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Biomedical subjects

D S Rootman

Publications and source records attributed to D S Rootman.

At least 37 records · Page 2Linked to original sources

The prevalence of positive hepatitis B, hepatitis C, and HIV serology in cornea donors prescreened by medical and social history in Ontario, Canada.

PURPOSE: To determine the prevalence of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) in the serum of cornea donors who had been previously screened by social and medical history by the Eye Bank of Canada, Ontario Division. METHOD: A retrospective examination of the donor records of the Eye Bank of Canada, Ontario Division, was conducted. A total of 3,228 records were examined covering the period from May 17, 1993 to May 31, 1996. RESULTS: The prevalence of HBV was determined to be 0.25%, HCV, 0.93%; and HIV, 0.031%. CONCLUSION: The data revealed that despite the use of medical and social history to prescreen, a small percentage of prescreened donors test serologically positive. A comparison of the prevalence of HBV, HCV, and HIV in the prescreened cornea donors to a similarly screened cohort of blood donors over a similar time period reveals a higher prevalence in all three diseases in the cohort of cornea donors. An examination of the demographic characteristics of the population as a whole versus the three groups with confirmed serology failed to show a significant difference between the seropositive and seronegative groups. This study confirms the value and necessity of serologic prescreening of cornea donors as is currently the standard of practice.

Adolescent↗

Endothelial cell analysis of corneas from donor eyes with an intraocular lens: a comparative study.

PURPOSE: Many eyes are received from patients who have undergone cataract surgery. Few data document the endothelial cell characteristics in these donor eyes, which have previously been disqualified for transplantation. We compared the endothelial characteristics of the corneas from eyes with intraocular lenses (IOLs) with a group of matching controls. METHODS: The corneal endothelial characteristics, including cell density, polymegethism, and pleomorphism, were prospectively obtained in 15 corneas from eyes with IOL implants and compared with 17 phakic control eyes. RESULTS: The mean cell densities (+/-SD) were 2,495 +/- 438 cells/mm2 for the eyes with implants and 2,576 +/- 264 cells/mm2 for the controls. The mean coefficient of variation was 0.307 +/- 0.04 and 0.323 +/- 0.04 for IOL and control group, respectively. No significant difference was found between the two groups (t test, power = 0.97 in detecting a mean difference of 20%). CONCLUSION: Many eyes with IOLs have endothelial cell densities comparable to those of phakic eyes. A decision to use specific corneas should be made individually based on endothelial cell analysis. Previous ocular surgery may not disqualify a corneal donor.

Aged↗

Pharmacokinetic differences between ocular inserts and eyedrops.

Controlled release ocular inserts have been found to increase the amount of drug which is absorbed into the aqueous humour when compared to eyedrops. Systemic absorption following delivery using a controlled release insert has been found to be dependent on the release rate of the insert. The objective of this study was to determine if ocular inserts affect drug absorption into other ocular tissues such as the conjunctiva and iris-ciliary body. Ocular absorption studies were performed using albino rabbits and ethylene-vinyl acetate controlled release devices containing timolol maleate. A compartmental model previously developed to simulate ocular absorption following eyedrop administration was modified and used to simulate these experiments. The conjunctival absorption coefficient calculated by the model and the AUC of the conjunctiva per mumol of delivered drug were found to be 2.7 and 42 times higher, respectively, for the ocular insert as compared to eyedrop administration. The increased conjunctiva absorption was likely the result of reduced tear mixing, which caused a high local concentration of timolol between the insert and the conjunctiva. The AUC of the iris-ciliary body per mumol of delivered drug was found to be 24 times higher for the ocular inserts as compared to eyedrop administration. The AUC of the iris-ciliary body was found to be 1.4 times higher than the AUC of the aqueous humour for eyedrop administration, but 9 times greater for delivery via the ocular inserts. Thus, the increased absorption into the iris-ciliary body and aqueous humour observed for ocular inserts is partially the result of an increase in the amount of drug which enters these tissues via penetration across the conjunctiva and sclera.

