Initial treatment for open-angle glaucoma- medical, laser, or surgical? Laser trabeculoplasty is the treatment of choice for chronic open-angle glaucoma.
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Biomedical subjects
Publications and source records attributed to H D Jampel.
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OBJECTIVE: To determine if there is an association between the surgical outcome of trabeculectomy and uric acid and ascorbic acid concentrations in the aqueous humor at the time of the procedure. PATIENTS, MATERIALS, AND METHODS: Aqueous humor samples were collected from the eyes of 169 of 249 adult patients who underwent trabeculectomy alone for any type of glaucoma between April 1989 and July 1995. Postoperatively, all medical records were reviewed and outcomes were classified as successful, unsuccessful, or indeterminate. The ascorbic acid and uric acid concentrations were determined in masked fashion by high-pressure liquid chromatography. Factors associated with surgical outcome were determined. RESULTS: Uric acid concentration was higher in unsuccessful eyes (mean+/-SD, 0.21+/-0.08 mmol/L, n=26) than in successful eyes (0.15+/-0.09 mmol/L, n=91, 95% confidence interval for difference, 0.02-0.10 mmol/L). Ascorbic acid levels were not significantly different in the eyes with unsuccessful (1129.9+/-601.9 micromol/L) and successful (1334.3+/-511.0 micromol/L) surgery (95% confidence interval for difference, -475.2 to 66.4 micromol/L, P=.13) surgery. Other factors associated with failure were previous surgery and surgery performed at the inferior limbus. A multiple polytomous logistic regression analysis was performed, after excluding the small number of operations performed at the inferior limbus. The odds ratio for failure increased by a factor of 1.68 for every 1-mmol/L increase in uric acid (95% confidence interval, 1.16-2.43, P=.006). CONCLUSIONS: Uric acid levels were higher at the time of surgery in eyes that had unsuccessful outcomes than in those with successful outcomes. No significant difference in ascorbic acid levels was detectable. A higher uric acid level in the aqueous humor is a risk factor for trabeculectomy failure and might be tested as a prognostic indicator [corrected].
OBJECTIVE: The authors determine if the intraoperative placement of paclitaxel powder in the subconjunctival space improves the outcome of glaucoma filtration surgery in rabbits. METHODS: A posterior lip sclerectomy was performed in the right eye of 24 New Zealand white rabbits. Before the conjunctiva was fully sutured, 8 mg of mannitol powder alone, or 8 mg of mannitol powder containing either 10 micrograms or 250 micrograms of paclitaxel, was placed in the subconjunctival space of six eyes each in masked fashion. An additional six animals were treated with episcleral application of a sponge soaked in a solution of 0.5 mg/ml of mitomycin C (MMC) for 5 minutes before the sclerectomy was performed. Intraocular pressure and bleb size were measured until the operation had failed or until the 7 weeks of observation had concluded. RESULTS: Both paclitaxel powder and MMC solution improved the outcome of filtration surgery in this model as measured by magnitude of intraocular pressure (IOP) lowering and duration of surgical success. No toxic effect of either drug was observed, although endophthalmitis was observed in eight animals followed for more than 3 weeks. CONCLUSION: The introduction of paclitaxel into the subconjunctival space at the conclusion of filtration surgery has an effect comparable to intraoperative MMC.
The debate about health care reform has centered around managed care and its ramifications. Medical savings accounts (MSAs), on the other hand, have been relegated to the background of the congressional discussion of health care reform. Conservative Republicans have advocated MSAs, whereas they have been denigrated by many liberals. The Clinton administration has threatened to veto any legislation that includes MSA provisions. I believe that MSAs are in general poorly understood by physicians and deserve closer attention. This article will explain what MSAs are and how they work. The advantages of MSAs will be discussed and examples of MSAs in action will be provided.
PURPOSE: To determine whether carbonic anhydrase isozyme (CA) III is expressed in the ciliary processes and lens. METHODS: Total RNA was isolated from rabbit ciliary epithelium and human ciliary processes and from the anterior lens of rabbit, cow, and human eyes. First-strand cDNA was synthesized, and the polymerase chain reaction (PCR) was performed using oligomer primers designed to amplify CA III sequences specifically. Selected PCR products were eluted from agarose gels, cloned, and sequenced. Northern blots were performed to confirm the presence of CA III in these tissues. RESULTS: Polymerase chain reaction products of the predicted size were generated from rabbit ciliary epithelium and from rabbit, bovine, and human lens. The sequence of the PCR product from human lens was identical to the published sequence of the corresponding region of the human CA III gene. The sequence of the PCR products from rabbit ciliary epithelium and bovine lens showed 88% and 97% identity, respectively, with the corresponding sequences for human CA III, suggesting that the PCR products corresponded to the rabbit and bovine orthologs. Northern blots confirmed the presence of CA III mRNA in the rabbit ciliary epithelium and in rabbit and bovine lens. CONCLUSIONS: mRNA for CA III is present in the intraocular tissues of rabbits, cows, and humans. The previous detection of CA III protein in the bovine lens is confirmed, and it extended to the lenses of other species, including humans. The detection of mRNA for CA III in the ciliary epithelium is new and suggests that the ciliary epithelium contains not only isozymes II and IV but isoenzyme III as well. Although the function of CA III in the eye is unknown, it may play a role in fluid transport and homeostasis.
