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Biomedical subjects

Carl B Camras

Publications and source records attributed to Carl B Camras.

At least 19 recordsLinked to original sources
PubMed2006

Effects of a prostaglandin DP receptor agonist, AL-6598, on aqueous humor dynamics in a nonhuman primate model of glaucoma.

This study examines, in 11 cynomolgus monkeys with unilateral laser-induced glaucoma, the ocular hypotensive mechanism of action of AL-6598, partial agonist at the DP and EP prostanoid receptors. In a crossover fashion, both eyes of each monkey were dosed twice daily with 25 microL of either AL-6598 0.01% or vehicle for 2 days and on the morning of the 3rd day. Measurements were made on day 3 of each treatment. Alternative treatments were separated by at least 2 weeks. Intraocular pressures (IOPs) were measured by pneumatonometry and aqueous flow and outflow facility by fluorophotometry. Uveoscleral outflow was calculated mathematically. In the normotensive eyes, compared to vehicle treatment, AL-6598 decreased IOP from 22.5 +/- 0.7 to 18.7 +/- 0.9 mmHg (P = 0.006), increased uveoscleral outflow from 0.47 +/- 0.17 to 1.22 +/- 0.17 microL/min (P = 0.03), and increased aqueous flow from 1.49 +/- 0.10 to 1.93 +/- 0.13 microL/min (P = 0.01). No measurement in AL-6598-treated hypertensive eyes was significantly different from vehicle treatment. It is concluded that AL-6598 reduces IOP by increasing uveoscleral outflow in normotensive eyes of ketamine-sedated monkeys, despite an increase in aqueous flow. This effect is different from that of PGD(2), which decreases aqueous flow, and of the selective DP receptor agonist, BW245C, which increases both outflow facility and uveoscleral outflow in addition to decreasing aqueous flow.

Animals↗
PubMed2005

Effects of travoprost on aqueous humor dynamics in monkeys.

PURPOSE: To determine the mechanism by which travoprost, a prodrug of a prostaglandin F2alpha analog, reduces intraocular pressure (IOP) in cynomolgus monkey eyes. METHODS: One eye each of 12 monkeys was treated with laser burns to the trabecular meshwork to elevate IOP. At least 4 months later (Baseline Day), IOP was measured by pneumatonometry (9:00 AM and 11:45 AM), and aqueous flow and outflow facility were determined by a fluorophotometric method. Uveoscleral outflow was calculated. Both eyes were treated with travoprost 0.004% at 9:00 AM and 5:00 PM for two days and at 9:30 AM on the third day (Treatment Day), when measurements were repeated as on Baseline Day. Statistical analyses were performed using two-tailed, paired t tests. RESULTS: On Treatment Day compared with Baseline Day, IOP in hypertensive eyes was reduced at 2.25 hours (25.8 +/- 11.2 vs 33.7 +/- 13.2 mm Hg; mean +/- standard error of the mean [SEM]; P = 0.02) and 16 hours (26.3 +/- 10.2 vs 35.1 +/- 13.6 mm Hg; P = 0.02) after treatment. The increase in uveoscleral outflow was not significant. In normotensive eyes, IOP was reduced at 2.25 hours (19.0 +/- 3.7 vs 23.0 +/- 4.0 mm Hg; P = 0.03) and 16 hours (20.7 +/- 5.4 vs 23.4 +/- 5.3 mm Hg; P = 0.01) after treatment, and uveoscleral outflow was significantly (P = 0.02) increased (1.02 +/- 0.43 vs 0.35 +/- 0.72 microL/min). CONCLUSION: Travoprost reduces IOP in normotensive monkey eyes by increasing uveoscleral outflow. The IOP reduction in hypertensive eyes is probably via the same mechanism, although the increased uveoscleral drainage did not reach statistical significance. Travoprost had no effect on aqueous flow or outflow facility.

Animals↗
PubMed2005

Latanoprost or brimonidine as treatment for elevated intraocular pressure: multicenter trial in the United States.

