cornea is antigenically altered by the initial infection. Subconjunctivally injected trifluridine was not effective.