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PURPOSE: Rabbits are used commonly for the evaluation of drugs and surgery to lower intraocular pressure (IOP). The authors compared the accuracy and variability of three tonometers for measuring IOP in rabbits. METHODS: The anterior chamber of adult rabbits was cannulated with a 25-gauge needle connected to an elevated bottle of balanced salt solution. The bottle was raised and lowered to control IOP. A fluid-filled pressure transducer also was placed in the anterior chamber. Intraocular pressure was decreased in increments of 5 to 10 cm H2O from 50 to 0 mm Hg and was recorded with each of these instruments: the hand-held applanation tonometer, the Tono-pen XL, and the pneumatonometer. RESULTS: The Tono-pen XL and the hand-held applanation tonometer underestimated the IOP, whereas the pneumatonometer slightly overestimated IOP. Under close stopcock conditions, at IOPs between 3 and 30 mm Hg, the Tono-pen XL was as accurate as the pneumatonometer but had a smaller variance; the hand-held applanation tonometer had lower accuracy and higher variability. CONCLUSIONS: The Tono-pen XL is the tonometer of choice for measuring IOP in rabbits within the range of IOP 3 to 30 mm Hg. All tonometers were less accurate when the IOP was elevated markedly.
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BACKGROUND: Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. METHODS: We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. RESULTS: VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P < 0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. CONCLUSIONS: Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
PURPOSE: Pharmacological modulation of wound healing after glaucoma filtration surgery is of great clinical interest, but there are only limited data available on drug pharmacokinetics following glaucoma filtration surgery. Therefore we have studied the in vivo release and tissue distribution of etoposide (VP-16) delivered subconjunctivally by a bioerodible drug-carrier during filtration surgery in rabbits. METHODS: Disks composed of the polyanhydride 1,3-bis(p-carboxyphenoxy) propane and sebacic acid (PCPP:SA) in a weight ratio of 25:75 and containing 1 mg of 3H-etoposide were placed subconjunctivally during posterior lip sclerectomy in one eye of albino rabbits. Animals were euthanized at various times after surgery and etoposide concentrations in fluids and tissues were determined using liquid scintillation counting. RESULTS: Release of etoposide from the implant was nearly linear over time, at 30 ug/day, except for a burst between days 6 and 7. By the twelfth postoperative day, 92% of the etoposide had been released. Steady state levels averaged 89 ng/mg in the conjunctiva and sclera, 195 ng/ml in the vitreous, and 29 ng/ml in serum. Drug levels in the aqueous humor, other ocular tissues, and in the contralateral eye were negligible. CONCLUSIONS: The concentration of etoposide delivered by a polyanhydride controlled release device on the ocular surface is sufficient to reduce fibroblast proliferation for at least 12 days after filtration surgery.
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PURPOSE: To determine the effect of taxol and etoposide, hydrophobic drugs with antifibrosis activity, on the outcome of filtration surgery in glaucomatous monkeys. METHODS: Elevated intraocular pressure was produced bilaterally in eight cynomolgus monkeys by laser treatment of the trabecular meshwork. Four animals subconjunctivally received a polyanhydride disk containing 1 mg etoposide at the time of posterior lip sclerectomy in one eye; the other eye received an identical disk without drug. Similarly, four animals received a disk containing 50 micrograms of taxol in one eye and a blank disk in the other. RESULTS: Eyes treated with taxol had lower intraocular pressures than control eyes from 20 days after surgery until death. Eyes with satisfactory filtration bleb appearance and patent fistulae on histologic examination had lower intraocular pressures. The intraocular pressure was lower and the duration of success longer in the etoposide-treated eyes (mean, 16 days) compared to that of the fellow eyes (mean, 10 days), but the difference was not statistically significant. CONCLUSIONS: Use of polyanhydride disks containing taxol, but not etoposide, had a marked beneficial effect on intraocular pressure and bleb appearance after experimental filtration surgery in monkeys. The difference between the two agents may result from the greater antiproliferative potency of taxol and its greater duration of release from the polymer.
