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Biomedical subjects

E J Higginbotham

Publications and source records attributed to E J Higginbotham.

At least 37 records · Page 2Linked to original sources

Transconjunctival mitomycin C as an adjunct to conventional glaucoma filtration surgery in rabbits.

PURPOSE: Subconjunctival mitomycin C has been used in glaucoma filtration surgery with success. A prospective, randomized, masked, placebo-controlled study was performed to evaluate whether single transconjunctival mitomycin C applied either preoperatively or postoperatively would enhance the success of filtration surgery in rabbits. METHODS: Two groups of 5 rabbits were studied. In Group I, a Weck-Cel sponge soaked in 0.5 mg/ml mitomycin C was applied transconjunctively for 7 minutes immediately before a full thickness filtering procedure. The other eye was treated similarly with a sponge soaked in balanced salt solution. Group II first underwent filtration surgery followed by treatment with either mitomycin-c or balanced salt solution 3 days later. Postoperative intraocular pressure, bleb status, and complications were evaluated. Treatment failure was defined as postoperative pressure within 4 mmHg of that determined preoperatively or the absence of bleb formation. RESULTS: In Group I, mean time to failure (+/- SD) was significantly longer (p = 0.03) in experimental eyes (30 +/- 15.1 days) than control eyes (8.6 +/- 0.8 days). In Group II, the time to failure was 12.4 (+/- 2.6) days versus 9.6 (+/- 2.5) days in the experimental and control eyes respectively, but this was not statistically significant (p = 0.10). Transient limbal vascularization and corneal haze were seen in all experimental eyes. Serious complications included late bleb rupture in eyes pretreated with mitomycin C (all eyes in Group I) and corneal decompensation (one mitomycin-c eye). CONCLUSIONS: This study demonstrates that a single preoperative tranconjunctival application of mitomycin-c is more effective at the time of surgery than an application applied in the intermediate postoperative period. Additional studies are needed, however, to further refine both the dose and timing of mitomycin-c application during filtration surgery.

Animals↗

Vasoactive intestinal peptide stimulation of human trabecular meshwork cell growth.

PURPOSE: To demonstrate that vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, is a growth factor of human trabecular meshwork (TM) cells in culture and in a corneoscleral explant organ culture treated with laser trabeculoplasty (LTP). METHODS: Proliferating human TM cells in cell cultures were incubated with VIP for 20 hours, followed by total cell number determination, using a Coulter counter. The percentage of proliferating TM cells was assessed, using an antibody against the proliferating cell nuclear antigen (PCNA). To test the growth effect of VIP on TM cells in situ, corneoscleral explants in organ cultures were first treated with argon LTP to initiate TM-cell proliferation and then were exposed to VIP for 48 hours. The mitotic TM cells were demonstrated immunocytochemically, using anti-PCNA in paraffin sections of the explants; and the total number of TM cells was determined after paraffin sections were counterstained by hematoxylin. RESULTS: Vasoactive intestinal peptide dose-dependently stimulated the proliferation of TM cells in cell culture. Treatment with 5 x 10(-10) M VIP resulted in a maximal increase of 40% in cell number. The effect of VIP was blocked by a VIP antagonist. The number of PCNA-stained TM cells and the total cell number in the TM in LTP-treated corneoscleral explants were increased by VIP. CONCLUSIONS: Exogenously applied VIP stimulated the proliferation of human TM cells in subconfluent cultures and in LTP-treated corneoscleral explants. In that LTP has been shown to increase the number of TM cells in situ, the growth stimulatory effect of VIP may help enhance this therapy.

Adolescent↗

Bleb-related endophthalmitis after trabeculectomy with mitomycin C.