Absorption↗

Perfluorodecalin corneal toxicity: five case reports.

Perfluorodecalin is a perfluorocarbon liquid used intraoperatively in retinal detachment repair. It is usually removed at the end of the procedure; however, residual amounts may be retained when poor corneal clarity or intraocular hemorrhage obscures the view. No clinical reports exist on the consequences of retained perfluorodecalin in the anterior segment. We report five cases in which perfluorodecalin was in prolonged contact with the cornea. The period of time for corneal pathology to occur and the role perfluorodecalin played in the etiology of such changes is discussed. A total of 348 patients with retinal detachments in one retinal practice underwent repair using pars plana vitrectomy combined with intraoperative perfluorodecalin between January 1992 and May 1994. Postoperatively, residual perfluorodecalin was observed in the anterior chamber in contact with the corneal endothelium in five patients. The patients were followed clinically for a period of up to 18 months. Four of five patients developed corneal changes from prolonged contact with perfluorodecalin. Corneal edema developed in the area perfluorodecalin-endothelial contact in three of five eyes. The period of perfluorodecalin-endothelial contact before corneal decompensation occurred ranged from 4 to 13 weeks. Two eyes required penetrating keratoplasties for progressive corneal edema. Corneal edema was reversed in one eye after removal of perfluorodecalin from the anterior chamber via multiple paracentesis. One of the remaining eyes developed deep corneal vascularization without edema in the area of perfluorodecalin contact after 12 months. These observations suggest that corneal toxicity may be induced by intraocular perfluorodecalin if it is allowed direct contact with the corneal endothelium for periods as short as 1 month. Some of these changes may be reversible if perfluorodecalin is aspirated from the anterior chamber. Further investigations are required to examine perfluorodecalin-induced corneal toxicity.

Adult↗

Antimetabolite interactions with epidermal growth factor.

Antimetabolites such as 5-fluorouracil and mitomycin C are known to delay wound healing. Epidermal growth factor (EGF) has been shown to accelerate corneal epithelial wound healing. This study was designed to investigate the effects of EGF on corneal epithelial healing that has been modified by antimetabolite treatment. New Zealand White rabbits were pretreated with either saline (controls) or 5-fluorouracil (5FU) injected subconjunctivally, or mitomycin C (MMC) applied topically. Circular anterior stromal wounds were created, followed by a 6-hour perfusion of normal saline or 50 micrograms/ml of EGF. Subconjunctival saline or 5FU, or topical MMC treatments were continued after wounding for a total of 6 days. Corneas were photographed and quantitative morphometry of the wound site was performed. Compared with saline controls, MMC significantly delayed wound healing (P < 0.05) whereas 5FU did not (P > 0.05). Compared with 5FU, MMC significantly delayed wound healing with either normal saline or EGF perfusion (P < 0.05). In the presence of either 5FU or MMC, EGF perfusion had no significant effect on the corneal wound-healing rate (P > 0.05). Corneal wound healing is not affected by subconjunctivally injected 5FU while it is delayed by topically applied MMC. EGF treatment does not overcome the inhibitory effects of MMC. EGF therapy may not be useful in the treatment of complications related to antimetabolite therapy.

Administration, Topical↗

In-vitro comparative study of a locally prepared corneal storage medium and Optisol.

