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Biomedical subjects

Herbert E Kaufman

Publications and source records attributed to Herbert E Kaufman.

At least 19 recordsLinked to original sources

Healing process at the flap edge in its influence in the development of corneal ectasia after LASIK.

PURPOSE: Post-laser in situ keratomileusis (LASIK) corneal ectasia is a progressive deformation of the gross corneal anatomy that occurs after surgery. However, this is a rare event even after deep lamellar keratoplasty. We hypothesize that the strength of the lamellar keratoplasty wound is derived from the sutures that enhance the wound edge healing response. This study compares, in a rabbit model, the stability of previously sutured and unsutured microkeratome flaps. METHODS: Unilateral 160-micro m-thick LASIK flaps using a mechanical microkeratome was performed in 20 rabbit eyes. Animals were then divided in two groups: In group A, the flap was left without sutures. In group B, the flap was sutured with 12 interrupted 10/0 nylon stitches that were removed after 3 weeks under general anesthesia. Six weeks after surgery, all rabbits had corneal topographies performed at their baseline intraocular pressure (IOP) (14 mmHg) and at two artificially increased pressures (25 and 45 mmHg) using an anterior chamber maintainer implanted in the inferior limbal area. The animals were humanely euthanized, and immunohistological analysis of the corneas was performed. RESULTS: A delta K1 value, which indicates the difference in the simulated keratometric value at baseline and the one measured at 25 mmHg, was calculated for all eyes. It showed a mean steepening effect of 2.74 D +/- 0.38 D in group A compared with 1.08 D +/- 0.27 D in group B (p < 0.05). Similarly, a delta K2 value, which indicates the difference in the simulated keratometric value at baseline and the one obtained at 45 mmHg, was registered. It showed a mean steepening effect of 3.02 D +/- 0.87 D in group A compared with 0.75 D +/- 0.44 D in group B (p < 0.05). Six weeks after surgery, the peripheral flap interface in group B consisted of 14.3% +/- 4.15% of positive monoclonal mouse anti-alpha smooth muscle actin (alpha-SMA) cells compared with 4.18 +/- 3.76% in group A (p < 0.05). CONCLUSIONS: The addition of sutures in the corneal flap after LASIK appears to reduce the amount of corneal steepening when the IOP is artificially increased up to 25 mmHg in this rabbit model. Our results suggest that an increase in the amount of myofibroblastas induced by the sutures may be responsible for this behavior. Corneal ectasia may be related to the clinically observed lack of corneal wound-healing at the edge of the flap that allows the cornea to bulge. By stimulating a stronger wound-healing response at the edge of the flap, the cornea may better resist steepening under increased IOP conditions and improve the long-term stability of LASIK surgery in borderline thin corneas.

Actins↗

The use of the Fugo Blade in corneal surgery: a preliminary animal study.

PURPOSE: To evaluate the performance of the Fugo Blade in cutting corneal tissue in animals, both in vitro and in vivo. METHODS: Corneal incisions were made on pig eyes using the Fugo Blade. The histologic characteristics of these cuts were then evaluated. Similar cuts were also performed in rabbit corneas in vivo and compared with cuts performed with mechanical blades. The rabbits were euthanized, and the corneas were obtained for histopathologic examination 14 days after surgery. RESULTS: Slit-lamp examinations and histologic findings showed that the Fugo Blade can produce sharp cuts in the cornea with minimal tissue damage beyond the edges of the incisions. It cuts without resistance and permits normal wound healing. CONCLUSIONS: Although the Fugo Blade is currently approved by the Food and Drug Administration for anterior capsulotomy, our study demonstrates that the Fugo Blade can safely and quickly produce resistance-free cuts in corneal tissue in animals, opening additional avenues for use of this device in corneal surgery.

Animals↗

How has confocal microscopy helped us in refractive surgery?