PURPOSE: To determine whether filtering blebs resulting from adjunctive use of mitomycin C (MMC) leads to an increased risk of endophthalmitis. METHODS: The authors retrospectively reviewed the records of 232 consecutive trabeculectomies performed at the W. K. Kellogg Eye Center with adjunctive use of MMC from May 1990 through June 1993. Data obtained from the records included patient age, sex, race, type of glaucoma, site of filtration surgery, concentration and duration of exposure to MMC, presence of early or late bleb leakage, and the occurrence of endophthalmitis. RESULTS: Three patients were lost to follow-up less than 1 month after surgery. A total of 229 eyes of 192 patients (11 women and 82 men) were included in the study. Mean follow-up of patients remaining free of infection was 18.5 +/- 10.8 months (range, 1-44 months). The overall incidence of bleb-related endophthalmitis was 2.6%. Endophthalmitis developed in 8% of patients (4 or 50) in whom an inferior approach was used and in 1.1% (2 or 179) in whom a superior approach was used (P = 0.02, Fisher's exact test). The estimated odds ratio for the development of endophthalmitis after trabeculectomy with adjunctive MMC for inferior versus superior filtration sites was 7.7. CONCLUSION: Short-term follow-up of trabeculectomies performed with adjunctive use of MMC demonstrates an overall incidence of endophthalmitis comparable to filtrationprocedures performed with 5-fluorouracil or without antifibrotic agents. However, inferior trabeculectomy performed with adjunctive MMC carries a significantly increased risk of bleb-related endophthalmitis compared with filters performed superiorly.

Aged↗

Prevent Blindness America visual field screening study. The Prevent Blindness America Glaucoma Advisory Committee.

PURPOSE: To assess the screening efficacy and practical use of two portable devices to detect moderate to severe visual field loss rapidly in population screening. METHODS: Henson visual field analysis and Damato campimetry for glaucoma were performed in a healthy adult population, to determine false-positive rates; in established glaucoma patients and suspects, to determine false-negative rates; and in a general adult population, to assess practical use in actual screenings. RESULTS: There were no false-positive test failures among the 82 normal subjects who completed the Henson two-step screening. Eighty of 83 normal subjects passed Damato campimetry, resulting in a false-positive rate of 3.6%. Among 83 glaucoma suspects and patients, the Henson test identified 49 (84%) of 58 subjects whose full-threshold fields from Humphrey perimetry were abnormal, 38 (97%) of 39 of whom had moderate to severe visual field loss. The Damato campimeter detected 55 (81%) of 68 subjects with any pathologic loss on full-threshold visual fields, 44 (92%) of 48 of whom had moderate to severe visual field loss. Among 1,278 subjects tested in general population screenings, 55 subjects (4.3%) failed either or both tests. CONCLUSIONS: The Henson visual field analyzer can discriminate moderately to severely diseased from normal visual fields with high sensitivity and specificity. The Damato campimeter can reliably detect moderate to severe visual field loss with a tolerably low false-positive rate. To overcome the weakness of glaucoma screening by tonometry alone, some forms of visual field testing may be acceptably brief (cost effective) and accurate (sensitive and specific).

Adolescent↗

Mitomycin C versus 5-fluorouracil in high-risk glaucoma filtering surgery. Extended follow-up.

PURPOSE: To compare the outcome of filtering surgery in high-risk patients using intraoperative mitomycin C (MMC) versus postoperative 5-fluorouracil (5-FU). METHODS: In a randomized clinical trial, the use of postoperative subconjunctival injections of 5-FU in 19 eyes of 19 patients was compared with a single intraoperative application of MMC in 20 eyes of 20 patients. All eyes were at high risk for failure of glaucoma filtering surgery. RESULTS: Follow-up ranged from 26 to 38 months (mean, 32.0 months). Three eyes in the MMC-treated group and two eyes in the 5-FU-treated group required subsequent surgery to control the IOP. Excluding these patients, intraocular pressure (IOP) averaged 9.0 +/- 4.9 mmHg in the MMC-treated eyes versus 16.3 +/- 4.6 mmHg in the 5-FU-treated eyes at the patient's last visit (P = 0.0003). Of the MMC-treated eyes, 81.3% had IOPs less than or equal to 12 mmHg compared with 26.7% of eyes in the 5-FU group (P = 0.0023). In the MMC-treated group, the average number of medications for IOP control at last visit was 0.5 +/- 0.8 compared with 1.6 +/- 1.3 in the 5-FU-treated group (P = 0.01). Late postoperative complications (those occurring more than 3 months after surgery) were similar for the two groups, with the exception of formation of a Tenon cyst in three of the eyes treated with MMC compared with none of the 5-FU-treated eyes. CONCLUSIONS: Eyes treated with MMC have lower IOP on fewer medications than eyes treated with 5-FU. Late postoperative complications are similar with the exception of an increased incidence of Tenon cyst formation in the MMC-treated eyes.