OBJECTIVE: To compare the in-vitro safety and efficacy of two corneal storage media, Optisol and H-Sol, a chondroitin-sulfate-based medium containing hydrocortisone prepared at the Eye Bank of Canada (Ontario Division). DESIGN: Twenty paired corneas from human donors (mean age 67.9 years) were randomly assigned for storage in corneal viewing chambers at 4 degrees C in Optisol (10 corneas) or H-Sol (10 corneas). The storage media were masked, and all measurements were done in a blinded fashion. OUTCOME MEASURES: Corneal clarity and thickness (measured at 0, 2, 4, 8 and 12 days), endothelial cell density and morphology (analysed at days 0 and 12). At day 12 cell viability was determined by staining with trypan blue and alizarin red S, and three randomly selected corneas from either medium were examined by scanning electron microscopy and transmission electron microscopy. RESULTS: Corneal thickness increased significantly from day 0 to day 12 in both Optisol and H-Sol, and corneal clarity decreased significantly in both media over this period (p < 0.05). At days 2, 4, 8 and 12 the corneas stored in Optisol were significantly thinner than those stored in H-Sol (p < 0.05). There were no significant differences between the media in any of the other indices studied. Endothelial cell density decreased significantly in both Optisol and H-Sol (p < 0.05). There were no within-group differences in percentage of cell loss, coefficient of variation of cell area, figure coefficient or percentage of hexagonal cells. CONCLUSIONS: The difference in corneal thickness between Optisol and H-Sol may have been due to the higher concentration of chondroitin sulfate in the former (2.5%, compared with 2% in H-Sol) or perhaps to the addition of other components to Optisol that are not present in H-Sol. Efforts continue to improve the formulation of H-Sol. Further studies are necessary to assess its safety and efficacy in vivo.

Aged↗

Clinical outcomes following penetrating keratoplasty using the Barron-Hessburg and Hanna corneal trephination systems.

Two corneal suction trephination systems currently in use are the Barron-Hessburg and the Hanna trephine. This study assessed the outcome of patients who received penetrating keratoplasty using these two systems. One hundred twenty-four eyes (62 with the Hanna system, 62 with the Barron-Hessburg system) from 98 patients undergoing penetrating keratoplasty were evaluated retrospectively. Best corrected spectacle acuity and corneal astigmatism were assessed 6 and 12 months after surgery. No significant difference was noted between the groups 6 months after surgery. At 12 months, a significant improvement in spectacle acuity was present with 55% of the Hanna group having visual acuity of 20/40 or better compared with 33% of the Barron-Hessburg group (p < 0.005). This difference was greater if eyes having the best visual prognoses were separately evaluated: 74% of the Hanna group had 20/40 vision or better compared with 41% of the Barron-Hessburg group (p < 0.005). In eyes having a good visual prognosis, a significant improvement in visual acuity was present, with 33% of the Hanna group improving nine or more lines compared with 9% of the Barron-Hessburg group (p < 0.05). Postoperative keratometric and refractive astigmatism were not different at 6 or 12 months. We found that visual recovery at 1 year is better using the Hanna system, especially in eyes with good visual prognoses.

Adult↗

A compartmental model for the ocular pharmacokinetics of cyclosporine in rabbits.

Studies were conducted in rabbits to determine the ocular distribution and elimination of cyclosporine, with the objective of developing a comprehensive pharmacokinetic model. Following a bolus dose into the anterior chamber, drug levels were measured in the aqueous humor, cornea, iris/ciliary body, lens, sclera, and conjunctiva. Cyclosporine was rapidly eliminated from the aqueous, but drug levels in ocular tissues persisted for in excess of 48 hours, particularly in the cornea and iris/ciliary body. The terminal elimination half life from these tissues was 45 hr and 30 hr, respectively, providing evidence that these tissues could act as a reservoir for the drug. It was found that a compartmental model accurately described the experimental data. A single compartment was used for each of the tissues and fluids sampled, except for the cornea, which was subdivided into two compartments, representing its tissue and aqueous regions.

Animals↗

Infectious crystalline keratopathy following trabeculectomy and low-dose topical steroids.