PURPOSE OF REVIEW: To summarize the known uses of in-vivo confocal microscopy in refractive surgery, highlighting the current developments in the field. RECENT FINDINGS: Examination of the cornea after laser in-situ keratomileusis demonstrated that the keratocyte density within the laser in-situ keratomileusis flap and anterior residual corneal bed continued to decline during the entire 3-year period of the study. The progressive loss of keratocytes in the flap and anterior portion of the residual corneal bed could have long-term implications in terms of corneal stability, refractive stability and cellular integrity after laser in-situ keratomileusis. Additional studies showed that the density of sub-basal nerves decreased by 90% 1 month after laser in-situ keratomileusis. At some point between 3 and 6 months after laser in-situ keratomileusis, the sub-basal nerves began to recover and by 2 years they had reached approximately 50% of their original preoperative density. Analysis of sub-basal nerve density after photorefractive keratectomy reported that the nerve density completely recovered to preoperative levels by 2 years. Other confocal microscopic studies demonstrated that the microscope can detect infectious organisms in vivo, without stains or dyes. SUMMARY: The confocal microscope is a unique diagnostic instrument that can be used to evaluate corneal healing, long-term stability and to assess complications after refractive surgery. The ability of the device to view in-vivo cellular detail, microorganisms, inflammatory cells, epitheliod cells, fibrosis and measure the postoperative thickness of the residual corneal bed after laser in-situ keratomileusis, in a noninvasive manner, highlights the unique capabilities of this instrument.

Cornea↗

Immunohistochemical analysis of orbital connective tissue specimens of patients with active Graves ophthalmopathy.

PURPOSE: To explore the immune mechanism of Graves ophthalmopathy (GO) by analyzing infiltrating cells in orbital connective tissue (OCT) specimens of patients with active GO using immunohistochemical methods. METHODS: Five OCT specimens obtained from patients with active GO and five control specimens obtained from forensic cadavers who died from nonmedical reasons were stained with anti-CD3, CD4, CD8, CD45RO, HLA-Dr, CD25, and TNF-alpha monoclonal antibodies. Positively stained cells were counted and results were interpreted as cell counts/mm2. Four of five GO patients had never been treated with any immunomodulating therapy. Only one had received oral prednisolone prior to tissue sampling, but this treatment had ceased 5 months before surgery. RESULTS: The retro-orbital tissue specimens obtained from forensic cadavers did not show any significant positive staining for any monoclonal antibody tested. However, the specimens from GO patients showed positively stained means of 36.66 +/- 4.61 HLA-Dr+, 12.8 +/- 3.42 CD8+, 11.8 +/- 1.78 CD4+, 16.6 +/- 1.81 CD3+, 21.2 +/- 3.12 CD45RO+, 10.4 +/- 2.07 TNF-alpha+, 7.2 +/- 1.48 CD25+, 3.2 +/- 1.09 CD4+CD8+, 4.6 +/- 1.67 CD4+CD45RO+, 2.8 +/- 0.83 CD8+CD45RO+, 1.6 +/- 0.89 CD4+CD25+, and 1.8 +/- 1 0.83 CD8+CD25+ cells/mm2. CONCLUSIONS: Our study supports that most of the infiltrating lymphocytic cells in the active stage of GO are T cells, and a significant proportion of them are CD45RO+ cells. Infiltration of OCT by HLA-Dr+, CD25+, and TNF-alpha cells suggests that Th1-type immune reaction with the interference of proinflammatory cytokine(s) (TNF-alpha) may be important in the pathogenesis of disease. Further studies are needed to understand the disease pathogenesis and may provide a scientific basis for future treatment alternatives for the disease (e.g., anti-cytokine treatment).

Antibodies, Monoclonal↗

Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation.