Antibiotics, Antineoplastic↗

Loss of cell-matrix cohesiveness after phagocytosis by trabecular meshwork cells.

PURPOSE: To investigate the response of trabecular meshwork cells to phagocytic events. METHODS: Cultured bovine trabecular meshwork cells were established and exposed to latex microspheres for 40 to 44 hours. After phagocytosis, the cohesiveness of cells to their underlying matrix was measured by the susceptibility to trypsin, as indicated by the time needed to be liberated from culture plates. The amounts of two cell attachment proteins, fibronectin and laminin, in both the phagocytically challenged and the control cultures were measured at various postphagocytosis time points with an enzyme-linked immunosorbent assay. The fibronectin and laminin network was visualized with immunostaining. The mRNA levels were analyzed by Northern blot. Zymography using gelatin-containing gels was also performed to examine the gelatinase activities. RESULTS: Compared with controls, cells in phagocytically challenged cultures were more sensitive to trypsin. At the 4- and 8-hour postphagocytosis time points, the trypsinization time needed to suspend cells from tissue culture plates was significantly shorter for phagocytically challenged cells. Also, at these two time points, reduced amounts of fibronectin and laminin, as well as disruption of the fibronectin-laminin network, were observed in the phagocytically challenged trabecular meshwork cultures. The mRNA level for fibronectin was reduced, and a slightly increased gelatinase activity was noted. The fibronectin and laminin levels returned to normal by 24 hours. CONCLUSIONS: Results suggest that after phagocytosis, trabecular meshwork cells exhibit a short-term loss in cell-matrix cohesiveness. Such a loss may be related to diminished levels of cell attachment proteins.

Animals↗

Adjunctive use of transconjunctival mitomycin-C in ab externo diode laser sclerostomy surgery in rabbits.

This study evaluates the role of transconjunctival mitomycin-C (MMC) in laser sclerostomy surgery. Sixteen albino rabbits underwent ab externo diode laser sclerostomy surgery in one eye (with the fellow eye as a control), with a single, intraoperative, 7-minute transconjunctival application of MMC (MMC group). Ten rabbits had the same sclerostomy surgery without MMC (NOMMC group). Successful filtration, defined as a difference in intraocular pressure less than 4 mm Hg between the operative and control eyes, lasted significantly longer in the MMC group (16.4 +/- 11.0 days) than in the NOMMC group (8.5 +/- 4.5 days) (P = .02). These data suggest that transconjunctival MMC can enhance the success of diode laser sclerostomy surgery in rabbits.

Animals↗

Ab-interno sclerostomy using a goniodiathermy instrument.

We describe the use of a new instrument designed to create a simultaneous goniopuncture with diathermy using an ab-interno technique. The goniodiathermy ab-interno procedure was first performed on three eyes of three cynomolgus monkeys. Intraocular pressure (IOP) assessment and histologic examination were performed over a 10-day period. A functioning filtration bleb with a patent sclerostomy was achieved in all of the experimental eyes. A pilot study involving four eyes of four glaucoma patients also was performed. Of these four, successful long-term functioning filtration areas with adequate lowering of IOP were achieved in only two. The remaining two required further surgical intervention. Although combining goniopuncture and diathermy into a one-step ab-interno procedure proved successful in the primates studied, the preliminary use of this new instrument as a method of creating a filter in humans raises questions regarding its clinical usefulness.

Adolescent↗

Long-term visual outcome of ocular hypotension after thermosclerostomy.

Maximum intraocular pressure reduction is often the goal of glaucoma filtering procedures. To evaluate whether surgically induced ocular hypotension adversely affects visual acuity, we reviewed the visual outcome of 87 eyes of 67 patients who had undergone thermosclerostomy with follow-up of at least two years. Final visual acuity was compared in three groups on the basis of postoperative intraocular pressure level (< or = 10.0 mm Hg; > 10.0 mm Hg and < or = 21.0 mm Hg; and eyes that did not consistently fit solely in either group [mixed]). Average loss in visual acuity measured 1.8 +/- 3.0, 2.2 +/- 2.9, and 1.2 +/- 2.1 Snellen lines, respectively (P = .542). These data suggest that hypotensive eyes are not at greater risk for visual loss after glaucoma filtering procedures compared to normotensive eyes.