A case of infectious crystalline keratopathy in a patient who had undergone trabeculectomy without 5-fluorouracil is described. Chronic low-dose topical steroids were employed. Crystalline keratopathy occurring in this setting has not been previously described. A 73-year-old diabetic women presented with feathery crystal-like corneal infiltrates. These were cultured and treated with antibiotics based on the sensitivities. The cultures showed a nutritional variant of Streptococcus that was difficult to grow on routine culture plates. It was sensitive to vancomycin. Resolution of the infection occurred with topical treatment. Infectious crystalline keratopathy is a rare but classical corneal infection. The microbiological characteristics that give rise to its clinical appearance and laboratory characteristics are discussed. A rationale for diagnosis and treatment is suggested.

Administration, Topical↗

Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy.

BACKGROUND: Haemophilus aphrophilus is a rare cause of ocular infection. It has been reported once as a cause of late-onset endophthalmitis in a patient with an inadvertent bleb after cataract surgery. We present a case of Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy. METHODS: A 56-year-old woman presented with a bleb infection 10 weeks after a mitomycin C augmented trabeculectomy at a University tertiary referral practice of one of the authors (GET). The causative organism was Haemophilus aphrophilus, identified by the Toronto Public Health Laboratory, Ontario, Canada. RESULTS: The bleb infection resolved following topical, subconjunctival and intravenous antibiotic therapy. A formal bleb revision was required to repair a persistent bleb leak. CONCLUSION: Patients who have had trabeculectomies augmented with mitomycin C may be predisposed to bleb infection with unusual organisms. Prompt diagnosis and treatment is necessary to control the infection. Increased awareness and communication with laboratory personnel may increase the isolation of this fastidious organism.

Anti-Bacterial Agents↗

Comparative cytoprotection of cultured corneal endothelial cells by water-soluble antioxidants against free-radical damage.

We reported previously that purpurogallin (PPG) markedly protects the cultured rabbit corneal endothelial cells (RCEC) against oxyradical damage generated with hypoxanthine (HX) and xanthine oxidase (XO)(1). In this study, we further compared the cytoprotective activities of PPG versus Trolox (TX, alpha-tocopherol, a water-soluble analogue of vitamin E) and ascorbate (Asc) in confluent cultured RCEC with phase contrast microscopy and confirmed by transmission electron microscopy. PPG prolonged survival of the oxyradical damaged cells longer than those without PPG present (18.6 +/- 1.4 min at 1.0 mM and 11.2 +/- 1.0 at 0.25 mM respectively vs. 7.3 +/- 0.8 min in control). At levels equimolar to PPG, TX, and Asc were less effective in delaying cell necrosis caused by HX and XO (p < 0.01). When exposed to superoxide radicals generated by menadione, RCEC necrosed at 29.8 +/- 1.5 min compared to PPG 47.2 +/- 1.0 min at 1.0 mM and 38.9 +/- 1.0 min at 0.25 mM. This was significantly different from TX and Asc at corresponding concentrations (p < 0.01). PPG scavenges not only HX-XO-generated oxyradicals, but also nonenzymatically produced superoxide radicals, more actively than two well known antioxidants--TX and Asc.

Animals↗

Comparative antioxidant protection of cultured rabbit corneal epithelium.

Oxygen-free radicals may injure the epithelium of corneas in storage awaiting transplantation. This study compared the cytoprotective effects of several antioxidants against oxygen-free radical injury to rabbit corneal epithelial cells in vitro. Cultured rabbit corneal epithelial cells were exposed to oxygen-free radicals generated by xanthine oxidase and hypoxanthine. The cytoprotective activities of various antioxidants on this system were compared using established morphologic criteria. The results demonstrated that purpurogallin at 1.0 mM delayed cell necrosis to 9.98 +/- 1.16 min compared with 2.96 +/- 0.67 min without antioxidant protection. This degree of protection was significantly different from that provided by ascorbate (1.0 mM), trolox (1.0 mM), superoxide dismutase + catalase, catalase (92,000 IU/L), mannitol (1.0 mM), and superoxide dismutase (24,200 IU/L) (p < 0.01). We concluded that purpurogallin effectively protects corneal epithelium from oxygen-free radical injury and may help prevent such injury in corneal preservation solutions.