PURPOSE: To compare the efficacy and tolerability of latanoprost or brimonidine in patients with elevated intraocular pressure (IOP). MATERIALS AND METHODS: This prospective, randomized, masked-evaluator, parallel-group, multicenter study in the United States included patients with primary open angle glaucoma or ocular hypertension. Patients received latanoprost 0.005% once daily (8:00 AM; n = 152) or brimonidine tartrate 0.2% twice daily (8:00 AM and 8:00 PM; n = 151). Patients underwent evaluation at screening, baseline (randomization), and after 0.5, 3, and 6 months of treatment. IOP was measured at 8:00 AM, 10:00 AM, noon, and 4:00 PM at baseline and the months 3 and 6 visits, and at 8:00 AM only at week 2. The main outcome measure was the difference in diurnal IOP change from baseline to month 6 between treatment groups. Adverse events were recorded at each visit. RESULTS: Baseline mean diurnal IOP levels were similar between groups. At month 6, the adjusted mean (+/- SEM) diurnal IOP reduction was 5.7 +/- 0.3 mm Hg in the latanoprost group and 3.1 +/- 0.3 mm Hg in patients receiving brimonidine (P < 0.001). The mean difference in diurnal IOP reduction was 2.5 +/- 0.3 mm Hg (95% CI: 1.9, 3.2; P < 0.001). Five times more patients receiving brimonidine than latanoprost were withdrawn from the study due to adverse events. CONCLUSION: Latanoprost instilled once daily is more effective and better tolerated than brimonidine administered twice daily for the treatment of patients with glaucoma or ocular hypertension. During therapy, the range of daily fluctuation of IOP is less for latanoprost compared with brimonidine.

Adult↗
PubMed2004

Increase in outflow facility with unoprostone treatment in ocular hypertensive patients.

OBJECTIVE: To determine the mechanism by which 0.15% unoprostone isopropyl reduces intraocular pressure (IOP) by studying 33 patients with ocular hypertension or primary open-angle glaucoma. METHODS: At baseline, IOP was determined by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, episcleral venous pressure by venomanometry, and uveoscleral outflow by mathematical calculation. Unoprostone was administered to one eye and placebo to the fellow eye of each patient twice daily in a randomized masked fashion. In patients who demonstrated an IOP reduction of 3 mm Hg or more in either eye on day 5 +/- 1 (n = 29), determinations were repeated on that day and on day 28 +/- 2. Treated eyes were compared with control eyes, and treatment days were compared with baseline by paired t tests. RESULTS: Compared with baseline, unoprostone significantly (P<.001) reduced IOP by a mean +/- SEM of 5.6 +/- 0.4 mm Hg and 4.8 +/- 0.6 mm Hg on days 5 and 28, respectively. The change from baseline with unoprostone was significantly (P<.001) greater than with placebo by 2.8 +/- 0.4 mm Hg on day 5 and by 3.2 +/- 0.5 mm Hg on day 28. Compared with baseline, unoprostone significantly (P</=.001) increased outflow facility by 0.05 +/- 0.01 and 0.08 +/- 0.02 microL.min(-1).mm Hg(-1) on days 5 and 28, respectively. The baseline-adjusted between-treatment differences were significant (P</=.04) on day 28 (0.06 +/- 0.02 microL.min(-1).mm Hg(-1)). Other measures were not different from placebo. CONCLUSION: In responsive patients, unoprostone decreased IOP by increasing outflow facility.

Adult↗
PubMed2004

Detection of the free acid of bimatoprost in aqueous humor samples from human eyes treated with bimatoprost before cataract surgery.

PURPOSE: To determine whether bimatoprost is hydrolyzed to its free acid after topical application in humans in vivo. DESIGN: Prospective, masked, and vehicle controlled. PARTICIPANTS: Thirty-one eyes of 31 patients with cataracts. METHODS: Beginning 7 days before scheduled cataract surgery, one eye of each patient was treated with bimatoprost 0.03% or vehicle once daily, with the last drop administered 2 to 12 hours before anterior chamber paracentesis before cataract surgery. In a masked fashion, aqueous humor specimens were assayed for bimatoprost and its free acid by high-pressure liquid chromatography and mass spectrometry. MAIN OUTCOME MEASURE: Detection of the free acid of bimatoprost in aqueous humor. RESULTS: Aqueous humor concentrations of the free acid of bimatoprost were 22.0+/-7.0 nmol/l (mean +/- standard error of the mean, n = 12) and 7.0+/-4.6 nmol/l (n = 8) at 2 and 12 hours, respectively, and below the limit of detection after vehicle (n = 10). Concentrations of bimatoprost (amide) were 5.7+/-1.4 and 1.1+/-0.4 nmol/l at 2 and 12 hours, respectively, and undetectable after vehicle. CONCLUSION: After topical application of bimatoprost in humans, a sufficient concentration of its free acid, a potent FPprostanoid receptor agonist, is found in the aqueous humor to account for its ability to reduce intraocular pressure.

Administration, Topical↗
PubMed2004

Effects on aqueous flow of dorzolamide combined with either timolol or acetazolamide.