PURPOSE: To determine the distribution of transforming growth factor type beta (TGF-beta) in the anterior segment of the human eye. This knowledge is important because TGF-beta may regulate various physiologic responses in the anterior segment by controlling cell proliferation and differentiation, angiogenesis, and extracellular matrix composition. METHODS: Immunohistochemical methods were used to localize the beta 1, beta 2, and beta 3 isoforms of TGF-beta in the anterior segment of the human eye. RESULTS: Eight of eight eyes (six eye bank specimens and two eyes enucleated because of choroidal melanoma) exhibited staining for at least one of the TGF-beta isoforms. TGF-beta 1 was found in superficial limbal epithelial cells (four of eight eyes) and in the stroma proximal to the ciliary processes (seven of eight eyes). TGF-beta 2 was found in superficial limbal epithelial cells (six of eight eyes), the conjunctival stroma (eight of eight eyes), in the ciliary processes (three of eight eyes), and in a diffuse distribution in the region of the radial and circular muscles of the ciliary body (eight of eight eyes). In addition, TGF-beta 2 was found in the stroma adjacent to the pigmented epithelium in the pars plana (eight of eight eyes). TGF-beta 3 was found in white blood cells in one of eight specimens; otherwise it was not found in the anterior segment. The corneal stroma, corneal endothelium, trabecular meshwork, iris, and ciliary epithelia did not exhibit immunoreactivity with the antibodies used in this study. CONCLUSION: TGF-beta 1 and TGF-beta 2 have a distinct and specific distribution in the anterior segment of the adult human eye.
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We designed and evaluated a new test for the detection of early glaucoma damage in 133 persons who were classified as normal, suspected of having glaucoma, or having glaucoma. The test stimulates the entire visual field with a flashing white light under dark-adapted conditions. It can be performed easily by a high proportion of subjects and is as reproducible as present psychophysical tests. Glaucomatous eyes were discriminated from normal with a diagnostic power of 0.91 as judged by receiver operating characteristic analysis, and specificity and sensitivity were 91% and 86%, respectively. Glaucoma suspects with an abnormal response to the whole-field scotopic test were more likely to have other signs indicating early optic nerve injury, including a greater proportion of borderline field defects, nerve fiber layer defects, or glaucomatous fellow eyes. Assessment of whole-field scotopic sensitivity may be useful in glaucoma screening.
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PURPOSE: The purpose of this study is to determine why a single intraoperative dose of mitomycin C (MMC) appears to promote the success of glaucoma filtration surgery. METHODS: Human Tenon's capsule fibroblasts were exposed to MMC and 5-fluorouracil (5-FU) in vitro at the concentrations and durations of exposure used clinically. Cell proliferation was assessed by quantification of 3H-thymidine uptake. Cell viability was studied using a sulfarhodamine B cell protein stain and by trypan blue exclusion. RESULTS: Neither MMC (0.4 mg/ml) nor 5-FU (40 mg/ml) were cytocidal. Both 1- and 5-minute exposures to MMC were antiproliferative. A 1-minute exposure to 0.4 mg/ml inhibited 3H-thymidine uptake by 77%. For the 5-minute exposure, 3H-thymidine uptake was inhibited by 50% at 0.06 mg/ml and by 90% at 0.4 mg/ml. For 5-FU, 3H-thymidine uptake was inhibited by 50% at 10 mg/ml and by 64% at 40 mg/ml. CONCLUSIONS: Mitomycin C probably does not improve the success of filtration surgery by killing fibroblasts. The ability of a brief exposure to MMC to improve filtration surgery may be due to an almost complete inhibition of proliferation. Alternatively, it may be due to sustained tissue binding, effects on other components of wound healing, such as cell migration and extracellular matrix production, or effects on the vasculature. A 1-minute exposure may be as effective as a 5-minute exposure.
In this study, an experimental model of glaucoma filtration surgery was used to evaluate the clinical and histologic effects of a single intraoperative topical application of mitomycin C. Argon laser treatment to the trabecular meshwork produced sustained elevation of intraocular pressure in monkeys. Eight eyes of four animals were randomly assigned to receive topical mitomycin C or balanced salt solution at the time of full-thickness sclerostomy. Surgical success was substantially increased in four of five eyes that received mitomycin C when compared with three eyes that received topical balanced salt solution. Mitomycin C was also effective in prolonging surgical success in two eyes that had previously undergone surgery and failed. No significant ocular toxicity was observed in eyes treated with mitomycin C. Histologic examination of mitomycin C-treated eyes showed patent sclerostomies and hypocellular, well-formed bleb cavities. A single intraoperative application of mitomycin C has a marked effect on postoperative wound healing after filtration surgery in monkeys.