Recurrent herpes virus infection, in which the virus reactivates from the nervous system and causes painful lesions in peripheral tissues, is a significant clinical problem. Our recent studies showing that the amount of cyclooxygenase 2 (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib, have indicated that the prostaglandin synthesis pathway--and in particular COX-2--may be an intermediate in the pathway to herpes viral reactivation. To further study this process, we infected the corneas of mice using topical application to a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1 (HSV-1) latency to be established in the trigeminal ganglia. Prior to the induction of viral reactivation, the mice were treated orally with celecoxib. Treated and untreated mice were induced to undergo reactivation by immersion in 43 degrees C water for 10 min. The shedding of virus at the ocular surface was determined by culturing ocular swabs with indicator cells. The presence of infectious virus in the trigeminal ganglion was evaluated by incubating ganglion homogenates with indicator cells and observing for cytopathic effect. Celecoxib treatment significantly suppressed viral reactivation when given prophylactically by the gastrointestinal route. The numbers of corneas and ganglia containing infectious virus were significantly lower in the celecoxib-treated animals, compared to the placebo-treated mice. These experiments demonstrate that a selective COX-2 inhibitor can suppress hyperthermic stress-induced herpes viral reactivation in the nervous system. It may be possible to use COX-2 inhibitors to prevent viral reactivation in high-risk patients by drug prophylaxis.

Animals↗

Topical tacrolimus ointment for treatment of refractory anterior segment inflammatory disorders.

PURPOSE: To report 4 cases of patients treated with topical tacrolimus ointment 0.03% for ocular inflammatory conditions refractory to traditional treatment. METHODS: Four patients were treated topically with tacrolimus 0.03% ointment twice daily: 2 patients with blepharokeratoconjunctivitis, 1 patient with severe atopic keratoconjunctivitis, and 1 patient with chronic follicular conjunctivitis. RESULTS: Three patients had a dramatic improvement of their ocular condition as early as 2 weeks after starting tacrolimus ointment. One patient developed a herpes simplex virus dendrite after 1 week of tacrolimus use. CONCLUSION: Tacrolimus ointment appears to be an effective alternative for certain ocular inflammatory conditions refractory to traditional treatments. There may be an increased risk of herpes simplex virus keratitis associated with topical use. Our results support previous literature of patients benefiting from topical tacrolimus use.

Administration, Topical↗

Preliminary in vitro evaluation of 2-octyl cyanoacrylate (Dermabond) to seal corneal incisions.

OBJECTIVE: To compare the efficacy of Dermabond with conventional nylon sutures for sealing linear corneal incisions. METHODS: A keratome knife was used to create a 4-mm full-thickness linear corneal incision anterior to the limbal arcade in 20 fresh pig eyes. The incision was sealed with Dermabond tissue adhesive or closed with 10-0 nylon sutures. A 27-gauge needle connected via tubing to a bottle containing balanced salt solution (BSS) was inserted into the anterior chamber. Infusion pressure was controlled by varying the height of the column of BSS. The tensile strength of the incisions was measured by increasing the infusion pressure to the point where leakage was noted. RESULTS: The mean height at which leakage was detected was 100.20 +/- 31.19 cm H(2)O (equivalent to a pressure of 73.70 +/- 22.99 mm Hg) for the nylon suture group (n = 10 eyes) and 113.80 +/- 31.20 cm H(2)O (equivalent to a pressure of 83.71 +/- 22.95 mm Hg) for the Dermabond group (n = 10 eyes). The difference was not significant (P = 0.343). CONCLUSIONS: The mean leakage pressures were comparable for the 2 groups. Either method of closure should be able to withstand any postoperative increases in intraocular pressure. Dermabond adhesive may be considered as an alternative to conventional sutures in corneal wound closure.

Animals↗

HSV-1 DNA in tears and saliva of normal adults.