PURPOSE: To determine the effect on aqueous flow of topical dorzolamide 2%, topical timolol 0.5%, or oral acetazolamide 250 mg when used alone or when dorzolamide is combined with either timolol or acetazolamide. METHODS: In 30 patients with ocular hypertension, aqueous flow and intraocular pressure (IOP) were determined at baseline and on the following combinations of drugs in a crossover design: (1) vehicle alone, (2) dorzolamide alone, (3) acetazolamide alone, (4) timolol alone, (5) dorzolamide + acetazolamide, and (6) dorzolamide + timolol. Treated eyes were compared with control eyes and comparisons were made between treatments. RESULTS: Compared with baseline, significant (P < 0.04) IOP reductions in the order of efficacy were: dorzolamide + timolol > dorzolamide + acetazolamide = acetazolamide = timolol > dorzolamide. Aqueous flow was reduced more by dorzolamide + timolol than by each drug alone (P < 0.04) and more by dorzolamide + acetazolamide than by dorzolamide alone (P < 0.04). CONCLUSION: The combination of dorzolamide and timolol demonstrated significant aqueous flow additivity and had greater IOP efficacy than the combination of dorzolamide and acetazolamide.

Acetazolamide↗
PubMed2003

Unoprostone isopropyl ester darkens iris color in pigmented rabbits with sympathetic denervation.

PURPOSE: Unoprostone isopropyl ester (unoprostone) -induced iris color darkening was evaluated in a rabbit model using a cyclooxygenase inhibitor, an alpha(1)-adrenergic antagonist, and sympathetic denervation. MATERIALS AND METHODS: Dutch-belted rabbits were divided into five groups based on type of surgery and eyedrop treatment to both eyes: (1) sham surgery (n = 7); (2) bilateral superior cervical ganglionectomy (SCGx, n = 7); (3) SCGx plus flurbiprofen 0.03% (n = 7); (4) SCGx plus thymoxamine 0.5% (n = 6); and (5) SCGx plus flurbiprofen and thymoxamine (n = 6). All rabbits were treated with unoprostone 0.12% to one eye and its vehicle to the contralateral eye twice daily for 43 weeks after SCGx. Periodic color photographs of paired eyes were scored for difference in eye color. Iris melanin and aqueous humor protein were measured at week 43. RESULTS: Twenty-three of the 26 rabbits with bilateral SCGx and unilateral unoprostone treatment demonstrated a darker iris color on the unoprostone-treated side. The average scores (demonstrating difference in iris color) comparing photographs of treated versus control eyes in the four SCGx groups were higher than those in the sham surgery group (P < 0.03), and higher than at week 0 (P < 0.001). The group pretreated with flurbiprofen and thymoxamine had the highest score of all groups. The aqueous humor protein in unoprostone-treated eyes was higher (P < or = 0.0001) than in vehicle-treated eyes. The melanin content of irides of the denervated groups was higher (P < or = 0.01) in unoprostone-treated than in vehicle-treated eyes. CONCLUSION: Unoprostone produced iris color darkening in pigmented rabbit eyes with sympathetic denervation. Pretreatment with flurbiprofen and thymoxamine appeared to enhance this effect but this was not statistically demonstrated by the study.

Adrenergic alpha-Antagonists↗
PubMed2003

Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma.

PURPOSE: This study determined the rate of response to latanoprost compared with timolol in patients with glaucoma or ocular hypertension, whether some patients convert from non-responders to responders after more prolonged therapy, and whether this conversion represents a delayed response or random fluctuation. METHODS: In a previously described, multicenter, randomized, double-masked, parallel group study, patients received either 0.005% latanoprost once daily (n = 128) or 0.5% timolol twice daily (n = 140) for 6 months. Intraocular pressure (IOP) was assessed at baseline and at 0.5, 1.5, 3, 4.5, and 6 months of treatment at 8 am on all visits, and also at noon and 4 pm at baseline and 6 months. Rate of response based on diurnal measurement at 6 months compared with baseline was assessed using several criteria for response. Eyes with an IOP reduction of less than 15% compared with baseline at 8 am arbitrarily were classified as non-responders at each of the 5 visits during treatment. Consistency of non-responder classifications for individual eyes was assessed. RESULTS: Mean IOP reduction was greater (P < 0.001) in latanoprost-versus timolol-treated patients throughout the course of therapy. A greater rate of response occurred in patients treated with latanoprost, and differences in response rates between the 2 drugs increased as the definitions of response became more stringent. A greater percentage of non-responders at any single visit were classified as responders at all other visits with latanoprost in comparison with timolol. CONCLUSIONS: Latanoprost produces a greater rate of response compared with timolol. A higher percentage of non-responders to latanoprost compared with timolol on any individual visit are responders on all other visits. Likewise, a higher proportion of patients who do not initially respond will become responders with continued treatment with latanoprost compared with timolol.

Antihypertensive Agents↗
PubMed2002

Emerging perspectives in glaucoma: optimizing 24-hour control of intraocular pressure.