Animals↗

Local efficacy of cyclosporine in corneal transplant therapy.

Studies were conducted to evaluate the efficacy of direct injections of cyclosporine (CsA) into the anterior chamber for the prevention of corneal allograft rejection in Dutch Belted rabbits. The mean survival time (MST) of grafts progressively increased from 50 to 89 days as the CsA concentration in the dose was increased from 1 to 10 mg/mL. Injection of 30 microL of 20 mg/mL CsA in olive oil prolonged graft survival to beyond 125 days without any signs of rejection. By comparison, the MST of allografts in control animals which received no therapy was 32 +/- 5 days, and the MST in animals administered a placebo of olive oil only was 31 +/- 4 days. The observed concentration dependence of the MST on CsA concentration is likely related to the time over which the drug delivery rate provides sufficient drug to achieve a therapeutic concentration in the aqueous humor; these studies suggest that the minimum delivery rate to the anterior chamber is between 200 and 325 ng/day. The efficacy of CsA was due to local delivery, and was likely not a systemic effect, because CsA was not detected in the systemic circulation at any time. This indicates that direct delivery of CsA to the eye can be useful in prolonging corneal graft survival, while minimizing systemic side effects. Separate experiments revealed that episodes of advanced rejection could not be reversed by a 30 microL dose of 20 mg/mL CsA to the anterior chamber, indicating the importance of avoiding long periods of subtherapeutic dosing.

Animals↗

Depot drug delivery system for 5-fluorouracil after filtration surgery in the rabbit.

We investigated the potential value of 50:50 poly (DL glycolic acid-lactic acid) (PGLA) copolymer as a degradable depot delivery system for 5-fluorouracil (5-FU) after filtration surgery. Analysis of retrieved discs after implantation in 22 eyes of 22 pigmented rabbits showed a dual drug release profile and polymer mass loss characteristics. In a second group of pigmented rabbits implantation of PGLA discs impregnated with 5-FU (22 eyes) significantly lengthened the survival time of filtration fistulae compared with discs without 5-FU (18 eyes) or no disc (10 eyes) (p < 0.0001). Use of PGLA copolymer impregnated with 5-FU could prove valuable for patients undergoing glaucoma filtering surgery.

Animals↗

Purpurogallin as a cytoprotector of cultured rabbit corneal endothelium.

We examined the protective properties of purpurogallin, a naturally occurring phenol, in delaying necrosis of cultured corneal endothelial cells caused by oxygen free radicals. Endothelial cell cultures were prepared from New Zealand white rabbits using microcarrier cell culture techniques. Corneal endothelial cells were treated with hypoxanthine (2 mM) and xanthine oxidase (67 IU/L) to generate free radicals. The criteria for cell necrosis were cytoplasmic shrinkage, dissolution of plasma membranes and presence of "haloes" around the cells on phase contrast microscopy, confirmed by transmission electron microscopy. More than 95% of second-generation cells exhibited morphologic evidence of necrosis within 4.62 +/- 0.82 minutes after exposure to oxyradicals. The addition of purpurogallin (0.25 or 1.0 mM) significantly increased time to cell necrosis to 8.18 +/- 0.83 and 11.59 +/- 1.71 minutes respectively (p < 0.05). Further studies are under way to determine whether purpurogallin may be useful in preventing endothelial cell damage in corneas preserved for corneal transplantation.

Animals↗

Releasable "U" suture for trabeculectomy surgery.

Overfiltration after glaucoma surgery can lead to significant complications. Tight suturing of the trabeculectomy flap reduces this problem but can lead to higher pressure and poor drainage of aqueous. Releasable sutures often leave irritating exposed suture ends. We describe a simple two-arm releasable suture technique that leaves no exposed suture ends until one arm of the suture is removed. Good control of postoperative pressure with few complications was achieved in 28 cases using this technique, which allows manipulation at the slit lamp of the trabeculectomy flap, obviating laser lysis of the sutures.

Glaucoma↗