PURPOSE: To assess the frequency of shedding of herpes simplex virus type 1 (HSV-1) DNA in tears and saliva of asymptomatic individuals. METHODS: Fifty subjects without signs of ocular herpetic disease participated. Serum samples from all subjects were tested for HSV IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and for HSV-1 by neutralization assay. HSV-1 DNA copy number and frequency of shedding were determined by real-time polymerase chain reaction (PCR) analysis of tear and saliva samples collected twice daily for 30 consecutive days. RESULTS: Thirty-seven (74%) of the 50 subjects were positive for HSV IgG by ELISA. The percentages of positive eye and mouth swabs were approximately equivalent: 33.5% (941/2806) and 37.5% (1020/2723), respectively. However, the percentage of samples with high HSV-1 genome copy numbers was greater in saliva than in tears, which may have been a result of the sample volume collected. Shedding frequency in tears was nearly the same in men (347/1003; 34.6%) and women (594/1705; 34.8%); in saliva, men had a higher frequency of shedding (457/1009; 45.3% vs. 563/1703; 33.1%, men versus women). Overall, 49 (98%) of 50 subjects shed HSV-1 DNA at least once during the course of the 30-day study. CONCLUSIONS: The percentage of asymptomatic subjects who intermittently shed HSV-1 DNA in tears or saliva was higher than the percentage of subjects with positive ELISA or neutralization antibodies to HSV. Because most HSV transmission occurs during asymptomatic shedding, further knowledge of the prevalence of HSV-1 DNA in tears and saliva is warranted to control its spread. Shedding is simple to study, and its suppression may be an efficient way to evaluate new antivirals in humans.

Adult↗

Corneal healing after uncomplicated LASIK and its relationship to refractive changes: a six-month prospective confocal study.

PURPOSE: To investigate corneal healing and the factor(s) possibly responsible for refractive changes after laser in situ keratomileusis (LASIK). METHODS: Twenty eyes of 10 patients who underwent LASIK for myopia were examined clinically and by real-time confocal microscopy for 6 months. Epithelial and posterior stromal thicknesses and the thickness of the keratocyte activation zone were measured, and refractive changes were compared with these values. Keratocyte morphology, flap thickness, and subbasal nerve fiber bundle morphology after LASIK were also investigated. RESULTS: No significant change was detected over time in epithelial thickness after LASIK treatment; however, the posterior stromal thickness was found to be significantly higher 1 month after surgery. A slight but statistically significant negative correlation was detected between the thickness of the keratocyte activation zone and the spheroequivalent refraction after LASIK. The subbasal nerve fiber bundle's morphology returned to its preoperative appearance 6 months after LASIK, but in the flap stroma the nerve fiber bundle morphology remained abnormal at 6 months after LASIK surgery. CONCLUSIONS: A weak but significant negative correlation between the thickness of the keratocyte activation zone and spheroequivalent refraction was found after LASIK. The different refractive properties of activated keratocytes may be responsible for the myopic shift after LASIK. Further studies are needed to clarify this hypothesis.

Adult↗

The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study.

PURPOSE: To investigate whether conjunctival inflammation represents a primary event in the pathogenesis of keratoconjunctivitis sicca or whether it is a secondary inflammatory reaction caused by enhanced mechanical irritation as a result of surface dryness and whether anti-inflammatory drops (corticosteroids and nonsteroidal anti-inflammatory) have therapeutic effects and are similar. DESIGN: Single-masked, randomized, prospective clinical trial. METHODS: Thirty-two keratoconjuctivitis patients with or without Sjögren syndrome were included in the study. The patients were randomized to three groups. Group 1 patients received a topical artificial tear substitute (ATS); group 2 received ATS plus nonsteroidal anti-inflammatory drops (NSAID); and group 3 received ATS plus topical corticosteroidal drops. The eye symptom severity scores, Schirmer test values, rose bengal and fluorescein staining scores were evaluated before treatment and 15 and 30 days after start of treatment. Impression cytology specimens were stained using immunohistochemical methods to detect the percentages of human leukocyte antigen II (HLA-DR) positive, Apo 2.7 positive, and periodic acid-Schiff positive cells. Statistical analyses were performed within and between groups. Group 3 patients had significantly lower symptom severity scores, fluorescein and rose bengal staining, and HLA-DR positive cells on days 15 and 30 compared with patients in other groups. They also had a significantly higher number of periodic acid-Schiff positive (goblet) cells in their impression cytology specimens on days 15 and 30 compared with the other patients. On day 30, group 3 patients had significant differences compared with their baseline measurements in terms of above-mentioned parameters. However, we did not detect a significant effect of any treatment schedule on the Shirmer test value and the numbers of Apo 2.7 cells in impression cytology specimens. CONCLUSION: Topical corticosteroids had a clearly beneficial effect both on the subjective and objective clinical parameters of moderate-to-severe dry eye patients. These effects were associated with the reduction of inflammation markers of conjunctival epithelial cells.