PURPOSE: To explore recent studies and clinical experience involving the importance of 24-hour control of intraocular pressure (IOP) in patients with glaucoma. METHODS: Roundtable discussion. RESULTS: During the discussion, the following concepts were identified: 1. Although the effect of IOP is continuous, IOP is infrequently measured in clinical practice. 2. Within an individual patient, measurements of IOP have considerable variability throughout 24 hours. 3. Recent studies have shown that healthy subjects and glaucoma patients may experience their highest IOP at night once they have lain down to sleep. 4. Low blood pressure levels related to an individual's circadian rhythm can occur simultaneous with high IOPs at night, reducing blood flow to the optic nerve head below critical levels and thus resulting in optic nerve damage. 5. Glaucoma medications that can maximally reduce IOP over 24 hours and minimally influence blood pressure should have theoretical and practical advantages for glaucoma management. CONCLUSIONS: The new knowledge about peak night-time IOPs is changing how physicians manage their patients in terms of drug selection and targeted IOP levels aimed at halting progression of glaucomatous optic nerve damage and visual field loss. Physicians are also taking into consideration the troublesome relationship between lowered systemic blood pressure and elevated IOP during the nighttime period.

Antihypertensive Agents↗
PubMed2002

Latanoprost and cholinergic agonists in combination.

Latanoprost, a prodrug of a prostaglandin F(2alpha) analog, is a potent ocular hypotensive agent, reducing intraocular pressure (IOP) primarily by increasing aqueous humor drainage through the uveoscleral outflow pathway. Initial assessments in animals found that high concentrations of cholinergic agonists reduced drainage through this pathway and attenuated the effects of a PGF(2alpha) analog. This raised the question of whether latanoprost would be effective when added to the treatment regimen of patients on pilocarpine or strong miotics. In published clinical studies, latanoprost was additive to the maximally tolerated medical therapy (which included cholinergic agonists) of glaucoma patients. Multiple doses of physostigmine in healthy volunteers did not block the effect of a single drop of latanoprost during a 1-day study. One study attempting to find the optimal timing of administration of latanoprost and pilocarpine claimed to show that additivity was best when pilocarpine was given one hour after latanoprost in the evening. Two other studies found that the timing of the doses was not important. To explain the additivity of latanoprost and pilocarpine, aqueous humor dynamics were assessed in ocular hypertensive patients treated for 1 week with each drug alone and then for one week in combination. The results showed that latanoprost increased uveoscleral outflow, pilocarpine increased outflow facility, and pilocarpine did not block or attenuate the uveoscleral outflow effect of latanoprost. The result was greater IOP reduction when these drugs were used in combination than when either drug was used alone. All available evidence demonstrates that addition of latanoprost to the treatment regime of patients already taking cholinergic agonists is an effective, although not necessarily the preferred, combination of medications for the treatment of elevated IOP.

Antihypertensive Agents↗
PubMed2002

Bimatoprost and travoprost: a review of recent studies of two new glaucoma drugs.

Bimatoprost (Lumigan [Allergan, Inc, Irvine CA]) and travoprost (Travatan [Alcon, Ft Worth, TX]) are two new intraocular pressure (IOP)-lowering drugs for use in patients with glaucoma and ocular hypertension. This review evaluates recent studies comparing these new drugs with timolol and with latanoprost. In each study, the statistical analyses support the conclusion that these agents were more effective than timolol and as effective as latanoprost in terms of their ability to reduce IOP. The side effect profiles for bimatoprost, latanoprost, and travoprost were similar, but with statistically higher occurrences of hyperemia and eyelash growth for bimatoprost or travoprost versus latanoprost or timolol.

Amides↗
PubMed2002

Putative side effects of prostaglandin analogs.

Anecdotal case reports describe the occurrence of cystoid macular edema, iritis, herpes simplex keratitis, periocular skin darkening, and headaches in patients treated with prostaglandin analogs for glaucoma. The purpose of this article is to critically analyze these anecdotal case reports in light of a few well-controlled, randomized clinical studies to determine whether conclusions can be made about a causal relationship between the use of prostaglandin analogs and the occurrence of these side effects. None of these putative side effects has been proven to be causally related to latanoprost therapy using valid scientific methodology. These possible side effects occur rarely. Cystoid macular edema, iritis, and herpes simplex keratitis occur in eyes with risk factors. To scientifically establish a causal relationship between drug therapy and rare side effects, repeated rechallenging with masked controls is required. With rare exception, such methodology has not been used with any of these putative side effects. Nevertheless, even without firm establishment of a causal relationship, caution is advised with the use of prostaglandin analogs in eyes with risk factors for cystoid macular edema, iritis, and herpes simplex keratitis until properly designed, large, controlled studies provide more definitive information.

Headache↗