Aged↗

Effects of antiglaucoma medications on bovine trabecular meshwork cells in vitro.

Using an in vitro culture system, we investigated the effects of five antiglaucoma drugs on growth and morphologic characteristics of bovine trabecular meshwork cells. Epinephrine hydrochloride (55-550 microM) and pilocarpine hydrochloride (0.8-16 mM), when added to the cultures for 3 days, inhibited trabecular cell growth in a dose-dependent manner. The lowest concentration at which the inhibitory effect was observed was 109 microM and 0.8 mM, respectively, for epinephrine and pilocarpine. Dipivefrin hydrochloride (26-260 microM), timolol maleate (116-1160 microM), and levobunolol hydrochloride (150-1500 microM) were also added to the cells for 3 days. These drugs caused a reduction in cell density, respectively, at concentrations higher than 103, 460, and 616 microM. Cell elongation was seen in cultures treated with epinephrine and dipivefrin, whereas levobunolol and timolol induced the cells to adopt a rounded appearance. Cells that had been exposed to pilocarpine were enlarged with numerous vacuoles. By scanning electron microscopic techniques, epinephrine, timolol, and levobunolol were found to retard the phagocytosis of latex beads by trabecular meshwork cells. Immunostaining with the use of antibodies to vimentin and actin revealed disorganization and condensation of cytoskeletal fibers in trabecular meshwork cells after treatment with epinephrine and dipivefrin. Little change was seen with comparable concentrations of a preservative, benzalkonium chloride, and a vehicle, Liquifilm tears. These results showed that antiglaucoma drugs, depending on their concentrations, may profoundly influence the growth and activity of trabecular meshwork cells.

Actins↗

Diode laser surgery. Ab interno and ab externo versus conventional surgery in rabbits.

BACKGROUND: Fibroblastic proliferation of subconjunctival tissues remains a primary mechanism of failure in filtration surgery. Minimizing the surgical manipulation of episcleral tissues may reduce scarring. Laser sclerostomy surgery involves minimal tissue dissection, and is gaining attention as a method of potentially improving filter duration in high-risk cases. METHODS: Twenty-five New Zealand rabbits underwent filtration surgery in one eye, and the fellow eye remained as the unoperated control. Ten rabbits underwent ab externo diode laser sclerostomy surgery, ten underwent ab interno diode sclerostomy surgery, and five had posterior sclerostomy procedures. Filtration failure was defined as a less-than-4-mmHg intraocular pressure (IOP) difference between the operative and control eyes. RESULTS: The mean time to failure for the ab externo, ab interno, and conventional posterior sclerostomy techniques measured 17.4 +/- 11.5, 13.1 +/- 6.7, and 6.0 +/- 3.1 days, respectively. In a comparison of the laser-treated groups with the conventional procedure, the time to failure was significantly longer (P = 0.02) for the ab externo filter. The mean ab interno sclerostomy duration was longer than the posterior lip procedure, but this difference was not statistically significant (P = 0.15). The overall level of IOP reduction was similar in the three groups. CONCLUSIONS: These data suggest that diode laser sclerostomy is a feasible technique in rabbits, and the ab externo approach resulted in longer filter duration than the conventional posterior lip procedure in this model.

Animals↗

Can the concentration of timolol or the frequency of its administration be reduced?

BACKGROUND: There is evidence that the ocular hypotensive effect of topical beta-blockers persists for at least 24 hours once beta-blockade has been achieved. In previous studies, the highest concentration of drug generally has been used for this purpose. METHOD: Home tonometry was performed with a self-tonometer by 14 patients to study the intraocular pressure (IOP) reduction of 0.5% timolol administered once daily in the morning or in the evening and of 0.25% timolol administered in the morning. The study was masked and included washout periods before and between the different regimens. At the end of each treatment period, the IOP was monitored five times daily for 3 days. RESULTS: No significant difference in mean reduction of IOP was found between the morning instillation of once daily 0.5% timolol compared with evening instillation of 0.5% timolol. In addition, there was no statistically significant difference in the mean IOP reduction between once daily administration of 0.25% versus 0.5% timolol. CONCLUSION: This study indicates that a lower concentration of timolol maleate used once daily may achieve maximum IOP reduction. The time of the single administration appears not to make any difference.

Adult↗