Administration, Topical↗

The effect of roscovitine on herpetic keratitis.

To determine the effect of roscovitine, a potent antiviral in tissue culture administered intramuscularly to rabbits or by eye drops to mice for the treatment of herpetic keratitis this study was commenced.New Zealand white rabbits infected with McKrae strain herpesvirus (HSV-1) were treated twice a day with 10mg Roscovitine or vehicle from day 3 to 7, or 1% trifluridine eye drops five times a day. Severity of keratitis was graded daily by a masked observer. ICR strain mice were randomized into 14 groups. Both corneas of the mice were scarified with a 25-gauge needle, and were inoculated with the KOS strain of HSV-1. Roscovitine was dissolved in Cremophor((R)) and tissue culture medium. Group 1A, 1B, 2A, and 2B mice were treated eight times daily with either 800 micro M Roscovitine or its vehicle. Trifluridine treated animals (groups 3A and 3B) received topical treatment five times daily. In groups 1A-3B, the treatment was begun two days prior to or two days after viral inoculation. Mice were examined on days 2, 3, 5, and 9 after infection. In rabbits, the severity of keratitis in animals treated with intramuscular roscovitine was not significantly different from that in vehicle-treated animals except on day 7 (p=0.0460). In mice, there was no significant difference between roscovitine and vehicle treatment at any time point studied. However, the trifluridine treated mice had significantly lower scores compared to the roscovitine or vehicle-treated mice. Although roscovitine dramatically suppresses viral replication in tissue culture studies, in vivo this drug failed to alter the course of HSV keratitis in rabbits or mice. Considering high cost of roscovitine and the poor efficacy in these experiments, we feel that roscovitine is not feasible antiviral agent for today.

Analysis of Variance↗

Human fibrin tissue adhesive for sutureless lamellar keratoplasty and scleral patch adhesion: a pilot study.

PURPOSE: To determine whether a fibrin adhesive can facilitate the performance of sutureless lamellar keratoplasty and attachment of amnion to bare sclera. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Six patients, 5 of whom underwent lamellar keratoplasty and 1 who received an amniotic patch of the sclera and cornea. Institutional review board approval was not required for these therapeutic treatments. METHODS: In 5 patients, the epithelium was removed from the corneal surface, a free cap, 200- micro m thick, was cut with a microkeratome, and a human fibrin tissue adhesive (Tisseel VH Fibrin Sealant; Baxter Healthcare Corporation, Glendale, CA) was applied to the cut surface of the corneal stroma. A 200- micro m thick, microkeratome-cut lamellar graft was placed in the stromal bed without sutures, and a bandage soft contact lens was applied. The lens was left in place for 1 week and then removed. In 1 patient, the adhesive was applied to bare sclera for attachment of amniotic membrane after removal of a conjunctival melanosis. All patients were followed up for 3 months after surgery. MAIN OUTCOME MEASURES: Tissue adhesion, corneal clarity, and visual acuity. RESULTS: All 5 lamellar grafts healed and remained clear, although final visual acuity varied with visual potential and astigmatism. The amniotic membrane graft also adhered well to the bare sclera. CONCLUSIONS: The fibrin adhesive provided satisfactory attachment without sutures for lamellar keratoplasty and amniotic patching. It should be effective for sealing of clear cornea incisions, LASIK flaps, and conjunctival and skin grafts. An adhesive that has been designed specifically for ophthalmic applications and is more convenient to use would be desirable.

Adolescent↗

Comparison of efficacy of topical and oral fluconazole treatment in experimental Aspergillus keratitis.

PURPOSE: To investigate the therapeutic role of topical and oral fluconazole treatment using a rabbit model of Aspergillus fumigatus keratitis. METHODS: Aspergillus fumigatus spores were injected into the corneal stroma of the right eye of 20 rabbits. Forty-eight hours later the rabbits were randomly divided into three groups. Group 1 rabbits (six) were treated with topical fluconazole (2 mg/ml, eight times daily), group 2 rabbits (seven) received oral fluconazole (37.5 mg/kg bid), and group 3 rabbits (seven) were untreated controls. The eyes were examined and photographed with a slit-lamp 2, 6, 10, 16, and 20 days after inoculation and an observer graded the corneas in a masked fashion. Corneal cultures were taken on days 2, 14, and 20 for fungus growth. RESULTS: At the beginning of treatment, the slit-lamp scores did not differ among three groups. However, on days 6, 10, 16, and 20 the treated groups had statistically significant lower scores compared to the untreated controls. No significant difference was observed between topical and oral treated groups at any examination point. All cultures were positive on day 2, but on days 16 and 20, there were significantly lower positive fungal cultures in both treatment groups compared to the control (p < 0.01, chi square test). CONCLUSION: Our study showed that both topical and oral fluconazole were effective in lessening the severity of fungal keratitis in a rabbit model and should be considered effective treatment alternatives in the therapy of Aspergillus fumigatus keratitis.

Administration, Oral↗

Human fibrin tissue glue for corneal lamellar adhesion in rabbits: a preliminary study.

PURPOSE: To evaluate the use of a human fibrin tissue adhesive in the adherence of corneal lamellar flaps in rabbit eyes. METHODS: Corneal flaps were made using a microkeratome in both eyes of six New Zealand white rabbits. In the right eyes, the flaps were glued with fibrin tissue adhesive; in the left eyes, flaps were allowed to heal without adhesive (controls). All eyes were treated with antibiotics and steroids once daily for 10 days. Slit-lamp biomicroscopy was performed 1 and 10 days after surgery. The rabbits with surviving flaps were euthanized and the corneas obtained for histopathologic examination 10 days after surgery. RESULTS: Slit-lamp examinations showed no interface deposits and no other signs of corneal toxicity. Histologically, a few inflammatory cells were seen in both the experimental and control eyes, and microscopic gapping and tissue debris were observed in three of the six control eyes. CONCLUSIONS: Human fibrin tissue glue was well tolerated in these eyes, with no or minimal corneal toxicity. Further studies are needed to determine the tensile strength of the adhesive bond in the cornea.

Animals↗

Differences in contact lens-induced responses in the corneas of Asian and non-Asian subjects.

PURPOSE: To investigate ethnic differences in corneal endothelia bleb formation and corneal swelling during contact lens wear under closed-eye conditions, with the use of lenses of varying oxygen transmissibilities (Dk/L) in Asian and non-Asian subjects METHODS: Asian and non-Asian contact-lens naive subjects were fitted with one of four different types of contact lenses at each 20-minute session. During lens wear, the eyelid was closed Endothelial bleb formation was determined by specular microscopy or confocal microscopy immediately on eye opening. Some Asian contact-lens naive subjects were asked to wear one of two types of lenses (Dk/L values of 24 and 175) on each eye for 1 hour Corneal swelling was determined immediately after opening of the eyes. RESULTS: Asian subjects had a significantly higher degree of endothelial bleb formation than the non-Asian population for all closed eye conditions, p=0.0001. There was no significant difference in endothelial bleb formation between closed eves with or without lenses in the non-Asian population. There was a significantly higher degree of bleb formation with low Dk/L lenses, < or = 40, compared to high Dk/L lenses, > or = 110, in Asian subjects, p=0.0001. CONCLUSIONS: There is a significant difference between Asian and non-Asian subjects in the corneal response to stress. Under a closed eyelid only contact lenses with very high levels of Dk/L do not cause cornea stress in Asian patients.

Black or African American↗